Pyrazole compounds as cullin ring ubiquitin ligase compounds

Abstract

This invention relates to compounds having the ability to regulate / stimulate / induce, particularly induce, the degradation of target proteins. Such target proteins may be proteins involved in diseases such as cancer, metabolic disorders, infectious diseases, and / or neurological disorders. This invention also relates to the use of compounds and compositions as pharmaceuticals, and pharmaceutical compositions comprising these compounds. (I)

Description

[0001] Invention Field

[0002] This invention relates to compounds having the ability to regulate / stimulate / induce (particularly induce ubiquitination of target proteins). The compounds of this invention can stimulate / induce the degradation of target proteins by ubiquitination of target proteins via cullin-RING ubiquitin ligase (CRL). Such target proteins may be proteins involved in diseases such as cancer, metabolic diseases, infectious diseases, and / or neurological diseases. This invention also relates to the use of compounds and compositions comprising these compounds as pharmaceuticals, and pharmaceutical compositions comprising these compounds. Specifically, the compounds of this invention can promote the degradation of proteins associated with cancer, metabolic diseases, infectious diseases, and / or neurological diseases. Furthermore, this invention relates to the use of compounds as pharmaceuticals, such as for treating cancer, metabolic diseases, infectious diseases, and / or neurological diseases, and to a method of treating diseases (such as cancer, metabolic diseases, infectious diseases, and / or neurological diseases) comprising administering the compounds of this invention. Background of the Invention

[0004] Protein degradation plays a central role in many cellular functions, including cell maintenance and normal function. Therefore, the degradation of proteins (such as those related to cellular functions, including maintenance) influences cell proliferation, differentiation, and death. Against this backdrop, reducing protein activity by inducing targeted protein degradation (TPD) through compounds, thereby removing the target protein, represents a promising research paradigm in drug discovery, compared to protein inhibitors that reduce activity simply by blocking it. Thus, utilizing cellular protein degradation pathways can provide methods to reduce or eliminate protein activity.

[0005] Until recently, small molecules that induce protein instability were often discovered incidentally. Examples include the estrogen receptor (ER) modulator fulvestrant, or CRL4. CRBN Modulators such as thalidomide and related compounds (e.g., lenalidomide or pomalidomide) (collectively referred to as "IMiDs," also known in the art as "molecular glues") represent approved drugs that clinically validate the concept of TPD as a therapeutic reality. In fact, lenalidomide became one of the most commercially successful drugs in 2018 with total revenue of $9.7 billion.

[0006] It is noteworthy that decades of research were required to decipher the molecular mechanism by which IMiDs act as small molecule degraders. Winter et al. (Winter, GE, Buckley, DL, Paulk, J., Roberts, J., Souza, A., De-Phagano, S., and Bradner, JE (2015) presented "Phthalimide Conjugation as a Strategy for Targeted Protein Degradation in Vivo." in vivo Target Protein Degradation (Science) Science (348, 1376-81) describes a rational strategy for promoting the TPD concept, describing the formation of heterobifunctional molecules by coupling IMiD-like chemical structures with known targeting ligands via flexible linkers. These heterobifunctional small molecules (often also referred to as "degraders") bind to target proteins (via interchangeable targeting ligands) and the E3 ligase CRL4. CRBN (That is, through IMiD-like chemical agents) it works. This induces molecular proximity between the target protein and the E3 ligase, prompting ubiquitination and proteolytic degradation of the former. Specifically, ubiquitin conjugation on the target protein is mediated by an enzyme cascade including E1 ubiquitin activators, E2 ubiquitin conjugates, and E3 ubiquitin ligases, which link ubiquitin to the target protein (Hershko et al., Nat. Med. 6, 1073–1081 (2000); Komander et al., Annu. Rev. Biochem. 81, 203–229 (2012)).

[0007] Therefore, the ubiquitin-proteasome pathway, as one of the major degradation pathways in cells, is a key pathway for regulating critical regulatory proteins and degrading misfolded and abnormal proteins. It has been found to be a valuable tool for degrading target proteins by covalently linking ubiquitin to them, especially in therapeutic applications.

[0008] There are certain precautions to take when developing heterobifunctional degraders (PROTACs) capable of hijacking CRBN ligase complexes. For example, only certain E3 ligases can be utilized by such heterobifunctional degraders. Therefore, the ligands typically bind to CRBN, VHL, cIAP, or MDM2. Furthermore, a portion of the structure of the heterobifunctional degrader of PROTACs is a ligand of the target protein, thus excluding the application of this technique to “ligandless” proteins (see, for example, Surade and Blundell (2012); Chemistry & Biology, Vol. 19, No. 1, pp. 42–50). Sometimes, the high molecular weight of the resulting heterobifunctional degrader can affect pharmacology and bioavailability.

[0009] There is a need for highly efficient small molecules that can bind to E3 ligase components, thus making them suitable for degrading the desired target proteins.

[0010] Small molecules can also modulate other components of the E3 ligase and ubiquitin-proteasome pathway through “molecular glue”-type mechanisms. In this way, such compounds can operate independently of the availability of accessible hydrophobic binding pockets. For example, IMiDs can induce co-linking with target proteins that are not naturally bound to CRBN, i.e., without requiring additional linkage to the target moiety. This, in turn, promotes ubiquitination and proteasome degradation of binding target proteins such as transcription factors IKZF1 and IKZF3. As another example, arylsulfonamides can redirect the activity of the E3 ligase DCAF15 to degrade the splicing factor RBM39 in a manner similar to IMiDs. Similarly, the plant hormone auxin is known to redirect the target space of the E3 ligase Tir1, thereby inducing the degradation of Aux / IAA transcriptional repressors.

[0011] To date, target proteins lacking hydrophobic binding pockets or binding sites that inactivate them have exceeded the scope of commonly used compounds that can be developed for therapeutic purposes. In other words, this method cannot achieve the degradation of target proteins, for example, those that do not possess accessible hydrophobic pockets or inhibitory binding sites. In this regard, important disease-related targets such as MYC, RAS, or β-catenin remain beyond the scope of therapeutic development.

[0012] Therefore, a new paradigm for drug design is urgently needed. In view of the above, the technical problem of this invention is to provide compounds capable of inducing ubiquitination of target proteins, particularly target proteins that need to be degraded in cells (such as cells involved in or related to disease). Specifically, the object of this invention is to provide compounds with highly efficient ability to induce the degradation of target proteins, particularly for target proteins that need to be degraded in cells, such as target proteins in cells related to or involved in disease.

[0013] The solution to this technical problem is provided by the embodiments defined below and characterized in the claims. Summary of the Invention

[0014] This invention relates to the compounds described herein, particularly compounds of formula (I), pharmaceutical compositions comprising the same, and their use in treating various diseases that can be treated by targeted degradation of specific proteins, namely, cyclin K (CCNK) and / or CDK12 and / or CDK13.

[0015] The compounds disclosed herein and in the context of this invention are capable of regulating / stimulating / inducing the degradation of target proteins, particularly ubiquitination of target proteins via cullin-RING ubiquitin ligase (CRL). In the context of this invention, the compounds have the ability to regulate / stimulate / induce, particularly by enhancing cullin-RING ubiquitin ligase activity / CRL activity, the ubiquitination of target proteins.

[0016] The compounds disclosed herein and in the context of this invention can be used specifically as the molecular gels described herein and in the appended examples.

[0017] Molecular glues can degrade target proteins by coordinating direct interactions between the target protein and cullin-RING ligases (CRLs). Molecular glues have the potential to induce the elimination of disease-related proteins that would otherwise be considered "undruggable." The mechanism of action of molecular glues can be illustrated by clinically approved thalidomide analogues (IMiDs) molecular glue / degrader. IMiDs and CRL4 CRBN The binding of E3 ligase leads to the recruitment of selected zinc finger transcription factors (TFs), resulting in their ubiquitination and subsequent proteasome degradation (Lu, G). et al. , Science 343, 305-309, doi:10.1126 / science.1244917 (2014); Kronke, J. et al. Science 343, 301-305, doi:10.1126 / science.1244851 (2014); Sievers, QL et al. Science 362, doi:10.1126 / science.aat0572 (2018); Gandhi, AK et al. British Journal of Hematology ( British journal of haematology ) 164, 811-821, doi:10.1111 / bjh.12708 (2014)).

[0018] Notably, IMiDs themselves do not possess measurable binding affinity for degraded transcription factors. However, they coordinate molecular recognition between ligases and transcription factors by inducing multiple protein-protein interactions near the binding interface. Certain aryl sulfonamides surrounding the clinically tested compound indisulam act as CRL4. DCAF15 The molecular glue between the ligase and the splicing factor RBM39 leads to the targeted degradation of the latter (Han, T). And others. Science , doi:10.1126 / science.aal3755 (2017); Uehara, T. et al., "Selective degradation of splicing factor CAPERalpha by anticancer sulfonamides". Nat Chem Biol 13, 675-680, doi:10.1038 / nchembio.2363 (2017); Bussiere, DE wait people Nat Chem Biol 16, 15-23, doi:10.1038 / s41589-019-0411-6 (2020); Ting, TC et al. Cell reports 29, 1499-1510.e1496, doi:10.1016 / j.celrep.2019.09.079 (2019); Faust, TB et al. Nat Chem Biol 16, 7-14, doi:10.1038 / s41589-019-0378-3 (2020); Du, X. et al. Structure (London, England: 1993) 27, 1625-1633.e1623, doi:10.1016 / j.str.2019.10.005 (2019).)

[0019] Therefore, the molecular gel mechanism can destabilize target proteins that were originally considered "unligandable", thus exceeding the scope of action of traditional small molecule inhibitors and heterobifunctional degraders.

[0020] The compounds of the present invention can induce the destabilization of disease-related target proteins, particularly cyclin K (CCNK) and / or CDK12 and / or CDK13. The compounds of the present invention particularly function as CCNK degraders. As described herein and as illustrated in the accompanying examples, the compounds of the present invention can degrade target proteins, particularly cyclin K (CCNK) and / or CDK12 and / or CDK13, independently of specific substrate receptors, which functionally distinguishes this mechanism from previously characterized degraders.

[0021] In this context, CDK12, CDK13, and / or CCNK may need or be desirable to be degraded in vivo or in vitro environments, such as in disease-associated or involved cells (e.g., cancer cells), where CDK12, CDK13, and / or CCNK should be degraded. Therefore, the target proteins disclosed herein and in the context of this invention can be cancer-associated target proteins, wherein one or more cancer-associated proteins are particularly selected from the group consisting of CDK12, CDK13, and CCNK.

[0022] One alternative approach to “inducing target protein ubiquitination” may include a direct conformational change in the target protein induced by binding to / interacting with the compound described herein. For example, binding of the compound described herein to a target protein may cause a conformational change in the protein, thereby stabilizing the interaction between one or more target proteins and one or more components of the E3 ligase complex, leading to ubiquitination and degradation of the one or more target proteins. Specifically, a compound binding to CDK12 / 13:CCNK may induce its interaction with the DDB1:CUL4B E3 ligase complex, leading to ubiquitination and degradation of CCNK. In this way, target proteins (e.g., CCNK) as described herein and illustrated in the accompanying examples may be degraded through direct or indirect binding mechanisms of the compound described herein, such as through binding of the compound to a target protein-associated protein. The compound may bind to CDK12 / 13 (which is associated with CCNK), thereby inducing ubiquitination and degradation of CCNK. This interaction is independent of the specific substrate receptor of the E3 ligase. Therefore, the compounds described herein and in the context of this invention can degrade one or more target proteins via E3 ligases without depending on the specific substrate receptor of the E3 ligase.

[0023] Specifically, the compounds of this invention can bind to the active sites of CDK12 / 13, thereby inducing a conformational change that promotes the binding of CDK12:CCNK and CDK13:CCNK to DDB1:CUL4B, respectively. Therefore, CDK12 and CDK13 primarily function to present CCNK to the ligase, leading to the degradation of CCNK, followed by a slightly reduced degradation of CDK12 and CDK13.

[0024] Therefore, it has been surprisingly found that the compounds of the present invention are capable of inducing the degradation of target proteins, particularly cyclin K (CCNK) and / or CDK12 and / or CDK13. It has also been found that in some embodiments, the compounds of formula (I) achieve favorable degradation kinetics of target proteins / target proteins (particularly CCNK).

[0025] On one hand, the present invention relates to compounds of formula (I) or their stereoisomers, tautomers, pharmaceutically acceptable salts or hydrates: (I) in, A is a 5-membered heteroaryl group comprising one or more identical or different heteroatoms selected from O, N, or S, wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the heteroaryl group is independently unsubstituted or substituted by one or more identical or different substituents R. A Substitution, provided that at least one substituent R A It exists on heteroaryl A; in, R A The group is a halogen, CN, C1-C6-alkyl, C1-C6-haloalkyl, 3 to 10 saturated or partially unsaturated carbocyclic group, carbocyclic-C1-C2-alkyl, carbon bicyclic group, carbon bicyclic-C1-C2-alkyl, heterocyclic group, heterocyclic-C1-C2-alkyl, heterobicyclic group, or heterobicyclic-C1-C2-alkyl, wherein the above heterocycle or heterobicycle contains one or more identical or different heteroatoms selected from O, N, or S, wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the above group is independently unsubstituted or substituented by one or more identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C4-alkyl; B is any of the following groups: , , , , , or ; In each case, the wavy line marks the connection to the rest of the molecule; and in, R B1 For H; R B2 It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; R B3 It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; R B4 It is H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; and R B5 For H; The condition is R B2 R B3 and R B4 At least one of them is different from H; X 1 For N or CR B6 ; Y 1 For N or CR B7 ; Z 1 For N or CR B8 ; The condition is X 1 Y 1 and Z 1 N is a subset of, but not exceeding, one of; R B6 For H; R B7 It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; R B8It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; R B9 It is H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; and R B10 For H; R B11 It is H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; and R B12 It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; R B13 It is H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; and R B14 It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; R B15It is H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; and R B16 It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; R B17 It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; and, R 1 It is H or C1-C4-alkyl.

[0026] In the preferred embodiment, A is a heteroaryl group. ; in, X 2 For N or NH; Y 2 For CH, CR A2 , N, NH or S; Z 2 For CH, CR A4 , N, NH or S; The condition is Y 2 and Z 2 At least one of them is different from CH, CR A2 or CR A4 ;and The wavy line marks the connection to the rest of the molecule; and... The dashed lines within the 5-membered ring indicate the presence of double bonds, thus forming an aromatic ring system; and Among them, R A2 R A3 and R A4 One or more identical or different substituents R on the heteroaryl A as defined in formula (I) above.A .

[0027] In another preferred embodiment, A is any of the following heteroaryl groups: , or ; In each case, the wavy line marks the connection to the rest of the molecule; and in, R A3 The group is a C1-C6-alkyl, C1-C6-haloalkyl, 3 to 10 saturated or partially unsaturated carbocyclic group, carbocyclic-C1-C2-alkyl, carbon bicyclic, carbon bicyclic-C1-C2-alkyl, heterocyclic, heterocyclic-C1-C2-alkyl, heterobicyclic, or heterobicyclic-C1-C2-alkyl, wherein the heterocycle or heterobicycle comprises one or more identical or different heteroatoms selected from O, N, or S, wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the above groups is independently unsubstituted or substituented by one or more identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C2-alkyl.

[0028] In another preferred embodiment, A is any of the following heteroaryl groups: or ; In each case, the wavy line marks the connection to the rest of the molecule; and in, R A3 The group is a C1-C6-alkyl, C1-C6-haloalkyl, 3- to 10-membered saturated carbocyclic group, carbocyclic-C1-C2-alkyl, carbon bicyclic, carbon bicyclic-C1-C2-alkyl, heterocyclic, heterocyclic-C1-C2-alkyl, heterobicyclic, or heterobicyclic-C1-C2-alkyl, wherein the heterocycle or heterobicycle comprises one or more identical or different heteroatoms selected from O, N, or S, wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the above groups is independently unsubstituted or substituented by one or more identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C2-alkyl.

[0029] In another preferred embodiment, R A3 It is any of the following groups: CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, C(CH3)3, CF3, , , , , , , , , , , , , , , , , , , , , , , , , , , , or ; The wavy line indicates the connection to group A in each case.

[0030] In another preferred embodiment, R A3 It is any of the following groups: CH(CH3)2、 , , , , , , , , , , , , , ; The wavy line indicates the connection to group A in each case.

[0031] In another preferred embodiment, R A3 for , The wavy line marks the connection to the A group.

[0032] In another preferred embodiment, B is

[0033] The wavy line marks the connection to the rest of the molecule; and...

[0034] in, R B1 For H; R B2 The possible values ​​are H, Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B3 The possible values ​​are H, Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B4 The possible values ​​are H, Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; and R B5 For H; The condition is R B2 R B3 and R B4 At least one of them is different from H.

[0035] In another preferred embodiment, B is

[0036] The wavy line marks the connection to the rest of the molecule; and...

[0037] in, R B7 It can be H, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B8 It can be H, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B9 It can be H, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; and R B10 For H.

[0038] In another preferred embodiment, R 1 For H.

[0039] In another preferred embodiment, R 1It is a C1-C4-alkyl group.

[0040] In another preferred embodiment, the compound is a compound of formula (IA). (IA).

[0041] In another preferred embodiment, the compound is a compound of formula (IB). (IB).

[0042] In another preferred embodiment, R 1 It is CH3.

[0043] In another preferred embodiment, the compound is selected from the group consisting of: (S)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, 2-(1-(4-chloro-5-methylpyridin-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, (S)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-(dimethylamino)pyridin-2-yl)-1H-pyrazol-4-yl)acetamide, (S)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazole-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(6-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(3-(methoxymethyl)phenyl)-1H-pyrazole-4-yl)acetamide, 2-(1-(4-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(4-methylpyridin-2-yl)-1H-pyrazole-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazole-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)acetamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(3-methoxyphenyl)-1H-pyrazole-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(m-tolyl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)acetamide, (S)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxetane-3-yl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (S)-N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, 2-(1-(4-chloro-5-methylpyridin-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, (S)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-(dimethylamino)pyridin-2-yl)-1H-pyrazol-4-yl)acetamide, (S)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)acetamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(6-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(methoxymethyl)phenyl)-1H-pyrazol-4-yl)acetamide, 2-(1-(4-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazole-5-yl)-2-(1-(4-methylpyridin-2-yl)-1H-pyrazole-4-yl)acetamide, N-(3-cyclopropyl-1H-pyrazole-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazole-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)acetamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-methoxyphenyl)-1H-pyrazol-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, and N-(3-Cyclopropyl-1H-pyrazole-5-yl)-2-(1-(3-fluorophenyl)-1H-pyrazole-4-yl)acetamide.

[0044] In another preferred embodiment, the compound is selected from the group consisting of: (S)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (S)-N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, and (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide.

[0045] In another preferred embodiment, the compound is selected from the group consisting of: (R)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (S)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; 2-(1-(2-chlorothiazol-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (R)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (S)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; 2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (R)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (S)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; 2-(1-(4-chlorothiazol-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (R)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (S)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; and 2-(1-(4-chlorothiazol-2-yl)-1H-pyrazole-4-yl)-N-(3-cyclopropyl-1H-pyrazole-5-yl)propionamide.

[0046] In another preferred embodiment, the compound is selected from the group consisting of: (S)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (S)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; and (S)-2-(1-(4-chlorothiazol-2-yl)-1H-pyrazole-4-yl)-N-(3-cyclopropyl-1H-pyrazole-5-yl)propionamide.

[0047] In another respect, the present invention relates to a pharmaceutical composition comprising a pharmaceutically acceptable amount of a compound of formula (I) as defined herein, and optionally a pharmaceutically acceptable carrier, diluent or excipient.

[0048] In another aspect, the present invention relates to the use of a compound of formula (I) as defined herein or a pharmaceutical composition comprising a compound of formula (I) as defined herein for medicinal purposes. Specifically, the present invention relates to a compound of formula (I) as defined herein or a pharmaceutical composition comprising a compound of formula (I) as defined herein for the treatment or prevention of cancer, metabolic diseases, neurological diseases, or infectious diseases. In a preferred embodiment, the present invention relates to the use of a compound of formula (I) as defined herein or a pharmaceutical composition comprising a compound of formula (I) as defined herein for the treatment or prevention of cancer.

[0049] In one embodiment, the cancer is a solid tumor. In another embodiment, the cancer is selected from the group consisting of: leukemia, particularly acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL), and chronic leukemia including chronic myeloid leukemia; lymphoma, particularly non-Hodgkin lymphoma and Hodgkin lymphoma; head and neck cancer; esophageal cancer; adenoid cystic carcinoma; osteosarcoma; ovarian cancer; Ewing's sarcoma; lung cancer; neuroblastoma; gastrointestinal cancer; endometrial cancer; cervical cancer; medulloblastoma; prostate cancer; breast cancer; thyroid cancer; meningioma; liver cancer; colorectal cancer; pancreatic cancer; chondrosarcoma; osteosarcoma; and kidney cancer.

[0050] In a preferred embodiment, the cancer is selected from the group consisting of lymphoma, liver cancer, breast cancer, neuroblastoma, cervical cancer, Ewing's sarcoma, and lung cancer, particularly MYCL-overexpressing lung cancer. In a more preferred embodiment, the cancer is selected from liver cancer, particularly hepatocellular carcinoma; breast cancer, particularly HER2-overexpressing breast cancer or triple-negative breast cancer; and neuroblastoma, particularly MYCN-overexpressing neuroblastoma.

[0051] In another preferred embodiment, the cancer is a cancer with HER2 overexpression accompanied by CDK12 overexpression.

[0052] Detailed description of the invention

[0053] The compounds of formula (I) described herein and in the accompanying examples degrade one or more target proteins, particularly CCNK, CD12, and / or CDK13, most likely through interactions with components of the cullin RING E3 ligase family, which are present in several family members of cullin RING E3 ligases. In particular, the family members of cullin RING E3 ligases can be diversified, for example, through their respective substrate receptors (e.g., CRBN or DCAF15). The compounds of formula (I) described herein can bind to components of the cullin RING E3 ligase family other than substrate receptors, and thus these compounds can degrade one or more target proteins independently of the substrate receptor. Therefore, the ability of molecular gels to degrade one or more target proteins by interacting with cullin RING E3 ligases may not be limited to specific family members of cullin RING E3 ligases.

[0054] The compounds of formula (I) described herein degrade one or more cancer-associated target proteins, particularly CDK12, CDK13, and / or cyclin K (CCNK). The mechanism of action of the compounds of formula (I) (which can be described as a “molecular glue”) leads to the degradation of one or more target proteins, particularly CDK12, CDK13, and / or cyclin K (CCNK) , which appears to depend on the ability of the molecular glue to coordinate protein-protein interactions between the cullin RING E3 ligase and one or more target proteins to be degraded. As described herein, this is achieved by stabilizing the interaction between CCNK-bound CDK12 and / or CDK13 and the cullin RING E3 ligase (particularly one or more components of the cullin RING E3 ligase, such as CUL4B and / or DDB1).

[0055] The preferred embodiments of the substituents in the compounds of formula (I) above will be described in further detail below. It should be understood that each preferred embodiment can be applied individually or in combination with other preferred embodiments. Furthermore, it should be understood that the preferred embodiments in each case also apply to stereoisomers, tautomers, pharmaceutically acceptable salts, and hydrates of the compounds of the present invention.

[0056] As described above, the compound of the present invention is a compound of formula (I): (I) Regarding ring A and its substituent R in compound of formula (I) A The following preferred implementation schemes are relevant.

[0057] As described above, in compound (I), A is a 5-membered heteroaryl group comprising one or more identical or different heteroatoms selected from O, N, or S, wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the heteroaryl group is independently unsubstituted or substituted by one or more identical or different substituents R. A Substitution, provided that at least one substituent R A It exists on heteroaryl A; in, R A The group is a halogen, CN, C1-C6-alkyl, C1-C6-haloalkyl, 3 to 10 saturated or partially unsaturated carbocyclic group, carbocyclic-C1-C2-alkyl, carbon bicyclic group, carbon bicyclic-C1-C2-alkyl, heterocyclic group, heterocyclic-C1-C2-alkyl, heterobicyclic group, or heterobicyclic-C1-C2-alkyl, wherein the above heterocycle or heterobicycle contains one or more identical or different heteroatoms selected from O, N, or S, wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the above group is independently unsubstituted or substituented by one or more identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C4-alkyl.

