Bicyclic tetrahydroazepine derivatives for the treatment of cancer

Abstract

The present invention relates to a compound represented by the general formula (I) TIFF2024506339001175.tif48170 (in the formula, X, Y, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 6a is as defined herein) The present invention provides novel bicyclic tetrahydroazepine derivatives having the formula:

Description

[Technical Field]

[0001] FIELD OF THE INVENTION The present invention relates to bicyclic tetrahydroazepine compounds that inhibit diacylglycerol kinase (DGK) α and ζ and are useful as T cell signaling 2 enhancers, their preparation and pharmaceutical compositions containing said compounds.

[0002] The compounds may be useful as immunotherapeutic agents for treating human diseases. More specifically, the compounds may be used alone or in combination with other immunotherapeutic agents to enhance anti-cancer immunity. [Background technology]

[0003] Background of the Invention Cancer immunity is a multistep process regulated by a series of negative immune checkpoints and positive costimulatory receptors and associated intracellular signaling cascades that, when effectively elicited, can achieve antitumor responses (Mellman, I., et al. (2011) Cancer Immunotherapy Comes of Age, Nature 480(7378), 480-489). Indeed, PD1 / PDL1 targeting and other immune checkpoint inhibitors have revolutionized cancer immunotherapy, yet more than 70% of patients still do not benefit from immune checkpoint blockade. Similarly, in the case of T cell bispecific antibodies, even in the most promising indication (non-Hodgkin's lymphoma), these T cell binders (TCBs) achieve complete remission in fewer than 50% of patients. T cell exhaustion appears to play a key role in many of these cases of primary or secondary resistance to cancer immunotherapy. A possible reason for this lack of efficacy is that T cell activation occurs via targeting and crosslinking of CD3 (signal 1) but without costimulation (signal 2), for example, via CD28 or 4-1BB. This hypothesis was clinically validated for CAR T-cell therapy, where it was shown that clinically relevant efficacy was only observed after incorporation of a costimulatory domain.

[0004] Diacylglycerol kinase (DGK) is a lipid kinase that catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA), thus limiting DAG regulation and promoting PA-dependent functions.

[0005] (Merida, I., Avila-Flores, A., and Merino, E. 2008: Diacylglycerol kinases: at the hub of cell signaling. Biochem. J. 409(1), 1-18). The DGK family consists of 10 isoforms that can be divided into five subtypes based on the presence of distinct regulatory domains within their structure. Beyond that, the current lack of structural data still prevents a more complete understanding of the mode of action of DGKs. Furthermore, information on certain prokaryotic DGKs and other lipid kinases, such as sphingosine kinase and phosphatidylinositol-3-kinase (PI3K), has provided limited insight into the DGK catalytic mechanisms, which appear to differ from those of classical kinases (Arranz-Nicolas, J. and Merida, I., 2020. Biological regulation of diacylglycerol kinases in normal and neoplastic tissues: New opportunities for cancer immunotherapy. Advances in Biological Regulation, Volume 75; Ma, Q., Gabelli, S.B., Raben, D.M., 2019: Diacylglycerol kinases: relationship to other lipid kinases. Adv Biol Regul 71, 104-110).

[0006] Although several isoforms within the DGK family have been described to play a role in cancer, the α and ζ isoforms are the most extensively studied in this regard. As PA producers, both enzymes are involved in various processes that promote tumor growth and metastasis. On the other hand, as DAG consumers, DGKα and ζ have been widely characterized as negative regulators of T cell responses (Riese, MJ, Moon, EK, Johnson, BD, Albelda, SM, 2016. Diacylglycerol kinases (DGKs): novel targets for improving T cell activity in cancer. Front Cell Dev Biol 4, 108; Noessner, E., 2017. DGK-alpha: a checkpoint in cancer-mediated immuno-inhibition and target for immunotherapy. Front Cell Dev Biol 5, 16; Sakane, F., Mizuno, S., Komenoi, S., 2016. Diacylglycerol kinases as emerging potential drug targets for a variety of diseases: an update. Front Cell Dev Biol 4, 82; Arranz-Nicolas, J. and Merida, I., 2020. Biological regulation of diacylglycerol kinases in normal and neoplastic tissues: New opportunities for cancer immunotherapy,Advances in Biological Regulation,Volume 75)

[0007] These two isozymes, DGKα and DGKζ, are active downstream of CD28 and other costimulatory receptors as well as the T cell receptor (TCR), and their function is to limit the amount of DAG produced and ultimately T cell activation (Merida, I., Andrada, E., Gharbi, S.I., Avila-Flores, A., 2015. Redundant and specialized roles for diacylglycerol kinases alpha and zeta in the control of T cell functions. Sci. Signal. 8(374); Shulga, Y.V., Topham, M.K., Epand, R.M., 2011. Regulation and functions of diacylglycerol kinases. Chem. Rev. 111(10), 6186-6208.). An overview of representative DGK-regulated signaling pathways is shown in Figure 1 (Sim, J.A.; Kim, J.; Yang, D. Beyond Lipid Signaling: Pleiotropic Effects of Diacylglycerol Kinases in Cellular Signaling. Int. J. Mol. Sci. 2020, 21, 6861): Activated PLC1 cleaves PIP2 in the plasma membrane to generate two secondary messengers, DAG and IP3. DAG activates PKC, Ras / MEK / ERK / AP-1, and NF-kB, while IP3 is involved in activating intracellular Ca2+ flux. Upregulated Ca2+ signaling then activates the transcription factor NFAT. Briefly, the production and levels of DAG determine the duration and strength of Ras / MEK / ERK- and PKC-dependent signaling pathways, which are central to T cell activation. Therefore, DGK acts as an intracellular checkpoint, and inhibition of DGK is expected to enhance T cell signaling pathways and T cell activation.

[0008] Experimental evidence suggests that enhanced DGK function and / or expression in tumor-infiltrating T cells (TILs) limits tumor destruction. Experiments using CAR T cells against human mesothelioma transplanted into nude mice demonstrated that tumor-infiltrating CAR T cells express high concentrations of surface inhibitory receptors and the inhibitory enzymes SHIP-1, DGKα, and DGKζ (Moon et al., 2014). Furthermore, high DGKα expression was also observed in TILs isolated from human renal tumors (Prinz et al., 2012). In mouse mesoCAR T cells, double deletion of DGKα and DGKζ resulted in enhanced cytokine expression and cytotoxicity against tumor cells (Riese et al., 2013). Similar results were obtained when expression of both DGKα and DGKζ was increased by CRISPR /

[0009] Human CAR T cells silenced using Cas9 have been reported (Jung et al., 2018). All of these studies support the rationale for targeting DGKα / ζ in the development of anticancer therapies (Arranz-Nicolas, J. and Merida, I., 2020. Biological regulation of diacylglycerol kinases in normal and neoplastic tissues: New opportunities for cancer immunotherapy, Advances in Biological Regulation, Volume 75; Riese, MJ, Moon, EK, Johnson, BD, Albelda, SM, 2016. Diacylglycerol kinases (DGKs): novel targets for improving T cell activity in cancer. Front Cell Dev Biol 4, 108). Knockout mouse models provide further evidence.Mice lacking either DGKα or DGKζ exhibited a hyperresponsive T cell phenotype and improved antitumor immune activity (Riese, MJ, Grewal, J., Das, J., Zou, T., Patil, V., Chakraborty, AK, Koretzky, GA, 2011. Decreased diacylglycerol metabolism enhances ERK activation and augments CD8+ T cell functional responses. J. Biol. Chem. 286(7), 5254-5265; Zha, Y., Marks, R., Ho, AW, Peterson, AC, Janardhan, S., Brown, I., Praveen, K., Stang, S., Stone, JC, Gajewski, TF, 2006. T cell energy is reversed by active Ras and is regulated by diacylglycerol kinase-alpha.Nat.Immunol.7(11),1166-1173;Olenchock,BA,Guo,R.,Carpenter,JH,Jordan,M.,Topham,MK,Koretzky,GA,Zhong,XP,2006a.Disruption of diacylglycerol metabolism impairs the induction of T cell energy.Nat.Immunol.7(11),1174-1181.).

[0010] Taken together, there is substantial evidence that DGKα and DGKζ are high-value targets for cancer immunotherapy. At the same time, there is a lack of compounds capable of potently inhibiting both DGKα and DGKζ with better selectivity over other diacylglycerol kinases, protein kinases, and / or other lipid kinases.

[0011] The present invention describes such dual DGKa / z inhibitors with superior selectivity over other protein kinases across safety / off-target panels and other lipid kinases. These compounds potently activate suboptimally stimulated T cells, thereby acting as intracellular enhancers of the costimulatory signaling cascade. These DGKa / z inhibitors have the potential to increase the proliferation, cytotoxicity, and longevity of targeted T cells, which may result in improved anti-cancer activity of CPI, CD3-engaged T cell bispecific, and CAR T cells. Furthermore, by engaging central signaling nodes of both the TCR and costimulatory receptors, it is plausible that these molecules could enhance both signals 1 and 2, thus achieving single-agent activity, for example, in inflammatory tumors.

[0012] There remains a need for new compounds that can activate and expand T cells, thus enabling the treatment, prevention and / or delay of cancer progression.

[0013] It is therefore an object of the present invention to provide compounds useful as T cell signaling 2 enhancers for the treatment or prevention or amelioration of such diseases that have improved therapeutic properties, in particular improved pharmacokinetic properties. Summary of the Invention

[0014] The first object of the present invention is to provide a compound of formula (I) TIFF0007821808000001.tif48170 (in the formula, X is C(R 7 ) or N, Y is S, S(O), S(O) 2、 S(O)N(R y ) and R 1 is a 5-membered heteroaryl, and R 1 is one or more R which may be the same or different 10 may be substituted with R 2 , R 3 and R 7are each independently hydrogen, halogen, or C 1~6 -Alkyl, C 2~6 -Alkynyl, hydroxy, cyano, halo-C 1~6 -Alkyl, N(R 8 R 8a ), C 1~6 -alkoxy, C 3~7 -cycloalkyl and 3- to 10-membered heterocyclyl; R 4 is C 5~14 -aryl and 5- to 14-membered heteroaryl; R 4 is one or more R which may be the same or different 11 may be substituted with R 5 is hydrogen, C 1~6 -alkyl, -C(O)(R 9 ), amino, amino-C 1~6 -alkyl and C 3~7 -cycloalkyl, The C in question 3~7 -Cycloalkyl is one or more C 1~6 -Alkyl, Amino, Amino-C 1~6 -alkyl-, R 6 and R 6a are each independently hydrogen and C 1~6 -alkyl, R 8 and R 8a are each independently hydrogen and C 1~6 -alkyl, R 9 is C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, Amino-C 1~6 -Alkyl- and -(C 1~6 -alkyl)-N(R 9a R 9b ) wherein the amino-C 1~6 -Alkyl is one or more hydroxy, hydroxy-C 1~6 -alkyl-, R 9a and R9b are each independently hydrogen and C 1~6 -alkyl, wherein C 1~6 -alkyl may be substituted with one or more hydroxy or or R 9a and R 9b together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 10 teeth, i) one or more halogens, C 2~6 -Alkynyl, halo-C 1~6 -Alkyl, amino, hydroxy, 5-6 membered heteroaryl, C 1~6 -Haloalkoxy, C 1~6 -alkoxy, 3-10 membered cycloalkyl, C 1~3 -alkyl, -N(R 10a R 10b ), -S(O)2(C 1~6 -alkyl), -S(O)2(C 1~6 -cycloalkyl), 3-10 membered heterocyclyl, phenyl, cyano, -C(O)N(R 10c R 10d ) optionally substituted with C 1~10 -alkyl, and 3- to 10-membered heterocyclyl, 3- to 10-membered cycloalkyl, and phenyl are each independently one or more C 1~10 -Alkyl, C 1~10 -alkoxy, -S(O)2(C 1~6 -alkyl), oxo, halogen, C 2~6 -alkynyl, optionally substituted with 3- to 10-membered cycloalkyl, C 1~10 - alkyl, ii) one or more halogens, C 1~10 -Alkyl, -S(O)2(C 1~6 alkyl), cyano, C 1~6 Haloalkyl, C 1~6 -alkoxy, hydroxy, oxo, amino, -C(O)N(R 10c R 10d ), =N(OH), hydroxy-C 1~6 - optionally substituted with alkyl, C 3~10 -cycloalkyl, iii) one or more halogens, C 1~10 -Alkyl, -S(O)2(C 1~6 -alkyl), -C 1~10 -Alkyl-C 1~4 -alkoxy, amino, -C(O)N(R 10h R 10i ), C 1~6 -haloalkyl, C 1~6 -Alkoxy, cyano, hydroxy-C 1~10 -Alkyl, oxo, -C(O)(C 1~6 -alkyl), -C(O)O-(R 10q ), C 3~10 -3-10 membered heterocyclyl optionally substituted by cycloalkyl; iv) one or more halogens, C 1~10 -Alkyl, -S(O)2(C 1~6 -alkyl), v)-N(R 10e R 10f ), vi)-OR 10g , vii) -C(O)NR 10h R 10i , viii) one or more C 1~10 -Alkyl, halogen, -SO2(C 1~6 heteroaryl, optionally substituted with alkyl; ix) oxo is selected from R 10a and R 10b are each independently hydrogen, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, -C(O)(R 10j ), amino-C 1~6 -Alkyl-, 3- to 10-membered heterocyclyl, -SO2(R 10k ), -C 1~6 -Alkyl-SO2(R 10k ) and -N(R 10l R 10m) and 3-10 membered heterocyclyl is C 1~6 -substituted with alkyl, or R 10a and R 10b together with the nitrogen atom to which they are attached, one or more halogens, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl; R 10c and R 10d are each independently hydrogen and C 1~6 -alkyl, R 10e and R 10f are each independently i) hydrogen, ii) optionally substituted with one or more cyano, in particular one cyano, halogen, hydroxy, C 1~6 - alkyl, iii)-C(O)R 10n , iv) one or more C 2~6 -optionally substituted by alkynyl, -C 1~10 Alkyl ((OC 1~10 alkyl) m ) (wherein m is an integer between 1 and 5 (more specifically, m is 2 or 3)), v) one or more halogen, hydroxy, oxo, C 1~10 -Alkyl, Halo-C 1~10 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, -C(O)O(R 10o ), -C(O)(R 10o ), -C(O)N(R 10p )(R 10p’ ), -SO2(C 1~6 -alkyl), optionally substituted by C2-6-alkynyl, C 3~10 -cycloalkyl, and vi) one or more halogen, hydroxy, oxo, C 1~10 -Alkyl, Halo-C 1~10 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6-alkoxy, -C(O)O(R 10o ), -C(O)(R 10o ), -C(O)N(R 10p )(R 10p’ ), -SO2(C 1~6 -alkyl), 3- to 10-membered heterocyclyl optionally substituted with 3- to 10-membered cycloalkyl is selected from R 10g is Halo-C 1~6 -Alkyl, cyano, -C 1~10 -alkyl-phenyl, -C 1~6 -Alkyl-C 3~7 -cycloalkyl and -C 1~6 -Alkoxy-halo-C 1~6 -alkyl, R 10h and R 10i are each independently hydrogen and C 1~6 -Alkyl, C 1~6 -haloalkyl, C 1~6 -alkyl and C 1~6 -haloalkyl may be optionally substituted with one or more hydroxy or R 10h and R 10i together with the nitrogen atom to which they are attached, may contain one or more halogens, hydroxyl, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl; R 10j is C 1~6 -Alkyl, Halo-C 1~6 -Alkyl-, hydroxy-C 1~6 -Alkyl- and amino-C 1~6 -alkyl-, R 10k is hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 10l and R 10m are each independently hydrogen and C 1~6 -alkyl, R 10n is C 1~6-Alkyl, Amino-C 1~6 -Alkyl-, Halo-C 1~6 -Alkyl, C 3~7 -cycloalkyl and 3- to 10-membered heterocyclyl, 3~7 -Cycloalkyl and 3- to 10-membered heterocyclyl are substituted with one or more halogens, C 1~6 - optionally substituted with alkyl, R 10o is C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 10p and R 10p’ are independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 10q is C 1~10 -Alkyl, C 1~6 -haloalkyl, aryl, heteroaryl, wherein aryl and heteroaryl are each independently one or more halogens, C 1~10 - optionally substituted with alkyl, R 11 teeth, i) halogens, ii) hydroxy, iii) cyano, iv) one or more of cyano, halogen, hydroxyl, C 3~7 -Optionally substituted with cycloalkyl, amino, aryl, -O-aryl, 5- to 6-membered heteroaryl, or 3- to 7-membered heterocyclyl; C 1~10 -alkyl, and 3- to 7-membered heterocyclyl and aryl are each selected from the group consisting of one or more C 1~6 -Alkyl, -SO2(C 1~6 -alkyl), optionally substituted with hydroxy, halogen, or cyano; C 1~10 - alkyl, v) one or more, particularly one, 3- to 10-membered heterocyclyl, optionally substituted with halogen, C 1~6 -alkoxy, vi) C 3~7 -cycloalkyl, vii) one or more halo-C1~6 -Alkyl, Hydroxy, C 1~6 -Alkyl, C 3~10 -cycloalkyl, C 1~6 -3-10 membered heterocyclyl optionally substituted by alkoxy or oxo; viii) one or more C 1~6 -Alkyl, 3-10 membered cycloalkyl, halogen, halo-C 1~6 -Alkyl, C 1~6 -alkoxy, C 1~6 -5-6 membered heteroaryl optionally substituted with haloalkoxy; ix) one or more halogens, cyano, C 1~6 -alkoxy, C 1~6 -haloalkyl, C 1~6 -Alkyl, C 1~6 -phenyl, optionally substituted by haloalkoxy; x)-O(R 11a ), xi)-C(O)N(R 11b R 11c ), xii)-SO2(R 11d ), xiii)-C(O)OR 11e , xiv)-C(O)R 11f , xv) oxo, xvi)-N(R 11g R 11h ), and xvii)-S(R 11k ) is selected from R 11a is C 1~12 -Alkyl, Halo-C 1~6 -Alkyl, Amino-C 1~12 -Alkyl-, hydroxy-C 1~6 -Alkyl-, cyano, C 2~6 -alkynyl, C 3~7 -cycloalkyl, 3- to 10-membered heterocyclyl, 3- to 10-membered -(C 1~6 -alkyl)heterocyclyl, 5-6 membered heteroaryl, phenyl, -C 1~6 -alkyl-phenyl, -C1~12 -Alkyl-C(O)N(R 11i R 11j ), -C 1~12 -Alkyl-NH-C(O)(C 1~6 -alkyl), -C 1~12 -alkoxy-NH-C(O)(C 1~6 -alkyl), -C 1~6 -Alkyl-NH-C(O)(C 1~6 -alkyl), -(CH2CH2O) n -CH2CH2NH2 and -(CH2CH2O) n -CH2CH 2- NH-C(O)(C 1~6 -alkyl), The C in question 1~12 -Alkyl, C 3~7 -cycloalkyl, 3- to 10-membered heterocyclyl, 5- to 6-membered heteroaryl, phenyl, and -C 1~6 -Alkyl-phenyl is substituted with one or more halogens, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, C 1~6 -alkoxyl, C 1~6 - optionally substituted with haloalkoxyl, cyano; n is an integer between 1 and 6, particularly n is 2 or 3; R 11b and R 11c are each independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl; or R 11b and R 11c together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 11d is hydrogen, C 1~6 -alkyl, -N(R 11l R 11m ), Halo-C 1~6 - selected from alkyl and phenyl, R 11e is hydrogen and C 1~6 -alkyl, R 11f is hydrogen, C1~6 - selected from alkyl and phenyl, R 11g and R 11h are each independently hydrogen, C 1~6 -alkyl, -(C 1~6 -alkyl)phenyl, halo-C 1~6 -Alkyl, -SO2(C 1~6 -Alkyl), -SO2(Halo-C 1~6 -alkyl) and -SO(C 1~6 -alkyl)2, R 11i and R 11j are each independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl; or R 11i and R 11j together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 11k is hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 11l and R 11m are each independently hydrogen and C 1~6 -alkyl; or R 11l and R 11m together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R y is hydrogen and C 1~6 -alkyl) or a pharmaceutically acceptable salt thereof.

[0015] A second object of the present invention is to provide a compound of formula (I) TIFF0007821808000002.tif48170 (in the formula, X is C(R 7 ) or N, Y is S, S(O), S(O) 2、 S(O)N(R y ) and R 1 is a 5-membered heteroaryl, and R 1 is one or more R which may be the same or different 10 may be substituted with R 2 , R 3 and R 7 are each independently hydrogen, halogen, or C 1~6 -Alkyl, C 2~6 -Alkynyl, hydroxy, cyano, halo-C 1~6 -Alkyl, N(R 8 R 8a ), C 1~6 -alkoxy, C 3~7 -cycloalkyl and 3- to 10-membered heterocyclyl; R 4 is C 5~14 -aryl and 5- to 14-membered heteroaryl; R 4 is one or more R which may be the same or different 11 may be substituted with R 5 is hydrogen, C 1~6 -alkyl, -C(O)(R 9 ), amino, amino-C 1~6 -alkyl and C 3~7 -cycloalkyl, The C in question 3~7 -Cycloalkyl is one or more C 1~6 -Alkyl, Amino, Amino-C 1~6 -alkyl-, R 6 and R 6a are each independently hydrogen and C 1~6 -alkyl, R 8 and R 8a are each independently hydrogen and C 1~6 -alkyl, R 9 is C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, Amino-C 1~6 -Alkyl- and -(C 1~6-alkyl)-N(R 9a R 9b ) wherein the amino-C 1~6 -Alkyl is one or more hydroxy, hydroxy-C 1~6 - optionally substituted with alkyl, R 9a and R 9b are each independently hydrogen and C 1~6 -alkyl, wherein C 1~6 -alkyl may be substituted with one or more hydroxy or or R 9a and R 9b together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 10 teeth, i) one or more halogens, C 2~6 -Alkynyl, halo-C 1~6 -Alkyl, amino, hydroxy, C 1~6 -alkoxy, -N(R 10a R 10b ), -S(O)2(C 1~6 -alkyl), -S(O)2(C1-6-cycloalkyl), 3- to 10-membered heterocyclyl, cyano, -C(O)N(R 10c R 10d ) optionally substituted with C 1~10 alkyl, and 3- to 10-membered heterocyclyl is one or more C 1~10 -alkyl, C1-10-alkoxy, oxo, optionally substituted with halogen, C 1~10 Alkyl, ii) one or more hydroxy, C 1~6 -Optionally substituted with alkoxy, amino, or phenyl, C 1~10 -haloalkyl, and phenyl is one or more C 1~10 -alkyl, optionally substituted with halogen, C 1~10 -haloalkyl, iii) one or more of amino, halogen, C 1~6 -haloalkyl, C 1~3 -alkyl, cyano, 3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl, C1~6 -Haloalkoxy, C 1~6 amino-C optionally substituted with alkoxy 1~10 -alkyl-, wherein the 3- to 10-membered heterocyclyl and the 3- to 10-membered cycloalkyl are selected from the group consisting of one or more halogens, C 2~6 -alkynyl, optionally substituted with 3- to 10-membered cycloalkyl, amino-C 1~10 -alkyl-, iv) Hydroxy-C 1~10 -alkyl-, v) C optionally substituted with one or more cyano 1~6 -alkoxy, vi) C 1~6 -Alkoxy-C 1~10 -alkyl-, vii) one or more halogens, C 1~10 -Alkyl, -S(O)2(C 1~6 alkyl), cyano, C 1~6 Haloalkyl, C 1~6 -alkoxy, hydroxy, oxo, amino, -C(O)N(R 10c R 10d ), =N(OH), hydroxy-C 1~6 - optionally substituted with alkyl, C 3~10 -cycloalkyl, viii) one or more halogens, C 1~10 -Alkyl, -S(O)2(C 1~6 -alkyl), -C 1~10 -Alkyl-C 1~4 -alkoxy, amino, -C(O)N(R 10h R 10i ), C 1~6 -haloalkyl, C 1~6 -Alkoxy, cyano, hydroxy-C 1~10 -Alkyl, oxo, -C(O)(C 1~6 -alkyl), -C(O)O-(R 10q ), C 3~10 -3-10 membered heterocyclyl optionally substituted by cycloalkyl; ix)-(C 1~6 -alkyl)-C 3~7 -cycloalkyl, x) one or more halogens, C 1~10 3-10-membered -(C 1~6 -alkyl)-heterocyclyl, xi) one or more halogens, C 1~10 -Alkyl, -S(O)2(C 1~6 -alkyl), xii) -(C 1~10 -alkyl)-phenyl, C 1~10 -Alkyl is C 1~6 -alkyl, optionally substituted with cyano, -(C 1~10 -alkyl)-phenyl, xiii) 5-6-membered -(C 1~10 -alkyl)-heteroaryl, xiv)-(alkoxy-C 1~10 -alkyl)-phenyl, xv)-(amino-C 1~10 -alkyl)-phenyl, xvi)-C 1~6 -Alkyl-SO2(C 1~6 -alkyl), xvii)-N(R 10e R 10f ), xviii)-OR 10g , and vix)-C(O)NR 10h R 10i , xx) One or more C 1~10 -Alkyl, halogen, -SO2(C 1~6 heteroaryl, optionally substituted with alkyl; xxi) Oxo is selected from R 10a and R 10b are each independently hydrogen, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, -C(O)(R 10j ), amino-C 1~6-Alkyl-, 3- to 10-membered heterocyclyl, -SO2(R 10k ), -C 1~6 -Alkyl-SO2(R 10k ) and -N(R 10l R 10m ) and 3-10 membered heterocyclyl is C 1~6 -substituted with alkyl, or R 10a and R 10b together with the nitrogen atom to which they are attached, one or more halogens, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl; R 10c and R 10d are each independently hydrogen and C 1~6 -alkyl, R 10e and R 10f are each independently i) hydrogen, ii) optionally substituted with one or more cyanos, in particular one cyano, C 1~6 - alkyl, iii) Halo-C 1~6 -alkyl and halo-C 1~6 -alkyl may be substituted with one or more hydroxy, halo-C 1~6 - alkyl, iv) Hydroxy-C 1~6 - alkyl, v)-C(O)R 10n , vi) one or more C 2~6 -optionally substituted by alkynyl, -C 1~10 Alkyl ((OC 1~10 alkyl) m ) (wherein m is an integer between 1 and 5 (more specifically, m is 2 or 3)), vii) one or more of halogen, hydroxy, oxo, C 1~10 -Alkyl, Halo-C 1~10 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, -C(O)O(R 10o), -C(O)(R 10o ), -C(O)N(R 10p )(R 10p’ ), -SO2(C 1~6 -alkyl), optionally substituted by C2-6-alkynyl, C 3~10 -cycloalkyl, viii) one or more halogen, hydroxy, oxo, C 1~10 -Alkyl, Halo-C 1~10 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, -C(O)O(R 10o ), -C(O)(R 10o ), -C(O)N(R 10p )(R 10p’ ), -SO2(C 1~6 -alkyl), 3- to 10-membered heterocyclyl optionally substituted by 3- to 10-membered cycloalkyl Selected from or or R 10e and R 10f together with the nitrogen atom to which they are attached, may contain one or more halogens, amino, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, C 3~7 -cycloalkyl, -C(O)O(C 1~6 -alkyl), R 10g is Halo-C 1~6 -Alkyl, C 1~6 -Alkyl-C 3~7 -cycloalkyl and C 1~6 -Alkoxy-halo-C 1~6 -alkyl, R 10h and R 10i are each independently hydrogen and C 1~6 -Alkyl, C 1~6 -haloalkyl, C 1~6 -alkyl and C 1~6-haloalkyl may be optionally substituted with one or more hydroxy or R 10h and R 10i together with the nitrogen atom to which they are attached, may contain one or more halogens, hydroxyl, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl; R 10j is C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl and amino-C 1~6 -alkyl-, R 10k is hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 10l and R 10m are each independently hydrogen and C 1~6 -alkyl, R 10n is C 1~6 -Alkyl, Amino-C 1~6 -Alkyl-, Halo-C 1~6 -Alkyl, C 3~7 -cycloalkyl and 3- to 10-membered heterocyclyl, 3~7 -Cycloalkyl and 3- to 10-membered heterocyclyl are substituted with one or more halogens, C 1~6 - optionally substituted with alkyl, R 10o is C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 10p and R 10p’ are independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 10q is C 1~10 -Alkyl, C 1~6 -haloalkyl, aryl, heteroaryl (aryl and heteroaryl are substituted with one or more halogens, C 1~10- optionally substituted with alkyl, R 11 teeth, i) halogens, ii) hydroxy, iii) cyano, iv) optionally substituted with one or more cyano, aryl, haloaryl; C 1~6 - alkyl, v) optionally substituted with one or more, particularly one, 3- to 10-membered heterocyclyl, C 1~6 -alkoxy, vi) Halo-C 1~6 - alkyl, vii) Amino-C 1~10 -alkyl-, viii) Hydroxy-C 1~6 - alkyl, ix) C 3~7 -cycloalkyl, x)-C 1~6 -Alkyl-C 3~7 -cycloalkyl, xi) one or more halo-C 1~6 -Alkyl, Hydroxy, C 1~6 -Alkyl, C 3~10 -cycloalkyl, C 1~6 -3-10 membered heterocyclyl optionally substituted by alkoxy or oxo; xii) one or more C 1~6 3- to 7-membered -(C 1~6 -alkyl)-heterocyclyl, xiii) one or more C 1~6 -Alkyl, 3-10 membered cycloalkyl, halogen, halo-C 1~6 -Alkyl, C 1~6 -alkoxy, C 1~6 -5-6 membered heteroaryl optionally substituted with haloalkoxy; xiv) one or more halogens, cyano, C 1~6 -Alkoxy, Halo-C 1~6 -Alkyl, C 1~6 -Haloalkoxy, C 1~6 -phenyl, optionally substituted with alkyl; xv) one or more -SO2(C 1~6 -alkyl), hydroxy, halogen, cyano-substituted -(C 1~6 -alkyl)-phenyl, xvi)-(C 1~6 -alkyl)-O-phenyl, xvii) 5-6-membered -(C 1~6 -alkyl)-heteroaryl, xviii)-O(R 11a ), xix)-C(O)N(R 11b R 11c ), xx)-SO2(R 11d ), xxi)-C(O)OR 11e , xxii)-C(O)R 11f , xxiii) oxo, xxiv)-N(R 11g R 11h ), xxv)-S(R 11k ), and xxvi)C 1~6 -Haloalkoxyl is selected from R 11a is C 1~12 -Alkyl, Halo-C 1~6 -Alkyl, Amino-C 1~12 -Alkyl-, hydroxy-C 1~6 -Alkyl, cyano, -C 1~6 -Alkyl, C 2~6 -alkynyl, C 3~7 -cycloalkyl, 3- to 10-membered heterocyclyl, 3- to 10-membered -(C 1~6 -alkyl)heterocyclyl, 5-6 membered heteroaryl, phenyl, -C 1~6 -alkyl-phenyl, -C 1~12 -Alkyl-C(O)N(R 11i R 11j ), -C 1~12 -Alkyl-NH-C(O)(C 1~6 -alkyl), -C 1~12 -alkoxy-NH-C(O)(C1~6 -alkyl), -C 1~6 -Alkyl-NH-C(O)(C 1~6 -alkyl), -(CH2CH2O) n -CH2CH2NH2 and -(CH2CH2O) n -CH2CH 2- NH-C(O)(C 1~6 -alkyl), The C in question 1~12 -Alkyl, C 3~7 -cycloalkyl, 3- to 10-membered heterocyclyl, 5- to 6-membered heteroaryl, phenyl, and -C 1~6 -Alkyl-phenyl is substituted with one or more halogens, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, C 1~6 -alkoxyl, C 1~6 - optionally substituted with haloalkoxyl, cyano; n is an integer between 1 and 6, R 11b and R 11c are each independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl; or R 11b and R 11c together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 11d is hydrogen, C 1~6 -alkyl, -N(R 11l R 11m ), Halo-C 1~6 - selected from alkyl and phenyl, R 11e is hydrogen and C 1~6 -alkyl, R 11f is hydrogen, C 1~6 - selected from alkyl and phenyl, R 11g and R 11h are each independently hydrogen, C 1~6 -alkyl, -(C 1~6 -alkyl)phenyl, halo-C 1~6-Alkyl, -SO2(C 1~6 -Alkyl), -SO2(Halo-C 1~6 -alkyl) and -SO(C 1~6 -alkyl)2; or R 11g and R 11h together with the nitrogen atom to which they are attached, form C 1~6 -Alkyl, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkoxy; R 11i and R 11j are each independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl; or R 11i and R 11j together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 11k is hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 11l and R 11m are each independently hydrogen and C 1~6 -alkyl; or R 11l and R 11m together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R y is hydrogen and C 1~6 -alkyl) or a pharmaceutically acceptable salt thereof.

[0016] The third object of the present invention is to provide a compound of formula (I) TIFF0007821808000003.tif48170 (in the formula, X is C(R 7 ) or N, Y is S, S(O), S(O) 2、 S(O)N(R y ) and R1 is a 5-membered heteroaryl, and R 1 is one or more R which may be the same or different 10 may be substituted with R 2 , R 3 and R 7 are each independently hydrogen, halogen, or C 1~6 -Alkyl, C 2~6 -Alkynyl, hydroxy, cyano, halo-C 1~6 -Alkyl, N(R 8 R 8a ), C 1~6 -alkoxy, C 3~7 -cycloalkyl and 3- to 10-membered heterocyclyl; R 4 is C 5~14 -aryl and 5- to 14-membered heteroaryl; R 4 is one or more R which may be the same or different 11 may be substituted with R 5 is hydrogen, C 1~6 -alkyl, -C(O)(R 9 ), amino, amino-C 1~6 -alkyl and C 3~7 -cycloalkyl, The C in question 3~7 -Cycloalkyl is one or more C 1~6 -Alkyl, Amino, Amino-C 1~6 - optionally substituted with alkyl, R 6 and R 6a are each independently hydrogen and C 1~6 -alkyl, R 8 and R 8a are each independently hydrogen and C 1~6 -alkyl, R 9 is C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, Amino-C 1~6 -alkyl and (C 1~6 -alkyl)-N(R9a R 9b ) wherein the amino-C 1~6 -Alkyl is one or more hydroxy, hydroxy-C 1~6 - optionally substituted with alkyl, R 9a and R 9b are each independently hydrogen and C 1~6 -alkyl, wherein C 1~6 -alkyl may be substituted with one or more hydroxy or or R 9a and R 9b together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 10 teeth, i) one or more halogens, C 2~6 -Alkynyl, halo-C 1~6 -Alkyl, amino, -N(R 10a R 10b ), -S(O)2(C 1~6 -alkyl), 3-10 membered heterocyclyl, cyano, -C(O)N(R 10c R 10d ) optionally substituted with C 1~10 - alkyl, ii) C 1~10 -haloalkyl, iii) Amino-C 1~10 -Alkyl iv) Hydroxy-C 1~10 - alkyl, v) C 1~6 -alkoxy, vi) C 1~6 -Alkoxy-C 1~10 - alkyl, vii) one or more halogens, C 1~10 -Alkyl, -S(O)2(C 1~6 -alkyl), hydroxy, oxo, amino, -C(O)N(R 10c R 10d ), =N(OH), hydroxy-C 1~6 - optionally substituted with alkyl, C 3~10 -cycloalkyl, viii) one or more halogens, C 1~10 -Alkyl, -S(O)2(C 1~6 -alkyl), cyano, hydroxy-C 1~10 -Alkyl, oxo, -C(O)(C 1~6 -alkyl), -C(O)O-(C 1~6 -alkyl), C 3~10 -3-10 membered heterocyclyl optionally substituted by cycloalkyl; ix)(C 1~6 -alkyl)-C 3~7 -cycloalkyl, x) one or more halogens, C 1~10 -3 to 10-membered (C 1~6 -alkyl)-heterocyclyl, xi) phenyl, optionally substituted with one or more halogens; xii) optionally substituted with one or more halogens, (C 1~10 -alkyl)-phenyl, C 1~10 -Alkyl is C 1~6 -alkyl, optionally substituted with cyano, (C 1~10 -alkyl)-phenyl, xiii) 5-6 membered (C 1~10 -alkyl)-heteroaryl, xiv) (alkoxy-C 1~10 -alkyl)-phenyl, xv) (amino-C 1~10 -alkyl)-phenyl, xvi)-C 1~6 -Alkyl-SO2(C 1~6 -alkyl), xvii)-N(R 10e R 10f ), xviii)-OR 10g , and xix)-C(O)NR 10h R 10i is selected from R 10a and R 10b are each independently hydrogen, C 1~6 -Alkyl, Halo-C1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, -C(O)(R 10j ), amino-C 1~6 -Alkyl, 3-10 membered heterocyclyl, -SO2(R 10k ), C 1~6 -Alkyl-SO2(R 10k ) and -N(R 10l R 10m ) and 3-10 membered heterocyclyl is C 1~6 -substituted with alkyl, or R 10a and R 10b together with the nitrogen atom to which they are attached, one or more halogens, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl; R 10c and R 10d are each independently hydrogen and C 1~6 -alkyl, R 10e and R 10f are each independently hydrogen, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, -C(O)R 10n , C 3~10 -cycloalkyl and 3- to 10-membered heterocyclyl, 3~10 -Cycloalkyl and 3- to 10-membered heterocyclyl are substituted with one or more of halogen, hydroxy, oxo, C 1~10 -Alkyl, Halo-C 1~10 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, -C(O)O(R 10o ), -C(O)(R 10o ), -C(O)N(R 10p )(R 10p’ ), -SO2(C 1~6 -alkyl), or R 10e and R 10ftogether with the nitrogen atom to which they are attached, may contain one or more halogens, amino, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, C 3~7 -cycloalkyl, -C(O)O(C 1~6 -alkyl), R 10g is Halo-C 1~6 -Alkyl, C 1~6 -Alkyl-C 3~7 -cycloalkyl and C 1~6 -Alkoxy-halo-C 1~6 -alkyl, R 10h and R 10i are each independently hydrogen and C 1~6 -alkyl; or R 10h and R 10i together with the nitrogen atom to which they are attached, may contain one or more halogens, hydroxyl, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl; R 10j is C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl and amino-C 1~6 -alkyl, R 10k is hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 10l and R 10m are each independently hydrogen and C 1~6 -alkyl, R 10n is C 1~6 -Alkyl, Amino-C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, C 3~7-cycloalkyl and 3- to 10-membered heterocyclyl, 3~7 -Cycloalkyl and 3- to 10-membered heterocyclyl are substituted with one or more halogens, C 1~6 - optionally substituted with alkyl, R 10o is C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 10p and R 10p’ are independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 11 teeth, i) halogens, ii) hydroxy, iii) cyano, iv) C optionally substituted with one or more cyanos 1~6 - alkyl, v) C 1~6 -alkoxy, vi) Halo-C 1~6 - alkyl, vii) Amino-C 1~10 -Alkyl viii) Hydroxy-C 1~6 - alkyl, ix) C 3~7 -cycloalkyl, x)C 1~6 -Alkyl-C 3~7 -cycloalkyl, xi) one or more halo- 1~6 -Alkyl, Hydroxy, C 1~6 -Alkyl, C 1~6 -3-10 membered heterocyclyl optionally substituted by alkoxy or oxo; xii) one or more C 1~6 -3 to 7-membered (C 1~6 -alkyl)-heterocyclyl, xiii) one or more C 1~6 -Alkyl, halogen, halo-C 1~6 -5-6 membered heteroaryl optionally substituted by alkyl; xiv) phenyl, optionally substituted with one or more halogens or cyanos; xv) one or more -SO2(C 1~6 -alkyl), hydroxy, halogen, cyano (C 1~6 -alkyl)-phenyl, xvi)(C 1~6 -alkyl)-O-phenyl, xvii) 5-6 membered (C 1~6 -alkyl)-heteroaryl, xviii)-O(R 11a ), xix)-C(O)N(R 11b R 11c ), xx)-SO2(R 11d ), xxi)-C(O)OR 11e , xxii)-C(O)R 11f , xxiii) oxo, xxiv)-N(R 11g R 11h ), and xxv)-S(R 11k ) is selected from R 11a is C 1~12 -Alkyl, Halo-C 1~6 -Alkyl, Amino-C 1~12 -Alkyl, Hydroxy-C 1~6 -Alkyl, cyano, -C 1~6 -Alkyl, C 2~6 -alkynyl, C 3~7 -cycloalkyl, 3- to 10-membered heterocyclyl, 5- to 6-membered heteroaryl, phenyl, -C 1~6 -Alkyl-phenyl, C 1~12 -Alkyl-C(O)N(R 11i R 11j ), -C 1~12 -Alkyl-NH-C(O)(C 1~6 -alkyl), -C 1~12 -alkoxy-NH-C(O)(C 1~6 -alkyl), -C 1~6-Alkyl-NH-C(O)(C 1~6 -alkyl), -(CH2CH2O) n -CH2CH2NH2 and -(CH2CH2O) n -CH2CH 2- NH-C(O)(C 1~6 -alkyl), The C in question 1~12 -Alkyl, C 3~7 -cycloalkyl, 3- to 10-membered heterocyclyl, 5- to 6-membered heteroaryl, phenyl, and C 1~6 -Alkyl-phenyl is substituted with one or more halogens, C 1~6 -Alkyl, Halo-C 1~6 -optionally substituted with alkyl, cyano, n is an integer between 1 and 6, particularly n is 2 or 3; R 11b and R 11c are each independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl; or R 11b and R 11c together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 11d is hydrogen, C 1~6 -alkyl, -N(R 11l R 11m ), Halo-C 1~6 - selected from alkyl and phenyl, R 11e is hydrogen and C 1~6 -alkyl, R 11f is hydrogen, C 1~6 - selected from alkyl and phenyl, R 11g and R 11h are each independently hydrogen, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, SO2(C 1~6 -alkyl), SO2(halo-C 1~6 -alkyl) and SO(C 1~6 -alkyl)2; or R 11g and R 11h together with the nitrogen atom to which they are attached, form C 1~6 -Alkyl, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkoxy; R 11i and R 11j are each independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl; or R 11i and R 11j together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 11k is hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 11l and R 11m are each independently hydrogen and C 1~6 -alkyl; or R 11l and R 11m together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R y is hydrogen and C 1~6 -alkyl) or a pharmaceutically acceptable salt thereof.

