Pyrrolopyridone Derivatives Useful in the Treatment of Cancer

Abstract

The present invention relates to compounds that contain a pyrrolopyridone core, as well as pharma- ceutically acceptable salts and compositions of such compounds. The compounds herein are useful as anti-inflammatory and / or other therapies.

Description

[Technical Field]

[0001] The present invention relates to compounds comprising a pyrrolopyridone core, as well as pharmaceutically acceptable salts and compositions of such compounds. The compounds herein are useful as anti-inflammatory and / or other therapies. Accordingly, the present disclosure also relates to compounds for use as pharmaceuticals, particularly for the treatment of inflammatory diseases.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to UK Patent Application No. 2109324.0 filed June 29, 2021 and UK Patent Application No. 2208160.8 filed June 1, 2022, the entire contents of which are incorporated herein by reference. [Background technology]

[0003] Bromodomain and extra-terminal (BET) proteins are a family of four bromodomain-containing (BRD) proteins (BRD2, BRD3, BRD4, and BRDT). All four members contain two BRDs (located alongside each other toward the N-terminus of the protein) and one extra-terminal domain (Shi, J. et al. Cancer Cell 25(2):210-225(2014)). The two BRDs in each BET protein are named bromodomain I (BD1) and bromodomain II (BD2). BRDs are functional protein domains containing a defined, primarily hydrophobic pocket that binds to acetylated lysine residues and are typically found in transcription factors (Shi, J. et al. Cancer Cell 25(2):210-225(2014)) or the N-terminal tails of histone proteins. BRDs function as epigenetic regulators, i.e., they functionally alter gene activity and expression without altering DNA sequence. For example, BRD4 recruits the transcription factor P-TEFb to promoters, leading to changes in the expression of genes involved in the cell cycle (Yang et al., Mol. Cell Biol. 28:967-976 (2008)). BRD2 and BRD3 also regulate growth-promoting genes (LeRoy et al., Mol. Cell 30:51-60 (2008)). Thus, BRDs play a role in transducing signals from acetylated lysine residues into various phenotypes. BETs are generally considered to be ubiquitously expressed in humans, with the exception of BRDT, which is typically expressed in the testis but is also expressed by some cancers (Ekaterina BF et al. Cell J. 19 (Suppl 1):1-8 (2017)).

[0004] BET proteins play a role in regulating biochemical pathways such as MYC, BCL2, FOSL1, P-TEFb, NFkB, and glucocorticoid signaling (Shi J. et al. Mol Cell. Jun 5;54(5):728-36(2014)), (Hajmirza A. Biomedicines. Feb 6;6(1).pii:E16(2018)), (Shan N. Elife. Sep 11;6.pii:e27861.(2017)), (Huang B. Mol Cell Biol. Mar;29(5):1375-87(2009)). Therefore, BET inhibitors are considered to have potential uses in a range of inflammatory diseases, cancer, infectious diseases, metabolic diseases, CNS disorders, fibrotic diseases, and cardiac diseases (Deanna AM et al. J Exp Med. Oct 21;210(11):2181-2190(2013)), (Rab KPet al. Trends Pharmacol. Sci. Mar;33(3):146-53(2012)), (Anna CB et al. J Immunol. Apr 1;190(7):3670-3678(2013)), (Zuber J. et al. Nature. Aug 3;478(7370):524-8.(2011)), (Montserrat PSet al. Epigenetics.;12(5):323-339(2017)), (Qiming D. et al. Sci Transl Med.May 17;9(390):eaah5084.(2017)), (Kristin MK et al.J Biol Chem.Aug 11;292(32):13284-13295(2017)), (Ning D.et al.PNAS December 22,112(51)15713-15718(2015)).

[0005] Inhibition of the BDII domain of BET proteins has been shown to affect inflammatory, metabolic, cancer, and fibrotic diseases (Gilan et al., Science 368, 387-394 (2020)), (LM Tsujikawa et al. Clin Epigenetics. 2019;11(1):102), (E. Faivre et al. Nature 578, 306-310 (2020)), (M. Zhang, et al. Cellular Signaling 61 (2019) 20-29).

[0006] Compounds that can inhibit or affect the function of BET proteins have the potential to regulate gene expression and treat diseases caused, at least in part, by aberrant regulation of BET protein activity. Several small molecules, including diazepine-, 3,5-dimethylisoxazole-, thiazol-2-one-, diazobenzene-, and 4-acylpyrrole-based compounds, have been reported to be effective in inhibiting BET (see M. Brand et al., ACS Chem. Biol. 2015, 10, 22-39; WO2011054553; WO2011054845). Compounds that can selectively inhibit the function of BDII over BD1 have the potential to regulate gene expression and treat diseases caused, at least in part, by aberrant regulation of BET protein activity, and may offer an improved therapeutic index. Several small molecules, including BY27, RVX-297, ABBV744, GSK046, GSK620, and GSK549, have been reported to be effective in selectively inhibiting the function of BET BDII over BET BD1 (Chen D. et. al. Eur J Med Chem 182, 2019, 111633), (Wells P Set. al. Proc. Natl. Acad. Sci. USA 2013, 110, 19754-19759), (Sheppard G Set. al. J. Med. Chem. 2020, 63, 10, 5585-5623), (Preston A. et. al. J. Med. Chem. 2020, 63, 17, 9070-9092), (Seal JT et. al. J. Med. Chem. 2020, 63, 17, 9093-9126). BDII-selective BET inhibitors have been shown to have improved therapeutic index and preclinical safety compared to pan-BET inhibitors (E. Faivre et al. Nature 578, 306-310 (2020)).

[0007] Compounds containing a 6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one moiety substituted at the 4- and / or 2-position are described in the following patent applications as being useful for inhibiting BET proteins: WO2017177955, WO2015081280, WO2014206150, WO2014206345, WO2013097601, WO2013097052, and WO2018130174.

[0008] WO2020216779A1 discloses compounds useful in anti-inflammatory and anti-cancer therapy.

[0009] WO2021068755 discloses compounds having BRD4 inhibitory activity and methods for preparing the same.

[0010] WO2018195155 discloses compounds for the treatment of diseases mediated by abnormal cell signaling, such as inflammatory disorders, cancer, and neoplastic diseases. The specific compounds described exhibit selective inhibitory activity against CBP compared to BRD4.

[0011] WO2021003310 discloses novel bromodomain and exoterminal domain (BET) inhibitors and therapeutic methods for treating conditions and diseases using the disclosed BET inhibitors. The disclosure provides novel BET protein inhibitors, their use as pharmaceuticals, compositions containing them, and methods for their preparation. Summary of the Invention

[0012] According to a first aspect, the present disclosure provides a compound of formula (I), or a pharmaceutically acceptable salt or N-oxide thereof: [ka] (In the formula, Ring A is independently selected from phenyl, 5-membered heterocyclyl, and 6-membered heterocyclyl; X 4 are independently selected from carbon and nitrogen; X5 are independently selected from carbon and nitrogen; R 1 is independently selected from C1-C3-alkyl, C1-C3-fluoroalkyl, C3-C4-cycloalkyl, and 4-membered heterocycloalkyl; R 2 are independently selected from 5-membered heterocyclyl, 6-membered heterocyclyl, and phenyl, each of which optionally contains 1 to 4 R 2a substituted with a group; R 2a are each independently ═O, ═S, halo, nitro, cyano, or NR 5 R 6 , OR 7 , S.R. 6 , SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , CO2R 6 , C(O)R 6 ,CONR 6 R 6 , C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C3-C6 cycloalkyl, and 4- to 6-membered heterocyclyl; R 3 are independently 3a , OR 3b , and NR 6 R 3b Selected from; R 3a are independently H, CN, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C2-C4-haloalkenyl, and C0-C3-alkylene-R 3c Selected from; R 3c are each independently selected from C3-C8-cycloalkyl, C5-C8-cycloalkenyl, 5- to 8-membered heterocycloalkenyl, 3- to 8-membered heterocycloalkyl, phenyl, and 5- or 6-membered heteroaryl; where R 3cWhen R is cycloalkyl, heterocycloalkyl, cycloalkenyl, or heterocycloalkenyl, 3c is 1 to 4 R 8 optionally substituted by a group; R 3c is phenyl or heteroaryl, R 3c is 1 to 5 R 9 is optionally replaced by; R 3b are independently C1-C4-alkyl, C2-C4-alkylene-O-C1-C4-alkyl, C1-C4-haloalkyl, and C0-C3-alkylene-R 3d Selected from; R 3d are each independently selected from C3-C8-cycloalkyl, 3- to 8-membered heterocycloalkyl, phenyl, and 5- or 6-membered heteroaryl; where R 3d When R is cycloalkyl or heterocycloalkyl, 3d is 1 to 4 R 8 optionally substituted with R 3d is phenyl or heteroaryl, R 3d is 1 to 5 R 9 optionally substituted with a group; R 4 are each independently ═O, ═S, halo, nitro, cyano, C0-C4-alkylene-NR 5 R 6 , C0-C4-alkylene-OR 7 , S.R. 6 , SOR 6 , C0-C4-alkylene-S(O)2R 6 , SO2NR 6 R 6 , C0-C4-alkylene-CO2R 6 , C0-C4-alkylene-C(O)R 6 , C0-C4-alkylene-CONR 6 R 6 , C1-C4-alkyl, C1-C4-alkyl-S(O)2R 6, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl; R 5 are each independently selected from H, C-C-alkyl, C(O)-C-C-alkyl, and S(O)-C-C-alkyl; or R 5 and R 6 and together with the nitrogen atom to which they are attached form 1 to 4 R 8 forming a C5-C8-heterocycloalkyl group optionally substituted by a group; R 6 are each independently selected from H and C1-C4-alkyl; or two R 6 groups are attached to the same nitrogen, and the two R 6 The groups, together with the nitrogen atom to which they are attached, may contain 1 to 4 R 8 optionally forming a C5-C8 heterocycloalkyl group optionally substituted by a group; R 7 are each independently selected from H, C-C-alkyl, C(O)-C-C-alkyl, and C-C-haloalkyl; R 8 are each independently ═O, ═S, fluoro, nitro, cyano, or NR 5 R 6 , OR 7 , S.R. 6 , SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , CO2R 6 , C(O)R 6 ,CONR 6 R 6 , C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, and cyclopropyl; R 9 are each independently halo, nitro, cyano, or NR 5 R 6 , OR 7 , S.R. 6, SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , CO2R 6 , C(O)R 6 ,CONR 6 R 6 , C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, and cyclopropyl; R x and R y are each independently H, halo, nitro, cyano, or NR 5 R 6 , OR 7 , S.R. 6 , SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , CO2R 6 , C(O)R 6 ,CONR 6 R 6 , C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C3-C4-cycloalkyl, and 4-membered heterocycloalkyl; m is an integer selected from 0, 1, 2, 3, and 4; Any of the above alkyl, alkylene, alkenyl, or cyclopropyl groups may each independently, where chemically possible, be selected from C1-C4-alkyl, oxo, fluoro, nitro, cyano, NR a R b , OR a , S.R. a , CO2R a , C(O)R a ,CONR a R a , S(O)R a , and S(O)2R a optionally substituted with 1 to 5 substituents selected from the group consisting of: a are each independently selected from H and C-C-alkyl; R bare each independently selected from H, C1-C4-alkyl, C(O)-C1-C4-alkyl, and S(O)2-C1-C4-alkyl).

[0013] In one or more embodiments, the compound of formula (I) may be an enantiomer, a mixture of enantiomers, a racemate, a diastereoisomer, a mixture of diastereoisomers, a geometric isomer, a mixture of geometric isomers, a tautomer, or a mixture of tautomers. The compound of formula (I) may also be in the form of a solvate or hydrate.

[0014] In one embodiment, the compound of formula (I) is a compound of formula (II): [ka] (In the formula, Ring A is independently selected from phenyl, 5-membered heterocyclyl, and 6-membered heterocyclyl; X 4 are independently selected from carbon and nitrogen; X 5 are independently selected from carbon and nitrogen; R 1 is independently selected from C1-C3-alkyl, C1-C3-fluoroalkyl, C3-C4-cycloalkyl, and 4-membered heterocycloalkyl; R 2 are independently selected from 5-membered heterocyclyl, 6-membered heterocyclyl, and phenyl, each of which optionally contains 1 to 4 R 2a substituted with a group; R 2a are each independently ═O, ═S, halo, nitro, cyano, or NR 5 R 6 , OR 7 , S.R. 6 , SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , CO2R 6 , C(O)R 6 ,CONR 6 R 6, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C3-C6 cycloalkyl, and 4- to 6-membered heterocyclyl; R 3 are independently 3a , OR 3b , and NR 6 R 3b Selected from; R 3a are independently H, CN, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C2-C4-haloalkenyl, and C0-C3-alkylene-R 3c Selected from; R 3c are each independently selected from C3-C8-cycloalkyl, C5-C8-cycloalkenyl, 5- to 8-membered heterocycloalkenyl, 3- to 8-membered heterocycloalkyl, phenyl, and 5- or 6-membered heteroaryl; where R 3c When R is cycloalkyl, heterocycloalkyl, cycloalkenyl, or heterocycloalkenyl, 3c is 1 to 4 R 8 optionally substituted by a group; R 3c is phenyl or heteroaryl, R 3c is 1 to 5 R 9 is optionally replaced by; R 3b are independently C1-C4-alkyl, C2-C4-alkylene-O-C1-C4-alkyl, C1-C4-haloalkyl, and C0-C3-alkylene-R 3d Selected from; R 3d are each independently selected from C3-C8-cycloalkyl, 3- to 8-membered heterocycloalkyl, phenyl, and 5- or 6-membered heteroaryl; where R 3d When R is cycloalkyl or heterocycloalkyl, 3d is 1 to 4 R 8 optionally substituted with R3d is phenyl or heteroaryl, R 3d is 1 to 5 R 9 optionally substituted with a group; R 4 are each independently ═O, ═S, halo, nitro, cyano, C0-C4-alkylene-NR 5 R 6 , C0-C4-alkylene-OR 7 , S.R. 6 , SOR 6 , C0-C4-alkylene-S(O)2R 6 , SO2NR 6 R 6 , C0-C4-alkylene-CO2R 6 , C0-C4-alkylene-C(O)R 6 , C0-C4-alkylene-CONR 6 R 6 , C1-C4-alkyl, C1-C4-alkyl-S(O)2R 6 , C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl; R 5 are each independently selected from H, C-C-alkyl, C(O)-C-C-alkyl, and S(O)-C-C-alkyl; or R 5 and R 6 and together with the nitrogen atom to which they are attached form 1 to 4 R 8 forming a C5-C8-heterocycloalkyl group optionally substituted by a group; R 6 are each independently selected from H and C1-C4-alkyl; or two R 6 groups are attached to the same nitrogen, and the two R 6 The groups, together with the nitrogen atom to which they are attached, may contain 1 to 4 R 8 optionally forming a C5-C8-heterocycloalkyl group, optionally substituted by a group; R 7are each independently selected from H, C-C-alkyl, C(O)-C-C-alkyl, and C-C-haloalkyl; R 8 are each independently ═O, ═S, fluoro, nitro, cyano, or NR 5 R 6 , OR 7 , S.R. 6 , SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , CO2R 6 , C(O)R 6 ,CONR 6 R 6 , C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, and cyclopropyl; R 9 are each independently halo, nitro, cyano, or NR 5 R 6 , OR 7 , S.R. 6 , SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , CO2R 6 , C(O)R 6 ,CONR 6 R 6 , C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, and cyclopropyl; m is an integer selected from 0, 1, 2, 3, and 4; Any of the above alkyl, alkylene, alkenyl, or cyclopropyl groups may each independently, where chemically possible, be selected from C1-C4-alkyl, oxo, fluoro, nitro, cyano, NR a R b , OR a , S.R. a , CO2R a , C(O)R a ,CONR a R a , S(O)R a , and S(O)2Ra optionally substituted with 1 to 5 substituents selected from the group consisting of: a are each independently selected from H and C-C-alkyl; R b are each independently selected from H, C1-C4-alkyl, C(O)-C1-C4-alkyl, and S(O)2-C1-C4-alkyl).

[0015] In one embodiment, the compound of formula (I) is a compound of formula (III): [ka] (In the formula, X 4 , X 5 , ring A, R 2a , R 3 , R 4 and m are as described above for compounds of formula (I); [ka] is independently selected from a single bond and a double bond; R 2b is independently selected from H, C1-C4-alkyl, C3-C6 cycloalkyl, and 4- to 6-membered heterocyclyl; X 1 are independently selected from carbon and nitrogen; X 2 and X 3 are each independently selected from carbon, nitrogen, oxygen, and sulfur; 2 or X 3 If one of the is oxygen or sulfur, X 2 and X 3 The other of these must be carbon; [ka] If is a double bond, X 2 and X 3 are each independently selected from carbon and nitrogen; n is an integer independently selected from 0, 1, 2, 3, and 4.2b may be H.

[0016] In one embodiment, the compound of formula (I) is a compound of formula (IV): [ka] (In the formula, X 4 , X 5 , ring A, R 2a , R 3 , R 4 , and m are as described above for compounds of formula (I), and n1 is independently an integer selected from 0, 1, and 2).

[0017] In one embodiment, the compound of formula (I) is a compound of formula (V): [ka] (In the formula, X 4 , X 5 , ring A, R 2a , R 3 , R 4 , and m are as described above for compounds of formula (I), and n2 is independently an integer selected from 0, 1, 2, 3, and 4).

[0018] In one embodiment, the compound of formula (I) is a compound of formula (VI): [ka] (In the formula, X 4 , X 5 , ring A, R 2a , R 3 , R 4 and m are as described above for compounds of formula (I); [ka] is independently selected from a single bond and a double bond; X 1 and X 8 are each independently selected from carbon and nitrogen; and n is an integer independently selected from 0, 1, 2, 3, and 4.

[0019] In one embodiment, the compound of formula (I) is a compound of formula (VII): [ka] (In the formula, X 4 , X 5 , ring A, R 2a , R 3 , R 4 and m are as described above for compounds of formula (I); X 9 , X 10 , and X 11 are each independently selected from carbon and nitrogen; and n is an integer independently selected from 0, 1, 2, 3, 4, and 5.

[0020] In one embodiment, the compound of formula (I) is a compound of formula (VIII): [ka] (In the formula, X 4 , X 5 , ring A, R 1 , R 2a , R 3 , R 4 and m are as described above for compounds of formula (I); and n is an integer independently selected from 0, 1, 2, 3, 4, and 5.

[0021] In one embodiment, the compound of formula (I) is a compound of formula (IX): [ka] (In the formula, R 2 , R 3b , and R 4 is as described above for compounds of formula (I); m is an integer selected from 0, 1, or 2; R 4aare independently selected from H, C-C-alkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl. 4a is independently selected from H, C1-C4-alkyl, and cyclopropyl.

[0022] In one embodiment, the compound of formula (I) is a compound of formula (X): [ka] (In the formula, R 2 , R 3a , and R 4 is as described above for compounds of formula (I); m is an integer selected from 0, 1, or 2; R 4a are independently selected from H, C1-C4-alkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl. 4a may be independently selected from H, C1-C4-alkyl, and cyclopropyl.

[0023] In one embodiment, the compound of formula (I) is a compound of formula (XI): [ka] (In the formula, R 2 and R 4 is as described above for compounds of formula (I); m is an integer selected from 0, 1, or 2; p is an integer selected from 0, 1, 2, 3, 4, and 5; R 4a are independently selected from H, C1-C4-alkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl. 4a may be independently selected from H, C1-C4-alkyl, and cyclopropyl.

[0024] In one embodiment, the compound of formula (I) is a compound of formula (XII): [ka] (In the formula, R 2a , R 3b , and R 4 is as described above for compounds of formula (I), [ka] R 2b , X 1 , X 2 , X 3 and n is as described above for compounds of formula (III); m is an integer selected from 0, 1, or 2; R 4a are independently selected from H, C1-C4-alkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl. 2b may be H. 4a may be independently selected from H, C1-C4-alkyl, and cyclopropyl.

[0025] In one embodiment, the compound of formula (I) is a compound of formula (XIII): [ka] (In the formula, R 2a , R 3b , R 4 and m are as described above for compounds of formula (I); [ka] is independently selected from a single bond and a double bond; X 1 and X 8 are each independently selected from carbon and nitrogen; n is an integer independently selected from 0, 1, 2, 3, and 4; R 4aare independently selected from H, C1-C4-alkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl. 4a may be independently selected from H, C1-C4-alkyl, and cyclopropyl.