[0058] In the preferred embodiment, A is a 5-membered heteroaryl group, comprising one or more, preferably one, two or three, more preferably two or three, or even more preferably two identical or different heteroatoms selected from O, N, or S, wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein the heteroaryl group is substituented by one or more, preferably one or two, more preferably one identical or different substituent R. A replace.

[0059] In a more preferred embodiment, A is a 5-membered heteroaryl group selected from the group consisting of imidazole, pyrazol, triazol, oxazol, isoxazol, isothiazol, and thiazolyl, preferably pyrazol, oxazol, and thiazolyl, more preferably pyrazol and thiazolyl, wherein the above heteroaryl group is independently substituent R by one or more, preferably one or two, more preferably one identical or different substituent. A replace.

[0060] If A is an isothiazol group, then R is preferred. A It is not CH3.

[0061] In another, more preferred embodiment, A is a 5-membered heteroaryl group selected from the group consisting of imidazole, pyrazol, triazol, oxazol, isoxazol, and thiazolyl, preferably pyrazol, oxazol, and thiazolyl, more preferably pyrazol and thiazolyl, wherein the above heteroaryl group is independently substituented by one or more, preferably one or two, more preferably one identical or different substituent R. A replace.

[0062] In a particularly preferred embodiment A is a pyrazolyl group, wherein the pyrazolyl group is substituent R by one or more, preferably one or two, more preferably one identical or different substituent R. A replace.

[0063] In another particularly preferred embodiment, A is a thiazolyl group, wherein the thiazolyl group is substituent R by one or more, preferably one or two, more preferably one identical or different substituent. A replace.

[0064] Furthermore, preferably, the heteroaryl A is linked to the amide moiety of the remainder of the molecule via a carbon atom. Furthermore, preferably, the heteroaryl A contains a plurality of heteroatoms, more preferably two or three heteroatoms, and particularly preferably two heteroatoms.

[0065] Therefore, in the preferred embodiment, A is a heteroaryl group A (A ); in, X 2 For N or NH; Y 2 For CH, CR A2 , N, NH, O or S; Z 2 For CH, CR A4 , N, NH, O or S; The condition is Y 2 and Z 2 At least one of them is different from CH, CR A2 or CR A4 ;and The wavy line marks the connection to the rest of the molecule; and... The dashed lines within the 5-membered ring indicate the presence of double bonds, thus forming an aromatic ring system; and Among them, R A2 R A3 and R A4 One or more identical or different substituents R on the heteroaryl A as defined for compounds of formula (I) A ; Make R A2 R A3 and R A4 Each is independently selected from the following groups: Halogen, CN, C1-C6-alkyl, C1-C6-haloalkyl, 3 to 10 saturated or partially unsaturated carbocyclic groups, carbocyclic-C1-C2-alkyl, carbon bicyclic, carbon bicyclic-C1-C2-alkyl, heterocyclic, heterocyclic-C1-C2-alkyl, heterobicyclic and heterobicyclic-C1-C2-alkyl, wherein the above heterocycles or heterobicycles contain one or more identical or different heteroatoms selected from O, N or S, wherein the N atom and / or S atom are independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the above groups is independently unsubstituted or substituented by one or more identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C4-alkyl.

[0066] Regarding the heteroaryl A Preferably, X 2 For N or NH; Y 2 For CH, CR A2 , N, NH or S; Z 2 For CH, CR A4 , N, NH or S; More preferably, X 2 For N or NH; Y 2 For CH, CR A2 , N or NH; Z 2 For CH, CR A4 , N, NH or S; Even more preferably, X 2 For N or NH; Y 2 For CH, CR A2 , N or NH; Z 2 For CH, CR A4 Or S; Even more preferably, X 2 For N or NH; Y 2 For N or NH; Z2 For CH or CR A4 CH is preferred; or X 2 Let N be the number of people in the group. Y 2 For CH or CR A2 CH is preferred; Z 2 For S, Particularly preferred, X 2 For N or NH; Y 2 For N or NH; Z 2 For CH or CR A4 CH is preferred.

[0067] As described above, in a particularly preferred embodiment, heteroaryl A comprises two heteroatoms. Therefore, in heteroaryl A... Among them, Y is particularly preferred. 2 and Z 2 One that is different from CH and CR A2 or CR A4 And Y 2 and Z 2 One of them is CH, CR A2 or CR A4 CH is preferred.

[0068] Furthermore, it should be understood that heteroaryl A or A Whether the nitrogen atom (N) or NH in the formula depends on the heteroaryl group (A or A). The aromatic ring system in the compound and the tautomers that may form therefrom. In particular, those skilled in the art will know that if the heteroaryl A ZhongX 2 Y 2 and Z 2 If only one of the atoms is a nitrogen atom and the remaining heteroatoms are O or S, then the nitrogen atom exists in the form of N. If the heteroaryl group A ZhongX 2 Y 2 and Z 2 If multiple nitrogen atoms are present in the group, then one of the nitrogen atoms exists in the form of NH, and the remaining nitrogen atoms exist in the form of N. Therefore, in heteroaryl A In the middle, X 2 Y 2 and Z 2 At most one of them is NH.

[0069] Furthermore, if heteroaryl A or A The presence of multiple nitrogen atoms in a compound (e.g., a pyrazolyl group) results in two distinct tautomers, which typically exist in chemical equilibrium in solution. The more thermodynamically stable tautomer exists in excess, and these two tautomers readily interconvert. Therefore, whenever only the heteroaryl A or A group of a compound of formula (I) is described... When referring to one of the two possible tautomers (e.g., in the case of a pyrazolyl group), it also refers to the other tautomer. For clarity, in the case of a pyrazolyl group, heteroaryl A or A The two possible tautomers are shown below: (A1-T1) and (A1-T2).

[0070] Therefore, when the heteroaryl A or A of the compound of formula (I) When described in this article in only one tautomer form (e.g., A1-T1 or A1-T2), it also refers to the heteroaryl A or A of the corresponding other tautomer form of the compound of formula (I). and mixtures thereof. Furthermore, for clarity, when the heteroaryl A or A of the compound of formula (I) When described in this article in different tautomer forms (e.g., A1-T1 and A1-T2), it also refers to their mixture.

[0071] Similarly, if the compound of formula (I) described herein contains a heteroaryl group A or A A tautomer form (e.g., Ia-T1 or Ia-T2) also refers to a form containing a heteroaryl A or A The corresponding tautomeric form of compound (I) and mixtures thereof. If this article describes heteroaryl A or A with different tautomeric forms... Compounds of formula (I) (e.g., Ia-T1 and Ia-T2) also refer to mixtures thereof.

[0072] In view of the above, in the preferred embodiment, A is any of the following heteroaryl groups: (A1-T1) (A1-T2) (A2-T1) (A2-T2) (A3) (A4) (A5) (A6) (A7) (A8) (A9) or (A10); In each case, the wavy line marks the connection to the rest of the molecule; and Among them, R A2 R A3 and R A4 One or more identical or different substituents R on the heteroaryl A as defined for compounds of formula (I) A ; Make R A2 R A3 and R A4 Each is independently selected from the following groups: Halogen, CN, C1-C6-alkyl, C1-C6-haloalkyl, 3 to 10 saturated or partially unsaturated carbocyclic groups, carbocyclic-C1-C2-alkyl, carbon bicyclic, carbon bicyclic-C1-C2-alkyl, heterocyclic, heterocyclic-C1-C2-alkyl, heterobicyclic and heterobicyclic-C1-C2-alkyl, wherein the above heterocycles or heterobicycles contain one or more identical or different heteroatoms selected from O, N or S, wherein the N atom and / or S atom are independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the above groups is independently unsubstituted or substituented by one or more identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C4-alkyl; Preferably, wherein, R A2 (If present) is a C1-C2-alkyl group, or a 3- to 10-membered saturated or partially unsaturated carbocyclic group; R A4 (If present) is a halogen, CN, C1-C2-alkyl, or a 3- to 10-membered saturated or partially unsaturated carbocyclic group; and R A3 The group is a halogen, CN, C1-C6-alkyl, C1-C6-haloalkyl, 3 to 10 saturated or partially unsaturated carbocyclic group, carbocyclic-C1-C2-alkyl, carbon bicyclic group, carbon bicyclic-C1-C2-alkyl, heterocyclic group, heterocyclic-C1-C2-alkyl, heterobicyclic group, or heterobicyclic-C1-C2-alkyl, wherein the above heterocycle or heterobicycle contains one or more identical or different heteroatoms selected from O, N, or S, wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the above group is independently unsubstituted or substituented by one or more identical or different substituents R. Y replace; in, R YIt is Cl, F or C1-C4-alkyl.

[0073] In a particularly preferred embodiment, R A3 The heteroaryl group A or A of the compound of formula (I) The only substituent R on A .

[0074] Therefore, in a more preferred embodiment, A is any of the following heteroaryl groups: (A1-T1) (A1-T2) (A5) (A6) (A9) or (A10); In each case, the wavy line marks the connection to the rest of the molecule, and R... A3 As defined above or in the following preferred embodiments.

[0075] In even more preferred embodiments, A is any of the following heteroaryl groups: (A1-T1) (A1-T2) (A6) or (A10); In each case, the wavy line marks the connection to the rest of the molecule, and R... A3 As defined above or in the following preferred embodiments.

[0076] In even more preferred embodiments, A is any of the following heteroaryl groups: (A1-T1) (A1-T2) or (A10); In each case, the wavy line marks the connection to the rest of the molecule, and R... A3 As defined above or in the following preferred embodiments.

[0077] In even more preferred embodiments, A is (A1-T1) or (A1-T2); In each case, the wavy line marks the connection to the rest of the molecule, and R... A3As defined above or in the following preferred embodiments.

[0078] In a particularly preferred embodiment A is (A1-T1); In each case, the wavy line marks the connection to the rest of the molecule, and R... A3 As defined above or in the following preferred embodiments.

[0079] In another particularly preferred embodiment, A is (A1-T2); In each case, the wavy line marks the connection to the rest of the molecule, and R... A3 As defined above or in the following preferred embodiments.

[0080] In a preferred embodiment, the compound of formula (I) is therefore a compound of formula (Ia-T1), (Ia-T2), or (Ib): (Ia-T1) (Ia-T2) or (Ib).

[0081] In one embodiment, the compound of formula (I) is a compound of formula (Ia-T1) or (Ia-T2): (Ia-T1) or (Ia-T2).

[0082] In another embodiment, the compound of formula (I) is the compound of formula (Ib): (Ib).

[0083] Particularly preferred compounds of formula (I) are compounds of formula (Ia-T1) or their tautomers (Ia-T2). In one particularly preferred embodiment, the compound of formula (I) is a compound of formula (Ia-T1). In another particularly preferred embodiment, the compound of formula (I) is a compound of formula (Ia-T2).

[0084] With regard to compounds of formula (I), especially compounds of formulas (Ia-T1), (Ia-T2) and (Ib), and heteroaryl A or A as defined above. With regard to preferred embodiments, particularly (A1-T1), (A1-T2), (A2-T1), (A2-T2), (A3), (A4), (A5), (A6), (A7), (A8), (A9), or (A10), especially (A1-T1), (A1-T2), (A5), (A6), (A9), or (A10), more preferably (A1-T1), (A1-T2), or (A10), and particularly preferably (A1-T1) or (A1-T2). The following concerns the substituent R... A R A2 R A3 and R A4 The preferred solution (if it exists) is relevant.

[0085] As described above, the heteroaryl group A of compound (I) has at least one substituent R. A In a preferred embodiment, the heteroaryl A is replaced by one, two, or three substituents R. A Substitution, wherein each substituent R is preferred A It is attached to the carbon atom of heteroaryl A. In a more preferred embodiment, heteroaryl A is replaced by one or two substituents R. A Substitution, wherein each substituent R is preferred A It is attached to the carbon atom of heteroaryl A. In an even more preferred embodiment, heteroaryl A is replaced by only one substituent R. A Substitution, wherein the preferred substituent R A It is attached to the carbon atom of the heteroaryl group A.

[0086] In another preferred embodiment, the heteroaryl A is at least modified by the substituent R. A3 The substituent R is represented A Replacement. In a more preferred embodiment, the heteroaryl A is replaced by R A3 The substituent R is represented A And two others by R A2 and R A4 The substituent R is represented A Substitution; more preferably, heteroaryl A is replaced by R A3 The substituent R is represented A And another one by R A2 Or R A4 The substituent R is represented A Replaced. In a particularly preferred embodiment, the heteroaryl A is replaced by only one of R A3 The substituent R is represented A replace.

[0087] Therefore, in one embodiment, the heteroaryl A is R A3 And two other substituents R A2and R A4 Substituted heteroaryl A In a preferred embodiment, the heteroaryl A is R A3 And another substituent R A2 Or R A4 Substituted heteroaryl A In a particularly preferred embodiment, the heteroaryl group is only affected by R. A3 Substituted heteroaryl A Therefore R A2 and R A4 It does not exist.

[0088] As mentioned above, R A The group is a halogen, CN, C1-C6-alkyl, C1-C6-haloalkyl, 3 to 10 saturated or partially unsaturated carbocyclic group, carbocyclic-C1-C2-alkyl, carbon bicyclic group, carbon bicyclic-C1-C2-alkyl, heterocyclic group, heterocyclic-C1-C2-alkyl, heterobicyclic group, or heterobicyclic-C1-C2-alkyl, wherein the above heterocycle or heterobicycle contains one or more identical or different heteroatoms selected from O, N, or S, wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the above group is independently unsubstituted or substituented by one or more identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C4-alkyl.

[0089] In the preferred embodiment, R A The heterocyclic group is a C1-C4-alkyl group, a C1-C4-haloalkyl group, a 3- to 10-membered saturated carbocyclic group, a carbocyclic-C1-C2-alkyl group, a carbocyclic group, a carbocyclic-C1-C2-alkyl group, a heterocyclic group, a heterocyclic-C1-C2-alkyl group, a heterobicyclic group, or a heterobicyclic-C1-C2-alkyl group, wherein the above-mentioned heterocycle or heterobicycle contains one or more, preferably one or two, more preferably one identical or different heteroatom selected from O, N, or S (preferably O or N), wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the above-mentioned group is independently unsubstituted or substituented by one or more identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C4-alkyl; Preferably, R Y It is Cl, F or C1-C2-alkyl; More preferably, R Y It is either F or CH3; Even more preferably, R Y It is F.

[0090] In a more preferred embodiment, R A The heterocyclic or heterobicyclic group comprises one or more, preferably one or two, more preferably one identical or different heteroatom selected from O, N, or S (preferably O or N), wherein the N atom and / or S atom are independently oxidized or unoxidized, and wherein each of the above rings is independently unsubstituted or substituented by one or more, preferably one or two identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C4-alkyl; Preferably, R Y It is Cl, F or C1-C2-alkyl; More preferably, R Y It is either F or CH3; Even more preferably, R Y It is F.

[0091] In even more preferred embodiments, R A The heterocyclic or heterobicyclic group is a C1-C4-alkyl group, a C1-C2-haloalkyl group, a 3- to 6-membered saturated carbocyclic group or a carbocyclic-C1-C2-alkyl group, a 3- to 6-membered saturated heterocyclic group or a heterocyclic-C1-C2-alkyl group, or a 7-membered saturated spirobicyclic group, wherein the above-mentioned heterocycle or heterobicycle contains one or more, preferably one or two, more preferably one identical or different heteroatom selected from O, N, or S (preferably O or N), wherein the N atom and / or S atom is independently oxidized or not oxidized, and wherein each of the above-mentioned rings is independently unsubstituted or substituented by one or more, preferably one or two identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C4-alkyl; Preferably, RY It is Cl, F or C1-C2-alkyl; More preferably, R Y It is either F or CH3; Even more preferably, R Y It is F.

[0092] In even more preferred embodiments, R A The spirocyclohexabicyclic group is CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, C(CH3)3, CF3, cyclopropyl, cyclobutyl, oxacyclobutyl, or a 7-membered saturated spirohexabicyclic group, wherein the spirohexabicyclic group contains a heteroatom selected from O, N, or S (preferably O or N, more preferably O), wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each of the rings is independently unsubstituted or substituted by one or more, preferably one or two identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C4-alkyl; Preferably, R Y It is Cl, F or C1-C2-alkyl; More preferably, R Y It is either F or CH3; Even more preferably, R Y It is F.

[0093] In even more preferred embodiments, R A It is any of the following groups: CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, C(CH3)3, CF3, , , , , , , , , , , , , , , , , , , , , , , , , , , , or ; The wavy line indicates the connection to group A in each case.

[0094] In a particularly preferred embodiment R A It is any of the following groups: CH(CH3)2、 (R A3 -1) (R A3 -2) (R A3 -3) (R A3 -4) (R A3 -5) (R A3 -6) (R A3 -6a) (R A3 -6b) (R A3 -7) (R A3 -7a) (R A3 -7b) (R A3 -7c) (R A3 -7d) or (R A3 -8); The wavy line indicates the connection to group A in each case.

[0095] The above text is about R. A The same implementation scheme defined also applies to different substituents R on heteroaryl A. A R A2 R A3 and R A4 .

[0096] Specifically, regarding R A3The above refers to R A The same preferred solutions described are related.

[0097] Therefore, in the preferred embodiment, R A3 The heterocyclic group is a C1-C4-alkyl group, a C1-C4-haloalkyl group, a 3- to 10-membered saturated carbocyclic group, a carbocyclic-C1-C2-alkyl group, a carbocyclic group, a carbocyclic-C1-C2-alkyl group, a heterocyclic group, a heterocyclic-C1-C2-alkyl group, a heterobicyclic group, or a heterobicyclic-C1-C2-alkyl group, wherein the above-mentioned heterocycle or heterobicycle contains one or more, preferably one or two, more preferably one identical or different heteroatom selected from O, N, or S (preferably O or N), wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the above-mentioned group is independently unsubstituted or substituented by one or more identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C4-alkyl; Preferably, R Y It is Cl, F or C1-C2-alkyl; More preferably, R Y It is either F or CH3; Even more preferably, R Y It is F.

[0098] In a more preferred embodiment, R A3 The heterocyclic or heterobicyclic group comprises one or more, preferably one or two, more preferably one identical or different heteroatom selected from O, N, or S (preferably O or N), wherein the N atom and / or S atom are independently oxidized or unoxidized, and wherein each of the above rings is independently unsubstituted or substituented by one or more, preferably one or two identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C4-alkyl; Preferably, R Y It is Cl, F or C1-C2-alkyl; More preferably, R Y It is either F or CH3; Even more preferably, R Y It is F.

[0099] In even more preferred embodiments, R A3 The heterocyclic or heterobicyclic group is a C1-C4-alkyl group, a C1-C2-haloalkyl group, a 3- to 6-membered saturated carbocyclic group or a carbocyclic-C1-C2-alkyl group, a 3- to 6-membered saturated heterocyclic group or a heterocyclic-C1-C2-alkyl group, or a 7-membered saturated spirobicyclic group, wherein the above-mentioned heterocycle or heterobicycle contains one or more, preferably one or two, more preferably one identical or different heteroatom selected from O, N, or S (preferably O or N), wherein the N atom and / or S atom is independently oxidized or not oxidized, and wherein each of the above-mentioned rings is independently unsubstituted or substituented by one or more, preferably one or two identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C4-alkyl; Preferably, R Y It is Cl, F or C1-C2-alkyl; More preferably, R Y It is either F or CH3; Even more preferably, R Y It is F.

[0100] In even more preferred embodiments, R A3 The spirocyclohexabicyclic group is CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, C(CH3)3, CF3, cyclopropyl, cyclobutyl, oxacyclobutyl, or a 7-membered saturated spirohexabicyclic group, wherein the spirohexabicyclic group contains a heteroatom selected from O, N, or S (preferably O or N, more preferably O), wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each of the rings is independently unsubstituted or substituted by one or more, preferably one or two identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C4-alkyl; Preferably, R Y It is Cl, F or C1-C2-alkyl; More preferably, RY It is either F or CH3; Even more preferably, R Y It is F.

[0101] In even more preferred embodiments, R A3 It is any of the following groups: CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, C(CH3)3, CF3, , , , , , , , , , , , , , , , , , , , , , , , , , , , or ; The wavy line indicates the connection to group A in each case.

[0102] In a particularly preferred embodiment, R A3 It is any of the following groups: CH(CH3)2、 (R A3 -1) (R A3 -2) (R A3 -3) (R A3 -4) (R A3 -5) (R A3 -6) (R A3 -6a) (R A3 -6b) (R A3 -7) (R A3 -7a) (R A3 -7b) (R A3 -7c) (R A3 -7d) or (R A3 -8); The wavy line indicates the connection to group A in each case.

[0103] In a preferred embodiment, R A Especially R A3 The cyclopropyl group is unsubstituted or has one or more, preferably one or two identical or different substituents R. Y Replace, where R Y It is F or CH3, preferably F. In this context, R is preferred. A Especially R A3 Selected from the following groups: (R) A3 -1), (R) A3 -5), (R) A3 -6), (R) A3 -6a), (R A3 -6b), (R A3 -7), (R) A3 -7a), (R A3 -7b), (R) A3 -7c) and (R A3 -7d).

[0104] In one implementation, R A Especially R A3 , Unsubstituted cyclopropyl (R) A3 -1). In another implementation, R A Especially R A3 For being substituents R by one or more, preferably one or two identical or different substituents. Y Substituted cyclopropyl, wherein R Y It is either F or CH3, preferably F. In this context, R... A Especially R A3 , Preferably selected from the group consisting of: (R) A3-5), (R) A3 -6), (R) A3 -6a), (R A3 -6b), (R A3 -7), (R) A3 -7a), (R A3 -7b), (R) A3 -7c) and (R A3 -7d).

[0105] In another preferred embodiment, R A Especially R A3 The cyclobutyl ring is unsubstituted or is replaced by one or more, preferably one or two identical or different substituents R. Y Replace, where R Y It is F or CH3, preferably F. In this context, R is preferred. A Especially R A3 Choose freely (R) A3 -2) and (R A3 -4) is a group.

[0106] In one implementation, R A Especially R A3 , is an unsubstituted cyclobutyl (R A3 -2). In another implementation, R A Especially R A3 For being substituents R by one or more, preferably one or two identical or different substituents. Y Substituted cyclobutyl, wherein R Y It is either F or CH3, preferably F. In this context, R... A Especially R A3 , Preferably (R) A3 -4).

[0107] In another preferred embodiment, R A Especially R A3 , It is an oxacyclobutyl or a 6- to 8-membered, preferably 7-membered saturated spiroheterobicyclic group, wherein the spiroheterobicyclic group contains a heteroatom selected from O, N, or S (preferably O or N, more preferably O), wherein the N atom and / or S atom are independently oxidized or unoxidized, and wherein each of the rings is independently unsubstituted or substituted by one or more, preferably one or two identical or different substituents R. Y Replaced, of which R Y It is F or CH3, preferably F. In this context, R is preferred. A Especially R A3It has not been replaced, and more importantly, it has the freedom of choice (R). A3 -3) and (R A3 The group consists of -10).

[0108] In another preferred embodiment, R A Especially R A3 , is CH(CH3)2.

[0109] In a more preferred embodiment, R A Especially R A3 The cyclopropyl group is unsubstituted or has one or more, preferably one or two identical or different substituents R. Y Replace, where R Y It is F or CH3, preferably F.

[0110] In a particularly preferred embodiment, R A Especially R A3 , is an unsubstituted cyclopropyl group, therefore

[0111] R A Especially R A3 , is the following group R A3 -1 (R A3 -1), The wavy line marks the connection to the A group.

[0112] Regarding R A2 (If it exists), the following preferred options are further relevant.

[0113] In the preferred embodiment, R A2 It is a halogen, CN, C1-C2-alkyl, or a 3 to 10-membered saturated or partially unsaturated carbocyclic group.

[0114] In a more preferred embodiment, R A2 It is a halogen, CN, or C1-C2-alkyl.

[0115] In even more preferred embodiments, R A2 It is a C1-C2-alkyl group.

[0116] In the most preferred implementation scheme, R A2 It is CH3.

[0117] As described above, with regard to the compounds of the present invention, it is preferable to have heteroaryl A or A There is no substituent R on it A2 .