[0017] A further object of the present invention is a process for preparing the compounds described herein or pharmaceutically acceptable salts thereof, comprising the steps of: a) Formula (IX) TIFF0007821808000004.tif46170 (in the formula, X, Y, R 1 , R 2 , R 3 , R 4 , R 6 , R 6a is as described herein, and PG is an amino protecting group. with a suitable deprotecting agent to give the compound of formula (I), 1 , R 2 , R 3 , R 4 , R 6 , R 6a is as described herein, and R 5 is hydrogen), or a pharmaceutically acceptable salt thereof; or b) Formula (Ia) TIFF0007821808000005.tif49170 (in the formula, X, Y, R 1 , R 2 , R 3 , R 4 , R 6 , R 6a is as described herein, and R 5 is hydrogen) in the presence of a base to form a compound of formula R 9 CO2H (in the formula, R 9 is as described herein) to give a compound of formula (I) or a pharmaceutically acceptable salt thereof, 5 is -C(O)(R 9 ) is formed.

[0018] A further object of the present invention is a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, prepared by the process described herein.

[0019] A further object of the present invention is a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use as a therapeutically active substance.

[0020] A further object of the present invention is a pharmaceutical composition comprising a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

[0021] A further object of the present invention is a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment, prevention and / or delay of progression of cancer.

[0022] A further object of the present invention is the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the treatment, prevention and / or delay of progression of cancer.

[0023] A further object of the present invention is the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment, prevention and / or delay of progression of cancer.

[0024] A further object of the present invention is a method for the treatment, prevention and / or delay of progression of cancer, which method comprises administering a therapeutically effective amount of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof.

[0025] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the invention, suitable methods and materials are described below.

[0026] All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety.

[0027] The nomenclature used in this application is based on IUPAC systematic nomenclature unless otherwise indicated. [Brief explanation of the drawings]

[0028] [Figure 1] Figure 1 provides an overview of representative DGK-regulated signaling pathways (Sim, J.A.; Kim, J.; Yang, D. Beyond Lipid Signaling: Pleiotropic Effects of Diacylglycerol Kinases in Cellular Signaling. Int. J. Mol. Sci. 2020, 21, 6861). DETAILED DESCRIPTION OF THE INVENTION

[0029] Detailed Description of the Invention definition The following general definitions apply regardless of whether the term in question appears alone or in combination with other groups.

[0030] The term "alkyl" refers to a group having a specified number of carbon atoms (i.e., C1 to C2). 10 refers to a saturated, straight-chain (i.e., unbranched) or branched monovalent hydrocarbon chain, or combinations thereof. Particular alkyl groups are those having 1 to 20 carbon atoms ("C1 to C10"). 20 alkyl"), those having 1 to 12 carbon atoms ("C1 12 alkyl), those having 1 to 10 carbon atoms ("C1 10 alkyl"), those having 1 to 8 carbon atoms ("C1-8 alkyl"), those having 1 to 6 carbon atoms ("C1-6 alkyl"), those having 2 to 6 carbon atoms ("C2-6 alkyl"), or those having 1 to 4 carbon atoms ("C 1~4 Examples of alkyl groups include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl; homologs and isomers of, for example, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like.

[0031] The term "alkynyl" refers to a group having a specified number of carbon atoms (i.e., C 2~10 "C" refers to an unsaturated, linear (i.e., unbranched) or branched monovalent hydrocarbon chain having at least one site of acetylenic unsaturation (i.e., having at least one moiety of the formula C≡C), or combinations thereof. Particular alkynyl groups are those having 2 to 20 carbon atoms ("C 2~20 alkynyl"), those having 2 to 8 carbon atoms ("C 2~8 alkynyl) with 2 to 6 carbon atoms ("C2~6 alkynyl) with 2 to 4 carbon atoms ("C 2~4 Examples of alkynyl groups include, but are not limited to, groups such as ethynyl (or acetylenyl), prop-1-ynyl, prop-2-ynyl (or propargyl), but-1-ynyl, but-2-ynyl, but-3-ynyl, homologs and isomers thereof.

[0032] The term "alkoxy" refers to an alkyl group, as defined above, attached to the parent molecular moiety through an oxygen atom. Unless otherwise specified, an alkoxy group contains 1 to 12 carbon atoms ("C 1~12 -alkoxy"), preferably 1 to 10 carbon atoms ("C 1~10 -alkoxy"), more preferably 1 to 6 carbon atoms ("C 1~6 In some preferred embodiments, alkoxy groups contain 1 to 4 carbon atoms. In yet other embodiments, alkoxy groups contain 1 to 3 carbon atoms. Some non-limiting examples of alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, and tert-butoxy.

[0033] The term "alkoxyalkyl" refers to an alkyl group in which at least one of the alkyl group's hydrogen atoms has been replaced with an alkoxy group. Preferably, "alkoxyalkyl" refers to an alkyl group in which one, two, or three, and most preferably one, hydrogen atom of the alkyl group has been replaced with an alkoxy group. Particularly preferred, but non-limiting, examples of alkoxyalkyl are methoxymethyl and 2-methoxyethyl.

[0034] The term "amino", alone or in combination with other groups, refers to NH2.

[0035] The term "aminoalkyl" refers to an alkyl group in which one or more of the alkyl group's hydrogen atoms has been replaced with an amino moiety.

[0036] The term "aromatic" is used in the literature, especially in the IUPAC Compendium of Chemical Terminology, 2 nd This shows the conventional concept of aromaticity as defined in "Aromaticity in Organic Compounds: A Brief Description of the Invention," Eds. Blackwell Scientific Publications, Oxford (1997).

[0037] The term "cyano," alone or in combination with other groups, refers to CN (ie, nitrile).

[0038] The term "cyanoalkyl" refers to an alkyl group in which one or more of the alkyl group's hydrogen atoms has been replaced with a cyano moiety.

[0039] The term "cycloalkyl" refers to monocyclic, bicyclic (including bridged bicyclic and cycloalkyl spiro moieties), or tricyclic rings and saturated or partially unsaturated carbocyclic moieties having 3 to 10 carbon atoms, i.e., (C3-C 10 ) cycloalkyl. The cycloalkyl moiety may be substituted with one or more substituents. In certain embodiments, the cycloalkyl contains 3 to 8 carbon atoms (i.e., (C3-C8) cycloalkyl). In other certain embodiments, the cycloalkyl contains 3 to 6 carbon atoms (i.e., (C3-C6) cycloalkyl). Examples of cycloalkyl moieties include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and their partially unsaturated (cycloalkenyl) derivatives (e.g., cyclopentenyl, cyclohexenyl, and cycloheptenyl), bicyclo[3.1.0]hexanyl, bicyclo[3.1.0]hexenyl, bicyclo[3.1.1]heptanyl, bicyclo[3.1.1]heptenyl, and bicyclo[1.1.1]pentane. The cycloalkyl moiety may be "spirocyclopropyl." The bond can be in a "spirocycloalkyl" or "cycloalkylspiro" fashion, such as TIFF0007821808000006.tif17170.

[0040] "Halo" or "halogen" refers to fluoro, chloro, bromo, and / or iodo. If a residue is substituted with more than one halogen, it can be referred to using a prefix corresponding to the number of halogen moieties attached, e.g., dihaloaryl, dihaloalkyl, trihaloaryl, etc., refer to aryl and alkyl substituted with two ("di") or three ("tri") halo groups, which may, but need not, be the same halo. Thus, 4-chloro-3-fluorophenyl is within the scope of dihaloaryl. An alkyl group in which one or more hydrogens have been replaced with a halo group is referred to as "haloalkyl," e.g., "C 1~6 A preferred haloalkyl group is trifluoroalkyl (-CF3).

[0041] Similarly, "haloalkoxy" refers to an alkoxy group in which at least one halogen replaces each H in the hydrocarbon that makes up the alkyl portion of the alkoxy group. Examples of haloalkoxy groups are difluoromethoxy (-OCHF2) and trifluoromethoxy (-OCF3).

[0042] The term "heteroaryl" refers to an aromatic heterocyclic monocyclic, bicyclic, or tricyclic ring system of 5 to 14 ring atoms, preferably 5 to 10 ring atoms, and more preferably 5 to 6 ring atoms, containing 1, 2, 3, or 4 heteroatoms selected from N, O, and S, with the remaining ring atoms being carbon. In some embodiments, a monocyclic heteroaryl ring can be 5 to 6-membered. Bicyclic heteroaryl ring systems include fused bicycles having two fused 5-membered heteroaryl rings (designated 5-5), fused bicycles having a 5-membered aryl ring and a fused 6-membered heteroaryl ring (designated 5-6 and 6-5), and bicycles having two fused 6-membered aryl rings (designated 6-6). Heteroaryl groups may be optionally substituted as defined herein. Examples of heteroaryl include pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, triazinyl, isoxazolyl, benzofuranyl, isothiazolyl, benzothienyl, benzothiophenyl, indolyl, aza-indolyl, isoindolyl, isobenzofuranyl, benzimidazolyl, benzoxazolyl, benzimidazolyl, benzoxazolyl, benzimidazolyl, benzoxazolyl, benzo ...

[0033] Most preferably, "5-membered heteroaryl" is selected from the group: Points to TIFF0007821808000007.tif78170.

[0043] The term "heterocycle" or "heterocyclyl" refers to a 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-membered monocyclic, 7-, 8-, 9-, and 10-membered bicyclic (including bridged bicyclic and cycloalkyl spiro moieties), or 10-, 11-, 12-, 13-, 14-, and 15-membered bicyclic heterocyclic moiety that is saturated or partially unsaturated and has one or more (e.g., 1, 2, 3, or 4) heteroatoms selected from oxygen, nitrogen, and sulfur within the ring, with the remaining ring atoms being carbon. In some embodiments, a heterocycle is a heterocyclic ring. In certain embodiments, heterocycle or heterocyclyl refers to a 4-, 5-, 6-, or 7-membered heterocycle. When used in reference to a ring atom of a heterocycle, nitrogen or sulfur may also be in oxidized form, and the nitrogen may be substituted with one or more (C1-C6) alkyl or groups. A heterocycle can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure. Any of the heterocycle ring atoms may be substituted with one or more substituents described herein. Examples of such saturated or partially unsaturated heterocycles include tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, pyrrolidonyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, pyrrolidine 1-oxide, N-hydroxypiperidine, 1-methylpiperidinyl, 1-methylpyridin ... Examples of heterocyclic rings include, but are not limited to, rolidine N-oxide, diazirinyl, and quinuclidinyl. The term heterocycle also includes groups in which a heterocycle is fused to one or more aryl, heteroaryl, or cycloalkyl rings, such as indolinyl, 3H-indolyl, chromanyl, azabicyclo[2.2.1]heptanyl, azabicyclo[3.1.0]hexanyl, azabicyclo[3.1.1]heptanyl, octahydroindolyl, or tetrahydroquinolinyl.

[0044] The term "aryl" refers to a cyclic aromatic hydrocarbon moiety having a monocyclic, bicyclic, or tricyclic aromatic ring of 5 to 14 carbon ring atoms ("C 5~14"-aryl"). Bicyclic aryl ring systems include fused bicycles having two fused 5-membered aryl rings (designated 5-5), fused bicycles having a 5-membered aryl ring and a fused 6-membered aryl ring (designated 5-6 and 6-5), and bicycles having two fused 6-membered aryl rings (designated 6-6). Aryl groups may be substituted as defined herein. Examples of aryl moieties include, but are not limited to, phenyl, naphthyl, phenanthryl, fluorenyl, indenyl, pentalenyl, azulenyl, and the like. The term "aryl" also includes partially hydrogenated derivatives of cyclic aromatic hydrocarbon moieties, provided that at least one ring of the cyclic aromatic hydrocarbon moiety is aromatic and each is optionally substituted.

[0045] The term "haloaryl" refers to an aryl in which at least one hydrogen has been replaced with a halogen.

[0046] The term "hydroxy", alone or in combination with other groups, refers to OH.

[0047] The term "hydroxyalkyl" refers to an alkyl group in which one or more of the alkyl group's hydrogen atoms has been replaced by a hydroxy moiety. Examples include alcohols and diols.

[0048] The term "oxo", alone or in combination with other groups, refers to =0.

[0049] The term "pharmaceutically acceptable salt" refers to salts that retain the biological effectiveness and properties of the free base or free acid, which are not biologically or otherwise undesirable. Salts are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like, especially hydrochloric acid, and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, N-acetylcysteine, and the like.

[0050] Particularly preferred pharmaceutically acceptable salts of compounds of formula (I) are the salts of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, and methanesulfonic acid.

[0051] The term "protecting group" (PG) refers to a group that selectively blocks a reactive site in a polyfunctional compound so that a chemical reaction, in the sense conventionally associated with synthetic chemistry, can be carried out selectively at an otherwise unprotected reactive site. The protecting group can be removed at an appropriate time. Exemplary protecting groups are amino-protecting groups, carboxy-protecting groups, or hydroxy-protecting groups. Particular protecting groups are tert-butoxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenylmethoxycarbonyl (Fmoc), and benzyl (Bn). Further particular protecting groups are tert-butoxycarbonyl (Boc) and fluorenylmethoxycarbonyl (Fmoc). An even more particular protecting group is tert-butoxycarbonyl (Boc). Exemplary protecting groups and their uses in organic synthesis are described, for example, in "Protective Groups in Organic Chemistry" by T.W. Greene and P.G.M. Hutts, 5th Ed., 2014, John Wiley & Sons, NY.

[0052] The terms "moiety" and "substituent" refer to an atom or a set of chemically bonded atoms that is attached to another atom or molecule by one or more chemical bonds, thereby forming a part of the molecule.

[0053] When indicating the number of substituents, the term "one or more" refers to a range from one substituent to the highest possible number of substitutions, i.e., replacement of one hydrogen to replacement of all hydrogens by substituents; particularly "one or more" refers to one, two, or three; most particularly "one or more" refers to one or two.

[0054] The term "optionally substituted" means unsubstituted or substituted. Generally, the substituents can be the same or different.

[0055] "Optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes cases where the event or circumstance occurs and cases where it does not occur. For example, "an aryl group optionally substituted with an alkyl group" means that the alkyl may be present but does not have to be present, and that the description includes situations where the aryl group is substituted with an alkyl group and situations where the aryl group is not substituted with an alkyl group.

[0056] The term "substituted" refers to the replacement of at least one of the hydrogen atoms of a compound or moiety with another substituent or moiety. Examples of such substituents include, but are not limited to, halogen, -OH, -CN, oxo, alkoxy, alkyl, alkylene, aryl, heteroaryl, haloalkyl, haloalkoxy, cycloalkyl, and heterocycle. For example, the term "haloalkyl" refers to the fact that one or more hydrogen atoms of an alkyl (defined below) have been replaced with one or more halogen atoms (e.g., trifluoromethyl, difluoromethyl, fluoromethyl, chloromethyl, etc.). In one aspect, as used herein, substitution can refer to at least one hydrogen atom of a compound or moiety described herein being replaced with a halogen or alkyl.

[0057] The term "therapeutically inert carrier" refers to any non-toxic ingredient, such as a disintegrant, binder, filler, solvent, buffer, isotonicity agent, stabilizer, antioxidant, surfactant, or lubricant, which has no therapeutic activity and is used in formulating a pharmaceutical product.

[0058] The term "therapeutically effective amount" refers to an amount of a compound or molecule of the invention that, when administered to a subject, (i) treats or prevents a particular disease, condition, or disorder, (ii) attenuates, alleviates, or eliminates one or more symptoms of a particular disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of a particular disease, condition, or disorder described herein. A therapeutically effective amount may vary depending on the compound, the disease state being treated, the severity of the disease being treated, the age and relative health of the subject, the route and form of administration, the judgment of the attending physician or veterinarian, and other factors.

[0059] Whenever a chiral carbon is present in a chemical structure, all stereoisomers associated with that chiral carbon are intended to be encompassed by the structure, both as pure stereoisomers and as mixtures thereof.

[0060] All the separate embodiments can be combined.

[0061] "EC x The term "EC" is the half-maximal effective concentration and refers to the plasma concentration of a particular compound required to achieve x% of the maximum of a particular effect in vivo. x Examples of " EC values" are used to indicate the plasma concentrations of a particular compound required to achieve 20%, 50%, and 100% of the maximum in vivo effect of a particular compound, respectively. 20 , E.C. 50 and EC 100 is.

[0062] As used herein, the term "prophylaxis" means may be suffering from or predisposed to the condition, disorder or symptom, This includes preventing or delaying the appearance of clinical symptoms of a condition, disorder or condition that occurs in a mammal, particularly a human, who has not yet experienced or exhibited clinical or subclinical symptoms of the condition, disorder or condition.

[0063] The term "cancer" refers to diseases characterized by the presence of a neoplasia or tumor, resulting from the abnormal and uncontrolled proliferation of cells (such cells are "cancer cells"). As used herein, the term cancer expressly includes, but is not limited to, hepatocellular carcinoma, malignant tumors and hyperproliferative disorders of the colon (colon cancer), lung cancer, breast cancer, prostate cancer, melanoma, and ovarian cancer.

[0064] The following abbreviations are used herein: BOP = benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate, brine = saturated aqueous NaCl solution, CAS = Chemical Abstracts Registry Number, CDI = 1,1'-carbonyldiimidazole, DBU = 1,8-diazabicyclo[5,4,0]undec-7-ene, DCM = dichloromethane, DDQ = 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, DMF = N,N-dimethylformamide, DI PEA = N,N-diisopropylethylamine, EDC = 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, ESI = electrospray ionization, EtOAc = ethyl acetate, EtOH = ethanol, h = hour(s), HATU = 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate, HBTU = O-benzotriazole-N,N, N',N'-Tetramethyl-uronium-hexafluorophosphate, HFIP = hexafluoroisopropanol, HOBt = hydroxybenzotriazole, HPLC = high performance liquid chromatography, m-CPBA = meta-chloroperoxybenzoic acid, MeCN = acetonitrile, MeI = methyloid, MeOH = methanol, min = min(s), MS = mass spectrum, NBS = N-bromosuccinimide, PE = petroleum ether, PyBroP = bromo-tris-pyrrolidino-phosphonium hexafluorophosphate, RT = room temperature, TBAF = tetrabutylammonium fluoride, TBAOH = tetrabutylammonium hydroxide, TBDMS = tert-butyldimethylsilyl, TEA = triethylamine, TFA = trifluoroacetic acid, THF = tetrahydrofuran, TMSOTF = trifluoromethanesulfonic acid trimethylsilyl ester, TLC = thin layer chromatography

[0065] Compounds of the Invention In certain embodiments, the present invention provides a compound of formula (I) TIFF0007821808000008.tif48170 (in the formula, X is C(R 7 ) or N, Y is S, S(O), S(O)2、 S(O)N(R y ) and R 1 is a 5-membered heteroaryl, and R 1 is one or more R which may be the same or different 10 may be substituted with R 2 , R 3 and R 7 are each independently hydrogen, halogen, or C 1~6 -Alkyl, C 2~6 -Alkynyl, hydroxy, cyano, halo-C 1~6 -Alkyl, N(R 8 R 8a ), C 1~6 -alkoxy, C 3~7 -cycloalkyl and 3- to 10-membered heterocyclyl; R 4 is C 5~14 -aryl and 5- to 14-membered heteroaryl; R 4 is one or more R which may be the same or different 11 may be substituted with R 5 is hydrogen, C 1~6 -alkyl, -C(O)(R 9 ), amino, amino-C 1~6 -alkyl and C 3~7 -cycloalkyl, The C in question 3~7 -Cycloalkyl is one or more C 1~6 -Alkyl, Amino, Amino-C 1~6 -alkyl-, R 6 and R 6a are each independently hydrogen and C 1~6 -alkyl, R 8 and R 8a are each independently hydrogen and C 1~6 -alkyl, R 9 is C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, Amino-C1~6 -Alkyl- and -(C 1~6 -alkyl)-N(R 9a R 9b ) wherein the amino-C 1~6 -Alkyl is one or more hydroxy, hydroxy-C 1~6 -alkyl-, R 9a and R 9b are each independently hydrogen and C 1~6 -alkyl, wherein C 1~6 -alkyl may be substituted with one or more hydroxy or or R 9a and R 9b together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 10 teeth, x) one or more halogens, C 2~6 -Alkynyl, halo-C 1~6 -Alkyl, amino, hydroxy, 5-6 membered heteroaryl, C 1~6 -Haloalkoxy, C 1~6 -alkoxy, 3-10 membered cycloalkyl, C 1~3 -alkyl, -N(R 10a R 10b ), -S(O)2(C 1~6 -alkyl), -S(O)2(C 1~6 -cycloalkyl), 3-10 membered heterocyclyl, phenyl, cyano, -C(O)N(R 10c R 10d ) optionally substituted with C 1~10 -alkyl, and 3- to 10-membered heterocyclyl, 3- to 10-membered cycloalkyl, and phenyl are each independently one or more C 1~10 -Alkyl, C 1~10 -alkoxy, -S(O)2(C 1~6 -alkyl), oxo, halogen, C 2~6 -alkynyl, optionally substituted with 3- to 10-membered cycloalkyl, C 1~10 - alkyl, xi) one or more halogens, C 1~10 -Alkyl, -S(O)2(C1~6 alkyl), cyano, C 1~6 Haloalkyl, C 1~6 -alkoxy, hydroxy, oxo, amino, -C(O)N(R 10c R 10d ), =N(OH), hydroxy-C 1~6 - optionally substituted with alkyl, C 3~10 -cycloalkyl, xii) one or more halogens, C 1~10 -Alkyl, -S(O)2(C 1~6 -alkyl), -C 1~10 -Alkyl-C 1~4 -alkoxy, amino, -C(O)N(R 10h R 10i ), C 1~6 -haloalkyl, C 1~6 -Alkoxy, cyano, hydroxy-C 1~10 -Alkyl, oxo, -C(O)(C 1~6 -alkyl), -C(O)O-(R 10q ), C 3~10 -3-10 membered heterocyclyl optionally substituted by cycloalkyl; xiii) one or more halogens, C 1~10 -Alkyl, -S(O)2(C 1~6 -alkyl), xiv)-N(R 10e R 10f ), xv)-OR 10g , xvi)-C(O)NR 10h R 10i , xvii) one or more C 1~10 -Alkyl, halogen, -SO2(C 1~6 heteroaryl, optionally substituted with alkyl; xviii) oxo is selected from R 10a and R 10b are each independently hydrogen, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, Hydroxy-C 1~6-Alkyl, C 1~6 -alkoxy, -C(O)(R 10j ), amino-C 1~6 -Alkyl-, 3- to 10-membered heterocyclyl, -SO2(R 10k ), -C 1~6 -Alkyl-SO2(R 10k ) and -N(R 10l R 10m ) and 3-10 membered heterocyclyl is C 1~6 -substituted with alkyl, or R 10a and R 10b together with the nitrogen atom to which they are attached, one or more halogens, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl; R 10c and R 10d are each independently hydrogen and C 1~6 -alkyl, R 10e and R 10f are each independently vii) hydrogen, viii) optionally substituted with one or more cyano, in particular one cyano, halogen, hydroxy; C 1~6 - alkyl, ix)-C(O)R 10n , x) one or more C 2~6 -optionally substituted by alkynyl, -C 1~10 Alkyl ((OC 1~10 alkyl) m ) (wherein m is an integer between 1 and 5 (more specifically, m is 2 or 3)), xi) one or more of halogen, hydroxy, oxo, C 1~10 -Alkyl, Halo-C 1~10 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, -C(O)O(R 10o ), -C(O)(R 10o ), -C(O)N(R 10p )(R 10p’ ), -SO2(C1~6 -alkyl), optionally substituted by C2-6-alkynyl, C 3~10 -cycloalkyl, and xii) one or more halogen, hydroxy, oxo, C 1~10 -Alkyl, Halo-C 1~10 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, -C(O)O(R 10o ), -C(O)(R 10o ), -C(O)N(R 10p )(R 10p’ ), -SO2(C 1~6 -alkyl), 3- to 10-membered heterocyclyl optionally substituted with 3- to 10-membered cycloalkyl is selected from R 10g is Halo-C 1~6 -Alkyl, cyano, -C 1~10 -alkyl-phenyl, -C 1~6 -Alkyl-C 3~7 -cycloalkyl and -C 1~6 -Alkoxy-halo-C 1~6 -alkyl, R 10h and R 10i are each independently hydrogen and C 1~6 -Alkyl, C 1~6 -haloalkyl, C 1~6 -alkyl and C 1~6 -haloalkyl may be optionally substituted with one or more hydroxy or R 10h and R 10i together with the nitrogen atom to which they are attached, may contain one or more halogens, hydroxyl, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl; R 10j is C 1~6 -Alkyl, Halo-C 1~6 -Alkyl-, hydroxy-C 1~6 -Alkyl- and amino-C 1~6 -alkyl-, R 10kis hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 10l and R 10m are each independently hydrogen and C 1~6 -alkyl, R 10n is C 1~6 -Alkyl, Amino-C 1~6 -Alkyl-, Halo-C 1~6 -Alkyl, C 3~7 -cycloalkyl and 3- to 10-membered heterocyclyl, 3~7 -Cycloalkyl and 3- to 10-membered heterocyclyl are substituted with one or more halogens, C 1~6 - optionally substituted with alkyl, R 10o is hydrogen, halogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 10p and R 10p’ are independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 10q is C 1~10 -Alkyl, C 1~6 -haloalkyl, aryl, heteroaryl, wherein aryl and heteroaryl are each independently one or more halogens, C 1~10 - optionally substituted with alkyl, R 11 teeth, i) halogens, ii) hydroxy, iii) cyano, iv) one or more of cyano, halogen, hydroxyl, C 3~7 -Optionally substituted with cycloalkyl, amino, aryl (e.g., phenyl), -O-aryl (e.g., -O-phenyl), 5- to 6-membered heteroaryl, 3- to 7-membered heterocyclyl, C 1~10 -alkyl, and 3- to 7-membered heterocyclyl and aryl are each selected from the group consisting of one or more C 1~6 -Alkyl, -SO2(C1~6 -alkyl), optionally substituted with hydroxy, halogen, or cyano; C 1~10 - alkyl, v) one or more, particularly one, 3- to 10-membered heterocyclyl, optionally substituted with halogen, C 1~6 -alkoxy, vi) C 3~7 -cycloalkyl, vii) one or more halo-C 1~6 -Alkyl, Hydroxy, C 1~6 -Alkyl, C 3~10 -cycloalkyl, C 1~6 -3-10 membered heterocyclyl optionally substituted by alkoxy or oxo; viii) one or more C 1~6 -Alkyl, 3-10 membered cycloalkyl, halogen, halo-C 1~6 -Alkyl, C 1~6 -alkoxy, C 1~6 -5-6 membered heteroaryl optionally substituted with haloalkoxy; ix) one or more halogens, cyano, C 1~6 -alkoxy, C 1~6 -haloalkyl, C1-6-haloalkoxy, C 1~6 -phenyl, optionally substituted with alkyl; x)-O(R 11a ), xi)-C(O)N(R 11b R 11c ), xii)-SO2(R 11d ), xiii)-C(O)OR 11e , xiv)-C(O)R 11f , xviii) oxo, xvi)-N(R 11g R 11h ), and xvii)-S(R 11k ) is selected from R 11a is C 1~12 -Alkyl, Halo-C 1~6-Alkyl, Amino-C 1~12 -Alkyl-, hydroxy-C 1~6 -Alkyl-, cyano, C 2~6 -alkynyl, C 3~7 -cycloalkyl, 3- to 10-membered heterocyclyl, 3- to 10-membered -(C 1~6 -alkyl)heterocyclyl, 5-6 membered heteroaryl, phenyl, -C 1~6 -alkyl-phenyl, -C 1~12 -Alkyl-C(O)N(R 11i R 11j ), -C 1~12 -Alkyl-NH-C(O)(C 1~6 -alkyl), -C 1~12 -alkoxy-NH-C(O)(C 1~6 -alkyl), -C 1~6 -Alkyl-NH-C(O)(C 1~6 -alkyl), -(CH2CH2O) n -CH2CH2NH2 and -(CH2CH2O) n -CH2CH 2- NH-C(O)(C 1~6 -alkyl), The C in question 1~12 -Alkyl, C 3~7 -cycloalkyl, 3- to 10-membered heterocyclyl, 5- to 6-membered heteroaryl, phenyl, and -C 1~6 -Alkyl-phenyl is substituted with one or more halogens, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, C 1~6 -alkoxyl, C 1~6 - optionally substituted with haloalkoxyl, cyano; n is an integer between 1 and 6, particularly n is 2 or 3; R 11b and R 11c are each independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl; or R 11b and R 11c together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R11d is hydrogen, C 1~6 -alkyl, -N(R 11l R 11m ), Halo-C 1~6 - selected from alkyl and phenyl, R 11e is hydrogen and C 1~6 -alkyl, R 11f is hydrogen, C 1~6 - selected from alkyl and phenyl, R 11g and R 11h are each independently hydrogen, C 1~6 -alkyl, -(C 1~6 -alkyl)phenyl, halo-C 1~6 -Alkyl, -SO2(C 1~6 -Alkyl), -SO2(Halo-C 1~6 -alkyl) and -SO(C 1~6 -alkyl)2, R 11i and R 11j are each independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl; or R 11i and R 11j together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 11k is hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 11l and R 11m are each independently hydrogen and C 1~6 -alkyl; or R 11l and R 11m together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R y is hydrogen and C 1~6 -alkyl) or a pharmaceutically acceptable salt thereof.