[0026] In one embodiment, the compound of formula (I) is a compound of formula (XIV): [ka] (In the formula, R 2a , R 3b , R 4 and m are as described above for formula (I); X 9 , X 10 , and X 11 are each independently selected from carbon and nitrogen; n is an integer independently selected from 0, 1, 2, 3, 4, and 5; R 4a are independently selected from H, C1-C4-alkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl. 4a may be independently selected from H, C1-C4-alkyl, and cyclopropyl.

[0027] In one embodiment, the compound of formula (I) is a compound of formula (XV): [ka] (In the formula, R 2a , R 3b , R 4 and m are as described above for formula (I); n is an integer independently selected from 0, 1, 2, 3, 4, and 5; R 4a are independently selected from H, C1-C4-alkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl. 4a may be independently selected from H, C1-C4-alkyl, and cyclopropyl.

[0028] In one embodiment, the compound of formula (I) is a compound of formula (XVI): [ka] (In the formula, R 2a , R 3b , R 4 and m are as described above for compounds of formula (I); [ka] , R 2b , X 1 , X 2 , X 3 and n are as described above for compounds of formula (III). 2b may be H.

[0029] In one embodiment, the compound of formula (I) is a compound of formula (XVII): [ka] (In the formula, X 4 , X 5 , R 2a , R 3 , and R 4 is as described above for compounds of formula (I), [ka] , R 2b , X 1 , X 2 , X 3 and n is as described above for compounds of formula (III); Each [ka] is independently selected from a single bond and a double bond; X 6 are independently selected from carbon and nitrogen; X 7are independently selected from carbon and nitrogen; n is an integer selected from 0, 1, 2, or 3. 2b may be H.

[0030] In one embodiment, the compound of formula (I) is a compound of formula (XVIII): [ka] (In the formula, X 4 , X 5 , R 2a , and R 4 is as described above for compounds of formula (I), [ka] , R 2b , X 1 , X 2 , X 3 and n is as described above for compounds of formula (III); Each [ka] is independently selected from a single bond and a double bond; X 6 are independently selected from carbon and nitrogen; X 7 are independently selected from carbon and nitrogen; m is an integer selected from 0, 1, 2, or 3; and p is an integer selected from 0, 1, 2, 3, 4, and 5.

[0031] In one embodiment, the compound of formula (I) is a compound of formula (XIX): [ka] (In the formula, R 2a , R 3b , and R 4 is as described above for compounds of formula (I); n1 is independently an integer selected from 0, 1, or 2; m is an integer selected from 0, 1, or 2; R 4a are independently selected from H, methyl, cyclopropyl, and oxetan-3-yl. 4a may be selected from H, methyl, and cyclopropyl.

[0032] In one embodiment, the compound of formula (I) is a compound of formula (XX): [ka] (In the formula, R 2a , R 3b , R 4 , and m are as described above for compounds of formula (I), and n1 is independently an integer selected from 0, 1, and 2).

[0033] In one embodiment, the compound of formula (I) is a compound of formula (XXI): [ka] (In the formula, X 4 , X 5 , R 2a , R 3 , R 4 is as described above for compounds of formula (I); Each [ka] is independently selected from a single bond and a double bond; X 6 are independently selected from carbon and nitrogen; X 7 are independently selected from carbon and nitrogen; n1 is independently an integer selected from 0, 1, and 2; m is an integer selected from 0, 1, 2, or 3).

[0034] In one embodiment, the compound of formula (I) is a compound of formula (XXII): [ka] (In the formula, X 4 , X 5 , R 2a , R 4 , and R 9 is as described above for compounds of formula (I); [ka] is independently selected from a single bond and a double bond; X 6 are independently selected from carbon and nitrogen; X 7 are independently selected from carbon and nitrogen; n1 is an integer selected from 0, 1, and 2; m is an integer selected from 0, 1, 2, or 3; and p is an integer selected from 0, 1, 2, 3, 4, and 5.

[0035] In one embodiment, the compound of formula (I) is a compound of formula (XXIII): [ka] (In the formula, X 4 , X 5 , R 2a , R 4 , and R 9 is as described above for compounds of formula (I), [ka] is independently selected from a single bond and a double bond; X 1 , X 6 , X 7 , and X 8 are each independently selected from carbon and nitrogen; n is an integer selected from 0, 1, 2, 3, or 4; m is an integer selected from 0, 1, 2, or 3; and p is an integer selected from 0, 1, 2, 3, 4, and 5.

[0036] In one embodiment, the compound of formula (I) is a compound of formula (XXIV): [ka] (In the formula, X 4 , X 5 , R 2a , R 4 , and R 9 is as described above for compounds of formula (I), [ka] is independently selected from a single bond and a double bond; X 6 , X 7 , X 9 , X 10 , and X 11 are each independently selected from carbon and nitrogen; n is an integer selected from 0, 1, 2, 3, 4, or 5; m is an integer selected from 0, 1, 2, or 3; and p is an integer selected from 0, 1, 2, 3, 4, and 5.

[0037] In one embodiment, the compound of formula (I) is a compound of formula (XXV): [ka] (In the formula, X 4 , X 5 , R 2a , R 4 , and R 9 is as described above for compounds of formula (I), [ka] is independently selected from a single bond and a double bond; X 6and X 7 are each independently selected from carbon and nitrogen; n is an integer selected from 0, 1, 2, 3, 4, or 5; m is an integer selected from 0, 1, 2, or 3; and p is an integer selected from 0, 1, 2, 3, 4, and 5.

[0038] In one embodiment, the compound of formula (I) is a compound of formula (XXVI): [ka] (In the formula, X 4 , X 5 , ring A, R 2a , R 3 , R 4 and m are as described above for compounds of formula (I), and R 2b is as described above for compounds of formula (III), and n7 is independently an integer selected from 0, 1, and 2).

[0039] In one embodiment, the compound of formula (I) is a compound of formula (XXVII): [ka] (In the formula, X 4 , X 5 , R 2a , R 4 , and R 9 is as described above for compounds of formula (I), and R 2b is as described above for compounds of formula (III); [ka] is independently selected from a single bond and a double bond; X 6 are independently selected from carbon and nitrogen; X 7 are independently selected from carbon and nitrogen; n7 is an integer selected from 0, 1, and 2; m is an integer selected from 0, 1, 2, or 3; and p is an integer selected from 0, 1, 2, 3, 4, and 5.

[0040] In one embodiment, the compound of formula (I) is a compound of formula (XXVIII): [ka] (In the formula, R 2a , R 3b , and R 4 is as described above for compounds of formula (I), and R 2b is as described above for compounds of formula (III); n7 is independently an integer selected from 0, 1, or 2; m is an integer selected from 0, 1, or 2; R 4a are independently selected from H, methyl, cyclopropyl and oxetan-3-yl.

[0041] In one embodiment, the compound of formula (I) is a compound of formula (XXIX): [ka] (In the formula, R 2a , R 3b , R 4 and m are as described above for compounds of formula (I), and R 2b is as described above for compounds of formula (III), and n7 is independently an integer selected from 0, 1, and 2).

[0042] In one embodiment, the compound of formula (I) is a compound of formula (XXX): [ka] (In the formula, X 4 , X 5 , R 2a , R 3 , R 4 is as described above for compounds of formula (I), and R2b is as described above for compounds of formula (III); Each [ka] is independently selected from a single bond and a double bond; X 6 are independently selected from carbon and nitrogen; X 7 are independently selected from carbon and nitrogen; n7 is independently an integer selected from 0, 1, and 2; m is an integer selected from 0, 1, 2, or 3).

[0043] In one embodiment, the compound of formula (I) is a compound of formula (XXXI): [ka] (In the formula, R 2a , R 4 , R 9 is as described above for compounds of formula (I), and R 2b is as described above for compounds of formula (III); m is an integer selected from 0, 1, and 2; p is an integer selected from 0, 1, 2, 3, 4, and 5; n7 is independently an integer selected from 0, 1, and 2; R 4a are independently selected from H, C1-C4-alkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl.

[0044] In one embodiment, the compound of formula (I) is a compound of formula (XXXII): [ka] (In the formula, R 2a , R 4 , R 9 is as described above for formula (I); m is an integer selected from 0, 1, and 2; p is an integer selected from 0, 1, 2, 3, 4, and 5; n is an integer independently selected from 0, 1, 2, 3, 4, and 5; R 4a are independently selected from H, C1-C4-alkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl.

[0045] In one embodiment, the compound of formula (I) is a compound of formula (XXXIII): [ka] (In the formula, R 2a , R 4 , R 9 is as described above for compounds of formula (I), and R 2b is as described above for compounds of formula (III); m is an integer selected from 0, 1, and 2; p is an integer selected from 0, 1, 2, 3, 4, and 5; n8 is independently an integer selected from 0, 1, and 2; R 4a are independently selected from H, C1-C4-alkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl.

[0046] In one embodiment, the compound of formula (I) is a compound of formula (XXXIV): [ka] (In the formula, X 4 , X 5 , ring A, R 2a , R 3 , R 4 and m are as described above for compounds of formula (I), and R 2b is as described above for compounds of formula (III), and n8 is independently an integer selected from 0, 1, and 2).

[0047] In one embodiment, the compound of formula (I) is a compound of formula (XXXV): [ka] (In the formula, R 2a , R 4 , R 9 is as described above for formula (I); m is an integer selected from 0, 1, and 2; p is an integer selected from 0, 1, 2, 3, 4, and 5; n14 is independently an integer selected from 0, 1, 2, 3, and 4; R 4a are independently selected from H, C1-C4-alkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl.

[0048] In one embodiment, the compound of formula (I) is a compound of formula (XXXVI): [ka] In the formula, X 4 , X 5 , ring A, R 2a , R 3 , R 4 , and m are as described above for compounds of formula (I), and n14 is independently an integer selected from 0, 1, 2, 3, and 4).

[0049] In one embodiment, the compound of formula (I) is a compound of formula (XXXVII): [ka] (In the formula, R 2a , R 4 , R 9 is as described above for formula (I); m is an integer selected from 0, 1, and 2; p is an integer selected from 0, 1, 2, 3, 4, and 5; n is an integer independently selected from 0, 1, 2, 3, 4, and 5; R 4a are independently selected from H, C1-C4-alkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl.

[0050] In one embodiment, the compound of formula (I) is a compound of formula (XXXVIII): [ka] (In the formula, R 2a , R 4 , R 9 is as described above for formula (I); m is an integer selected from 0, 1, and 2; p is an integer selected from 0, 1, 2, 3, 4, and 5; n14 is independently an integer selected from 0, 1, 2, 3, and 4; R 4a are independently selected from H, C1-C4-alkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl.

[0051] The following embodiments apply to any compound of Formula (I)-(XXXVIII). These embodiments are independent and interchangeable. Any one embodiment can be combined with any other embodiment, where chemically permissible. In other words, any of the features described in the following embodiments can be combined (where chemically permissible) with features described in one or more other embodiments. In particular, if a compound is exemplified or described herein, any two or more of the embodiments listed below, including that compound and expressed at any level of generality, can be combined to provide further embodiments that form part of the present disclosure.

[0052] In one embodiment, R 1 is C1-C3-alkyl. In one embodiment, R 1is C1-C3-fluoroalkyl. In one embodiment, R 1 is C-cycloalkyl. In one embodiment, R 1 are independently selected from C1-alkyl, C1-fluoroalkyl, and C3-cycloalkyl. Preferably, R 1 is a C1-alkyl, i.e., methyl.

[0053] In one embodiment, R 2 teeth [ka] (wherein: [ka] are independently selected from a single bond and a double bond; X 1 are independently selected from carbon and nitrogen; X 2 and X 3 are each independently selected from carbon, nitrogen, oxygen, and sulfur; 2 or X 3 If one of the is oxygen or sulfur, X 2 and X 3 The other of these must be carbon; [ka] If is a double bond, X 2 and X 3 are each independently selected from carbon and nitrogen; and n is an integer independently selected from 0, 1, 2, 3, and 4.

[0054] In one embodiment, R 2 teeth, [ka] (wherein: [ka] are independently selected from a single bond and a double bond; R 2b are independently selected from H, C1-C4-alkyl, C3-C6 cycloalkyl, and 4- to 6-membered heterocyclyl.

[0055] In one embodiment, R 2 teeth [ka] is.

[0056] In one embodiment, X 1 is carbon. In one embodiment, X 1 is nitrogen.

[0057] In one embodiment, X 2 and X 3 are each independently selected from carbon and nitrogen. 2 and X 3 are each independently selected from carbon and oxygen. 2 and X 3 are carbons.

[0058] In one embodiment, R 2 is 1 to 4 R 2a is a 5-membered heterocyclyl group optionally substituted with a group.

[0059] In one embodiment, R 2 teeth [ka] wherein n1 is independently an integer selected from 0, 1, and 2.

[0060] In one embodiment, R 2 teeth [ka] wherein n2 is independently an integer selected from 0, 1, 2, and 3.

[0061] In one embodiment, R 2 teeth [ka] wherein n3 is independently an integer selected from 0, 1, and 2.

[0062] In one embodiment, R 2 teeth [ka] wherein n4 is independently an integer selected from 0, 1, and 2.

[0063] In one embodiment, R 2 teeth [ka] wherein n5 is independently an integer selected from 0 and 1.

[0064] In one embodiment, R 2 teeth [ka] wherein n6 is an integer independently selected from 0, 1, 2, 3, and 4.

[0065] In one embodiment, R 2 teeth [ka] wherein n7 is independently an integer selected from 0, 1, 2, and 3.

[0066] In one embodiment, R 2 teeth [ka] wherein n8 is independently an integer selected from 0, 1, 2, and 3.

[0067] In one embodiment, R 2 teeth [ka] wherein n9 is an integer independently selected from 0, 1, and 2.

[0068] In one embodiment, R 2 teeth [ka] wherein n11 is independently an integer selected from 0, 1, and 2.

[0069] R 2b is independently selected from H, C1-C4-alkyl, C3-C6 cycloalkyl, and 4- to 6-membered heterocyclyl. 2b may be H. 2b may be selected from H, C1-C4-alkyl, and cyclopropyl. 2b may be selected from C1-C4-alkyl and cyclopropyl. 2b may be C1-C4-alkyl, for example methyl. 2b R may be a 4- to 6-membered heterocyclyl. 2b may be oxetanyl or azetidinyl. In one embodiment, R 2b is oxetanyl. In one embodiment, R 2b is oxetan-3-yl.

[0070] In one embodiment, R 2 teeth [ka] wherein n1 is independently an integer selected from 0, 1, and 2.

[0071] In one embodiment, R 2 teeth [ka] wherein n2 is independently an integer selected from 0, 1, 2, and 3.

[0072] In one embodiment, R 2 teeth [ka] wherein n3 is independently an integer selected from 0, 1, and 2.

[0073] In one embodiment, R 2 teeth [ka] wherein n4 is independently an integer selected from 0, 1, and 2.

[0074] In one embodiment, R 2 teeth [ka] wherein n5 is independently an integer selected from 0 and 1.

[0075] In one embodiment, R 2 teeth [ka] wherein n6 is an integer independently selected from 0, 1, 2, 3, and 4.

[0076] In one embodiment, R 2 teeth [ka] wherein n7 is independently an integer selected from 0, 1, 2, and 3.

[0077] In one embodiment, R 2 teeth [ka] wherein n8 is independently an integer selected from 0, 1, 2, and 3. In one embodiment, R 2a is not C1-C4-alkyl. In one embodiment, R 2a is not methyl.

[0078] In one embodiment, R 2 teeth [ka] wherein n9 is an integer independently selected from 0, 1, and 2.

[0079] In one embodiment, R 2 teeth [ka] wherein n10 is independently an integer selected from 0, 1, and 2.

[0080] In one embodiment, R 2 teeth [ka] wherein n11 is independently an integer selected from 0, 1, and 2.

[0081] In one embodiment, R 2 teeth [ka] wherein n12 is independently an integer selected from 0, 1, 2, 3, and 4.

[0082] In one embodiment, R 2 teeth [ka] wherein n13 is independently an integer selected from 0, 1, 2, 3, 4, and 5.

[0083] In one embodiment, R 2 teeth [ka] wherein n14 is independently an integer selected from 0, 1, 2, 3, and 4.

[0084] In one embodiment, R 2 teeth [ka] wherein n14 is independently an integer selected from 0, 1, 2, 3, and 4.

[0085] In one embodiment, R 2 teeth [ka] wherein n14 is independently an integer selected from 0, 1, 2, 3, and 4.

[0086] In one embodiment, R 2 teeth [ka] wherein n15 is independently an integer selected from 0, 1, 2, and 3.

[0087] In one embodiment, R 2 teeth [ka] wherein n15 is independently an integer selected from 0, 1, 2, and 3.

[0088] In one embodiment, R 2 teeth [ka] wherein n15 is independently an integer selected from 0, 1, 2, and 3.

[0089] In one embodiment, R 2 teeth [ka] wherein n15 is independently an integer selected from 0, 1, 2, and 3.

[0090] In one embodiment, R 2 teeth [ka] wherein n16 is independently an integer selected from 0, 1, 2, 3, and 4.

[0091] In one embodiment, R 2 is a substituted or unsubstituted imidazolidine or a substituted or unsubstituted imidazoline.

[0092] In one embodiment, R 2 is a substituted or unsubstituted thiazole or a substituted or unsubstituted isothiazole.

[0093] In one embodiment, R 2 is a substituted or unsubstituted thiazole.

[0094] In one embodiment, R 2 is a substituted or unsubstituted pyridazine (unsaturated or saturated), a substituted or unsubstituted pyrimidine (unsaturated or saturated), a substituted or unsubstituted pyrazine, or a substituted or unsubstituted piperazine.

[0095] In one embodiment, R 2 is a substituted or unsubstituted triazine or a substituted or unsubstituted triazinane.

[0096] In one embodiment, R 2 is a substituted or unsubstituted pyridone.

[0097] In one embodiment, R 2 is a substituted or unsubstituted pyrazolidine or a substituted or unsubstituted pyrazoline.

[0098] R 2 In embodiments where R is shown to contain an NH group in the ring, the nitrogen atom may be, where chemically possible, R as defined herein. 2a substituted with NR groups and, where chemically possible, 2a It should be understood that the group may be provided.

[0099] In one embodiment, R 2a are each independently ═O, halo, nitro, cyano, or NR 5 R 6 , OR 7 , S.R. 6 , S(O)2R 6 , SO2NR 6 R 6 , CO2R 6 , C(O)R 6 ,CONR 6 R 6 , C1-C4-alkyl, C1-C4-haloalkyl, C3-C6 cycloalkyl, and 4- to 6-membered heterocyclyl.

[0100] In one embodiment, R 2a are each independently: =O, halo, cyano, COR 6 , C(O)R 6 , C1-C4-alkyl, C1-C4-haloalkyl, C3-C6 cycloalkyl, and 4- to 6-membered heterocyclyl.

[0101] In one embodiment, R 2a are each independently =O, halo, cyano, S(O)R 6 , CO2R 6 ,CONR 6 R 6 , C1-C4-alkyl, C1-C4-haloalkyl, C3-C6 cycloalkyl, and 4- to 6-membered heterocyclyl.

[0102] In one embodiment, R2a are each independently =O, halo, cyano, S(O)R 6 , CO2R 6 ,CONR 6 R 6 , C1-C2-alkyl, C1-C2-haloalkyl, C3-C4 cycloalkyl, and 4- to 6-membered heterocyclyl.

[0103] In one embodiment, R 2a are each independently =O, halo, cyano, S(O)R 6 , CO2R 6 ,CONR 6 R 6 , C1-C2-alkyl, C1-C2-haloalkyl, cyclopropyl, cyclobutyl, and 4-membered heterocyclyl.

[0104] In one embodiment, R 2a are each independently =O, halo, cyano, S(O)R 6 , CO2R 6 ,CONR 6 R 6 , C1-C2-alkyl, C1-C2-haloalkyl, and 4-membered heterocyclyl.

[0105] In one embodiment, R 2a are each independently: =O, halo, OR 7 , C1-C4-alkyl, and C1-C4-haloalkyl.

[0106] In one embodiment, R 2a are each independently halo, OR 7 , C1-C4-alkyl, and C1-C4-haloalkyl. In one embodiment, R 2a are each independently selected from halo, C-C-alkyl, and C-C-haloalkyl. 2a are each independently selected from C-alkyl and C-haloalkyl. 2a is C1-C4-alkyl, for example methyl.

[0107] In one embodiment, n is an integer selected from 0, 1 and 2. In one embodiment, n is 2. In one embodiment, n is 0. Preferably, n is 1. In one embodiment, when n is 1, R 2 is X 3 is bonded to.

[0108] In one embodiment, n1 is 0. Preferably, n1 is 1. In one embodiment, when n1 is 1, R 2a is X 3 is bonded to.