[0118] Regarding R A4 (If it exists), the following preferred options are further relevant.

[0119] In the preferred embodiment, R A4 It is a halogen, CN, C1-C2-alkyl, or a 3 to 10-membered saturated or partially unsaturated carbocyclic group.

[0120] In a more preferred embodiment, R A4 It is a halogen, CN, or C1-C2-alkyl.

[0121] In even more preferred embodiments, R A4 It is a C1-C2-alkyl group.

[0122] In the most preferred implementation scheme, R A4 It is CH3.

[0123] As described above, with regard to the compounds of the present invention, it is preferable to have heteroaryl A or A There is no substituent R on it A4 .

[0124] In view of the above, according to embodiments C-1 to C-30, for heteroaryl A (including the corresponding substituent R thereon) A3 In this regard, the following meanings are preferred.

[0125] Table C

[0126] Of particular relevance are implementation plans C-1 to C-15, especially C-2.

[0127] Therefore, in a preferred embodiment of the present invention, A is any of the following heteroaryl groups: (A1-T1 ), (A1-T2 )or (A10 Preferably; (A1-T1 ) or (A1-T2 ), In each case, the wavy line marks the connection to the rest of the molecule.

[0128] Therefore, in the preferred embodiment, the compound of formula (I) is of formula (Ia-T1) (Ia-T2) ) or (Ib Compounds: (Ia-T1 ), (Ia-T2 ),or (Ib ).

[0129] In one embodiment, the compound of formula (I) is of formula (Ia-T1) ) or (Ia-T2 Compounds: (Ia-T1 ), (Ia-T2 ).

[0130] In another embodiment, the compound of formula (I) is of formula (Ib) Compounds: (Ib ).

[0131] The particularly preferred compound of formula (I) is of formula (Ia-T1) ) compounds or their tautomers (Ia-T2) In a particularly preferred embodiment, the compound of formula (I) is of formula (Ia-T1). In another particularly preferred embodiment, the compound of formula (I) is of formula (Ia-T2). ) compounds.

[0132] Regarding compounds of formula (I) and formulas (Ia-T1), (Ia-T2), (Ib), (Ia-T1) (Ia-T2) ), (Ib Compounds, preferably of formulas (Ia-T1), (Ia-T2), (Ia-T1) ) and (Ia-T2 ) compounds, especially (Ia-T1 ) and (Ia-T2 With regard to compounds, and heteroaryl A or A as defined above (In particular, with regard to the preferred embodiments of A1-T1, A1-T2, A2-T1, A2-T2, A3, A4, A5, A6, A7, A8, A9 or A10, preferably A1-T1, A1-T2 or A10), especially with regard to any of the embodiments C1 to C30 in Table C (especially A1-T1) A1-T2 Or A10 Regarding B and its substituent R, the following applies. B1 To R B17 The preferred implementation scheme is relevant.

[0133] As described above, in compound (I), B is any of the following groups: (B1) (B2) (B10) (B5) (B6) (B11) or (B9); In each case, the wavy line marks the connection to the rest of the molecule; and in, R B1 R B5 R B6 and R B10 Each of them is H; R B2 To R B4 R B7 To R B9 and R B11 To R B17 Each of these is independently H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2-, or C1-C4-dimethylaminoalkyl; The condition is R B2 R B3 and R B4 At least one of them is different from H; X 1 For N or CR B6 N is preferred. Y 1 For N or CR B7 ; preferably CRB7 ; Z 1 For N or CR B8 ; preferably CR B8 ; The condition is X 1 Y 1 and Z 1 N is one of the possible values, but no more than one.

[0134] In a more preferred embodiment, B is any of the following groups: (B1) (B2) (B3) (B4) (B5) (B6) (B7) (B8) or (B9); In each case, the wavy line marks the connection to the rest of the molecule; And X 1 Y 1 and Z 1 and R B1 To R B14 Each of them is as defined above or as defined in the following preferred embodiments.

[0135] In a more preferred embodiment, B is any of the following groups: (B1) (B2) (B3) (B4) (B5) (B6); The wavy line marks the connection to the rest of the molecule in each case; and X... 1 Y 1 and Z 1 and R B1 To R B14 Each of them is as defined above or as defined in the following preferred embodiments.

[0136] In even more preferred embodiments, B is any of the following groups: (B1) (B2); The wavy line marks the connection to the rest of the molecule in each case; and X... 1 Y 1 and Z 1 and R B1 To R B10 Each of them is as defined above or as defined in the following preferred embodiments.

[0137] In a particularly preferred embodiment B is (B1); The wavy line marks the connection to the rest of the molecule in each case; and R... B1 To R B5 Each of them is as defined above or as defined in the following preferred embodiments.

[0138] In another particularly preferred embodiment, B is (B2); Preferred (B2 ); The wavy line marks the connection to the rest of the molecule in each case; and X... 1 Y 1 and Z 1 and R B6 To R B10 Each of them is as defined above or as defined in the following preferred embodiments.

[0139] Therefore, in a preferred embodiment of the present invention, the compound of formula (I) is a compound of formula (Ic) or (Id): (Ic) or (Id) Where R 1 R B2 To R B4 R B7 To R B9 And A as described above with respect to formula (I). Preferably, R 1 R B2 To R B4 and / or R B7 To R B9As defined in the preferred embodiments below, and A as defined in the preferred embodiments above. In a more preferred embodiment, A is A1-T1, A1-T2, or A10, preferably A1-T1 or A1-T2. In a particularly preferred embodiment, A is A1-T1. A1-T2 Or A10 Preferably A1-T1 Or A1-T2 Furthermore, R is particularly preferred. 1 It is CH3.

[0140] With regard to ring B of compound (I), particularly with regard to the preferred embodiment of ring B described above, and with regard to compounds of formulas (Ic) and (Id), the following concerns the substituent R B2 To R B4 R B7 To R B9 and R B11 To R B17 The preferred solution is relevant.

[0141] As mentioned above, R B2 To R B4 R B7 To R B9 and R B11 To R B17 Each of (if present) is independently H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2-, or C1-C4-dimethylaminoalkyl; The condition is R B2 R B3 and R B4 At least one of them is different from H.

[0142] In the preferred embodiment, R B2 To R B4 R B7 To R B9 and R B11 To R B17 Each of (if present) is independently H, Cl, F, CN, N(CH3)2, CH3, cyclopropyl, cyclobutyl, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2.

[0143] In a more preferred embodiment, R B2 To R B4 R B7 To R B9 and R B11 To R B17 Each of the following (if present) is independently H, Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2.

[0144] Regarding R as phenyl B1 of ring B B2 R B3 and R B4 Especially in any preferred embodiment of ring B as defined above, and in compounds of formula (Ic), the following preferred embodiments are particularly relevant.

[0145] In the preferred embodiment, R B2 The possible values ​​are H, Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3, or CH2N(CH3)2; R B3 The possible values ​​are H, Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3, or CH2N(CH3)2; R B4 The possible values ​​are H, Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3, or CH2N(CH3)2; The condition is R B2 R B3 and R B4 At least one of them is different from H.

[0146] In a more preferred embodiment, R B2 The possible values ​​are H, Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B3 The possible values ​​are H, Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B4 The possible values ​​are H, Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; The condition is R B2 R B3 and R B4 At least one of them is different from H.

[0147] As mentioned above, R B2R B3 and R B4 At least one of them is different from H. Furthermore, regarding ring B (especially B1), R is preferred. B2 R B3 and R B4 At least one of them is H. Therefore, in a preferred embodiment, B1 contains one or two substituents, namely R. B2 R B3 and R B4 At least one of them is different from H, and R B2 R B3 and R B4 At least one of them is H. In one embodiment, B1 contains a substituent, namely R. B2 R B3 and R B4 One of them is different from H, and R B2 R B3 and R B4 Two of them are H. In another embodiment, B1 contains two substituents, namely R. B2 R B3 and R B4 The two in are different from H, and R B2 R B3 and R B4 One of them is H. In a particularly preferred embodiment, R B3 For H.

[0148] Therefore, in even more preferred embodiments, R B2 The possible values ​​are H, Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B3 The possible values ​​are H, Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B4 The possible values ​​are H, Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; and The condition is R B2 R B3 and R B4 At least one of them is different from H, and R B2 R B3 and R B4 One of them is H.

[0149] In even more preferred embodiments, R B2 The possible values ​​are H, Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; RB3 For H; R B4 The possible values ​​are H, Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; and The condition is R B2 and R B4 At least one of them is different from H.

[0150] In even more preferred embodiments, R B2 The possible values ​​are H, Cl, F, CN, CH3, CHF2, OCH3, or CH2OCH3; R B3 For H; R B4 It can be Cl, F, or CN; The condition is R B2 and R B4 At least one of them is different from H.

[0151] Therefore, if B is B1, especially in the preferred embodiment of B as defined above, B1 is preferably any of the following groups: (B1-a) (B1-b) (B1-c) or (B1-d); More preferably, (B1-a) or (B1-c); In each case, the wavy line marks the connection to the rest of the molecule; And among them, R B2 (If present) the following are Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2; R B3 (If present) the following are Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2; R B4 (If present) the following are Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2; Preferably, R B2 (If present) is Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; RB3 (If present) is Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B4 (If present) is Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; More preferably, R B2 (If present) is Cl, F, CN, CH3, CHF2, OCH3, or CH2OCH3; R B3 (If present) it is Cl, F, CN or CH3; R B4 (If it exists) is Cl, F or CN.

[0152] In a particularly preferred embodiment, B1 is B1-a. In another particularly preferred embodiment, B1 is B1-c.

[0153] In one embodiment, B is a group B1-a. In this regard, it is preferred that... R B2 The compounds are Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; and R B4 It can be Cl, F, CN, CH3, CHF2, CF3, OCH3 or CH2OCH3.

[0154] More preferably, R B2 It can be Cl, F, CN, CH3, CHF2, or OCH3; and R B4 It can be Cl, F, CN, CH3, CHF2 or OCH3.

[0155] Even more preferably, R B2 It can be Cl, F, CN, CH3, CHF2, or OCH3; and R B4 It can be Cl, F, or CN.

[0156] Therefore, in a particularly preferred embodiment, B is any of the following groups: (B1-a-1) (B1-a-2) (B1-a-3) (B1-a-4) (B1-a-5) (B1-a-6) (B1-a-7) (B1-a-8) (B1-a-9) (B1-a-10) (B1-a-11) or (B1-a-12); In each case, the wavy line marks the connection to the rest of the molecule.

[0157] In one embodiment, B is a group B1-b. In this regard, it is preferred that... R B2 The compounds are Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; and R B3 It can be Cl, F, CN, CH3, CHF2, CF3, OCH3 or CH2OCH3.

[0158] More preferably, R B2 It can be Cl, F, CN, CH3 or CH2OCH3; and R B3 It can be Cl, F, CN or CH3.

[0159] More preferably, R B2 It can be Cl, F, CN, CH3 or OCH3; and R B3 It can be Cl, F, or CH3.

[0160] Therefore, in a particularly preferred embodiment, B is any of the following groups: (B1-b-1) (B1-b-2) (B1-b-3) (B1-b-4) (B1-b-5) (B1-b-6) or (B1-b-7); In each case, the wavy line marks the connection to the rest of the molecule.

[0161] In one embodiment, B is a group B1-c. In this regard, it is preferred that... R B2 It can be Cl, F, CN, CH3, CHF2, CF3, OCH3 or CH2OCH3.

[0162] More preferably, R B2 It can be Cl, F, CN, CH3, CHF2, OCH3 or CH2OCH3.

[0163] Therefore, in a particularly preferred embodiment, B is any of the following groups: (B1-c-1) (B1-c-2) (B1-c-3) (B1-c-4) (B1-c-5) (B1-c-6) (B1-c-7) or (B1-c-8).

[0164] In one embodiment, B is a group B1-d. In this regard, it is preferred that... R B3 It can be Cl, F, CN, CH3, CHF2, CF3, OCH3 or CH2OCH3.

[0165] More preferably, R B3 It can be Cl, F, CN or CH3.

[0166] Therefore, in a particularly preferred embodiment, B is any of the following groups: (B1-d-1) (B1-d-2) (B1-d-3) or (B1-d-4).

[0167] Regarding X in pyridyl B2 as ring B 1 Y 1 Z 1 and R B7 R B8 and R B9 In particular, the following preferred embodiments are especially relevant in any preferred embodiment of ring B as defined above, and in compounds of formula (Id).

[0168] As stated above, with regard to B (especially B2), X is preferred. 1 Let N be the number of elements. Therefore, Y is preferred. 1 For CR B7 And Z 1 For CR B8 Furthermore, pyridyl B2 is preferably pyridyl B2. : (B2 ); The wavy line marks the connection between the molecule and the rest of the molecule.

[0169] Regarding B2 and B2 and the substituent R in the compound of formula (Id) B7 R B8 and R B9 The preferred option is

[0170] R B7 The possible values ​​are H, Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B8 The possible values ​​are H, Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B9 The possible values ​​are H, Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; In a more preferred embodiment, R B7 The possible values ​​are H, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B8 The possible values ​​are H, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B9 It can be H, CN, N(CH3)2, CH3, CHF2, CF3, OCH3 or CH2OCH3.

[0171] In even more preferred embodiments, R B7 It can be H, CH3, N(CH3)2 or OCH3; R B8 It can be H, CH3, N(CH3)2 or OCH3; R B9 It can be H, CH3, N(CH3)2 or OCH3.

[0172] In addition, regarding B2 and B2 Preferably, there exists R B7 R B8 and R B9 At least one (preferably one or two) is H. Therefore, in a preferred embodiment, B2 (especially B2) The presence of R is free from or contains one or two (preferably one or two, more preferably one) substituents. B7 R B8 and R B9 At least one (preferably one or two, more preferably two) is H.

[0173] In one implementation, B2 (especially B2) It contains one substituent, namely the present R. B7 R B8 and R B9 A different R from H, and which exists B7 R B8 and R B9 Two of them are H. In another implementation, B2 (especially B2) It contains two substituents, namely the present R B7 R B8 and R B9 Two different from H, and R exist. B7 R B8 and R B9 One of them is H. In a particularly preferred embodiment, B2 (especially B2) One or two (preferably one) substituents on R are located in R B7 Or R B9 The position, i.e., Z 1 For N or CR B8 , where R B8 H is preferred; Z is the preferred choice. 1 For CR B8 , where R B8 For H.

[0174] Therefore, if B is B2 or B2 In particular, in any preferred embodiment of B as defined above, B2 or B2 Preferably, any of the following groups: (B2 -a) (B2 -b) (B2 -c) (B2 -d) (B2 -e), (B2 -f) or (B2 -g); More preferably, (B2 -a) (B2 -c) (B2 -d) (B2 -f) or (B2 -g); Even more preferably, (B2 -d) or (B2 -f); In each case, the wavy line marks the connection to the rest of the molecule; And among them, R B7 (If present) the following are Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2; R B8 (If present) the following are Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2; R B9 (If present) the following are Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2; Preferably, R B7 (If present) is CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B8 (If present) is CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B9 (If present) is CN, N(CH3)2, CH3, CHF2, CF3, OCH3 or CH2OCH3.

[0175] More preferably, R B7 (If present) it is CH3, N(CH3)2 or OCH3; R B8 (If present) it is CH3, N(CH3)2 or OCH3; R B9 (If present) it is CH3, N(CH3)2 or OCH3.

[0176] In a particularly preferred embodiment, B2 or B2 For B2 -d. In another particularly preferred embodiment, B2 or B2 For B2 -f.

[0177] In one embodiment, B is a group B2. -a. In this regard, it is preferable that, R B7 The possible values ​​are Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; and R B9 It can be Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3 or CH2OCH3.

[0178] In a more preferred embodiment, R B7 It can be CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; and R B9 It can be CN, N(CH3)2, CH3, CHF2, CF3, OCH3 or CH2OCH3.

[0179] In even more preferred embodiments, R B7 It can be CH3, N(CH3)2 or OCH3; R B9 It can be CH3, N(CH3)2 or OCH3.

[0180] In another embodiment, B is the group B2. -b. In this regard, it is preferable that, R B7 The possible values ​​are Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; and R B8 It can be Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3 or CH2OCH3.

[0181] In a more preferred embodiment, R B7 It can be CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; and R B8It can be CN, N(CH3)2, CH3, CHF2, CF3, OCH3 or CH2OCH3.

[0182] In even more preferred embodiments, R B7 It can be CH3, N(CH3)2 or OCH3; R B8 It can be CH3, N(CH3)2 or OCH3.

[0183] In another embodiment, B is the group B2. -c. In this regard, it is preferable that, R B9 The possible values ​​are Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; and R B8 It can be Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3 or CH2OCH3.

[0184] In a more preferred embodiment, R B9 The compounds are Cl, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; and R B8 It can be CN, N(CH3)2, CH3, CHF2, CF3, OCH3 or CH2OCH3.

[0185] In a more preferred embodiment, R B9 It can be Cl, CH3, N(CH3)2 or OCH3; R B8 It can be CH3, N(CH3)2 or OCH3.

[0186] In even more preferred embodiments, R B9 For Cl; R B8 It is CH3.

[0187] Therefore, in a particularly preferred embodiment, B is a group consisting of: (B2 -c-1), In each case, the wavy line marks the connection to the rest of the molecule.

[0188] In another embodiment, B is the group B2. -d. In this regard, it is preferable that, RB9 It can be Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3 or CH2OCH3.

[0189] In a more preferred embodiment, R B9 It can be Cl, CH3, N(CH3)2 or OCH3.

[0190] Therefore, in a particularly preferred embodiment, B is any of the following groups: (B2 -d-1) (B2 -d-2) (B2 -d-3) or (B2 -d-4), In each case, the wavy line marks the connection to the rest of the molecule.

[0191] In another embodiment, B is the group B2. -e. In this regard, it is preferable that, R B8 It can be Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3 or CH2OCH3.

[0192] In a more preferred embodiment, R B9 It can be Cl, F, CH3, N(CH3)2 or OCH3.

[0193] In even more preferred embodiments, R B9 It is either F or OCH3.

[0194] Therefore, in a particularly preferred embodiment, B is any of the following groups: (B2 -e-1) or (B2 -e-2), In each case, the wavy line marks the connection to the rest of the molecule.

[0195] In another embodiment, B is the group B2. -f. In this regard, it is preferable to have, R B7 It can be Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3 or CH2OCH3.

[0196] In a more preferred embodiment, R B7 It can be Cl, CH3, N(CH3)2 or OCH3.

[0197] Therefore, in a particularly preferred embodiment, B is any of the following groups: (B2 -f-1) (B2 -f-2), (B2 -f-3) or (B2 -f-4), In each case, the wavy line marks the connection to the rest of the molecule.

[0198] In another embodiment, B is unsubstituted pyridyl B2. In this context, B in one embodiment is any of the following groups: (B2 -g), (B2-h) or (B2-i), preferred (B2 -g), In each case, the wavy line marks the connection to the rest of the molecule.

[0199] Regarding the R of the thiazole group B3 B11 The following preferred options are relevant.

[0200] In the preferred embodiment, R B11 The derivatives are H, Cl, F, CN, N(CH3)2, CH3, cyclopropyl, cyclobutyl, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2.

[0201] In a more preferred embodiment, R B11 It can be H, Cl, CN, CH3, cyclopropyl, CHF2, or OCH3.

[0202] In even more preferred embodiments, R B11 It can be H, Cl, or CH3.

[0203] Therefore, in a particularly preferred embodiment, B is a group consisting of: (B3-1), In each case, the wavy line marks the connection to the rest of the molecule.

[0204] Therefore, in another particularly preferred embodiment, B is a group consisting of: (B3-2), In each case, the wavy line marks the connection to the rest of the molecule.

[0205] Therefore, in another particularly preferred embodiment, B is a group consisting of: (B3-3), In each case, the wavy line marks the connection to the rest of the molecule.

[0206] Regarding the R of the thiazole group B4 B12 The following preferred options are relevant.

[0207] In the preferred embodiment, R B12 The derivatives are H, Cl, F, CN, N(CH3)2, CH3, cyclopropyl, cyclobutyl, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2.

[0208] In a more preferred embodiment, R B12 It can be H, Cl, CN, CH3, cyclopropyl, CHF2, or OCH3.

[0209] In even more preferred embodiments, R B12 It can be H, Cl, or CH3.

[0210] Therefore, in a particularly preferred embodiment, B is a group consisting of: (B4-1), In each case, the wavy line marks the connection to the rest of the molecule.

[0211] Therefore, in another particularly preferred embodiment, B is a group consisting of:

[0212] (B4-2), In each case, the wavy line marks the connection to the rest of the molecule.

[0213] Therefore, in another particularly preferred embodiment, B is a group consisting of: (B3-3), In each case, the wavy line marks the connection to the rest of the molecule.

[0214] Regarding the R of the thiazole group B5 B13 The following preferred options are relevant.

[0215] In the preferred embodiment, R B13 The derivatives are H, Cl, F, CN, N(CH3)2, CH3, cyclopropyl, cyclobutyl, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2.

[0216] In a more preferred embodiment, R B13 It can be H, Cl, CN, CH3, cyclopropyl, CHF2, or OCH3.

[0217] In even more preferred embodiments, R B13 It can be H, Cl, or CH3.

[0218] Therefore, in a particularly preferred embodiment, B is a group consisting of: (B5-1), In each case, the wavy line marks the connection to the rest of the molecule.

[0219] Therefore, in another particularly preferred embodiment, B is a group consisting of:

[0220] (B5-2), In each case, the wavy line marks the connection to the rest of the molecule.

[0221] Therefore, in another particularly preferred embodiment, B is a group consisting of: (B5-3), In each case, the wavy line marks the connection to the rest of the molecule.

[0222] Regarding the R of the thiazole group B6 B14 The following preferred options are relevant.

[0223] In the preferred embodiment, R B14 The derivatives are H, Cl, F, CN, N(CH3)2, CH3, cyclopropyl, cyclobutyl, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2.

[0224] In a more preferred embodiment, R B14 It can be H, Cl, CN, CH3, cyclopropyl, CHF2, or OCH3.

[0225] In even more preferred embodiments, R B14 It can be H, Cl, or CH3.

[0226] In a particularly preferred embodiment, R B14 For Cl, B can be the following groups: (B6-1), In each case, the wavy line marks the connection to the rest of the molecule.

[0227] In another particularly preferred embodiment, R B14 The form is CH3, such that B is a group with the following characteristics: (B6-2), In each case, the wavy line marks the connection to the rest of the molecule.

[0228] In another particularly preferred embodiment, R B14 H is present, such that B is a group with the following characteristics: (B6-3), In each case, the wavy line marks the connection to the rest of the molecule.

[0229] Regarding the R of the thiazole group B10 B11 and R B12 The following preferred options are relevant.

[0230] In the preferred embodiment, R B11 The derivatives are H, Cl, F, CN, N(CH3)2, CH3, cyclopropyl, cyclobutyl, CHF2, CF3, OCH3, CH2OCH3, or CH2N(CH3)2; and R B12 The derivatives are H, Cl, F, CN, N(CH3)2, CH3, cyclopropyl, cyclobutyl, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2.

[0231] In a more preferred embodiment, R B11 The derivatives are H, Cl, CN, CH3, cyclopropyl, CHF2, or OCH3; and R B12 It can be H, Cl, CN, CH3, cyclopropyl, CHF2, or OCH3.

[0232] In even more preferred embodiments, R B11 It can be H, Cl, or CH3.

[0233] R B12 It can be H, Cl, or CH3.

[0234] In a particularly preferred embodiment, R B11 and R B12 One of them is H, and R B11 and R B12 The other component is H, Cl, or CH3. Therefore, the thiazole group B10 is preferably the thiazole group B3 or B4.

[0235] Regarding the R of the thiophene group B7 B15 The following preferred options are relevant.

[0236] In the preferred embodiment, R B15 The derivatives are H, Cl, F, CN, N(CH3)2, CH3, cyclopropyl, cyclobutyl, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2.

[0237] In a more preferred embodiment, R B15 It can be H, Cl, CN, CH3, cyclopropyl, CHF2, or OCH3.

[0238] In even more preferred embodiments, R B15 It can be H, Cl, or CH3.

[0239] Regarding the R of the thiophene group B8 B16 The following preferred options are relevant.

[0240] In the preferred embodiment, R B16 The derivatives are H, Cl, F, CN, N(CH3)2, CH3, cyclopropyl, cyclobutyl, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2.