[0066] In another embodiment, the present invention provides a compound of formula (I): TIFF0007821808000009.tif48170 (in the formula, X is C(R 7 ) or N, Y is S, S(O), S(O) 2、 S(O)N(R y ) and R 1 is a 5-membered heteroaryl, and R 1 is one or more R which may be the same or different 10 may be substituted with R 2 , R 3 and R 7 are each independently hydrogen, halogen, or C 1~6 -Alkyl, C 2~6 -Alkynyl, hydroxy, cyano, halo-C 1~6 -Alkyl, N(R 8 R 8a ), C 1~6 -alkoxy, C 3~7 -cycloalkyl and 3- to 10-membered heterocyclyl; R 4 is C 5~14 -aryl and 5- to 14-membered heteroaryl; R 4 is one or more R which may be the same or different 11 may be substituted with R 5 is hydrogen, C 1~6 -alkyl, -C(O)(R 9 ), amino, amino-C 1~6 -alkyl and C 3~7 -cycloalkyl, The C in question 3~7 -Cycloalkyl is one or more C 1~6 -Alkyl, Amino, Amino-C 1~6 -alkyl-, R 6 and R 6a are each independently hydrogen and C 1~6 -alkyl, R 8 and R 8a are each independently hydrogen and C 1~6 -alkyl, R 9 is C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, Amino-C 1~6 -Alkyl- and -(C 1~6 -alkyl)-N(R 9a R 9b ) wherein the amino-C 1~6 -Alkyl is one or more hydroxy, hydroxy-C 1~6 - optionally substituted with alkyl, R 9a and R 9b are each independently hydrogen and C 1~6 -alkyl, wherein C 1~6 -alkyl may be substituted with one or more hydroxy or or R 9a and R 9b together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 10 teeth, xxii) one or more halogens, C 2~6 -Alkynyl, halo-C 1~6 -Alkyl, amino, hydroxy, C 1~6 -alkoxy, -N(R 10a R 10b ), -S(O)2(C 1~6 -alkyl), -S(O)2(C1-6-cycloalkyl), 3- to 10-membered heterocyclyl, cyano, -C(O)N(R 10c R 10d ) optionally substituted with C 1~10 alkyl, and 3- to 10-membered heterocyclyl is one or more C 1~10 -alkyl, C1-10-alkoxy, oxo, optionally substituted with halogen, C 1~10 Alkyl, xxiii) one or more hydroxy, C 1~6 -Optionally substituted with alkoxy, amino, or phenyl, C1~10 -haloalkyl, and phenyl is one or more C 1~10 -alkyl, optionally substituted with halogen, C 1~10 -haloalkyl, xxiv) one or more amino, halogen, C 1~6 -haloalkyl, C 1~3 -alkyl, cyano, 3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl, C 1~6 -Haloalkoxy, C 1~6 amino-C optionally substituted with alkoxy 1~10 -alkyl-, and the 3- to 10-membered heterocyclyl and 3- to 10-membered cycloalkyl are selected from the group consisting of one or more halogens, C 2~6 -alkynyl, optionally substituted with 3- to 10-membered cycloalkyl, amino-C 1~10 -alkyl-, xxv) Hydroxy-C 1~10 -alkyl-, xxvi) C optionally substituted with one or more cyano 1~6 -alkoxy, xxvii)C 1~6 -Alkoxy-C 1~10 -alkyl-, xxviii) one or more halogens, C 1~10 -Alkyl, -S(O)2(C 1~6 alkyl), cyano, C 1~6 Haloalkyl, C 1~6 -alkoxy, hydroxy, oxo, amino, -C(O)N(R 10c R 10d ), =N(OH), hydroxy-C 1~6 - optionally substituted with alkyl, C 3~10 -cycloalkyl, xxix) one or more halogens, C 1~10 -Alkyl, -S(O)2(C 1~6 -alkyl), -C 1~10 -Alkyl-C 1~4 -alkoxy, amino, -C(O)N(R 10h R 10i ), C 1~6 -haloalkyl, C 1~6-Alkoxy, cyano, hydroxy-C 1~10 -Alkyl, oxo, -C(O)(C 1~6 -alkyl), -C(O)O-(R 10q ), C 3~10 -3-10 membered heterocyclyl optionally substituted by cycloalkyl; xxx)-(C 1~6 -alkyl)-C 3~7 -cycloalkyl, xxxi) one or more halogens, C 1~10 3-10-membered -(C 1~6 -alkyl)-heterocyclyl, xxxii) one or more halogens, C 1~10 -Alkyl, -S(O)2(C 1~6 -alkyl), xxxiii) -(C 1~10 -alkyl)-phenyl, C 1~10 -Alkyl is C 1~6 -alkyl, optionally substituted with cyano, -(C 1~10 -alkyl)-phenyl, xxxiv) 5-6-membered -(C 1~10 -alkyl)-heteroaryl, xxxv)-(alkoxy-C 1~10 -alkyl)-phenyl, xxxvi)-(amino-C 1~10 -alkyl)-phenyl, xxxvii)-C 1~6 -Alkyl-SO2(C 1~6 -alkyl), xxxviii)-N(R 10e R 10f ), xxxix)-OR 10g , and xl)-C(O)NR 10h R 10i , xli) one or more C 1~10 -Alkyl, halogen, -SO2(C 1~6heteroaryl, optionally substituted with alkyl; xlii) oxo is selected from R 10a and R 10b are each independently hydrogen, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, -C(O)(R 10j ), amino-C 1~6 -Alkyl-, 3- to 10-membered heterocyclyl, -SO2(R 10k ), -C 1~6 -Alkyl-SO2(R 10k ) and -N(R 10l R 10m ) and 3-10 membered heterocyclyl is C 1~6 -substituted with alkyl, or R 10a and R 10b together with the nitrogen atom to which they are attached, one or more halogens, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl; R 10c and R 10d are each independently hydrogen and C 1~6 -alkyl, R 10e and R 10f are each independently ix) hydrogen, x) optionally substituted with one or more cyanos, in particular one cyano, C 1~6 - alkyl, xi) Halo-C 1~6 -alkyl and halo-C 1~6 -alkyl may be substituted with one or more hydroxy, halo-C 1~6 - alkyl, xii) Hydroxy-C 1~6 - alkyl, xiii)-C(O)R 10n , xiv) one or more C 2~6-optionally substituted by alkynyl, -C 1~10 Alkyl ((OC 1~10 alkyl) m ) (wherein m is an integer between 1 and 5 (more specifically, m is 2 or 3)), xv) one or more halogen, hydroxy, oxo, C 1~10 -Alkyl, Halo-C 1~10 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, -C(O)O(R 10o ), -C(O)(R 10o ), -C(O)N(R 10p )(R 10p’ ), -SO2(C 1~6 -alkyl), optionally substituted by C2-6-alkynyl, C 3~10 -cycloalkyl, and xvi) one or more halogen, hydroxy, oxo, C 1~10 -Alkyl, Halo-C 1~10 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, -C(O)O(R 10o ), -C(O)(R 10o ), -C(O)N(R 10p )(R 10p’ ), -SO2(C 1~6 -alkyl), 3- to 10-membered heterocyclyl optionally substituted by 3- to 10-membered cycloalkyl Selected from or or R 10e and R 10f together with the nitrogen atom to which they are attached, may contain one or more halogens, amino, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, C 3~7 -cycloalkyl, -C(O)O(C 1~6 -alkyl), R 10g is Halo-C 1~6 -Alkyl, C1~6 -Alkyl-C 3~7 -cycloalkyl and C 1~6 -Alkoxy-halo-C 1~6 -alkyl, R 10h and R 10i are each independently hydrogen and C 1~6 -Alkyl, C 1~6 -haloalkyl, C 1~6 -alkyl and C 1~6 -haloalkyl may be optionally substituted with one or more hydroxy or R 10h and R 10i together with the nitrogen atom to which they are attached, may contain one or more halogens, hydroxyl, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl; R 10j is C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl and amino-C 1~6 -alkyl-, R 10k is hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 10l and R 10m are each independently hydrogen and C 1~6 -alkyl, R 10n is C 1~6 -Alkyl, Amino-C 1~6 -Alkyl-, Halo-C 1~6 -Alkyl, C 3~7 -cycloalkyl and 3- to 10-membered heterocyclyl, 3~7 -Cycloalkyl and 3- to 10-membered heterocyclyl are substituted with one or more halogens, C 1~6 - optionally substituted with alkyl, R 10o is C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 10p and R 10p’ are independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 10q is C 1~10 -Alkyl, C 1~6 -haloalkyl, aryl, heteroaryl, wherein aryl and heteroaryl are each independently one or more halogens, C 1~10 - optionally substituted with alkyl, R 11 teeth, i) halogens, ii) hydroxy, iii) cyano, iv) optionally substituted with one or more cyano, aryl, haloaryl; C 1~6 - alkyl, v) optionally substituted with one or more, particularly one, 3- to 10-membered heterocyclyl, C 1~6 -alkoxy, vi) Halo-C 1~6 - alkyl, vii) Amino-C 1~10 -alkyl-, viii) Hydroxy-C 1~6 - alkyl, ix) C 3~7 -cycloalkyl, x)-C 1~6 -Alkyl-C 3~7 -cycloalkyl, xi) one or more halo-C 1~6 -Alkyl, Hydroxy, C 1~6 -Alkyl, C 3~10 -cycloalkyl, C 1~6 -3-10 membered heterocyclyl optionally substituted by alkoxy or oxo; xii) one or more C 1~6 3- to 7-membered -(C 1~6 -alkyl)-heterocyclyl, xiii) one or more C 1~6 -Alkyl, 3-10 membered cycloalkyl, halogen, halo-C1~6 -Alkyl, C 1~6 -alkoxy, C 1~6 -5-6 membered heteroaryl optionally substituted with haloalkoxy; xiv) one or more halogens, cyano, C 1~6 -Alkoxy, Halo-C 1~6 -Alkyl, C 1~6 -Haloalkoxy, C 1~6 -phenyl, optionally substituted with alkyl; xv) one or more -SO2(C 1~6 -alkyl), hydroxy, halogen, cyano-substituted -(C 1~6 -alkyl)-phenyl, xvi)-(C 1~6 -alkyl)-O-phenyl, xvii) 5-6-membered -(C 1~6 -alkyl)-heteroaryl, xviii)-O(R 11a ), xix)-C(O)N(R 11b R 11c ), xx)-SO2(R 11d ), xxi)-C(O)OR 11e , xxii)-C(O)R 11f , xviii) oxo, xxiv)-N(R 11g R 11h ), xxv)-S(R 11k ), and xxvi)C 1~6 -Haloalkoxyl is selected from R 11a is C 1~12 -Alkyl, Halo-C 1~6 -Alkyl, Amino-C 1~12 -Alkyl-, hydroxy-C 1~6 -Alkyl, cyano, -C 1~6 -Alkyl, C 2~6 -alkynyl, C 3~7-cycloalkyl, 3- to 10-membered heterocyclyl, 3- to 10-membered -(C 1~6 -alkyl)heterocyclyl, 5-6 membered heteroaryl, phenyl, -C 1~6 -alkyl-phenyl, -C 1~12 -Alkyl-C(O)N(R 11i R 11j ), -C 1~12 -Alkyl-NH-C(O)(C 1~6 -alkyl), -C 1~12 -alkoxy-NH-C(O)(C 1~6 -alkyl), -C 1~6 -Alkyl-NH-C(O)(C 1~6 -alkyl), -(CH2CH2O) n -CH2CH2NH2 and -(CH2CH2O) n -CH2CH 2- NH-C(O)(C 1~6 -alkyl), The C in question 1~12 -Alkyl, C 3~7 -cycloalkyl, 3- to 10-membered heterocyclyl, 5- to 6-membered heteroaryl, phenyl, and -C 1~6 -Alkyl-phenyl is substituted with one or more halogens, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, C 1~6 -alkoxyl, C 1~6 - optionally substituted with haloalkoxyl, cyano; n is an integer between 1 and 6, R 11b and R 11c are each independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl; or R 11b and R 11c together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 11d is hydrogen, C 1~6 -alkyl, -N(R 11l R 11m ), Halo-C 1~6 - selected from alkyl and phenyl, R 11e is hydrogen and C 1~6 -alkyl, R 11f is hydrogen, C 1~6 - selected from alkyl and phenyl, R 11g and R 11h are each independently hydrogen, C 1~6 -alkyl, -(C 1~6 -alkyl)phenyl, halo-C 1~6 -Alkyl, -SO2(C 1~6 -Alkyl), -SO2(Halo-C 1~6 -alkyl) and -SO(C 1~6 -alkyl)2; or R 11g and R 11h together with the nitrogen atom to which they are attached, form C 1~6 -Alkyl, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkoxy; R 11i and R 11j are each independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl; or R 11i and R 11j together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 11k is hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 11l and R 11m are each independently hydrogen and C 1~6 -alkyl; or R 11l and R 11m together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R y is hydrogen and C 1~6 -alkyl) or a pharmaceutically acceptable salt thereof.

[0067] A particular embodiment of the present invention is a compound of formula (I) TIFF0007821808000010.tif48170 (in the formula, X is C(R 7 ) or N, Y is S, S(O), S(O) 2、 S(O)N(R y ) and R 1 is a 5-membered heteroaryl, and R 1 is one or more R which may be the same or different 10 may be substituted with R 2 , R 3 and R 7 are each independently hydrogen, halogen, or C 1~6 -Alkyl, C 2~6 -Alkynyl, hydroxy, cyano, halo-C 1~6 -Alkyl, N(R 8 R 8a ), C 1~6 -alkoxy, C 3~7 -cycloalkyl and 3- to 10-membered heterocyclyl; R 4 is C 5~14 -aryl and 5- to 14-membered heteroaryl; R 4 is one or more R which may be the same or different 11 may be substituted with R 5 is hydrogen, C 1~6 -alkyl, -C(O)(R 9 ), amino, amino-C 1~6 -alkyl and C 3~7 -cycloalkyl, The C in question 3~7 -Cycloalkyl is one or more C 1~6 -Alkyl, Amino, Amino-C 1~6 - optionally substituted with alkyl, R 6 and R 6aare each independently hydrogen and C 1~6 -alkyl, R 8 and R 8a are each independently hydrogen and C 1~6 -alkyl, R 9 is C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, Amino-C 1~6 -alkyl and (C 1~6 -alkyl)-N(R 9a R 9b ) wherein the amino-C 1~6 -Alkyl is one or more hydroxy, hydroxy-C 1~6 - optionally substituted with alkyl, R 9a and R 9b are each independently hydrogen and C 1~6 -alkyl, wherein C 1~6 -alkyl may be substituted with one or more hydroxy or or R 9a and R 9b together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 10 teeth, i) one or more halogens, C 2~6 -Alkynyl, halo-C 1~6 -Alkyl, amino, -N(R 10a R 10b ), -S(O)2(C 1~6 -alkyl), 3-10 membered heterocyclyl, cyano, -C(O)N(R 10c R 10d ) optionally substituted with C 1~10 - alkyl, ii) C 1~10 -haloalkyl, iii) Amino-C 1~10 -Alkyl iv) Hydroxy-C 1~10 - alkyl, v) C 1~6 -alkoxy, vi) C1~6 -Alkoxy-C 1~10 - alkyl, vii) one or more halogens, C 1~10 -Alkyl, -S(O)2(C 1~6 -alkyl), hydroxy, oxo, amino, -C(O)N(R 10c R 10d ), =N(OH), hydroxy-C 1~6 - optionally substituted with alkyl, C 3~10 -cycloalkyl, viii) one or more halogens, C 1~10 -Alkyl, -S(O)2(C 1~6 -alkyl), cyano, hydroxy-C 1~10 -Alkyl, oxo, -C(O)(C 1~6 -alkyl), -C(O)O-(C 1~6 -alkyl), C 3~10 -3-10 membered heterocyclyl optionally substituted by cycloalkyl; ix)(C 1~6 -alkyl)-C 3~7 -cycloalkyl, x) one or more halogens, C 1~10 -3 to 10-membered (C 1~6 -alkyl)-heterocyclyl, xi) phenyl, optionally substituted with one or more halogens; xii) optionally substituted with one or more halogens, (C 1~10 -alkyl)-phenyl, 1~10 -Alkyl is C 1~6 -alkyl, optionally substituted with cyano, (C 1~10 -alkyl)-phenyl, xiii) 5-6 membered (C 1~10 -alkyl)-heteroaryl, xiv) (alkoxy-C 1~10 -alkyl)-phenyl, xv) (amino-C 1~10 -alkyl)-phenyl, xvi)-C 1~6 -Alkyl-SO2(C 1~6-alkyl), xvii)-N(R 10e R 10f ), xviii)-OR 10g , and xix)-C(O)NR 10h R 10i is selected from R 10a and R 10b are each independently hydrogen, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, -C(O)(R 10j ), amino-C 1~6 -Alkyl, 3-10 membered heterocyclyl, -SO2(R 10k ), C 1~6 -Alkyl-SO2(R 10k ) and -N(R 10l R 10m ) and 3-10 membered heterocyclyl is C 1~6 -substituted with alkyl, or R 10a and R 10b together with the nitrogen atom to which they are attached, one or more halogens, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl; R 10c and R 10d are each independently hydrogen and C 1~6 -alkyl, R 10e and R 10f are each independently hydrogen, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, -C(O)R 10n , C 3~10 -cycloalkyl and 3- to 10-membered heterocyclyl, 3~10 -Cycloalkyl and 3- to 10-membered heterocyclyl are substituted with one or more of halogen, hydroxy, oxo, C 1~10-Alkyl, Halo-C 1~10 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, -C(O)O(R 10o ), -C(O)(R 10o ), -C(O)N(R 10p )(R 10p’ ), -SO2(C 1~6 -alkyl), or R 10e and R 10f together with the nitrogen atom to which they are attached, may contain one or more halogens, amino, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl, C 1~6 -alkoxy, C 3~7 -cycloalkyl, -C(O)O(C 1~6 -alkyl), R 10g is Halo-C 1~6 -Alkyl, C 1~6 -Alkyl-C 3~7 -cycloalkyl and C 1~6 -Alkoxy-halo-C 1~6 -alkyl, R 10h and R 10i are each independently hydrogen and C 1~6 -alkyl; or R 10h and R 10i together with the nitrogen atom to which they are attached, may contain one or more halogens, hydroxyl, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl; R 10j is C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, Hydroxy-C 1~6 -Alkyl and amino-C 1~6 -alkyl, R 10k is hydrogen, C 1~6 -Alkyl and halo-C1~6 -alkyl, R 10l and R 10m are each independently hydrogen and C 1~6 -alkyl, R 10n is C 1~6 -Alkyl, Amino-C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, C 3~7 -cycloalkyl and 3- to 10-membered heterocyclyl, 3~7 -Cycloalkyl and 3- to 10-membered heterocyclyl are substituted with one or more halogens, C 1~6 - optionally substituted with alkyl, R 10o is C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 10p and R 10p’ are independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 11 teeth, i) halogens, ii) hydroxy, iii) cyano, iv) C optionally substituted with one or more cyanos 1~6 - alkyl, v) C 1~6 -alkoxy, vi) Halo-C 1~6 - alkyl, vii) Amino-C 1~10 -Alkyl viii) Hydroxy-C 1~6 - alkyl, ix) C 3~7 -cycloalkyl, x)C 1~6 -Alkyl-C 3~7 -cycloalkyl, xi) one or more halo- 1~6 -Alkyl, Hydroxy, C 1~6 -Alkyl, C 1~6-3-10 membered heterocyclyl optionally substituted by alkoxy or oxo; xii) one or more C 1~6 -3 to 7-membered (C 1~6 -alkyl)-heterocyclyl, xiii) one or more C 1~6 -Alkyl, halogen, halo-C 1~6 -5-6 membered heteroaryl optionally substituted by alkyl; xiv) phenyl, optionally substituted with one or more halogens or cyanos; xv) one or more -SO2(C 1~6 -alkyl), hydroxy, halogen, cyano (C 1~6 -alkyl)-phenyl, xvi)(C 1~6 -alkyl)-O-phenyl, xvii) 5-6 membered (C 1~6 -alkyl)-heteroaryl, xviii)-O(R 11a ), xix)-C(O)N(R 11b R 11c ), xx)-SO2(R 11d ), xxi)-C(O)OR 11e , xxii)-C(O)R 11f , xviii) oxo, xxiv)-N(R 11g R 11h ), and xxv)-S(R 11k ) is selected from R 11a is C 1~12 -Alkyl, Halo-C 1~6 -Alkyl, Amino-C 1~12 -Alkyl, Hydroxy-C 1~6 -Alkyl, cyano, -C 1~6 -Alkyl, C 2~6 -alkynyl, C 3~7-cycloalkyl, 3- to 10-membered heterocyclyl, 5- to 6-membered heteroaryl, phenyl, -C 1~6 -Alkyl-phenyl, C 1~12 -Alkyl-C(O)N(R 11i R 11j ), -C 1~12 -Alkyl-NH-C(O)(C 1~6 -alkyl), -C 1~12 -alkoxy-NH-C(O)(C 1~6 -alkyl), -C 1~6 -Alkyl-NH-C(O)(C 1~6 -alkyl), -(CH2CH2O) n -CH2CH2NH2 and -(CH2CH2O) n -CH2CH 2- NH-C(O)(C 1~6 -alkyl), The C in question 1~12 -Alkyl, C 3~7 -cycloalkyl, 3- to 10-membered heterocyclyl, 5- to 6-membered heteroaryl, phenyl, and C 1~6 -Alkyl-phenyl is substituted with one or more halogens, C 1~6 -Alkyl, Halo-C 1~6 -optionally substituted with alkyl, cyano, n is an integer between 1 and 6, R 11b and R 11c are each independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl; or R 11b and R 11c together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 11d is hydrogen, C 1~6 -alkyl, -N(R 11l R 11m ), Halo-C 1~6 - selected from alkyl and phenyl, R 11e is hydrogen and C 1~6 -alkyl, R 11fis hydrogen, C 1~6 - selected from alkyl and phenyl, R 11g and R 11h are each independently hydrogen, C 1~6 -Alkyl, Halo-C 1~6 -Alkyl, SO2(C 1~6 -alkyl), SO2(halo-C 1~6 -alkyl) and SO(C 1~6 -alkyl)2; or R 11g and R 11h together with the nitrogen atom to which they are attached, form C 1~6 -Alkyl, C 1~6 -forms a 3- to 10-membered heterocyclyl optionally substituted by alkoxy; R 11i and R 11j are each independently hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl; or R 11i and R 11j together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R 11k is hydrogen, C 1~6 -Alkyl and halo-C 1~6 -alkyl, R 11l and R 11m are each independently hydrogen and C 1~6 -alkyl; or R 11l and R 11m together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R y is hydrogen and C 1~6 -alkyl) or a pharmaceutically acceptable salt thereof.

[0068] In one embodiment, there is provided a compound described herein, or a pharmaceutically acceptable salt thereof, having the formula (IA): TIFF0007821808000011.tif48170 (in the formula, X, Y, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 6a is as defined herein) is a compound of

[0069] Furthermore, the specific X, Y, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 6a , R 7 , R 8 , R 8a , R 9 , R 9a , R 9b , R 10 , R 10a , R 10b , R 10c , R 10d , R 10e , R 10f , R 10g , R 10h , R 10i , R 10j , R 10k , R 10l , R 10m , R 10n , R 10o , R 10p , R 10p’ , R 10q , R 11 , R 11a , R 11b , R 11c , R 11d , R 11e , R 11f , R 11g , R 11h , R 11i , R 11j , R 11k , R 11l , R 11m , and R y and other X, Y, R groups as disclosed herein. 1 , R2 , R 3 , R 4 , R 5 , R 6 , R 6a , R 7 , R 8 , R 8a , R 9 , R 9a , R 9b , R 10 , R 10a , R 10b , R 10c , R 10d , R 10e , R 10f , R 10g , R 10h , R 10i , R 10j , R 10k , R 10l , R 10m , R 10n , R 10o , R 10p , R 10p’ , R 10q , R 11 , R 11a , R 11b , R 11c , R 11d , R 11e , R 11f , R 11g , R 11h , R 11i , R 11j , R 11k , R 11l , R 11m , and R y It may be combined with any other embodiment relating to the above.

[0070] In one embodiment, X is N or C(R 7 ) and R 7 Provided are compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein is hydrogen or halogen.

[0071] In certain embodiments, there are provided compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein X is CH.

[0072] In one embodiment, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein Y is SO or S(O)2.

[0073] In one embodiment, R 1 At least one R 10 , more specifically, one R 10 or a pharmaceutically acceptable salt thereof, wherein the compound is substituted with

[0074] In one embodiment, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 1 teeth, Selected from TIFF0007821808000012.tif79170.

[0075] In one embodiment, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 1 teeth, Selected from TIFF0007821808000013.tif89170, R 1 is one or more R which may be the same or different as defined herein 10 and more specifically, R 1 is one R 10 may be substituted with.

[0076] In certain embodiments, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 1 teeth, Selected from TIFF0007821808000014.tif26170.

[0077] In one embodiment, R 2 But hydrogen, halogens, C 1~6 -alkyl, hydroxy or N(R 8 R 8a or a pharmaceutically acceptable salt thereof.

[0078] In more particular embodiments, there are provided compounds of formula (I) as described herein, or pharmaceutically acceptable salts thereof, wherein R 1 teeth, Selected from TIFF0007821808000015.tif26170, R 1 is R 1 may be the same or different as defined herein; 10 and more specifically, R 1 is one R 10 may be substituted with.

[0079] In certain embodiments, R 8 and R 8a are each independently hydrogen and C 1~6 -alkyl.

[0080] In another particular embodiment, R 2 is hydrogen, halogen or C 1~6 Provided are compounds of formula (I) as described herein, wherein R is -alkyl, or a pharmaceutically acceptable salt thereof.

[0081] In certain embodiments, R 2 is hydrogen, fluorine or methyl; or a pharmaceutically acceptable salt thereof.

[0082] In more particular embodiments, R 2 is hydrogen, fluorine, or a pharmaceutically acceptable salt thereof.

[0083] In one embodiment, R 3 Provided are compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

[0084] In one embodiment, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R4 teeth, Selected from TIFF0007821808000016.tif18170.

[0085] In one embodiment, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 4 teeth, Selected from TIFF0007821808000017.tif18170, R 4 is one or more R as defined herein 11 and more specifically, R 4 is one R 11 may be substituted with.

[0086] In another embodiment, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 4 teeth, The file is TIFF0007821808000018.tif17170.

[0087] In yet another embodiment, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 4 teeth, TIFF0007821808000019.tif17170, R 4 is one or more R as defined herein 11 and more specifically, R 4 is one R 11 may be substituted with.

[0088] In one embodiment, R 5 is hydrogen or -C(O)(R 9 or a pharmaceutically acceptable salt thereof.

[0089] In certain embodiments, R 5 is hydrogen or -C(O)(amino-C 1~6-alkyl), or a pharmaceutically acceptable salt thereof.

[0090] In more particular embodiments, R 5 is hydrogen or —C(O)(CH 2 NH 2 ), or a pharmaceutically acceptable salt thereof.

[0091] In one embodiment, R 6 and R 6a Provided are compounds of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

[0092] In certain embodiments, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 10 teeth, i) one or more C 2~6 -alkynyl, optionally substituted with cyano, C 1~10 - alkyl, ii) C 1~5 -Optionally substituted with alkoxy, amino, or phenyl, C 1~10 -haloalkyl, wherein phenyl is optionally substituted with one or more halogens; C 1~10 -haloalkyl, iii) C, optionally substituted with one or more halogens 3~10 -cycloalkyl, iv) one or more halogens, C 1~10 -phenyl, optionally substituted with alkyl; v) one or more halogens, C 1~10 heteroaryl optionally substituted with alkyl; vi) one or more C 1~10 -Alkyl, C 3~10 -cycloalkyl, C 1~6 -haloalkyl, halogen, -C 1~10 -Alkyl-C 1~4 -alkoxy, -C(O)OC 1~5 -3-10 membered heterocyclyl optionally substituted by alkyl; vii) C1~10 -Alkyl, C 1~10 -haloalkyl, C 3~10 -amino optionally substituted with cycloalkyl; 3~10 -Cycloalkyl is one or more C 1~5 -Alkyl, optionally substituted with halogen, amino is selected from.

[0093] In one embodiment, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 10 is C 1~10 -Alkyl, C 2~6 -alkynyl-substituted C 1~10 -Alkyl, C 1~10 -haloalkyl, amino-C 1~10 -Alkyl, Hydroxy-C 1~10 -Alkyl, C 3~10 -cycloalkyl, C substituted with one or more halogens 3~10 -cycloalkyl, phenyl substituted with one or more halogens, (C 1~10 -alkyl)-phenyl, (alkoxy-C 1~10 -alkyl)-phenyl, 3- to 10-membered heterocyclyl, one or more C 1~10 -3-10 membered heterocyclyl substituted with alkyl and halogen, and -N(R 10e R 10f ) is selected.

[0094] In certain embodiments, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 10 is C 1~10 -Alkyl, C 2~6 -alkynyl-substituted C 1~10 -Alkyl, C 1~10 -haloalkyl, amino-C 1~10 -Alkyl-, hydroxy-C 1~10 -Alkyl, C 3-10 -cycloalkyl, C substituted with one or more halogens 3-10-cycloalkyl, phenyl substituted with one or more halogens, -(C 1~10 -alkyl)-phenyl, -(alkoxy-C 1~10 -alkyl)-phenyl, 3- to 10-membered heterocyclyl, one or more C 1~10 -3-10 membered heterocyclyl, heteroaryl, one or more C substituted with alkyl and halogen 1~10 -heteroaryl substituted with alkyl, heteroaryl substituted with one or more halogens, and -N(R 10e R 10f ) is selected.

[0095] In one embodiment, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 10 is C 1~10 -Alkyl, C 1~10 -haloalkyl, C substituted with one or more halogens 3~10 -cycloalkyl, hydroxy-C 1~10 -Alkyl, C 2~6 -alkynyl-substituted C 1~10 -alkyl, 3- to 10-membered heterocyclyl, one or more C 1~10 -3-10 membered heterocyclyl substituted with alkyl and halogen, and -NH(C 3~7 -cycloalkyl).

[0096] In more particular embodiments, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, wherein R 10are tert-butyl, methyl 3-azabicyclo[3.1.1]heptane-3-carboxylate, 3-oxa-8-azabicyclo[3.2.1]octan-8-yl, 3,3-(difluorocyclobutyl)aminoyl, (trifluoromethyl)cyclopropyl, 2,2-difluoromorpholin-4-yl, 5,5-difluoro-1-methyl-3-piperidyl, 2,2,2-trifluoroethyl, (3,3-difluoro-1-methyl-cyclobutyl)aminoyl, o-tolyl, cyclobutyl aminoyl, 2-methyl-propanenitrile, 6-fluoro-2-methyl-3-pyridyl, 1,2,2,2-tetrafluoro-1-methoxy-ethyl, 4-oxa-7-azaspiro[2.5]octan-7-yl, ethyl, 1-amino-2,2,2-trifluoro-1-methyl-ethyl, morpholinyl, 1-amino-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl, methyl(2,2,2-trifluoroethyl)amino, 2,2-difluoromorpholin-4-yl, tert- t-butylaminoyl, cyclohexylaminoyl, methyl 4-methylpiperidine-1-carboxylate, 2-oxa-5-azabicyclo[4.1.0]heptan-5-yl, 2-(trifluoromethyl)morpholin-4-yl, 3,3-difluorocyclohexyl, 1,1-dimethylbut-3-ynyl, 3,3-difluorocyclobutyl, isobutyl, methyl 3,3-difluoropiperidine-1-carboxylate, difluorocyclopentyl, trifluoromethylmorpholinyl, 2, 2-difluorospiro[3.3]heptan-6-yl, difluorocyclohexyl, 5,5-difluoro-1-(2-methoxyethyl)-3-piperidyl, 1-ethyl-5,5-difluoro-3-piperidyl, 2-cyclopropyltetrahydrofuran-2-yl, 3-fluoro-1-methyl-3-piperidyl, 6-fluoro-2-methyl-3-pyridyl, 2-fluoro-6-methyl-phenyl, fluorophenyl, 1,2,2,2-tetrafluoro-1-methoxy-ethyl.

[0097] In certain embodiments, R 10is selected from ethyl, tertbutyl, isopropyl, —CHCF, —C((CH))F, —C((CH))CHOH, —C((CH))CHCCH, difluorocyclohexyl, difluorocyclobutyl, piperidyl substituted with fluorine and methyl, morpholinyl, and —NH(cyclopentyl), or a pharmaceutically acceptable salt thereof.

[0098] In one embodiment, R 11 But halogen, C 1~6 -Haloalkoxy, C 1~6 -alkoxy, -OR 11a , C 1~6 -Alkyl, cyano-substituted C 1~6 -alkyl.

[0099] In one embodiment, R 11 But halogen, C 1~6 -Haloalkoxy, C 1~6 -alkoxy, -O-aryl, -OC 3~10 -cycloalkyl, C 1~6 -Alkyl, cyano-substituted C 1~6 -alkyl.

[0100] In one embodiment, R 11 But halogen, -O(R 11a ), cyano, amino-C 1~10 -Alkyl-, -SO2(C 1~6 -alkyl) and one or more halo-C 1~6 -3-10 membered heterocyclyl substituted with alkyl, or a pharmaceutically acceptable salt thereof.

[0101] In one embodiment, R 11is selected from chloro, fluoro, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, phenoxy, 2-methyl-propanenitrile, isopropoxy, methoxy, cyclopentoxy, or a pharmaceutically acceptable salt thereof.

[0102] In one embodiment, R 11 But halogen, -O(R 11a ), cyano, amino-C 1~10 -Alkyl-, -SO2(C 1~6 -alkyl) and one or more halo-C 1~6 -3-10 membered heterocyclyl substituted with alkyl, or a pharmaceutically acceptable salt thereof.

[0103] In certain embodiments, R 11a But C 1~12 -Alkyl, halo- 1~6 -alkyl, 3- to 7-membered heterocycloalkyl and amino-C 1~12 -alkyl.

[0104] In more particular embodiments, R 11 But halogen, -O(halo-C 1~6 -alkyl), -O(C 1~6 -alkyl), cyano and one or more halo-C 1~6 -3-10 membered heterocyclyl substituted with alkyl, or a pharmaceutically acceptable salt thereof.

[0105] In even more particular embodiments, R 11 is selected from chlorine, —OCF 3 , —OCH 3 , cyano, and 3-trifluoromethyl-diazirin-3-yl; or a pharmaceutically acceptable salt thereof.

[0106] In an even more particular embodiment, there is provided a compound of formula (I), as described herein, or a pharmaceutically acceptable salt thereof: X is N or C(R 7 ) and Y is S, SO or S(O)2; R 1 teeth, Selected from TIFF0007821808000020.tif69170, R 2 is hydrogen, halogen, C 1~6 -alkyl, hydroxy or N(R 8 R 8a ) and R 3 is hydrogen, R 4 teeth, Selected from TIFF0007821808000021.tif18170, R 5 is hydrogen or -C(O)(R 9 ) and R 6 and R 6a is hydrogen, R 7 is hydrogen or halogen, R 8 and R 8a are each independently hydrogen and C 1~6 -alkyl, R 9 is amino-C 1~6 -alkyl, R 10 is C 1~10 -Alkyl, C 2~6 -alkynyl-substituted C 1~10 -Alkyl, C 1~10 -haloalkyl, amino-C 1~10 -Alkyl, Hydroxy-C 1~10 -Alkyl, C 3~10 -cycloalkyl, C substituted with one or more halogens 3~10 -cycloalkyl, phenyl substituted with one or more halogens, (C 1~10 -alkyl)-phenyl, (alkoxy-C1~10 -alkyl)-phenyl, 3- to 10-membered heterocyclyl, one or more C 1~10 -3-10 membered heterocyclyl substituted with alkyl and halogen, and -N(R 10e R 10f ) and R 10e is hydrogen and R 10f is C 3~7 -cycloalkyl, R 11 is a halogen, -O(R 11a ), cyano, amino-C 1~10 -Alkyl, -S(O2)(C 1~6 -alkyl) and one or more halo-C 1~6 -3-10 membered heterocyclyl substituted with alkyl; R 11a is C 1~12 -Alkyl, Halo-C 1~6 -Alkyl, 3- to 7-membered heterocycloalkyl, amino-C 1~12 -alkyl.

[0107] In another embodiment, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: X is N or C(R 7 ) and Y is S, SO or S(O)2; R 1 teeth, Selected from TIFF0007821808000022.tif69170, R 1 is one or more R which may be the same or different 10 may be substituted with R 2 is hydrogen, halogen, C 1~6 -alkyl, hydroxy or N(R 8 R 8a ) and R 3 is hydrogen, R 4 teeth, Selected from TIFF0007821808000023.tif18170, R 5 is hydrogen or -C(O)(R 9 ) and R 6 and R 6a is hydrogen, R 7 is hydrogen or halogen, R 8 and R 8a are each independently hydrogen and C 1~6 -alkyl, R 9 is amino-C 1~6 -alkyl, R 10 is C 1~10 -Alkyl, C 2~6 -alkynyl-substituted C 1~10 -Alkyl, C 1~10 -haloalkyl, amino-C 1~10 -Alkyl, Hydroxy-C 1~10 -Alkyl, C 3~10 -cycloalkyl, C substituted with one or more halogens 3~10 -cycloalkyl, phenyl substituted with one or more halogens, (C 1~10 -alkyl)-phenyl, (alkoxy-C 1~10 -alkyl)-phenyl, 3- to 10-membered heterocyclyl, one or more C 1~10 -3-10 membered heterocyclyl substituted with alkyl and halogen, and -N(R 10e R 10f ) and R 10e is hydrogen and R 10f is C 3~7 -cycloalkyl, R 11 is a halogen, -O(R 11a ), cyano, amino-C 1~10 -Alkyl, -S(O2)(C 1~6 -alkyl) and one or more halo-C 1~6 -3-10 membered heterocyclyl substituted with alkyl; R 11a is C 1~12 -Alkyl, Halo-C 1~6 -Alkyl, 3- to 7-membered heterocycloalkyl, amino-C 1~12 -alkyl.

[0108] In certain embodiments, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: X is N or C(R 7 ) and Y is S, SO or S(O)2; R 1 teeth, Selected from TIFF0007821808000024.tif75170, R 1 is one or more R which may be the same or different 10 may be substituted with R 2 is hydrogen, halogen, C 1~6 -alkyl, hydroxy or N(R 8 R 8a ) and R 3 is hydrogen, R 4 teeth, Selected from TIFF0007821808000025.tif30170, R 5 is hydrogen or -C(O)(R 9 ) and R 6 and R 6a is hydrogen, R 7 is hydrogen or halogen, R 8 and R 8a are each independently hydrogen and C 1~6 -alkyl, R 9 is amino-C 1~6 -alkyl, R 10 is C 1~10 -Alkyl, C 2~6-alkynyl-substituted C 1~10 -Alkyl, C 1~10 -haloalkyl, amino-C 1~10 -Alkyl, Hydroxy-C 1~10 -Alkyl, C 3~10 -cycloalkyl, C substituted with one or more halogens 3~10 -cycloalkyl, phenyl substituted with one or more halogens, (C 1~10 -alkyl)-phenyl, (alkoxy-C 1~10 -alkyl)-phenyl, 3- to 10-membered heterocyclyl, one or more C 1~10 -3-10 membered heterocyclyl substituted with alkyl and halogen, -N(R 10e R 10f ) and R 10e is hydrogen and R 10f is C 3~7 -cycloalkyl, R 11 is a halogen, -O(R 11a ), cyano, amino-C 1~10 -Alkyl, -S(O2)(C 1~6 -alkyl) and one or more halo-C 1~6 -3-10 membered heterocyclyl substituted with alkyl; R 11a is C 1~12 -Alkyl, Halo-C 1~6 -Alkyl, 3- to 7-membered heterocycloalkyl, amino-C 1~12 -alkyl.

[0109] In a more particular embodiment, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: X is CH, Y is SO or S(O)2; R 1 teeth, Selected from TIFF0007821808000026.tif18170, R 2 But hydrogen, halogens, C 1~6 -alkyl, R 3 is hydrogen, R 4 teeth, TIFF0007821808000027.tif17170, R 5 is hydrogen or -C(O)(amino-C 1~6 -alkyl), R 6 and R 6a is hydrogen, R 10 is C 1~10 -Alkyl, C 1~10 -haloalkyl, C substituted with one or more halogens 3~10 -cycloalkyl, hydroxy-C 1~10 -Alkyl, C 2~6 -alkynyl-substituted C 1~10 -alkyl, 3- to 10-membered heterocyclyl, one or more C 1~10 -3-10 membered heterocyclyl substituted with alkyl and halogen, -NH(C 3~7 -cycloalkyl), R 11 is a halogen, -O(halo-C 1~6 -alkyl), -O(C 1~6 -alkyl), cyano, one or more halo-C 1~6 -3-10 membered heterocyclyl substituted with alkyl.

[0110] In another particular embodiment, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: X is CH; Y is SO or S(O)2; R 1 teeth, Selected from TIFF0007821808000028.tif18170, R 2 is hydrogen, fluorine or methyl, R 3 is hydrogen, R 4 teeth, Selected from TIFF0007821808000029.tif17170 R 5 is hydrogen or —C(O)(CH2NH2), R 6 and R 6a is hydrogen, R 10 is selected from ethyl, tertbutyl, isopropyl, —CHCF, —C((CH)F, —C((CH))CHOH, —C((CH))CHCCH, difluorocyclohexyl, difluorocyclobutyl, piperidyl substituted with fluorine and methyl, morpholinyl, —NH(cyclopentyl); R 11 is selected from chlorine, —OCF3, —OCH3, cyano, 3-trifluoromethyl-diazirin-3-yl.

[0111] In a more particular embodiment, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: X is CH; Y is SO or S(O)2; R 1 teeth, Selected from TIFF0007821808000030.tif25170, R 1 may be the same or different, and one or more R 10 may be substituted with R 2 is hydrogen, halogen, C 1~6 -alkyl, R 3 is hydrogen, R 4 teeth, TIFF0007821808000031.tif35170, R 5 is hydrogen or -C(O)(amino-C 1~6 -alkyl), R 6 and R 6a is hydrogen, R 10 teeth, One or more C's2~6 -alkynyl, optionally substituted with cyano, C 1~10 - alkyl, C 1~5 -Optionally substituted with alkoxy, amino, or phenyl, C 1~10 -haloalkyl, wherein phenyl is optionally substituted with one or more halogens; C 1~10 -haloalkyl C, optionally substituted with one or more halogens 3~10 -cycloalkyl, One or more halogens, C 1~10 -phenyl, optionally substituted with alkyl; One or more halogens, C 1~10 heteroaryl optionally substituted with alkyl; One or more C's 1~10 -Alkyl, C 3~10 -cycloalkyl, C 1~6 -haloalkyl, halogen, -C 1~10 -Alkyl-C 1~4 -alkoxy, -C(O)OC 1~5 -3-10 membered heterocyclyl optionally substituted by alkyl; C 1~10 -Alkyl, C 1~10 -haloalkyl, C 3~10 -amino optionally substituted with cycloalkyl; 3~10 -Cycloalkyl is one or more C 1~5 -Alkyl, optionally substituted with halogen, amino is selected from R 11 is a halogen, -O(halo-C 1~6 -alkyl), -O(C 1~6 -alkyl), cyano, one or more halo-C 1~6 -3-10 membered heterocyclyl substituted with alkyl.