[0109] In one embodiment, n is an integer selected from 0, 1 and 2. In one embodiment, n2 is 2. In one embodiment, n2 is 0. In one embodiment, n2 is 1.

[0110] In one embodiment, n3 is 0. Preferably, n3 is 1. In one embodiment, when n3 is 1, R 2a is X 3 is bonded to.

[0111] In one embodiment, n4 is 2. In one embodiment, n4 is 0. In one embodiment, n4 is 1.

[0112] In one embodiment, n5 is 0. In one embodiment, n5 is 1.

[0113] In one embodiment, n6 is 0. In one embodiment, n6 is 1. In one embodiment, n6 is 2. In one embodiment, n6 is 3.

[0114] In one embodiment, n7 is 0. In one embodiment, n7 is 1. In one embodiment, n7 is 2. In one embodiment, n7 is 3.

[0115] In one embodiment, n8 is 0. In one embodiment, n8 is 1. In one embodiment, n8 is 2. In one embodiment, n8 is 3.

[0116] In one embodiment, n9 is 0. In one embodiment, n9 is 1. In one embodiment, n9 is 2.

[0117] In one embodiment, n10 is 0. In one embodiment, n10 is 1. In one embodiment, n10 is 2.

[0118] In one embodiment, n11 is 0. In one embodiment, n11 is 1. In one embodiment, n11 is 2.

[0119] In one embodiment, n12 is 0. In one embodiment, n12 is 1. In one embodiment, n12 is 2.

[0120] In one embodiment, n13 is 0. In one embodiment, n13 is 1. In one embodiment, n13 is 2. In one embodiment, n13 is 3.

[0121] In one embodiment, n14 is 0. In one embodiment, n14 is 1. In one embodiment, n14 is 2. In one embodiment, n14 is 3.

[0122] In one embodiment, n15 is 0. In one embodiment, n15 is 1. In one embodiment, n15 is 2. In one embodiment, n15 is 3.

[0123] In one embodiment, n16 is 0. In one embodiment, n16 is 1. In one embodiment, n16 is 2.

[0124] In one embodiment, R 2 teeth, [ka] is selected from.

[0125] In one embodiment, R 2 teeth, [ka] is selected from.

[0126] In one embodiment, R 2 teeth [ka] is.

[0127] In one embodiment, R 2 teeth, [ka] is selected from.

[0128] In one embodiment, R 2 teeth, [ka] is selected from.

[0129] In one embodiment, R 2 teeth, [ka] is selected from.

[0130] In one embodiment, X 4 is carbon. In one embodiment, X 4 is nitrogen.

[0131] In one embodiment, X 5 is carbon. In one embodiment, X 5 is nitrogen.

[0132] In one embodiment, ring A is a phenyl ring. In one embodiment, ring A is a 5- or 6-membered heterocyclyl. In one embodiment, ring A is a 5- or 6-membered heteroaryl. In one embodiment, ring A is a 5-membered heteroaryl ring. In one embodiment, ring A is a 6-membered heterocyclyl ring. In one embodiment, ring A is a 6-membered heteroaryl ring.

[0133] In one embodiment, when ring A is a 5-membered heterocyclyl, it is not pyrrolidone.

[0134] In one embodiment, Ring A is phenyl. In one embodiment, Ring A is pyridone. The pyridine may be substituted on the nitrogen with a C1-C4-alkyl group, cyclopropyl, cyclobutyl, or a 4-membered heterocycloalkyl group. The pyridone may be substituted on the nitrogen with either a C1-C4-alkyl group or a cyclopropyl group. In one embodiment, Ring A is an N-C1-C4-alkylpyridone. In one embodiment, Ring A is pyridine. In one embodiment, Ring A is pyrrole. In one embodiment, Ring A is imidazole. In one embodiment, Ring A is pyrazole. In one embodiment, Ring A is triazole. In one embodiment, Ring A is tetrazole.

[0135] In one embodiment, [ka] teeth [ka] and In the formula, R 4a is H, C1-C4-alkyl (e.g., methyl), cyclopropyl, cyclobutyl, 4- to 6-membered heterocycloalkyl, SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , C0-C4-alkylene-CO2R 6 , C0-C4-alkylene-C(O)R 6 , C0-C4-alkylene-CONR 6 R 6 , C1-C4-alkyl-S(O)2R 6 , C2-C4-Alkylene-NR 5 R 6 , C2-C4-alkylene-OR 7 , and cyclopropyl-OR a Optionally, R3 is OR 3b In one embodiment, heterocycloalkyl is oxetanyl or azetidinyl.

[0136] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is H, C1-C4-alkyl (e.g., methyl), cyclopropyl, SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , C0-C4-alkylene-CO2R 6 , C0-C4-alkylene-C(O)R 6 , C0-C4-alkylene-CONR 6 R 6 , C1-C4-alkyl-S(O)2R 6 , C2-C4-Alkylene-NR 5 R 6 , C2-C4-alkylene-OR 7 , and cyclopropyl-OR a Optionally, R 3 is OR 3b is.

[0137] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is selected from H, C-C-alkyl (e.g., methyl), cyclopropyl, cyclobutyl, and 4-membered heterocycloalkyl, and optionally R 3 is OR 3b R 4amay be selected from C1-C4-alkyl (e.g., methyl), cyclopropyl, and oxetan-3-yl.

[0138] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is selected from H, C-C-alkyl (e.g., methyl), and cyclopropyl, and optionally R 3 is OR 3b R 4a may be selected from C1-C4-alkyl (e.g. methyl), and cyclopropyl.

[0139] In one embodiment, [ka] teeth [ka] and In the formula, R 4a is H, C1-C4-alkyl (e.g., methyl), cyclopropyl, cyclobutyl, 4-membered heterocycloalkyl, SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , C0-C4-alkylene-CO2R 6 , C0-C4-alkylene-C(O)R 6 , C0-C4-alkylene-CONR 6 R 6 , C1-C4-alkyl-S(O)2R 6 , C2-C4-Alkylene-NR 5 R 6 , C2-C4-alkylene-OR 7 , and cyclopropyl-OR a Optionally, R3 is OR 3b is.

[0140] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is H, C1-C4-alkyl (e.g., methyl), cyclopropyl, SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , C0-C4-alkylene-CO2R 6 , C0-C4-alkylene-C(O)R 6 , C0-C4-alkylene-CONR 6 R 6 , C1-C4-alkyl-S(O)2R 6 , C2-C4-Alkylene-NR 5 R 6 , C2-C4-alkylene-OR 7 , and cyclopropyl-OR a Optionally, R 3 is OR 3b is.

[0141] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is selected from H, C-C-alkyl (e.g., methyl), cyclopropyl, cyclobutyl, and 4-membered heterocycloalkyl, and optionally R 3 is OR 3b R 4amay be selected from C1-C4-alkyl (e.g., methyl), cyclopropyl, and oxetan-3-yl.

[0142] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is selected from H, C-C-alkyl (e.g., methyl), and cyclopropyl, and optionally R 3 is OR 3b R 4a may be selected from C1-C4-alkyl (e.g. methyl), and cyclopropyl.

[0143] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is H, C1-C4-alkyl (e.g., methyl), cyclopropyl, cyclobutyl, 4-membered heterocycloalkyl, SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , C0-C4-alkylene-CO2R 6 , C0-C4-alkylene-C(O)R 6 , C0-C4-alkylene-CONR 6 R 6 , C1-C4-alkyl-S(O)2R 6 , C2-C4-Alkylene-NR 5 R 6 , C2-C4-alkylene-OR 7 , and cyclopropyl-OR a Optionally, R3 is OR 3b is.

[0144] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is H, C1-C4-alkyl (e.g., methyl), cyclopropyl, SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , C0-C4-alkylene-CO2R 6 , C0-C4-alkylene-C(O)R 6 , C0-C4-alkylene-CONR 6 R 6 , C1-C4-alkyl-S(O)2R 6 , C2-C4-Alkylene-NR 5 R 6 , C2-C4-alkylene-OR 7 , and cyclopropyl-OR a Optionally, R 3 is OR 3b is.

[0145] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is selected from H, C-C-alkyl (e.g., methyl), cyclopropyl, cyclobutyl, and 4-membered heterocycloalkyl, and optionally R 3 is OR 3b R 4amay be selected from C1-C4-alkyl (e.g., methyl), cyclopropyl, and oxetan-3-yl.

[0146] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is selected from H, C-C-alkyl (e.g., methyl), and cyclopropyl, and optionally R 3 is OR 3b R 4a may be selected from C1-C4-alkyl (e.g. methyl), and cyclopropyl.

[0147] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is H, C1-C4-alkyl (e.g., methyl), cyclopropyl, cyclobutyl, 4-membered heterocycloalkyl, SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , C0-C4-alkylene-CO2R 6 , C0-C4-alkylene-C(O)R 6 , C0-C4-alkylene-CONR 6 R 6 , C1-C4-alkyl-S(O)2R 6 , C2-C4-Alkylene-NR 5 R 6 , C2-C4-alkylene-OR 7 , and cyclopropyl-OR a Optionally, R3 is OR 3b is.

[0148] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is H, C1-C4-alkyl (e.g., methyl), cyclopropyl, SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , C0-C4-alkylene-CO2R 6 , C0-C4-alkylene-C(O)R 6 , C0-C4-alkylene-CONR 6 R 6 , C1-C4-alkyl-S(O)2R 6 , C2-C4-Alkylene-NR 5 R 6 , C2-C4-alkylene-OR 7 , and cyclopropyl-OR a Optionally, R 3 is OR 3b is.

[0149] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is selected from H, C-C-alkyl (e.g., methyl), cyclopropyl, cyclobutyl, and 4-membered heterocycloalkyl, and optionally R 3 is OR 3b R 4amay be selected from C1-C4-alkyl (e.g., methyl), cyclopropyl, and oxetan-3-yl.

[0150] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is selected from H, C-C-alkyl (e.g., methyl), and cyclopropyl, and optionally R 3 is OR 3b R 4a may be selected from C1-C4-alkyl (e.g. methyl), and cyclopropyl.

[0151] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is H, C1-C4-alkyl (e.g., methyl), cyclopropyl, cyclobutyl, 4-membered heterocycloalkyl, SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , C0-C4-alkylene-CO2R 6 , C0-C4-alkylene-C(O)R 6 , C0-C4-alkylene-CONR 6 R 6 , C1-C4-alkyl-S(O)2R 6 , C2-C4-Alkylene-NR 5 R 6 , C2-C4-alkylene-OR 7 , and cyclopropyl-OR a Optionally, R3 is OR 3b is.

[0152] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is H, C1-C4-alkyl (e.g., methyl), cyclopropyl, SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , C0-C4-alkylene-CO2R 6 , C0-C4-alkylene-C(O)R 6 , C0-C4-alkylene-CONR 6 R 6 , C1-C4-alkyl-S(O)2R 6 , C2-C4-Alkylene-NR 5 R 6 , C2-C4-alkylene-OR 7 , and cyclopropyl-OR a Optionally, R 3 is OR 3b is.

[0153] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is selected from H, C-C-alkyl (e.g., methyl), cyclopropyl, cyclobutyl, and 4-membered heterocycloalkyl, and optionally R 3 is OR 3b R 4amay be selected from C1-C4-alkyl (e.g., methyl), cyclopropyl, and oxetan-3-yl.

[0154] In one embodiment, [ka] teeth [ka] and; In the formula, R 4a is selected from H, C-C-alkyl (e.g., methyl), and cyclopropyl, and optionally R 3 is OR 3b R 4a may be selected from C1-C4-alkyl (e.g. methyl), and cyclopropyl.

[0155] In one embodiment, [ka] teeth [ka] and optionally, R 3 is OR 3b is.

[0156] In one embodiment, [ka] teeth [ka] and optionally, R 3 is R 3a is.

[0157] In one embodiment, [ka] teeth [ka] and; In the formula, R 4b is S(O)2R 6 , C1-C4-alkyl, C1-C4-alkyl-S(O)2R 6 , C1-C4-haloalkyl, cyclopropyl, and cyclobutyl; and optionally R 3 is R 3a is.

[0158] In one embodiment, [ka] teeth [ka] and; In the formula, R 4b is S(O)2R 6 , C1-C4-alkyl, C1-C4-alkyl-S(O)2R 6 , C-C-haloalkyl, and cyclopropyl; optionally, R 3 is R 3a is.

[0159] In one embodiment, [ka] teeth [ka] and optionally, R 3 is R 3a is.

[0160] In one embodiment, [ka] teeth [ka] and optionally, R3 is R 3a is.

[0161] In one embodiment, [ka] teeth [ka] wherein: m is an integer selected from 0, 1, and 2; p is an integer selected from 0, 1, 2, 3, 4, and 5; R 4a are independently selected from H, C1-C4-alkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl.

[0162] In one embodiment, R 3 are independently 3a and OR 3b In one embodiment, R 3 is R 3a In one embodiment, R 3 is OR 3b When ring A is a 5-membered heteroaryl group, R 3 is R 3a When ring A is a pyridone group, R 3 is R 3a When ring A is phenyl or pyridone, R 3 is OR 3b may be.

[0163] In one embodiment, R 3a are independently H, CN, C1-C4-alkyl, C2-C4-alkenyl, C1-C4-haloalkyl, C2-C4-haloalkenyl, and C0-C3-alkylene-R 3c Selected from; R 3care each independently selected from C3-C8-cycloalkyl, C5-C8-cycloalkenyl, 3- to 8-membered heterocycloalkyl, phenyl, and 5- to 6-membered heteroaryl; R 3c When R is cycloalkyl or heterocycloalkyl, 3c is 1 to 4 R 8 optionally substituted with R 3c is phenyl or heteroaryl, R 3c is 1 to 5 R 9 is optionally substituted with a group.

[0164] In one embodiment, R 3a are independently CN, C-C-alkyl, C-C-haloalkyl, C-C-haloalkenyl, and C-C-alkylene-R 3c Selected from; R 3c are each independently selected from C3-C8-cycloalkyl, C5-C8-cycloalkenyl, 5- to 8-membered heterocycloalkenyl, 3- to 8-membered heterocycloalkyl, and phenyl; R 3c When R is cycloalkyl, heterocycloalkyl, cycloalkenyl, or heterocycloalkenyl, 3c is 1 to 4 R 8 optionally substituted with R 3c is phenyl, R 3c is 1 to 5 R 9 The group is optionally substituted.

[0165] In one embodiment, R 3a are independently CN, C-C-alkyl, C-C-haloalkyl, C-C-haloalkenyl, and C-C-alkylene-R 3c Selected from; R 3c are each independently selected from C3-C8-cycloalkyl, C5-C8-cycloalkenyl, 3- to 8-membered heterocycloalkyl, and phenyl; R 3cWhen R is cycloalkyl or heterocycloalkyl, 3c is 1 to 4 R 8 optionally substituted with R 3c is phenyl, R 3c is 1 to 5 R 9 The group is optionally substituted.

[0166] In one embodiment, R 3a are independently C-C-alkyl, C-C-haloalkyl, C-haloalkenyl, and C-C-alkylene-R 3c Selected from; R 3c are each independently selected from C3-C6-cycloalkyl, C5-C6-cycloalkenyl, 5- to 6-membered heterocycloalkenyl, 4- to 6-membered heterocycloalkyl, and phenyl; R 3c When R is cycloalkyl, heterocycloalkyl, cycloalkenyl, or heterocycloalkenyl, 3c is 1 to 4 R 8 optionally substituted with R 3c is phenyl, R 3c is 1 to 5 R 9 The group is optionally substituted.

[0167] In one embodiment, R 3a are independently C-C-alkyl, C-C-haloalkyl, C-haloalkenyl, and C-C-alkylene-R 3c Selected from; R 3c are each independently selected from C3-C6-cycloalkyl, C5-C6-cycloalkenyl, 4- to 6-membered heterocycloalkyl, and phenyl; R 3c When R is cycloalkyl or heterocycloalkyl, 3c is 1 to 4 R 8 optionally substituted with R 3c is phenyl, R 3c is 1 to 5 R 9The group is optionally substituted.

[0168] In one embodiment, R 3a is C0-C3-alkylene-R 3c and; R 3c are each independently selected from C-cycloalkyl, C-cycloalkenyl, 6-membered heterocycloalkenyl, 6-membered heterocycloalkyl, and phenyl; R 3c is cycloalkyl, cycloalkenyl, heterocycloalkenyl, or heterocycloalkyl, then R 3c is 1 to 4 R 8 optionally substituted with R 3c is phenyl, R 3c is 1 to 5 R 9 The group is optionally substituted.

[0169] In one embodiment, R 3a is C0-C3-alkylene-R 3c and; R 3c are each independently selected from C-cycloalkyl, C-cycloalkenyl, 6-membered heterocycloalkyl, and phenyl; R 3c When R is cycloalkyl, cycloalkenyl, or heterocycloalkyl, 3c is 1 to 4 R 8 optionally substituted with R 3c is phenyl, R 3c is 1 to 5 R 9 The group is optionally substituted.

[0170] In one embodiment, R 3a is C0-C3-alkylene-R 3c and;R 3c is phenyl; R 3c is 1 to 5 R 9 The group is optionally substituted.

[0171] In one embodiment, R 3a is phenyl, and 1 to 3 R 9Optionally substituted with a group R 3c , R 3a , or R 3 When is phenyl, the phenyl is substituted with 1 to 3 R 9 It may be substituted with a group.

[0172] In one embodiment, R 3a is R 3c and;R 3c is phenyl and R 3c is one or two R 9 group, and the para position on the phenyl group is unsubstituted.

[0173] In one embodiment, R 3a is C-C-alkyl. In one embodiment, R 3a is C-C-haloalkyl. In one embodiment, R 3a is C-C-haloalkenyl. In one embodiment, R 3a is C0-C3-alkylene-R 3c and R 3c are each independently selected from C-C-cycloalkyl, C-C-cycloalkenyl, 5- to 6-membered heterocycloalkenyl, and 4- to 6-membered heterocycloalkyl. 3a is C-C-cycloalkyl. In one embodiment, R 3a is C-C-cycloalkenyl. In one embodiment, R 3a is a 5-6 membered heterocycloalkenyl. In one embodiment, R 3a is a 4-membered heterocycloalkyl. In one embodiment, R 3a is a 5-membered heterocycloalkyl. In one embodiment, R 3a is a 6-membered heterocycloalkyl. 3a or R 3c When R is cycloalkyl or heterocycloalkyl, 3c is 1 to 4 R 8 It may be substituted with a group.

[0174] In one embodiment, R 3ais C-C-alkyl. In one embodiment, R 3a is C-C-haloalkyl. In one embodiment, R 3a is C-C-haloalkenyl. In one embodiment, R 3a is C0-C3-alkylene-R 3c and R 3c are each independently selected from C-C-cycloalkyl, C-C-cycloalkenyl, and 4- to 6-membered heterocycloalkyl. 3a is C-C-cycloalkyl. In one embodiment, R 3a is C-C-cycloalkenyl. In one embodiment, R 3a is a 4-membered heterocycloalkyl. In one embodiment, R 3a is a 5-membered heterocycloalkyl. In one embodiment, R 3a is a 6-membered heterocycloalkyl. 3a or R 3c When R is cycloalkyl or heterocycloalkyl, 3c is 1 to 4 R 8 It may be substituted with a group.

[0175] In one embodiment, R 3 is selected from phenyl or -O-phenyl, and R 3 is 1 to 5 R 9 In one embodiment, R 3 is unsubstituted phenyl. In one embodiment, R 3 is -O-phenyl and R 3 is two R 9 is substituted with a group.

[0176] In one embodiment, R 3 teeth [ka] is.

[0177] In one embodiment, R 3 teeth [ka] is.

[0178] When ring A is a 5-membered heteroaryl, R 3a may be optionally substituted phenyl. When ring A is a 5-membered heteroaryl, R 3a may be an optionally substituted 6-membered heteroaryl.

[0179] In one embodiment, R 3a teeth, [ka] is selected from.

[0180] In one embodiment, R 3b are independently C1-C4-alkyl, C2-C4-alkylene-O-C1-C4-alkyl, C1-C4-haloalkyl, and C0-C3-alkylene-R 3d Selected from; R 3d are each independently selected from C3-C8-cycloalkyl, 3- to 8-membered heterocycloalkyl, and phenyl; where R 3d When R is cycloalkyl or heterocycloalkyl, 3d is 1 to 4 R 8 optionally substituted with R 3d is phenyl, R 3d is 1 to 5 R 9 is optionally substituted with a group.

[0181] In one embodiment, R 3b are independently C4-alkyl, C2-C4-alkylene-O-C1, C4-haloalkyl, and C0-C3-alkylene-R 3d Selected from;R 3d are each independently selected from C3-C6-cycloalkyl, 4- to 6-membered heterocycloalkyl, and phenyl; where R 3dWhen R is cycloalkyl or heterocycloalkyl, 3d is 1 to 4 R 8 optionally substituted with R 3d is phenyl, R 3d is 1 to 5 R 9 is optionally substituted with a group.