[0241] In a more preferred embodiment, R B16 It can be H, Cl, CN, CH3, cyclopropyl, CHF2, or OCH3.

[0242] In even more preferred embodiments, R B16 It can be H, Cl, or CH3.

[0243] Regarding the R of the thiophene group B9 B17The following preferred options are relevant.

[0244] In the preferred embodiment, R B17 The derivatives are H, Cl, F, CN, N(CH3)2, CH3, cyclopropyl, cyclobutyl, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2.

[0245] In a more preferred embodiment, R B17 It can be H, Cl, CN, CH3, cyclopropyl, CHF2, or OCH3.

[0246] In even more preferred embodiments, R B17 It can be H, Cl, or CH3.

[0247] Regarding R of the thiophene group B11 B11 and R B12 The following preferred options are relevant.

[0248] In the preferred embodiment, R B11 The derivatives are H, Cl, F, CN, N(CH3)2, CH3, cyclopropyl, cyclobutyl, CHF2, CF3, OCH3, CH2OCH3, or CH2N(CH3)2; and R B12 The derivatives are H, Cl, F, CN, N(CH3)2, CH3, cyclopropyl, cyclobutyl, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2.

[0249] In a more preferred embodiment, R B11 The derivatives are H, Cl, CN, CH3, cyclopropyl, CHF2, or OCH3; and R B12 It can be H, Cl, CN, CH3, cyclopropyl, CHF2, or OCH3.

[0250] In even more preferred embodiments, R B11 It can be H, Cl, or CH3.

[0251] R B12 It can be H, Cl, or CH3.

[0252] In a particularly preferred embodiment, R B15 and R B16 One of them is H, and R B15 and R B16The other component is H, Cl, or CH3. Therefore, the thiophene group B11 is preferably the thiophene group B7 or B8.

[0253] Therefore, in a preferred embodiment of the present invention, B is any of the following groups: (B1-a) (B1-b) (B1-c) (B1-d), (B2 -a) (B2 -b) (B2 -c) (B2 -d) (B2 -e) or (B2 -f), (B2 -g), (B3) (B4) (B5) (B6); (B7) (B8) or (B9); More preferably, (B1-a) (B1-b) (B1-c) (B1-d), (B2 -a) (B2 -b) (B2 -c) (B2 -d) (B2 -e) or (B2 -f), (B2 -g), (B3) (B4) (B5) (B6); Even more preferably, (B1-a) (B1-b) (B1-c) (B1-d), (B2 -a) (B2 -b) (B2 -c) (B2 -d) (B2 -e), (B2 -f), (B2 -g); Even more preferably, (B1-a) (B1-b) (B1-c) (B1-d), (B2 -a) (B2 -c) (B2 -d) (B2 -f) or (B2 -g); Even more preferably, (B1-a) (B1-c) (B2 -d) or (B2 -f); The wavy line marks the connection to the rest of the molecule in each case; and R... B2 To R B4 R B7 To R B9 and R B11 To RB17 As mentioned above, this applies to B1-a, B1-b, B1-c, B1-d, and B2. -a、B2 -b、B2 -c、B2 -d、B2 -e、B2 Defined by -f, B3, B4, B5, B6, B7, B8, or B9.

[0254] In a more preferred embodiment, B is any of the following groups: (B1-a) (B1-b) (B1-c) or (B1-d), More preferably, (B1-a) or (B1-c); The wavy line marks the connection to the rest of the molecule in each case; and R... B2 To R B4 As defined above for B1-a, B1-b, B1-c, or B1-d, Preferably, R B2 (If present) the following are Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2; R B3 (If present) the following are Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2; R B4 (If present) the following are Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2; More preferably, R B2 (If present) is Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B3 (If present) is Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B4 (If present) is Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; Even more preferably, R B2 (If present) is Cl, F, CN, CH3, CHF2, OCH3, or CH2OCH3; R B3 (If present) it is Cl, F, CN or CH3; R B4 (If it exists) is Cl, F or CN.

[0255] In one particularly preferred embodiment, B is B1-a. In another particularly preferred embodiment, B is B1-c.

[0256] In another, more preferred embodiment, B is (B2 -a) (B2 -b) (B2 -c) (B2 -d) (B2 -e), (B2 -f), (B2 -g); More preferably, (B2 -a) (B2 -c) (B2 -d) (B2 -f) or (B2 -g); Even more preferably, (B2 -d) or (B2 -f); The wavy line marks the connection to the rest of the molecule in each case; and R... B7 To R B9 As mentioned above regarding B2 -a、B2 -b、B2 -c、B2 -d、B2 -e or B2 Defined by -f Preferably, R B7 (If present) the following are Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2; R B8 (If present) the following are Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2; R B9 (If present) the following are Cl, F, CN, N(CH3)2, CH3, CHF2, CF3, OCH3, CH2OCH3 or CH2N(CH3)2; More preferably, R B7 (If present) is CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B8 (If present) is CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B9 (If present) is CN, N(CH3)2, CH3, CHF2, CF3, OCH3, or CH2OCH3; Even more preferably, R B7 (If present) it is CH3, N(CH3)2 or OCH3; R B8 (If present) it is CH3, N(CH3)2 or OCH3; R B9 (If present) it is CH3, N(CH3)2 or OCH3.

[0257] In a particularly preferred embodiment, B is B2. -d. In another particularly preferred embodiment, B is B2. -f.

[0258] In a preferred embodiment of the invention, the compound of formula (I) is therefore a compound of formula (Ic-1), (Ic-2), (Id-1), or (Id-2): (Ic-1) (Ic-2) (Id-1) or (Id-2), Where R 1 R B2 R B4 R B7 R B9 And A is as described above for formula (I). Preferably, R 1 As defined in the preferred implementation scheme below, and A, R B2 R B4 R B7 and / or R B9 As defined in the preferred embodiments above. In the preferred embodiments, A is A1-T1, A1-T2, or A10, preferably A1-T1 or A1-T2. In a particularly preferred embodiment, A is A1-T1. A1-T2 Or A10 Preferably A1-T1 Or A1-T2 Furthermore, R is particularly preferred. 1 It is CH3.

[0259] In a particularly preferred embodiment, B is a subset selected from the following groups: (B1-a-1) (B1-a-2) (B1-a-3) (B1-a-4) (B1-a-5) (B1-a-6) (B1-a-7) (B1-a-8) (B1-a-9) (B1-a-10) (B1-a-11) (B1-a-12) (B1-b-1) (B1-b-2) (B1-b-3) (B1-b-4) (B1-b-5) (B1-b-6) (B1-b-7) (B1-c-1) (B1-c-2) (B1-c-3) (B1-c-4) (B1-c-5) (B1-c-6) (B1-c-7) (B1-c-8) (B1-d-1) (B1-d-2) (B1-d-3) (B1-d-4) (B2 -c-1) (B2 -d-1) (B2 -d-2) (B2 -d-3) (B2 -d-4) (B2 -e-1) (B2 -e-2) (B2 -f-1) (B2 -f-2), (B2 -f-3), (B2 -f-4), (B2 -g), (B2-h) (B2-i) (B3-1) (B3-2) (B3-3) (B4-1) (B4-2) (B5-1) (B5-2) (B5-3) (B6-1) (B6-2) and (B6-3) In each case, the wavy line marks the connection to the rest of the molecule.

[0260] In even more preferred embodiments, B is a subset selected from the following groups: (B1-a-1) (B1-a-2) (B1-a-3) (B1-a-4) (B1-a-5) (B1-a-6) (B1-a-7) (B1-a-8) (B1-a-9) (B1-a-10) (B1-a-11) (B1-a-12) (B1-c-1) (B1-c-2) (B1-c-3) (B1-c-4) (B1-c-5) (B1-c-6) (B1-c-7) (B2 -d-1) (B2 -d-2) (B2 -d-3) (B2 -d-4) (B2 -f-1) (B2 -f-2), (B2 -f-3) and (B2 -f-4).

[0261] In view of the above, the following meanings of ring B according to embodiments D-1 to D-76 of Table D are preferred.

[0262] Table D

[0263] The most preferred implementation schemes are D1, D3, D8, D10, D21-D32, D40-D46, D53-D56 and D59-D62 of Table D.

[0264] Regarding compounds of formula (I) and formulas (Ia-T1), (Ia-T2), (Ib), (Ia-T1) (Ia-T2) ), (Ib For compounds of formula (Ia-T1), (Ic), (Id), (Ic-1), (Ic-2), (Id-1), and (Id-2), especially those of formula (Ia-T1), (Ia-T2) Compounds (Ic-1), (Ic-2), (Id-1), and (Id-2), and heteroaryl A or A with respect to the above definition. With regard to the preferred embodiments, particularly A1-T1, A1-T2, A2-T1, A2-T2, A3, A4, A5, A6, A7, A8, A9 or A10, especially A1-T1, A1-T2 or A10, particularly any of the embodiments C1 to C30 in Table C, especially A1-T1 and A1-T2 Furthermore, with regard to the preferred embodiments of B as defined above, particularly B1-a, B1-b, B1-c, B1-d, and B2 -a、B2 -b、B2 -c、B2 -d、B2 -e、B2 -f、B2 -g, B3, B4, B5 and B6, especially B1-a, B1-c, B2 -d and B2 -f, especially any of the embodiments D21-D76 in Table D, particularly any of D21-D32, D40-D46, D53-D56 and D59-D62 in Table D, the following regarding substituent R 1 The preferred implementation scheme is relevant.

[0265] As described above, in compound (I), R 1 It is H or C1-C4-alkyl.

[0266] In the preferred embodiment, R 1 It is H or C1-C2-alkyl.

[0267] In a more preferred embodiment, R 1 It can be H or CH3.

[0268] In a particularly preferred embodiment, R1 It is CH3.

[0269] In one embodiment of the present invention, R 1 H is used. Compounds of this type (I) are called compounds of formula (I.1).

[0270] In another embodiment of the invention, R 1 It is a C1-C4-alkyl group.

[0271] In a more preferred embodiment, R 1 It is a C1-C2-alkyl group.

[0272] In a particularly preferred embodiment, R 1 It is CH3. Compounds of this type (I) are called compounds of formula (I.2).

[0273] If R 1 In one embodiment of the invention, the compound of formula (I) is not H, but rather a compound of formula (IA): (IA); Where A and B are as defined above for formula (I), preferably as defined in the preferred embodiment described above, and R 1 It is a C1-C4-alkyl group, preferably a C1-C2-alkyl group, and more preferably CH3.

[0274] In a particularly preferred embodiment, R 1 It is CH3. These compounds are called compounds of formula (IA.2).

[0275] In one embodiment, with regard to the compounds of formulas (IA) and (IA.2), A is preferably A1-T1, A1-T2, or A10, especially any of embodiments C1 to C30 in Table C, with A1-T1 being preferred. A1-T2 Or A10 Especially A1-T1 Or A1-T2 In another preferred embodiment, with respect to compounds of formulas (IA) and (IA.2), B is preferably B1-a, B1-b, B1-c, B1-d, or B2. -a、B2 -b、B2 -c、B2 -d、B2 -e、B2 -f、B2 Any of B1-g, B3, B4, B5, or B6, especially B1-a, B1-c, or B2. -d or B2 Any of -f, especially any of the implementation schemes D21-D76 in Table D, particularly any of D21-D32, D40-D46, D53-D56 and D59-D62 in Table D.

[0276] In another embodiment of the invention, the compound of formula (I) is a compound of formula (IB): (IB), Where A and B are as defined above for formula (I), preferably as defined in the preferred embodiment described above, and R 1 It is a C1-C4-alkyl group, preferably a C1-C2-alkyl group, and more preferably CH3.

[0277] In a particularly preferred embodiment, R 1 It is CH3. These compounds are called compounds of formula (IB.2).

[0278] In one embodiment, with respect to the compounds of formulas (IB) and (IB.2), A is preferably A1-T1, A1-T2, or A10, especially any of embodiments C1 to C30 in Table C, with A1-T1 being preferred. A1-T2 Or A10 Especially A1-T1 Or A1-T2 In another preferred embodiment, with respect to compounds of formulas (IB) and (IB.2), B is preferably B1-a, B1-b, B1-c, B1-d, or B2. -a、B2 -b、B2 -c、B2 -d、B2 -e、B2 -f、B2 Any of B1-g, B3, B4, B5, or B6, especially B1-a, B1-c, or B2. -d or B2 Any of -f, especially any of the implementation schemes D21-D76 in Table D, particularly any of D21-D32, D40-D46, D53-D56 and D59-D62 in Table D.

[0279] In certain embodiments of the invention, in the compound of formula (I), a combination of the following embodiments is preferred: Table 1 Compound of formula (I.1), wherein A is Al-T1 or Al-T2, R A3 For R A3 -1, and B corresponds to a row in table D in each case.

[0280] Table 2

[0281] Compound of formula (I.2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -1, and B corresponds to a row in table D in each case.

[0282] Table 3

[0283] Compound of formula (I.1), wherein A is Al-T1 or Al-T2, R A3 For R A3 -2, and B corresponds to a row in table D in each case.

[0284] Table 4

[0285] Compound of formula (I.2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -2, and B corresponds to a row in table D in each case.

[0286] Table 5

[0287] Compound of formula (I.1), wherein A is Al-T1 or Al-T2, R A3 For R A3 -3, and B corresponds to a row in Table D in each case.

[0288] Table 6

[0289] Compound of formula (I.2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -3, and B corresponds to a row in Table D in each case.

[0290] Table 7

[0291] Compound of formula (I.1), wherein A is Al-T1 or Al-T2, R A3 For R A3 -4, and B corresponds to a row in Table D in each case.

[0292] Table 8

[0293] Compound of formula (I.2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -4, and B corresponds to a row in Table D in each case.

[0294] Table 9

[0295] Compound of formula (I.1), wherein A is Al-T1 or Al-T2, R A3 For R A3 -5, and B corresponds to a row in Table D in each case.

[0296] Table 10

[0297] Compound of formula (I.2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -5, and B corresponds to a row in Table D in each case.

[0298] Table 11

[0299] Compound of formula (I.1), wherein A is Al-T1 or Al-T2, R A3 For R A3 -6, and B corresponds to a row in Table D in each case.

[0300] Table 12

[0301] Compound of formula (I.2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -6, and B corresponds to a row in Table D in each case.

[0302] Table 13

[0303] Compound of formula (I.1), wherein A is Al-T1 or Al-T2, R A3 For R A3 -6a or R A3 -6b, and B corresponds to a row in Table D in each case.

[0304] Table 14

[0305] Compound of formula (I.2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -6a or R A3 -6b, and B corresponds to a row in Table D in each case.

[0306] Table 15

[0307] Compound of formula (I.1), wherein A is Al-T1 or Al-T2, R A3 For R A3 -7, and B corresponds to a row in Table D in each case.

[0308] Table 16

[0309] Compound of formula (I.2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -7, and B corresponds to a row in Table D in each case.

[0310] Table 17

[0311] Compound of formula (I.1), wherein A is Al-T1 or Al-T2, R A3 For R A3 -7a or R A3 -7b, and B corresponds to a row in Table D in each case.

[0312] Table 18

[0313] Compound of formula (I.2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -7a or R A3 -7b, and B corresponds to a row in Table D in each case.

[0314] Table 19

[0315] Compound of formula (I.1), wherein A is Al-T1 or Al-T2, R A3 For R A3 -7c or R A3 -7d, and B corresponds to a row in Table D in each case.

[0316] Table 20

[0317] Compound of formula (I.2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -7c or R A3 -7d, and B corresponds to a row in Table D in each case.

[0318] Table 21

[0319] Compound of formula (I.1), wherein A is Al-T1 or Al-T2, R A3 For R A3 -8, and B corresponds to a row in Table D in each case.

[0320] Table 22

[0321] Compound of formula (I.2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -8, and B corresponds to a row in Table D in each case.

[0322] Table 23

[0323] Compound of formula (I.1), wherein A is A10, R A3 For R A3 -1, and B corresponds to a row in table D in each case.

[0324] Table 24

[0325] Compound of formula (I.2), wherein A is A10, R A3 For R A3 -1, and B corresponds to a row in table D in each case.

[0326] Table 25

[0327] Compound of formula (I.1), wherein A is A10, R A3 For R A3 -2, and B corresponds to a row in table D in each case.

[0328] Table 26

[0329] Compound of formula (I.2), wherein A is A10, R A3 For R A3 -2, and B corresponds to a row in table D in each case.

[0330] Table 27

[0331] Compound of formula (I.1), wherein A is A10, R A3 For R A3 -3, and B corresponds to a row in Table D in each case.

[0332] Table 28

[0333] Compound of formula (I.2), wherein A is A10, R A3 For R A3 -3, and B corresponds to a row in Table D in each case.

[0334] Table 29

[0335] Compound of formula (I.1), wherein A is A10, R A3 For R A3 -4, and B corresponds to a row in Table D in each case.

[0336] Table 30

[0337] Compound of formula (I.2), wherein A is A10, R A3 For R A3 -4, and B corresponds to a row in Table D in each case.

[0338] Table 31

[0339] Compound of formula (I.1), wherein A is A10, R A3 For R A3 -5, and B corresponds to a row in Table D in each case.

[0340] Table 32

[0341] Compound of formula (I.2), wherein A is A10, R A3 For R A3 -5, and B corresponds to a row in Table D in each case.

[0342] Table 33

[0343] Compound of formula (I.1), wherein A is A10, R A3 For R A3 -6, and B corresponds to a row in Table D in each case.

[0344] Table 34

[0345] Compound of formula (I.2), wherein A is A10, R A3 For R A3 -6, and B corresponds to a row in Table D in each case.

[0346] Table 35

[0347] Compound of formula (I.1), wherein A is A10, R A3 For R A3 -6a or R A3 -6b, and B corresponds to a row in Table D in each case.

[0348] Table 36

[0349] Compound of formula (I.2), wherein A is A10, R A3 For R A3 -6a or R A3 -6b, and B corresponds to a row in Table D in each case.

[0350] Table 37

[0351] Compound of formula (I.1), wherein A is A10, R A3 For R A3 -7, and B corresponds to a row in Table D in each case.

[0352] Table 38

[0353] Compound of formula (I.2), wherein A is A10, R A3 For R A3 -7, and B corresponds to a row in Table D in each case.

[0354] Table 39

[0355] Compound of formula (I.1), wherein A is A10, R A3 For R A3 -7a or R A3 -7b, and B corresponds to a row in Table D in each case.

[0356] Table 40

[0357] Compound of formula (I.2), wherein A is A10, R A3 For R A3 -7a or R A3 -7b, and B corresponds to a row in Table D in each case.

[0358] Table 41

[0359] Compound of formula (I.1), wherein A is A10, R A3 For R A3 -7c or R A3 -7d, and B corresponds to a row in Table D in each case.

[0360] Table 42

[0361] Compound of formula (I.2), wherein A is A10, R A3 For R A3 -7c or R A3 -7d, and B corresponds to a row in Table D in each case.

[0362] Table 43

[0363] Compound of formula (I.1), wherein A is A10, R A3 For R A3 -8, and B corresponds to a row in Table D in each case.

[0364] Table 44

[0365] Compound of formula (I.2), wherein A is A10, R A3 For R A3 -8, and B corresponds to a row in Table D in each case.

[0366] Table 45

[0367] Compounds of formula (IA2), wherein A is A1-T1 or A1-T2, R A3 For R A3 -1, and B corresponds to a row in table D in each case.

[0368] Table 46

[0369] Compounds of formula (IA2), wherein A is A1-T1 or A1-T2, RA3 For R A3 -2, and B corresponds to a row in table D in each case.

[0370] Table 47

[0371] Compounds of formula (IA2), wherein A is A1-T1 or A1-T2, R A3 For R A3 -3, and B corresponds to a row in Table D in each case.

[0372] Table 48

[0373] Compounds of formula (IA2), wherein A is A1-T1 or A1-T2, R A3 For R A3 -4, and B corresponds to a row in Table D in each case.

[0374] Table 49

[0375] Compounds of formula (IA2), wherein A is A1-T1 or A1-T2, R A3 For R A3 -5, and B corresponds to a row in Table D in each case.

[0376] Table 50

[0377] Compounds of formula (IA2), wherein A is A1-T1 or A1-T2, R A3 For R A3 -6、R A3 -6a or R A3 -6b, and B corresponds to a row in Table D in each case.

[0378] Table 51

[0379] Compounds of formula (IA2), wherein A is A1-T1 or A1-T2, R A3 For R A3 -7、R A3 -7a, R A3 -7b、R A3 -7c or R A3 -7d, and B corresponds to a row in Table D in each case.

[0380] Table 52

[0381] Compounds of formula (IA2), wherein A is A1-T1 or A1-T2, R A3 For R A3 -8, and B corresponds to a row in Table D in each case.

[0382] Table 53

[0383] Compound of formula (IA2), where A is A10, R A3 For R A3 -1, and B corresponds to a row in table D in each case.

[0384] Table 54

[0385] Compound of formula (IA2), where A is A10, R A3 For R A3 -2, and B corresponds to a row in table D in each case.

[0386] Table 55

[0387] Compound of formula (IA2), where A is A10, R A3 For R A3 -3, and B corresponds to a row in Table D in each case.

[0388] Table 56

[0389] Compound of formula (IA2), where A is A10, R A3 For R A3 -4, and B corresponds to a row in Table D in each case.

[0390] Table 57

[0391] Compound of formula (IA2), where A is A10, R A3 For R A3 -5, and B corresponds to a row in Table D in each case.

[0392] Table 58

[0393] Compound of formula (IA2), where A is A10, R A3 For R A3 -6、R A3 -6a or R A3 -6b, and B corresponds to a row in Table D in each case.

[0394] Table 59

[0395] Compound of formula (IA2), where A is A10, R A3 For R A3 -7、R A3 -7a, R A3 -7b、R A3 -7c or R A3 -7d, and B corresponds to a row in Table D in each case.

[0396] Table 60

[0397] Compound of formula (IA2), where A is A10, R A3 For R A3 -8, and B corresponds to a row in Table D in each case.

[0398] Table 61

[0399] Compounds of formula (IB2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -1, and B corresponds to a row in table D in each case.

[0400] Table 62

[0401] Compounds of formula (IB2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -2, and B corresponds to a row in table D in each case.

[0402] Table 63

[0403] Compounds of formula (IB2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -3, and B corresponds to a row in Table D in each case.

[0404] Table 64

[0405] Compounds of formula (IB2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -4, and B corresponds to a row in Table D in each case.

[0406] Table 65

[0407] Compounds of formula (IB2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -5, and B corresponds to a row in Table D in each case.

[0408] Table 66

[0409] Compounds of formula (IB2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -6、R A3 -6a or R A3 -6b, and B corresponds to a row in Table D in each case.

[0410] Table 67

[0411] Compounds of formula (IB2), wherein A is Al-T1 or Al-T2, R A3For R A3 -7、R A3 -7a, R A3 -7b、R A3 -7c or R A3 -7d, and B corresponds to a row in Table D in each case.

[0412] Table 68

[0413] Compounds of formula (IB2), wherein A is Al-T1 or Al-T2, R A3 For R A3 -8, and B corresponds to a row in Table D in each case.

[0414] Table 69

[0415] Compound of formula (IB2), where A is A10, R A3 For R A3 -1, and B corresponds to a row in table D in each case.

[0416] Table 70

[0417] Compound of formula (IB2), where A is A10, R A3 For R A3 -2, and B corresponds to a row in table D in each case.

[0418] Table 71

[0419] Compound of formula (IB2), where A is A10, R A3 For R A3 -3, and B corresponds to a row in Table D in each case.

[0420] Table 72

[0421] Compound of formula (IB2), where A is A10, R A3 For R A3 -4, and B corresponds to a row in Table D in each case.

[0422] Table 73

[0423] Compound of formula (IB2), where A is A10, R A3 For R A3 -5, and B corresponds to a row in Table D in each case.

[0424] Table 74

[0425] Compound of formula (IB2), where A is A10, R A3 For R A3 -6、R A3 -6a or RA3 -6b, and B corresponds to a row in Table D in each case.

[0426] Table 75

[0427] Compound of formula (IB2), where A is A10, R A3 For R A3 -7、R A3 -7a, R A3 -7b、R A3 -7c or R A3 -7d, and B corresponds to a row in Table D in each case.

[0428] Table 76

[0429] Compound of formula (IB2), where A is A10, R A3 For R A3 -8, and B corresponds to a row in Table D in each case.