[0112] In another particular embodiment, there is provided a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof: X is CH; Y is SO or S(O)2; R 1 teeth, Selected from TIFF0007821808000032.tif25170 R 1 is one or more R which may be the same or different 10 may be substituted with R 2 is hydrogen, fluorine or methyl, R 3 is hydrogen, R 4 teeth, Selected from TIFF0007821808000033.tif35170, R 5 is hydrogen or —C(O)(CH2NH2), R 6 and R 6a is hydrogen, R 10are tert-butyl, methyl 3-azabicyclo[3.1.1]heptane-3-carboxylate, 3-oxa-8-azabicyclo[3.2.1]octan-8-yl, 3,3-(difluorocyclobutyl)aminoyl, (trifluoromethyl)cyclopropyl, 2,2-difluoromorpholin-4-yl, 5,5-difluoro-1-methyl-3-piperidyl, 2,2,2-trifluoroethyl, (3,3-difluoro-1-methyl-cyclobutyl)aminoyl, o-tolyl, cyclobutyl methylaminoyl, 2-methyl-propanenitrile, 6-fluoro-2-methyl-3-pyridyl, 1,2,2,2-tetrafluoro-1-methoxy-ethyl, 4-oxa-7-azaspiro[2.5]octan-7-yl, ethyl, 1-amino-2,2,2-trifluoro-1-methyl-ethyl, morpholinyl, 1-amino-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl, methyl(2,2,2-trifluoroethyl)amino, 2,2-difluoromorpholin-4-yl, te rt-butylaminoyl, cyclohexylaminoyl, methyl 4-methylpiperidine-1-carboxylate, 2-oxa-5-azabicyclo[4.1.0]heptan-5-yl, 2-(trifluoromethyl)morpholin-4-yl, 3,3-difluorocyclohexyl, 1,1-dimethylbut-3-ynyl, 3,3-difluorocyclobutyl, isobutyl, methyl 3,3-difluoropiperidine-1-carboxylate, difluorocyclopentyl, trifluoromethylmorpholinyl, 2 , 2-difluorospiro[3.3]heptan-6-yl, difluorocyclohexyl, 5,5-difluoro-1-(2-methoxyethyl)-3-piperidyl, 1-ethyl-5,5-difluoro-3-piperidyl, 2-cyclopropyltetrahydrofuran-2-yl, 3-fluoro-1-methyl-3-piperidyl, 6-fluoro-2-methyl-3-pyridyl, 2-fluoro-6-methyl-phenyl, fluorophenyl, 1,2,2,2-tetrafluoro-1-methoxy-ethyl, R 11 is selected from chlorine, —OCF3, —OCH3, cyano, 3-trifluoromethyl-diazirin-3-yl.

[0113] In even more particular embodiments, there are provided compounds of formula (I) described herein selected from: (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)-1,2,4-oxadiazol-3-yl]-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-ethyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[3-fluoro-1-(2-methoxyethyl)-3-piperidyl]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)-1,2,4-oxadiazol-3-yl]-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-8-fluoro-5-[(4-fluorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-morpholino-1,2,4-oxadiazol-3-yl)-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-3-yl]-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-3-yl]-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-Amino-8-fluoro-5-[(6-isopropoxy-3-pyridyl)methyl]-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[2-(difluoromethyl)morpholin-4-yl]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-7-[5-[2-(trifluoromethyl)morpholin-4-yl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-(5-morpholino-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-7-[5-[2-(trifluoromethyl)morpholin-4-yl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 3-[5-[(3R)-3-amino-5-[[4-(cyclopentoxy)phenyl]methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]pyrrolidine-1-carboxylate; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-[2-(trifluoromethyl)morpholin-4-yl]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-8-fluoro-5-[(5-isopropoxy-2-pyridyl)methyl]-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2-Amino-N-[(3R)-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]acetamide (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(6-methyl-3-pyridyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,6-dimethyl-3-pyridyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-8-fluoro-7-[5-[2-(hydroxymethyl)tetrahydrofuran-2-yl]-1,2,4-oxadiazol-3-yl]-1,1-dioxo-5-[(4-phenoxyphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2-[5-[(3R)-3-amino-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methyl-propanenitrile; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(1-fluoro-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-8-fluoro-7-[5-(1-fluoro-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-5-[(4-fluorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(2,2-difluoromorpholin-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[(4-phenoxyphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(3-aminooxetan-3-yl)-1,2,4-oxadiazol-3-yl]-8-fluoro-5-[[4-(4-methoxyphenyl)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(6-fluoro-2-methyl-3-pyridyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-methyl-4-methylsulfonyl-phenyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-methyl-5-methylsulfonyl-phenyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-methyl-3-pyridyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[(1R,5S)-3-oxa-8-azabicyclo[3.2.1]octan-8-yl]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-dimethylmorpholin-4-yl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2-methyl-4-methylsulfonyl-phenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 3-[3-[(3R)-3-amino-5-[[4-(cyclopentoxy)phenyl]methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]pyrrolidine-1-carboxylate (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluoromorpholin-4-yl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[[4-(cyclopentoxy)phenyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-8-fluoro-7-[5-(3-fluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-5-[(4-phenoxyphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(6-fluoro-2-methyl-3-pyridyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,6-dimethyl-3-pyridyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluoro-1-methoxy-cyclohexyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-fluoro-6-methyl-phenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; Methyl 4-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-4-methoxy-piperidine-1-carboxylate; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(5-methyl-1,3,4-oxadiazol-2-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl N-[2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methyl-1-(trifluoromethyl)propyl]carbamate; (3R)-3-amino-7-[5-(2-amino-3,3,3-trifluoro-1,1-dimethyl-propyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-N-(3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)-1,2,4-oxadiazole-5-carboxamide; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[2-(hydroxymethyl)tetrahydrofuran-2-yl]-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-8-fluoro-7-[5-(5-methyl-1,3,4-oxadiazol-2-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-[1-amino-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl]-1,2,4-oxadiazol-3-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-8-fluoro-7-[5-(5-methyl-1,3,4-oxadiazol-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[2-(trifluoromethyl)morpholin-4-yl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-8-fluoro-7-[5-[2-(hydroxymethyl)tetrahydrofuran-2-yl]-1,2,4-oxadiazol-3-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2-fluorophenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-(p-tolyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-fluorophenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(m-tolyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(p-tolyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-oxa-5-azabicyclo[2.2.1]heptane-5-carboxylate (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-1-tetrahydropyran-4-yl-ethyl)-1,2,4-oxadiazol-3-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-N-(2,2-difluoropropyl)-1,2,4-oxadiazole-5-carboxamide; (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-7-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-N-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole-5-carboxamide; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-(5-phenyl-1,3,4-oxadiazol-2-yl)-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(o-tolyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-(5-phenyl-1,3,4-oxadiazol-2-yl)-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 3-[5-[(3R)-3-amino-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]pyrrolidine-1-carboxylate; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(5-methyl-2-pyridyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(6-methyl-3-pyridyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[(3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)amino]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[[1-(2-hydroxyethyl)cyclohexyl]amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-benzyl-8-fluoro-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(3-aminooxetan-3-yl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(6-fluoro-3-pyridyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[(4-phenoxyphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(5-fluoro-2-pyridyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluoropropylamino)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2-[[3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]amino]-2-methyl-propanenitrile (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(1-methoxycyclopropyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-(2,2,2-trifluoro-1-methoxy-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4-methoxytetrahydropyran-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(1,1,2,2,2-pentafluoroethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one N-[11-[4-[[(3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-5-yl]methyl]phenoxy]undecyl]-3-[2,2-difluoro-12-(1H-pyrrol-2-yl)-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-penta (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(1-methoxy-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(1-ethynylcyclohexyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-imino-1-oxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(9,9-difluoro-3-oxa-7-azabicyclo[3.3.1]nonan-7-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[4,4-difluoro-3-(hydroxymethyl)-1-piperidyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-dimethylmorpholin-4-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one Methyl 4-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-4-cyano-piperidine-1-carboxylate (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluoro-1,8-diazaspiro[4.5]decan-8-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(1-methyl-1-pyrrolidin-1-yl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[4-methyl-1-oxido-1-(2,2,2-trifluoroethyl)piperidin-1-ium-4-yl]-1,2,4-oxadiazol-3-yl]-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; 2-[4-[[(3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-5-yl]methyl]phenyl]-2-methyl-propanenitrile (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(1S,5R)-6,6-difluoro-3-azabicyclo[3.1.1]heptan-3-yl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-4-methyl-piperidine-4-carbonitrile; (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[[1,1-dimethyl-4-(2-prop-2-ynoxyethoxy)butyl]amino]-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one 3-[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-N,N-dimethyl-1,2,4-oxadiazole-5-carboxamide; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(6-chloropyridazin-3-yl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoroethylamino)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[1,1-dimethyl-4-[2-(2-prop-2-ynoxyethoxy)ethoxy]butyl]-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[2-(5,5-difluoro-1-methylsulfonyl-3-piperidyl)tetrazol-5-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 5-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]tetrazol-2-yl]-3,3-difluoro-piperidine-1-carboxylate 2-[[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]amino]-2-methyl-propanenitrile; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[4-methyl-1-(2,2,2-trifluoroethyl)-4-piperidyl]-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluoropropylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1-bicyclo[1.1.1]pentanylamino)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[(3,3,3-trifluoro-1-methyl-propyl)amino]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[(4-tetrahydropyran-4-yloxyphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[3-[(3R)-3-amino-8-fluoro-1-imino-1,4-dioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate Methyl 1-[3-[(3R)-3-amino-8-fluoro-1,4-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 4,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1-imino-1-oxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-7-(2-tert-butyltetrazol-5-yl)-8-fluoro-1,1-dioxo-5-[[4-(tetrahydropyran-4-ylmethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-8-fluoro-1,1-dioxo-5-[[4-(tetrahydropyran-4-ylmethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(cyclopropoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[3-[(3R)-3-amino-8-fluoro-1,4-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 4,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-7-[2-(1-acetyl-5,5-difluoro-3-piperidyl)tetrazol-5-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one N-[(3R)-5-[(4-chlorophenyl)methyl]-7-[2-(5,5-difluoro-3-piperidyl)tetrazol-5-yl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]acetamide; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(1,5,5-trimethyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(cyclohexoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[3-[(3R)-3-amino-8-fluoro-1,4-dioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 4,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-3-Amino-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one (3R)-3-Amino-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[[(1S)-1-methyl-2-(trifluoromethoxy)ethyl]amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-benzyl-7-[2-(5,5-difluoro-1-methyl-3-piperidyl)tetrazol-5-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[2-(5,5-difluoro-1-methyl-3-piperidyl)tetrazol-5-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[[4-(tetrahydropyran-4-ylmethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-7-[8-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazin-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-8-fluoro-5-[(4-fluorophenyl)methyl]-1-oxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-8-fluoro-5-[(4-fluorophenyl)methyl]-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[[4-[[5-(trifluoromethyl)-2-pyridyl]oxy]phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[3-[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(4-fluorophenoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate Methyl 1-[3-[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-7-(2-tert-butyltetrazol-5-yl)-8-fluoro-5-[(4-fluorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-1-oxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-1-oxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-1-oxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-1-oxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-ethyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Isopropyl 1-[3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate Ethyl 1-[3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[1-(2,2-difluorocyclopropyl)ethylamino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[1-(2,2-difluorocyclopropyl)ethylamino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[1-(3,3-difluorocyclobutyl)ethylamino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[(3,3,3-trifluoro-1,1-dimethyl-propyl)amino]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[1-methyl-1-(2,2,2-trifluoroethylamino)ethyl]-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 3-[3-[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]pyrrolidine-1-carboxylate; Methyl 1-[5-[(3R)-3-amino-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-5-[(6-isopropoxy-3-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[[3-(trifluoromethyl)cyclobutyl]amino]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoroethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 1-[5-[(3R)-3-amino-1,1,4-trioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-3-amino-7-[5-[(3-chloro-1-bicyclo[1.1.1]pentanyl)amino]-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(1,1,2,2,2-pentafluoroethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluoro-1-methyl-cyclobutyl)amino]-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-[(3R)-1-methylpyrrolidin-3-yl]tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-[(3S)-1-methylpyrrolidin-3-yl]tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-N,N-dimethyl-1,2,4-oxadiazole-5-carboxamide; 3-[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-N,N-dimethyl-1,2,4-oxadiazole-5-carboxamide; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[1-(5,5-difluoro-1-methyl-3-piperidyl)pyrazol-4-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-[(2-amino-3,3,3-trifluoro-propyl)amino]-1,2,4-oxadiazol-3-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[(4-pyrrolidin-1-ylphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (6-methyl-3-pyridyl)4-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-4-methyl-piperidine-1-carboxylate; (3R)-3-amino-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-5-[(5-isopropoxy-2-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(1-ethyl-4-methyl-4-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2-[3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-2-methyl-propanenitrile; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-dimethyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroethyl 4-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-4-methyl-piperidine-1-carboxylate; Methyl 4-[3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-4-methyl-piperidine-1-carboxylate; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[[1-(2,2,2-trifluoroethyl)-3-piperidyl]amino]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[2-(2-amino-3,3,3-trifluoro-propyl)tetrazol-5-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 4-[3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-N,4-dimethyl-piperidine-1-carboxamide; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[4-methyl-1-(pyrrolidine-1-carbonyl)-4-piperidyl]-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[(2,2,2-trifluoro-1-methyl-ethyl)amino]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 3-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]tetrazol-2-yl]pyrrolidine-1-carboxylate (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclobutyl)amino]-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(4-cyclopropylpiperazin-1-yl)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(4-methoxy-1-piperidyl)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(cyclopropylmethoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(2,2-difluoroethoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-but-2-ynoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-morpholinophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[3-(trifluoromethyl)piperazin-1-yl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroacetic acid (3R)-3-amino-1,1-dioxo-7-[5-(1,1,2,2,2-pentafluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclohexyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclobutyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluoro-1-methyl-cyclobutyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2-[4-[[(3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-5-yl]methyl]phenyl]-2-methyl-propanenitrile (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluoro-1-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-morpholino-1,2,4-oxadiazol-3-yl)-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(cyclobutylamino)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-7-[2-(1-acetyl-3-piperidyl)tetrazol-5-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-(1-methyl-3-piperidyl)tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(3-tert-butyl-1,2,4-triazol-1-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-7-[5-[1-methyl-1-(methylamino)ethyl]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[3-(dimethylamino)-1,1-dimethyl-propyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 3-[(3R)-3-Amino-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-N-tert-butyl-1,2,4-oxadiazole-5-carboxamide 3-[(3R)-3-Amino-8-fluoro-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-N-tert-butyl-1,2,4-oxadiazole-5-carboxamide 3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-N-tert-butyl-1,2,4-oxadiazole-5-carboxamide 3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-N-tert-butyl-1,2,4-oxadiazole-5-carboxamide (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(dimethylamino)methyl]-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-[5-(1-aminocyclopentyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[cyclopropyl(methyl)amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[methyl(2,2,2-trifluoroethyl)amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[[3,3-difluoro-1-(methoxymethyl)cyclobutyl]amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-7-[5-(4-aminotetrahydropyran-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-[5-(1-aminocyclohexyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(1-hydroxy-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroacetic acid (3R)-3-Amino-7-(2-tert-butyltetrazol-5-yl)-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(2-tert-butyltetrazol-5-yl)-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-(1-methylsulfonyl-3-piperidyl)tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluoro-1-methyl-cyclobutyl)amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclobutyl)amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclohexyl)amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(4-tert-butylimidazol-1-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5-oxa-2-azaspiro[3.4]octan-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2-cyclopropyltetrahydrofuran-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(2-cyclopropyltetrahydrofuran-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-7-[5-(3-acetyl-3-azabicyclo[3.1.0]hexan-1-yl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 3-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]azetidine-1-carboxylate; 2,2,2-trifluoroacetic acid (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluoromorpholin-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoroethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(3-methylsulfonyl-3-azabicyclo[3.1.0]hexan-1-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3-azabicyclo[3.1.0]hexane-3-carboxylate (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-(1-methylsulfonylpyrrolidin-3-yl)tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(2-hydroxyspiro[3.3]heptan-6-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-[3-(chloromethyl)-3-(hydroxymethyl)azetidin-1-yl]-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methoxy-acetonitrile; (3R)-3-amino-1,1-dioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-(1-methylsulfonyl-4-piperidyl)tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(5-oxa-2-azaspiro[3.4]octan-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(6-oxa-2-azaspiro[3.5]nonan-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(cyclopentoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-(1,1,2,2,2-pentafluoroethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 7-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-5-azaspiro[2.4]heptane-5-carboxylate; 2-[5-[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methyl-propanenitrile; (3R)-3-amino-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-7-[5-[(1R,5S)-8-azabicyclo[3.2.1]octane-8-carbonyl]-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(5-methylsulfonyl-5-azaspiro[2.4]heptan-7-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-7-[5-(1-acetyl-4-piperidyl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(2-methyltetrazol-5-yl)-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-(1-methylpyrrolidin-3-yl)tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-7-[2-(1-acetyl-4-piperidyl)tetrazol-5-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-7-[5-(3-acetyl-3-azabicyclo[4.1.0]heptan-1-yl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(3-methylsulfonyl-3-azabicyclo[4.1.0]heptan-1-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3-azabicyclo[4.1.0]heptane-3-carboxylate; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(isopropylamino)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(2-azaspiro[3.3]heptan-2-yl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 5-[[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]amino]-3,3-difluoro-piperidine-1-carboxylate; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluoro-1-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-dimethylmorpholin-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3-fluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 4-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]piperidine-1-carboxylate (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-ethyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 3-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]pyrrolidine-1-carboxylate (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-methyl-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-methyl-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methyl-propanenitrile; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(5,5-difluoro-3-piperidyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-7-[5-(3-azabicyclo[4.1.0]heptan-1-yl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-7-[5-(5-acetyl-5-azaspiro[2.4]heptan-7-yl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluoropiperidine-1-carbonyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-methyl-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]propanenitrile; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(3-methylsulfonyl-3-azabicyclo[3.1.1]heptan-1-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate; Methyl 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methyl-propanenitrile; (3R)-7-[5-(3-acetyl-3-azabicyclo[3.1.1]heptan-1-yl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-ethyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroacetic acid (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-ethyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[4-(dimethylamino)-1,1-dimethyl-butyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclopentyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(4,4-difluorocyclohexyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(1,3-dimethylazetidin-3-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(tert-butylamino)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]cyclopropanecarbonitrile; 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]propanenitrile; Methyl 3-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]piperidine-1-carboxylate (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluoropyrrolidine-1-carbonyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(2-aminospiro[3.3]heptan-6-yl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-oxa-7-azaspiro[3.5]nonan-7-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one 4-[[(3R)-3-amino-8-fluoro-7-[5-(2-hydroxy-1,1-dimethyl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-5-yl]methyl]benzonitrile; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(5-amino-3,3-difluoro-1-piperidyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-[1-(chloromethyl)-2-hydroxy-1-methyl-ethyl]-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 5-[(3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-N-isopropyl-N-methyl-1,3,4-oxadiazole-2-carboxamide (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(1-cyclopropyl-5,5-difluoro-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-[4-(chloromethyl)-4-(hydroxymethyl)-1-piperidyl]-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-methylsulfonylethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 5-[(3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-N-tert-butyl-1,3,4-oxadiazole-2-carboxamide (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(isopropoxymethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[5,5-difluoro-1-(2-methoxyethyl)-3-piperidyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one 5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-3-tert-butyl-1,3,4-oxadiazol-2-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-methyltetrahydrofuran-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(4-amino-1,1-dimethyl-butyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(1,3-dimethyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[(1-ethyl-3-piperidyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(3-amino-4,4-difluoro-1-piperidyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[2-(1,1-dioxo-1,4-thiazinan-4-yl)-1,1-dimethyl-ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one 5-[(3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-N,N-dimethyl-1,3,4-oxadiazole-2-carboxamide (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(1-ethyl-5,5-difluoro-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(1-methylpyrrolidin-3-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 5-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3,3-difluoro-piperidine-1-carboxylate (3R)-3-amino-7-[5-(2-azaspiro[3.3]heptan-2-yl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(isopropylamino)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluoro-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(1-cyclopropyl-4-piperidyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-dimethylmorpholin-4-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[6-(cyclopentoxy)-3-pyridyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[1,1-dimethyl-2-(2-oxo-1-piperidyl)ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methyl-propanenitrile; 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]propanenitrile; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(3-methylazetidin-3-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methylsulfonyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[5,5-difluoro-1-(2-hydroxyethyl)-3-piperidyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[1-(hydroxymethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(cyclobutylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-7-[5-(1-acetyl-5,5-difluoro-3-piperidyl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-(3-ethyl-1,2,4-triazol-1-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-7-[5-(4-acetylpiperazin-1-yl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-isobutyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-methylpiperazin-1-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[2-[2-hydroxyethyl(methyl)amino]-1,1-dimethyl-ethyl]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[1,1-dimethyl-2-(2-oxopyrrolidin-1-yl)ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[1,1-dimethyl-2-(4-methylpiperazin-1-yl)ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[1,1-dimethyl-2-(tetrahydrofuran-3-ylamino)ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(5-isopropoxy-2-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[1,1-dimethyl-2-(oxetan-3-ylamino)ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(3,4-difluorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chloro-3-fluoro-phenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluoro-1-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(1,1-dimethyl-2-morpholino-ethyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[2-(dimethylamino)-1,1-dimethyl-ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(6-isopropoxy-3-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[2-(4,4-difluoro-1-piperidyl)-1,1-dimethyl-ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-(2-hydroxy-1,1-dimethyl-ethyl)tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-(2-hydroxy-2-methyl-propyl)tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(cyclopropylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[1,1-dimethyl-2-(1-piperidyl)ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorospiro[3.3]heptan-6-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(dimethylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[(3-methylazetidin-1-yl)methyl]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; Methyl 4-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-4-methyl-piperidine-1-carboxylate; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-methyl-1-methylsulfonyl-4-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(cyclohexylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[3-(difluoromethyl)azetidin-3-yl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-7-[5-(2-amino-1,1-dimethyl-ethyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(6-oxaspiro[3.4]octan-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(3-fluoro-4-methylsulfonyl-phenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-ethyloxazol-2-yl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-imino-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(2-fluoro-4-methylsulfonyl-phenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-N,N,2-trimethyl-propanamide; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[3-(2-hydroxy-1,1-dimethyl-ethyl)-1,2,4-oxadiazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[[4-(3-hydroxyoxetan-3-yl)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-hydroxy-1,1-dimethyl-ethyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroacetic acid (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-hydroxy-1,1-dimethyl-ethyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[(4-phenoxyphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[[4-(2-hydroxyethoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroacetic acid (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-9-methyl-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[1-(cyclopropylmethyl)pyrazol-4-yl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroacetic acid (3R)-7-[5-(1-acetyl-4-methyl-4-piperidyl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-methylimino-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-N,2-dimethyl-propanamide; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(2-cyclopropylpyrimidin-5-yl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(6-chloro-3-pyridyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (2R,3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-2-methyl-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[5-[(4-chlorophenyl)methyl]-3-pyridyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-methyl-4-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-methyltetrahydropyran-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroacetic acid (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-imino-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-chloro-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2-[4-[[(3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-5-yl]methyl]phenoxy]acetamide; 1,1,1,3,3,3-Hexafluoropropan-2-ol; N-[11-[4-[[(3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-5-yl]methyl]phenoxy]undecyl]acetamide; (2S)-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]-2-(methylamino)propanamide (2S)-2-Amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]butanamide (2S)-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]-3-hydroxy-2-(methylamino)propanamide (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(cyclopentoxy)phenyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-[2,2,2-trideuterio-1,1-bis(trideuteriomethyl)ethyl]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(4-ethyltriazol-1-yl)-8-fluoro-2,3-dihydro-1,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[4-[(4-chlorophenyl)methyl]triazol-1-yl]-8-fluoro-2,3-dihydro-1,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(4-ethyltriazol-1-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[4-[(4-chlorophenyl)methyl]triazol-1-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(4-tert-butyltriazol-1-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(1-ethyltriazol-4-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(2-ethyltetrazol-5-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-(1H-pyrazol-5-yl)-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyl-1H-1,2,4-triazol-3-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazol-5-yl]-2,3-dihydropyrido[3,2-b][1,4]thiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(3-ethyl-1,2,4-oxadiazol-5-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-(3-propyl-1,2,4-oxadiazol-5-yl)-2,3-dihydro-1λ 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[3-[(4-chlorophenyl)methyl]-1,2,4-oxadiazol-5-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-[3-(benzyloxymethyl)-1,2,4-oxadiazol-5-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazol-5-yl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-[3-(aminomethyl)-1,2,4-oxadiazol-5-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(3-ethyl-1,2,4-oxadiazol-5-yl)-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(3-tert-butylisoxazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(2,2-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(3,3-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-8-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (2S)-N-[(3R)-8-Fluoro-1,1,4-trioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]-2-(methylamino)propanamide; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(3,3,3-trifluoropropyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1-amino-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(1-fluoro-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluoroethyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-Benzothiazepin-4-one: (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclopentyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorocyclopentyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclobutyl)methyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(tetrahydropyran-4-ylmethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(4,4,4-trifluorobutyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclobutyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorocyclobutyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-(5-tetrahydropyran-4-yl-1,3,4-oxadiazol-2-yl)-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-fluoroethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-isopropyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-hydroxy-1,1-dimethyl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(azetidin-1-yl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(4-ethyloxazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-6-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(3-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; 4-[[(3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-5-yl]methyl]benzonitrile; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[(4-tetrahydrofuran-3-yloxyphenyl)methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(2,2-difluoroethoxy)phenyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(difluoromethoxy)phenyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-(2-pyridylmethyl)-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(6-methoxy-3-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[[4-(aminomethyl)phenyl]methyl]-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(2-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(5-methoxy-2-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(4-methylsulfonylphenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(4-methoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(4-fluorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[[2-(aminomethyl)-4-chloro-phenyl]methyl]-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[[4-(11-aminoundecoxy)phenyl]methyl]-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 λ 6 ,5,5-benzothiazepin-3-yl]acetamide; N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]propanamide; (2S)-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]-2-hydroxy-butanamide; N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]butanamide; (2S)-2-Amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]propanamide; (2S)-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]-2-(methylamino)butanamide; 3-Amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]propanamide; N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]-2-(methylamino)acetamide; 2-Amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]acetamide; 4-Amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]butanamide; (3R)-3-amino-8-bromo-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-methyl-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-hydroxy-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-(dimethylamino)-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3,8-diamino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(1-tert-butylpyrazol-4-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; ((3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(1-ethylpyrazol-4-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(1-ethylpyrazol-3-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(4-tert-butylpyrazol-1-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(3-tert-butylpyrazol-1-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(4-ethylpyrazol-1-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(1-ethyl-1,2,4-triazol-3-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(1-tert-butyl-1,2,4-triazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(1-tert-butylpyrazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyl-1,2,4-oxadiazol-3-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1,1-dimethylbut-3-ynyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-[3-(trifluoromethyl)diazirin-3-yl]phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1,1-dimethylbut-3-ynyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 4 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 4 ,5-benzothiazepin-4-one; 3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-morpholino-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(cyclopentylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyltetrazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one or a pharmaceutically acceptable salt thereof.

[0114] In certain embodiments, there is provided a compound of formula (I) described herein selected from the following: (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(4-ethyltriazol-1-yl)-8-fluoro-2,3-dihydro-1,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[4-[(4-chlorophenyl)methyl]triazol-1-yl]-8-fluoro-2,3-dihydro-1,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(4-ethyltriazol-1-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[4-[(4-chlorophenyl)methyl]triazol-1-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(4-tert-butyltriazol-1-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(1-ethyltriazol-4-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(2-ethyltetrazol-5-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-(1H-pyrazol-5-yl)-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyl-1H-1,2,4-triazol-3-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazol-5-yl]-2,3-dihydropyrido[3,2-b][1,4]thiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(3-ethyl-1,2,4-oxadiazol-5-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-(3-propyl-1,2,4-oxadiazol-5-yl)-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[3-[(4-chlorophenyl)methyl]-1,2,4-oxadiazol-5-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-[3-(benzyloxymethyl)-1,2,4-oxadiazol-5-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazol-5-yl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-[3-(aminomethyl)-1,2,4-oxadiazol-5-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(3-ethyl-1,2,4-oxadiazol-5-yl)-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(3-tert-butylisoxazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(2,2-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(3,3-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-8-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (2S)-N-[(3R)-8-Fluoro-1,1,4-trioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]-2-(methylamino)propanamide; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(3,3,3-trifluoropropyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1-amino-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(1-fluoro-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluoroethyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-Benzothiazepin-4-one: (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclopentyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorocyclopentyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclobutyl)methyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(tetrahydropyran-4-ylmethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(4,4,4-trifluorobutyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclobutyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorocyclobutyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-(5-tetrahydropyran-4-yl-1,3,4-oxadiazol-2-yl)-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-fluoroethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-isopropyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-hydroxy-1,1-dimethyl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(azetidin-1-yl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(4-ethyloxazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-6-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(3-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; 4-[[(3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-5-yl]methyl]benzonitrile; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[(4-tetrahydrofuran-3-yloxyphenyl)methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(2,2-difluoroethoxy)phenyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(difluoromethoxy)phenyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-(2-pyridylmethyl)-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(6-methoxy-3-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[[4-(aminomethyl)phenyl]methyl]-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(2-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(5-methoxy-2-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(4-methylsulfonylphenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(4-methoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(4-fluorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[[2-(aminomethyl)-4-chloro-phenyl]methyl]-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[[4-(11-aminoundecoxy)phenyl]methyl]-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5,5-benzothiazepin-3-yl]acetamide; N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]propanamide; (2S)-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]-2-hydroxy-butanamide; N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]butanamide; (2S)-2-Amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6,5-benzothiazepin-3-yl]propanamide; (2S)-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]-2-(methylamino)butanamide; 3-Amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]propanamide; N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]-2-(methylamino)acetamide; 2-Amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]acetamide; 4-Amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]butanamide; (3R)-3-amino-8-bromo-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-methyl-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-hydroxy-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-(dimethylamino)-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3,8-diamino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(1-tert-butylpyrazol-4-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; ((3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(1-ethylpyrazol-4-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(1-ethylpyrazol-3-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(4-tert-butylpyrazol-1-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(3-tert-butylpyrazol-1-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(4-ethylpyrazol-1-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(1-ethyl-1,2,4-triazol-3-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(1-tert-butyl-1,2,4-triazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(1-tert-butylpyrazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyl-1,2,4-oxadiazol-3-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1,1-dimethylbut-3-ynyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-[3-(trifluoromethyl)diazirin-3-yl]phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1,1-dimethylbut-3-ynyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 4 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 4,5-benzothiazepin-4-one; 3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-morpholino-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(cyclopentylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyltetrazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one or a pharmaceutically acceptable salt thereof.

[0115] In a most specific embodiment, there is provided a compound of formula (I) as described herein, selected from: Methyl 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate 2-Amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]acetamide (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride 2-Amino-N-[(3R)-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]acetamide (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclobutyl)amino]-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-imino-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (2S)-2-Amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]propanamide (3R)-3-Amino-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-7-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-[5-(2,2-difluoromorpholin-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[(4-phenoxyphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; formic acid (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclobutyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (2S)-2-Amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]butanamide (3R)-3-Amino-8-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluoro-1-methyl-cyclobutyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride 2-[4-[[(3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-5-yl]methyl]phenyl]-2-methyl-propanenitrile (3R)-3-amino-7-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-7-(2-tert-butyltetrazol-5-yl)-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(o-tolyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(cyclobutylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride 2-[5-[(3R)-3-Amino-8-fluoro-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methyl-propanenitrile; Hydrochloride (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(6-isopropoxy-3-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazol-5-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(6-fluoro-2-methyl-3-pyridyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(4-methoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-Hexafluoropropan-2-ol; Hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-morpholino-1,2,4-oxadiazol-3-yl)-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-amino-7-[5-[1-amino-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl]-1,2,4-oxadiazol-3-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[methyl(2,2,2-trifluoroethyl)amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyltetrazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluoromorpholin-4-yl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(tert-butylamino)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-morpholino-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-Hexafluoropropan-2-ol; Hydrochloride (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(cyclohexylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-Hexafluoropropan-2-ol; Hydrochloride (3R)-3-Amino-7-(1-tert-butyl-1,2,4-triazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 4-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-4-methyl-piperidine-1-carboxylate; Hydrochloride (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-(3-ethyl-1,2,4-oxadiazol-5-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)-1,2,4-oxadiazol-3-yl]-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; hydrochloride (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chloro-3-fluoro-phenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-[2-(trifluoromethyl)morpholin-4-yl]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-7-[5-(3,3-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-Hexafluoropropan-2-ol (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluoromorpholin-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-7-[5-(1,1-dimethylbut-3-ynyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-3-yl]-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclobutyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-isobutyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 5-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3,3-difluoro-piperidine-1-carboxylate (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclopentyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[2-(trifluoromethyl)morpholin-4-yl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorospiro[3.3]heptan-6-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-Hexafluoropropan-2-ol; Hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-[5,5-difluoro-1-(2-methoxyethyl)-3-piperidyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(1-ethyl-5,5-difluoro-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(2-cyclopropyltetrahydrofuran-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-7-[5-(3-fluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(6-fluoro-2-methyl-3-pyridyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[[4-(cyclopentoxy)phenyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-fluoro-6-methyl-phenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-Hexafluoropropan-2-ol; Hydrochloride (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(cyclopentoxy)phenyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(cyclopentoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-Amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[(4-phenoxyphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride or a pharmaceutically acceptable salt thereof.

[0116] In certain embodiments, there is provided a compound of formula (I) described herein selected from the following: (3R)-3-Amino-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]- 8-Fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-Amino-8-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]- 5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)- 8-Fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]- 8-Fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]- 8-Fluoro-7-[5-(1-fluoro-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluorocyclohexyl)- 1,3,4-Oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorocyclohexyl)- 1,3,4-Oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclobutyl)- 1,3,4-Oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]- 8-Fluoro-7-(5-isopropyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]- 8-Fluoro-7-[5-(2-hydroxy-1,1-dimethyl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; 4-[[(3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)- 8-Fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-5-yl]methyl]benzonitrile; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)- 8-Fluoro-5-[(4-methoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; 2-Amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]- 8-Fluoro-1,1,4-trioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-3-yl]acetamide; (3R)-3-Amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]- 8-Methyl-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-Amino-7-(1-tert-butylpyrazol-4-yl)-5-[(4-chlorophenyl)methyl]- 8-Fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-Amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[(4-chlorophenyl)methyl]- 8-Fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1,1-dimethylbut-3-ynyl)-1,3,4-oxadiazol-2-yl]- 8-Fluoro-1,1-dioxo-5-[[4-[3-(trifluoromethyl)diazirin-3-yl]phenyl]methyl]-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)- 5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro- 1-Methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-oxo-5- [[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 4 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-oxo-5- [[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ 4 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7 -(5-morpholino-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7- [5-(cyclopentylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-5- [(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyltetrazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ 6 ,5-benzothiazepin-4-one or a pharmaceutically acceptable salt thereof.

[0117] In the description herein, if there is a discrepancy between a depicted structure and a name given to that structure, the depicted structure prevails. Furthermore, if the stereochemistry of a structure or portion of a structure is not indicated, for example, with a bold wedge or a dotted line, the structure or portion of the structure is intended to encompass all of its stereoisomers. However, in some cases where multiple chiral centers are present, the structure and name may be represented as a single enantiomer to aid in describing the relative stereochemistry.

[0118] Unless otherwise indicated, "a compound of the formula" or "a compound of formula" or "compounds of the formula" or "compounds of formula" refers to any compound selected from the genus of compounds defined by that formula (including any pharmaceutically acceptable salt of any such compound, unless otherwise specified).

[0119] Certain compounds may exhibit tautomerism. Tautomeric compounds can exist as two or more interconvertible species. Prototropic tautomers result from the migration of a covalently bonded hydrogen atom between two atoms. Tautomers generally exist in equilibrium, and attempts to isolate individual tautomers usually result in mixtures whose chemical and physical properties match those of the compound. The position of the equilibrium depends on the chemical features within the molecule. For example, in many aliphatic aldehydes and ketones, such as acetaldehyde, the keto form predominates, whereas in phenols, the enol form predominates. Common protic tautomers include keto / enol (-C(=O)-CH-←→-C(-OH)=CH-), amide / imidic acid (-C(=O)-NH-←→-C(-OH)=N-), and amidine (-C(=NR)-NH-←→-C(-NHR)=N-) tautomers. The latter two are particularly common in heteroaryl and heterocyclic rings, and the present invention encompasses all tautomeric forms of the compounds.

[0120] Furthermore, the present invention includes all optical isomers of the compounds of formula (I), i.e., diastereoisomers, diastereomeric mixtures, racemic mixtures, all corresponding enantiomers and / or tautomers thereof, and solvates thereof.

[0121] Compounds of formula (I) may contain one or more asymmetric centers and thus occur as racemates, racemic mixtures, single enantiomers, diastereomeric mixtures, and individual diastereomers. Additional asymmetric centers may be present depending on the nature of the various substituents on the molecule. Each such asymmetric center independently produces two optical isomers, and all possible optical isomers and diastereomers, both as mixtures and as pure or partially purified compounds, are intended to be encompassed by the present invention. The present invention is meant to encompass all such isomeric forms of these compounds. The independent syntheses of these diastereomers or their chromatographic separations can be achieved as known in the art by appropriate modification of the methods disclosed herein. Their absolute stereochemistry can be determined by X-ray crystallography of crystalline products or crystalline intermediates, which are derivatized, if necessary, with a reagent containing an asymmetric center of known absolute configuration. If desired, racemic mixtures of the compounds can be separated to isolate the individual enantiomers. Resolution can be carried out by methods known in the art, such as coupling a racemic mixture of a compound to an enantiomerically pure compound to form a diastereomeric mixture, followed by separation of the individual diastereomers by standard methods such as fractional recrystallization or chromatography.

[0122] In embodiments in which optically pure enantiomers are provided, optically pure enantiomer means that the compound contains greater than 90% by weight of the desired isomer, specifically greater than 95% by weight of the desired isomer, or more specifically greater than 99% by weight of the desired isomer, the weight percentages being based on the total weight of the isomer(s) of the compound. Chirally pure or chirally enriched compounds can be prepared by chirally selective synthesis or by separation of enantiomers. Separation of enantiomers can be carried out on the final product or on a suitable intermediate.