[0182] In one embodiment, R 3b is C0-C3-alkylene-R 3d and;R 3d are each independently selected from C-C-cycloalkyl, 4- to 6-membered heterocycloalkyl, and phenyl; R 3d When R is cycloalkyl or heterocycloalkyl, 3d is 1 to 4 R 8 optionally substituted with R 3d is phenyl, R 3d is 1 to 5 R 9 is optionally substituted with a group.

[0183] In one embodiment, R 3b is C0-C3-alkylene-R 3d and;R 3d are each independently selected from C-cycloalkyl, 6-membered heterocycloalkyl, and phenyl; R 3d When R is cycloalkyl or heterocycloalkyl, 3d is 1 to 4 R 8 optionally substituted with R 3d is phenyl, R 3d is 1 to 5 R 9 is optionally substituted with a group.

[0184] In one embodiment, R 3b is C0-C3-alkylene-R 3d and;R 3d is phenyl; R 3d is 1 to 5 R 9 is optionally substituted with a group.

[0185] In one embodiment, R 3b is phenyl, and 1 to 3 R 9 The group is optionally substituted.

[0186] In one embodiment, R 3b is C0-C3-alkylene-R 3d and;R 3d are each independently selected from C3-C6-cycloalkyl and 4- to 6-membered heterocycloalkyl; R 3d is 1 to 4 R 8 The group is optionally substituted.

[0187] In one embodiment, R 3b is C0-C3-alkylene-R 3d and;R 3d is C3-C6-cycloalkyl; R 3d is 1 to 4 R 8 The group is optionally substituted.

[0188] In one embodiment, R 3b is C0-C3-alkylene-R 3d and;R 3d is a 4- to 6-membered heterocycloalkyl; R 3d is 1 to 4 R 8 The group is optionally substituted.

[0189] In one embodiment, R 3b is a 4- to 6-membered heterocycloalkyl; 1 to 4 R 8 In one embodiment, R 3b is a 4-membered heterocycloalkyl; 8 In one embodiment, R 3b is a 5-membered heterocycloalkyl; 1 to 3 R 8 In one embodiment, R 3b is a 6-membered heterocycloalkyl; 1 to 4 R 8 The group is optionally substituted.

[0190] In one embodiment, R 3b is C1-C4-alkyl. In one embodiment, R 3b is C2-C4-alkylene-O-C1-C4-alkyl. In one embodiment, R 3b is C1-C4-haloalkyl.

[0191] In one embodiment, R 3b is C-C-alkyl. In one embodiment, R 3b is C2-C4-alkylene-O-C1-C4-alkyl. In one embodiment, R 3b is C3-C4-haloalkyl.

[0192] When ring A is a 5-membered heteroaryl, R 3b may be an optionally substituted C-cycloalkyl. When ring A is a 5-membered heteroaryl, R 3b may be an optionally substituted 6-membered heterocycloalkyl. When ring A is a 5-membered heteroaryl, R 3b may be substituted or unsubstituted phenyl. When ring A is a 5-membered heteroaryl, R 3b may be an optionally substituted 6-membered heteroaryl.

[0193] In one embodiment, R 3b teeth, [ka] is selected from.

[0194] In one embodiment, R 4 each independently represents cyano, C0-C4-alkylene-NR 5 R 6 , C0-C4-alkylene-OR 7 , S(O)2R 6 , C1-C4-alkyl, 4- to 6-membered heterocycloalkyl, C1-C4-alkyl-S(O)2R 6 and C1-C4-haloalkyl.

[0195] In one embodiment, R 4 each independently represents cyano, C0-C4-alkylene-NR 5 R 6 , C0-C4-alkylene-OR 7 , S(O)2R 6 , C1-C4-alkyl, C1-C4-alkyl-S(O)2R 6 and C1-C4-haloalkyl.

[0196] In one embodiment, R 4 each independently represents cyano, C0-C4-alkylene-NR 5 R 6 , C0-C4-alkylene-OR 7 , S(O)2R 6 , C1-C2-alkyl, 4-membered heterocycloalkyl, C(CH3)2OH, C1-C2-alkyl-S(O)2R 6 and C1-C2-haloalkyl.

[0197] In one embodiment, R 4 each independently represents cyano, C0-C4-alkylene-NR 5 R 6 , C0-C4-alkylene-OR 7 , S(O)2R 6 , C1-C2-alkyl, C(CH3)2OH, C1-C2-alkyl-S(O)2R 6 and C1-C2-haloalkyl.

[0198] In one embodiment, R 4 are each independently C0-C4-alkylene-NR 5 R 6 , S(O)2R 6 , C1-alkyl, 4-membered heterocycloalkyl, C(CH3)2OH, C1-alkyl-S(O)2R 6 and C1-haloalkyl.

[0199] In one embodiment, R 4 are each independently C0-C4-alkylene-NR 5 R6 , S(O)2R 6 , C1-alkyl, C(CH3)2OH, C1-alkyl-S(O)2R 6 and C1-haloalkyl.

[0200] In one embodiment, R 4 are each independently cyano, NR 5 R 6 , OR 7 , S(O)2R 6 , C1-C2-alkyl, 4-membered heterocycloalkyl, C(CH3)2OH, C1-C2-alkyl-S(O)2R 6 and C1-C2-haloalkyl.

[0201] In one embodiment, R 4 are each independently cyano, NR 5 R 6 , OR 7 , S(O)2R 6 , C1-C2-alkyl, C(CH3)2OH, C1-C2-alkyl-S(O)2R 6 and C1-C2-haloalkyl.

[0202] In one embodiment, R 4 are each independently, NR 5 R 6 , S(O)2R 6 , C1-alkyl, oxetanyl (e.g., oxetan-3-yl), C(CH3)2OH, C1-alkyl-S(O)2R 6 and C1-haloalkyl.

[0203] In one embodiment, R 4 are each independently, NR 5 R 6 , S(O)2R 6 , C1-alkyl, C(CH3)2OH, C1-alkyl-S(O)2R 6 and C1-haloalkyl.

[0204] In one embodiment, R 4are independently N(H)S(O)2Me, S(O)2MeR 6 , C(CH3)2OH, C1-alkyl-S(O)2Me.

[0205] In one embodiment, m is an integer selected from 0, 1, and 2. In one embodiment, m is 2. In one embodiment, m is 1. In one embodiment, m is 0.

[0206] In one embodiment, R 4a is H. In one embodiment, R 4a is methyl. In one embodiment, R 4a is cyclopropyl. In one embodiment, R 4a is a 4-membered heterocycloalkyl. In one embodiment, R 4a is oxetanyl. In one embodiment, R 4a is oxetan-3-yl. In one embodiment, R 4a is oxetanyl or azetidinyl. In one embodiment, R 4a is independently selected from H, C-C-alkyl, and cyclopropyl. 4a is independently selected from C-C-alkyl, cyclopropyl, and cyclobutyl. 4a is cyclopropyl.

[0207] In one embodiment, R 4b is S(O)2R 6 In one embodiment, R 4b is C1-C4-alkyl. In one embodiment, R 4b is C1-C4-alkyl-S(O)2R 6 In one embodiment, R 4b is C-C-haloalkyl. In one embodiment, R 4b is cyclopropyl.

[0208] In one embodiment, R 4bis selected from S(O)2-C1-C3-alkyl, e.g., S(O)2Me. In one embodiment, R 4b is C1-C4-alkyl, e.g., methyl. In one embodiment, R 4b is C1-C4-alkyl-S(O)2-C1-C4-alkyl, for example -CH2-S(O)2-Me.

[0209] In one embodiment, R 5 are each independently selected from H, C1-C4-alkyl, and S(O)2-C1-C4-alkyl.

[0210] In one embodiment, R 5 is S(O)-C-C-alkyl, and optionally R 5 is S(O)-C-alkyl. In one embodiment, R 5 is H. In one embodiment, R 5 is methyl.

[0211] In one embodiment, R 6 are each independently selected from H and C1-C4-alkyl. In one embodiment, R 6 is H. In one embodiment, R 6 is methyl.

[0212] In one embodiment, R 7 are each independently selected from H, C1-C4-alkyl, and C1-C4-haloalkyl.

[0213] In one embodiment, R 7 are each independently selected from H and C1-C4-alkyl.

[0214] In one embodiment, R 7 are each independently selected from H, C1-C2-alkyl, and C1-C2-haloalkyl.

[0215] In one embodiment, R 7are each independently selected from H and C1-C2-alkyl.

[0216] In one embodiment, R 7 are each independently H.

[0217] In one embodiment, R 8 are each independently ═O, fluoro, nitro, cyano, or NR 5 R 6 , OR 7 , C(O)R 6 , C1-C4-alkyl, C1-C4-haloalkyl, and cyclopropyl.

[0218] In one embodiment, R 8 are each independently ═O, fluoro, or C(O)R 6 , C1-C2-alkyl, and C1-C2-haloalkyl.

[0219] In one embodiment, R 8 are each independently ═O, fluoro, and C(O)R 6 In one embodiment, R 8 are each independently selected from ═O, fluoro, and C(O)Me.

[0220] In one embodiment, R 9 are each independently halo, nitro, cyano, or NR 5 R 6 , OR 7 , C(O)R 6 , C1-C4-alkyl, C1-C4-haloalkyl, and cyclopropyl.

[0221] In one embodiment, R 9 are each independently selected from halo, C1-C4-alkyl, and C1-C4-haloalkyl.

[0222] In one embodiment, R 9are each independently selected from halo, C1-C2-alkyl, and C1-C2-haloalkyl.

[0223] In one embodiment, R 9 are each independently selected from halo and C-C-alkyl. 9 are each independently selected from fluoro and methyl.

[0224] In embodiments, R x and R y are each independently H, halo, nitro, cyano, or NR 5 R 6 , OR 7 , S.R. 6 , C1-C4-alkyl, C1-C4-haloalkyl, and C3-C4-cycloalkyl.

[0225] In one embodiment, R x and R y are each independently selected from H, halo, cyano, C1-C2-alkyl, C1-C2-haloalkyl, and C3-cycloalkyl.

[0226] In one embodiment, R x is H. In one embodiment, R y is H. In one embodiment, R x and R y are H, respectively.

[0227] In one embodiment, either the alkyl or alkenyl groups may each independently be selected from oxo, fluoro, NR a R b , OR a , and S(O)2R a optionally substituted with 1 to 5 substituents selected from the group consisting of: a are each independently selected from H and C1-C4-alkyl; R bare each independently selected from H, C1-C4-alkyl, C(O)-C1-C4-alkyl, and S(O)2-C1-C4-alkyl.

[0228] In one embodiment, X 6 is carbon. In one embodiment, X 6 is nitrogen.

[0229] In one embodiment, X 7 is carbon. In one embodiment, X 7 is nitrogen.

[0230] In an embodiment, p is an integer selected from 0, 1, 2, and 3. In one embodiment, p is 3. In one embodiment, p is 2. In one embodiment, p is 1. In one embodiment, p is 0.

[0231] In one embodiment, the compound according to formula (I) is [ka] Selected from TIFF2024523491000158.tif236159TIFF2024523491000159.tif223159.

[0232] In one embodiment, the compound according to formula (I) is [ka] is selected from.

[0233] In one embodiment, the compound according to formula (I) is [ka] Selected from TIFF2024523491000162.tif210159.

[0234] In one embodiment, the compound according to formula (I) is R 2is selected from structures that are saturated or unsaturated 6-membered heterocycles having one nitrogen atom, which may be substituted or unsubstituted at any position and may include pyridones, as described herein.

[0235] In one embodiment, the compound according to formula (I) is R 2 is selected from structures that are saturated or unsaturated 6-membered heterocyclic rings having two nitrogen atoms, which may be substituted or unsubstituted at any position as described herein.

[0236] In one embodiment, the compound according to formula (I) is R 2 is selected from structures which are saturated or unsaturated 6-membered heterocycles having 3 nitrogen atoms, which may be substituted or unsubstituted at any position as described herein.

[0237] In one embodiment, the compound according to formula (I) is R 2 is selected from structures that are saturated or unsaturated five-membered heterocyclic rings having one nitrogen atom, which may be substituted or unsubstituted at any position, as described herein.

[0238] In one embodiment, the compound according to formula (I) is R 2 is selected from structures that are saturated or unsaturated five-membered heterocyclic rings having two nitrogen atoms, which may be substituted or unsubstituted at any position as described herein.

[0239] In one embodiment, the compound according to formula (I) is R 2 is selected from structures that are saturated or unsaturated five-membered heterocyclic rings having three nitrogen atoms, which may be substituted or unsubstituted at any position, as described herein.

[0240] In one embodiment, the compound according to formula (I) is R 2 is selected from structures that are saturated or unsaturated 5-membered heterocyclic rings having one nitrogen atom and one sulfur atom, which may be substituted or unsubstituted at any position as described herein.

[0241] In one embodiment, the compound according to formula (I) is [ka] isn't it.

[0242] In one embodiment, the compound according to formula (I) is [ka] isn't it.

[0243] The present inventors have found that certain compounds of the present disclosure can improve metabolic stability.The present inventors have also found that certain compounds of the present disclosure can have increased activity against BRD4 BD2.The present inventors have also found that certain compounds of the present disclosure can enhance selectivity for BRD4 BD2 over BRD4 BD1.The present inventors have also found that certain compounds of the present disclosure can improve bioavailability.

[0244] According to a second aspect, the present disclosure provides a pharmaceutical composition comprising a compound as defined in the first aspect and one or more pharmaceutically acceptable excipients.

[0245] According to a third aspect, the present disclosure provides a compound as defined in the first aspect or a pharmaceutical composition as defined in the second aspect for use as a medicament.

[0246] According to a fourth aspect, the present disclosure provides the use of a compound as defined in the first aspect or a pharmaceutical composition as defined in the second aspect for the manufacture of a medicament.

[0247] According to a fifth aspect, the present disclosure provides a compound as defined in the first aspect or a pharmaceutical composition as defined in the second aspect for use in a method for the treatment or prevention of inflammatory diseases, such as inflammatory skin disorders, respiratory diseases, gastrointestinal diseases, eye diseases, cancer, rheumatic diseases, demyelinating diseases, and fibrotic diseases.

[0248] According to a sixth aspect, the present disclosure provides a method of treating or preventing an inflammatory disease, such as an inflammatory skin disorder, a respiratory disease, a gastrointestinal disease, an eye disease, cancer, a rheumatic disease, a demyelinating disease, and a fibrotic disease, said method comprising administering to a subject an effective amount of a compound as defined in the first aspect, or a pharmaceutical composition as defined in the second aspect.

[0249] According to a seventh aspect, the present disclosure provides use of a compound as defined in the first aspect, or a pharmaceutical composition as defined in the second aspect, for the manufacture of a medicament for the treatment or prevention of inflammatory diseases, such as inflammatory skin disorders, respiratory diseases, gastrointestinal diseases, eye diseases, cancer, rheumatic diseases, demyelinating diseases, and fibrotic diseases, said method comprising administering to a subject an effective amount of a compound as defined in the first aspect, or a pharmaceutical composition as defined in the second aspect.

[0250] According to an eighth aspect, the present disclosure provides a method of inhibiting the activity of a bromodomain and exo-terminal protein in a subject, said method comprising administering to the subject an effective amount of a compound defined in the first aspect, or a pharmaceutical composition defined in the second aspect.

[0251] According to a ninth aspect, the present disclosure provides a method of treating a disorder associated with bromodomain and exo-terminal protein activity in a subject, said method comprising administering to the subject an effective amount of a compound defined in the first aspect, or a pharmaceutical composition defined in the second aspect.

[0252] Selective BET BDII inhibitors, such as the compounds disclosed herein, are useful and can be used, in one or more embodiments, to treat or ameliorate the following non-limiting examples of disorders and diseases:

[0253] Selective BET BDII inhibitors, such as the compounds disclosed herein, are useful and can be used, in one or more embodiments, to treat or ameliorate inflammatory, immune, and autoimmune disorders, including diseases that have or may have an inflammatory or autoimmune component.

[0254] Inflammatory, immune, or autoimmune disorders include acne, inflammatory acne, acne fulminant, angiofibroma, nodular papulopustular acne, acne conglomerata, acute erysipelas, alopecia, alopecia areata, alopecia totalis, atopic dermatitis, alopecia universalis, autoimmune bullous skin diseases such as pemphigus vulgaris (PV) or bullous pemphigoid (BP), bacterial skin infections, viral skin infections, bullous diseases, cellulitis, skin abscesses, carbuncles, Chronic hand eczema, cutaneous mastocytosis, dermal diseases, dermatological pain, skin inflammation, contact dermatitis, dermatitis, dermatitis herpetiformis, dermatomyositis, lipodystrophy and chronic atypical neutrophilic dermatosis with elevated body temperature (CANDLE), neutrophilic dermatitis such as pyoderma gangrenosum and Sweets' syndrome, paronychia, edematous palmoplantar pustulosis, erythema multiforme, erythema nodosum, granuloma annulare, pemphigus, epidermal necrolytic pemphigus, paraneoplastic pemphigus, rubra Symptoms include: eczema, eczema, folliculitis, furuncle, gustatory sweating, hyperhidrosis, Hailey-Hailey disease, urticaria, hidradenitis suppurativa, hypertrophic scars, impetigo, ichthyosis, ischemic necrosis, keloids, necrotizing subcutaneous infections, actinic keratosis, keratosis pilaris, hidradenoma, molluscum contagiosum, lichen planus, Netherton syndrome, pityriasis erythematosus pilaris, psoriasis, pruritus, prurigo nodularis, rash, rosacea, pediculosis, pityriasis rosea, scleroderma, scalded skin syndrome The skin disorder may be selected from: skin rash, skin inflammation, skin sensitization (e.g., contact dermatitis or allergic contact dermatitis), skin trauma or injury, post-operative or post-surgical skin conditions, wounds, burns (including chemical, electrical fire, friction, radiation, temperature-related, hot and cold), sunburn, scars, scabies, skin ulcers, urticaria pigmentosa, hives and chronic idiopathic pruritus, vitiligo, warts, and xerosis.

[0255] The inflammatory, immune, or autoimmune disorder may be a respiratory disease selected from asthma, bronchiectasis, bronchiolitis, byssinosis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, hypersensitivity pneumonitis, mesothelioma, pneumoconiosis, (idiopathic) pulmonary fibrosis, rhinitis, sinusitis, and sarcoidosis.

[0256] The inflammatory, immune, or autoimmune disorder can be a gastrointestinal disorder selected from celiac disease, Crohn's disease, eosinophilic esophagitis, inflammatory bowel disease, retroperitoneal fibrosis, and ulcerative colitis.

[0257] The inflammatory, immune, or autoimmune disorder can be an ocular disease selected from conjunctivitis, dry eye syndrome, iritis, keratitis, macular degeneration, myasthenia gravis, scleritis, Sjogren's syndrome, and uveitis.

[0258] The inflammatory, immune, or autoimmune disorder can be a cardiovascular or related disease selected from cerebrovascular disease, aortic disease, arrhythmia, atherosclerosis, aneurysm, angina, stroke, carditis, cardiac hypertrophy, cardiomyopathy, endocarditis, coronary artery disease, deep vein thrombosis, heart attack, heart disease, heart failure, Marfan syndrome, myocarditis, peripheral arterial disease, pericarditis, pulmonary embolism, rheumatic heart disease, thrombosis, valvular heart disease, ventricular disease, ventricular dysfunction, and vascular disease.

[0259] Inflammatory, immune, or autoimmune disorders include, but are not limited to, Addison's disease, AIDS, ankylosing spondylitis, atherosclerosis, arthritis, Behcet's disease, cryopyrin-associated periodic syndromes (CAPS), chronic kidney disease (nephritis, nephropathy, hypertensive nephropathy, HIV-associated nephropathy, IgA nephropathy, familial Mediterranean fever, focal segmental glomerulosclerosis, Graves' disease, juvenile arthritis, lymphangitis, lymphadenitis, lupus nephritis, minimal change disease, neurofibromatosis, polycystic kidney disease, and tubulointerstitial nephritis), acute kidney injury or condition (ischemia-reperfusion induced, cardiac and major surgery induced, percutaneous coronary intervention induced, radiocontrast induced, ruptured kidney disease, or kidney disease). The systemic indication may be selected from: chronic obstructive pulmonary disease (COPD), ...

[0260] The inflammatory, immune, or autoimmune disorder can be an autoimmune disease or indication in which immunosuppression is desirable, for example, to avoid organ transplant rejection and graft-versus-host disease (chronic or acute).