[0430] In a particularly preferred embodiment of the invention, the compound of formula (I) is selected from the group consisting of: (S)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(4-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(4-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(4-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-N-(5-(tert-butyl)-1H-pyrazol-3-yl)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-(tert-butyl)-1H-pyrazol-3-yl)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-(tert-butyl)-1H-pyrazol-3-yl)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(3,3-difluorocyclobutyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(3,3-difluorocyclobutyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(3,3-difluorocyclobutyl)-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(methoxymethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(methoxymethyl)phenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(methoxymethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)butyramide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)butyramide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)butyramide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chloro-4-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-4-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-4-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(2-chlorothiazo-5-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, 2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, (S)-2-(1-(4-chloro-3-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(4-chloro-3-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(4-chloro-3-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-cyano-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-5-yl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, 2-(1-(4-chloro-5-methylpyridin-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, (S)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methylthiazo-2-yl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(thiazo-4-yl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(thiazo-2-yl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(5-methylthiazo-2-yl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-(dimethylamino)pyridin-2-yl)-1H-pyrazol-4-yl)acetamide, (S)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazole-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(4-(dimethylamino)pyridin-2-yl)-1H-pyrazole-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(6-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,4-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,4-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,4-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(3-(methoxymethyl)phenyl)-1H-pyrazole-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(3-((dimethylamino)methyl)phenyl)-1H-pyrazole-4-yl)acetamide, 2-(1-(4-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(4-methylpyridin-2-yl)-1H-pyrazole-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazole-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)acetamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(3-methoxyphenyl)-1H-pyrazole-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(pyridin-2-yl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(pyridin-3-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, N-(5-Cyclopropylthiazo-2-yl)-2-(1-(m-tolyl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(m-tolyl)-1H-pyrazol-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropylthiazo-2-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)acetamide, N-(5-Cyclopropylthiazo-2-yl)-2-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)acetamide, 2-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-(trifluoromethyl)thiazolyl-2-yl)acetamide, 2-(1-(p-Tolyl)-1H-pyrazol-4-yl)-N-(5-(trifluoromethyl)thiazol-2-yl)acetamide, 2-(1-(4-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(trifluoromethyl)thiazolyl-2-yl)acetamide, (S)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxetane-3-yl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (S)-N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(4-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(4-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(4-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-N-(3-(tert-butyl)-1H-pyrazol-5-yl)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-(tert-butyl)-1H-pyrazol-5-yl)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-(tert-butyl)-1H-pyrazol-5-yl)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(3,3-difluorocyclobutyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(3,3-difluorocyclobutyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(3,3-difluorocyclobutyl)-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(methoxymethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(methoxymethyl)phenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(methoxymethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)butyramide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)butyramide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)butyramide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chloro-4-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-4-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-4-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(2-chlorothiazo-5-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, 2-(1-(4-chlorothiazol-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, (S)-2-(1-(4-chloro-3-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(4-chloro-3-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(4-chloro-3-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-cyano-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-5-yl)-1H-pyrazol-4-yl)acetamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, 2-(1-(4-chloro-5-methylpyridin-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, (S)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methylthiazo-2-yl)-1H-pyrazol-4-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(thiazo-4-yl)-1H-pyrazol-4-yl)acetamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(thiazo-2-yl)-1H-pyrazol-4-yl)acetamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(5-methylthiazo-2-yl)-1H-pyrazol-4-yl)acetamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-(dimethylamino)pyridin-2-yl)-1H-pyrazol-4-yl)acetamide, (S)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-(dimethylamino)pyridin-2-yl)-1H-pyrazol-4-yl)acetamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(6-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,4-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,4-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,4-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(methoxymethyl)phenyl)-1H-pyrazol-4-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-((dimethylamino)methyl)phenyl)-1H-pyrazol-4-yl)acetamide, 2-(1-(4-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazole-5-yl)-2-(1-(4-methylpyridin-2-yl)-1H-pyrazole-4-yl)acetamide, N-(3-cyclopropyl-1H-pyrazole-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazole-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)acetamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-methoxyphenyl)-1H-pyrazol-4-yl)acetamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(pyridin-2-yl)-1H-pyrazol-4-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(pyridin-4-yl)-1H-pyrazol-4-yl)acetamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(pyridin-3-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(m-tolyl)-1H-pyrazol-4-yl)acetamide, and N-(3-Cyclopropyl-1H-pyrazole-5-yl)-2-(1-(3-fluorophenyl)-1H-pyrazole-4-yl)acetamide.

[0431] In even more preferred embodiments of the present invention, the compound of formula (I) is selected from the group consisting of: (S)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, 2-(1-(4-chloro-5-methylpyridin-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, (S)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-(dimethylamino)pyridin-2-yl)-1H-pyrazol-4-yl)acetamide, (S)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazole-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(6-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(3-(methoxymethyl)phenyl)-1H-pyrazole-4-yl)acetamide, 2-(1-(4-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(4-methylpyridin-2-yl)-1H-pyrazole-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazole-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)acetamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(3-methoxyphenyl)-1H-pyrazole-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(m-tolyl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)acetamide, (S)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxetane-3-yl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (S)-N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, 2-(1-(4-chloro-5-methylpyridin-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, (S)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-(dimethylamino)pyridin-2-yl)-1H-pyrazol-4-yl)acetamide, (S)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)acetamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(6-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(methoxymethyl)phenyl)-1H-pyrazol-4-yl)acetamide, 2-(1-(4-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazole-5-yl)-2-(1-(4-methylpyridin-2-yl)-1H-pyrazole-4-yl)acetamide, N-(3-cyclopropyl-1H-pyrazole-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazole-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)acetamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-methoxyphenyl)-1H-pyrazol-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, and N-(3-Cyclopropyl-1H-pyrazole-5-yl)-2-(1-(3-fluorophenyl)-1H-pyrazole-4-yl)acetamide.

[0432] In another particularly preferred embodiment of the invention, the compound of formula (I) is selected from the group consisting of: (S)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (S)-N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, and (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide.

[0433] In another particularly preferred embodiment of the invention, the compound of formula (I) is selected from the group consisting of: (R)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (R)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (R)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxetane-3-yl)-1H-pyrazol-5-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, and (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide.

[0434] In another particularly preferred embodiment of the invention, the compound of formula (I) is selected from the group consisting of: 2-(1-(4-cyanothiazol-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; 2-(1-(4-cyanothiazol-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (R)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-(difluoromethyl)thiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-(difluoromethyl)thiazo-4-yl)-1H-pyrazol-4-yl)propionamide; N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-(difluoromethyl)thiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-(difluoromethyl)thiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-(difluoromethyl)thiazo-4-yl)-1H-pyrazol-4-yl)propionamide; N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-(difluoromethyl)thiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (R)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (S)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; 2-(1-(2-chlorothiazol-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (R)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (S)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; 2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (R)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (S)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; 2-(1-(4-chlorothiazol-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (R)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (S)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; 2-(1-(4-chlorothiazol-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-(difluoromethyl)thiazo-2-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-(difluoromethyl)thiazo-2-yl)-1H-pyrazol-4-yl)propionamide; N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-(difluoromethyl)thiazo-2-yl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-(difluoromethyl)thiazo-2-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-(difluoromethyl)thiazo-2-yl)-1H-pyrazol-4-yl)propionamide; N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-(difluoromethyl)thiazo-2-yl)-1H-pyrazol-4-yl)propionamide; (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methylthiazo-2-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methylthiazo-2-yl)-1H-pyrazol-4-yl)propionamide; N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methylthiazo-2-yl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methylthiazo-2-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methylthiazo-2-yl)-1H-pyrazol-4-yl)propionamide; and N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methylthiazolyl-2-yl)-1H-pyrazol-4-yl)propionamide.

[0435] In another particularly preferred embodiment of the invention, the compound of formula (I) is selected from the group consisting of: (R)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (S)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; 2-(1-(2-chlorothiazol-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (R)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (S)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; 2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (R)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (S)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; 2-(1-(4-chlorothiazol-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (R)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (S)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; and 2-(1-(4-chlorothiazol-2-yl)-1H-pyrazole-4-yl)-N-(3-cyclopropyl-1H-pyrazole-5-yl)propionamide.

[0436] In another particularly preferred embodiment of the invention, the compound of formula (I) is selected from the group consisting of: (S)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (S)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; and (S)-2-(1-(4-chlorothiazol-2-yl)-1H-pyrazole-4-yl)-N-(3-cyclopropyl-1H-pyrazole-5-yl)propionamide.

[0437] In another particularly preferred embodiment of the invention, the compound of formula (I) is selected from the group consisting of: (R)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (R)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (R)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; and (R)-2-(1-(4-chlorothiazol-2-yl)-1H-pyrazole-4-yl)-N-(3-cyclopropyl-1H-pyrazole-5-yl)propionamide.

[0438] In a particularly preferred embodiment of the invention, the compound of formula (I) is selected from the group consisting of:

[0439] and

[0440] In another particularly preferred embodiment of the invention, the compound of formula (I) is selected from the group consisting of: and .

[0441] As used herein, the term "cancer cell" refers to a tumor cell that has the ability to proliferate in dependence on a specific oncogene expressed in the cancer cell. Cancer cells may include primary cultured cells, cell lines, or cancer stem cells. As used herein, "dependence" on cell proliferation refers to an oncogene addiction or state of addiction, in which cells depend on a specific oncogene for proliferation. Whether a cell depends on a specific oncogene for proliferation can be confirmed by treating the cell with an inhibitor of that specific oncogene and then assessing the proliferative capacity of the treated cell. For example, the cells used in the context of the methods of this invention may be cancer cells.

[0442] On one hand, this invention relates to the use of a compound in medicine. The term "medicine" as used herein is intended as a general term encompassing both prescription and over-the-counter drugs. The use of a compound in medicine should be understood as useful in maintaining health or promoting recovery from a disease (preferably cancer). Furthermore, the term "medicine" includes any form of medicine, including but not limited to, for example, pills, ointments, creams, powders, ointments, capsules, injections, drops, vitamins, and suppositories. The scope of this invention is not limited to the type, form, or dosage of medicine. The compound described herein and in the context of this invention can be used for the treatment or prevention of cancer, metabolic diseases, neurological diseases, or infectious diseases. In this regard, the compound described herein and in the context of this invention can be used directly or indirectly to degrade proteins associated with cancer, metabolic diseases, neurological diseases, or infectious diseases via the E3 ligase described herein. For example, as shown in the proteomics analysis in Example 5 of WO 2021 / 074414, proteins associated with cancer, metabolic diseases, neurological diseases, or infectious diseases can be downregulated after degradation of CCNK by the E3 ligase.

[0443] Specifically, proteins associated with neurological disorders (such as HECTD1, MBP, and FEM1A) are downregulated after CCNK degradation. As another example, proteins associated with metabolic disorders (such as HMMR, LMNA, and TMPO) are also downregulated after CCNK degradation. As yet another example, proteins associated with infectious diseases (such as ICAM2, CALCOCO2, and CDC6) are downregulated after CCNK degradation. As yet another example, cancer-related proteins (such as BUB1, BUB1B, MCM10, CDCA7, and CDC6) are all downregulated after CCNK degradation. Therefore, proteins downregulated after CCNK degradation include those associated with cancer, metabolic diseases, neurological disorders, or infectious diseases.

[0444] In one aspect of the invention, a chemical compound or agent is used to treat cancer, wherein preferred cancers are listed above.

[0445] The terms “disorder,” “disease,” or “condition” used interchangeably herein refer to any condition that benefits from treatment with a composition described herein (e.g., a pharmaceutical composition) (e.g., a composition comprising a fusion protein of the present invention (e.g., a pharmaceutical composition)). This includes both chronic and acute disorders or diseases, including pathological conditions that predispose the mammal to the associated disorder.

[0446] The terms “pharmaceutical composition” or “pharmaceutical formulation” refer to a formulation in a form that makes the bioactivity of the active ingredient contained therein effective and that does not contain any additional components that would have unacceptable toxicity to a subject who would be administered the pharmaceutical composition.

[0447] The term "pharmaceuticalally acceptable" as used in conjunction with the compositions of this invention means that the molecular entity and other components of such compositions are physiologically tolerable and generally do not produce adverse effects when administered to mammals (e.g., humans). The term "pharmaceuticalally acceptable" may also refer to substances approved by federal or state regulatory agencies, or listed in the United States Pharmacopeia or other recognized pharmacopoeias for mammals (particularly humans). "Pharmaceuticalally acceptable carrier" refers to a component of a pharmaceutical composition or formulation that is non-toxic to the subject, other than the active ingredient. Pharmaceutically acceptable carriers include, but are not limited to, buffers, excipients, stabilizers, or preservatives. Such pharmaceutically acceptable carriers may be sterile liquids, such as water, saline solutions, aqueous glucose solutions, aqueous glycerol solutions, and oils (including oils of petroleum, animal, plant, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, etc.). Suitable pharmaceutical carriers are described in AR Gennaro's Remington's Pharmaceutical Sciences, 20th edition.

[0448] As used herein, “treatment” (and its grammatical variations such as “treat” or “treating”) refers to a clinical intervention aimed at altering the natural course of a disease in an individual being treated, which may be implemented during the preventative phase or clinicopathological process. The desired effects of treatment include, but are not limited to: preventing the onset or recurrence of disease, relieving symptoms, reducing any direct or indirect pathological consequences of the disease, slowing the rate of disease progression, improving or mitigating the disease state, and achieving remission or improved prognosis. “Remission” or its equivalents refer to both therapeutic and preventative measures aimed at improving, preventing, slowing (reducing), reducing, or inhibiting a disease or condition, such as the formation of atherosclerotic plaques. Individuals requiring treatment include those who already have the disease or condition, those susceptible to the disease or condition, or those who need to prevent the disease or condition.

[0449] As used herein, the term "cancer" refers to any malignant tumor of the tissue and cell types described above. Examples of cancer may include cancers caused by abnormal adherent cells or cancers caused by abnormal blood cells (e.g., leukemia, lymphoma, multiple myeloma). In one embodiment, the cancer is a solid tumor. In another embodiment, the cancer is selected from the group consisting of: leukemia, particularly acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL), and chronic leukemia including chronic myeloid leukemia; lymphoma, particularly non-Hodgkin's lymphoma and Hodgkin's lymphoma; head and neck cancer; esophageal cancer; adenoid cystic carcinoma; osteosarcoma; ovarian cancer; Ewing's sarcoma; lung cancer; neuroblastoma; gastrointestinal cancer; endometrial cancer; cervical cancer; medulloblastoma; prostate cancer; esophageal cancer; breast cancer; thyroid cancer; meningioma; liver cancer; colorectal cancer; pancreatic cancer; chondrosarcoma; osteosarcoma; and kidney cancer.

[0450] As described above, cancers treated according to the present invention and by the means and methods provided herein can be cancers associated with cell cycle regulators, such as cyclin-dependent kinases or transcriptional kinases, such as CDK12, CDK13, and / or cyclins, such as CCNK. As used herein, "cancers associated with CDK12, CDK13, and / or CCNK" also includes cancers associated with complexes of CDK12 / 13 and CCNK. With appropriate modifications, this also applies to other disorders discussed herein, such as neurological disorders / diseases, metabolic disorders / diseases, and / or infectious diseases. In the context of the present invention, these diseases may also be associated with cell cycle regulators, such as cyclin-dependent kinases or transcriptional kinases, such as CDK12, CDK13, and / or cyclins, such as CCNK.

[0451] There are existing descriptions suggesting that CCNK degradation induces genomic instability in cancers such as prostate cancer (see Wu et al. 2018, Cell, June 14, 2018; 173(7):1770-1782.e14. doi: 10.1016 / j.cell.2018.04.034), and is considered effective against cancers associated with mutations in DNA damage-response genes, such as those described in Table 1 of Nature Review Cancer by Lord et al. 2016 (February 2016; 16(2):110-20. doi: 10.1038 / nrc.2015.21. Epub January 18, 2016).

[0452] Furthermore, descriptions have shown that CCNK degradation is particularly effective in cancers associated with elevated cyclin E1 levels. Therefore, as described in this article, cancers associated with cell cycle regulators such as CDK12, CDK13, and / or CCNK include, but are not limited to, cancers with cyclin E1 overexpression, such as breast cancer, ovarian cancer, melanoma, bladder cancer, gastric cancer, gastric adenocarcinoma, squamous cell carcinoma of the lung, adenocarcinoma of the lung, glioblastoma multiforme, and colorectal cancer; see Lei et al., Nature Communications, May 14, 2018; 9(1):1876.

[0453] In cancer-related terms such as "cancer cell" and "cancer gene (oncogene)," "cancer" can also have the same meaning. Cancer cells can originate from any mammal species. Such mammal species can include, for example, humans, monkeys, cattle, pigs, mice, rats, guinea pigs, hamsters, and rabbits. For clinical application, the mammal species is preferably human. Therefore, cancer cells can be cancer cells isolated from or derived from patients with cancer. Cancer cells can be uninfected cells or virus-infected cells. Examples of oncopathic viruses capable of infecting cells include Epstein-Barr virus, hepatitis viruses, human papillomavirus, human T-cell leukemia virus, and Kaposi's sarcoma-associated herpesvirus. Cancer cells can also be cancer cells derived from embryonic stem cells, adult stem cells, or artificial stem cells (e.g., iPS cells) generated from normal cells. The cancer cells derived from the artificial cells of this invention can express intrinsic oncogenes. The term "intrinsic oncogene" as used herein refers to an oncogene responsible for the proliferation of cancer cells, which is expressed by cancer cells that can be used as material for establishing the artificial cells of this invention. For example, CDK12, CDK13 and / or CCNK may play a role in cancer proliferation, including but not limited to breast cancer, ovarian cancer, melanoma, bladder cancer, gastric cancer, gastric adenocarcinoma, squamous cell carcinoma of the lung, adenocarcinoma of the lung, glioblastoma multiforme and colorectal cancer.

[0454] On one hand, the present invention also relates to a method of treating cancer, comprising administering a chemical compound or agent to a patient suffering from cancer. For example, the compound may be a compound that binds to one or more proteins to be degraded, wherein said one or more proteins are cancer-related proteins, and may be a kinase, such as a kinase selected from the group consisting of cyclin-dependent kinases and / or transcriptional kinases (such as CDK12, CDK13) and / or cyclins (such as CCNK). In this context, the present invention may relate to a method of treating cancer comprising administering a chemical compound or agent to a patient suffering from cancer, wherein the compound may be a compound that binds to one or more proteins selected from the group consisting of CDK12, CDK13, and / or CCNK. For example, the chemical compound or agent is used to treat cancer, wherein the cancer may be selected from lymphoma (especially non-Hodgkin lymphoma and Hodgkin lymphoma), liver cancer, breast cancer, neuroblastoma, cervical cancer, Ewing's sarcoma, lung cancer, ovarian cancer, melanoma, bladder cancer, head and neck cancer, prostate cancer, pancreatic cancer, esophageal cancer, gastric cancer, gastric adenocarcinoma, squamous cell carcinoma of the lung, adenocarcinoma of the lung, glioblastoma multiforme, and colorectal cancer.

[0455] "Solid tumor cancer" or "solid carcinoma" refers to an abnormal mass of tissue that typically does not contain cysts or fluid-filled areas. Solid tumors can be benign (non-cancerous) or malignant (cancerous). Therefore, the term "solid tumor cancer" refers to a malignant solid tumor. Different types of solid tumors are named according to the type of cells that form them. Examples of solid tumor cancers include sarcomas, carcinomas, and lymphomas. Leukemia (blood cancer) typically does not form solid tumors.

[0456] "Patient," "individual," or "subject" refers to a mammal. Mammals include, but are not limited to, domesticated animals (such as cattle, sheep, cats, dogs, and horses), primates (such as humans and non-human primates such as monkeys), rabbits, and rodents (such as mice and rats). In some respects, the patient, individual, or subject is a human. In one implementation, the patient may be a "cancer patient," that is, a patient who is suffering from or at risk of suffering from one or more symptoms of cancer.

[0457] It should be understood that the specific dose level for any particular patient will depend on a variety of factors, including the activity of the particular compound used, age, weight, general health status, sex, diet, timing of administration, route of administration, excretion rate, drug combination, and the pathogenesis and severity of the particular disease being treated.

[0458] The terms “optional,” “optionally,” and “may” as used herein indicate that the referred feature may or may not be present. Whenever the terms “optional,” “optionally,” or “may” are used, the invention specifically relates to two possibilities: the corresponding feature is present, or the corresponding feature is not present. For example, the statement “X is optionally substituted by Y” (or “X may be substituted by Y”) means that X is substituted by Y or not substituted. Similarly, if a component of a composition is specified as “optional,” the invention specifically relates to two possibilities: the corresponding component is present (included in the composition) or the corresponding component is not present in the composition. It should be understood that when a list of groups is preceded by the statement “optionally substituted,” the statement “optionally substituted” applies to each of the individual groups in the list, and not just the first item in the list.

[0459] As used in this article, the term "halogen" refers to a fluorine group (-F), a chlorine group (-Cl), a bromine group (-Br), or an iodine group (-I).

[0460] As used herein, the term "alkyl" refers to a monovalent, saturated, acyclic (i.e., non-cyclic) hydrocarbon group, which may be straight-chain or branched. Therefore, "alkyl" does not contain any carbon-carbon double or triple bonds. The term "alkyl" preferably refers to a C16-C16 group. 1-6 Alkyl group. "C" 1-6 "alkyl" refers to an alkyl group having 1 to 6 carbon atoms. Preferred exemplary alkyl groups are methyl, ethyl, propyl (e.g., n-propyl or isopropyl), or butyl (e.g., n-butyl, isobutyl, sec-butyl, or tert-butyl). Unless otherwise defined, the term "alkyl" more preferably refers to C14. 1-4 Alkyl, more preferably methyl or ethyl, and even more preferably methyl. The term “alkoxy” as used herein refers to “-O-alkyl”, where “alkyl” is as defined above.

[0461] As used herein, the term "alkoxyalkyl" refers to an alkoxy group, as defined herein, typically having 1 to 4 carbon atoms, preferably 1 to 2 carbon atoms, more preferably 1 carbon atom, which is bonded to the remainder of the molecule by an alkyl group, as defined herein, typically having 1 to 4 carbon atoms, preferably 1 to 2 carbon atoms, more preferably 1 carbon atom. Therefore, it refers to an alkyl group bonded to another alkyl group via an oxygen atom, which is subsequently bonded to the remainder of the molecule, i.e., "-alkyl-O-alkyl". Examples of alkoxyalkyl groups are methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, etc.

[0462] As used herein, the term "dimethylaminoalkyl" refers to a dimethylamino group (N(CH3)2) that is bonded to the remainder of the molecule by an alkyl group as defined herein (typically having 1 to 4 carbon atoms, preferably 1 to 2 carbon atoms, more preferably 1 carbon atom), i.e., "–alkyl–N(CH3)2".

[0463] As used herein, the term "haloalkyl" refers to an alkyl group substituted with one or more (preferably 1 to 6, more preferably 1 to 3) halogen atoms, said halogen atoms being independently selected from fluorine, chlorine, bromine, and iodine, and preferably all fluorine atoms. It should be understood that the maximum number of halogen atoms is limited by the number of available linking sites, and therefore depends on the number of carbon atoms contained in the alkyl portion of the haloalkyl group. "Haloalkyl" may, for example, refer to -CF3, -CHF2, -CH2F, -CF2-CH3, -CH2-CF3, -CH2-CHF2, -CH2-CF2-CH3, -CH2-CF2-CF3, or -CH(CF3)2. As used herein, the term "haloalkoxy" refers to "–O–haloalkyl", wherein "haloalkyl" is as defined above.

[0464] As used in this article, "heteroalkyl" refers to an alkyl group in which one or two –CH2– groups are independently selected from –O–, –S–, and –N(C 1-6 Alkyl) group substitution. Preferred examples are alkoxy groups, such as methoxy groups. As used herein, the term "alkenyl" refers to a monovalent unsaturated acyclic hydrocarbon group, which may be straight-chain or branched and contains one or more (e.g., one or two) carbon-carbon double bonds, but does not contain any carbon-carbon triple bonds. The term "C" 2-6 "Alkenyl" refers to an alkenyl group having 2 to 6 carbon atoms. Preferred exemplary alkenyl groups are vinyl, propenyl (e.g., propyl-1-en-1-yl, propyl-1-en-2-yl, or propyl-2-en-1-yl), butenyl, butadienyl (e.g., but-1,3-dien-1-yl or but-1,3-dien-2-yl), pentenyl, or pentadienyl (e.g., isoprene). Unless otherwise defined, the term "alkenyl" preferably refers to C 2-6 alkenyl, more preferably C 2-4 Alkenyl group.