[0123] In some embodiments, compounds of formula (I) are isotopically labeled by having one or more atoms therein replaced by an atom having a different atomic mass or mass number. Such isotopically labeled (i.e., radiolabeled) compounds of formula (I) are considered to be within the scope of the present disclosure. Examples of isotopes that can be incorporated into compounds of formula (I) include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, and iodine, respectively, e.g., 2 H, 3 H, 11 C. 13 C. 14 C. 13 N, 15 N, 15 O. 17 O. 18 O. 31 P, 32 P, 35 S, 18 F, 36 Cl, 123 I, and 125 Certain isotopically labeled compounds of formula (I), for example those incorporating a radioactive isotope, are useful in drug and / or substrate tissue distribution studies. The radioactive isotope tritium, i.e., 3 H and carbon-14, i.e., 14 C are particularly useful for this purpose given their ease of incorporation and ready means of detection. For example, compounds of formula (I) can be enriched with 1, 2, 5, 10, 25, 50, 75, 90, 95, or 99% of a given isotope.

[0124] Heavier isotopes, such as deuterium, i.e. 2 Substitutions such as H may result in greater metabolic stability and may confer certain therapeutic advantages, for example, by increasing in vivo half-life or requiring lower dosages.

[0125] 11 C. 18 F, 15 O and 13Substitution with positron emitting isotopes, such as N, can be useful in positron emission tomography (PET) studies for examining substrate receptor occupancy. Isotopically labeled compounds of formula (I) can generally be prepared by conventional techniques known to those skilled in the art, or by methods analogous to those described in the Examples set forth below, substituting an appropriate isotopically labeled reagent for the previously employed non-isotopically labeled reagent.

[0126] Manufacturing method Methods for preparing the compounds of formula (I) described herein, or pharmaceutically acceptable salts thereof, are also an object of the present invention.

[0127] The preparation of the compounds of formula (I) of the present invention can be carried out by sequential or convergent synthetic routes. The synthesis of the present invention is shown in the following general scheme. The skills required to carry out the reactions and purification of the resulting products are known to those skilled in the art. The substituents and indices used in the following process descriptions have the meanings given herein unless indicated to the contrary.

[0128] If one of the starting materials, intermediates or compounds of formula (I) contains one or more functional groups that are not stable or reactive under the reaction conditions of one or more reaction steps, suitable protecting groups (such as those described in "Protective Groups in Organic Chemistry", T.W. Greene and P.G.M. Hutts, 5th Edition, 2014, John Wiley & Sons, NY) can be introduced prior to a critical step by applying methods well known in the art. Such protecting groups can be removed at a later stage of the synthesis using standard methods described in the literature.

[0129] When the starting material or intermediate contains a stereocenter, the compound of formula (I) may be obtained as a mixture of diastereomers or enantiomers, which can be separated by methods well known in the art, such as chiral HPLC, chiral SFC, or chiral crystallization. Racemates can be separated into their antipodes via diastereomeric salts, for example, by crystallization with an optically pure acid, or by separating the antipodes by specific chromatographic methods using either a chiral adsorbent or a chiral eluent. Starting materials and intermediates containing a stereocenter can also be separated to obtain diastereomerically / enantiomerically enriched starting materials and intermediates. The use of such diastereomerically / enantiomerically enriched starting materials and intermediates in the synthesis of the compound of formula (I) generally results in the respective diastereomerically / enantiomerically enriched compound of formula (I).

[0130] Those skilled in the art will recognize that in the synthesis of compounds of formula (I), unless otherwise desired, an "orthogonal protecting group strategy" can be applied to cleave some protecting groups one at a time without affecting other protecting groups in the molecule. The principle of orthogonal protection is well known in the art and has been described in the literature (e.g., Barany and R.B. Merrifield, J. Am. Chem. Soc. 1977, 99, 7363; H. Waldmann et al., Angew. Chem. Int. Ed. Engl. 1996, 35, 2056).

[0131] Those skilled in the art will recognize that the reaction sequence may vary depending on the reactivity and nature of the intermediates.

[0132] More specifically, compounds of formula (I) can be prepared by the methods described below, the methods described in the Examples, or similar methods. Suitable reaction conditions for the individual reaction steps are known to those skilled in the art. For literature-described reaction conditions affecting the described reactions, see, for example, Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition, Richard C. Larock, John Wiley & Sons, New York, NY, 1999. The reactions could be easily carried out with or without a solvent. There are no particular restrictions on the nature of the solvent used, so long as it does not adversely affect the reaction or the reagents involved and is capable of dissolving the reagents to at least some extent. The described reactions can occur over a wide range of temperatures, and the exact reaction temperature is not critical to the present invention. It is convenient to carry out the described reactions at temperatures ranging from -78°C to reflux. The reaction time required for the reaction can also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents. However, a period of 0.5 hours to several days is usually sufficient to obtain the intermediates and compounds described. The reaction order is not limited to the order shown in the scheme, but the order of the reaction steps can be freely changed depending on the starting materials and their respective reactivities.

[0133] If the starting materials or intermediates are not commercially available or their synthesis is not described in the literature, they can be prepared analogously to existing procedures for similar analogs or as outlined in the experimental section.

[0134] In one embodiment, the compounds of formula (I) described herein or pharmaceutically acceptable salts thereof are a) Formula (IX) TIFF0007821808000034.tif46170 (in the formula, X, Y, R 1 , R 2 , R 3 , R 4 , R 6 , R 6ais as described herein, and PG is an amino protecting group. with a suitable deprotecting agent to give the compound of formula (I), 1 , R 2 , R 3 , R 4 , R 6 , R 6a is as described herein, and R 5 is hydrogen), or a pharmaceutically acceptable salt thereof; or b) Formula (Ia) TIFF0007821808000035.tif49170 (in the formula, X, Y, R 1 , R 2 , R 3 , R 4 , R 6 , R 6a is as described herein, and R 5 is hydrogen) in the presence of a base to form a compound of formula R 9 CO2H (in the formula, R 9 is as described herein) to give a compound of formula (I) or a pharmaceutically acceptable salt thereof, 5 is -C(O)(R 9 ) to form It can be prepared by a process comprising:

[0135] The present compounds of formula (I) or pharmaceutically acceptable salts thereof may be prepared by the methods described below (Scheme 1), together with synthetic methods known in the art of organic chemistry, or modifications and derivatizations that are familiar to those skilled in the art. TIFF0007821808000036.tif129170 Scheme 1

[0136] Suitable starting materials for the preparation of compounds of formula (I) are compounds of formula (II) 2 is F or Cl, and X 1 is already R 1 or Br) or a nitro compound followed by R 1The compound of formula (II) can be synthesized as follows: -CO2 alkyl. Compounds of formula (II) can be reacted with an appropriately protected cysteine ​​derivative (III) in a solvent such as 1,2-dichloroethane in the presence of a base such as DIPEA at elevated temperatures to give compounds of formula (IV). A preferred protecting group (PG) for cysteine ​​derivatives (III) is Boc. The nitro group in compounds of formula (IV) can be reduced using iron in the presence of either hydrogen chloride or ammonium chloride in a solvent mixture of water and ethanol at elevated temperatures to give compounds of formula (V). Alternatively, this conversion can be achieved by catalytic hydrogenation. Compounds of formula (V) can be cyclized to compounds of formula (VI) using standard amide coupling conditions. Preferably, this cyclization is carried out using 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (50% solution in EtOAc) with a base such as DIPEA in a solvent such as DMF at room temperature. Compounds of formula (VI) and Y 1 is Cl, Br, I or a sulfonate group in the presence of a base such as potassium carbonate, optionally with an additive such as potassium iodide, in a solvent such as DMSO or DMF at room temperature to obtain a compound of formula (VIII). 1 In the case of compounds of formula (VIII) where is Br or -CO2 alkyl, these groups can be converted at this stage into the substituent R 1 Compounds of formula (VIII) can then be converted to compounds of formula (IX) where Y is S(O) or S(O)2 by reaction with an appropriate amount of an oxidizing agent such as m-CPBA in a solvent such as DCM at room temperature. Alternatively, compounds of formula (VIII) can be synthesized by reaction with an appropriate amount of an oxidizing agent such as m-CPBA in a solvent such as DCM at room temperature to form compounds of formula (IX) where Y is S(O) or S(O)2. y ) and R y can be converted to a compound of formula (IX) where Y is hydrogen. Typical conditions include iodobenzene diacetate in the presence of ammonium carbonate in a solvent such as methanol at room temperature. y ) and R y C 1~6 -alkyl, the compound of formula (IX) is y ) and Ry is hydrogen, in a solvent such as dioxane, in the presence of copper(II) acetate and pyridine as a base, at reflux temperature, 1~6 -alkylboronic acid [Org. Biomol. Chem., 2017, 15, 8493]. Final deprotection provides compounds of formula (I). When the N-protecting group (PG) is Boc, typical conditions for this deprotection step include TFA in a solvent such as DCM at room temperature, hydrogen chloride in a solvent such as dioxane or ethyl acetate at room temperature, or hexafluoroisopropanol at reflux temperature. Alternatively, the protecting group (PG) of compounds of formula (VIII) can be cleaved accordingly to provide compounds of formula (I) in which Y is S. Furthermore, the substituent R 1 and R 4 may contain functional groups that may be modified before removal of the N-protecting group (PG) or may require the use of appropriate protecting groups during synthesis. These protecting groups may be removed before removal of the N-protecting group (PG) or may be removed simultaneously using appropriate methods [Peter G.M.Wuts, Greene's Protective Groups in Organic Synthesis, 5th Edition, Hoboken, NJ: Wiley-Interscience]. 5 Compounds of formula (I) where is hydrogen can be converted to the carboxylic acid derivative R using standard amide coupling conditions such as HATU in the presence of a base such as DIPEA in a solvent such as THF at room temperature. 9 By reaction with CO2H, R 5 -C(O)(R 9 ) can be converted into a compound of formula (I) wherein the substituent R 9 If contains a functional group that needs to be protected during this coupling step, the protecting group can be removed in an additional step using appropriate conditions.

[0137] Alternatively, compounds of formula (I) where Y is (O) 2 can be prepared as shown in Scheme 2. TIFF0007821808000037.tif77170 Scheme 2

[0138] Compounds of formula (VI) can be converted to compounds of formula (X) by reaction with an oxidizing agent such as m-CPBA in a solvent such as DCM at room temperature. The reaction of compounds of formula (X) with compounds of formula (VII) to give compounds of formula (XI) and their subsequent conversion to compounds of formula (I) (where Y is S(O2)) can be achieved using the reaction conditions described for the similar step in Scheme 1. X 1 is Br or -CO2 alkyl, these groups can be substituted with the substituent R at any stage of the synthesis (for compounds of formula (VI), (X) or (XI)) using the methods described for the following schemes: 1 can be synthesized into

[0139] 5-membered heteroaryl R 1 Compounds of formula (I) where is a 1,3,4-oxadiazolyl group may be prepared as shown in Scheme 3. TIFF0007821808000038.tif118170 Scheme 3

[0140] X 1 Compounds of formula (VIII), where R is COMe, can be converted to compounds of formula (XII) by reaction with an alkali hydroxide, such as LiOH, NaOH, or KOH, in a mixture of solvents such as MeOH, THF, and water at room temperature. Compounds of formula (XII) can be reacted with hydrazine hydrate, after activation with a suitable reagent, such as CDI, in a solvent such as THF at room temperature, to give compounds of formula (XIII). Compounds of formula (XIII) can be converted to carboxylic acids R using standard amide coupling conditions, such as HATU, in the presence of a base, such as DIPEA, in a solvent such as THF at room temperature. 10 The coupling product of formula (XIV) can be reacted with COH. The coupling product of formula (XIV) can be cyclized to a compound of formula (XV) using a dehydrating reagent such as Burgess's reagent at room temperature. Conversion of a compound of formula (XV) to a compound of formula (XVI) and then to a compound of formula (I) can be achieved using the reaction conditions described for the similar steps in Scheme 1.

[0141] 5-membered heteroaryl R 1 Compounds of formula (I) where is a 1,2,4-oxadiazolyl group may be prepared as shown in Scheme 4. TIFF0007821808000039.tif85170 Scheme 4

[0142] Compounds of formula (XII) can be coupled to amidine R using standard amide coupling conditions such as HBTU in the presence of a base such as DIPEA in a solvent such as DMF at room temperature. 10 C(NH)NH2 to give a compound of formula (XVII). Reaction of compound of formula (XVII) with NBS in the presence of DBU in EtOAc at room temperature can give a compound of formula (XVIII) [Tetrahedron 74(2018)4613-4618]. Conversion of compound of formula (XVIII) to compound of formula (XIX) and then to compound of formula (I) can be achieved using the reaction conditions described for the similar steps in Scheme 1.

[0143] 5-membered heteroaryl R 1 Compounds of formula (I) where is a 1,2,3-triazolyl group may be prepared as shown in Scheme 5. TIFF0007821808000040.tif131170 Scheme 5

[0144] X 1 Compounds of formula (VIII) where is Br can be converted to compounds of formula (XX) by Sonogashira coupling with trimethylsilylacetylene. Typical conditions include bis(triphenylphosphine)palladium(II) chloride and copper(I) iodide as catalysts in the presence of a base such as DIPEA in a solvent such as THF at room temperature. Reaction of compounds of formula (XX) with KF in MeOH gives compounds of formula (XXI), which can be reacted with azide R in the presence of CuSO 5H O and sodium ascorbate in a solvent mixture of MeOH and water. 12 Optionally, the azide R can be converted to a compound of formula (XXII) by reaction with N3. 12 N3 is the amine R12 It can be prepared in situ from NH and 1H-imidazole-1-sulfonyl azide hydrochloride. Conversion of compounds of formula (XXII) to compounds of formula (XXIII) and then to compounds of formula (I) can be achieved using the reaction conditions described for the analogous steps in Scheme 1.

[0145] 5-membered heteroaryl R 1 Compounds of formula (I) where is a pyrazolyl group can be prepared as shown in Scheme 6. TIFF0007821808000041.tif106170 Scheme 6

[0146] X 1 Compounds of formula (VIII), where is Br, can be converted to compounds of formula (XXV) by Suzuki coupling with boronic acids or boronic esters (XXIV). Typical reaction conditions include the use of Pd(dppf)Cl as a catalyst in the presence of KPO in a mixture of dioxane and water at reflux temperature. Conversion of compounds of formula (XXV) to compounds of formula (XXVI) and then to compounds of formula (I) can be achieved using the reaction conditions described for the similar steps in Scheme 1.

[0147] Alternatively, a 5-membered heteroaryl R 1 Compounds of formula (I) where is a pyrazolyl group can be prepared as shown in Scheme 7. TIFF0007821808000042.tif99170 Scheme 7

[0148] X 1Compounds of formula (VIII) where is Br can be converted to compounds of formula (XXVIII) by reaction with pyrazole (XXVII) in the presence of CuI, trans-N,N'-dimethylcyclohexane-1,2-diamine and potassium carbonate in toluene as solvent at reflux temperature. Conversion of compounds of formula (XXVIII) to compounds of formula (XXIX) and then to compounds of formula (I) can be achieved using the reaction conditions described for the similar steps in Scheme 1.

[0149] Alternatively, a 5-membered heteroaryl R 1 Compounds of formula (I) where is a pyrazolyl group may also be prepared as shown in Scheme 8. TIFF0007821808000043.tif130170 Scheme 8

[0150] X 1 Compounds of formula (VIII) where Br can be converted to compounds of formula (XXX) by reaction with 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane in the presence of Pd(dppf)Cl·CHCl and potassium acetate in dioxane at 80°C. Compounds of formula (XXX) can be converted to compounds of formula (XXXII) by Chan-Lam coupling with pyrazole (XXXI). Typical reaction conditions include Cu(OAc) in the presence of TEA in acetonitrile at 30°C under an oxygen atmosphere. Conversion of compounds of formula (XXXII) to compounds of formula (XXXIII) and subsequently to compounds of formula (I) can be achieved using the reaction conditions described for the similar steps in Scheme 1.

[0151] 5-membered heteroaryl R 1 Compounds of formula (I) where is a 1,2,4 triazolyl group can be prepared as shown in Scheme 9. TIFF0007821808000044.tif84170 Scheme 9

[0152] Suzuki coupling of a compound of formula (XXX) with triazolyl bromide (XXXIV) provides a compound of formula (XXXV). Typical reaction conditions include the use of Pd(dppf)Cl as a catalyst in the presence of KPO in a mixture of dioxane and water at reflux temperature. Conversion of a compound of formula (XXXV) to a compound of formula (XXXVI) and then to a compound of formula (I) can be achieved using the reaction conditions described for the similar steps in Scheme 1.

[0153] 5-membered heteroaryl R 1 Compounds of formula (I) where is a tetrazolyl group may be prepared as shown in Scheme 10. TIFF0007821808000045.tif135170 Scheme 10

[0154] X 1 Compounds of formula (VIII) where is Br can be converted to compounds of formula (XXXVII) using a mixture of zinc cyanide, zinc powder, t-Bu3P, and Pd2(dba)3 in DMF at elevated temperatures. Conversion of compounds of formula (XXXVII) to compounds of formula (XXXVIII) can be achieved by reaction with an azide reagent such as azidotrimethylsilane in the presence of tetra-N-butylammonium fluoride trihydrate in toluene at elevated temperatures. To obtain compounds of formula (XXXVIII) from compounds of formula (XXXIX), the reagent R can be reacted with azidotrimethylsilane in the presence of a base such as potassium carbonate in a solvent such as DMF at room temperature. 10 The substituent R can be prepared by various methods, such as by reaction with Y (wherein Y is Cl, Br, or I). 10 Conversion of a compound of formula (XXXIX) to a compound of formula (XL) and then to a compound of formula (I) can be achieved using the reaction conditions described for the analogous steps in Scheme 1.

[0155] 5-membered heteroaryl R 1 Compounds of formula (I) where is a 1,2,3 triazolyl group may be prepared as shown in Scheme 11. TIFF0007821808000046.tif176170 Scheme 11

[0156] 5-membered heteroaryl R 1 A suitable starting material for the synthesis of compounds of formula (I) in which is a 1,2,3 triazolyl group is a fluoro-nitro-amine of formula (XLI). Reaction of compounds of formula (XLI) with cysteine ​​derivatives (III) to give compounds of formula (XLII), followed by cyclization to compounds of formula (XLIII), and reaction with compounds of formula (VII) to give compounds of formula (XLIV) can be achieved using conditions described for similar reaction steps in Scheme 1. Conversion of nitro compounds of formula (XLIV) to anilines of formula (XLV) can be achieved using zinc powder in the presence of ammonium chloride in a solvent such as MeOH at elevated temperature. Reaction of compounds of formula (XLV) with first isopentyl nitrite and azidotrimethylsilane, followed by acetylene of formula (XLVI), in the presence of copper(I) oxide in a solvent such as acetonitrile at room temperature gives compounds of formula (XLVII). Conversion of a compound of formula (XLVII) to a compound of formula (XLVIII) and then to a compound of formula (I) can be achieved using the reaction conditions described for the analogous steps in Scheme 1.

[0157] 5-membered heteroaryl R 1 Compounds of formula (I) where is an isoxazolyl group may be prepared as shown in Scheme 12. TIFF0007821808000047.tif88170 Scheme 12

[0158] Acetylenic compounds of formula (XXI) can be reacted with oximes of formula (XLIX) in the presence of aqueous sodium hypochlorite and TEA in a solvent such as DCM at 30° C. to give compounds of formula (L). Conversion of compounds of formula (L) to compounds of formula (LI) and then to compounds of formula (I) can be achieved using the reaction conditions described for the similar steps in Scheme 1.

[0159] 5-membered heteroaryl R1 Compounds of formula (I) where is a 1,2,4 triazolyl group and Y is S(2) may be prepared as shown in Scheme 13. TIFF0007821808000048.tif89170 Scheme 13

[0160] Carboxylic acids of formula (XII) can be reacted with amidrazones of formula (LII) in the presence of an activating agent such as HATU and a base such as TEA in a solvent such as DMF to give the corresponding coupling products, which upon heating cyclize to compounds of formula (LIII). Oxidation of compounds of formula (LIII) with m-CPBA in a solvent such as DCM followed by cleavage of the N-protecting group (PG) gives compounds of formula (I).

[0161] 5-membered heteroaryl R 1 Compounds of formula (I) where is a 1,2,4-oxadiazolyl group may be prepared as shown in Scheme 14. TIFF0007821808000049.tif88170 Scheme 14

[0162] Nitrile compounds of formula (XXXVII) can be reacted with hydroxylamine hydrochloride in the presence of a base such as potassium carbonate in a solvent such as ethanol at elevated temperatures to give amidoxime compounds of formula (LV, where R is H). Standard amide coupling conditions can be used to couple compounds of formula (LV, where R is H) with carboxylic acids R using an activating agent such as CDI, EDC / HOBt or HATU in the presence of a base such as DIPEA in a solvent such as DMF, THF or acetonitrile. 10 When reacted with COH, a coupling intermediate (LV, where R is -C(O)R) is formed which, upon heating, cyclizes to the corresponding compound of formula (LVI). 10 Alternatively, the coupling intermediate (LV, where R is —C(O)R 10) can be isolated and the cyclization step can be carried out either by heating in a solvent such as toluene or by reaction with TBAOH in a solvent such as THF. Conversion of compounds of formula (LVI) to compounds of formula (LVII) and then to compounds of formula (I) can be achieved using the reaction conditions described for the similar steps in Scheme 1.

[0163] 5-membered heteroaryl R 1 Compounds of formula (I) where is an oxazolyl group may be prepared as shown in Scheme 15. TIFF0007821808000050.tif130170 Scheme 15

[0164] Compounds of formula (XII) can be reacted with amino alcohols of formula (LVIII) using standard amide coupling conditions such as HATU in the presence of a base such as DIPEA in a solvent such as DMF at room temperature to give compounds of formula (LIX). Cyclization of compounds of formula (LIX) to compounds of formula (LX) can be achieved using a dehydrating reagent such as Burgess's reagent in a solvent such as THF at elevated temperatures. Reaction of compounds of formula (LX) with DDQ in toluene at elevated temperatures gives compounds of formula (LXI). Conversion of compounds of formula (LXI) to compounds of formula (LXII) and then to compounds of formula (I) can be achieved using the reaction conditions described for the similar steps in Scheme 1.

[0165] 5-membered heteroaryl R 1 is a 1,3,4-oxadiazolyl group, and R 10 is N(R 10e R 10f ) and Y is S(O2), can be prepared as shown in Scheme 16. TIFF0007821808000051.tif86170 Scheme 16

[0166] Compounds of formula (XIII) can be first reacted with CS₂ in DMF at elevated temperature, followed by reaction with methyl iodide in the presence of TEA at room temperature to give compounds of formula (LXIII). Oxidation of compounds of formula (LXIII) with an oxidizing agent such as KMnO₄ in a solvent mixture of water and acetic acid at temperatures between 0 and 5°C gives compounds of formula (LXIV). Compounds of formula (LXIV) can be prepared by the oxidation of amines HN(R) to OH in the presence of a base such as potassium carbonate in a solvent such as DMF at room temperature. 10e R 10f The compound of formula (LXV) can be obtained by reaction with N-protecting group (PG). Cleavage of the N-protecting group (PG) gives the compound of formula (I).

[0167] Alternatively, a 5-membered heteroaryl R 1 is a 1,3,4-oxadiazolyl group, and R 10 is N(R 10e R 10f ) and Y is S(O2), compounds of formula (I) can be prepared as shown in Scheme 17. TIFF0007821808000052.tif88170 Scheme 17

[0168] Compounds of formula (XIII) can be reacted with CDI in THF in the presence of a base such as TEA at room temperature to give compounds of formula (LXVI). Compounds of formula (LXVI) can be oxidized with an oxidizing agent such as m-CPBA in a solvent such as DCM at room temperature to give compounds of formula (LXVII). Compounds of formula (LXVII) can be converted to amines HN(R 10e R 10f ) to give the compound of formula (LXV) [Org. Lett., 2008, Vol. 10, 1755-1758]. Cleavage of the N-protecting group (PG) gives the compound of formula (I).

[0169] 5-membered heteroaryl R 1 is a 1,2,4-oxadiazolyl group, and R 10 is N(R 10e R 10f) and Y is S(O2), can be prepared as shown in Scheme 18. TIFF0007821808000053.tif76170 Scheme 18

[0170] Compounds of formula (LV, where R is H) can be reacted with CDI in THF in the presence of a base such as TEA at room temperature to give compounds of formula (LXVIII). Compounds of formula (LXVIII) can be converted to amines HN(R 10e R 10f The compound of formula (LXIX) can be converted to a compound of formula (LXIX) by reaction with m-CPBA. Oxidation of the compound of formula (LXIX) with an oxidizing agent such as m-CPBA in a solvent such as DCM at room temperature gives a compound of formula (LXX). Cleavage of the N-protecting group (PG) gives a compound of formula (I).

[0171] Alternatively, a 5-membered heteroaryl R 1 is a 1,2,4-oxadiazolyl group, and R 10 is N(R 10e R 10f ) and Y is S(O2), compounds of formula (I) can be prepared as shown in Scheme 19. TIFF0007821808000054.tif75170 Scheme 19

[0172] Reaction of compound of formula (XXXVII) with an oxidizing agent such as m-CPBA in a solvent such as DCM at room temperature provides compound of formula (LXXI), which can be converted to compound of formula (LXXII) by reaction with hydroxylamine hydrochloride in the presence of a base such as sodium bicarbonate in a solvent such as methanol at elevated temperature. Subsequent conversion of compound of formula (LXXII) to compound of formula (I) can be achieved using the reaction conditions described for the similar step in Scheme 18.

[0173] 5-membered heteroaryl R 1 is a 1,3,4-oxadiazolyl group, and R 10 is N(R10e R 10f ) and Y is S(O2), can be prepared as shown in Scheme 20. TIFF0007821808000055.tif78170 Scheme 20

[0174] In the presence of a base such as aqueous sodium bicarbonate in a solvent such as 1,2-dichloroethane, the amine HN(R 10e )(R 10f Reaction of (XIII) with triphosgene, followed by reaction with a hydrazide compound of formula (XIII), provides a compound of formula (LXXIV). Compounds of formula (LXXIV) can be cyclized to compounds of formula (LXXV) by using a reagent such as p-toluenesulfonyl chloride and DIPEA at room temperature. Oxidation of compounds of formula (LXXV) to compounds of formula (LXV) and conversion to compounds of formula (I) can be achieved using the reaction conditions described for the similar steps in Scheme 1.

[0175] Pharmaceutical Compositions and Administration Another object of the present invention is a pharmaceutical composition comprising a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

[0176] The compounds of formula (I) and their pharmaceutically acceptable salts can be used as medicines in the form of pharmaceutical preparations. Pharmaceutical preparations can be administered to the body orally (for example, in the form of tablets, coated tablets, dragees, hard and soft gelatin capsules, solutions, emulsions, or suspensions), nasally (for example, in the form of nasal drops), or rectally (for example, in the form of suppositories). However, administration can also be carried out parenterally, such as intramuscularly or intravenously (for example, in the form of injections). Administration can also be carried out topically, for example, transdermally, or in the form of eye drops or ear drops.

[0177] The compounds of formula (I) and their pharmaceutically acceptable salts can be processed with pharmaceutically inert inorganic or organic carriers for the manufacture of pharmaceutical preparations such as tablets, coated tablets, sugar-coated tablets, hard gelatin capsules, injectable solutions or topical preparations, etc. Lactose, corn starch or its derivatives, talc, stearic acid or its salts, etc. can be used as such carriers, for example, for tablets, coated tablets, sugar-coated tablets and hard gelatin capsules.

[0178] Suitable carriers for soft gelatin capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols, etc. However, depending on the nature of the active substance, no carrier is usually required in the case of soft gelatin capsules.

[0179] Suitable carriers for the production of solutions and syrups are, for example, water, alcohols, polyols, saccharose, glucose, invert sugar, vegetable oil and the like.

[0180] Suitable carriers for injection solutions are, for example, water, alcohols, polyols, glycerol, vegetable oils and the like.

[0181] Suitable carriers for suppositories are, for example, natural or hardened oils, waxes, fats, semi-liquid or liquid polyols and the like.

[0182] Suitable carriers for topical ophthalmic formulations are, for example, cyclodextrin, mannitol, or many other carriers and additives known in the art.

[0183] Furthermore, the pharmaceutical preparations may contain preservatives, solubilizers, viscosity-increasing substances, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorings, salts for varying osmotic pressure, buffers, masking agents or antioxidants. The pharmaceutical formulations of the present invention may further contain other therapeutically valuable substances.

[0184] Medicaments comprising compounds of formula (I) or pharmaceutically acceptable salts thereof and therapeutically inactive excipients are also an object of the present invention, as are processes for their preparation, which involve bringing one or more compounds of formula (I) and / or pharmaceutically acceptable salts thereof, and, if desired, one or more other therapeutically valuable substances, together with one or more pharmaceutically acceptable excipients, into a galenical dosage form.

[0185] The dosage may vary within a wide range and, of course, must be adjusted to the individual requirements in each specific case. Generally, for oral administration, a daily dosage of about 0.1 mg to 20 mg / kg body weight, preferably 0.5 mg to 4 mg / kg body weight (e.g., about 300 mg / person), preferably divided into 1 to 3 individual doses, each of which may consist of the same amount, may be appropriate. For topical administration, the formulation may contain 0.001% to 15% by weight of the drug, and the required dose, which may be between 0.1 and 25 mg, may be administered as a single dose per day, a single dose per week, multiple doses (2 to 4 times per day), or multiple doses per week. However, it is clear that, where indicated, the upper or lower limits set forth herein may be exceeded.

[0186] The pharmaceutical composition of the present invention may be prepared as follows.

[0187] Preparation of Pharmaceutical Compositions Containing Compounds of the Invention

[0188] Tablet formulation (wet granulation) TIFF0007821808000056.tif99170Manufacturing Instructions: 1. Mix ingredients 1, 2, 3 and 4 and granulate with purified water. 2. Dry the granules at 50°C. 3. Pass the granules through a suitable grinding device. 4. Add ingredient 5, mix for 3 minutes and compress in a suitable press.

[0189] Capsule formulation TIFF0007821808000057.tif99170Manufacturing Instructions: 1. Mix ingredients 1, 2 and 3 in a suitable mixer for 30 minutes. 2. Add ingredients 4 and 5 and mix for 3 minutes. 3. Fill into suitable capsules.

[0190] injection solution TIFF0007821808000058.tif63170Manufacturing Instructions: A compound of formula (I) (partially) is dissolved in a mixture of polyethylene glycol 400 and water for injection. The pH is adjusted to 5.0 with acetic acid. The remaining amount of water is added to adjust the volume to 1.0 ml. The solution is filtered, filled into vials using an appropriate overage, and sterilized.

[0191] Indications The compounds of formula (I) can be used in an effective amount to treat subjects, particularly humans, suffering from cancer.

[0192] In one aspect, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use as a therapeutically active substance.

[0193] In a further aspect, the present invention provides a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for use in the treatment, prevention and / or delay of progression of cancer.

[0194] In a further aspect, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the treatment, prevention and / or delay of progression of cancer.

[0195] In a further aspect, the present invention provides the use of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment, prevention and / or delay of progression of cancer.

[0196] In a further aspect, the present invention provides a method for the treatment, prevention and / or delay of progression of cancer, which method comprises administering a therapeutically effective amount of a compound of formula (I) as described herein, or a pharmaceutically acceptable salt thereof.

[0197] As used herein, the terms "treatment" or "treating" and grammatical variations thereof refer to therapeutic therapy. With respect to a particular condition, treating means: (1) ameliorating the condition or one or more biological manifestations of the condition; (2) interfering with (a) one or more points in the biological cascade that leads to or causes the condition, or (b) one or more biological manifestations of the condition; (3) alleviating one or more symptoms, effects, or side effects associated with the condition or its treatment; or (4) slowing the progression of the condition or one or more biological manifestations of the condition. Prophylactic therapy using the methods and / or compositions of the present invention is also contemplated. Those skilled in the art will understand that "prevention" is not an absolute term. In medicine, "prevention" is understood to refer to the prophylactic administration of a drug to substantially reduce the likelihood or severity of a condition or its biological manifestations, or to delay the onset of such a condition or its biological manifestations. Prophylactic therapy is appropriate when a subject is considered to be at high risk for developing cancer, for example, when the subject has a strong family history of cancer or when the subject has been exposed to a carcinogen.

[0198] As immunotherapeutics that act on immune cells rather than directly on cancer cells, the present disclosure may also be envisioned for use as an anti-cancer vaccine, including approaches in which immune cells are cultured and engineered ex vivo and the molecules disclosed herein are used as a means of costimulating the ex vivo engineered cells.

[0199] In one embodiment, the cancer is a blood cancer, such as lymphoma, leukemia, or myeloma. Blood cancers contemplated herein include one or more leukemias, such as B-cell acute lymphoblastic leukemia ("BALL"), T-cell acute lymphoblastic leukemia ("TALL", acute lymphoblastic leukemia (ALL); one or more chronic leukemias, including but not limited to, chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL); B-cell prolymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, hairy cell leukemia These include, but are not limited to, small cell or large cell follicular lymphoma, malignant lymphoproliferative conditions, mucosa-associated lymphoid tissue (MALT) lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndromes, non-Hodgkin's lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenstrom's macroglobulinemia, and "preleukemia," which are a diverse collection of hematological conditions united by the ineffective production (or dysplasia) of myeloid blood cells.

[0200] In further embodiments, the cancer is a non-hematological cancer, such as a sarcoma, carcinoma, or melanoma. Non-hematological cancers contemplated herein include, but are not limited to, neuroblastoma, renal cell carcinoma, colon cancer, colorectal cancer, breast cancer, epithelial squamous cell carcinoma, melanoma, gastric cancer, brain cancer, lung cancer (e.g., non-small cell lung cancer - NSCLC), pancreatic cancer, cervical cancer, ovarian cancer, liver cancer, bladder cancer, prostate cancer, testicular cancer, thyroid cancer, uterine cancer, adrenal cancer, and head and neck cancer.

[0201] Co-administration of compounds of formula (I) and other agents The compound of formula (I) or a salt thereof, or the compounds disclosed herein or a pharmaceutically acceptable salt thereof, can be used alone or in combination with other drugs for treatment. For example, the second drug in a combined pharmaceutical formulation or administration regimen may have complementary activity to the compound of formula (I) so that they do not adversely affect each other. The compounds can be administered together in a single pharmaceutical composition or separately. In one embodiment, the compound or a pharmaceutically acceptable salt can be co-administered with a cytotoxic agent to treat proliferative diseases and cancer.

[0202] The term "co-administering" refers to the simultaneous administration or separate, sequential administration in any manner of a compound of Formula (I) or a salt thereof, or a compound disclosed herein or a pharmaceutically acceptable salt thereof, and additional active pharmaceutical ingredient(s), including cytotoxic agents and radiation therapy. If not administered simultaneously, the compounds are administered in close temporal proximity to each other. Furthermore, it does not matter whether the compounds are administered in the same dosage form; for example, one compound may be administered topically and the other orally.

[0203] Typically, any drug with anti-cancer activity can be co-administered. Examples of such drugs can be found in Cancer Principles and Practice of Oncology by V.T.Devita and S.Heilman (editors), 6th edition (February 15, 2001), Lippincott Williams & Wilkins Publishers. Those skilled in the art will be able to identify which drug combinations are useful based on the specific characteristics of the drugs and the disease involved.

[0204] In one aspect, the present invention provides a pharmaceutical composition as described herein, further comprising an additional therapeutic agent.

[0205] In one embodiment, the additional therapeutic agent is a chemotherapeutic agent.

[0206] In one embodiment, the additional therapeutic agent is a cytotoxic agent.

[0207] In one embodiment, the additional therapeutic agent is a cancer immunotherapeutic agent.

[0208] As used herein, the term "cytotoxic agent" refers to a substance that inhibits or prevents the function of cells and / or causes cell death or destruction. Cytotoxic agents include radioisotopes (AT 211 , I 131 , I 125 , Y 90 ,Re 186 ,Re 188 , Sm 153 , Bi 212 , P 32 , Pb 212 , and radioactive isotopes of Lu); chemotherapeutic agents; growth inhibitory agents; enzymes and fragments thereof, such as nucleolytic enzymes; and toxins (including fragments and / or variants thereof), such as small molecule toxins or enzymatically active toxins of bacterial, fungal, plant, or animal origin.

[0209] Exemplary cytotoxic agents may be selected from anti-microtubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase II inhibitors, antimetabolites, topoisomerase I inhibitors, hormones and hormone analogs, signal transduction pathway inhibitors, non-receptor tyrosine kinase angiogenesis inhibitors, immunotherapeutic agents, pro-apoptotic agents, LDH-A inhibitors, fatty acid biosynthesis inhibitors, cell cycle signaling inhibitors, HDAC inhibitors, proteasome inhibitors, and inhibitors of cancer metabolism.