[0261] Selective BET BDII inhibitors, such as the compounds disclosed herein, are useful and can be used in one or more embodiments to treat or ameliorate cancer.

[0262] Cancers include acoustic neuroma, anal cancer, bladder cancer, Bowen's disease, brain cancer, breast cancer, basal cell carcinoma, bile duct carcinoma, bronchial carcinoma, choriocarcinoma, embryonal carcinoma, cystadenocarcinoma, epithelial carcinoma, medullary carcinoma, NUT midline carcinoma (NMC), papillary carcinoma, papillary adenocarcinoma, renal cell carcinoma, sebaceous gland carcinoma, small cell lung cancer, squamous cell carcinoma, and sweat gland carcinoma, cervical cancer, chordoma, colon cancer, colorectal cancer, craniopharyngioma, proliferative changes (dysplasia and metaplasia), endometrial cancer, ependymoma, esophageal cancer, essential thrombocythemia, estrogen receptor positive breast cancer, Ewing's tumor, genital cancer, cervical cancer, vulvar cancer, vulvar intraepithelial neoplasia (VIN), vaginal cancer, Germ cell testicular cancer, gastrointestinal cancer, gastric cancer, glioblastoma, glioma, heavy chain disease, hemangioblastoma, hepatocellular carcinoma, liver cancer, hormone-insensitive prostate cancer, keratinocyte carcinoma, kidney cancer, leukemia including acute leukemia, acute lymphocytic leukemia, acute myeloid leukemia, acute myeloid leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic, and promyelocytic), acute T-cell leukemia, chronic leukemia, chronic lymphocytic leukemia, chronic myeloid (granulocytic) leukemia, chronic myeloid leukemia, erythroleukemia, lymphocytic obstructive leukemia, and myeloid leukemia, liver cancer, lung cancer, T-cell or lymphoid malignancies of B-cell origin, cutaneous T-cell lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma, lymphomas (Hodgkin's and non-Hodgkin's), including cutaneous (skin) lymphoma, malignant tumors and hyperproliferative disorders of the bladder, breast, colon, lung, ovary, pancreas, prostate, skin, and uterus, advanced malignancies, medulloblastoma, melanoma, meningioma, Merkel cell carcinoma, mesothelioma, metastatic cancer, multiple myeloma, myeloma, pancreatic cancer, myelofibrosis, myeloproliferative neoplasms, neuroblastoma, non-small cell lung cancer, head and neck cancer, oligodendroglioma, The cancer may be a skin cancer or a systemic cancer selected from oral cancer, ovarian cancer, pancreatic cancer, pinealoma, polycythemia vera, prostate cancer, rectal cancer, retinoblastoma, chondrosarcoma, endothelial sarcoma, fibrosarcoma, gliosarcoma, leiomyosarcoma, liposarcoma, lymphangioendothelial sarcoma, lymphangiosarcoma, myxosarcoma, Castleman's disease and Kaposi's sarcoma, osteogenic sarcoma, and rhabdomyosarcoma, seminoma, skin cancer, skin adnexal tumors, and sarcomas, small cell lung cancer, solid tumors, gastric cancer, synovioma, testicular tumor, thyroid cancer, uterine cancer, Waldenstrom's macroglobulinemia, and Wilms' tumor.

[0263] Selective BET BDII inhibitors, such as the compounds disclosed herein, can be used, in one or more embodiments, to provide male contraception.

[0264] Selective BET BDII inhibitors, such as the compounds disclosed herein, may be used in one or more embodiments to treat or ameliorate obesity, dyslipidemia, cholesterolemia, hypercholesterolemia, Alzheimer's disease, metabolic syndrome, fatty liver, type I diabetes, type II diabetes, and complications from diabetes, insulin resistance, and diabetic retinopathy or diabetic neuropathy.

[0265] Selective BET BDII inhibitors, such as the compounds disclosed herein, can be used in one or more embodiments to treat or ameliorate immune system dysfunction, viral diseases, bacterial diseases, yeast diseases, non-inflammatory acne, allergic diseases, asthma, food allergies, rhinitis, IL-6 pathway-related diseases, immune responses, and hyperproliferative disorders.

[0266] Selective BET BDII inhibitors, such as the compounds disclosed herein, can be used in one or more embodiments to treat or ameliorate Aicardi-Goutieres syndrome, chilblain lupus, stimulator of interferon genes-associated vasculopathy with onset in infancy (SAVI), Singleton-Merten syndrome, retinal vasculopathy with cerebral leukodystrophy, autoimmune uveitis, lupus, systemic sclerosis, autoimmune thyroid disease, allograft rejection, graft-versus-host disease, allograft rejection, and graft-versus-host reaction.

[0267] Selective BET BDII inhibitors, such as the compounds disclosed herein, can be used in one or more embodiments to treat or ameliorate disorders caused by viruses, such as Epstein-Barr virus (EBV), HIV, HTLV1, chickenpox, herpes simplex virus infection, varicella zoster virus (VZV), and human papillomavirus (HPV) disease.

[0268] Selective BET BDII inhibitors, such as the compounds disclosed herein, can be used in one or more embodiments to treat or ameliorate mucous cervicitis (MPC), urethritis, agranulocytic urethritis (NGU), vulvar disorders, vulvodynia, vulvar pain, vulvar dystrophy, pelvic inflammation, endometritis, salpingitis, oophoritis, dyspareunia, anal and rectal disorders, perianal inflammation / fistula, anal fissure, anal warts, hemorrhoids, anal itch, pruritus ani, fecal incontinence, constipation, and polyps of the colon and rectum.

[0269] Selective BET BDII inhibitors, such as the compounds disclosed herein, can be used in one or more embodiments in restoring or promoting the restoration of integrity to areas of damaged or injured tissue, skin or mucosa, as well as in reducing and ameliorating scar formation or scarring.

[0270] Selective BET BDII inhibitors, such as the compounds disclosed herein, can be used in one or more embodiments to treat or ameliorate pyoderma gangrenosum (PG), palmar-plantar pustulosis (PPP), and generalized pustulosis (GPP).

[0271] Selective BET BDII inhibitors, such as the compounds disclosed herein, can be used in one or more embodiments to treat or ameliorate Crohn's disease, multiple sclerosis, rheumatoid arthritis, sinusitis, and ulcerative colitis.

[0272] Selective BET BDII inhibitors, such as the compounds disclosed herein, can be used in one or more embodiments to treat or ameliorate cryopyrin-associated periodic syndromes (CAPS), cardiovascular disease, cerebrovascular disease, familial Mediterranean fever, Graves' disease, liver fibrosis, neurofibrosis, myocarditis, pericarditis, prostate disease, prostatitis, benign prostatic hyperplasia (BPH), systemic mastocytosis, and warm autoimmune hemolytic anemia.

[0273] Selective BET BDII inhibitors, such as the compounds disclosed herein, can be used in one or more embodiments to treat or ameliorate angiofibromas, chronic hand eczema, cutaneous mastocytosis, urticaria pigmentosa, neutrophilic dermatoses such as pyoderma gangrenosum and Sweets' syndrome, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated body temperature (CANDLE), ichthyosis, keloids, scars, hypertrophic scars, Netherton syndrome, pruritus, prurigo nodularis, and urticaria pigmentosa.

[0274] Selective BET BDII inhibitors, such as the compounds disclosed herein, are useful and can be used, in one or more embodiments, to alleviate, diagnose, or prevent any disease, disorder, or condition from one or more of the above non-limiting examples of disorders and diseases in humans.

[0275] Treatment or improvement with a composition comprising a selective BET BDII inhibitor, such as a compound disclosed herein or a salt thereof (or a combination thereof), can be effective in some embodiments when applied orally, in some other embodiments when applied by injection, in some other embodiments when applied topically, and in some further embodiments when applied topically and orally, or when applied by injection and topically, or when applied orally and by injection. In one or more embodiments, treatment or improvement with a composition comprising a selective BET BDII inhibitor, such as a compound disclosed herein or a salt thereof (or a combination thereof), can be effective orally if the compound has good bioavailability, for example, > about 25%.

[0276] In one or more embodiments, the compounds disclosed herein are active against BRD4 BD2 and selective over BRD4 BD1. In one or more embodiments, BET BDII-selective protein inhibitors exhibit greater than about 100-fold selectivity, greater than about 200-fold selectivity, greater than about 250-fold selectivity, greater than about 300-fold selectivity, greater than about 350-fold selectivity, greater than about 400-fold selectivity, greater than about 500-fold selectivity, greater than about 600-fold selectivity, greater than about 700-fold selectivity, greater than about 800-fold selectivity, greater than about 900-fold selectivity, or greater than about 1000-fold selectivity for BDII over BD1, for example, depending on structure. In one embodiment, a BET BDII-selective protein inhibitor exhibits greater than about 200-fold selectivity. In one or more embodiments, the BET BDII selective protein inhibitor exhibits an IC50 against BRD4 BDII of < about 0.2 μM, < about 0.15 μM, < about 0.1 μM, or < about 0.05 μM. In one or more embodiments, the BET BDII selective protein inhibitor exhibits an IC50 in the range of < about 0.2 μM to < about 0.05 μM.

[0277] In addition to compounds that exhibit activity and selectivity, other factors in the selection of promising drug candidates can include, for example, plasma stability, clearance, pK, and bioavailability. For orally administered drug candidates, increased bioavailability can result in, for example, a lower gastrointestinal dose and potentially fewer side effects.

[0278] In one or more embodiments, the BET BDII selective protein inhibitor exhibits a mouse plasma stability of greater than about 70%, greater than about 75%, greater than about 80%, greater than about 85%, greater than about 90%, or greater than about 95% at 120 minutes. In one embodiment, the BET BDII selective protein inhibitor exhibits a mouse plasma stability of about 90% or greater at 120 minutes.

[0279] In some embodiments, BET BDII selective protein inhibitors with mouse plasma stability of about or greater than 90% at 120 minutes are promising drug candidates, although compounds with lower mouse plasma stability may, in some other embodiments, be useful in certain circumstances.

[0280] In one or more embodiments, the BET BDII selective protein inhibitor exhibits a mouse microsomal stability of < about 5, < about 4, < about 3, < about 2, or < about 1 ml / min per gram of liver. In one embodiment, the BET BDII selective protein inhibitor exhibits a mouse microsomal stability of < about 2 ml / min per gram of liver.

[0281] In some embodiments, BET BDII selective protein inhibitors with mouse microsomal stabilities of < about 2 ml / min per gram of liver are promising drug candidates, although compounds with lower mouse microsomal stabilities may, in some other embodiments, be useful in certain circumstances.

[0282] In one or more embodiments, the BET BDII selective protein inhibitor exhibits a rat microsomal stability half-life of > about 20 minutes, > about 20 minutes, > about 30 minutes, > about 40 minutes, > about 50 minutes, or > about 60 minutes. In one embodiment, the BET BDII selective protein inhibitor exhibits a rat microsomal stability half-life of > about 30 minutes.

[0283] In some embodiments, BET BDII selective protein inhibitors with rat microsomal stability and a half-life of >approximately 30 minutes are promising drug candidates, although compounds with lower rat microsomal stability may, in some other embodiments, be useful in certain circumstances.

[0284] In one or more embodiments, the BET BDII selective protein inhibitor exhibits an IL-22 IC50 of < about 250 nM, < about 50 nM, or < about 10 nM, and / or an IL-17A IC50 of < about 250 nM, < about 50 nM, or < about 10 nM. In one embodiment, the BET BDII selective protein inhibitor exhibits an IL-22 IC50 of < about 20 nM and / or an IL-17A IC50 of < about 20 nM.

[0285] In some embodiments, BET BDII selective protein inhibitors with an IL-22 IC50 of < about 20 nM and / or an IL-17A IC50 of < about 20 nM are promising drug candidates, although compounds with lower activity may, in some other embodiments, be useful in certain circumstances.

[0286] In one or more embodiments, the BET BDII selective protein inhibitor exhibits a bioavailability of > about 12%, > about 20%, > about 25%, > about 30%, > about 40%, > about 50%, > about 60%, > about 70%, > about 80%, > about 90%, or > about 95%. In one embodiment, the BET BDII selective protein inhibitor exhibits a bioavailability of > about 25%. In one embodiment, the BET BDII selective protein inhibitor has a bioavailability of > about 55%.

[0287] In one or more embodiments, BET BDII selective protein inhibitors with a bioavailability of > about 25% are promising, and those > about 55% are advantageous drug candidates for oral administration, although compounds with a bioavailability of about 25% or less may, in some embodiments, be useful in certain circumstances.

[0288] In one or more embodiments, some compounds have good activity and greater than about 200-fold selectivity, as well as two or more or all of the following features: an IL-22 IC50 of < about 20 nM, an IL-17A IC50 of < about 20 nM, a bioavailability of > about 25%, a mouse plasma stability of about 90% or greater than 90% at 120 minutes, a mouse microsomal stability of < about 2 ml / min per gram of liver, and a rat microsomal stability half-life of > about 30 minutes.

[0289] In one or more embodiments, some compounds have good activity and greater than about 200-fold selectivity, in addition to two or more or all of the following features: an IL-22 IC50 of < about 10 nM, an IL-17A IC50 of < about 10 nM, a bioavailability of > about 25% or > about 55%, a mouse plasma stability of about 90% or greater than 90% at 120 minutes, a mouse microsomal stability of < about 2 ml / min per gram of liver, and a rat microsomal stability half-life of > about 30 minutes.

[0290] In some embodiments, when applied topically, the compounds disclosed herein may be effective when the compound is delivered to the skin primarily or substantially via a low level of transdermal penetration. In some embodiments, when applied topically, the compounds disclosed herein may be effective when the compound is delivered primarily or substantially via transdermal penetration. In some embodiments, when applied topically, the compounds disclosed herein may be effective when the compound is delivered intradermally and transdermally. In some embodiments, penetration of the compound into the epidermis may be greater than that into the dermis. In some embodiments, penetration of the compound into the dermis may be greater than that into the epidermis. In some embodiments, penetration of the compound in the dermis is similar to penetration in the epidermis. In some embodiments, the concentration of the compound per unit volume in the epidermis may be greater than the concentration in the dermis. In some embodiments, the concentration of the compound per unit volume in the dermis may be greater than the concentration in the epidermis. In some embodiments, the concentration of the compound per unit volume in the dermis is similar to the concentration in the epidermis.

[0291] Compositions comprising a compound disclosed herein or a salt thereof (or combinations thereof) can, in one or more embodiments, be administered bucally, by inhalation (e.g., spray, nebulizer, or powder puff), epidurally, by injection (including intraarticularly, intravenously, orally, subcutaneously, intramyocardially, intraperitoneally, intramuscularly, intravascularly, or infusion), intradermally, intraperitoneally, intrapulmonary, intraarticularly (e.g., by injection), nasally, orally, parenterally, rectally, sublingually, topically, transdermally, vaginally, or via an implanted reservoir.

[0292] Pharmaceutical compositions of the present disclosure may be suitable for topical or transdermal administration.

[0293] Examples of dosage forms for topical or transdermal administration of a compound of the present disclosure or its salts include creams, drops, lotions, emulsions, foams, gels, inhalants, mousses, ointments, pastes, patches, powders, solutions, or sprays.

[0294] In some embodiments, compositions comprising the novel compounds disclosed herein or their salts (or combinations thereof) can be administered to young children. In some embodiments, compositions comprising the disclosed compounds or their salts (or combinations thereof) can be administered to adolescents or teenagers. In some embodiments, compositions comprising the disclosed compounds or their salts (or combinations thereof) can be administered to adults.

[0295] The present disclosure may also be defined according to any one of the following numbered clauses: 1. Compound (I) of formula (I) or a pharmaceutically acceptable salt or N-oxide thereof: [ka] (In the formula, X 4 are independently selected from carbon and nitrogen; X 5 are independently selected from carbon and nitrogen; Ring A is independently selected from phenyl and 5- or 6-membered heterocyclyl; R 1 is independently selected from C1-C3-alkyl, C1-C3-fluoroalkyl, and C3-cycloalkyl; R 2 is 1 to 4 R 2a is a 5-membered heterocyclyl group optionally substituted with a group; R 2a are each independently: =O, halo, OR 7 , C1-C4-alkyl, and C1-C4-haloalkyl; R 3 are each independently R 3a , OR 3b , or NR 6 R 3b Selected from; R 3a are independently H, CN, C1-C4-alkyl, C2-C4-alkenyl, C1-C4-haloalkyl, C2-C4-haloalkenyl, and C0-C3-alkylene-R 3c Selected from; R 3c are each independently selected from C3-C8-cycloalkyl, C5-C8-cycloalkenyl, 3- to 8-membered heterocycloalkyl, phenyl, and 5- to 6-membered heteroaryl; R 3c When R is cycloalkyl or heterocycloalkyl, 3c is 1 to 4 R 8 optionally substituted with R 3c is phenyl or heteroaryl, R 3c is 1 to 5 R 9 optionally substituted with a group; R 3b are independently C1-C4-alkyl, C2-C4-alkylene-O-C1-C4-alkyl, C1-C4-haloalkyl, and C0-C3-alkylene-R 3d Selected from; R 3dare each independently selected from C3-C8-cycloalkyl, 3- to 8-membered heterocycloalkyl, phenyl, and 5- or 6-membered heteroaryl; where R 3d When R is cycloalkyl or heterocycloalkyl, 3d is 1 to 4 R 8 optionally substituted with R 3d is phenyl or heteroaryl, R 3d is 1 to 5 R 9 optionally substituted with a group; R 4 are each independently ═O, ═S, halo, nitro, cyano, C0-C4-alkylene-NR 5 R 6 , C0-C4-alkylene-OR 7 , S.R. 6 , SOR 6 , C0-C4-alkylene-S(O)2R 6 , SO2NR 6 R 6 , C0-C4-alkylene-CO2R 6 , C0-C4-alkylene-C(O)R 6 , C0-C4-alkylene-CONR 6 R 6 , C1-C4-alkyl, C1-C4-alkyl-S(O)2R 6 , C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, and cyclopropyl; R 5 are each independently selected from H, C-C-alkyl, C(O)-C-C-alkyl, and S(O)-C-C-alkyl; or R 5 and R 6 and together with the nitrogen atom to which they are attached form 0 to 4 R 8 forming a C5-C8-heterocycloalkyl group optionally substituted by a group; R 6 are each independently selected from H and C1-C4-alkyl; or two R 6 groups are attached to the same nitrogen, and the two R 6The groups, together with the nitrogen atom to which they are attached, may contain 0 to 4 R 8 optionally forming a C5-C8-heterocycloalkyl group, optionally substituted by a group; R 7 are each independently selected from H, C-C-alkyl, C(O)-C-C-alkyl, and C-C-haloalkyl; R 8 are each independently ═O, ═S, fluoro, nitro, cyano, or NR 5 R 6 , OR 7 , S.R. 6 , SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , CO2R 6 , C(O)R 6 ,CONR 6 R 6 , C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, and cyclopropyl; R 9 are each independently halo, nitro, cyano, or NR 5 R 6 , OR 7 , S.R. 6 , SOR 6 , S(O)2R 6 , SO2NR 6 R 6 , CO2R 6 , C(O)R 6 ,CONR 6 R 6 , C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, and cyclopropyl; n is an integer selected from 0, 1, 2, 3, and 4; m is an integer selected from 0, 1, 2, 3, and 4; Any of the aforementioned alkyl, alkylene, or cyclopropyl groups may each independently, where chemically possible, be selected from C1-C4-alkyl, oxo, fluoro, nitro, cyano, NR a Rb , OR a , S.R. a , CO2R a , C(O)R a ,CONR a R a , S(O)R a , and S(O)2R a optionally substituted with 1 to 5 substituents selected from the group consisting of: a are each independently selected from H and C-C-alkyl; R b are each independently selected from H, C1-C4-alkyl, C(O)-C1-C4-alkyl, and S(O)2-C1-C4-alkyl).

[0296] 2.R 1 2. The compound according to clause 1, wherein is methyl.

[0297] 3.R 2 but [ka] 3. The compound of clause 1 or 2, wherein n1 is independently an integer selected from 0, 1 and 2.

[0298] 4.R 2 but [ka] 3. The compound of clause 1 or 2, wherein n2 is independently an integer selected from 0, 1, 2, and 3.

[0299] 5.R 2 but [ka] and n3 is independently an integer selected from 0, 1 and 2.

[0300] 6.R 2 but [ka] and n4 is independently an integer selected from 0, 1 and 2.

[0301] 7.R 2 but [ka] and n5 is independently an integer selected from 0 and 1.

[0302] 8. The compound according to any one of clauses 1 to 7, wherein ring A is phenyl.