[0465] As used herein, the term "alkynyl" refers to a monovalent unsaturated acyclic hydrocarbon group, which may be straight-chain or branched, containing one or more (e.g., one or two) carbon-carbon triple bonds, and optionally one or more carbon-carbon double bonds. The term "C..." 2-6 "Alynyl" refers to an alkynyl group having 2 to 6 carbon atoms. Preferred exemplary alkynyl groups are ethynyl, propynyl, or butynyl. Unless otherwise defined, the term "alkynyl" preferably refers to C... 2-6 Alkyne group, more preferably C 2-4 Alkyne group.

[0466] As used herein, the term "aryl" refers to a monocyclic aromatic hydrocarbon ring group. Unless otherwise defined, "aryl" preferably has 6 to 14 ring atoms, more preferably 6 to 10 ring atoms, and most preferably refers to phenyl.

[0467] As used herein, the term "bicyclic aryl" refers to an aromatic hydrocarbon cyclic group containing two bridging or fused ring systems, wherein the two bridging or fused ring systems contain at least one aromatic ring (e.g., a ring system consisting of two fused rings, wherein at least one of these fused rings is an aromatic ring; or a bridging ring system consisting of two rings, wherein at least one bridging ring is an aromatic ring). "Bicyclic aryl" may, for example, refer to a naphthyl group. Unless otherwise defined, a "bicyclic aryl" group preferably has 10 ring atoms.

[0468] As used herein, the term “heteroaryl” refers to a monocyclic aromatic ring group comprising one or more (e.g., one, two, three or four) cyclic heteroatoms independently selected from O, S and N, with the remaining ring atoms being carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form oxo groups). "Heteroaryl" may refer, for example, to thienyl (i.e., thienyl), furanyl (i.e., furanyl), benzofuranyl, isobenzofuranyl, chromenyl, xanthonyl, phenoxathiinyl, pyrroleyl (e.g., 2H-pyrroleyl), imidazolyl, pyrazolyl, pyridinyl (i.e., pyridinyl; e.g., 2-pyridinyl, 3-pyridinyl or 4-pyridinyl), pyrazinyl, pyrimidinyl, pyridazinyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, furazolyl, 1H-tetrazoleyl or 2H-tetrazoleyl. Unless otherwise defined, "heteroaryl" preferably refers to a 5- to 8-membered ring; even more preferably a 5- or 6-membered monocycle containing one or more (e.g., one, two or three) cyclic heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbocyclic atoms are optionally oxidized.

[0469] As used herein, the term "bicyclic heteroaryl" refers to an aromatic ring group comprising two rings (preferably fused rings), one or both of which are aromatic rings. "Bicyclic heteroaryl" may, for example, refer to benzo[b]thiopheneyl, benzofuranyl, isobenzofuranyl, chromenyl, indoleazinyl, isoindoleyl, indoleyl (e.g., 3H-indoleyl), indazoleyl, purinyl, isoquinolinyl, quinolinyl, phthalazinyl, naphthidyl, quinoxolinyl, cenolinyl, 1,2-benzisoxazol-3-yl, benzothiazolyl, benzoxazolyl, benzoisoxazolyl, benzimidazolyl, coumarinyl, or chromoneyl. Unless otherwise defined, a "bicyclic heteroaryl" preferably has 8 to 12 ring atoms, more preferably 9 or 10 ring atoms.

[0470] It should be understood that expressions such as "five- or six-membered heterocyclic group" indicate a heterocyclic group having five or six atoms in the ring. Similarly, expressions such as "five- to ten-membered heteroaryl" indicate a heteroaryl group having five to ten atoms in one or two rings. Therefore, in the context of cyclic groups, "x-membered" indicates the number x of ring atoms in one or more rings, but does not imply any limitation on the number of non-cyclic atoms (such as hydrogen atoms, which are usually present as substituents on the ring).

[0471] As used herein, the term "cycloalkyl" generally refers to a monocyclic alicyclic group having 3 to 10 or 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, and cyclodecyl, or cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Cyclopropyl and cyclobutyl are preferred.

[0472] Unless otherwise stated, the terms "carbocyclic," "carbocyclyl," or "carbocycle" generally comprise 3 to 10-membered monocyclic rings, preferably 4 to 8, 3 to 6, or 5 to 7-membered monocyclic rings, more preferably 3, 4, 5, or 6-membered monocyclic rings containing 3 to 10, preferably 4 to 8, 3 to 6, or 5 to 7, more preferably 3, 4, 5, or 6 carbon atoms. Unless otherwise stated, carbocycles can be saturated, partially or fully unsaturated, or aromatic, where saturation means the presence of only single bonds, partial or fully unsaturated means the presence of one or more double bonds in appropriate positions, but not satisfying the Hückel rule for aromaticity, and aromatic means satisfying the Hückel (4n + 2) rule. The term "carbocycles" also encompasses "aryl." The term "aryl" or "aromatic carbocyclic" refers to an aromatic carbocyclic ring with a carbon atom as a ring member, preferably a six-membered aromatic carbocyclic ring with a carbon atom as a ring member. A preferred example is phenyl. Therefore, unless otherwise stated, the term "carbocyclic" or "carbocyclic group" may particularly cover cycloalkyl, cycloalkenyl, and phenyl. Preferably, the term "carbocyclic" or "carbocyclic group" covers phenyl and cycloalkyl, such as phenyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0473] The term "carbobicyclic" or "carbobicyclyl" generally refers to a bicyclic ring consisting of 5 to 14, preferably 7 to 12, or 6 to 10, more preferably 7 or 10 carbon atoms. The bicyclic ring can be saturated, partially or fully unsaturated, or aromatic, where saturation means the presence of only single bonds, partial or fully unsaturated means the presence of one or more double bonds in appropriate positions but not satisfying the Hückel rule for aromaticity, and aromatic means satisfying the Hückel (4n + 2) rule. Preferably, with respect to a bicyclic ring, the term "aromatic" means that both rings of the bicyclic portion are aromatic; thus, for example, a 10-membered aromatic bicyclic ring has 8 π electrons. Therefore, unless otherwise stated, the term "carbobicylce" or "carbobicyclyl" may specifically cover bicyclic alkyl groups, bicyclic alkenyl groups, and bicyclic aromatic groups, such as bicyclohexane (decahydronaphthalene), bicycloheptane (e.g., norbornane), bicyclooctane (e.g., bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, or bicyclo[4.2.0]octane), bicyclononane (e.g., bicyclo[3.3.1]nonane or bicyclo[4.3.0]nonane), bicyclodecane (e.g., bicyclo[4.4.0]decane), bicycloundecane (e.g., bicyclo[3.3.3]undecane), norbornene, naphthalene, etc. The carbobicyl group may be a bridged carbobicyl group, a fused carbobicyl group, or a spirocarbobicyl group. Preferably, the carbobicyl group is a spirocarbobicyl group.

[0474] As used herein, the term "carbocycloalkyl" refers to a carbocyclic group as defined herein, which is bonded to the remainder of the molecule via an alkyl group typically having one to two carbon atoms, preferably one carbon atom. Preferably, the term "carbocycloalkyl" refers to a phenylalkyl or cycloalkylalkyl group, which refers to the corresponding group bonded to the remainder of the molecule via an alkyl group. Preferred examples of carbocycloalkyl groups include benzyl (i.e., benzyl), phenethyl, cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, and cyclohexylethyl.

[0475] As used herein, the term “carbon bicycloalkyl” refers to a carbon bicycloalkyl group as defined herein, which is connected to the remainder of the molecule by an alkyl group that typically has one to two carbon atoms (preferably one carbon atom).

[0476] Unless otherwise stated, the term "spirocarbobicyclic group" or "spirocarbobicycle" as used herein generally refers to a 7- to 10, preferably 7- to 9, more preferably 7 or 8-membered bicyclic ring comprising 7 to 10, preferably 7- to 9-membered, more preferably 7 or 8 carbon atoms, wherein the two rings are connected by a single shared carbon atom. The spirocarbobicycle may be saturated or partially unsaturated, wherein saturation means the presence of only single bonds, and partial unsaturation means the presence of one or more double bonds in appropriate positions, without satisfying Hückel's rule for aromaticity. Preferably, the spirocarbobicycle is saturated.

[0477] Unless otherwise stated, the term "heterocycle" or "heterocyclic group" generally includes 3 to 10-membered rings, preferably 4 to 8-membered or 5 to 7-membered rings, more preferably 5- or 6-membered rings, and particularly 6-membered monocyclic rings. Unless otherwise stated, heterocycles can be saturated, partially or completely unsaturated, or aromatic, wherein saturation means the presence of only single bonds, partial or complete unsaturation means the presence of one or more double bonds in appropriate positions but not satisfying the Hückel rule for aromaticity, and aromaticity means satisfying the Hückel (4n + 2) rule. Heterocycles typically contain one or more, for example 1, 2, 3, or 4, preferably 1, 2, or 3, more preferably 1 or 2, and even more preferably 1 heteroatom selected from N, O, and S as ring members, wherein the S atom as a ring member can be in the form of S, SO, or SO2. The remaining ring members are carbon atoms. In a preferred embodiment, the heterocycle is a saturated heterocycle, preferably a 4- to 6-membered saturated heterocycle comprising one or more (e.g., 1, 2, or 3, preferably 1 or 2, more preferably 1) heteroatoms selected from N, O, and S as ring members, wherein the S atom as a ring member may be present in the form of S, SO, or SO2. Examples of aromatic heterocycles are provided below in conjunction with the definition of "hetaryl". "Hetaryls" or "heteroaryls" are included in the term "heterocycle". Saturated or partially or fully unsaturated heterocycles typically comprise 1, 2, 3, 4, or 5, preferably 1, 2, or 3, heteroatoms selected from N, O, and S as ring members, wherein the S atom as a ring member may be present in the form of S, SO, or SO2. Those skilled in the art will understand that S, SO, or SO2 are as follows:

[0478] Furthermore, it is possible for those skilled in the art to know the resonance structure of the oxidized form. Unless otherwise stated, saturated heterocycles typically comprise 3 to 10, preferably 4 to 8, or 5 to 7, more preferably 4 to 6 monocycles containing 3 to 10, preferably 4 to 8, or 5 to 7, more preferably 5 or 6 atoms, including at least one heteroatom, such as oxobutane, azabutane, pyrrolidine, tetrahydrothiophene, tetrahydrofuran, piperidine, tetrahydropyran, dioxane, morpholine, or piperazine.

[0479] Unless otherwise stated, the term "heterobicyclic" or "heterobicyclic group" generally includes bicyclic rings with 6 to 14 members, preferably 7 to 12 members, or 8 to 10 members, more preferably 8 or 9 members. Heterobicyclic rings can be saturated, partially or completely unsaturated, or aromatic, where saturation means the presence of only single bonds, partial or complete unsaturation means the presence of one or more double bonds in appropriate positions but not satisfying the Hückel rule for aromaticity, and aromaticity means satisfying the Hückel (4n + 2) rule. For "aromatic," it is sufficient that one of the two rings in the bicyclic portion is aromatic and the other is non-aromatic. Heterobicyclic rings typically contain one or more (e.g., 1, 2, 3, or 4, preferably 1, 2, or 3) heteroatoms selected from N, O, and S as ring members, wherein the S atom as a ring member can be in the form of S, SO, or SO2. The remaining ring members are carbon atoms. Examples of heterobicyclic compounds include benzofuranyl, benzothiophenyl, indolyl, indazole, benzimidazolyl, benzooxazolyl, benzooxazadiazolyl, benzothiadiazolyl, benzooxazazinyl, quinolinyl, isoquinolinyl, purine, 1,8-naphthodinyl, pteridinyl, pyrido[3,2-d]pyrimidinyl, pyridinimidazolyl, triethylenediamine, or quinine ring, etc. The heterobicyclic compound can be a fused heterobicyclic group, a spiroheterobicyclic group, or a bridged heterobicyclic group, preferably a spiroheterobicyclic group.

[0480] The terms “hetaryl” or “heteroaryl” or “aromatic heterocycle” or “aromatic heterocyclic ring” include monocyclic 5- or 6-membered aromatic heterocycles whose ring members contain 1, 2, 3 or 4 heteroatoms selected from N, O and S, wherein the S atom as a ring member may be in the form of S, SO or SO2. Examples of 5- or 6-membered aromatic heterocycles include pyridyl (also known as pyridinyl), i.e., 2-, 3-, or 4-pyridyl; pyrimidinyl, i.e., 2-, 4-, or 5-pyrimidinyl; pyrazinyl; pyridazinyl, i.e., 3-, or 4-pyridazinyl; thiopheneyl, i.e., 2-, or 3-thiopheneyl; furanyl, i.e., 2-, or 3-furanyl; pyrroleyl, i.e., 2-, or 3-pyrroleyl; oxazolyl, i.e., 2-, 3-, or 5-oxazolyl; isoxazolyl, i.e., 3-, 4-, or 5-isooxazolyl; thiazolyl, i.e., 2-, 3-, or 5-thiazolyl; isothiazolyl, i.e., 3-, 4-, or 5-isothiazolyl; pyrazolyl, i.e., 1-, 3-, 4-, or 5-pyrazolyl; i.e., 1 -, 2-, 4- or 5-imidazolyl; oxadiazole, such as 2- or 5-[1,3,4]oxadiazole, 4- or 5-(1,2,3-oxadiazole)yl, 3- or 5-(1,2,4-oxadiazole)yl, 2- or 5-(1,3,4-thiadiazole)yl; thiadiazole, such as 2- or 5-(1,3,4-thiadiazole)yl, 4- or 5-(1,2,3-thiadiazole)yl, 3- or 5-(1,2,4-thiadiazole)yl; triazole, such as 1H-, 2H- or 3H-1,2,3-triazol-4-yl, 2H-triazol-3-yl, 1H-, 2H- or 4H-1,2,4-triazolyl; and tetrazolyl, i.e. 1H- or 2H-tetrazolyl. Unless otherwise stated, the term "hetaryl" also includes "aromatic heterobicyclic compounds" as defined above.

[0481] As used herein, the term "heterocyclic alkyl" refers to a heterocyclic group as defined herein, which is bonded to the remainder of the molecule by an alkyl group typically having one to two carbon atoms, preferably one carbon atom. Examples of heterocyclic alkyl groups include pyridinylmethyl, pyrimidinylmethyl, pyrazolylmethyl, and piperidinylmethyl.

[0482] As used herein, the term "heterocyclic alkyl" refers to a heterocyclic group as defined herein, which is bonded to the remainder of the molecule by an alkyl group typically having one to two carbon atoms, preferably one carbon atom. Examples of heterocyclic alkyl groups include pyridinylmethyl, pyrimidinylmethyl, pyrazolylmethyl, and piperidinylmethyl.

[0483] Unless otherwise stated, the term "spiroheterocyclic group" or "spiroheterocyclic" as used herein generally refers to a 7- to 10-membered, preferably 7- to 9-membered, more preferably 7- or 8-membered bicyclic group, wherein the cyclic group comprises one or more (e.g., 1, 2, 3, or 4, preferably 1, 2, or 3, more preferably 1 or 2, even more preferably 1) cyclic heteroatoms independently selected from O, S, and N, with the remaining cyclic atoms being carbon atoms, wherein one or more S-ring atoms (if present) and / or one or more N-ring atoms (if present) are optionally oxidized. The spiroheterocyclic ring may be saturated or partially unsaturated, wherein saturation means the presence of only single bonds, and partial unsaturation means the presence of one or more double bonds in appropriate positions without satisfying Hückel's rule for aromaticity. Preferably, the spiroheterocyclic ring is saturated.

[0484] The terms used herein, such as “binding to at least one member of the E3 ligase complex,” do not necessarily mean that the binding must occur directly with a portion of the E3 ligase. Rather, the compound may bind to a protein that is part of the E3 ligase complex, or to a protein that interacts with the E3 ligase complex (optionally as part of a protein complex, before or after the compound binds to the protein).

[0485] Those skilled in the art will understand that the substituents contained in the compounds of the present invention (especially compounds of formula (I)) can be linked to the remainder of their respective compounds at multiple different positions for each specific substituent. Unless otherwise defined, the preferred positions for each specific substituent are as shown in the examples.

[0486] Unless otherwise expressly stated or contradicted in the context, the terms “a,” “an,” and “the” used herein are used interchangeably with “one or more” and “at least one.” Thus, for example, a composition comprising “one” of the compounds of the present invention (particularly compounds of formula (I)) may be interpreted as a composition comprising “one or more” of the compounds of the present invention.

[0487] Unless otherwise explicitly stated or contradicted by context, the term “comprising” (or “comprise”, “comprises”), “contain”, “contains”, “containing”) as used herein has the meaning of “particularly comprising”, that is, “containing in addition to other optional elements…”. In addition, the term also includes the narrower meanings of “consistently composed of” and “composed of”. For example, the term “A comprises B and C” means “A particularly comprises B and C”, where A may contain other optional elements (e.g., “A comprises B, C, and D” also falls into this category), but the term also includes the meanings of “A is essentially composed of B and C” and “A is composed of B and C” (i.e., A contains no other components besides B and C).

[0488] Furthermore, unless otherwise stated, any reference to industry standards, pharmacopoeias, or manufacturers' manuals refers to the latest version available on the priority date (i.e., the earliest application date) of this instruction manual.

[0489] The scope of this invention covers all pharmaceutically acceptable salt forms of the compounds provided herein (especially the compounds of formula (I)), which can be formed, for example, by protonation of an atom carrying a lone pair of electrons that is readily protonated (e.g., an amino group) with an inorganic or organic acid, or by forming a salt of an acid group (e.g., a carboxylic acid group) with a physiologically acceptable cation. Exemplary base addition salts include, for example: alkali metal salts, such as sodium or potassium salts; alkaline earth metal salts, such as calcium or magnesium salts; zinc salts; ammonium salts; aliphatic amine salts, such as trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, procaine, meglumine, ethylenediamine, or choline salts; aralkylamine salts, such as N,N-dibenzylethylenediamine, benzylamine, or phenethylamine; heterocyclic aromatic amine salts, such as pyridine, methylpyridine, quinoline, or isoquinoline; quaternary ammonium salts, such as tetramethylammonium, tetraethylammonium, benzyltrimethylammonium, benzyltriethylammonium, benzyltributylammonium, methyltrioctylammonium, or tetrabutylammonium; and basic amino acid salts, such as arginine, lysine, or histidine. Exemplary acid addition salts include, for example: inorganic acid salts, such as hydrochlorides, hydrobroms, hydroiodates, sulfates (e.g., sulfates or hydrogen sulfates), nitrates, phosphates (e.g., phosphates, hydrogen phosphates, or dihydrogen phosphates), carbonates, bicarbonates, perchlorates, borates, or thiocyanates; and organic acid salts, such as acetates, propions, buties, valerates, hexanoates, heptates, octanoates, cyclopentylpropionates, decanoates, undecanoates, oleates, stearates, lactates, maleates, oxalates, fumarates, tartrates, malates, and citrates. Succinate, adipate, gluconate, glycolate, nicotinate, benzoate, salicylate, ascorbate, pamoate (emborate), camphorate, gluconate or neopentanoate; sulfonates, such as methanesulfonate, ethanesulfonate, 2-hydroxyethanesulfonate, benzenesulfonate, p-toluenesulfonate, 2-naphthalenesulfonate, 3-benzenesulfonate or camphorsulfonate; glycerophosphates; and acidic amino acid salts, such as aspartate or glutamate.

[0490] Furthermore, the scope of this invention covers the compounds provided herein, particularly the compounds of this invention (especially compounds of formula (I)) as hydrates. The term "hydrate," when referring to a compound of formula (I), means a compound of formula (I) containing water or its constituent elements (i.e., H and OH). Preferably, the hydrate of a compound of formula (I) is a compound of formula (I) in which water molecules are incorporated into its crystal structure without altering its chemical structure. It should be understood that the hydrates of the compounds provided herein (especially the compounds of this invention) also include hydrates of pharmaceutically acceptable salts of the corresponding compounds.

[0491] Furthermore, the compounds provided herein (particularly those of formula (I)) can exist in various isomers, particularly stereoisomers (e.g., including geometric isomers (or cis / trans isomers), enantiomers, and diastereomers) or tautomers. All such isomers of the compounds provided herein, whether in mixture form or in pure or substantially pure form, are considered part of this invention. Regarding stereoisomers, this invention covers the isolated optical isomers of the compounds according to the invention and any mixtures thereof (particularly including racemic mixtures / racemates). Racemates can be resolved by physical methods, such as fractional crystallization, separation or crystallization of diastereomer derivatives, or separation by chiral column chromatography. Single optical isomers can also be obtained by forming a salt of the racemate with an optically active acid, followed by crystallization. This invention also covers any tautomers of the compounds provided herein.

[0492] The scope of this invention also covers compounds provided herein, particularly compounds of formula (I), wherein one or more atoms are replaced by specific isotopes of the corresponding atoms. For example, this invention covers compounds of formula (I), wherein one or more hydrogen atoms (or, for example, all hydrogen atoms) are replaced by deuterium atoms (i.e., 2 H; also known as "D") substitution. Therefore, the present invention also covers deuterium-rich compounds of formula (I). Naturally occurring hydrogen is an isotopic mixture containing about 99.98 mol-% hydrogen 1 ( 1 H) and approximately 0.0156 mol% deuterium ( 2 The deuterium content at one or more hydrogen positions in a compound of formula (I) can be increased using deuteration techniques known in the art. For example, a compound of formula (I) or a reactant or precursor used to synthesize a compound of formula (I) can be subjected to an H / D exchange reaction using, for example, heavy water (D₂O). Other suitable deuteration techniques are described in: Atzrodt J et al. Bioorg Med Chem , 20(18), 5658-5667, 2012; William JS et al., Journal of Labeled Compounds and Radiopharmaceuticals , 53(11-12), 635-644, 2010; or Modvig A et al., J Org Chem ,79, 5861-5868, 2014. The content of deuterium can be determined by mass spectrometry or nuclear magnetic resonance spectroscopy. Unless otherwise expressly stated, the preferred compound (I) is not enriched for deuterium. Therefore, unless otherwise stated, the preferred compound (I) contains naturally occurring hydrogen atoms or 1 H hydrogen atom.

[0493] This invention also covers the compounds provided herein, particularly compounds of formula (I), wherein one or more atoms are replaced by positron-emitting isotopes of the corresponding atoms, for example...18 F, 11 C 13 N、 15 O、 76 Br、 77 Br、 120 I and / or 124 I. Such compounds can be used as tracers or imaging probes in positron emission tomography (PET). Therefore, the present invention includes: (i) compounds of formula (I) wherein one or more fluorine atoms (e.g., all fluorine atoms) are... 18 (ii) Compounds of formula (I) in which one or more carbon atoms (e.g., all carbon atoms) are replaced by F atoms. 11 C atoms are substituted; (iii) compounds of formula (I) wherein one or more nitrogen atoms (e.g., all nitrogen atoms) are substituted. 13 (iv) Compound of formula (I) wherein one or more oxygen atoms (e.g., all oxygen atoms) are substituted with N atoms. 15 O atom substitution; (v) Compound of formula (I), wherein one or more bromine atoms (e.g., all bromine atoms) are substituted. 76 Br atom substitution; (vi) compounds of formula (I) wherein one or more bromine atoms (e.g., all bromine atoms) are substituted. 77 Br atom substitution; (vii) compounds of formula (I) wherein one or more iodine atoms (e.g., all iodine atoms) are substituted. 120 I atom substitution; and (viii) compounds of formula (I) wherein one or more iodine atoms (e.g., all iodine atoms) are substituted. 124 I atom substitution. Generally, it is preferred that none of the atoms in the compound of formula (I) are substituted with a specific isotope.

[0494] The compounds provided herein, particularly those of formula (I), may be administered as compounds on their own or formulated as pharmaceuticals. Pharmaceutical / pharmaceutical compositions may optionally comprise one or more pharmaceutically acceptable excipients, such as carriers, diluents, fillers, disintegrants, lubricants, binders, colorants, pigments, stabilizers, preservatives, antioxidants, and / or solubilizers.