[0210] "Chemotherapeutic agents" include chemical compounds useful in the treatment of cancer. Examples of chemotherapeutic agents include erlotinib (TARCEVA®, Genentech / OSI Pharm.), bortezomib (VELCADE®, Millennium Pharm.), disulfiram, epigallocatechin gallate, salinosporamide A, carfilzomib, 17-AAG (geldanamycin), radicicol, lactate dehydrogenase A (LDH-A), fulvestrant (FASLODEX®, AstraZeneca), sunitib (SUTENT®, Pfizer / Sugen), letrozole (FEMARA®, Novartis), and rivaroxaban. is), imatinib mesylate (GLEEVEC®, Novartis), finasunate (VATALANIB®, Novartis), oxaliplatin (ELOXATIN®, Sanofi), 5-FU (5-fluorouracil), leucovorin, rapamycin (sirolimus, RAPAMUNE®, Wyeth), lapatinib (TYKERB®, GSK572016, GlaxoSmithKline), lonafamib (SCH 66336), sorafenib (NEXAVAR®, Bayer Labs), gefitinib (IRESSA®, AstraZeneca), AG1478, alkylating agents such as thiotepa and CYTOXAN® cyclophosphamide, alkylsulfonates such as busulfan, improsulfan, and piposulfan, aziridines such as benzodopa, carboquone, mesuredopa, and uredopa, altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide, and trimethylmelamine, acetogenins (especially bullatacin and bullatacinone), camptothecins (including topotecan and irinotecan), bryostatin, kallistatin, CC-1065 (including its azozelesin, carzelesin, and bizelesin synthetic analogs), cryptophycins (especially cryptophycin 1 and cryptophycin 8), corticosteroids (including prednisone and prednisolone), cyproterone acetate,5a-reductase inhibitors, including finasteride and dutasteride, vorinostat, romidepsin, panobinostat, valproic acid, mocetinostat, dolastatins, aldesleukin, talc, duocarmycins (including synthetic analogues KW-2189 and CB1-TMI), eleutherobin, pancratistatin, sarcodictiin, spongistatins, nitrogen mustards, e.g., chlorambucil, chromafazine, chlorophosphamide, estradiol mustard, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembicine, phenesterine, prednimustine, trofosfamide, uracil mustard, nitrosoureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimnustine, antibiotics such as enediyne antibiotics (e.g., calicheamicin, particularly calicheamicin γ1I and calicheamicin chol (Angew Chem. Inti. Ed. Engl. 1994) 33:183-186); dynemycins (including dynemycin A); bisphosphonates such as clodronate; esperamicin. and neocarzinostatin chromophores and related chromoproteins (enediyne antibiotic chromophores), aclacinomycin, actinomycin, ausramycin, azaserine, bleomycin, cactinomycin, carabicin, caminomycin, carzinophilin, chromomycin, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, Adriamycin (doxorubicin), morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcelomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycin, peplomycin, porfiromycin, puromycin, queramycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; antimetabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid analogs such as denopterin, methotrexate, pteropterin, trimetrexate; fludarabine, 6-mercaptopurine,Purine analogs such as thiamiprine and thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, and floxuridine; androgens such as calucelone, dromostanolone propionate, epitiostanol, mepitiostane, and testolactone; antiadrenal drugs such as aminoglutethimide, mitotane, and trilostane; folic acid supplements such as furoic acid; aceglatone; aldophosphamide glycosides; aminolevulinic acid; eniluracil; amsacrine; bestravcil; bisantrene; edatraxate; defoamine; demecolcine; diaziquone; elfomitine; elliptinium acetate; epothilone; etoglucide; gallium nitrate; hydroxyurea; lentinan; lonidynin; maytansine drugs such as maytansine and ansamitocins steroids; mitoguazone; mitoxantrone; mopidamol; nitraelin; pentostatin; phenamet; pirarubicin; losoxantrone; podophyllic acid; 2-ethylhydrazide; procarbazine; PSK® polysaccharide complex (JHS Natural Products, Eugene, Oregon); razoxane; rhizoxin; schizofuran; spirogermanium; tenuazonic acid; triazicone; 2,2',2"-trichlorotriethylamine; trichothecenes (especially T-2 toxin, veracrine A, roridin A, anguidine); urethane; vindesine, dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside ("Ara-C"); cyclophosphamide; thiotepa; taxoids, e.g., TAXOL (paclitaxel; Bristol-Myers Squibb Oncology, Princeton, NJ), ABRAXANE® (Cremophor-free), an albumin-engineered nanoparticle formulation of paclitaxel (American Pharmaceutical Partners, Schaumburg, IL), and TAXOTERE® (docetaxel,doxetaxel; Sanofi-Aventis; chlorambucil; GEMZAR® (gemcitabine); 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin and carboplatin; vinblastine; etoposide (VP-16); ifosfamide; mitoxantrone; vincristine; NAVELBINE® (vinorelbine); novantrone; teniposide; edatrexate; daunomycin; aminopterin; capecitabine (XELODA®); ibandronate; CPT-II; the topoisomerase inhibitor RFS2000; difluoromethylorutine (DMFO); retinoids such as retinoic acid; and pharmaceutically acceptable salts, acids, and derivatives of any of the above.

[0211] Chemotherapeutic agents include (i) antihormonal agents that act to regulate or inhibit hormone action on tumors, such as antiestrogens and selective estrogen receptor modulators (SERMs), for example, tamoxifen (including NOLVADEX (registered trademark) and tamoxifen citrate), raloxifene, droxifene, iodoxifene, 4-hydroxytamoxifen, trihydroxyphene, ketoxifene, and LY1; 17018, onapristone, and FARESTON® (toremifine citrate); (ii) aromatase inhibitors that inhibit the enzyme aromatase, which regulates estrogen production in the adrenal glands, such as 4(5)-imidazole, aminoglutethimide, MEGASE® (megstrol acetate), AROMASIN® (exemestane; Pfizer), formestany, fadrozole, RIVISOR® (vorozole), FEMARA® (letrozole; Novartis), and ARIMIDEX® (anastrozole; AstraZeneca); (iii) antiandrogens such as flutamide, nilutamide, bicalutamide, leuprolide, and goserelin; buserelin, tripterelin, medroxyprogesterone acetate, diethylstilbestrol, Premarin, fluoxymesterone, all-trans retinol, (iv) protein kinase inhibitors; (v) lipid kinase inhibitors; (vi) antisense oligonucleotides, particularly agents that inhibit the expression of genes in signal transduction pathways involved in abnormal cell growth, such as PKC-alpha, Ralf, and H-Ras; (vii) ribozymes such as VEGF expression inhibitors (e.g., ANGIOZYME®), HER2 expression inhibitors; (viii) vaccines such as gene therapy vaccines, for example, ALLOVECTIN®, LEUVECTIN®, VAXID®; PROLEUKIN®, rIL-2; topoisomerase I inhibitors such as LURTOTECAN®; ABARELIX® rmRH; and (ix) pharmaceutically acceptable salts, acids, and derivatives of any of the above.

[0212] Chemotherapeutic agents also include antibodies such as alemtuzumab (Campath), bevacizumab (AVASTIN®, Genentech), cetuximab (ERBITUX®, Imclone), panitumumab (VECTIBIX®, Amgen), rituximab (RITUXAN®, Genentech / Biogen Idec), pertuzumab (OMNITARG®, 2C4, Genentech), trastuzumab (HERCEPTIN®, Genentech), tositumomab (Bexxar, Corixia), and the antibody-drug conjugate, gemtuzumab ozogamicin (MYLOTARG®, Wyeth). Additional humanized monoclonal antibodies with therapeutic potential as agents in combination with the compounds of the invention include apolizumab, aselizumab, atlizumab, bapineuzumab, bivatuzumab mertansine, cantuzumab mertansine, cedelizumab, celizumab pegol, cidfusituzumab, cidtuzumab, daclizumab, eculizumab, efalizumab, epratuzumab, erlizumab, felvizumab, fontolizumab, gemtuzumab ozogamicin, inotuzumab ozogamicin, ipilimumab, labetuzumab, lintuzumab, matuzumab, mepolizumab, motavizumab, nat ... tuzumab, nimotuzumab, norobizumab, numavizumab, ocrelizumab, omalizumab, palivizumab, pascolizumab, pecfusituzumab, pexelizumab, pexelizumab, ralivizumab, ranibizumab, reslivizumab, reslizumab, reslizumab, reslivizumab, rovelizumab, lupizumab, sibrotuzumab, siplizumab, sontuzumab, tacatatuzumab tetraxetan, tadoxizumab, talizumab, tefibazumab, tocilizumab, toralizumab, tucotuzumab selmoreukin, tuxituuzumab, umavizumab, urtoxazumab, ustekinumab, visilizumab, and interleukin-12 and anti-interleukin-12 (ABT-874 / J695, Wyeth Research and Abbott Laboratories), a human-sequence only, full-length IgG1λ antibody genetically engineered to recognize the p40 protein.

[0213] Chemotherapeutic agents also include "EGFR inhibitors," which refer to compounds that bind to or otherwise directly interact with EGFR and inhibit or reduce the signaling activity of EGFR, alternatively referred to as "EGFR antagonists." Examples of such agents include antibodies and small molecules that bind to EGFR.Examples of antibodies that bind to EGFR include MAb 579 (ATCC CRL HB 8506), MAb 455 (ATCC CRL HB 8507), MAb 225 (ATCC CRL 8508), MAb 528 (ATCC CRL 8509) (see U.S. Pat. No. 4,943,533, Mendelsohn et al.), and variants thereof, such as chimerized 225 (C225 or cetuximab; ERBUTIX®) and reshaped human 225 (H225) (WO 96 / 40210, Imclone Systems, Inc.). Inc.), IMC-11F8, a fully human, EGFR-targeting antibody (Imclone), antibodies that bind type II mutant EGFR (U.S. Pat. No. 5,212,290), humanized and chimeric antibodies that bind EGFR as described in U.S. Pat. No. 5,891,996, and human antibodies that bind EGFR, such as ABX-EGF or panitumumab (WO 98 / 50433, Abgenix / Amgen), EMD 55900 (Stragliotto et al., Eur. J. Cancer 32A:636-640 (1996)), EMD7200 (matuzumab), a humanized EGFR antibody against EGFR that competes with both EGF and TGF-α for EGFR binding (EMD / Merck), the human EGFR antibodies, HuMax-EGFR (GenMab), E1.1, E2.4, E2.5, E6.2, E6.4, E2.11, E6.3, and E7.6.3, known as fully human antibodies and described in U.S. Pat. No. 6,235,883, MDX-447 (Medarex Inc), and mAb 806 or humanized mAb 806 (Johns et al. al., J. Biol. Chem. 279(29):30375-30384 (2004)). Anti-EGFR antibodies can be conjugated to cytotoxic agents to generate immunoconjugates (see, e.g., European Patent Application Publication No. 659,439 A2, Merck Patent GmbH).EGFR antagonists include those described in U.S. Patent Nos. 5,616,582, 5,457,105, 5,475,001, 5,654,307, 5,679,683, 6,084,095, 6,265,410, 6,455,534, 6,521,620, 6,596,726, 6,713,484, 5,770,599, 6,140,332, and 5,866,572. , 6,399,602, 6,344,459, 6,602,863, 6,391,874, 6,344,455, 5,760,041, 6,002,008, and 5,747,498, and the following PCT publications: WO 98 / 14451, WO 98 / 50038, WO 99 / 09016, and WO 99 / 24037.Specific small molecule EGFR antagonists include OSI-774 (CP-358774, erlotinib, TARCEVA®, Genentech / OSI Pharmaceuticals), PD183805 (CI 1033, 2-propenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-quinazolinyl]-, dihydrochloride, Pfizer Inc.), ZD1839, gefitinib (IRESSA®) 4-(3'-chloro-4'-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline, AstraZeneca), ZM105180 ((6-amino-4-(3-methylphenyl-amino)-quinazoline, Zeneca), BIBX-1382 (N8-(3-chloro-4-fluoro-phenyl)-N2-(1-methyl-piperidin-4-yl)-pyrimido[5,4-d]pyrimidine-2,8-diamine, Boehringer Ingelheim), Ingelheim), PKI-166 ((R)-4-[4-[(1-phenylethyl)amino]-1H-pyrrolo[2,3-d]pyrimidin-6-yl]-phenol; (R)-6-(4-hydroxyphenyl)-4-[(1-phenylethyl)amino]-7H-pyrrolo[2,3-d]pyrimidine); CL-387785 (N-[4-[(3-bromophenyl)amino]-6-quinazolinyl]-2-butynamide), EKB-569 (N-[4-[(3-chloro-4-fluorophenyl)amino]-3-cyano- 7-ethoxy-6-quinolinyl]-4-(dimethylamino)-2-butynamide) (Wyeth), AG1478 (Pfizer); AG1571 (SU5271, Pfizer), and dual EGFR / HER2 tyrosine kinase inhibitors, such as lapatinib (TYKERB®, GSK572016 or N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6[5[[[2methylsulfonyl)ethyl]amino]methyl]-2-furanyl]-4-quinazolinamine).

[0214] Chemotherapeutic agents include "tyrosine kinase inhibitors," such as the EGFR-targeted drugs described in the previous paragraph; small molecule HER2 tyrosine kinase inhibitors, such as TAK165 available from Takeda; CP-724,714, an oral selective inhibitor of ErbB2 receptor tyrosine kinase (Pfizer and OSI); dual HER inhibitors, such as EKB-569 (available from Wyeth), which preferentially binds to EGFR but inhibits both HER2 and EGFR-overexpressing cells; lapatinib (GSK572016, available from Glaxo-SmithKline), an oral HER2 and EGFR tyrosine kinase inhibitor; PKI-166 (available from Novartis); pan-HER inhibitors, such as canertinib (CI-1033, Pharmacia); Raf-1 inhibitors, such as ISIS, which inhibits Raf-1 signaling. antisense drug ISIS-5132 available from Pharmaceuticals; non-HER-targeted TK inhibitors such as imatinib mesylate (GLEEVEC®, available from GlaxoSmithKline); multi-targeted tyrosine kinase inhibitors such as sunitinib (SUTENT®, available from Pfizer); VEGF receptor tyrosine kinase inhibitors such as vatalanib (PTK787 / ZK222584, available from Novartis / Schering AG); the MAPK extracellular regulated kinase I inhibitor CI-1040 (available from Pharmacia); quinazolines such as PD 153035, 4-(3-chloroanilino)quinazoline; pyridopyrimidines; pyrimidopyrimidines; pyrrolopyrimidines such as CGP 59326, CGP 60261, and CGP 62706; pyrazolopyrimidine, 4-(phenylamino)-7H-pyrrolo[2,3-d]pyrimidine; curcumin (diferuloylmethane, 4,5-bis(4-fluoroanilino)phthalimide); tyrphostins containing a nitrothiophene moiety; PD-0183805 (Warner-Lamber); antisense molecules (e.g., those that bind to HER-encoding nucleic acids); quinoxalines (U.S. Patent No. 5,804,396); tryphostins (U.S. Patent No. 5,804,396); ZD6474 (Astra Zeneca);PTK-787 (Novartis / Schering AG); pan-HER inhibitors, such as CI-1033 (Pfizer); Affinitac (ISIS 3521, Isis / Lilly); imatinib mesylate (GLEEVEC®); PKI 166 (Novartis); GW2016 (GlaxoSmithKline); CI-1033 (Pfizer); EKB-569 (Wyeth); Semaxinib (Pfizer); ZD6474 (AstraZeneca); PTK-787 (Novartis / Schering AG); INC-1C11 (Imclone), rapamycin (sirolimus, RAPAMUNE®); or the following patent publications: U.S. Pat. No. 5,804,396, WO 1999 / 09016 (American Cyanamid), WO 1998 / 43960 (American Cyanamid), 1997 / 38983 (Warner Lambert), 1999 / 06378 (Warner Lambert), 1999 / 06396 (Warner Lambert), 1996 / 30347 (Pfizer, Inc.), 1996 / 33978 (Zeneca), 1996 / 3397 (Zeneca), and 1996 / 33980 (Zeneca).

[0215] Chemotherapeutic agents include dexamethasone, interferon, colchicine, metoprine, cyclosporine, amphotericin, metronidazole, alemtuzumab, alitretinoin, allopurinol, amifostine, arsenic trioxide, asparaginase, BCG (raw), bevacizumab, bexarotene, cladribine, clofarabine, darbepoetin alfa, denileukin, dexrazoxane, epoetin alfa, erlotinib, filgrastim, histrelin acetate, ibritumomab, interferon alfa-2a, and interferon alfa. Also included are benzodiazepine-2b, lenalidomide, levamisole, mesna, methoxsalen, nandrolone, nelarabine, nofetumomab, oprelvekin, palifermin, pamidronate, pegademase, pegaspargase, pegfilgrastim, pemetrexed disodium, plicamycin, porfimer sodium, quinacrine, rasburicase, sargramostim, temozolomide, VM-26, 6-TG, toremifene, tretinoin, ATRA, valrubicin, zoledronate, and zoledronic acid, and pharmaceutically acceptable salts thereof.

[0216] Chemotherapeutic agents include hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, triamcinolone acetonide, triamcinolone alcohol, mometasone, amcinonide, budesonide, desonide, fluocinonide, fluocinolone acetonide, betamethasone, betamethasone sodium phosphate, dexamethasone, dexamethasone sodium phosphate, fluocortolone, and hydrocortisone-17. -butyrate, hydrocortisone-17-valerate, aclometasone dipropionate, betamethasone valerate, betamethasone dipropionate, prednicarbate, clobetasone-17-butyrate, clobetasone-17-propionate, fluocortolone caproate, fluocortolone pivalate, and fluprednidene acetate; phenylalanine-glutamine-glycine (PEG) and its D-form (feG) (IMULAN) Immunoselective anti-inflammatory peptides (ImSAIDs) such as BioTherapeutics, LLC; antirheumatic drugs such as azathioprine, cyclosporine (cyclosporine A), D-penicillamine, gold salts, hydroxychloroquine, leflunomide, minocycline, and sulfasalazine; etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), cetolithumab pegol (Cimzia), and golimumab (Symptoms); tumor necrosis factor alpha (TNFα) blockers such as lebrikizumab (Kineret); interleukin 1 (IL-1) blockers such as anakinra (Kineret); T-cell costimulation blockers such as abatacept (Orencia); interleukin 6 (IL-6) blockers such as tocilizumab (ACTEMERA®); interleukin 13 (IL-13) blockers such as lebrikizumab; interferon alpha (IFN) blockers such as rontalizumab; beta 7 integrin blockers such as rhuMAb Beta7; IgE pathway blockers such as anti-M1 prime; secreted homotrimeric LTa3 and membrane-bound heterotrimeric LTa1 / β2 blockers such as anti-lymphotoxin alpha (LTa); radioisotopes (e.g., At 211 , I 131 , I 125 , Y 90 ,Re 186 ,Re 188 , Sm 153 , Bi 212 , P32 、Pb 212, and radioactive isotopes of Lu); various investigational drugs such as thioplatin, PS-341, phenylbutyrate, ET-18-OCH3, and farnesyltransferase inhibitors (L-739749, L-744832); polyphenols such as quercetin, resveratrol, piceatannol, epigallocatechin gallate, theaflavins, flavanols, procyanidins, betulinic acid and its derivatives; autophagy inhibitors such as chloroquine; delta-9-tetrahydrocannabinol (dronabinol, MARINOL®); beta-lapachone; lapachol; colchicine; betulinic acid; acetylcamptothecin, scopolectin, and 9-aminocamptothecin; podophyllotoxin; tegafur (UFTORAL®); bexarotene (TARGRETIN®); clodronate (e.g., BONEFOS®) ) or OSTAC®), etidronate (DIDROCAL®), NE-58095, zoledronic acid / zoledronate (ZOMETA®), alendronate (FOSAMAX®), pamidronate (AREDIA®), tiludronate (SKELID®), or risedronate (ACTONEL®); as well as epidermal growth factor receptor (EGF-R); vaccines such as the THERATOPE® vaccine; perifosine, COX-2 inhibitors (e.g., celecoxib or etoricoxib), proteosome inhibitors (e.g., PS341); CCI-779; tipifarnib (R11577); orafenib, ABT510; Bcl-2 inhibitors such as oblimersen sodium (GENASENSE®); pixantrone; lonafarnib (SCH 6636, SARASAR™); and pharmaceutically acceptable salts, acids, or derivatives of any of the foregoing; and combinations of two or more of CHOP, which is an abbreviation for the combination therapy of cyclophosphamide, doxorubicin, vincristine, and prednisolone, and FOLFOX, which is an abbreviation for the treatment regimen with oxaliplatin in combination with 5-FU and leucovorin (ELOXATIN™).

[0217] In another embodiment, the compound of Formula (I) can be co-formulated with a cancer immunotherapeutic agent. Cancer immunotherapeutic agents include, for example, small molecule drugs, antibodies, or other biological or small molecules. Examples of biological cancer immunotherapeutic agents include, but are not limited to, cancer vaccines, antibodies, and cytokines. In one aspect, the antibody is a monoclonal antibody. In another aspect, the monoclonal antibody is humanized or human. In another aspect, the antibody is a bispecific antibody.

[0218] In one aspect, the cancer immunotherapeutic agent is either (i) an agonist of a stimulatory (including costimulatory) receptor or (ii) an antagonist of an inhibitory (including co-inhibitory) signal on T cells, both of which result in amplification of antigen-specific T cell responses (often referred to as immune checkpoint modulators).

[0219] Certain stimulatory and inhibitory molecules are members of the immunoglobulin superfamily (IgSF). One important family of membrane-bound ligands that bind to costimulatory or costimulatory receptors is the B7 family, which includes B7-1, B7-2, B7-H1 (PD-L1), B7-DC (PD-L2), B7-H2 (ICOS-L), B7-H3, B7-H4, B7-H5 (VISTA), and B7-H6. Another family of membrane-bound ligands that bind to costimulatory or coinhibitory receptors are CD40 and CD40L, OX-40, OX-40L, CD70, CD27L, CD30, CD30L, 4-1BBL, CD137 (4-1BB), TRAIL / Apo2-L, TRAILR1 / DR4, TRAILR2 / DR5, TRAILR3, TRAILR4, OPG, RANK, RANKL, TWEAKR / Fnl4, TWEAK, BAFFR, EDAR, XEDAR, TACI, APRIL, BCMA, LTfiR, LIGHT, DcR3, HVEM, VEGI / TL1A, TRAMP / DR3, EDAR, EDA1, XEDAR, EDA2, TNFR1, lymphotoxin alpha / TNP beta, TNFR2, TNFα, LTTR, lymphotoxin a It is a TNF family molecule that binds to cognate TNF receptor family members, including 1β2, FAS, FASL, RELT, DR6, TROY, and NGFR.

[0220] In one aspect, a T cell response may be stimulated by a combination of a compound of Formula (I) and (i) an antagonist of a protein that inhibits T cell activation (e.g., an immune checkpoint inhibitor), such as CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, TIM-3, Galectin-9, CEACAM-1, BTLA, CD69, Galectin-1, TIGIT, CD113, GPR56, VISTA, 2B4, CD48, GARP, PD1H, LAIR1, TIM-1, and TIM-4, and (ii) one or more of B7-1, B7-2, CD28, 4-1BB (CD137), 4-1BBL, ICOS, ICOS-L, OX40, OX40L, GITR, GITRL, CD70, CD27, CD40, DR3, and CD28H.

[0221] Other drugs that can be combined with the compound of formula (I) for the treatment of cancer include antagonists of inhibitory receptors on NK cells or agonists of activating receptors on NK cells. For example, the compound of formula (I) can be combined with a KIR antagonist such as lirilumab.

[0222] Still other agents for combination therapy include agents that inhibit or deplete macrophages or monocytes, including CSF-1R antagonists such as CSF-1R antagonist antibodies, including but not limited to RG7155 or FPA-008.

[0223] In another aspect, the compounds of formula (I) can be used in conjunction with one or more agents that include agonistic agents that ligate positive costimulatory receptors, blocking agents that attenuate signaling through inhibitory receptors, antagonists, and one or more agents that systemically increase the frequency of anti-tumor T cells, agents that overcome different immunosuppressive pathways within the tumor microenvironment (e.g., blocking inhibitory receptor binding (e.g., PD-L1 / PD-1 interactions), depleting or inhibiting Tregs (e.g., using anti-CD25 monoclonal antibodies (e.g., daclizumab) or by ex vivo anti-CD25 bead depletion), inhibiting metabolic enzymes such as IDO, or reversing / preventing T cell anergy or exhaustion), and innate immune activation and / or inflammation at the tumor site.

[0224] In some embodiments, the cancer immunotherapeutic agent is a CTLA-4 antagonist, such as an antagonistic CTLA-4 antibody. Suitable CTLA-4 antibodies include, for example, YERVOY (ipilimumab) or tremelimumab. In another aspect, the cancer immunotherapeutic agent is a PD-1 antagonist, e.g., an antagonist PD-1 antibody. Suitable PD-1 antibodies include, for example, OPDIVO (nivolumab), KEYTRUDA (pembrolizumab), or MEDI-0680 (AMP-514; WO 2012 / 145493). Cancer immunotherapeutic agents can also include pidilizumab (CT-011), although its specificity for PD-1 binding has been questioned. Another approach to targeting the PD-1 receptor is a recombinant protein called AMP-224, which consists of the extracellular domain of PD-L2 (B7-DC) fused to the Fc portion of IgG1.

[0225] In another embodiment, the cancer immunotherapeutic agent is a PD-L1 antagonist, e.g., an antagonist PD-L1 antibody. Suitable PD-L1 antibodies include, for example, TECENTRIQ (atezolizumab) (RG7446; WO 2010 / 077634), durvalumab (MEDI4736), BMS-936559 (WO 2007 / 005874), and MSB0010718C (WO 2013 / 79174).

[0226] In another embodiment, the cancer immunotherapeutic agent is a LAG-3 antagonist, such as an antagonist LAG-3 antibody. Suitable LAG-3 antibodies include, for example, BMS-986016 (WO 2010 / 19570, WO 2014 / 08218), or IMP-731 or IMP-321 (WO 2008 / 132601, WO 2009 / 44273).

[0227] In another aspect, the cancer immunotherapeutic agent is a CD137 (4-1BB) agonist, such as an agonist CD137 antibody. Suitable CD137 antibodies include, for example, urelumab and PF-05082566 (WO 2012 / 32433).

[0228] In another embodiment, the cancer immunotherapeutic agent is a GITR agonist, such as an agonistic GITR antibody. Suitable GITR antibodies include, for example, BMS-986153, BMS-986156, TRX-518 (WO 2006 / 105021, WO 2009 / 009116), and MK-4166 (WO 2011 / 028683).

[0229] In another embodiment, the cancer immunotherapeutic agent is an IDO antagonist. Suitable IDO antagonists include, for example, INCB-024360 (WO 2006 / 122150, WO 2007 / 75598, WO 2008 / 36653, WO 2008 / 36642), indoximod, or NLG-919 (WO 2009 / 73620, WO 2009 / 1156652, WO 2011 / 56652, WO 2012 / 142237).

[0230] In another embodiment, the cancer immunotherapeutic agent is an OX40 agonist, e.g., an agonist OX40 antibody. Suitable OX40 antibodies include, for example, MEDI-6383 or MEDI-6469. In another embodiment, the cancer immunotherapeutic agent is an OX40L antagonist, e.g., an antagonist OX40 antibody. Suitable OX40L antagonists include, for example, RG-7888 (WO 06 / 029879).

[0231] In another aspect, the cancer immunotherapeutic agent is a CD40 agonist, e.g., an agonist CD40 antibody. I...

Claims

1. Formula (I) (In the formula, X is C(R ７ ) or N, Y is S, S(O), S(O) ２、 S(O)N(R ｙ ) and R １ is a 5-membered heteroaryl, and R １ represents one or more R １０ may be substituted with R ２ , R ３ and R ７ are each independently hydrogen, halogen, or C １～６ -Alkyl, C ２～６ -alkynyl, hydroxy, cyano, halo-C １～６ -alkyl, N(R ８ R ８ａ ), C １～６ -alkoxy, C ３～７ - selected from cycloalkyl and 3- to 10-membered heterocyclyl; R ４ is C ５～１４ -aryl and 5- to 14-membered heteroaryl, R ４ represents one or more R １１ may be substituted with R ５ is hydrogen, C １～６ -alkyl, -C(O)(R ９ ), amino, amino-C １～６ -Alkyl and C ３～７ -cycloalkyl, Said C ３～７ -Cycloalkyl is one or more C １～６ -Alkyl, amino, amino-C １～６ -alkyl-, R ６ and R ６ａ are each independently hydrogen and C １ ~ ６ - alkyl, R ８ and R ８ａ are each independently hydrogen and C １ ~ ６ - alkyl, R ９ is C １～６ -Alkyl, hydroxy-C １～６ -Alkyl, amino-C １～６ -alkyl- and -(C １～６ -alkyl)-N(R ９ａ R ９ｂ ) wherein said amino-C １～６ -Alkyl may be one or more hydroxy, hydroxy-C １～６ -alkyl-, R ９ａ and R ９ｂ are each independently hydrogen and C １～６ -alkyl, wherein said C １～６ - alkyl may be substituted with one or more hydroxy; or R ９ａ and R ９ｂ together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R １０ teeth, i) one or more halogens, C ２～６ -alkynyl, halo-C １～６ - alkyl, amino, hydroxy, 5-6 membered heteroaryl, C １～６ -haloalkoxy, C １～６ -alkoxy, 3- to 10-membered cycloalkyl, C １～３ -alkyl, -N(R １０ａ R １０ｂ ), -S(O) ２ (C １～６ -alkyl), -S(O)2(C １～６ -cycloalkyl), 3- to 10-membered heterocyclyl, phenyl, cyano, —C(O)N(R １０ｃ R １０ｄ ) optionally substituted with C １～１０ - alkyl, 3- to 10-membered heterocyclyl, 3- to 10-membered cycloalkyl, and phenyl may be one or more C １～１０ -Alkyl, C １～１０ -alkoxy, -S(O) ２ (C １～６ -alkyl), oxo, halogen, C ２～６ -alkynyl, optionally substituted with 3- to 10-membered cycloalkyl, C １～１０ - alkyl, ii) one or more halogens, C １～１０ -alkyl, -S(O) ２ (C １～６ alkyl), cyano, C １～６ Haloalkyl, C １～６ -alkoxy, hydroxy, oxo, amino, -C(O)N(R １０ｃ R １０ｄ ), ═N(OH), hydroxy-C １～６ - optionally substituted with alkyl, C ３～１０ -cycloalkyl, iii) one or more halogens, C １～１０ -alkyl, -S(O) ２ (C １～６ -alkyl), -C １～１０ -Alkyl-C １～４ -alkoxy, amino, -C(O)N(R １０ｈ R １０ｉ ), C １～６ -haloalkyl, C １～６ -alkoxy, cyano, hydroxy-C １～１０ -alkyl, oxo, -C(O)(C １～６ -alkyl), -C(O)O-(R １０ｑ ), C ３～１０ -3-10 membered heterocyclyl optionally substituted by cycloalkyl, iv) one or more halogens, C １～１０ -alkyl, -S(O) ２ (C １～６ -alkyl), phenyl, v)-N(R １０ｅ R １０ｆ )、 vi)-OR １０ｇ 、 | １０ｈ ( １０ｉ 、 viii) one or more C １～１０ -Alkyl, halogen, -SO ２ (C １～６ heteroaryl, optionally substituted with alkyl; ix) oxo is selected from R １０ａ and R １０ｂ are each independently hydrogen, C １～６ -Alkyl, halo-C １～６ -Alkyl, hydroxy-C １～６ -Alkyl, C １～６ -alkoxy, -C(O)(R １０ｊ ), amino-C １～６ -alkyl-, 3- to 10-membered heterocyclyl, -SO ２ (R １０ｋ ), -C １～６ -Alkyl-SO ２ (R １０ｋ ) and -N(R １０ｌ R １０ｍ ) wherein 3- to 10-membered heterocyclyl is selected from C １～６ - optionally substituted with alkyl, or R １０ａ and R １０ｂ together with the nitrogen atom to which they are attached, one or more halogens, C １～６ - forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl, R １０ｃ and R １０ｄ are each independently hydrogen and C １～６ - alkyl, R １０ｅ and R １０ｆ are each independently i) hydrogen, ii) optionally substituted with one or more cyano, halogen, or hydroxy; １～６ - alkyl, i))i｣｣ １０ｎ 、 iv) one or more C ２～６ -optionally substituted by alkynyl, -C １～１０ Alkyl ((O-C １～１０ alkyl) ｍ ) wherein m is an integer between 1 and 5; v) one or more of halogen, hydroxy, oxo, C １～１０ -Alkyl, halo-C １～１０ -Alkyl, hydroxy-C １～６ -Alkyl, C １～６ -alkoxy, -C(O)O(R １０ｏ ), —C(O)(R １０ｏ ), -C(O)N(R １０ｐ ) (R １０ｐ’ ), -SO ２ (C １～６ -alkyl), optionally substituted by C2-6-alkynyl, C ３～１０ -cycloalkyl, and vi) one or more of halogen, hydroxy, oxo, C １～１０ -Alkyl, halo-C １～１０ -Alkyl, hydroxy-C １～６ -Alkyl, C １～６ -alkoxy, -C(O)O(R １０ｏ ), —C(O)(R １０ｏ ), -C(O)N(R １０ｐ ) (R １０ｐ’ ), -SO ２ (C １～６ -alkyl), 3- to 10-membered heterocyclyl optionally substituted with 3- to 10-membered cycloalkyl is selected from R １０ｇ Halo-C １～６ -Alkyl, cyano, -C １～１０ -alkyl-phenyl, -C １～６ -Alkyl-C ３～７ -cycloalkyl and -C １～６ -alkoxy-halo-C １～６ - alkyl, R １０ｈ and R １０ｉ are each independently hydrogen and C １～６ -Alkyl, C １～６ -haloalkyl, C １～６ -Alkyl and C １～６ -haloalkyl may be optionally substituted with one or more hydroxy; or R １０ｈ and R １０ｉ together with the nitrogen atom to which they are attached, represent one or more halogens, hydroxy, C １～６ - forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl, R １０ｊ is C １～６ -Alkyl, halo-C １～６ -Alkyl-, hydroxy-C １～６ -Alkyl- and amino-C １～６ -alkyl-, R １０ｋ is hydrogen, C １～６ -Alkyl and halo-C １～６ - alkyl, R １０ｌ and R １０ｍ are each independently hydrogen and C １～６ - alkyl, R １０ｎ is C １～６ -Alkyl, amino-C １～６ -Alkyl-, halo-C １～６ -Alkyl, C ３～７ -cycloalkyl and 3- to 10-membered heterocyclyl, wherein C ３～７ - cycloalkyl and 3- to 10-membered heterocyclyl are selected from the group consisting of one or more halogens, C １～６ - optionally substituted with alkyl, R １０ｏ is C １～６ -Alkyl and halo-C １～６ - alkyl, R １０ｐ and R １０ｐ’ are independently hydrogen, C １～６ -Alkyl and halo-C １～６ - alkyl, R １０ｑ is C １～１０ -Alkyl, C １～６ - haloalkyl, aryl, heteroaryl, wherein aryl and heteroaryl are selected from one or more halogens, C １～１０ - optionally substituted with alkyl, R １１ teeth, i) halogens, ii) hydroxy, iii) cyano, iv) one or more of cyano, halogen, hydroxyl, C ３～７ -Optionally substituted with cycloalkyl, amino, aryl, -O-aryl, 5- to 6-membered heteroaryl, 3- to 7-membered heterocyclyl, C １～１０ - alkyl, 3- to 7-membered heterocyclyl and aryl may be one or more C １～６ -Alkyl, -SO ２ (C １～６ -alkyl), optionally substituted with hydroxy, halogen or cyano, C １～１０ - alkyl, v) one or more 3- to 10-membered heterocyclyl, optionally substituted with halogen, C １～６ -alkoxy, vi) C ３～７ -cycloalkyl, vii) one or more halo-C １～６ -Alkyl, hydroxy, C １～６ -Alkyl, C ３～１０ -cycloalkyl, C １～６ -3- to 10-membered heterocyclyl optionally substituted by alkoxy or oxo; viii) one or more C １～６ -alkyl, 3- to 10-membered cycloalkyl, halogen, halo-C １～６ -Alkyl, C １～６ -alkoxy, C １～６ -5-6 membered heteroaryl optionally substituted with haloalkoxy; ix) one or more of halogen, cyano, C １～６ -alkoxy, C １～６ -haloalkyl, C １～６ -haloalkoxy, C １～６ -phenyl optionally substituted with alkyl, x)-O(R １１ａ )、 ｾi)-C(O)N(R １１ｂ R １１ｃ ), xii)-SO ２ (R １１ｄ )、 xiii)-C(O)OR １１ｅ 、 xiv)-C(O)R １１ｆ 、 xv) oxo, xvi)-N(R １１ｇ R １１ｈ ), and xvii)-S(R １１ｋ ) is selected from R １１ａ is C １～１２ -Alkyl, halo-C １～６ -Alkyl, amino-C １～１２ -Alkyl-, hydroxy-C １～６ -Alkyl-, cyano, C ２～６ -alkynyl, C ３～７ -cycloalkyl, 3- to 10-membered heterocyclyl, 3- to 10-membered -(C １～６ -alkyl)heterocyclyl, 5- to 6-membered heteroaryl, phenyl, -C １～６ -alkyl-phenyl, -C １～１２ -alkyl-C(O)N(R １１ｉ R １１ｊ ), -C １～１２ -Alkyl-NH-C(O)(C １～６ -alkyl), -C １～１２ -alkoxy-NH-C(O)(C １～６ -alkyl), -C １～６ -Alkyl-NH-C(O)(C １－６ -alkyl), -(CH ２ CH ２ O) ｎ -CH ２ CH ２ NH ２ and -(CH ２ CH ２ O) ｎ -CH ２ CH ２－ NH-C(O)(C １～６ -alkyl), Said C １～１２ -Alkyl, C ３～７ -cycloalkyl, 3- to 10-membered heterocyclyl, 5- to 6-membered heteroaryl, phenyl, and -C １～６ -Alkyl-phenyl is selected from the group consisting of one or more halogens, C １～６ -Alkyl, halo-C １～６ -Alkyl, C １～６ -alkoxyl, C １～６ -optionally substituted with haloalkoxyl, cyano, n is an integer between 1 and 6; R １１ｂ and R １１ｃ are each independently hydrogen, C １～６ -Alkyl and halo-C １～６ - alkyl; or R １１ｂ and R １１ｃ together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R １１ｄ is hydrogen, C １～６ -alkyl, -N(R １１ｌ R １１ｍ ), Halo-C １～６ - selected from alkyl and phenyl, R １１ｅ is hydrogen and C １～６ - alkyl, R １１ｆ is hydrogen, C １～６ - selected from alkyl and phenyl, R １１ｇ and R １１ｈ are each independently hydrogen, C １～６ -alkyl, -(C １～６ -alkyl)phenyl, halo-C １～６ -Alkyl, -SO ２ (C １～６ -alkyl), -SO ２ (Halo-C １～６ -alkyl) and -SO(C １～６ -alkyl) ２ is selected from R １１ｉ and R １１ｊ are each independently hydrogen, C １～６ -Alkyl and halo-C １～６ - alkyl; or R １１ｉ and R １１ｊ together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R １１ｋ is hydrogen, C １～６ -Alkyl and halo-C １～６ - alkyl, R １１ｌ and R １１ｍ are each independently hydrogen and C １～６ - alkyl; or R １１ｌ and R １１ｍ together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R ｙ is hydrogen and C １～６ -alkyl) or a pharmaceutically acceptable salt thereof.