[0303] 9. The compound according to any one of clauses 1 to 7, wherein ring A is a pyridone.

[0304] 10. The compound according to clause 9, wherein the pyridone is substituted on the nitrogen with either a C1-C4-alkyl group or a cyclopropyl group.

[0305] 11. [ka] but [ka] and;R 4a 11. The compound according to clause 9 or 10, wherein is selected from H, C1-C4-alkyl, and cyclopropyl.

[0306] 12. The compound according to any one of clauses 1 to 7, wherein ring A is a 5-membered heteroaryl.

[0307] 13.R 3 R 3a 13. The compound according to any one of clauses 1 to 12, wherein

[0308] 14.R 3a is phenyl and 1 to 3 R 914. The compound according to clause 13, optionally substituted with a group.

[0309] 15.R 3 OR 3b 13. The compound according to any one of clauses 1 to 12, wherein

[0310] 16.R 3b is phenyl and 1 to 3 R 9 16. The compound according to clause 15, optionally substituted with a group.

[0311] 17.R 3b C0-C3-alkylene-R 3d and;R 3d are each independently selected from C3-C6-cycloalkyl and 4- to 6-membered heterocycloalkyl; R 3d However, 1 to 4 R 8 16. The compound according to clause 15, optionally substituted with a group.

[0312] 18. The compound according to formula (I) [ka] 2. The compound according to clause 1, selected from:

[0313] 19. A pharmaceutical composition comprising a compound according to any one of clauses 1 to 18 and one or more pharmaceutically acceptable excipients.

[0314] 20. A compound according to any one of clauses 1 to 18 for use as a medicament.

[0315] 21. A compound according to any one of clauses 1 to 18 for use in the treatment of a disease selected from inflammatory disorders, immune disorders, and autoimmune disorders.

[0316] 22. A compound according to any one of clauses 1 to 18 for use in the treatment of cancer. DETAILED DESCRIPTION OF THE INVENTION

[0317] As used herein, the term "about" has its ordinary meaning in the context of pharmaceutical and cosmetic formulations and allows for reasonable variation in amounts that achieve the same effect, typically within plus or minus 30%. For example, if an amount of "about 1" is provided, this amount can be up to 1.3 or as low as 0.70. If "about X" results in a value greater than 100%, in some embodiments, the term can be read as reflecting that the total of the minimum amounts of the other components has been reduced to up to 100% by weight. Similarly, it will be understood by those skilled in the art that as X decreases to the extent that the amounts of the other components are appropriately increased. As will be understood by those skilled in the art, there is a degree of reasonable flexibility in formulating compositions, such that if one or more components vary, even if the amount is slightly outside the range, a good formulation can still be achieved. Therefore, to account for this possibility, amounts are modified by about. In some embodiments, for example, the amounts of the formulation components can be read as if the term "about" were prefixed. In one or more other embodiments, for example, it can be read without the term "about". In some embodiments, these numbers can be read with the term "about" prefixed. In one or more other embodiments, the numbers can be read without the term "about". In one or more narrower embodiments, unless the context indicates otherwise, "about" can be plus or minus 15%. If "about" is used in relation to ">X" or "<X" or a series of such alternatives, in some embodiments, it can include about X. If "about" is used at the start of a series of alternative amounts of ">about X" or "<about X" or "about>X" or "about<X", in some embodiments, it can be understood to include "about" before all of the other alternative amounts in the series.

[0318] C m -C n The term "-C" refers to a group having from m to n carbon atoms. For example, the term "C0" refers to a group having 0 carbon atoms.

[0319] The term "alkyl" refers to a monovalent, straight or branched, saturated hydrocarbon chain. For example, C1-C6-alkyl can refer to methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, and n-hexyl. An alkyl group can be unsubstituted or substituted with one or more substituents.

[0320] The term "alkylene" refers to a divalent, straight, saturated hydrocarbon chain. For example, C1-C3-alkylene can refer to methylene, ethylene, or propylene. An alkylene group can be unsubstituted or substituted with one or more substituents. For example, the term "C0-alkylene" refers to a group in which the alkylene chain is absent. For example, "C0-alkylene-R a " is R a Refers to...

[0321] The term "haloalkyl" refers to a hydrocarbon chain substituted with at least one halogen atom, each independently selected from fluorine, chlorine, bromine, and iodine. The halogen atom can be located at any position on the hydrocarbon chain. For example, C1-C6-haloalkyl can refer to chloromethyl, fluoromethyl, trifluoromethyl, chloroethyl, such as 1-chloromethyl and 2-chloroethyl, trichloroethyl, such as 1,2,2-trichloroethyl, 2,2,2-trichloroethyl, fluoroethyl, such as 1-fluoromethyl and 2-fluoroethyl, trifluoroethyl, such as 1,2,2-trifluoroethyl and 2,2,2-trifluoroethyl, chloropropyl, trichloropropyl, fluoropropyl, or trifluoropropyl. A haloalkyl group can be a fluoroalkyl group, i.e., a hydrocarbon chain substituted with at least one fluorine atom. Thus, a haloalkyl group can have any amount of halogen substituents. The group can contain a single halogen substituent, two or three halogen substituents, or be saturated with halogen substituents.

[0322] The term "alkenyl" refers to a branched or straight hydrocarbon chain containing at least one double bond. The double bond(s) may exist as E or Z isomers. The double bond may be at any possible position on the hydrocarbon chain. For example, "C2-C6-alkenyl" may refer to ethenyl, propenyl, butenyl, butadienyl, pentenyl, pentadienyl, hexenyl, and hexadienyl. Alkenyl groups can be unsubstituted or substituted with one or more substituents.

[0323] The term "alkynyl" refers to a branched or straight hydrocarbon chain containing at least one triple bond. The triple bond may be located at any possible position on the hydrocarbon chain. C2-C6 alkynyl may refer to, for example, ethynyl, propynyl, butynyl, pentynyl, and hexynyl. An alkynyl group can be unsubstituted or substituted with one or more substituents.

[0324] The term "cycloalkyl" refers to a saturated hydrocarbon ring system containing 3, 4, 5, or 6 carbon atoms. For example, "C3-C6-cycloalkyl" can refer to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. Cycloalkyl groups can be unsubstituted or substituted with one or more substituents.

[0325] The term "y- to z-membered heterocycloalkyl" refers to a y- to z-membered heterocycloalkyl group. Thus, it can refer to a cyclic or bicyclic saturated or partially saturated group having y to z atoms in the ring system and containing one or two heteroatoms independently selected from O, S, and N (i.e., one or two of the atoms forming the ring system are selected from O, S, and N). Partially saturated means that the ring can contain one or two double bonds. This is particularly true for monocyclic rings having five or six members. The double bond is typically between two carbon atoms, but can also be between a carbon atom and a nitrogen atom. Examples of heterocycloalkyl groups include oxirane, aziridine, thiirane, oxetane, azetidine, thietane, piperidine, piperazine, morpholine, thiomorpholine, pyrrolidine, tetrahydrofuran, tetrahydrothiophene, dihydrofuran, tetrahydropyran, dihydropyran, dioxane, and azepine. A heterocycloalkyl group can be unsubstituted or substituted with one or more substituents.

[0326] An aryl group can be any aromatic carbocyclic ring system (i.e., a ring system containing 2(2n+1) π electrons). An aryl group can have 6 to 10 carbon atoms in the ring system. An aryl group is typically a phenyl group. An aryl group can be a naphthyl group or a biphenyl group.

[0327] The term "heterocyclyl" refers to a ring containing 1 to 4 heteroatoms independently selected from O, S, and N. The ring can be a heterocycloalkyl ring (including both saturated and partially saturated rings) or a heteroaryl ring. The term "heterocyclyl" also encompasses tautomers of hydroxyheteroaryl groups, such as pyridones, and tautomers of hydroxyheteroaryl groups substituted on nitrogen, such as N-alkylpyridones.

[0328] The term "heterocycloalkenyl" refers to a partially saturated ring containing 1 to 2 heteroatoms independently selected from O, S, and N.

[0329] The term "heteroaryl" refers to any aromatic (i.e., a ring system containing 2(2n+1) π-electrons) five- or six-membered ring system containing one to four heteroatoms independently selected from O, S, and N (i.e., one to four of the atoms forming the ring system are selected from O, S, and N). Thus, any heteroaryl group can be independently selected from five-membered heteroaryl groups in which the heteroaromatic ring is substituted with one to four heteroatoms independently selected from O, S, and N, and six-membered heteroaryl groups in which the heteroaromatic ring is substituted with one to three (e.g., one to two) nitrogen atoms. Specifically, heteroaryl groups can be independently selected from pyrrole, furan, thiophene, pyrazole, imidazole, oxazole, isoxazole, triazole, oxadiazole, thiadiazole, tetrazole, pyridine, pyridazine, pyrimidine, pyrazine, and triazine.

[0330] Variables that can be selected from "carbon" and "nitrogen" (i.e., X 1 , X 2 , X 3 , X 4 , X 5 etc.), the carbon or nitrogen may additionally contain hydrogen and / or the specified substituents in the ring system (i.e., -R 2a , R 4 ) can be understood.

[0331] Optional substituents (i.e., -R 2a , R 4 ), it is understood that in ring systems representing the formula (I), substituents, when present, may replace a hydrogen on any carbon or nitrogen of the ring system.

[0332] Compounds of the present disclosure that contain one or more asymmetric carbon atoms can exist as two or more stereoisomers. Certain compounds of the present disclosure may exist in specific geometric and / or stereoisomeric forms, and the present disclosure contemplates all such compounds, including cis and trans isomers, R- and S-enantiomers, diastereomers, racemic mixtures thereof, and other mixtures, within the scope of the present disclosure. Additional asymmetric carbon atoms may be present in substituents such as alkyl groups. All such isomers and mixtures thereof are included in the present disclosure.

[0333] When a compound of the present disclosure contains a double bond, such as a C=C or C=N group, geometric cis / trans (or Z / E) isomers are possible. When structural isomers are interconvertible via a low energy barrier, tautomeric isomerism ("tautomerism") can occur. This can take the form of, for example, proton tautomers in compounds of the present disclosure containing imino, keto, or oxime groups, or so-called valence tautomers in compounds containing aromatic moieties. Thus, a single compound may exhibit more than one type of isomerism.

[0334] Included within the scope of this disclosure are all stereoisomeric, geometric isomeric, and tautomeric forms of the disclosed compounds, including compounds exhibiting more than one type of isomerism, and mixtures of one or more thereof. Also included are acid addition or base salts in which the counterion is optically active, e.g., d-lactate or l-lysine, or racemic, e.g., dl-tartrate or dl-arginine.

[0335] Cis / trans isomers can be separated by conventional techniques well known to those skilled in the art, such as chromatography and fractional crystallization.

[0336] Conventional techniques for the preparation / isolation of individual enantiomers include chiral synthesis from resolution of a suitable optically pure precursor or racemate (or racemate of a salt or derivative), if necessary, using, for example, chiral high-pressure liquid chromatography (HPLC). The chiral compounds of the present disclosure (and their chiral precursors) can be obtained in enantiomerically enriched form by chromatography, typically using HPLC, on an asymmetric resin using a mobile phase consisting of a hydrocarbon, typically heptane or hexane, containing about 0 to about 50% by volume, typically about 2% to about 20% isopropanol, and, for example, about 0 to about 5% by volume of an alkylamine, such as about 0.1% diethylamine. Concentration of the eluate yields the enriched mixture.

[0337] Alternatively, the racemate (or racemic precursor) may be reacted with a suitable optically active compound, for example, an alcohol, or, if the compound of the present disclosure contains an acidic or basic moiety, with a base or acid such as 1-phenylethylamine or tartaric acid. The resulting diastereomeric mixture may be separated by chromatography and / or fractional crystallization, and one or both of the diastereoisomers may be converted to the corresponding pure enantiomer(s) by means well known to those skilled in the art.

[0338] When any racemate crystallizes, two different types of crystals are possible. The first type is the racemate (true racemate) mentioned above, where one homogeneous form of crystal is produced containing both enantiomers in equimolar amounts. The second type is the racemic mixture or conglomerate, where two forms of crystal are produced in equimolar amounts, each containing a single enantiomer.

[0339] Both crystalline forms present in a racemic mixture have identical physical properties, but may have different physical properties than the true racemate. Racemic mixtures can be separated by conventional techniques known to those skilled in the art. See, for example, "Stereochemistry of Organic Compounds" by EL Eliel and SH Wilen (Wiley, 1994).

[0340] The present disclosure also includes all pharmaceutically acceptable isotopically labeled compounds of Formula (I) and their syntheses, wherein one or more atoms are replaced by an atom having the same atomic number but an atomic mass or mass number different from the atomic mass or mass number usually found in nature.

[0341] Examples of isotopes suitable for inclusion in compounds of the present disclosure include hydrogen isotopes, e.g. 2 H and 3 H, carbon isotopes, e.g. 11 C. 13 C, and 14 C, chlorine isotopes, e.g. 36 Cl, fluorine isotopes, e.g. 18 F, iodine isotopes, e.g. 123 I and 125 I, nitrogen isotopes, e.g. 13 N and 15 N, oxygen isotopes, e.g. 15 O. 17 O, and 18 O, phosphorus isotopes, e.g. 32 P, as well as sulfur isotopes, e.g. 35 Examples include S.

[0342] Isotopically labeled compounds can generally be prepared by conventional techniques known to those skilled in the art, or by processes similar to those described, substituting the appropriate isotopically labeled reagent for the previously used non-isotopically labeled reagent.

[0343] Suitable pharmaceutically acceptable salts include, but are not limited to, salts of pharmaceutically acceptable inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid, boric acid, sulfamic acid, and hydrobromic acid, or salts of pharmaceutically acceptable organic acids such as acetic acid, propionic acid, butyric acid, tartaric acid, maleic acid, hydroxymaleic acid, fumaric acid, malic acid, citric acid, lactic acid, mucic acid, gluconic acid, benzoic acid, succinic acid, oxalic acid, phenylacetic acid, methanesulfonic acid, toluenesulfonic acid, benzenesulfonic acid, salicylic acid, sulfanilic acid, aspartic acid, glutamic acid, edetic acid, stearic acid, palmitic acid, oleic acid, lauric acid, pantothenic acid, tannic acid, ascorbic acid, and valeric acid. Suitable base salts are formed from bases which form non-toxic salts. Examples include the aluminum, arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, lysine, magnesium, meglumine, olamine, potassium, sodium, tromethamine, and zinc salts. Hemisalts of acids and bases can also be formed, such as hemisulfate and hemicalcium salts.

[0344] The activity of the compounds of the present disclosure can be assessed by a variety of in silico, in vitro, and in vivo assays. In silico analysis of various compounds has been shown to be predictive of ultimate in vitro activity, as well as in vivo activity.

[0345] References to "treating" or "treatment" should be understood to include prevention and alleviation of confirmed symptoms of a condition. Thus, "treating" or "treatment" of a condition, disorder, or condition includes (1) preventing or delaying the appearance of clinical symptoms of the condition, disorder, or condition in a person who may be afflicted with or susceptible to the condition, disorder, or condition, but who has not experienced or displayed clinical or subclinical symptoms of the condition, disorder, or condition; (2) inhibiting the condition, disorder, or condition, i.e., arresting, alleviating, or delaying the onset of the disease or its recurrence (in the case of maintenance therapy), or at least one clinical or subclinical symptom thereof; or (3) palliating or alleviating the disease, i.e., causing regression of the condition, disorder, or condition, or at least one clinical or subclinical symptom thereof.

[0346] A "therapeutically effective amount" includes the amount of a compound that, when administered to a mammal for treating a disease, is sufficient to effect such treatment for the disease. The "therapeutically effective amount" will vary depending on the compound, the disease and its severity, and the age, weight, etc., of the mammal to be treated.

[0347] The compounds of the present disclosure, or pharmaceutically acceptable salts thereof, may be used per se, but will generally be administered in the form of a pharmaceutical composition in which the compounds of the present disclosure, or pharmaceutically acceptable salts thereof, are combined with a pharmaceutically acceptable adjuvant, diluent, or carrier.

[0348] Conventional procedures for the selection and preparation of suitable pharmaceutical formulations are described, for example, in "Pharmaceuticals - The Science of Dosage Form Designs", MEAulton, Churchill Livingstone, 1988.

[0349] Depending on the dosage form of the compounds of the present disclosure, pharmaceutical compositions used to administer the compounds of the present disclosure will, in some embodiments, comprise from about 0.005 to about 99 wt.% of a compound of the present disclosure, or from about 0.05 to about 80 wt.% of a compound of the present disclosure, or from about 0.10 to about 70 wt.% of a compound of the present disclosure, or from about 0.10 to about 50 wt.% of a compound of the present disclosure (all weight percentages based on the total composition). In some embodiments, pharmaceutical compositions used to administer the compounds of the present disclosure will comprise from about 0.005 to about 40 wt.% of a compound of the present disclosure, or from about 0.005 to about 30 wt.% of a compound of the present disclosure, or from about 0.010 to about 20 wt.% of a compound of the present disclosure, or from about 0.010 to about 10% wt.% of a compound of the present disclosure, or from about 0.005 to about 5% wt.% of a compound of the present disclosure. or about 0.005 to about 2% w / w of a compound of the present disclosure, or about 0.005 to about 1% w / w of a compound of the present disclosure, or about 0.005 to about 0.5% w / w of a compound of the present disclosure, or about 0.010 to about 1% w / w of a compound of the present disclosure, or about 0.010 to about 0.5% w / w of a compound of the present disclosure (all weight percentages based on the total composition).

[0350] Pharmaceutical compositions can be administered topically (e.g., to the skin), for example, in the form of creams, ointments, gels, lotions, solutions, suspensions; or systemically, for example, by oral administration in the form of tablets, lozenges, hard or soft capsules, solutions, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups or elixirs; or by parenteral administration (including intra-articular, intravenous, intracoronary, subcutaneous, intramyocardial, intraperitoneal, intramuscular, intravascular, or infusion) in the form of sterile aqueous or oily solutions, suspensions or emulsions for injection; by rectal administration in the form of suppositories or enemas; by inhalation, for example, as a finely divided powder or liquid aerosol or mist; or by administration by inhalation (e.g., as a finely divided powder).

[0351] For oral administration, the compounds of the present disclosure may be mixed with adjuvants or carriers such as lactose, saccharose, sorbitol, mannitol; starches such as potato starch, corn starch, or amylopectin; cellulose derivatives; binders such as gelatin or polyvinylpyrrolidone; and / or lubricants such as magnesium stearate, calcium stearate, polyethylene glycol, wax, paraffin, etc., and then compressed into tablets. If coated tablets are required, the cores prepared as described above may be coated with a concentrated sugar solution, which may contain, for example, gum arabic, gelatin, talc, and titanium dioxide. Alternatively, tablets may be coated with a suitable polymer dissolved in a readily volatile organic solvent. Thus, compositions intended for oral use may contain, for example, one or more colorants, sweeteners, flavorings, and / or preservatives.

[0352] For the preparation of soft gelatin capsules, the compounds of the present disclosure may be mixed with, for example, vegetable oil or polyethylene glycol.Hard gelatin capsules may contain granules of the compounds using any of the above-mentioned tablet excipients.Hard gelatin capsules may also be filled with liquid or semisolid preparations of the compounds of the present disclosure.Liquid preparations for oral administration may be in the form of syrups or suspensions, for example, solutions containing the compounds of the present disclosure, the balance being a mixture of sugar and ethanol, water, glycerol, and propylene glycol.Optionally, such liquid preparations may contain colorants, flavorings, sweeteners (e.g., saccharin), preservatives, and / or carboxymethylcellulose as a thickening agent, or other excipients known to those skilled in the art.

[0353] For intravenous (parenteral) administration, the compounds of the present disclosure may be administered as a sterile aqueous or oily solution.

[0354] The magnitude of the therapeutic or prophylactic dose of the compounds of the present disclosure will naturally vary, in accordance with well-known principles of medicine, depending on the nature and severity of the condition, the concentration of the compound required for efficacy in isolated cells, the concentration of the compound required for efficacy in experimental animals, the age and sex of the animal or patient, and the route of administration.

[0355] Dosage levels, frequency of administration, and duration of treatment of the compounds of the present disclosure are expected to vary depending on the formulation and clinical indication, age, and coexisting conditions of the patient.

[0356] An effective amount of a compound of the present disclosure for use in treating a condition is an amount sufficient to achieve symptomatic relief in the symptoms of the condition in a warm-blooded animal, particularly a human, to reduce the physical manifestations of the condition, or to slow the progression of the condition.