[0495] The pharmaceutical composition may contain one or more solubilizers, such as polyethylene glycol (including polyethylene glycols with molecular weights in the range of about 200 to about 5,000 Da, such as PEG 200, PEG 300, PEG 400 or PEG 600), ethylene glycol, propylene glycol, glycerin, nonionic surfactants, tyloxapol, polysorbate 80, polyethylene glycol-15-hydroxystearate (e.g., Kolliphor), etc. ®HS 15, CAS No. 70142-34-6), phospholipids, lecithin, myristoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearyl phosphatidylcholine, cyclodextrin, α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, hydroxyethyl-β-cyclodextrin, hydroxypropyl-β-cyclodextrin, hydroxyethyl-γ-cyclodextrin, hydroxypropyl-γ-cyclodextrin, dihydroxypropyl-β-cyclodextrin, sulfobutyl ether-β-cyclodextrin, sulfobutyl ether-γ-cyclodextrin, glucosyl-α-cyclodextrin, glucosyl- β-Cyclodextrin, disaccharismatic-β-cyclodextrin, maltosyl-α-cyclodextrin, maltosyl-β-cyclodextrin, maltosyl-γ-cyclodextrin, maltotriosesyl-β-cyclodextrin, maltotriosesyl-γ-cyclodextrin, disaccharismatic-β-cyclodextrin, methyl-β-cyclodextrin, carboxyalkyl sulfides, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, vinyl acetate copolymer, vinylpyrrolidone, sodium dodecyl sulfate, sodium dioctyl sulfosuccinate, or any combination thereof.

[0496] Pharmaceutical compositions can be formulated using techniques known to those skilled in the art, such as those disclosed in Remington: The Science and Practice of Pharmacy (Pharmaceutical Press, 22nd edition). Pharmaceutical compositions can be formulated into dosage forms for oral or parenteral administration, such as intramuscular, intravenous, subcutaneous, intradermal, intraarterial, intracardiac, rectal, nasal, topical, aerosol, or vaginal administration. Oral dosage forms include coated and uncoated tablets, soft gelatin capsules, hard gelatin capsules, lozenges, tablets, solutions, emulsions, suspensions, syrups, elixirs, powders and granules for reconstitution, dispersible powders and granules, pharmaceutical gum, chewable tablets, and effervescent tablets. Parenteral dosage forms include solutions, emulsions, suspensions, dispersibles, and powders and granules for reconstitution. Emulsions are a preferred dosage form for parenteral administration. Rectal and vaginal dosage forms include suppositories and oval suppositories. Nasal dosage forms can be administered via inhalation and blowing, such as through a metered-dose inhaler. Topical dosage forms include creams, gels, ointments, ointments, patches, and transdermal delivery systems.

[0497] The compounds provided herein, particularly those of formula (I), or the pharmaceutical compositions described above comprising such compounds, may be administered to a subject via any convenient route of administration, whether systemic / peripheral or at the desired site of action, including but not limited to one or more of the following routes: oral (e.g., as tablets, capsules, or ingestible solutions), topical (e.g., transdermal, intranasal, ocular, buccal, and sublingual), parenteral (e.g., using injection or infusion techniques, including, for example, by injection, such as subcutaneous, intradermal, intramuscular, intravenous, intraarticular, intracardiac, intrasheath, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subepidermal, intra-articular, subarachnoid, or intrasternal, such as by receptacle implantation, such as subcutaneous or intramuscular), pulmonary (e.g., by inhalation or blowing therapy, such as via aerosol, such as through the mouth or nose), gastrointestinal, intrauterine, intraocular, subcutaneous, ocular (including intravitreal or anterior chamber), rectal, or vaginal administration.

[0498] If the compound or pharmaceutical composition is administered via a parenteral route, examples of such administration include one or more of the following methods: intravenous, intra-arterial, intraperitoneal, intrathecal, intraventricular, intraurethral, ​​intrasternal, intracardiac, intramuscular, or subcutaneous administration of the compound or pharmaceutical composition, and / or administration using infusion techniques. For parenteral administration, the compound is preferably used in the form of a sterile aqueous solution, which may contain other substances, such as sufficient salt or glucose, to make the solution isotonic with blood. If necessary, the aqueous solution should be appropriately buffered (preferably with a pH of 3 to 9). Suitable parenteral formulations can be readily prepared under sterile conditions using standard pharmaceutical techniques well known to those skilled in the art.

[0499] The compound or pharmaceutical composition may also be administered orally in the form of tablets, capsules, oval suppositories, elixirs, solutions or suspensions, and may contain flavoring agents or coloring agents for immediate release, delayed release, modulated release, sustained release, pulsatile release or controlled release applications.

[0500] Tablets may contain excipients such as microcrystalline cellulose, lactose, sodium citrate, calcium carbonate, calcium hydrogen phosphate, and glycine; disintegrants such as starch (preferably corn starch, potato starch, or cassava starch), sodium carboxymethyl starch, croscarmellose sodium, and certain complex silicates; and granulation binders such as polyvinylpyrrolidone, hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), sucrose, gelatin, and gum arabic. Additionally, lubricants such as magnesium stearate, stearic acid, glyceryl behenate, and talc may be included. Similar types of solid compositions may also be used as fillers for gelatin capsules. Preferred excipients in this regard include lactose, starch, cellulose, or high molecular weight polyethylene glycol. For aqueous suspensions and / or elixirs, the formulation may be mixed with various sweeteners or flavorings, colorants or dyes, emulsifiers and / or suspending agents, and diluents (such as water, ethanol, propylene glycol, and glycerin) and combinations thereof.

[0501] Alternatively, the compounds or pharmaceutical compositions may be administered in the form of suppositories or vaginal suppositories, or topically applied in the form of gels, hydrogels, lotions, solutions, creams, ointments, or powders. The compounds of the present invention can also be administered through the skin or transdermally, for example using skin patches.

[0502] The compound or pharmaceutical composition may also be administered via a sustained-release system. Suitable examples of sustained-release compositions include a semi-permeable polymer matrix in the form of a molded article, such as a film or microcapsule. Sustained-release matrices include, for example, polylactide (see, for example, US 3,773,919), copolymers of L-glutamic acid and γ-ethyl-L-glutamic acid ester (Sidman, U. et al., Biopolymers 22:547-556 (1983)), poly(2-hydroxyethyl methacrylate) (R. Langer et al., J. Biomed. Mater. Res. 15:167-277 (1981) and R. Langer, Chem. Tech. 12:98-105 (1982)), ethylene vinyl acetate (R. Langer et al., ibid.), or poly-D-(-)-3-hydroxybutyric acid (EP133988). Sustained-release pharmaceutical compositions may also include compounds encapsulated in liposomes. Liposomes containing the compounds of the present invention can be prepared by methods known in the art, such as DE3218121; Epstein et al. (Proc. Natl. Acad. Sci. (USA) 82:3688-3692 (1985)); Hwang et al. (Proc. Natl. Acad. Sci. (USA) 77:4030-4034 (1980)); EP0052322; EP0036676, EP088046; EP0143949; EP0142641; JP 83-118008; US 4,485,045; US4,544,545 and EP0102324.

[0503] The compound or pharmaceutical composition may also be administered via the pulmonary, rectal, or ocular routes. For ophthalmic use, it may be formulated as a micronized suspension in isotonic, pH-adjusted sterile saline, or preferably as a solution in isotonic, pH-adjusted sterile saline, optionally in combination with a preservative (e.g., benzalkonium chloride). Alternatively, it may be formulated as an ointment (e.g., petrolatum).

[0504] It is also envisioned to prepare dry powder formulations of the compounds provided herein (particularly compounds of formula (I)) for pulmonary administration, particularly inhalation. Such dry powders can be prepared by spray drying under conditions that produce substantially amorphous, glassy, ​​or substantially crystalline bioactive powders. Therefore, dry powders of the compounds of the present invention can be prepared according to the emulsification / spray drying methods disclosed in WO 99 / 16419 or WO 01 / 85136. Solution formulations of the compounds of the present invention can be spray-dried, for example, as typically as described in the 5th edition of the Spray Drying Handbook (K. Masters, John Wiley & Sons, Inc., NY (1991)), WO 97 / 41833, or WO 03 / 053411.

[0505] For topical application to the skin, the compounds or pharmaceutical compositions may be formulated as suitable ointments containing active compounds suspended or dissolved in, for example, a mixture of one or more of the following: mineral oil, liquid petrolatum, white petrolatum, propylene glycol, emulsified wax, and water. Alternatively, they may be formulated as suitable lotions or creams suspended or dissolved in, for example, a mixture of one or more of the following: mineral oil, sorbitan monostearate, polyethylene glycol, liquid paraffin, polysorbate 60, cetyl wax, 2-octyldodecanool, benzyl alcohol, and water.

[0506] Therefore, this invention relates to the compounds or pharmaceutical compositions provided herein, wherein the corresponding compounds or pharmaceutical compositions are administered via any of the following routes: oral administration; local administration, including percutaneous, intranasal, ocular, oral, or sublingual routes; parenteral administration using injection or infusion techniques, including subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrasheathal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subepidermal, intraarticular, subarachnoid, intrasternal, intravenous, intraurethral, ​​or intracranial routes; pulmonary administration, including inhalation or blowing therapy; gastrointestinal administration; intrauterine administration; intraocular administration; subcutaneous administration; ophthalmic administration, including intravitreal or intra-anterior chamber administration; rectal administration; or vaginal administration. Particularly preferred routes of administration are oral or parenteral administration.

[0507] Typically, the physician will determine the most suitable actual dose for the individual subject. For any given individual subject, the specific dose level and frequency of administration can vary and will depend on a variety of factors, including the activity of the particular compound used, the metabolic stability and duration of action of the compound, age, weight, general health condition, sex, diet, route and timing of administration, excretion rate, drug combination, severity of the specific condition, and the individual subject being treated.

[0508] Suggested, but not limiting, doses of the compounds of the invention for oral administration to humans (approximately 70 kg body weight) may be from 0.05 to 8000 mg, preferably from 0.1 mg to 4000 mg of the active ingredient per unit dose. A unit dose may be administered, for example, 1 to 3 times daily. A unit dose may also be administered 1 to 7 times weekly, for example, not exceeding once daily. Another exemplary dose of the compounds of formula (I) for oral administration to humans is 50 to 200 mg / kg body weight / day, particularly 100 mg / kg / day. It should be understood that routine adjustments to the dose may be necessary based on the patient's / subject's age and weight, as well as the severity of the condition to be treated. The precise dosage and route of administration will ultimately be determined at the discretion of the attending physician or veterinarian.

[0509] The compounds provided herein, particularly compounds of formula (I) or pharmaceutical compositions comprising such compounds, can be administered as a monotherapy (e.g., without the administration of any other therapeutic agent, or without the administration of any other therapeutic agent that treats or prevents the same disease as compound (I)). However, compounds of formula (I) or pharmaceutical compositions comprising formula (I) can also be administered in combination with one or more other therapeutic agents. If a compound of formula (I) is used in combination with a second therapeutic agent that is active against the same disease or condition, the dosage of each compound may differ from the dosage when used alone, particularly a lower dosage of each compound. Combinations of compounds of formula (I) with one or more other therapeutic agents (e.g., BRD4 inhibitors, preferably direct BRD4 inhibitors) may include: simultaneous / concomitant administration of compound (I) and other therapeutic agents (achieved by a single pharmaceutical formulation or separate pharmaceutical formulations), or sequential / separate administration of compound (I) and other therapeutic agents. If sequential administration is used, the compound of formula (I) of the present invention or one or more other therapeutic agents may be administered first. If simultaneous administration is used, one or more other therapeutic agents may be contained in the same pharmaceutical formulation as compound (I), or administered in one or more different (separate) pharmaceutical formulations.

[0510] Preferably, one or more other therapeutic agents administered in combination with the compounds of the present invention are anticancer drugs. Anticancer drugs administered in combination with the compounds of formula (I) according to the present invention may, for example, be selected from: tumor angiogenesis inhibitors (e.g., protease inhibitors, epidermal growth factor receptor kinase inhibitors, or vascular endothelial growth factor receptor kinase inhibitors); cytotoxic drugs (e.g., antimetabolites, such as purine and pyrimidine analogue antimetabolites); antimitotic agents (e.g., microtubule stabilizers or antimitotic alkaloids); platinum coordination complexes; antitumor antibiotics; alkylating agents (e.g., nitrogen mustard or nitrosourea); endocrine drugs (e.g., corticosteroids, androgens, antiandrogens, estrogens, antiestrogens, aromatase inhibitors, gonadotropin-releasing hormone agonists, or somatostatin analogues); or compounds that target enzymes or receptors overexpressed in tumor cells and / or otherwise involved in the dysregulation of specific metabolic pathways (e.g., ATP and GTP phosphodiesterase inhibitors). Inhibitors, histone deacetylase inhibitors, protein kinase inhibitors (such as serine, threonine, and tyrosine kinase inhibitors, such as Abelson protein tyrosine kinase inhibitors), and various growth factors, their receptors, and corresponding kinase inhibitors (such as epidermal growth factor receptor kinase inhibitors, vascular endothelial growth factor receptor kinase inhibitors, fibroblast growth factor inhibitors, insulin-like growth factor receptor inhibitors, and platelet-derived growth factor receptor kinase inhibitors); methionine, aminopeptidase inhibitors, proteasome inhibitors, cyclooxygenase inhibitors (such as cyclooxygenase-1 or cyclooxygenase-2 inhibitors), topoisomerase inhibitors (such as topoisomerase I or topoisomerase II inhibitors), poly-ADP-ribose polymerase inhibitors (PARP inhibitors), and epidermal growth factor receptor (EGFR) inhibitors / antagonists.

[0511] Alkylating agents that can be used in combination with the compounds of this invention as anticancer drugs may include, for example: nitrogen mustard (such as cyclophosphamide, mechlorethamine (chlormethine)), uramustine, melphalan, chlorambucil, ifosfamide, bendamustine, or trofosfamide), anitrosourea (such as carmustine, streptozocin, fotemustine, lomustine, nimustine, prednimustine, ranimustine, or semustine), and alkyl sulfonates. Sulfonates (e.g., busulfan, mannosulfan, or treosulfan), aziridines (e.g., hexamethylmelamine (altretamine), triethylenemelamine, ThioTEPA (N,N'N'-triethylenethiophosphoramide), carboquone or triaziquone), hydrazines (e.g., procarbazine), atriazenes (e.g., dacarbazine), or an imidazotetrazine (e.g., temozolomide).

[0512] Platinum coordination complexes that can be used in combination with the compounds of the present invention as anticancer drugs may be, for example, cisplatin, carboplatin, nedaplatin, oxaliplatin, satraplatin, or triplatin tetranitrate.

[0513] Cytotoxic drugs that can be used in combination with the compounds of the present invention as anticancer drugs can be, for example, antimetabolites, including folic acid analog antimetabolites (such as aminopterin, methotrexate, pemetrexed or raltitrexed), purine analog antimetabolites (such as cladribine, clofarabine, fludarabine, 6-mercaptopurine (including its prodrug form azathioprine), pentostatin or 6-thioguanine), and pyrimidine analog antimetabolites (such as cytarabine, decitabine, 5-fluorouracil (including its prodrug forms capecitabine and tegafur), fluorouracil, gemcitabine, enoxabin or sapattabine).

[0514] Antimitotic agents that can be used in combination with the compounds of this invention as anticancer drugs include, but are not limited to: taxanes (such as docetaxel, larotaxel, oxaliplatin, paclitaxel / taxanthin, testathiazide) or albumin-bound paclitaxel (such as abraxane). ® Vinca alkaloids (such as vincristine, vinblastine, vinflunine, vindesin or vinorelbine), epothilones (such as epothilone A, epothilone B, epothilone C, epothilone D, epothilone E or epothilone F) or epothilone B analogues (such as ixaprone / azaepothilone B).

[0515] Antitumor antibiotics that can be used in combination with the compounds of the present invention as anticancer drugs may be, for example, anthracyclines (such as aclarubicin, daunorubicin, doxorubicin, epirubicin, idarubicin, amrubicin, pirarubicin, valrubicin, or zorubicin), anthraquinones (such as mitoxantrone or pixantrone), or antitumor antibiotics isolated from Streptomyces (such as actinomycins (including actinomycin D), bleomycin, mitomycin (including mitomycin C), or plicamycin).

[0516] Tyrosine kinase inhibitors that can be used in combination with the compounds of the present invention as anticancer drugs may include, for example: axitinib, bosutinib, cediranib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, lestaurtinib, nilotinib, semaxanib, sorafenib, sunitinib, axitinib, nintedanib, ponatinib, or vandetanib.

[0517] The topoisomerase inhibitors that can be used in combination with the compounds of the present invention as anticancer drugs may be, for example, topoisomerase I inhibitors (such as irinotecan, topotecan, camptothecin, belotecan, rubitecan, or lamellarin D) or topoisomerase II inhibitors (such as amsacrine, etoposide, etoposide phosphate, teniposide, or doxorubicin).

[0518] PARP inhibitors that can be used in combination with the compounds of the present invention as anticancer drugs may be, for example, BMN-673, olaparib, rucaparib, veliparib, CEP 9722, MK 4827, BGB-290 or 3-aminobenzamide.

[0519] EGFR inhibitors / antagonists that can be used in combination with the compounds of this invention as anticancer drugs include, for example, gefitinib, erlotinib, lapatinib, afatinib, neratinib, ABT-414, dacomitinib, AV-412, and PD. 153035, vandetanib, PKI-166, pelitinib, canertinib, icotinib, poziotinib, BMS-690514, CUDC-101, AP26113, XL647, cetuximab, panitumumab, zalutumumab, nimotuzumab, or matuzumab.

[0520] Other anticancer drugs may also be used in combination with the compounds of this invention. Anticancer drugs may include biological or chemical molecules such as TNF-related apoptosis-inducing ligand (TRAIL), tamoxifen, amsacrine, bexarotene, estramustine, irofulven, trabectedin, cetuximab, panitumumab, tositumomab, alemtuzumab, bevacizumab, edrecolomab, gemtuzumab, alvocidib, seliciclib, aminolevulinic acid, methylaminolevulinate, efaproxiral, and porphyrin sodium. sodium, talaporfin, temoporfin, verteporfin, alitretinoin, tretinoin, anagrelide, arsenic trioxide, atrasentan, bortezomib, carmofur, celecoxib, demecolcine, elesclomol, elsamitrucin, etoglucid, chlorhexidine Lonidamine, lucanthone, masoprocol, mitobronitol, mitoguazone, mitotane, oblimersen, omacetaxine, sitimagene, ceradenovec, tegafur, testolactone, tiazofurine, tipifarnib, vorinostat, or iniparib.

[0521] In addition, biological agents targeting tumor markers / factors / cytokines involved in cancer or proliferative diseases, such as antibodies, antibody fragments, antibody constructs (e.g., single-chain constructs), and / or modified antibodies (e.g., CDR transplantation antibodies, humanized antibodies, "fully humanized" antibodies, etc.), can be used in combination with the compounds of this invention for combination therapy. Examples of such biomolecules are anti-HER2 antibodies (e.g., trastuzumab, Herceptin®), anti-CD20 antibodies (e.g., rituximab, Rituxan®, MabThera®, Reditux®), anti-CD19 / CD3 constructs (see, for example, EP1071752), and anti-TNF antibodies (see, for example, Taylor PC. Antibody therapy for rheumatoid arthritis. Curr Opin Pharmacol. 2003. 3(3):323-328). Other antibodies, antibody fragments, antibody constructs, and / or modified antibodies used in combination therapy with the compounds of the present invention can be found, for example: Taylor PC. Curr Opin Pharmacol. 2003. 3(3):323-328; or Roxana A. Maedica. 2006. 1(1):63-65.

[0522] In particular, the anticancer drugs that can be used in combination with the compounds of the present invention can be immuno-oncology therapeutic agents (e.g., antibodies (e.g., monoclonal or polyclonal antibodies), antibody fragments, antibody constructs (e.g., single-chain constructs), or modified antibodies (e.g., CDR transplanted antibodies, humanized antibodies, or “fully humanized” antibodies)) that target any one of CTLA-4, PD-1 / PD-L1, TIM3, LAG3, OX4, CSF1R, IDO, or CD40. These immuno-oncology agents include, for example: anti-CTLA-4 antibodies (especially antagonistic or pathway-blocking anti-CTLA-4 antibodies; such as ipilimumab or tremelimumab), anti-PD-1 antibodies (especially antagonistic or pathway-blocking anti-PD-1 antibodies; such as nivolumab (BMS-936558), pembrolizumab (MK-3475), pidilizumab (CT-011), AMP-224, or APE02058), and anti-PD-L1 antibodies (especially pathway-blocking anti-PD-L1 antibodies; such as BMS-936559, M...). Anti-TIM3 antibodies (especially pathway-blocking anti-TIM3 antibodies), anti-LAG3 antibodies (especially antagonistic or pathway-blocking anti-LAG3 antibodies; e.g., BMS-986016, IMP701, or IMP731), anti-OX4 antibodies (especially agonistic anti-OX4 antibodies; e.g., MEDI0562), anti-CSF1R antibodies (especially pathway-blocking anti-CSF1R antibodies; e.g., IMC-CS4 or RG7155), anti-IDO antibodies (especially pathway-blocking anti-IDO antibodies), or anti-CD40 antibodies (especially agonistic anti-CD40 antibodies; e.g., CP-870, 893, or Chi Lob7 / 4). Other immuno-oncology agents are known in the art and described, for example: Kyi C et al., FEBS Lett, 2014, 588(2):368-76; Intlekofer AM et al., J Leukoc Biol, 2013, 94(1):25-39; Callahan MK et al., J Leukoc Biol, 2013, 94(1):41-53; Ngiow SF et al., Cancer Res, 2011, 71(21):6567-71; and Blattman JN et al., Science, 2004, 305(5681):200-5.

[0523] BRD4 inhibitors (preferably direct BRD4 inhibitors) can also be used in combination with compounds of formula (I) as other therapeutic agents.

[0524] The above compositions are readily available for use in pharmaceutical formulations. The components of such compositions can be administered sequentially or concurrently / concomitantly in pharmaceutical formulations, alone or in combination, via any convenient route. When administered sequentially, the compounds of the present invention (particularly compounds of formula (I) or their pharmaceutically acceptable salts or hydrates) or other therapeutic agents may be administered first. When administered concurrently, the combination may be administered in the same pharmaceutical composition or in different pharmaceutical compositions. When combined in the same formulation, it should be understood that the two or more compounds must be stable and compatible with each other and with the other components of the formulation. When formulated individually, they can be provided in any convenient formulation form.

[0525] The compounds provided herein, particularly those of formula (I), may also be administered in combination with physical therapy, such as radiotherapy. Radiotherapy may be initiated before, after, or simultaneously with the administration of the compounds of the present invention. For example, radiotherapy may be initiated 1–10 minutes, 1–10 hours, or 24–72 hours after administration of the compound. However, these time ranges should not be construed as limiting. The subject is exposed to radiation, preferably gamma radiation, which may be provided in a single dose or multiple doses administered over hours, days, and / or weeks. Gamma radiation may be administered according to standard radiotherapy protocols, using standard doses and administration regimens.

[0526] Therefore, the present invention relates to the use of a compound of formula (I) or a pharmaceutically acceptable salt or hydrate thereof, or a pharmaceutical composition comprising any of the foregoing substances in combination with a pharmaceutically acceptable excipient, for the treatment or prevention of cancer, wherein the compound or pharmaceutical composition is administered in combination with one or more anticancer drugs and / or in combination with radiotherapy.

[0527] However, compounds of formula (I) can also be used as monotherapy, particularly in the monotherapy or prevention of cancer (i.e., without the administration of any other anticancer agents before the discontinuation of treatment with the compound of formula (I)). Accordingly, the present invention also relates to the use of compounds of formula (I) or pharmaceutically acceptable salts or hydrates thereof, or pharmaceutical compositions comprising any of the foregoing substances in combination with pharmaceutically acceptable excipients, for the monotherapy or prevention of cancer.