2. The compound is represented by formula (I) (In the formula, X is C(R ７ ) or N, Y is S, S(O), S(O) ２、 S(O)N(R ｙ ) and R １ is a 5-membered heteroaryl, and R １ represents one or more R １０ may be substituted with R ２ , R ３ and R ７ are each independently hydrogen, halogen, or C １～６ -Alkyl, C ２～６ -alkynyl, hydroxy, cyano, halo-C １～６ -alkyl, N(R ８ R ８ａ ), C １～６ -alkoxy, C ３～７ - selected from cycloalkyl and 3- to 10-membered heterocyclyl; R ４ is C ５～１４ -aryl and 5- to 14-membered heteroaryl, R ４ represents one or more R １１ may be substituted with R ５ is hydrogen, C １～６ -alkyl, -C(O)(R ９ ), amino, amino-C １～６ -Alkyl and C ３～７ -cycloalkyl, Said C ３～７ -Cycloalkyl is one or more C １～６ -Alkyl, amino, amino-C １～６ -alkyl-, R ６ and R ６ａ are each independently hydrogen and C １～６ - alkyl, R ８ and R ８ａ are each independently hydrogen and C １～６ - alkyl, R ９ is C １～６ -Alkyl, hydroxy-C １～６ -Alkyl, amino-C １～６ -alkyl- and -(C １～６ -alkyl)-N(R ９ａ R ９ｂ ) wherein said amino-C １～６ -Alkyl may be one or more hydroxy, hydroxy-C １～６ - optionally substituted with alkyl, R ９ａ and R ９ｂ are each independently hydrogen and C １～６ -alkyl, wherein said C １～６ - alkyl may be substituted with one or more hydroxy; or R ９ａ and R ９ｂ together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R １０ teeth, i) one or more halogens, C ２～６ -alkynyl, halo-C １～６ -Alkyl, amino, hydroxy, C １～６ -alkoxy, -N(R １０ａ R １０ｂ ), -S(O) ２ (C １～６ -alkyl), -S(O)2(C1-6-cycloalkyl), 3- to 10-membered heterocyclyl, cyano, -C(O)N(R １０ｃ R １０ｄ ) optionally substituted with C １～１０ alkyl, and 3- to 10-membered heterocyclyl is one or more C １～１０ -alkyl, C1-10 alkoxy, oxo, optionally substituted with halogen, C １～１０ Alkyl, ii) one or more hydroxy, C １～６ -Optionally substituted with alkoxy, amino or phenyl, C １～１０ - haloalkyl, wherein phenyl is selected from the group consisting of one or more C １～１０ - alkyl, optionally substituted with halogen, C １～１０ -haloalkyl, iii) one or more of amino, halogen, C １～６ -haloalkyl, C １～３ -alkyl, cyano, 3- to 10-membered cycloalkyl, 3- to 10-membered heterocyclyl, C １～６ -haloalkoxy, C １～６ amino-C optionally substituted with alkoxy １～１０ -alkyl-, where 3- to 10-membered heterocyclyl and 3- to 10-membered cycloalkyl are selected from the group consisting of one or more halogens, C ２～６ -alkynyl, optionally substituted with 3- to 10-membered cycloalkyl, amino-C １～１０ -alkyl-, iv) Hydroxy-C １～１０ -alkyl-, v) C optionally substituted with one or more cyano １～６ -alkoxy, vi) C １～６ -alkoxy-C １～１０ -alkyl-, vii) one or more halogens, C １～１０ -alkyl, -S(O) ２ (C １～６ alkyl), cyano, C １～６ Haloalkyl, C １～６ -alkoxy, hydroxy, oxo, amino, -C(O)N(R １０ｃ R １０ｄ ), ═N(OH), hydroxy-C １～６ - optionally substituted with alkyl, C ３～１０ -cycloalkyl, viii) one or more halogens, C １～１０ -alkyl, -S(O) ２ (C １～６ -alkyl), -C １～１０ -Alkyl-C １～４ -alkoxy, amino, -C(O)N(R １０ｈ R １０ｉ ), C １～６ -haloalkyl, C １～６ -alkoxy, cyano, hydroxy-C １～１０ -alkyl, oxo, -C(O)(C １～６ -alkyl), -C(O)O-(R １０ｑ ), C ３～１０ -3-10 membered heterocyclyl optionally substituted by cycloalkyl, ix)-(C １～６ -alkyl)-C ３～７ -cycloalkyl, x) one or more halogens, C １～１０ 3- to 10-membered -(C １～６ -alkyl)-heterocyclyl, xi) one or more halogens, C １～１０ -alkyl, -S(O) ２ (C １～６ -alkyl), phenyl, xii) -(C １～１０ -alkyl)-phenyl, １～１０ -Alkyl is C １～６ -alkyl, optionally substituted with cyano, -(C １～１０ -alkyl)-phenyl, xiii) 5-6 membered -(C １～１０ -alkyl)-heteroaryl, xiv)-(alkoxy-C １～１０ -alkyl)-phenyl, xv)-(amino-C １～１０ -alkyl)-phenyl, xvi)-C １～６ -Alkyl-SO ２ (C １～６ -alkyl), xvii)-N(R １０ｅ R １０ｆ )、 xviii)-OR １０ｇ , and vix)-C(O)NR １０ｈ R １０ｉ 、 xx) one or more C １～１０ -Alkyl, halogen, -SO ２ (C １～６ heteroaryl, optionally substituted with alkyl; xxi) oxo is selected from R １０ａ and R １０ｂ are each independently hydrogen, C １～６ -Alkyl, halo-C １～６ -Alkyl, hydroxy-C １～６ -Alkyl, C １～６ -alkoxy, -C(O)(R １０ｊ ), amino-C １～６ -alkyl-, 3- to 10-membered heterocyclyl, -SO ２ (R １０ｋ ), -C １～６ -Alkyl-SO ２ (R １０ｋ ) and -N(R １０ｌ R １０ｍ ) wherein 3- to 10-membered heterocyclyl is selected from C １～６ - optionally substituted with alkyl, or R １０ａ and R １０ｂ together with the nitrogen atom to which they are attached, one or more halogens, C １～６ - forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl, R １０ｃ and R １０ｄ are each independently hydrogen and C １～６ - alkyl, R １０ｅ and R １０ｆ are each independently i) hydrogen, ii) optionally substituted with one or more cyanos, C １～６ - alkyl, iii) Halo-C １～６ -alkyl and halo-C １～６ -alkyl optionally substituted with one or more hydroxy, halo-C １～６ - alkyl, iv) Hydroxy-C １～６ - alkyl, v)-C(O)R １０ｎ 、 vi) one or more C ２～６ -optionally substituted by alkynyl, -C １～１０ Alkyl ((O-C １～１０ alkyl) ｍ ) wherein m is an integer between 1 and 5; vii) one or more of halogen, hydroxy, oxo, C １～１０ -Alkyl, halo-C １～１０ -Alkyl, hydroxy-C １～６ -Alkyl, C １～６ -alkoxy, -C(O)O(R １０ｏ ), —C(O)(R １０ｏ ), -C(O)N(R １０ｐ ) (R １０ｐ’ ), -SO ２ (C １～６ -alkyl), optionally substituted by C2-6-alkynyl, C ３～１０ -cycloalkyl, and viii) one or more of halogen, hydroxy, oxo, C １～１０ -Alkyl, halo-C １～１０ -Alkyl, hydroxy-C １～６ -Alkyl, C １～６ -alkoxy, -C(O)O(R １０ｏ ), —C(O)(R １０ｏ ), -C(O)N(R １０ｐ ) (R １０ｐ’ ), -SO ２ (C １～６ -alkyl), 3- to 10-membered heterocyclyl optionally substituted by 3- to 10-membered cycloalkyl Selected from or or R １０ｅ and R １０ｆ together with the nitrogen atom to which they are attached, represent one or more halogens, amino, C １～６ -Alkyl, halo-C １～６ -Alkyl, hydroxy-C １～６ -Alkyl, C １～６ -alkoxy, C ３～７ -cycloalkyl, -C(O)O(C １～６ -alkyl), R １０ｇ Halo-C １～６ -Alkyl, C １～６ -Alkyl-C ３～７ -cycloalkyl and C １～６ -alkoxy-halo-C １～６ - alkyl, R １０ｈ and R １０ｉ are each independently hydrogen and C １～６ -Alkyl, C １～６ -haloalkyl, C １～６ -Alkyl and C １～６ -haloalkyl may be optionally substituted with one or more hydroxy; or R １０ｈ and R １０ｉ together with the nitrogen atom to which they are attached, represent one or more halogens, hydroxy, C １～６ - forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl, R １０ｊ is C １～６ -Alkyl, halo-C １～６ -Alkyl, hydroxy-C １～６ -Alkyl and amino-C １～６ -alkyl-, R １０ｋ is hydrogen, C １～６ -Alkyl and halo-C １～６ - alkyl, R １０ｌ and R １０ｍ are each independently hydrogen and C １～６ - alkyl, R １０ｎ is C １～６ -Alkyl, amino-C １～６ -Alkyl-, halo-C １～６ -Alkyl, C ３～７ -cycloalkyl and 3- to 10-membered heterocyclyl, wherein C ３～７ - cycloalkyl and 3- to 10-membered heterocyclyl are selected from the group consisting of one or more halogens, C １～６ - optionally substituted with alkyl, R １０ｏ is C １～６ -Alkyl and halo-C １～６ - alkyl, R １０ｐ and R １０ｐ’ are independently hydrogen, C １～６ -Alkyl and halo-C １～６ - alkyl, R １０ｑ is C １～１０ -Alkyl, C １～６ - haloalkyl, aryl, heteroaryl, wherein aryl and heteroaryl are selected from one or more halogens, C １～１０ - optionally substituted with alkyl, R １１ teeth, i) halogens, ii) hydroxy, iii) cyano, iv) optionally substituted with one or more cyano, aryl, haloaryl; １～６ - alkyl, v) C is optionally substituted with one or more 3- to 10-membered heterocyclyls. １～６ -alkoxy, vi) Halo-C １～６ - alkyl, vii) Amino-C １～１０ -alkyl-, viii) Hydroxy-C １～６ - alkyl, ix) C ３～７ -cycloalkyl, x)-C １－６ -Alkyl-C ３～７ -cycloalkyl, xi) one or more halo-C １～６ -Alkyl, hydroxy, C １～６ -Alkyl, C ３～１０ -cycloalkyl, C １～６ -3- to 10-membered heterocyclyl optionally substituted by alkoxy or oxo; xii) one or more C １～６ 3- to 7-membered -(C １～６ -alkyl)-heterocyclyl, xiii) one or more C １～６ -alkyl, 3- to 10-membered cycloalkyl, halogen, halo-C １～６ -Alkyl, C １～６ -alkoxy, C １～６ -5-6 membered heteroaryl optionally substituted with haloalkoxy; xiv) one or more halogens, cyano, C １～６ -alkoxy, halo-C １～６ -Alkyl, C １～６ -haloalkoxy, C １～６ -phenyl optionally substituted with alkyl, xv) one or more -SO ２ (C １～６ alkyl), hydroxy, halogen, cyano-substituted -(C １～６ -alkyl)-phenyl, xvi)-(C １～６ -alkyl)-O-phenyl, xvii) 5-6 membered-(C １～６ -alkyl)-heteroaryl, xviii)-O(2 １１ａ )、 xix)-C(O)N(R １１ｂ R １１ｃ ) xx)-SO ２ (R １１ｄ )、 xxi)-C(O)OR １１ｅ 、 xxyii)-C(O)R １１ｆ 、 xxiii) oxo, xxiv)-N(R １１ｇ R １１ｈ )、 xxv)-S(R １１ｋ ), and xxvi) C １～６ -haloalkoxyl is selected from R １１ａ is C １～１２ -Alkyl, halo-C １～６ -Alkyl, amino-C １～１２ -Alkyl-, hydroxy-C １～６ -Alkyl, cyano, -C １～６ -Alkyl, C ２～６ -alkynyl, C ３～７ -cycloalkyl, 3- to 10-membered heterocyclyl, 3- to 10-membered -(C １～６ -alkyl)heterocyclyl, 5- to 6-membered heteroaryl, phenyl, -C １～６ -alkyl-phenyl, -C １～１２ -alkyl-C(O)N(R １１ｉ R １１ｊ ), -C １～１２ -Alkyl-NH-C(O)(C １～６ -alkyl), -C １～１２ -alkoxy-NH-C(O)(C １～６ -alkyl), -C １～６ -Alkyl-NH-C(O)(C １～６ -alkyl), -(CH ２ CH ２ O) ｎ -CH ２ CH ２ NH ２ and -(CH ２ CH ２ O) ｎ -CH ２ CH ２－ NH-C(O)(C １～６ -alkyl), Said C １～１２ -Alkyl, C ３～７ -cycloalkyl, 3- to 10-membered heterocyclyl, 5- to 6-membered heteroaryl, phenyl, and -C １～６ -Alkyl-phenyl is selected from the group consisting of one or more halogens, C １～６ -Alkyl, halo-C １～６ -Alkyl, C １～６ -alkoxyl, C １～６ -optionally substituted with haloalkoxyl, cyano, n is an integer between 1 and 6; R １１ｂ and R １１ｃ are each independently hydrogen, C １～６ -Alkyl and halo-C １～６ - alkyl; or R １１ｂ and R １１ｃ together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R １１ｄ is hydrogen, C １～６ -alkyl, -N(R １１ｌ R １１ｍ ), Halo-C １～６ - selected from alkyl and phenyl, R １１ｅ is hydrogen and C １～６ - alkyl, R １１ｆ is hydrogen, C １～６ - selected from alkyl and phenyl, R １１ｇ and R １１ｈ are each independently hydrogen, C １～６ -alkyl, -(C １～６ -alkyl)phenyl, halo-C １～６ -Alkyl, -SO ２ (C １～６ -alkyl), -SO ２ (Halo-C １～６ -alkyl) and -SO(C １～６ -alkyl) ２ Selected from or or R １１ｇ and R １１ｈ together with the nitrogen atom to which they are attached, form C １～６ -Alkyl, C １～６ - forms a 3- to 10-membered heterocyclyl optionally substituted by alkoxy, R １１ｉ and R １１ｊ are each independently hydrogen, C １～６ -Alkyl and halo-C １～６ - alkyl; or R １１ｉ and R １１ｊ together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R １１ｋ is hydrogen, C １～６ -Alkyl and halo-C １～６ - alkyl, R １１ｌ and R １１ｍ are each independently hydrogen and C １～６ - alkyl; or R １１ｌ and R １１ｍ together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R ｙ is hydrogen and C １～６ -alkyl) 2. The compound of claim 1, wherein:

3. The compound is represented by formula (I) (In the formula, X is C(R ７ ) or N, Y is S, S(O), S(O) ２、 S(O)N(R ｙ ) and R １ is a 5-membered heteroaryl, and R １ represents one or more R １０ may be substituted with R ２ , R ３ and R ７ are each independently hydrogen, halogen, or C １～６ -Alkyl, C ２～６ -alkynyl, hydroxy, cyano, halo-C １～６ -alkyl, N(R ８ R ８ａ ), C １～６ -alkoxy, C ３～７ - selected from cycloalkyl and 3- to 10-membered heterocyclyl; R ４ is C ５～１４ -aryl and 5- to 14-membered heteroaryl, R ４ represents one or more R １１ may be substituted with R ５ is hydrogen, C １～６ -alkyl, -C(O)(R ９ ), amino, amino-C １～６ -Alkyl and C ３～７ -cycloalkyl, Said C ３～７ -Cycloalkyl is one or more C １～６ -Alkyl, amino, amino-C １～６ - optionally substituted with alkyl, R ６ and R ６ａ are each independently hydrogen and C １ ~ ６ - alkyl, R ８ and R ８ａ are each independently hydrogen and C １～６ - alkyl, R ９ is C １～６ -Alkyl, hydroxy-C １～６ -Alkyl, amino-C １～６ -Alkyl and (C １～６ -alkyl)-N(R ９ａ R ９ｂ ) wherein said amino-C １～６ -Alkyl may be one or more hydroxy, hydroxy-C １～６ - optionally substituted with alkyl, R ９ａ and R ９ｂ are each independently hydrogen and C １～６ -alkyl, wherein said C １～６ - alkyl may be substituted with one or more hydroxy; or R ９ａ and R ９ｂ together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R １０ teeth, i) one or more halogens, C ２～６ -alkynyl, halo-C １～６ -Alkyl, amino, -N(R １０ａ R １０ｂ ), -S(O) ２ (C １～６ -alkyl), 3- to 10-membered heterocyclyl, cyano, —C(O)N(R １０ｃ R １０ｄ ) optionally substituted with C １～１０ - alkyl, ii) C １～１０ -haloalkyl, iii) Amino-C １～１０ -Alkyl iv) Hydroxy-C １～１０ - alkyl, v) C １～６ -alkoxy, vi) C １～６ -alkoxy-C １～１０ - alkyl, vii) one or more halogens, C １～１０ -alkyl, -S(O) ２ (C １～６ -alkyl), hydroxy, oxo, amino, -C(O)N(R １０ｃ R １０ｄ ), ═N(OH), hydroxy-C １～６ - optionally substituted with alkyl, C ３～１０ -cycloalkyl, viii) one or more halogens, C １～１０ -alkyl, -S(O) ２ (C １～６ -alkyl), cyano, hydroxy-C １～１０ -alkyl, oxo, -C(O)(C １～６ -alkyl), -C(O)O-(C １～６ -alkyl), C ３～１０ -3-10 membered heterocyclyl optionally substituted by cycloalkyl, ix) (C １～６ -alkyl)-C ３～７ -cycloalkyl, x) one or more halogens, C １～１０ -3-10-membered (C １～６ -alkyl)-heterocyclyl, xi) phenyl, optionally substituted with one or more halogens; xii) optionally substituted with one or more halogens; (C １～１０ -alkyl)-phenyl, １～１０ -Alkyl is C １～６ -alkyl, optionally substituted with cyano, (C １～１０ -alkyl)-phenyl, xiii) 5-6 membered (C １～１０ -alkyl)-heteroaryl, xiv) (alkoxy-C １～１０ -alkyl)-phenyl, xv) (amino-C １ ~ １０ -alkyl)-phenyl, xvi)-C １～６ -Alkyl-SO ２ (C １～６ -alkyl), xvii)-N(R １０ｅ R １０ｆ )、 xviii)-OR １０ｇ , and 8ix)-C(O)NR １０ｈ R １０ｉ is selected from R １０ａ and R １０ｂ are each independently hydrogen, C １～６ -Alkyl, halo-C １～６ -Alkyl, hydroxy-C １～６ -Alkyl, C １～６ -alkoxy, -C(O)(R １０ｊ ), amino-C １～６ -alkyl, 3- to 10-membered heterocyclyl, -SO ２ (R １０ｋ ), C １～６ -Alkyl-SO ２ (R １０ｋ ) and -N(R １０ｌ R １０ｍ ) wherein 3- to 10-membered heterocyclyl is selected from C １～６ - optionally substituted with alkyl, or R １０ａ and R １０ｂ together with the nitrogen atom to which they are attached, one or more halogens, C １～６ - forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl, R １０ｃ and R １０ｄ are each independently hydrogen and C １～６ - alkyl, R １０ｅ and R １０ｆ are each independently hydrogen, C １～６ -Alkyl, halo-C １～６ -Alkyl, hydroxy-C １～６ -alkyl, -C(O)R １０ｎ , C ３～１０ -cycloalkyl and 3- to 10-membered heterocyclyl, wherein C ３～１０ -Cycloalkyl and 3- to 10-membered heterocyclyl are selected from the group consisting of one or more of halogen, hydroxy, oxo, C １～１０ -Alkyl, halo-C １～１０ -Alkyl, hydroxy-C １～６ -Alkyl, C １～６ -alkoxy, -C(O)O(R １０ｏ ), —C(O)(R １０ｏ ), -C(O)N(R １０ｐ ) (R １０ｐ’ ), -SO ２ (C １～６ -alkyl), or R １０ｅ and R １０ｆ together with the nitrogen atom to which they are attached, represent one or more halogens, amino, C １～６ -Alkyl, halo-C １～６ -Alkyl, hydroxy-C １～６ -Alkyl, C １～６ -alkoxy, C ３～７ -cycloalkyl, -C(O)O(C １～６ -alkyl), R １０ｇ Halo-C １～６ -Alkyl, C １～６ -Alkyl-C ３～７ -cycloalkyl and C １～６ -alkoxy-halo-C １～６ - alkyl, R １０ｈ and R １０ｉ are each independently hydrogen and C １～６ - alkyl; or R １０ｈ and R １０ｉ together with the nitrogen atom to which they are attached, represent one or more halogens, hydroxy, C １～６ - forms a 3- to 10-membered heterocyclyl optionally substituted by alkyl, R １０ｊ is C １～６ -Alkyl, halo-C １～６ -Alkyl, hydroxy-C １～６ -Alkyl and amino-C １～６ - alkyl, R １０ｋ is hydrogen, C １～６ -Alkyl and halo-C １～６ - alkyl, R １０ｌ and R １０ｍ are each independently hydrogen and C １～６ - alkyl, R １０ｎ is C １～６ -Alkyl, amino-C １～６ -Alkyl, halo-C １～６ -Alkyl, C ３～７ -cycloalkyl and 3- to 10-membered heterocyclyl, wherein C ３～７ - cycloalkyl and 3- to 10-membered heterocyclyl are selected from the group consisting of one or more halogens, C １～６ - optionally substituted with alkyl, R １０ｏ is C １～６ -Alkyl and halo-C １～６ - alkyl, R １０ｐ and R １０ｐ’ are independently hydrogen, C １～６ -Alkyl and halo-C １～６ - alkyl, R １１ teeth, i) halogens, ii) hydroxy, iii) cyano, iv) C optionally substituted with one or more cyano １～６ - alkyl, v) C １～６ -alkoxy, vi) Halo-C １～６ - alkyl, vii) Amino-C １～１０ -Alkyl viii) Hydroxy-C １～６ - alkyl, ix) C ３～７ -cycloalkyl, x) C １～６ -Alkyl-C ３～７ -cycloalkyl, xi) one or more halo-C １～６ -Alkyl, hydroxy, C １～６ -Alkyl, C １～６ -3- to 10-membered heterocyclyl optionally substituted by alkoxy or oxo; xii) one or more C １～６ -3- to 7-membered (C １～６ -alkyl)-heterocyclyl, xiii) one or more C １～６ -Alkyl, halogen, halo-C １～６ - 5-6 membered heteroaryl optionally substituted by alkyl, xiv) phenyl, optionally substituted with one or more halogens or cyanos; xv) one or more -SO ２ (C １～６ -alkyl), hydroxy, halogen, cyano (C １～６ -alkyl)-phenyl, xvi) (C １～６ -alkyl)-O-phenyl, xvii) 5-6 membered (C １～６ -alkyl)-heteroaryl, xviii)-O(2 １１ａ )、 xix)-C(O)N(R １１ｂ R １１ｃ ) xx)-SO ２ (R １１ｄ )、 xxi)-C(O)OR １１ｅ 、 xxyii)-C(O)R １１ｆ 、 xxiii) oxo, xxiv)-N(R １１ｇ R １１ｈ ), and xxv)-S(R １１ｋ ) is selected from R １１ａ is C １～１２ -Alkyl, halo-C １～６ -Alkyl, amino-C １～１２ -Alkyl, hydroxy-C １～６ -Alkyl, cyano, -C １－６ -Alkyl, C ２～６ -alkynyl, C ３～７ -cycloalkyl, 3- to 10-membered heterocyclyl, 5- to 6-membered heteroaryl, phenyl, -C １～６ -alkyl-phenyl, C １～１２ -alkyl-C(O)N(R １１ｉ R １１ｊ ), -C １～１２ -Alkyl-NH-C(O)(C １～６ -alkyl), -C １～１２ -alkoxy-NH-C(O)(C １～６ -alkyl), -C １～６ -Alkyl-NH-C(O)(C １－６ -alkyl), -(CH ２ CH ２ O) ｎ -CH ２ CH ２ NH ２ and -(CH ２ CH ２ O) ｎ -CH ２ CH ２－ NH-C(O)(C １～６ -alkyl), Said C １～１２ -Alkyl, C ３～７ -cycloalkyl, 3- to 10-membered heterocyclyl, 5- to 6-membered heteroaryl, phenyl and C １～６ -Alkyl-phenyl is selected from the group consisting of one or more halogens, C １～６ -Alkyl, halo-C １～６ -optionally substituted with alkyl, cyano, n is an integer between 1 and 6; R １１ｂ and R １１ｃ are each independently hydrogen, C １～６ -Alkyl and halo-C １～６ - alkyl; or R １１ｂ and R １１ｃ together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R １１ｄ is hydrogen, C １～６ -alkyl, -N(R １１ｌ R １１ｍ ), Halo-C １～６ - selected from alkyl and phenyl, R １１ｅ is hydrogen and C １～６ - alkyl, R １１ｆ is hydrogen, C １～６ - selected from alkyl and phenyl, R １１ｇ and R １１ｈ are each independently hydrogen, C １～６ -Alkyl, halo-C １～６ -Alkyl, SO ２ (C １～６ -alkyl), SO ２ (Halo-C １～６ -alkyl) and SO(C １～６ -alkyl) ２ Selected from or or R １１ｇ and R １１ｈ together with the nitrogen atom to which they are attached, form C １～６ -Alkyl, C １～６ - forms a 3- to 10-membered heterocyclyl optionally substituted by alkoxy, R １１ｉ and R １１ｊ are each independently hydrogen, C １～６ -Alkyl and halo-C １～６ - alkyl; or R １１ｉ and R １１ｊ together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R １１ｋ is hydrogen, C １～６ -Alkyl and halo-C １～６ - alkyl, R １１ｌ and R １１ｍ are each independently hydrogen and C １～６ - alkyl; or R １１ｌ and R １１ｍ together with the nitrogen atom to which they are attached form a 3- to 10-membered heterocyclyl; R ｙ is hydrogen and C １～６ -alkyl) 3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, which is:

4. The compound has the formula (IA) (In the formula, X, Y, R １ , R ２ , R ３ , R ４ , R ５ , R ６ , R ６ａ is as defined in any one of claims 1 to 3) 4. The compound according to claim 1, wherein the compound is:

5. R １ However, at least one R １０ The compound of any one of claims 1 to 4, substituted with

6. X is N or C(R ７ ) and R ７ The compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein is hydrogen or halogen.

7. 7. The compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, wherein X is CH.

8. Y is S(O) or S(O) ２ The compound according to any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein:

9. R １０ but, i) one or more C ２～６ -alkynyl, optionally substituted with cyano, C １～１０ - alkyl, ii) C １～５ -Optionally substituted with alkoxy, amino or phenyl, C １～１０ -haloalkyl, wherein the phenyl is optionally substituted with one or more halogens; C １～１０ -haloalkyl, iii) optionally substituted with one or more halogens, C ３～１０ -cycloalkyl, iv) one or more halogens, C １～１０ -phenyl optionally substituted with alkyl, v) one or more halogens, C １～１０ heteroaryl optionally substituted with alkyl, vi) one or more C １～１０ -Alkyl, C ３～１０ -cycloalkyl, C １～６ -haloalkyl, halogen, -C １～１０ -Alkyl-C １～４ -alkoxy, -C(O)O-C １～５ -3-10 membered heterocyclyl optionally substituted by alkyl, vii) C １～１０ -Alkyl, C １～１０ -haloalkyl, C ３～１０ -amino optionally substituted with cycloalkyl, ３～１０ -Cycloalkyl is one or more C １～５ -Alkyl, optionally substituted with halogen, amino 9. The compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, selected from:

10. R １０ But C １～１０ -Alkyl, C ２～６ -alkynyl-substituted C １～１０ -Alkyl, C １～１０ -haloalkyl, amino-C １～１０ -Alkyl-, hydroxy-C １～１０ -Alkyl, C ３～１０ -cycloalkyl, C substituted with one or more halogens ３～１０ -cycloalkyl, phenyl substituted with one or more halogens, -(C １～１０ -alkyl)-phenyl, -(alkoxy-C １～１０ -alkyl)-phenyl, 3- to 10-membered heterocyclyl, one or more C １～１０ - 3-10 membered heterocyclyl, heteroaryl, substituted with alkyl and halogen, one or more C １～１０ -alkyl-substituted heteroaryl, heteroaryl substituted with one or more halogens, and -N(R １０ｅ R １０ｆ 10. The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, selected from:

11. R １０ But C １～１０ -Alkyl, C ２～６ -alkynyl-substituted C １～１０ -Alkyl, C １～１０ -haloalkyl, amino-C １～１０ -Alkyl, hydroxy-C １～１０ -Alkyl, C ３～１０ -cycloalkyl, C substituted with one or more halogens ３～１０ -cycloalkyl, phenyl substituted with one or more halogens, (C １～１０ -alkyl)-phenyl, (alkoxy-C １～１０ -alkyl)-phenyl, 3- to 10-membered heterocyclyl, one or more C １～１０ -3-10 membered heterocyclyl substituted with alkyl and halogen, and -N(R １０ｅ R １０ｆ 11. The compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, selected from:

12. R １０ But C １～１０ -Alkyl, C １～１０ -haloalkyl, C substituted with one or more halogens ３～１０ -cycloalkyl, hydroxy-C １～１０ -Alkyl, C ２～６ -alkynyl-substituted C １～１０ - alkyl, 3- to 10-membered heterocyclyl, one or more C １～１０ - 3- to 10-membered heterocyclyl substituted with alkyl and halogen, and -NH(C ３～７ -cycloalkyl), or a pharmaceutically acceptable salt thereof.

13. R １０ tert-butyl, methyl 3-azabicyclo[3.1.1]heptane-3-carboxylate, 3-oxa-8-azabicyclo[3.2.1]octan-8-yl, 3,3-(difluorocyclobutyl)aminoyl, (trifluoromethyl)cyclopropyl, 2,2-difluoromorpholin-4-yl, 5,5-difluoro-1-methyl-3-piperidyl, 2,2,2-trifluoroethyl, (3,3-difluoro-1-methyl-cyclobutyl)aminoyl, o-tolyl, cyclobutylaminoyl, 2-methyl methyl-propanenitrile, 6-fluoro-2-methyl-3-pyridyl, 1,2,2,2-tetrafluoro-1-methoxy-ethyl, 4-oxa-7-azaspiro[2.5]octan-7-yl, ethyl, 1-amino-2,2,2-trifluoro-1-methyl-ethyl, morpholinyl, 1-amino-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl, methyl(2,2,2-trifluoroethyl)amino, 2,2-difluoromorpholin-4-yl, tert-butylaminoyl, cyclohexyl Aminoyl, methyl 4-methylpiperidine-1-carboxylate, 2-oxa-5-azabicyclo[4.1.0]heptan-5-yl, 2-(trifluoromethyl)morpholin-4-yl, 3,3-difluorocyclohexyl, 1,1-dimethylbut-3-ynyl, 3,3-difluorocyclobutyl, isobutyl, methyl 3,3-difluoropiperidine-1-carboxylate, difluorocyclopentyl, trifluoromethylmorpholinyl, 2,2-difluorospiro[3.3]heptan-6-yl, difluoro 13. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, selected from fluorocyclohexyl, 5,5-difluoro-1-(2-methoxyethyl)-3-piperidyl, 1-ethyl-5,5-difluoro-3-piperidyl, 2-cyclopropyltetrahydrofuran-2-yl, 3-fluoro-1-methyl-3-piperidyl, 6-fluoro-2-methyl-3-pyridyl, 2-fluoro-6-methyl-phenyl, fluorophenyl, and 1,2,2,2-tetrafluoro-1-methoxy-ethyl.

14. R １０ is ethyl, tert-butyl, isopropyl, -CH ２ CF ３ , -C((CH ３ ) ２ ) F, -C((CH ３ ) ２ ) CH ２ OH, -C((CH ３ ) ２ ) CH ２ CCH ３ , difluorocyclohexyl, difluorocyclobutyl, piperidyl substituted with fluorine and methyl, morpholinyl, and -NH(cyclopentyl), or a pharmaceutically acceptable salt thereof.

15. R １ but, is selected from R １ is one or more R １０ and R 10 is as defined in any one of claims 1 or 9 to 14, or a pharmaceutically acceptable salt thereof.

16. R １ but, is selected from R １ represents one or more R １０ and R 10 is as defined in any one of claims 1 or 9 to 14, or a pharmaceutically acceptable salt thereof.

17. R ２ But hydrogen, halogen, C １～６ - alkyl, hydroxy or N(R ８ R ８ａ 17. The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein

18. R ８ and R ８ａ are each independently hydrogen and C １～６ 18. The compound of any one of claims 1 to 17, or a pharmaceutically acceptable salt thereof, wherein:

19. R ２ is hydrogen, halogen or C １～６ - alkyl, or a pharmaceutically acceptable salt thereof.

20. R ２ The compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof, wherein is hydrogen, fluorine or methyl.

21. R ２ The compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof, wherein is hydrogen or fluorine.

22. R ３ The compound according to any one of claims 1 to 21, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

23. R １１ But halogen, C １～６ -haloalkoxy, C １～６ -alkoxy, -O-R １１ａ , C １～６ -C substituted with alkyl, cyano １～６ 23. The compound of any one of claims 1 to 22, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from: - alkyl.

24. R １１ But halogen, C １～６ -haloalkoxy, C １～６ -alkoxy, -O-aryl, -O-C ３～１０ -cycloalkyl, C １～６ -C substituted with alkyl, cyano １～６ 24. The compound of any one of claims 1 to 23, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from: - alkyl.

25. R １１ is halogen, -O(R １１ａ ), cyano, amino-C １～１０ -Alkyl-, -SO ２ (C １～６ -alkyl) and one or more halo-C １～６ 25. The compound of any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein the heterocyclyl is selected from 3- to 10-membered heterocyclyl substituted with alkyl.

26. R １１ａ But C １～１２ -Alkyl, halo-C １～６ -alkyl, 3- to 7-membered heterocycloalkyl and amino-C １～１２ 26. The compound of any one of claims 1 to 25, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from: - alkyl.

27. R １１ is halogen, -O(halo-C １～６ -alkyl), -O(C １～６ -alkyl), cyano and one or more halo-C １～６ 27. The compound of any one of claims 1 to 26, or a pharmaceutically acceptable salt thereof, wherein the heterocyclyl is selected from 3- to 10-membered heterocyclyl substituted with -alkyl.

28. R １１ is halogen, -O(R １１ａ ), Cyano, C １～６ -haloalkoxy, amino-C １～１０ -Alkyl-, -SO ２ (C １～６ -alkyl) and one or more halo-C １～６ 28. The compound of any one of claims 1 to 27, or a pharmaceutically acceptable salt thereof, wherein the heterocyclyl is selected from 3- to 10-membered heterocyclyl substituted with -alkyl.

29. R １１ is selected from chloro, fluoro, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, phenoxy, 2-methyl-propanenitrile, isopropoxy, methoxy, cyclopentoxy, or a pharmaceutically acceptable salt thereof.

30. R １１ But chlorine, -OCF ３ , -OCH ３ 30. The compound of any one of claims 1 to 29, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from: 3-trifluoromethyl-diazirin-3-yl;

31. R ４ but, and R ４ is one or more R according to any one of claims 1 or 23 to 30. １１ 31. The compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt thereof, optionally substituted with:

32. R ４ but, and R ４ is one or more R according to any one of claims 1 or 23 to 30. １１ 32. The compound according to any one of claims 1 to 31, or a pharmaceutically acceptable salt thereof, optionally substituted with:

33. R ５ is hydrogen or —C(O)(R ９ 33. The compound according to any one of claims 1 to 32, or a pharmaceutically acceptable salt thereof, wherein

34. R ５ is hydrogen or —C(O)(amino-C １～６ -alkyl), or a pharmaceutically acceptable salt thereof.

35. R ５ is hydrogen or —C(O)(CH ２ NH ２ 35. The compound according to any one of claims 1 to 34, or a pharmaceutically acceptable salt thereof, wherein

36. R ６ and R ６ａ 36. The compound of any one of claims 1 to 35, or a pharmaceutically acceptable salt thereof, wherein is hydrogen.

37. X is N or C(R ７ ) and Y is S, SO or S(O) ２ and R １ but, and R １ is one or more R １０ may be substituted with R ２ But hydrogen, halogen, C １～６ - alkyl, hydroxy or N(R ８ R ８ａ ) and R ３ is hydrogen, R ４ but, is selected from R ５ is hydrogen or —C(O)(R ９ ) and R ６ and R ６ａ is hydrogen, R ７ is hydrogen or halogen, R ８ and R ８ａ are each independently hydrogen and C １～６ - alkyl, R ９ However, amino-C １～６ - alkyl, R １０ But C １～１０ -Alkyl, C ２～６ -alkynyl-substituted C １～１０ -Alkyl, C １～１０ -haloalkyl, amino-C １～１０ -Alkyl, hydroxy-C １～１０ -Alkyl, C ３～１０ -cycloalkyl, C substituted with one or more halogens ３～１０ -cycloalkyl, phenyl substituted with one or more halogens, (C １～１０ -alkyl)-phenyl, (alkoxy-C １～１０ -alkyl)-phenyl, 3- to 10-membered heterocyclyl, one or more C １～１０ - 3-10 membered heterocyclyl, heteroaryl, substituted with alkyl and halogen, one or more C １～１０ -alkyl-substituted heteroaryl, heteroaryl substituted with one or more halogens, and -N(R １０ｅ R １０ｆ ) are selected from R １０ｅ is hydrogen, and R １０ｆ is C ３～７ -cycloalkyl, R １１ is halogen, -O(R １１ａ ), cyano, amino-C １～１０ -Alkyl, C １～６ -haloalkoxy, -S(O ２ ) (C １～６ -alkyl) and one or more halo-C １～６ - 3-10 membered heterocyclyl substituted by alkyl; R １１ａ But C １～１２ -Alkyl, halo-C １～６ -alkyl, 3- to 7-membered heterocycloalkyl, amino-C １～１２ 37. The compound of any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from: - alkyl.