[0357] The amount of active ingredient that is combined with one or more excipients to produce a single dosage form will necessarily vary depending upon the host treated and the particular route of administration. For example, a formulation intended for oral administration to humans will generally contain, for example, from about 0.5 mg to about 0.5 g of active agent (more suitably, from about 0.5 to about 100 mg, e.g., from about 1 to about 30 mg), compounded with an appropriate and convenient amount of excipient, which may vary from about 5 to about 98 or about 99 percent by weight of the total composition.

[0358] For the compounds of the present disclosure, the dosage will naturally vary depending on the compound used, the dosage form, the desired treatment, and the specific disorder. When used for therapeutic or prophylactic purposes, the compounds of the present disclosure are generally administered at a daily dose ranging from, for example, about 0.1 mg / kg to about 100 mg / kg, about 1 mg / kg to about 75 mg / kg, about 1 mg / kg to about 50 mg / kg, about 1 mg / kg to about 20 mg / kg, or about 5 mg / kg to about 10 mg / kg body weight, administered in divided doses if necessary. Generally, when parenteral administration is used, a smaller dose will be administered. Thus, for example, when administered intravenously or intraperitoneally, a dose ranging from, for example, about 0.1 mg / kg to about 30 mg / kg body weight will generally be used. Similarly, when administered intraarticularly, a dose ranging from, for example, about 0.01 mg / kg to about 30 mg / kg body weight can generally be used. For administration by inhalation, a dose ranging from, for example, about 0.05 mg / kg to about 25 mg / kg body weight will be used. Suitably, the compounds of the present disclosure are administered orally, for example, in the form of tablets or capsules. The daily dose administered orally can be, for example, a total daily dose selected from about 1 mg to about 1000 mg, about 5 mg to about 1000 mg, about 10 mg to about 750 mg, or about 25 mg to about 500 mg. Typically, a unit dosage form will contain about 0.5 mg to about 0.5 g of the compounds of the present disclosure.

[0359] The compounds of the present disclosure can be administered together with other active compounds as part of a treatment plan.The other active compounds can be administered simultaneously with, after, or before the administration of the compounds of the present disclosure.The pharmaceutical preparations containing the compounds of the present disclosure can also contain one or more other active compounds.The other active compounds can be anti-cancer agents, anti-inflammatory agents, antibacterial agents, antiviral agents, antiemetic agents, antithrombotic agents, or compounds that change metabolism.

[0360] Throughout this description and the claims, the words "comprise" and "contain" and variations thereof mean "including, but not limited to," and are not intended to exclude (and do not exclude) other moieties, adjuncts, components, integers, or steps. Throughout this detailed description and the claims, the singular encompasses the plural unless the context requires otherwise. In particular, where the indefinite article is used, the specification should be understood to contemplate both the plural and the singular unless the context requires otherwise.

[0361] It should be understood that any feature, integer, property, compound, chemical moiety, or group described in connection with a particular aspect, embodiment, or example of the present disclosure is applicable to any other aspect, embodiment, or example described herein, to the extent not inconsistent therewith. All features disclosed herein (including any accompanying claims, abstract, and drawings) and / or all steps of any disclosed method or process may be combined in any combination, except combinations in which at least some of such features and / or steps are mutually exclusive. The disclosure is not limited to the details of any foregoing embodiment. The disclosure extends to any novel feature or any novel combination of features disclosed herein (including any accompanying claims, abstract, and drawings), or any novel feature or any novel combination of steps of any disclosed method or process.

[0362] It will be understood that various modifications can be made to the embodiments disclosed herein. Therefore, the above description should not be construed as limiting, but merely as exemplifications of preferred embodiments. For example, the above-described functions implemented as the best mode for carrying out the disclosure are for illustrative purposes only. Those skilled in the art can implement other configurations and methods without departing from the scope and spirit of the present disclosure. Moreover, those skilled in the art will envision other modifications within the scope and spirit of the specification appended hereto.

[0363] The reader's attention is directed to all documents and literature filed contemporaneously with or prior to this application and published herewith in connection with this application, the contents of all such documents and literature being incorporated herein by reference. Example Abbreviation [Table 1] TIFF2024523491000175.tif203162TIFF2024523491000176.tif190162TIFF2024523491000177.tif103159

[0364] Device Reactions using microwave irradiation were carried out in a Biotage Initiator microwave.

[0365] Normal phase TLC was performed on precoated silica plates (Kieselgel 60 F) with visualization by ultraviolet light (UV 254 / 365 nm) and / or ninhydrin solution. 254 , BDH).

[0366] Flash chromatography was performed using Combiflash Companion Rf (Teledyne ISCO) and pre-packed silica gel columns purchased from Grace Davison Discovery Science or SiliCycle, or silica gel columns manually packed in glass columns using Finar silica mesh size 100-200.

[0367] Preparative HPLC separations were performed using either an A) Shimadzu LC-20AP purification system equipped with a UV detector, or B) an Agilent 1200 Series infinity-II purification system equipped with a UV detector, or C) a Waters 2545 Binary Gradient Module connected to a Waters 2489 UV / Visible detector. On all instruments, HPLC chromatographic separations were performed using the indicated mobile phases on one of the following columns: A) Xbridge Prep, C18, OBD 19x250mm, 5µm; B) Virdis Prep Silica, 2-EP-OBD, 250x19mm, 5µm; C) YMC-Actus Triart Prep C18-S, 250x20mm-5µm, 12nm; D) Sunfire prep C18 column, 30x150mm, 5µm; E) Xselect CSH F-Phenyl OBD column, 19x250mm, 5µm; F) XBridge Prep Phenyl OBD column, 19x150mm, 5µm; G) Xselect CSH C18 OBD column, 30x150mm, 5µm.

[0368] 1 H NMR, 13 C NMR spectra were recorded on a Bruker AVANCE III HD 400 MHz spectrometer (400 MHz 1 H NMR and 100 MHz 13 C NMR), or Bruker AVANCE III HD 300MHz (at 300MHz) 1 H NMR at 75 MHz 13C NMR), or Bruker AVANCE NEO 400 MHz spectrometer (at 400 MHz 1 H NMR, 100 MHz 13 C NMR. Chemical shifts (δ) are in all cases expressed in ppm, recorded using residual solvent as an internal reference. Signal splitting patterns are described as singlets (s), doublets (d), triplets (t), quartets (q), multiplets (m), broad bands (br), or combinations thereof. Coupling constants (J) are expressed to the nearest 0.5 Hz.

[0369] LC-MS analysis and chromatographic separation were performed on a Waters Acquity Ultra performance LC coupled to a Waters QDA mass detector coupled to a Waters diode array detector, or on an Agilent Technologies 1200 series HPLC coupled to an Agilent Technologies 6130 quadrupole LC / MS coupled to an Agilent diode array detector. The column used for both was a Waters XBridge column (50 mm × 2.1 mm, 2.5 μm particle size). Compounds were analyzed in mobile phase A: 0.1% formic acid in Milli-Q water (pH = 2.70), mobile phase B: Milli-Q water. Elute with 0.1% formic acid in water:acetonitrile (10:90) at T = 0 min (97% A, 3% B) flow rate: 0.8 mL / min; T = 0.75 min (97% A, 3% B) flow rate: 0.8 mL / min, gradient to T = 2.7 min (2% A, 98% B) flow rate: 0.8 mL / min, T = 3 min (0% A, 100% B) flow rate: 1 mL / min, T = 3.5 min (0% A, 100% B) flow rate: 1 mL / min, gradient to T = 3.51 min (97% A, 3% B) flow rate: 0.8 mL / min; end of run at T = 4 min (97% A, 3% B) flow rate: 0.8 mL / min, or a gradient of 5–95% acetonitrile / water + 0.1% ammonia. Alternatively, a Shimadzu LMCS-2020 was used with A) an Ascentis Express C18 30 mm x 3.0 nm column, and compounds were eluted with a gradient of mobile phase A: water (0.1% FA) and mobile phase B: acetonitrile (0.1% FA) at T = 0.01 min (95% A, 5% B) at a flow rate of 1.50 L / min; at T = 1.80 min (60% A, 40% B) at a flow rate of 1.50 L / min; gradient to T = 2.00 min (0% A, 100% B), followed by a 0.7 min hold at a flow rate of 1.50 mL / min, with the end of the run at T = 2.80 min at a flow rate of 1.50 mL / min; or B) an HPH C18 Used with a 50 mm x 3.0 mm column, the compounds were separated using mobile phase A: water (0.04% NH3H2O), mobile phase B: acetonitrile, T = 2.20 min (30% A, 70% B) flow rate: 1.50 L / min, T = 2.40 min (5% A, 95% B), followed by a 0.40 min hold, flow rate: 1.50 L / min, T = 2.85 min (10% A, 90% B), flow rate: 1.C) With an HPH C18 50mm x 3.0mm column, compounds were eluted with a gradient of mobile phase A: water (0.1% FA), mobile phase B: acetonitrile (0.1% FA) at T=0.01 min (95% A, 5% B), flow rate: 1.50 L / min, T=1.80 min (40% A, 60% B), flow rate: 1.50 L / min, T=2.00 min (0% A, 100% B), followed by a 0.7 min hold; flow rate: 1.50 mL / min, gradient to T=2.74 min (95% A, 5% B), end of run at T=2.80 min, flow rate: 1.50 mL / min; D) With an EVO C18 Compounds were eluted with a 50 mm x 3.0 mm column using a gradient of mobile phase A: water (5 mM NH4HCO3), mobile phase B: acetonitrile, T = 0.01 min (90% A, 10% B) at a flow rate of 1.50 L / min, T = 2.00 min (30% A, 70% B) at a flow rate of 1.50 L / min, T = 2.20 min (5% A, 95% B), followed by a 0.40 min hold at a flow rate of 1.50 L / min, T = 2.75 min (90% A, 10% B) at a flow rate of 1.50 L / min; end of run at T = 2.80 min at a flow rate of 1.50 L / min; or E) Ascentis Express C18 Compounds were eluted with a 30 mm x 3.0 nm column using a gradient of mobile phase A: water (5 mM NH4HCO3), mobile phase B: acetonitrile, T = 0.01 min (90% A, 10% B) flow rate: 1.50 L / min, T = 2.00 min (30% A, 70% B) flow rate: 1.50 L / min, gradient to T = 2.20 min (5% A, 95% B), then hold for 0.4 min, T = 2.75 min (90% A, 10% B) flow rate: 1.50 L / min, end of run at T = 2.80 min, flow rate: 1.50 L / min.

[0370] Solvents and reagents were purchased from commercial sources and used without further purification. Dry solvents were purchased in sealed, secure bottles and stored using molecular sieves.

[0371] Compounds and compounds were named using the naming application in ChemDraw Professional 19.1.

[0372] Preparation process Certain compounds of the present disclosure can be synthesized according to the general methods disclosed herein. Certain compounds of the present disclosure can be synthesized according to, or analogously to, the syntheses provided in the Examples.

[0373] The following schemes illustrate methods for synthesizing compounds of the present disclosure: Schemes 1-4 show routes for preparing general intermediates of the present disclosure.

[0374] Scheme 1 [ka]

[0375] Scheme 2 [ka]

[0376] Scheme 3 [ka]

[0377] Scheme 4 [ka]

[0378] Scheme 5 [ka]

[0379] Scheme 6 [ka]

[0380] Scheme 7 [ka]

[0381] General Scheme 1 shows a general route for the preparation of compounds of the present disclosure via Suzuki coupling of intermediates followed by reduction, oxidation, ring condensation, and deprotection.

[0382] General Scheme 1 [ka]

[0383] General Scheme 1a shows a general route for the preparation of compounds of the present disclosure via Suzuki coupling of intermediates (1H) and (2H), followed by reduction, oxidation, ring condensation, and deprotection.

[0384] General Scheme 1a [ka]

[0385] General Scheme 2 shows a general route for the preparation of compounds of the present disclosure via Suzuki coupling of intermediates, followed by Pd coupling, reduction, oxidation, ring condensation, and deprotection.

[0386] General Scheme 2 [ka]

[0387] General Scheme 2a shows a general route for the preparation of compounds of the present disclosure via Suzuki coupling of intermediates (1H) and (3D), followed by Pd coupling, reduction, oxidation, ring condensation, and deprotection.

[0388] General Scheme 2a [ka] General Scheme 3 shows a general route for the preparation of compounds of the present disclosure via the formation of a coupling partner from (15A), followed by Pd coupling, Pd coupling, and deprotection.

[0389] General Scheme 3 [ka]

[0390] General Scheme 3a shows a general route for the preparation of compounds of the present disclosure via the formation of a coupling partner from (6C), followed by Pd coupling with (2H), Pd coupling, and deprotection.

[0391] General Scheme 3a [ka]

[0392] General Scheme 3b shows a general route for the preparation of compounds of the present disclosure via the formation of a coupling partner from (6C), followed by Pd coupling with (2H), deprotection, and Pd coupling.

[0393] General Scheme 3b [ka]

[0394] General Scheme 3c shows a general route for the preparation of compounds of the present disclosure via Pd coupling from (9C), followed by partner coupling formation, Pd coupling with (2H), and deprotection.

[0395] General Scheme 3c [ka]

[0396] General Scheme 4 shows a general route for the preparation of compounds of the present disclosure via Pd coupling from (12D), followed by Pd coupling with (7A), Pd coupling, and deprotection.