[0528] According to the present invention, the subject or patient to be treated can be an animal (e.g., a non-human animal), a vertebrate, a mammal, a rodent (e.g., a guinea pig, hamster, rat, or mouse), a canine (e.g., a dog), a feline (e.g., a cat), a suidae (e.g., a pig), an equine (e.g., a horse), a primate or ape (e.g., a monkey or ape, such as a marmoset, baboon, gorilla, chimpanzee, orangutan, or gibbon), or a human. According to the present invention, the treatment is intended for animals of economic, agricultural, or scientific importance. Organisms of scientific importance include, but are not limited to, mice, rats, and rabbits. Lower organisms, such as fruit flies (e.g., Drosophila melanogaster), are also included. Drosophila melagonaster )) and nematodes (such as Caenorhabditis elegans ( ... Caenorhabditis elegans Animals of agricultural importance can also be used for scientific research. Non-limiting examples of animals of agricultural importance include sheep, cattle, and pigs, while animals of economic importance, such as cats and dogs, can be considered. Preferably, the subject / patient is a mammal. More preferably, the subject / patient is a human or a non-human mammal (e.g., guinea pig, hamster, rat, mouse, rabbit, dog, cat, horse, monkey, ape, marmoset, baboon, gorilla, chimpanzee, orangutan, gibbon, sheep, cattle, or pig). Most preferably, the subject / patient is a human.

[0529] The term "prevention" as used herein for a disorder or disease (e.g., "prevention" of cancer) is also well known in the art. For example, patients / subjects suspected of being susceptible to a disorder or disease may particularly benefit from prevention of that disorder or disease. Subjects / patients may have a susceptibility or predisposition to a disorder or disease, including but not limited to a genetic predisposition. Such a predisposition can be determined by standard methods or assays, such as using genetic markers or phenotypic indicators. It should be understood that the disorder or disease to be prevented according to the present invention has not yet been diagnosed or cannot be diagnosed in the patient / subject (e.g., the patient / subject does not exhibit any clinical or pathological symptoms). Therefore, the term "prevention" includes the use of the compounds of the present invention prior to any clinical and / or pathological symptoms being diagnosed or identified or potentially diagnosed or identified by an attending physician.

[0530] Cyclin-dependent kinases (CDKs) belong to the Ser / Thr kinase family and integrate into multiple signal transduction pathways, playing a central role in several key cellular processes. CDK12 and its homolog CDK13 belong to the "transcriptional" CDK category. Transcription of protein-coding genes is regulated by RNA polymerase II. Phosphorylation of residues in its C-terminal domain (CTD) coordinates the production of mature mRNA transcripts. Phosphorylation of Ser2 promotes the elongation of RNA polymerase II along the gene body, a key mechanism in the transcriptional regulation of CDK12 (Genes & Development 2010, 24:2303-2316). CDK12 and CDK13 bind to their obligate chaperone, cyclin K, to regulate various cellular processes, including transcriptional elongation, precursor mRNA splicing, and cell cycle progression. Furthermore, CDK12 knockdown is associated with the downregulation of genes involved in homologous recombination and DNA damage response (DDR) (Genes & Development 2011, 25:2158-2172). Therefore, maintaining genome stability appears to be a crucial function of this protein.

[0531] CDK12 is frequently dysregulated in human cancers and is an attractive therapeutic target. In severe ovarian cancer, CDK12 mutations are associated with decreased expression of DDR genes (such as BRCA1, FANCI, ATM, ATR, or FANCD2) and increased sensitivity to PARP inhibitors. (Cancer Res, 2016, 76(7) 1182; Nucleic Acids Research, 2015, Vol. 43, 2575-2589).

[0532] The frequency and distribution of CDK12 protein expression were assessed in an independent breast cancer cohort using immunohistochemistry (IHC), and correlated with results and genomic status. The study found that 21% of unselected primary breast cancers exhibited high CDK12 expression, while 10.5% showed CDK12 deficiency. Overexpression of CDK12 in breast cancer cells has been shown to regulate pre-mRNA splicing processes involved in DDR and tumorigenesis (Nucleic Acids Res., 2017, Jun 20;45(11):6698-6716). Disruption of cyclin-dependent kinase 12 (CDK12) is known to lead to DNA repair defects and sensitivity to platinum salts and PARP1 / 2 inhibitors. Interestingly, CDK12 deficiency was associated with reduced expression of many DDR proteins, including ATR, Ku70 / Ku80, PARP1, DNA-PK, and γH2AX, suggesting a novel mechanism of CDK12-related DDR dysregulation in breast cancer. This may have significant therapeutic implications, particularly for triple-negative breast cancer. (Molecular Cancer Therapeutics (2018), 17(1), 306-315).

[0533] Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family with tyrosine kinase activity. HER2 amplification or overexpression occurs in approximately 15-30% of breast cancers and 10-30% of gastric / gastroesophageal cancers, serving as a prognostic and predictive biomarker. HER2 overexpression is also observed in other cancers such as ovarian cancer, endometrial cancer, bladder cancer, lung cancer, colon cancer, and head and neck cancer. The introduction of HER2-targeted therapy has significantly improved the prognosis of patients with HER2-positive breast cancer and gastric / gastroesophageal cancer (Mol Biol Int. 2014; 2014: 852748). In breast cancer, HER2 is a commonly amplified and overexpressed portion of the 17q12-q21 locus. 17q12-q21 amplicon typically contains several neighboring genes, including MED1, GRB7, MSL1, CASC3, and TOP2A. In 71% of cases, the HER2 amplicon also contained the CDK12 gene (Cell Division, Vol. 12, Article No. 7 (2017)). High CDK12 expression due to co-amplification of CDK12 and HER2 in breast cancer patients is associated with disease recurrence and poor survival (EMBO Rep (2019)20:e48058).

[0534] Designing selective ATP-competitive kinase inhibitors is challenging due to the high similarity of ATP binding sites and the difficulty in overcoming extremely high intracellular ATP concentrations. To date, all CDK12 inhibitors in clinical trials are pan-CDK inhibitors (Dinaciclib). Degradation of the target protein thus becomes an attractive alternative strategy, especially when such degraders can overcome common problems of ATP-competitive kinase inhibitors, such as poor permeability, low oral bioavailability, poor central nervous system penetration, and high levels of P-gp and BCRP1-mediated efflux.

[0535] This invention relates to compounds that induce cyclin K degradation and thus selectively inactivate CDK12 and CDK13 via a "molecular glue" mechanism. This is achieved by stabilizing the interaction between the CDK12 / cyclin K complex and the Cullin-RING E3 ligase. The CRL is a multi-subunit complex consisting of a Cullin scaffold (e.g., CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL5, CUL7, CUL9) and a substrate receptor (SR) (e.g., CRBN, VHL, DCAF15) recruited via a linker subunit (e.g., DDB1, SKP1, ELOB / C) to confer target specificity to the complex. Target proteins presented by the SRs are labeled by ubiquitin transfer via an E2 enzyme recruited to the CRL for proteasomal degradation. In this invention, CDK12 / cyclin K interacts with the CRL complex containing CUL4A or CUL4B and DDB1. CDK12 directly binds to DDB1 and acts as an alternative SR to expose cyclin K for ubiquitination.

[0536] Cyclin K degradation is a characteristic of some (but not all) CDK12 inhibitors. The interaction between CDK12 and DDB1 is partly driven by the interaction between the inhibitor and DDB1. Therefore, only CDK12 inhibitors that simultaneously occupy the kinase active site and fill the hydrophobic pocket of DDB1 can promote cyclin K degradation. For example, studies have found that the pan-CDK inhibitor CR8 induces cyclin K degradation through this mechanism, while the CDK12 selective covalent inhibitor THZ-531 did not. However, predicting the cyclin K degradation properties of CDK12 inhibitors or designing cyclin K degrading agents is not straightforward. Therefore, all reported cyclin K degrading agents are serendipitous discoveries.

[0537] It is believed that CDK12 and CDK13 have highly overlapping target spaces (Liang et al., 2015), thus CDK13 can compensate for the loss of CDK12 enzyme activity. Cyclin K is a common obligate chaperone for both CDK12 and CDK13 and is required for the activity of both. Therefore, cyclin K degraders would impair the activity of both kinases simultaneously, potentially circumventing this compensatory signaling.

[0538] Restoration of CDK12 activity after treatment with a cyclin K degrading agent requires the resynthesis of cyclin K. Cyclin K is a relatively long-lived protein, reportedly with a half-life exceeding 12 hours. Therefore, the compounds of this invention are expected to have therapeutic effects in cells and tumors far exceeding the duration of molecular exposure. This advantageous decoupling between pharmacokinetics and pharmacodynamics can be used to further optimize the selective characterization of these molecules and reduce dosing regimens.

[0539] Example

[0540] Example 1: Synthesis

[0541] Abbreviation list:

[0542] Instrument Specifications: NMR: Bruker Avance DRX 500 Varian UNITYplus 400 Proton nuclear magnetic resonance (NMR) spectra were recorded at 400 MHz or 500 MHz. Chemical shifts (δ) are given in parts per million (ppm) and listed at high field with tetramethylsilane as a reference. Peaks are described as singlets (s), doublets (d), triplets (t), quartets (q), quintets, multiplets (m), and broad peaks (br.).

[0543] LCMS: The Shimadzu LCMS-2020 series LC / MSD system is equipped with a PDA SPD-M40 and a Shimadzu LCMS-2020 mass spectrometer.

[0544] The Shimadzu LCMS-2020 series LC / MSD system is equipped with a PDA\ELSD SPD-M40 / LT III and a Shimadzu LCMS-2020 mass spectrometer.

[0545] The Shimadzu LCMS-2020 series LC / MSD system is equipped with a PDA\ELSD SPD-M40 / 3300HP and a Shimadzu LCMS-2020 mass spectrometer.

[0546] The Shimadzu LCMS-2020 series LC / MSD system is equipped with a PDA SPD-M20A and a Shimadzu LCMS-2020 mass spectrometer.

[0547] The Shimadzu LCMS-2020 series LC / MSD system is equipped with a PDA / ELSD SPD-M20A / 3300HP and a Shimadzu LCMS-2020 mass spectrometer.

[0548] Method A: Column: EVO C18 3.0 x 50 mm, 2.6 μm Temperature: 40°C Mobile phase A: Water containing 5 mM NH4HCO3 Mobile phase B: Acetonitrile (MeCN) Flow rate: 1.5 mL / min Elution gradient: 0.01 min - 10% B, 1.20 min - 95% B, 1.70 min - 95% B, 1.75 min - 10% B Injection volume: 0.5 μL Ionization mode: Electrospray ionization (ESI) Scan range: m / z 90-900 PDA: 254nm, 220nm, 200nm Method B: Column: Express C18 3.0 x 30 mm, 2.6 μm Temperature: 40°C Mobile phase A: Water containing 0.1% FA Mobile phase B: Acetonitrile Flow rate: 1.5 mL / min Elution gradient: 0.01 min - 5% B, 0.80 min - 95% B, 1.20 min - 95% B, 1.25 min - 5% B Injection volume: 0.5 μL Ionization mode: Electrospray ionization (ESI) Scan range: m / z 50-1500 PDA: 254nm, 220nm, 200nm Method C: Column: EVO C18 3.0 x 50 mm, 2.6 μm Temperature: 40°C Mobile phase A: Water containing 5 mM NH4HCO3 Mobile phase B: Acetonitrile Flow rate: 1.5 mL / min Elution gradient: 0.01 min - 10% B, 2.00 min - 70% B, 2.20 min - 95% B, 2.60 min - 95% B, 2.75 min - 10% B Injection volume: 0.5 μL Ionization mode: Electrospray ionization (ESI) Scan range: m / z 90-900 PDA: 254nm, 220nm, 200nm Method D: Column: Express C18 3.0 x 30 mm, 2.6 μm Temperature: 40°C Mobile phase A: Water containing 0.1% FA Mobile phase B: Acetonitrile Flow rate: 1.5 mL / min Elution gradient: 0.01 min - 5% B, 2.10 min - 95% B, 2.60 min - 95% B, 2.75 min - 5% B Injection volume: 0.5 μL Ionization mode: Electrospray ionization (ESI) Scan range: m / z 90-900 PDA: 254nm, 220nm, 200nm Method E: Chromatographic column: HPH C18 3.0 x 50 mm Temperature: 40°C Mobile phase A: Water containing 0.1% FA Mobile phase B: Acetonitrile containing 0.1% FA Flow rate: 1.5 mL / min Elution gradient: 0.01 min - 5% B, 1.20 min - 100% B, 1.75 min - 100% B, 1.85 min - 5% B Injection volume: 0.5 μL Ionization mode: Electrospray ionization (ESI) Scan range: m / z 90-900 PDA: 254nm, 220nm, 200nm Method F: Column: EC C18 3.0 x 30 mm Temperature: 40°C Mobile phase A: Water containing 0.05% TFA Mobile phase B: Acetonitrile containing 0.05% TFA Flow rate: 1.5 mL / min Elution gradient: 0.01 min - 5% B, 0.80 min - 100% B, 1.20 min - 100% B, 1.25 min - 5% B Injection volume: 0.5 μL Ionization mode: Electrospray ionization (ESI) Scan range: m / z 90-900 PDA: 254nm, 220nm, 200nm Method G: Chromatographic column: HPH C18 50 x 3.0 mm, 2.6 μm Temperature: 40°C Mobile phase A: Water containin...

Claims

1. A compound of formula (I) or a stereoisomer, tautomer, pharmaceutically acceptable salt or hydrate thereof: (I) in, A is a 5-membered heteroaryl group comprising one or more identical or different heteroatoms selected from O, N, or S, wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the heteroaryl group is independently unsubstituted or substituted by one or more identical or different substituents R. A Substitution, provided that at least one substituent R A It exists on heteroaryl A; in, R A The group is a halogen, CN, C1-C6-alkyl, C1-C6-haloalkyl, 3 to 10 saturated or partially unsaturated carbocyclic group, carbocyclic-C1-C2-alkyl, carbon bicyclic group, carbon bicyclic-C1-C2-alkyl, heterocyclic group, heterocyclic-C1-C2-alkyl, heterobicyclic group, or heterobicyclic-C1-C2-alkyl, wherein the above heterocycle or heterobicycle contains one or more identical or different heteroatoms selected from O, N, or S, wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the above group is independently unsubstituted or substituented by one or more identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C4-alkyl; B is any of the following groups: 、 、 、 、 、 or ; In each case, the wavy line marks the connection to the rest of the molecule; and in, R B1 For H; R B2 It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; R B3 It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; R B4 It is H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; and R B5 For H; The condition is R B2 R B3 and R B4 At least one of them is different from H; X 1 For N or CR B6 ; Y 1 For N or CR B7 ; Z 1 For N or CR B8 ; The condition is X 1 Y 1 and Z 1 N is a subset of, but not exceeding, one of; R B6 For H; R B7 It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; R B8 It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; R B9 It is H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; and R B10 For H; R B11 It is H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; and R B12 It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; R B13 It is H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; and R B14 It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; R B15 It is H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; and R B16 It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; R B17 It can be H, halogen, CN, N(CH3)2, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C2-alkoxy-C1-C2-alkyl, C1-C4-alkyl-S-, C1-C4-alkyl-S(O)2- or C1-C4-dimethylaminoalkyl; and, R 1 It is H or C1-C4-alkyl.

2. The compound according to claim 1, wherein, A is one of the following heteroaryl groups: ； in, X 2 For N or NH; Y 2 For CH, CR A2 , N, NH or S; Z 2 For CH, CR A4 , N, NH or S; The condition is Y 2 and Z 2 At least one of them is different from CH, CR A2 or CR A4 ;and The wavy line marks the connection to the rest of the molecule; and... The dashed lines within the 5-membered ring indicate the presence of double bonds, thus forming an aromatic ring system; and Among them, R A2 R A3 and R A4 Represents one or more identical or different substituents R on the heteroaryl A as defined in claim 1. A .

3. The compound according to claim 1 or 2, wherein, A is any of the following heteroaryl groups: , or ; In each case, the wavy line marks the connection to the rest of the molecule; and in, R A3 The group is a C1-C6-alkyl, C1-C6-haloalkyl, 3 to 10 saturated or partially unsaturated carbocyclic group, carbocyclic-C1-C2-alkyl, carbon bicyclic, carbon bicyclic-C1-C2-alkyl, heterocyclic, heterocyclic-C1-C2-alkyl, heterobicyclic, or heterobicyclic-C1-C2-alkyl, wherein the heterocycle or heterobicycle comprises one or more identical or different heteroatoms selected from O, N, or S, wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the above groups is independently unsubstituted or substituented by one or more identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C2-alkyl.

4. The compound according to any one of claims 1 to 3, wherein, A is any of the following heteroaryl groups: or ; In each case, the wavy line marks the connection to the rest of the molecule; and in, R A3 The group is a C1-C6-alkyl, C1-C6-haloalkyl, 3- to 10-membered saturated carbocyclic group, carbocyclic-C1-C2-alkyl, carbon bicyclic, carbon bicyclic-C1-C2-alkyl, heterocyclic, heterocyclic-C1-C2-alkyl, heterobicyclic, or heterobicyclic-C1-C2-alkyl, wherein the heterocycle or heterobicycle comprises one or more identical or different heteroatoms selected from O, N, or S, wherein the N atom and / or S atom is independently oxidized or unoxidized, and wherein each substituted carbon atom or heteroatom in the above groups is independently unsubstituted or substituented by one or more identical or different substituents R. Y replace; in, R Y It is Cl, F or C1-C2-alkyl.

5. The compound according to any one of claims 2 to 4, wherein, R A3 It is any of the following groups: CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, C(CH3)3, CF3, 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , or ; The wavy line indicates the connection to group A in each case.

6. The compound according to any one of claims 2 to 5, wherein, R A3 It is any of the following groups: CH(CH3)2、 、 、 、 、 、 、 、 、 、 、 、 、 、 ； The wavy line indicates the connection to group A in each case.

7. The compound according to any one of claims 2 to 6, wherein, R A3 for ， The wavy line marks the connection to the A group.

8. The compound according to any one of claims 1 to 7, wherein, B is The wavy line marks the connection to the rest of the molecule; and... in, R B1 For H; R B2 The possible values ​​are H, Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B3 The possible values ​​are H, Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B4 The possible values ​​are H, Cl, F, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; and R B5 For H; The condition is R B2 R B3 and R B4 At least one of them is different from H.

9. The compound according to any one of claims 1 to 7, wherein, B is The wavy line marks the connection to the rest of the molecule; and... in, R B7 It can be H, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B8 It can be H, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; R B9 It can be H, CN, CH3, CHF2, CF3, OCH3, or CH2OCH3; and R B10 For H.

10. The compound according to any one of claims 1 to 9, wherein, R 1 For H.

11. The compound according to any one of claims 1 to 9, wherein, R 1 It is a C1-C4-alkyl group.

12. The compound according to claim 11, wherein the compound is a compound of formula (IA): (IA).

13. The compound according to claim 11, wherein the compound is a compound of formula (IB): (IB).

14. The compound according to any one of claims 1 to 9 or 11 to 13, wherein, R 1 It is CH3.

15. The compound according to any one of claims 1 to 9, wherein the compound is selected from the group consisting of: (S)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, 2-(1-(4-chloro-5-methylpyridin-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, (S)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-(dimethylamino)pyridin-2-yl)-1H-pyrazol-4-yl)acetamide, (S)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazole-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(6-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(3-(methoxymethyl)phenyl)-1H-pyrazole-4-yl)acetamide, 2-(1-(4-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(4-methylpyridin-2-yl)-1H-pyrazole-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazole-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)acetamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazole-3-yl)-2-(1-(3-methoxyphenyl)-1H-pyrazole-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(m-tolyl)-1H-pyrazol-4-yl)acetamide, N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)acetamide, (S)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxetane-3-yl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (S)-N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, 2-(1-(4-chloro-5-methylpyridin-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, (S)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-(dimethylamino)pyridin-2-yl)-1H-pyrazol-4-yl)acetamide, (S)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)acetamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methylpyridin-2-yl)-1H-pyrazol-4-yl)acetamide, 2-(1-(6-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(methoxymethyl)phenyl)-1H-pyrazol-4-yl)acetamide, 2-(1-(4-chloropyridin-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (R)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, N-(3-cyclopropyl-1H-pyrazole-5-yl)-2-(1-(4-methylpyridin-2-yl)-1H-pyrazole-4-yl)acetamide, N-(3-cyclopropyl-1H-pyrazole-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazole-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)acetamide, 2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)acetamide, N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-methoxyphenyl)-1H-pyrazol-4-yl)acetamide, 2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)acetamide, and N-(3-Cyclopropyl-1H-pyrazole-5-yl)-2-(1-(3-fluorophenyl)-1H-pyrazole-4-yl)acetamide.

16. The compound according to any one of claims 1 to 9, 11, 12 or 14, wherein the compound is selected from the group consisting of: (S)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(oxecyclobutane-3-yl)-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-(-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-(2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide, (S)-2-(1-(3-cyano-5-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)phenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methoxyphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(oxecyclobutane-3-yl)-1H-pyrazol-5-yl)propionamide, (S)-N-(3-Cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3-fluoro-5-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-cyano-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1R,2S)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((1S,2R)-2-fluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-(2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((R)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-((S)-2,2-difluorocyclopropyl)-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-fluoro-3-methylphenyl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-methoxyphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(4-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chloro-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(6-methoxypyridin-2-yl)-1H-pyrazol-4-yl)propionamide, (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclobutyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chloro-5-methylphenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-cyanophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-2-(1-(3-chloro-4-fluorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide, (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(3,5-difluorophenyl)-1H-pyrazol-4-yl)propionamide, and (S)-2-(1-(3-chlorophenyl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide.

17. The compound according to any one of claims 1 to 9, 11 or 14, wherein the compound is selected from the group consisting of: (R)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (R)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (S)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; 2-(1-(2-chlorothiazol-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (R)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (S)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; 2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (R)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (R)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (R)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (S)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; 2-(1-(4-chlorothiazol-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (R)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (S)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; and 2-(1-(4-chlorothiazol-2-yl)-1H-pyrazole-4-yl)-N-(3-cyclopropyl-1H-pyrazole-5-yl)propionamide.

18. The compound according to any one of claims 1 to 9, 11, 12 or 14, wherein the compound is selected from the group consisting of: (S)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-(difluoromethyl)-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(5-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-3-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-(2-oxaspiro[3.3]heptane-6-yl)-1H-pyrazol-5-yl)-2-(1-(3-cyano-5-fluorophenyl)-1H-pyrazol-4-yl)propionamide; (S)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; (S)-2-(1-(2-chlorothiazo-4-yl)-1H-pyrazol-4-yl)-N-(3-cyclopropyl-1H-pyrazol-5-yl)propionamide; (S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-N-(3-cyclopropyl-1H-pyrazol-5-yl)-2-(1-(2-methylthiazo-4-yl)-1H-pyrazol-4-yl)propionamide; (S)-2-(1-(4-chlorothiazo-2-yl)-1H-pyrazol-4-yl)-N-(5-cyclopropyl-1H-pyrazol-3-yl)propionamide; and (S)-2-(1-(4-chlorothiazol-2-yl)-1H-pyrazole-4-yl)-N-(3-cyclopropyl-1H-pyrazole-5-yl)propionamide.

19. A pharmaceutical composition comprising a pharmaceutically acceptable amount of the compound according to any one of claims 1 to 18, and optionally a pharmaceutically acceptable carrier, diluent, or excipient.

20. Use in medicine of the compound according to any one of claims 1 to 18 or the pharmaceutical composition according to claim 19.

21. Use of the compound according to any one of claims 1 to 18 or the pharmaceutical composition according to claim 19 for the treatment or prevention of cancer, metabolic diseases, nervous system diseases, or infectious diseases, preferably for the treatment or prevention of cancer, wherein particularly preferably, the cancer is selected from the group consisting of: leukemia, particularly acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL), and chronic leukemia including chronic myeloid leukemia; lymphoma, particularly non-Hodgkin lymphoma and Hodgkin lymphoma; head and neck cancer; esophageal cancer; adenoid cystic carcinoma; osteosarcoma; ovarian cancer; Ewing's sarcoma; lung cancer; neuroblastoma; gastrointestinal cancer; endometrial cancer; cervical cancer; medulloblastoma; prostate cancer; breast cancer; thyroid cancer; meningioma; liver cancer; colorectal cancer; pancreatic cancer; chondrosarcoma; osteosarcoma; and kidney cancer.

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