38. X is N or C(R ７ ) and Y is S, SO or S(O) ２ and R １ but, and R １ is one or more R １０ may be substituted with R ２ But hydrogen, halogen, C １～６ - alkyl, hydroxy or N(R ８ R ８ａ ) and R ３ is hydrogen, R ４ but, is selected from R ５ is hydrogen or —C(O)(R ９ ) and R ６ and R ６ａ is hydrogen, R ７ is hydrogen or halogen, R ８ and R ８ａ are each independently hydrogen and C １～６ - alkyl, R ９ However, amino-C １～６ - alkyl, R １０ But C １～１０ -Alkyl, C ２～６ -alkynyl-substituted C １～１０ -Alkyl, C １～１０ -haloalkyl, amino-C １～１０ -Alkyl, hydroxy-C １～１０ -Alkyl, C ３～１０ -cycloalkyl, C substituted with one or more halogens ３～１０ -cycloalkyl, phenyl substituted with one or more halogens, (C １～１０ -alkyl)-phenyl, (alkoxy-C １～１０ -alkyl)-phenyl, 3- to 10-membered heterocyclyl, one or more C １～１０ -3-10 membered heterocyclyl substituted with alkyl and halogen, -N(R １０ｅ R １０ｆ ) are selected from R １０ｅ is hydrogen, and R １０ｆ is C ３～７ -cycloalkyl, R １１ is halogen, -O(R １１ａ ), cyano, amino-C １～１０ -alkyl, -S(O ２ ) (C １～６ -alkyl) and one or more halo-C １～６ - 3-10 membered heterocyclyl substituted by alkyl; R １１ａ But C １～１２ -Alkyl, halo-C １～６ -alkyl, 3- to 7-membered heterocycloalkyl, amino-C １～１２ 38. The compound of any one of claims 1 to 37, or a pharmaceutically acceptable salt thereof, wherein:

39. X is CH; Y is SO or S(O) ２ and R １ but, and R １ is one or more R １０ may be substituted with R ２ But hydrogen, halogen, C １～６ - alkyl, R ３ is hydrogen, R ４ but, and R ５ is hydrogen or —C(O)(amino-C １～６ -alkyl), R ６ and R ６ａ is hydrogen, R １０ but, One or more C ２～６ -alkynyl, optionally substituted with cyano, C １～１０ - alkyl, C １～５ -Optionally substituted with alkoxy, amino or phenyl, C １～１０ -haloalkyl, wherein the phenyl is optionally substituted with one or more halogens; C １～１０ -haloalkyl, C, optionally substituted with one or more halogens; ３～１０ -cycloalkyl, one or more halogens, C １～１０ -phenyl optionally substituted with alkyl, one or more halogens, C １～１０ heteroaryl optionally substituted with alkyl, One or more C １～１０ -Alkyl, C ３～１０ -cycloalkyl, C １～６ -haloalkyl, halogen, -C １～１０ -Alkyl-C １～４ -alkoxy, -C(O)O-C １～５ -3-10 membered heterocyclyl optionally substituted by alkyl, C １～１０ -Alkyl, C １～１０ -haloalkyl, C ３～１０ -amino optionally substituted with cycloalkyl, ３～１０ -Cycloalkyl is one or more C １～５ -Alkyl, optionally substituted with halogen, amino is selected from R １１ is halogen, -O(halo-C １～６ -alkyl), -O(C １～６ -alkyl), cyano, one or more halo-C １～６ 39. The compound of any one of claims 1 to 38, or a pharmaceutically acceptable salt thereof, wherein the heterocyclyl is selected from 3- to 10-membered heterocyclyl substituted with -alkyl.

40. X is CH; Y is SO or S(O) ２ and R １ but, and R １ is one or more R １０ may be substituted with R ２ is hydrogen, fluorine or methyl, R ３ is hydrogen, R ４ but, is selected from R ５ is hydrogen or —C(O)(CH ２ NH ２ ) and R ６ and R ６ａ is hydrogen, R １０ tert-butyl, methyl 3-azabicyclo[3.1.1]heptane-3-carboxylate, 3-oxa-8-azabicyclo[3.2.1]octan-8-yl, 3,3-(difluorocyclobutyl)aminoyl, (trifluoromethyl)cyclopropyl, 2,2-difluoromorpholin-4-yl, 5,5-difluoro-1-methyl-3-piperidyl, 2,2,2-trifluoroethyl, (3,3-difluoro-1-methyl-cyclobutyl)aminoyl, o-tolyl, cyclobutyl methylaminoyl, 2-methyl-propanenitrile, 6-fluoro-2-methyl-3-pyridyl, 1,2,2,2-tetrafluoro-1-methoxy-ethyl, 4-oxa-7-azaspiro[2.5]octan-7-yl, ethyl, 1-amino-2,2,2-trifluoro-1-methyl-ethyl, morpholinyl, 1-amino-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl, methyl(2,2,2-trifluoroethyl)amino, 2,2-difluoromorpholin-4-yl, te rt-butylaminoyl, cyclohexylaminoyl, methyl 4-methylpiperidine-1-carboxylate, 2-oxa-5-azabicyclo[4.1.0]heptan-5-yl, 2-(trifluoromethyl)morpholin-4-yl, 3,3-difluorocyclohexyl, 1,1-dimethylbut-3-ynyl, 3,3-difluorocyclobutyl, isobutyl, methyl 3,3-difluoropiperidine-1-carboxylate, difluorocyclopentyl, trifluoromethylmorpholinyl, 2 , 2-difluorospiro[3.3]heptan-6-yl, difluorocyclohexyl, 5,5-difluoro-1-(2-methoxyethyl)-3-piperidyl, 1-ethyl-5,5-difluoro-3-piperidyl, 2-cyclopropyltetrahydrofuran-2-yl, 3-fluoro-1-methyl-3-piperidyl, 6-fluoro-2-methyl-3-pyridyl, 2-fluoro-6-methyl-phenyl, fluorophenyl, 1,2,2,2-tetrafluoro-1-methoxy-ethyl, R １１ But chlorine, -OCF ３ , -OCH ３ 40. The compound of any one of claims 1 to 39, wherein the compound is selected from: cyano, 3-trifluoromethyl-diazirin-3-yl; or a pharmaceutically acceptable salt thereof.

41. (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)-1,2,4-oxadiazol-3-yl]-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-ethyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[3-fluoro-1-(2-methoxyethyl)-3-piperidyl]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)-1,2,4-oxadiazol-3-yl]-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-8-fluoro-5-[(4-fluorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-morpholino-1,2,4-oxadiazol-3-yl)-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-3-yl]-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-3-yl]-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-8-fluoro-5-[(6-isopropoxy-3-pyridyl)methyl]-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[2-(difluoromethyl)morpholin-4-yl]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-7-[5-[2-(trifluoromethyl)morpholin-4-yl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1 lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-morpholino-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-7-[5-[2-(trifluoromethyl)morpholin-4-yl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1 lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 3-[5-[(3R)-3-amino-5-[[4-(cyclopentoxy)phenyl]methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]pyrrolidine-1-carboxylate; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-[2-(trifluoromethyl)morpholin-4-yl]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-8-fluoro-5-[(5-isopropoxy-2-pyridyl)methyl]-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2-amino-N-[(3R)-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]acetamide (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(6-methyl-3-pyridyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,6-dimethyl-3-pyridyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-8-fluoro-7-[5-[2-(hydroxymethyl)tetrahydrofuran-2-yl]-1,2,4-oxadiazol-3-yl]-1,1-dioxo-5-[(4-phenoxyphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2-[5-[(3R)-3-amino-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methyl-propanenitrile; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(1-fluoro-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-8-fluoro-7-[5-(1-fluoro-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-5-[(4-fluorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(2,2-difluoromorpholin-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[(4-phenoxyphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(3-aminooxetan-3-yl)-1,2,4-oxadiazol-3-yl]-8-fluoro-5-[[4-(4-methoxyphenyl)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(6-fluoro-2-methyl-3-pyridyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-methyl-4-methylsulfonyl-phenyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-methyl-5-methylsulfonyl-phenyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-methyl-3-pyridyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(1R,5S)-3-oxa-8-azabicyclo[3.2.1]octan-8-yl]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-dimethylmorpholin-4-yl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2-methyl-4-methylsulfonyl-phenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 3-[3-[(3R)-3-amino-5-[[4-(cyclopentoxy)phenyl]methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]pyrrolidine-1-carboxylate (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluoromorpholin-4-yl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[[4-(cyclopentoxy)phenyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-8-fluoro-7-[5-(3-fluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-5-[(4-phenoxyphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(6-fluoro-2-methyl-3-pyridyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,6-dimethyl-3-pyridyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluoro-1-methoxy-cyclohexyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-fluoro-6-methyl-phenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; Methyl 4-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-4-methoxy-piperidine-1-carboxylate; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(5-methyl-1,3,4-oxadiazol-2-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl N-[2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methyl-1-(trifluoromethyl)propyl]carbamate; (3R)-3-amino-7-[5-(2-amino-3,3,3-trifluoro-1,1-dimethyl-propyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; 3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-N-(3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)-1,2,4-oxadiazole-5-carboxamide; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[2-(hydroxymethyl)tetrahydrofuran-2-yl]-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-8-fluoro-7-[5-(5-methyl-1,3,4-oxadiazol-2-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-[1-amino-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl]-1,2,4-oxadiazol-3-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-8-fluoro-7-[5-(5-methyl-1,3,4-oxadiazol-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[2-(trifluoromethyl)morpholin-4-yl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-8-fluoro-7-[5-[2-(hydroxymethyl)tetrahydrofuran-2-yl]-1,2,4-oxadiazol-3-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2-fluorophenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-(p-tolyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-fluorophenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(m-tolyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(p-tolyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-oxa-5-azabicyclo[2.2.1]heptane-5-carboxylate (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-1-tetrahydropyran-4-yl-ethyl)-1,2,4-oxadiazol-3-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-N-(2,2-difluoropropyl)-1,2,4-oxadiazole-5-carboxamide; (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-7-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-[1-(trifluoromethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-N-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole-5-carboxamide; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-(5-phenyl-1,3,4-oxadiazol-2-yl)-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(o-tolyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-(5-phenyl-1,3,4-oxadiazol-2-yl)-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 3-[5-[(3R)-3-amino-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]pyrrolidine-1-carboxylate; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(5-methyl-2-pyridyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(6-methyl-3-pyridyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[(3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)amino]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[[1-(2-hydroxyethyl)cyclohexyl]amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-benzyl-8-fluoro-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(3-aminooxetan-3-yl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(6-fluoro-3-pyridyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[(4-phenoxyphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(5-fluoro-2-pyridyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluoropropylamino)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2-[[3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]amino]-2-methyl-propanenitrile (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(1-methoxycyclopropyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-(2,2,2-trifluoro-1-methoxy-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4-methoxytetrahydropyran-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(1,1,2,2,2-pentafluoroethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one N-[11-[4-[[(3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-5-yl]methyl]phenoxy]undecyl]-3-[2,2-difluoro-12-(1H-pyrrol-2-yl)-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-penta (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(1-methoxy-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(1-ethynylcyclohexyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-imino-1-oxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(9,9-difluoro-3-oxa-7-azabicyclo[3.3.1]nonan-7-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[4,4-difluoro-3-(hydroxymethyl)-1-piperidyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-dimethylmorpholin-4-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one Methyl 4-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-4-cyano-piperidine-1-carboxylate (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluoro-1,8-diazaspiro[4.5]decan-8-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(1-methyl-1-pyrrolidin-1-yl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[4-methyl-1-oxido-1-(2,2,2-trifluoroethyl)piperidin-1-ium-4-yl]-1,2,4-oxadiazol-3-yl]-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; 2-[4-[[(3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-5-yl]methyl]phenyl]-2-methyl-propanenitrile (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(1S,5R)-6,6-difluoro-3-azabicyclo[3.1.1]heptan-3-yl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-4-methyl-piperidine-4-carbonitrile; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[[1,1-dimethyl-4-(2-prop-2-ynoxyethoxy)butyl]amino]-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one 3-[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-N,N-dimethyl-1,2,4-oxadiazole-5-carboxamide; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(6-chloropyridazin-3-yl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoroethylamino)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[1,1-dimethyl-4-[2-(2-prop-2-ynoxyethoxy)ethoxy]butyl]-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[2-(5,5-difluoro-1-methylsulfonyl-3-piperidyl)tetrazol-5-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 5-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]tetrazol-2-yl]-3,3-difluoro-piperidine-1-carboxylate 2-[[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]amino]-2-methyl-propanenitrile; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[4-methyl-1-(2,2,2-trifluoroethyl)-4-piperidyl]-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluoropropylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1-bicyclo[1.1.1]pentanylamino)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[(3,3,3-trifluoro-1-methyl-propyl)amino]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[(4-tetrahydropyran-4-yloxyphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[3-[(3R)-3-amino-8-fluoro-1-imino-1,4-dioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate Methyl 1-[3-[(3R)-3-amino-8-fluoro-1,4-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 4,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1-imino-1-oxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(2-tert-butyltetrazol-5-yl)-8-fluoro-1,1-dioxo-5-[[4-(tetrahydropyran-4-ylmethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-8-fluoro-1,1-dioxo-5-[[4-(tetrahydropyran-4-ylmethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(cyclopropoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[3-[(3R)-3-amino-8-fluoro-1,4-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 4,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-7-[2-(1-acetyl-5,5-difluoro-3-piperidyl)tetrazol-5-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one N-[(3R)-5-[(4-chlorophenyl)methyl]-7-[2-(5,5-difluoro-3-piperidyl)tetrazol-5-yl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]acetamide; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(1,5,5-trimethyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(cyclohexoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[3-[(3R)-3-amino-8-fluoro-1,4-dioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 4,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-3-amino-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one (3R)-3-amino-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1 lambda 4,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[[(1S)-1-methyl-2-(trifluoromethoxy)ethyl]amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-benzyl-7-[2-(5,5-difluoro-1-methyl-3-piperidyl)tetrazol-5-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[2-(5,5-difluoro-1-methyl-3-piperidyl)tetrazol-5-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[[4-(tetrahydropyran-4-ylmethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-7-[8-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazin-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-8-fluoro-5-[(4-fluorophenyl)methyl]-1-oxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-8-fluoro-5-[(4-fluorophenyl)methyl]-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[[4-[[5-(trifluoromethyl)-2-pyridyl]oxy]phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[3-[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(4-fluorophenoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate Methyl 1-[3-[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(2-tert-butyltetrazol-5-yl)-8-fluoro-5-[(4-fluorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-1-oxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-1-oxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-1-oxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-1-oxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-ethyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; Isopropyl 1-[3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate Ethyl 1-[3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[1-(2,2-difluorocyclopropyl)ethylamino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[1-(2,2-difluorocyclopropyl)ethylamino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[1-(3,3-difluorocyclobutyl)ethylamino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[(3,3,3-trifluoro-1,1-dimethyl-propyl)amino]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[1-methyl-1-(2,2,2-trifluoroethylamino)ethyl]-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 3-[3-[(3R)-3-amino-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]pyrrolidine-1-carboxylate; Methyl 1-[5-[(3R)-3-amino-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[[4-(trifluoromethylsulfonyl)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-5-[(6-isopropoxy-3-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[[3-(trifluoromethyl)cyclobutyl]amino]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoroethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 1-[5-[(3R)-3-amino-1,1,4-trioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate (3R)-3-amino-7-[5-[(3-chloro-1-bicyclo[1.1.1]pentanyl)amino]-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[(3-fluoro-1-bicyclo[1.1.1]pentanyl)amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(1,1,2,2,2-pentafluoroethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluoro-1-methyl-cyclobutyl)amino]-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-[(3R)-1-methylpyrrolidin-3-yl]tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-[(3S)-1-methylpyrrolidin-3-yl]tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-N,N-dimethyl-1,2,4-oxadiazole-5-carboxamide; 3-[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-N,N-dimethyl-1,2,4-oxadiazole-5-carboxamide; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[1-(5,5-difluoro-1-methyl-3-piperidyl)pyrazol-4-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-[(2-amino-3,3,3-trifluoro-propyl)amino]-1,2,4-oxadiazol-3-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[(4-pyrrolidin-1-ylphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (6-methyl-3-pyridyl)4-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-4-methyl-piperidine-1-carboxylate; (3R)-3-amino-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-5-[(5-isopropoxy-2-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(1-ethyl-4-methyl-4-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2-[3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-2-methyl-propanenitrile; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-dimethyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroethyl 4-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-4-methyl-piperidine-1-carboxylate; Methyl 4-[3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-4-methyl-piperidine-1-carboxylate; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[[1-(2,2,2-trifluoroethyl)-3-piperidyl]amino]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[2-(2-amino-3,3,3-trifluoro-propyl)tetrazol-5-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 4-[3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,2,4-oxadiazol-5-yl]-N,4-dimethyl-piperidine-1-carboxamide; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[4-methyl-1-(pyrrolidine-1-carbonyl)-4-piperidyl]-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[(2,2,2-trifluoro-1-methyl-ethyl)amino]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 3-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]tetrazol-2-yl]pyrrolidine-1-carboxylate (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclobutyl)amino]-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(4-cyclopropylpiperazin-1-yl)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(4-methoxy-1-piperidyl)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(cyclopropylmethoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(2,2-difluoroethoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-but-2-ynoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-morpholinophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[3-(trifluoromethyl)piperazin-1-yl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroacetic acid (3R)-3-amino-1,1-dioxo-7-[5-(1,1,2,2,2-pentafluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclohexyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclobutyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluoro-1-methyl-cyclobutyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2-[4-[[(3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-5-yl]methyl]phenyl]-2-methyl-propanenitrile (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluoro-1-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-morpholino-1,2,4-oxadiazol-3-yl)-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(cyclobutylamino)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-7-[2-(1-acetyl-3-piperidyl)tetrazol-5-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-(1-methyl-3-piperidyl)tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(3-tert-butyl-1,2,4-triazol-1-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-[1-methyl-1-(methylamino)ethyl]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[3-(dimethylamino)-1,1-dimethyl-propyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; 3-[(3R)-3-amino-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda-6,5-benzothiazepin-7-yl]-N-tert-butyl-1,2,4-oxadiazole-5-carboxamide 3-[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda-6,5-benzothiazepin-7-yl]-N-tert-butyl-1,2,4-oxadiazole-5-carboxamide 3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-N-tert-butyl-1,2,4-oxadiazole-5-carboxamide 3-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-N-tert-butyl-1,2,4-oxadiazole-5-carboxamide (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(dimethylamino)methyl]-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(1-aminocyclopentyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[cyclopropyl(methyl)amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[methyl(2,2,2-trifluoroethyl)amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[[3,3-difluoro-1-(methoxymethyl)cyclobutyl]amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(4-aminotetrahydropyran-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(1-aminocyclohexyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(1-hydroxy-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroacetic acid (3R)-3-amino-7-(2-tert-butyltetrazol-5-yl)-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(2-tert-butyltetrazol-5-yl)-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-(1-methylsulfonyl-3-piperidyl)tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluoro-1-methyl-cyclobutyl)amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclobutyl)amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclohexyl)amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(4-tert-butylimidazol-1-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5-oxa-2-azaspiro[3.4]octan-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2-cyclopropyltetrahydrofuran-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2-cyclopropyltetrahydrofuran-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-7-[5-(3-acetyl-3-azabicyclo[3.1.0]hexan-1-yl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 3-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]azetidine-1-carboxylate; 2,2,2-trifluoroacetic acid (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluoromorpholin-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoroethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(3-methylsulfonyl-3-azabicyclo[3.1.0]hexan-1-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3-azabicyclo[3.1.0]hexane-3-carboxylate (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-(1-methylsulfonylpyrrolidin-3-yl)tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2-hydroxyspiro[3.3]heptan-6-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-[3-(chloromethyl)-3-(hydroxymethyl)azetidin-1-yl]-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methoxy-acetonitrile; (3R)-3-amino-1,1-dioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-(1-methylsulfonyl-4-piperidyl)tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(5-oxa-2-azaspiro[3.4]octan-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(6-oxa-2-azaspiro[3.5]nonan-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(cyclopentoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-(1,1,2,2,2-pentafluoroethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 7-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-5-azaspiro[2.4]heptane-5-carboxylate; 2-[5-[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methyl-propanenitrile; (3R)-3-amino-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-[(1R,5S)-8-azabicyclo[3.2.1]octane-8-carbonyl]-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(5-methylsulfonyl-5-azaspiro[2.4]heptan-7-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-7-[5-(1-acetyl-4-piperidyl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(2-methyltetrazol-5-yl)-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-(1-methylpyrrolidin-3-yl)tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-7-[2-(1-acetyl-4-piperidyl)tetrazol-5-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-7-[5-(3-acetyl-3-azabicyclo[4.1.0]heptan-1-yl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(3-methylsulfonyl-3-azabicyclo[4.1.0]heptan-1-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3-azabicyclo[4.1.0]heptane-3-carboxylate; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(isopropylamino)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(2-azaspiro[3.3]heptan-2-yl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 5-[[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]amino]-3,3-difluoro-piperidine-1-carboxylate; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluoro-1-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-dimethylmorpholin-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3-fluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Methyl 4-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]piperidine-1-carboxylate (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-ethyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one Methyl 3-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]pyrrolidine-1-carboxylate (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-methyl-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-methyl-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methyl-propanenitrile; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(5,5-difluoro-3-piperidyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(3-azabicyclo[4.1.0]heptan-1-yl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-7-[5-(5-acetyl-5-azaspiro[2.4]heptan-7-yl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluoropiperidine-1-carbonyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-methyl-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]propanenitrile; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(3-methylsulfonyl-3-azabicyclo[3.1.1]heptan-1-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate; Methyl 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methyl-propanenitrile; (3R)-7-[5-(3-acetyl-3-azabicyclo[3.1.1]heptan-1-yl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-ethyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroacetic acid (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-ethyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[4-(dimethylamino)-1,1-dimethyl-butyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclopentyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(4,4-difluorocyclohexyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(1,3-dimethylazetidin-3-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(tert-butylamino)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]cyclopropanecarbonitrile; 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]propanenitrile; Methyl 3-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]piperidine-1-carboxylate (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluoropyrrolidine-1-carbonyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(2-aminospiro[3.3]heptan-6-yl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-oxa-7-azaspiro[3.5]nonan-7-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one 4-[[(3R)-3-amino-8-fluoro-7-[5-(2-hydroxy-1,1-dimethyl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-5-yl]methyl]benzonitrile; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(5-amino-3,3-difluoro-1-piperidyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-[1-(chloromethyl)-2-hydroxy-1-methyl-ethyl]-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-N-isopropyl-N-methyl-1,3,4-oxadiazole-2-carboxamide (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(1-cyclopropyl-5,5-difluoro-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-[4-(chloromethyl)-4-(hydroxymethyl)-1-piperidyl]-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-methylsulfonylethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-N-tert-butyl-1,3,4-oxadiazole-2-carboxamide (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(isopropoxymethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[5,5-difluoro-1-(2-methoxyethyl)-3-piperidyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one 5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-3-tert-butyl-1,3,4-oxadiazol-2-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-methyltetrahydrofuran-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(4-amino-1,1-dimethyl-butyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(1,3-dimethyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(1-ethyl-3-piperidyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(3-amino-4,4-difluoro-1-piperidyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[2-(1,1-dioxo-1,4-thiazinan-4-yl)-1,1-dimethyl-ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one 5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-N,N-dimethyl-1,3,4-oxadiazole-2-carboxamide (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(1-ethyl-5,5-difluoro-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(1-methylpyrrolidin-3-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 5-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3,3-difluoro-piperidine-1-carboxylate (3R)-3-amino-7-[5-(2-azaspiro[3.3]heptan-2-yl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(isopropylamino)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluoro-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(1-cyclopropyl-4-piperidyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-dimethylmorpholin-4-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[6-(cyclopentoxy)-3-pyridyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[1,1-dimethyl-2-(2-oxo-1-piperidyl)ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methyl-propanenitrile; 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]propanenitrile; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(3-methylazetidin-3-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methylsulfonyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[5,5-difluoro-1-(2-hydroxyethyl)-3-piperidyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[1-(hydroxymethyl)cyclopropyl]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(cyclobutylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-7-[5-(1-acetyl-5,5-difluoro-3-piperidyl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(3-ethyl-1,2,4-triazol-1-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-7-[5-(4-acetylpiperazin-1-yl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-isobutyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-methylpiperazin-1-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[2-[2-hydroxyethyl(methyl)amino]-1,1-dimethyl-ethyl]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[1,1-dimethyl-2-(2-oxopyrrolidin-1-yl)ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[1,1-dimethyl-2-(4-methylpiperazin-1-yl)ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[1,1-dimethyl-2-(tetrahydrofuran-3-ylamino)ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(5-isopropoxy-2-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[1,1-dimethyl-2-(oxetan-3-ylamino)ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(3,4-difluorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chloro-3-fluoro-phenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluoro-1-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(1,1-dimethyl-2-morpholino-ethyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[2-(dimethylamino)-1,1-dimethyl-ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(6-isopropoxy-3-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[2-(4,4-difluoro-1-piperidyl)-1,1-dimethyl-ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-(2-hydroxy-1,1-dimethyl-ethyl)tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[2-(2-hydroxy-2-methyl-propyl)tetrazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(cyclopropylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[1,1-dimethyl-2-(1-piperidyl)ethyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorospiro[3.3]heptan-6-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(dimethylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-[(3-methylazetidin-1-yl)methyl]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; Methyl 4-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-4-methyl-piperidine-1-carboxylate; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-methyl-1-methylsulfonyl-4-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(cyclohexylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[3-(difluoromethyl)azetidin-3-yl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-7-[5-(2-amino-1,1-dimethyl-ethyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(6-oxaspiro[3.4]octan-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(3-fluoro-4-methylsulfonyl-phenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-ethyloxazol-2-yl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-imino-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(2-fluoro-4-methylsulfonyl-phenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-N,N,2-trimethyl-propanamide; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[3-(2-hydroxy-1,1-dimethyl-ethyl)-1,2,4-oxadiazol-5-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[[4-(3-hydroxyoxetan-3-yl)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-hydroxy-1,1-dimethyl-ethyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroacetic acid (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-hydroxy-1,1-dimethyl-ethyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[(4-phenoxyphenyl)methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[[4-(2-hydroxyethoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroacetic acid (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-9-methyl-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[1-(cyclopropylmethyl)pyrazol-4-yl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroacetic acid (3R)-7-[5-(1-acetyl-4-methyl-4-piperidyl)-1,3,4-oxadiazol-2-yl]-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-methylimino-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; 2-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-N,2-dimethyl-propanamide; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(2-cyclopropylpyrimidin-5-yl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(6-chloro-3-pyridyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (2R,3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-2-methyl-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[5-[(4-chlorophenyl)methyl]-3-pyridyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-methyl-4-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-methyltetrahydropyran-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2,2,2-trifluoroacetic acid (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 4,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-imino-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-chloro-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 2-[4-[[(3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-5-yl]methyl]phenoxy]acetamide; 1,1,1,3,3,3-hexafluoropropan-2-ol; N-[11-[4-[[(3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-5-yl]methyl]phenoxy]undecyl]acetamide; (2S)-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]-2-(methylamino)propanamide (2S)-2-amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]butanamide (2S)-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]-3-hydroxy-2-(methylamino)propanamide (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(cyclopentoxy)phenyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-[2,2,2-trideuterio-1,1-bis(trideuteriomethyl)ethyl]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(4-ethyltriazol-1-yl)-8-fluoro-2,3-dihydro-1,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[4-[(4-chlorophenyl)methyl]triazol-1-yl]-8-fluoro-2,3-dihydro-1,5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(4-ethyltriazol-1-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[4-[(4-chlorophenyl)methyl]triazol-1-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(4-tert-butyltriazol-1-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(1-ethyltriazol-4-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(2-ethyltetrazol-5-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-(1H-pyrazol-5-yl)-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyl-1H-1,2,4-triazol-3-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazol-5-yl]-2,3-dihydropyrido[3,2-b][1,4]thiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(3-ethyl-1,2,4-oxadiazol-5-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-(3-propyl-1,2,4-oxadiazol-5-yl)-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[3-[(4-chlorophenyl)methyl]-1,2,4-oxadiazol-5-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-[3-(benzyloxymethyl)-1,2,4-oxadiazol-5-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazol-5-yl]-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-[3-(aminomethyl)-1,2,4-oxadiazol-5-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(3-ethyl-1,2,4-oxadiazol-5-yl)-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(3-tert-butylisoxazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(2,2-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1,5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(3,3-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-8-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (2S)-N-[(3R)-8-fluoro-1,1,4-trioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ ６ ,5-benzothiazepin-3-yl]-2-(methylamino)propanamide; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(3,3,3-trifluoropropyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1-amino-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(1-fluoro-1-methyl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluoroethyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(4,4-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one: (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclopentyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorocyclopentyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclobutyl)methyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(tetrahydropyran-4-ylmethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(4,4,4-trifluorobutyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclobutyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorocyclobutyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-(5-tetrahydropyran-4-yl-1,3,4-oxadiazol-2-yl)-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-fluoroethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-isopropyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-hydroxy-1,1-dimethyl-ethyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(azetidin-1-yl)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(4-ethyloxazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-6-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(3-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; 4-[[(3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ ６ ,5-benzothiazepin-5-yl]methyl]benzonitrile; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[(4-tetrahydrofuran-3-yloxyphenyl)methyl]-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(2,2-difluoroethoxy)phenyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(difluoromethoxy)phenyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-(2-pyridylmethyl)-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(6-methoxy-3-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[[4-(aminomethyl)phenyl]methyl]-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(2-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(5-methoxy-2-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(4-methylsulfonylphenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(4-methoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(4-fluorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[[2-(aminomethyl)-4-chloro-phenyl]methyl]-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[[4-(11-aminoundecoxy)phenyl]methyl]-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 λ ６ ,5,5-benzothiazepin-3-yl]acetamide; N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ ６ ,5-benzothiazepin-3-yl]propanamide; (2S)-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ ６ ,5-benzothiazepin-3-yl]-2-hydroxy-butanamide; N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ ６ ,5-benzothiazepin-3-yl]butanamide; (2S)-2-amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ ６ ,5-benzothiazepin-3-yl]propanamide; (2S)-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ ６ ,5-benzothiazepin-3-yl]-2-(methylamino)butanamide; 3-amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ ６ ,5-benzothiazepin-3-yl]propanamide; N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ ６ ,5-benzothiazepin-3-yl]-2-(methylamino)acetamide; 2-amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ ６ ,5-benzothiazepin-3-yl]acetamide; 4-amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1λ ６ ,5-benzothiazepin-3-yl]butanamide; (3R)-3-amino-8-bromo-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-methyl-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-hydroxy-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-(dimethylamino)-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3,8-diamino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(1-tert-butylpyrazol-4-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; ((3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(1-ethylpyrazol-4-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(1-ethylpyrazol-3-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(4-tert-butylpyrazol-1-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(3-tert-butylpyrazol-1-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(4-ethylpyrazol-1-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(1-ethyl-1,2,4-triazol-3-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(1-tert-butyl-1,2,4-triazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(1-tert-butylpyrazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyl-1,2,4-oxadiazol-3-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1,1-dimethylbut-3-ynyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-[3-(trifluoromethyl)diazirin-3-yl]phenyl]methyl]-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-[5-(1,1-dimethylbut-3-ynyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ ４ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1λ ４ , 5-benzothiazepin-4-one; 3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-morpholino-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(cyclopentylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-7-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one; (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyltetrazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1λ ６ , 5-benzothiazepin-4-one or a pharmaceutically acceptable salt thereof.

42. Methyl 1-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3-azabicyclo[3.1.1]heptane-3-carboxylate 2-amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]acetamide (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride 2-amino-N-[(3R)-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]acetamide (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclobutyl)amino]-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-imino-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride salt (2S)-2-amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]propanamide (3R)-3-amino-7-(2-tert-butyltetrazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[[4-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-7-[5-[1-(trifluoromethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(2,2-difluoromorpholin-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-5-[(4-phenoxyphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Formic acid (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; hydrochloride salt (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluorocyclobutyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (2S)-2-amino-N-[(3R)-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-3-yl]butanamide (3R)-3-amino-8-fluoro-1,1-dioxo-7-[5-(2,2,2-trifluoroethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[(3,3-difluoro-1-methyl-cyclobutyl)amino]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride salt 2-[4-[[(3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-5-yl]methyl]phenyl]-2-methyl-propanenitrile (3R)-3-amino-7-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(5,5-difluoro-1-methyl-3-piperidyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1-oxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; hydrochloride salt (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride salt (3R)-3-amino-7-(2-tert-butyltetrazol-5-yl)-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(o-tolyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(cyclobutylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride 2-[5-[(3R)-3-amino-8-fluoro-1,1,4-trioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-2-methyl-propanenitrile; Hydrochloride (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(6-isopropoxy-3-pyridyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazol-5-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(6-fluoro-2-methyl-3-pyridyl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,3,4-oxadiazol-2-yl]-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(1-amino-2,2,2-trifluoro-1-methyl-ethyl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride salt (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(4-methoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-morpholino-1,2,4-oxadiazol-3-yl)-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-7-[5-[1-amino-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl]-1,2,4-oxadiazol-3-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride salt (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[methyl(2,2,2-trifluoroethyl)amino]-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(5-ethyltetrazol-2-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluoromorpholin-4-yl)-1,2,4-oxadiazol-3-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(tert-butylamino)-1,3,4-oxadiazol-2-yl]-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-morpholino-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; Hydrochloride (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride salt (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(cyclohexylamino)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; Hydrochloride (3R)-3-amino-7-(1-tert-butyl-1,2,4-triazol-3-yl)-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 4-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-4-methyl-piperidine-1-carboxylate; Hydrochloride (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-(3-ethyl-1,2,4-oxadiazol-5-yl)-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)-1,2,4-oxadiazol-3-yl]-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[(4-chloro-3-fluoro-phenyl)methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-5-[(4-isopropoxyphenyl)methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-1,1-dioxo-7-[5-[2-(trifluoromethyl)morpholin-4-yl]-1,3,4-oxadiazol-2-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-7-[5-(3,3-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluoromorpholin-4-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-oxa-5-azabicyclo[4.1.0]heptan-5-yl)-1,2,4-oxadiazol-3-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-7-[5-(1,1-dimethylbut-3-ynyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-5-[[4-(trifluoromethoxy)phenyl]methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-oxa-7-azaspiro[2.5]octan-7-yl)-1,2,4-oxadiazol-3-yl]-1-oxo-2,3-dihydro-1lambda 4,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclobutyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-(5-isobutyl-1,3,4-oxadiazol-2-yl)-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one Methyl 5-[5-[(3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1,4-trioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-7-yl]-1,3,4-oxadiazol-2-yl]-3,3-difluoro-piperidine-1-carboxylate (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclopentyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-[2-(trifluoromethyl)morpholin-4-yl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorospiro[3.3]heptan-6-yl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-Hexafluoropropan-2-ol; hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3,3-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2,2-difluorocyclohexyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1 lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-[5,5-difluoro-1-(2-methoxyethyl)-3-piperidyl]-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(1-ethyl-5,5-difluoro-3-piperidyl)-1,3,4-oxadiazol-2-yl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(2-cyclopropyltetrahydrofuran-2-yl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-7-[5-(3-fluoro-1-methyl-3-piperidyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(6-fluoro-2-methyl-3-pyridyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-7-(5-tert-butyl-1,2,4-oxadiazol-3-yl)-5-[[4-(cyclopentoxy)phenyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(2-fluoro-6-methyl-phenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; 1,1,1,3,3,3-hexafluoropropan-2-ol; Hydrochloride (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(cyclopentoxy)phenyl]methyl]-8-fluoro-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[[4-(cyclopentoxy)phenyl]methyl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-7-[5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl]-1,1-dioxo-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one (3R)-3-amino-5-[(4-chlorophenyl)methyl]-8-fluoro-1,1-dioxo-7-[5-(1,2,2,2-tetrafluoro-1-methoxy-ethyl)-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; Hydrochloride (3R)-3-amino-7-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-8-fluoro-1,1-dioxo-5-[(4-phenoxyphenyl)methyl]-2,3-dihydro-1lambda 6,5-benzothiazepin-4-one; hydrochloride or a pharmaceutically acceptable salt thereof.

43. Formula (IX) (In the formula, X, Y, R １ , R ２ , R ３ , R ４ , R ６ , R ６ａ is as defined in any one of claims 1 to 34, and PG is an amino protecting group. with a suitable deprotecting agent to give the compound of formula (I) １ , R ２ , R ３ , R ４ , R ６ , R ６ａ is as defined in any one of claims 1 to 34, and R ５ is hydrogen), or a pharmaceutically acceptable salt thereof; or Formula (I') (In the formula, X, Y, R １ , R ２ , R ３ , R ４ , R ６ , R ６ａ is as defined in any one of claims 1 to 34, and R ５ is hydrogen) in the presence of a base to a compound of formula R ９ CO ２ H (wherein, R ９ is as defined in any one of claims 1 to 30) to obtain a compound of formula (I) or a pharmaceutically acceptable salt thereof ５ is -C(O)(R ９ ) to form 43. A process for the preparation of a compound according to any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof, comprising:

44. A pharmaceutical composition comprising the compound according to any one of claims 1 to 42 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

45. 45. The pharmaceutical composition of claim 44, further comprising an additional therapeutic agent.

46. A pharmaceutical for treating, preventing and / or delaying the progression of cancer, comprising a compound according to any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof.

47. 47. The medicament of claim 46, wherein the cancer is associated with aberrant diacylglycerol kinase signaling, and the diacylglycerol kinase is selected from DGKα and / or DGKζ.

48. the cancer is selected from the group consisting of B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, hairy cell leukemia, small cell or large cell follicular lymphoma, malignant lymphoproliferative conditions, MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndromes, 48. The pharmaceutical agent of claim 46 or 47, wherein the cancer is selected from the group consisting of non-Hodgkin's lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenstrom's macroglobulinemia, preleukemia, sarcoma, carcinoma, melanoma, neuroblastoma, renal cell carcinoma, colon cancer, colorectal cancer, breast cancer, epithelial squamous cell carcinoma, melanoma, gastric cancer, brain cancer, lung cancer, pancreatic cancer, cervical cancer, ovarian cancer, liver cancer, bladder cancer, prostate cancer, testicular cancer, thyroid cancer, uterine cancer, adrenal cancer, and head and neck cancer.

49. 43. Use of a compound according to any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment, prevention and / or delay of progression of cancer.

50. A pharmaceutical for inhibiting the activity of at least one diacylglycerol kinase selected from DGKα and DGKζ, comprising a compound according to any one of claims 1 to 42, or a pharmaceutically acceptable salt thereof.

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