[0397] General Scheme 4 [ka] Example 1: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(5-methyl-1H-imidazol-2-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 1: (E)-2-(5-bromo-2-methoxy-3-nitropyridin-4-yl)-N,N-dimethylethan-1-amine 5-Bromo-2-methoxy-4-methyl-3-nitropyridine (50 g, 202 mmol) was dissolved in DMF (410 mL) under nitrogen and heated to 80° C. DMF-DMA (224 mL, 1.686 mol) was added over 20 minutes. The resulting dark solution was heated at 95° C. TLC (4:1 heptane / EA) after 5 hours showed no residual SM. The mixture was cooled to room temperature and poured into ice-water (1100 mL). The resulting suspension was stirred for 15 minutes and then filtered. The collected red solid was washed with water and dried under vacuum at 50° C. overnight (56.6 g, 61%). The material was used directly in Preparation 2 without further purification. 1 H NMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 7.02 (d, J=13.7 Hz, 1H), 4.94 (d, J=13.7 Hz, 1H), 3.97 (s, 3H), 2.94 (s, 6H). Preparation 2: 4-Bromo-7-methoxy-1H-pyrrolo[2,3-c]pyridine (E)-2-(5-Bromo-2-methoxy-3-nitropyridin-4-yl)-N,N-dimethylethan-1-amine (23.3 g, 77.1 mmol) was partially dissolved in methanol (1100 mL) and ammonium chloride (23.3 g, 436 mmol), followed by water (140 mL). Iron powder (23.3 g, 417 mmol) was added, and the mixture was heated under reflux. The reaction mixture was stirred using an overhead stirrer. After 5 hours, an additional aliquot of iron powder (23.3 g, 417 mmol) was added, and heating was continued overnight. The mixture was cooled, and solid Na2CO3 was added. The mixture was filtered through a pad of Celite and dried under vacuum. The residue was triturated with 4:1 heptane / ethyl acetate. The mixture was filtered through a pad of silica. The filtrate was evaporated. The residue was purified on silica eluting with 100:0 to 80:20 heptane / ethyl acetate. Solvent reduction gave an off-white solid (3.7 g, 21%). HPLC R (Agilent, acidic, 3.5 min): 1.46 min, MS: m / z 229.0 [M+H] + Preparation 3: 4-Bromo-7-methoxy-1-tosyl-1H-pyrrolo[2,3-c]pyridine Sodium hydride (60% w / w, 7.90 g, 198 mmol) was suspended in THF (290 mL) under nitrogen and cooled to below 4 °C in an ice bath. 4-Bromo-7-methoxy-1H-pyrrolo[2,3-c]pyridine (14.0 g, 61.7 mmol) was dissolved in THF (290 mL) and added dropwise over 30 min (gas evolution was observed, and the reaction temperature rose to 5 °C due to the generation of an exotherm). The maroon mixture was stirred at room temperature for 45 min and then cooled to 3 °C. 4-Methylbenzenesulfonyl chloride (15.7 g, 82.1 mmol) was dissolved in THF (290 mL) and added dropwise. The resulting gray suspension was stirred with cooling for 1.5 h and then at room temperature for 1 h. TLC (3:2 heptane / ethyl acetate) showed no residual SM. The reaction mixture was quenched by the dropwise addition of saturated aqueous NH4Cl (300 mL). After stirring the mixture for 5 minutes, the phases were separated. The aqueous phase was extracted with ethyl acetate (2 x 300 mL). The combined organics were washed (brine), dried (MgSO), filtered, and evaporated to an oil that crystallized upon cooling to give a light brown solid (26.2 g, 99%). The material was used directly in Preparation 4 without further purification. HPLC R (Agilent, acidic, 3.5 min): 1.94 min, m / z = 383.1 [M+H] + . Preparation 4: 4-Bromo-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 4-Bromo-7-methoxy-1-tosyl-1H-pyrrolo[2,3-c]pyridine (26.2 g, 65.3 mmol) was suspended in ethanol (50 mL) and hydrogen bromide (48% w / w, 280 mL) was added in a steady stream. The resulting mixture was heated at 90°C. After 2 hours, TLC (3:2 heptane / ethyl acetate) showed no residual SM. The reaction mixture was cooled to room temperature and then cooled in an ice bath with stirring for 30 minutes. The mixture was filtered, and the cream-colored solid was collected and washed with water. The solid was dried under vacuum at 50°C overnight (22.5 g, 94%). The material was used directly in Preparation 5 without further purification. HPLC R(Agilent, acidic, 3.5 min): 1.59 min, m / z = 369.0 [M+H] + Preparation 5: 4-Bromo-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 4-Bromo-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (22.5 g, 61.3 mmol) was dissolved in DMF (225 mL) under nitrogen. The mixture was cooled to 3 °C, and sodium hydride (60% w / w, 3.06 g, 76.6 mmol) was added portionwise, resulting in gas evolution and an exotherm to 5 °C. The mixture was stirred with cooling for 20 minutes. After gas evolution ceased, iodomethane (7.63 mL, 123 mmol) was added dropwise, resulting in an exotherm that raised the reaction temperature to 10 °C. The mixture was stirred with cooling for 15 minutes, then at room temperature for 15 minutes. LCMS after 2 hours showed no residual SM. The reaction mixture was quenched by the dropwise addition of water (100 mL, gas evolution and exotherm to 39 °C). The mixture was extracted with ethyl acetate (3 × 300 mL). The combined organics were washed (brine), dried (Na2SO4), filtered and evaporated. The crude product was triturated with TBME and filtered. The collected off-white solid was washed with TBME and dried under vacuum (15 g, 64%). HPLC R (Agilent, basic, 6.0 min): 4.0 min, m / z = 382.9 [M+H] + . Preparation 6: Ethyl 4-bromo-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate 4-Bromo-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (1.3 g, 3.4 mmol) in THF (100 mL) was cooled to -78 °C. LDA (2.03 mL, 4.06 mmol) was added dropwise, and the resulting solution was stirred at this temperature for 30 minutes. Ethyl carbonochloridate (0.39 mL, 4.06 mmol) was added, and the reaction was stirred at -78 °C for 1 hour. Ethyl acetate (500 mL) was added, and the organics were washed with 2 x 500 mL of water, followed by 1 x 500 mL of saturated brine solution. The organics were then separated, dried (MgSO), and then concentrated to dryness. The crude material was then purified by flash column chromatography eluting with an ethyl acetate / heptane gradient (0-100%). The desired fractions were combined, dried and reacted to give the title compound (770 mg, 50%). HPLC R (Agilent, acidic, 3.5 min): 1.85 min, m / z = 453.8 [M] + . Preparation 7: Ethyl 6-methyl-7-oxo-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate To a flask containing XPhos (76 mg, 0.16 mmol), ethyl 4-bromo-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate (710 mg, 1.6 mmol), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (813 mg, 3.2 mmol), and potassium acetate (188 mg, 1.92 mmol) was added 1,4-dioxane (20 mL), and the suspension was degassed for 10 min. Pd2(dba)3 (30 mg, 0.032 mmol) was added, and the mixture was degassed for an additional 1 min. The reaction was heated at 80 °C overnight. The reaction was diluted with ethyl acetate and washed with 50% brine. The organics were dried, filtered, and concentrated to a yellow / brown oil. The product was purified by flash chromatography on silica gel (20 g) eluting with an ethyl acetate / heptane gradient (0-80%). Fractions corresponding to the product were combined and concentrated to give the title compound (437 mg, 56%). HPLC R (Agilent, acidic, 3.5 min): 2.10 min, m / z = 501.1 [M+H] + . Preparation 8: 2-Chloro-5-fluoropyridine 1-oxide Trifluoroacetic acid (2.4 L, 8v) was placed in a 5 L four-neck RBF at 0 °C. 2-Chloro-5-fluoropyridine (300 g, 229.02 mmol) was added dropwise to the pre-cooled mixture over 20 minutes using an addition funnel. 30% hydrogen peroxide (450 mL, 39.70 mmol) was slowly added to the reaction mixture. The resulting mixture was heated at 75 °C for 16 hours. TLC (5.0:5.0 hexanes:ethyl acetate) showed no residual SM. Trifluoroacetic acid (2.3 L) was isolated by vacuum distillation. The resulting mixture was diluted with cold water (2000 mL) and 70% aqueous ammonia solution (500 mL) was added. The aqueous fraction was extracted with dichloromethane (6 x 2000 mL). The combined organics were washed (brine), dried (NaSO), filtered, and evaporated. The residue was triturated with n-pentane. Solvent reduction gave a light brown solid (314g, 93.32%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 0.453 min, m / z = 147.96 [M+H] 1 H NMR (400 MHz, DMSO d6) δ 8.82 (m, 1H), 7.88 (m, 1H), 7.44 (m, 1H). Preparation 9: 2-Chloro-5-fluoro-4-nitropyridine 1-oxide 2-Chloro-5-fluoropyridine 1-oxide (100 g, 677.9 mmol) was dissolved in HSO (500 mL, 5V) in a 5 L four-neck RBF at room temperature. The resulting mixture was heated to 90 °C. A pre-stirred solution of HSO (1000 mL, 10V) and HNO (283 mL, 6777.9 mmol) at 0 °C was added dropwise to the reaction mixture at 90 °C. The reaction mixture was stirred at the same temperature for 2 h. TLC (5.0:5.0 hexane:ethyl acetate) showed no residual SM. The resulting mixture was cooled to room temperature, and ice (5 kg) was added portionwise with stirring. The aqueous fraction was extracted with ethyl acetate (2 × 1000 mL), and the combined organics were washed (NaHCO solution), dried (NaSO), filtered, and evaporated. The resulting mixture was triturated with hexane (2 × 50 mL). Solvent reduction gave a pale yellow solid (68g, 53.87%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 0.830 min, m / z = 193.12 [M+H] + . 1 H NMR (400 MHz, DMSO d6) δ 8.82 (d, J=6.8 Hz, 1H), 8.82 (d, J=8.8 Hz, 1H). Preparation 10: 2-chloro-5-(2,6-dimethylphenoxy)-4-nitropyridine 1-oxide 2-Chloro-5-fluoro-4-nitropyridine-1-oxide (178.5 g, 934.5 mmol) was dissolved in dimethylformamide (892.5 mL, 5V) under nitrogen. Potassium carbonate (768.20 g, 5,607 mmol) was added to the reaction mixture and stirred for 30 minutes. 2,6-Dimethylphenol (119.71 g, 981.28 mmol) was added to the reaction mixture and stirred at room temperature for 4 hours. TLC (7.0:3.0 hexane:ethyl acetate) showed no residual SM. The resulting mixture was quenched with water (1000 mL) and stirred for 30 minutes. The resulting residue was filtered and triturated with n-hexane. The solid was dried under vacuum at 45° C. overnight (245 g, 89.67%). 1H NMR (400 MHz, DMSO d6) δ 8.72 (s, 1H), 7.42 (s, 1H), 7.23 (m, 3H), 2.14(s, 6H). Preparation 11: 2,4-Dibromo-5-(2,6-dimethylphenoxy)pyridine 1-oxide 2-Chloro-5-(2,6-dimethylphenoxy)-4-nitropyridine-1-oxide (40 g, 13.5 mmol) was dissolved in acetyl bromide (200 mL, 5V) at room temperature under nitrogen. The resulting mixture was heated to 75 °C, and acetyl bromide (200 mL, 5V) was added dropwise. The reaction mixture was stirred at the same temperature for 4 h. TLC (5.0:5.0 hexane:ethyl acetate) showed no residual SM. The resulting mixture was slowly poured into cold water (5000 mL). The aqueous fraction was extracted with ethyl acetate (2 × 2000 mL). The combined organics were washed (NaHCO solution), dried (NaSO), filtered, and evaporated. Solvent reduction gave a light brown solid (26 g, 51.35%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.97 min, m / z = 372.0 [M+H] + . 1 H NMR (400 MHz, DMSO d6) δ 8.42 (s, 1H), 7.21 (m, 4H), 2.10 (s, 6H). Preparation 12: 2,4-Dibromo-5-(2,6-dimethylphenoxy)pyridine 2,4-Dibromo-5-(2,6-dimethylphenoxy)pyridine 1-oxide (200 g, 539.08 mmol) was dissolved in chloroform (2000 mL, 10 V) under nitrogen. Phosphorus tribromide (200 mL, 1 V) was added dropwise to the reaction mixture over 30 minutes and stirred at 55 °C for 2 hours. TLC (5.0:5.0 hexanes:ethyl acetate) showed no residual SM. The resulting mixture was slowly poured into cold water (5000 mL). The aqueous fraction was extracted with ethyl acetate (2 × 2000 mL). The combined organics were washed (NaHCO solution), dried (NaSO), filtered, and evaporated. Solvent reduction gave a light brown solid (130 g, 67.91%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 2.67 min, m / z = 356.1 [M+H] + . 1 H NMR (400 MHz, DMSO d6) δ 8.16 (s, 1H), 7.36 (s, 1H), 7.20-7.18 (m, 3H), 2.07 (s, 6H). Preparation 13: 4-Bromo-5-(2,6-dimethylphenoxy)pyridin-2-ol 2,4-Dibromo-5-(2,6-dimethylphenoxy)pyridine (10 g, 28.24 mmol) was dissolved in tert-butanol (125 mL, 12.5 V) in an autoclave at room temperature. Potassium hydroxide (15.8 g, 282.40 mmol) was added to the reaction mixture, which was stirred at 150 °C for 16 h. TLC (9.0:1.0 DCM:methanol) showed no residual SM. The reaction mixture was cooled to 0 °C, and ice was added. The mixture was acidified with 2 N HCl to adjust the pH to 2. The resulting fractions were extracted with DCM (2 × 700 mL). The combined organics were washed (brine solution), dried (NaSO), filtered, and evaporated. The residue was triturated with ethyl acetate (100 mL). Solvent reduction gave a light brown solid (4 g, 48.55%) (LCMS purity 43.68%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.69 min, m / z = 294.0 [M+H] + 1 H NMR (400 MHz, DMSO d6) δ 11.27 (br s, 1H), 7.18-7.09 (m, 3H), 6.92 (s, 1H), 6.36 (s, 1H), 2.09 (s, 6H). Preparation 14: 4-Bromo-5-(2,6-dimethylphenoxy)-1-methylpyridin-2(1H)-one 4-Bromo-5-(2,6-dimethylphenoxy)pyridin-2-ol (22.78 g, 77.7 mmol) was dissolved in DMF (227.8 mL, 10 v) under nitrogen. Cesium carbonate (76.01 g, 233.2 mmol) was added to the reaction mixture and cooled to 0 °C. MeI (176.5 g, 1244 mmol) was added dropwise to the reaction mixture and stirred at room temperature for 2 h. TLC (9.0:1.0 DCM:methanol) showed no residual SM. The reaction mixture was quenched with water (500 mL) and extracted with DCM (3 × 500 mL). The combined organics were washed (brine solution), dried (NaSO), filtered, and evaporated. The residue was purified on silica eluting with 39.0:61.0 acetonitrile:HO. Solvent reduction gave an off-white solid (10 g, 41.90%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.81 min, m / z = 310.0 [M+H] + . 1 H NMR (400 MHz, DMSO d6) δ 7.17-7.08 (m, 3H), 6.92 (s, 1H), 6.73 (s, 1H), 3.26 (s, 3H), 2.12 (s, 6H). Preparation 15: Ethyl 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate 4-Bromo-5-(2,6-dimethylphenoxy)pyridin-2-ol (3.0 g, 9.7 mmol) was dissolved in 1,4-dioxane (80 mL) and water (13.3 mL). Ethyl 6-methyl-7-oxo-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate (8.30 g, 16.6 mmol) was added to the reaction mixture, followed by KPO (5.17 g, 24.4 mmol). The suspension was degassed with argon for 30 minutes. Pd(dba)3 (0.44 g, 0.48 mmol) and X-Phos (0.22 g, 0.48 mmol) were added to the reaction mixture, and the resulting dark solution was heated at 100 °C for 2 h. TLC (9:1 ethyl acetate:MeOH) showed no residual SM. The mixture was cooled to room temperature and quenched by the addition of water (50 mL). After stirring the mixture for 5 min, the phases were separated. The aqueous phase was extracted with ethyl acetate (3 × 50 mL). The combined organics were dried (Na2SO4), filtered, and evaporated. The residue was purified on silica eluting with 06:94 methanol:EtOAc to give an off-white solid (3.1 g, 52.99%) upon solvent reduction. LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 2.12 min, m / z = 602.15 [M+H] + . 1 H NMR (400 MHz, DMSO d6) δ 8.34 (d, J = 8.4 Hz, 2H), 7.87 (s, 1H), 7.50 (d, J = 8.0 Hz, 2H), 7.12-7.02 (m, 4H), 6.70 (s, 1H), 6.50 (s, 1H), 4.38 - 4.32 (m, 2H), 3.54 (s, 3H), 3.31 (s, 3H), 2.42 (s, 3H), 2.06 (s, 6H), 1.31 (t, J = 6.8 Hz, 3H) Preparation 16: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(hydroxymethyl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Ethyl 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate (2.4 g, 3.99 mmol) was dissolved in DCM (240 mL) under argon, and the reaction mixture was cooled to −20° C. DIBAL-H (11.92 g, 83.8 mmol) was added dropwise to the reaction mixture at −20° C. over 6 hours. TLC (9:1 DCM:MeOH) showed no residual SM. The mixture was diluted with DCM (240 mL) and quenched by the addition of NaOH solution (300 mL). The resulting mixture was passed through a Celite filter. The mixture was separated, and the aqueous layer was re-extracted with DCM (240 mL). The combined organics were dried (Na2SO4), filtered and evaporated. The residue was purified on silica eluting with 3:97 methanol:DCM to give an off-light yellow solid on solvent reduction (0.8g, 34%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.768 min, m / z = 560.11 [M+H] + 1 H NMR: (400 MHz, DMSO) δ 8.16 (d, J=8.4 Hz, 2H), 7.70 (s, 1H), 7.40 (d, J=8.0 Hz, 2H), 7.11-7.02 (m, 3H), 6.66 (d, J=9.2 Hz, 2H), 6.45 (s, 1H), 5.61 (t, J=5.6 Hz, 1H), 4.92 (d, J=5.6Hz, 2H), 3.45 (s, 3H), 3.31 (s, 3H), 2.37 (s, 3H), 2.06 (s, 6H). Preparation 17: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carbaldehyde 4-(5-(2,6-Dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(hydroxymethyl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.9 g, 1.60 mmol) was dissolved in DCM (9 mL). Manganese oxide (0.84 g, 9.64 mmol) was added, and the reaction mixture was heated to 50° C. for 4 h. TLC (9:1 DCM:MeOH) showed no residual SM. The mixture was filtered through Celite and concentrated. Solvent reduction gave a pale yellow solid (0.80 g, 89%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 2.022 min, m / z = 558.16 [M+H] + 1 H NMR: (400 MHz, DMSO) δ 10.30 (s, 1H), 8.26 (d, J=8.4Hz, 2H), 7.84 (s, 1H), 7.47 (d, J=8.4 Hz, 2H), 7.28 (s, 1H), 7.10-7.03 (m, 3H), 6.70 (s, 1H), 6.50 (s, 1H), 3.52 (s, 3H), 3.33 (s, 3H), 2.42 (s, 3H), 2.05 (s, 6H). Preparation 18: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(5-methyl-1H-imidazol-2-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carbaldehyde (0.12 g, 0.21 mmol) was dissolved in methanol (2.4 mL) under nitrogen. Ammonium carbonate (0.06 g, 0.63 mmol) was added to the reaction mixture and stirred at room temperature for 30 minutes. 2-Oxopropanal (0.077 g, 1.07 mmol) was added to the reaction mixture. The reaction mixture was heated at 50° C. for 5 hours. TLC (9.5:0.5 DCM:methanol) showed no residual SM. The reaction mixture was cooled to 0° C. Sodium hydroxide (0.042 g, 1.05 mmol) was added to the reaction mixture. The dark solution was stirred at 100° C. for 2 hours. TLC (9:1 DCM:methanol) showed no residual SM. The resulting solution was directly concentrated under reduced pressure. The resulting residue was purified by preparative HPLC purification (instrument A, column A) eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. Lyophilization gave a white solid (0.03 g, 40.12%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.294 min, m / z = 456.1 [M+H] + 1 H NMR (400 MHz, DMSO) δ 12.829 (s, 1H), 7.663 (s, 1H), 7.523 (s, 1H), 7.303 (s, 1H), 7.118-7.056 (m, 3H), 6.752 (s, 1H), 6.603 (s, 1H), 3.622 (s, 3H), 3.348 (s, 3H), 2.348 (s, 3H), 2.081 (s, 6H). NOTE: One exchangeable -NH has not been observed. Example 2: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(1H-imidazol-2-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 19: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(1H-imidazol-2-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 4-(5-(2,6-Dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carbaldehyde (0.2 g, 0.35 mmol) was dissolved in methanol (4 mL) under nitrogen. Ammonium hydroxide (2 mL, 10 V) was added to the reaction, and the reaction mixture was stirred at room temperature for 30 minutes. Oxalaldehyde (0.208 g, 3.5 mmol) was added to the reaction mixture at room temperature. The reaction mixture was heated at 50° C. TLC (9.5:0.5 DCM:methanol) after 16 hours showed no residual SM. The reaction mixture was cooled to 0° C. Sodium hydroxide (0.071 g, 1.79 mmol) was added to the reaction mixture. The dark solution of the reaction was stirred at 100°C for 3 hours. TLC (9:1 DCM:methanol) showed no residual SM. The resulting solution was directly concentrated under reduced pressure in vacuo. The resulting residue was purified by preparative HPLC purification (instrument B; column B) eluting with a gradient of 0.1% methanolic ammonia in heptane and acetonitrile. Lyophilization gave a white solid (0.01 g, 6.2%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.267 min, m / z = 442.1 [M+H] + 1H NMR (400 MHz, DMSO) δ 12.364 (br s, 1H), 7.533 (s, 1H), 7.116-7.098 (m, 3H), 7.062-7.046 (m, 2H), 6.833 (s, 1H), 6.676 (s, 1H), 6.573 (s, 1H), 3.592 (s, 3H), 2.095 (s, 6H), 1.293-1.228 (m, 3H). NOTE: One exchangeable -NH has not been observed. Example 3: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(5-(trifluoromethyl)-1H-imidazol-2-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 20: 3,3,3-trifluoro-2-oxopropanal 3,3-Dibromo-1,1,1-trifluoroacetone (1.0 g, 3.70 mmol) was dissolved in water (5 mL). The resulting solution was stirred at room temperature for 5 minutes. Sodium acetate (1.2 g, 14.8 mmol) was added to the reaction mixture at room temperature. The resulting solution was stirred at 100° C. for 16 hours. TLC (9.5:0.5 DCM / methanol) showed no residual SM. The reaction mixture was diluted with water (50 mL). After stirring the mixture for 5 minutes, the phases were separated. The aqueous phase was extracted with ethyl acetate (6×50 mL). The combined organics were washed (brine), dried (NaSO), filtered, and evaporated to give a yellow liquid (0.5 g). This material was used in the next step without purification. Preparation 21: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-2-(5-(trifluoromethyl)-1H-imidazol-2-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 4-(5-(2,6-Dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carbaldehyde (0.2 g, 0.359 mmol) and 3,3,3-trifluoro-2-oxopropanal (0.362 g, 2.870 mmol) were dissolved in methanol (4 mL). The resulting solution was stirred at 0 °C for 5 minutes. To the reaction mixture was added 25% NH4OH solution (1 mL) at 0 °C. TLC (9.5:0.5 DCM / methanol) showed no residual SM. The reaction mixture was concentrated under reduced pressure to give the crude material. The residue was purified on silica gel eluting with 2.5% methanol in DCM. Solvent reduction gave a brown solid (0.160 g, 67.22%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.104 min, m / z = 664.19 [M+H] + Preparation 22: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(5-(trifluoromethyl)-1H-imidazol-2-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 4-(5-(2,6-Dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-2-(5-(trifluoromethyl)-1H-imidazol-2-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.100 g, 0.15 mmol) was dissolved in 1 M TBAF solution (5 mL) at room temperature. The resulting solution was stirred at room temperature for 4 hours. TLC (9.5:0.5 DCM / methanol) showed no residual SM. The reaction mixture was concentrated under reduced pressure to give the crude material. The residue was purified by preparative HPLC purification (Instrument A, Column C) eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. Lyophilization gave a white solid (0.006 g, 7.82%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.739 min, m / z = 510.12 [M+H] + 1H NMR: (400 MHz, DMSO) δ 12.89 (s, 1H), 12.48 (s, 1H), 7.97 (s, 1H), 7.57 (s, 1H), 7.12-7.03 (m, 3H), 6.96 (s, 1H), 6.69 (s, 1H), 6.58 (s, 1H), 3.60 (s, 3H), 3.33(s, 3H), 2.09 (s, 6H). Example 4: 2-(4,5-dihydro-1H-imidazol-2-yl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 23: 2-(4,5-dihydro-1H-imidazol-2-yl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 4-(5-(2,6-Dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carbaldehyde (0.3 g, 0.538 mmol) and ethane-1,2-diamine (0.033 g, 0.565 mmol) were dissolved in DCM (7.5 mL, 25 Vol). The resulting solution was stirred at 0° C. for 15 min. NBS (0.1 g, 0.565 mmol) was added to the reaction mixture at 0° C. TLC (9:1 DCM / methanol) showed no residual SM. The reaction mixture was quenched with saturated NaHCO (50 mL). After stirring the mixture for 5 min, the phases were separated. The aqueous phase was extracted with ethyl acetate (2 x 20 mL). The combined organics were washed (brine), dried (Na2SO4), filtered and evaporated under reduced pressure to give a pale green solid (0.220 g, 68.42%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.44 min, m / z = 598.1 [M+H] + Preparation 24: 2-(4,5-dihydro-1H-imidazol-2-yl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 2-(4,5-Dihydro-1H-imidazol-2-yl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.175 g, 0.29 mmol) was dissolved in 1,4-dioxane (2 mL, 22 Vol). Sodium hydroxide (0.058 g, 1.46 mmol) was added to the reaction mixture, followed by water (0.1 mL) at room temperature. The resulting solution was heated at 100° C. for 2 hours. TLC (9.5:0.5 DCM / methanol) showed no residual SM. The reaction mixture was concentrated under reduced pressure to give a crude yellow solid. This was purified by preparative HPLC purification (instrument A, column A) eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. Lyophilization gave a white solid (0.010 g, 8.47%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.213 min, m / z = 444.07 [M+H] + 1H NMR: (400 MHz, DMSO) δ 7.45 (s, 1H), 7.11 (d, J = 7.2 Hz, 2H), 7.06 (t, J = 6.4 Hz, 1H), 6.88 (s, 1H), 6.64 (s, 1H), 6.56 (s, 1H), 3.64 (s, 4H), 3.55 (s, 3H), 3.31 (s, 3H), 2.08 (s, 6H). Example 5: 6-methyl-2-(5-methyl-1H-imidazol-2-yl)-4-(1-methyl-2-oxo-5-phenyl-1,2-dihydropyridin-4-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 25: 5-Bromo-4-iodopyridin-2-amine 4-Iodopyridin-2-amine (20.0 g, 90.90 mmol) was dissolved in ACN (800 mL) under nitrogen. N-Bromosuccinamide (16.3 g, 91.8 mmol) was added to the reaction mixture at room temperature. The resulting suspension was stirred at room temperature for 16 hours. TLC (3:7 hexane / EA) showed no residual SM. The resulting solution was directly concentrated under reduced pressure in vacuo, and DCM (200 mL) was added. The combined organics were washed (brine), dried (Na2SO4), filtered, and evaporated to give an oil. The product was purified by flash column chromatography on silica eluting with 90:10 hexane / ethyl acetate. Fractions corresponding to the product were combined and concentrated to give an off-white solid (25 g, 92.01%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.22 min, m / z = 298.8 [M+H] + 1H NMR: (400 MHz, DMSO) δ 8.01 (s, 1H), 7.05 (s, 1H), 6.27 (s, 2H). Preparation 26: 5-Bromo-4-iodopyridin-2(1H)-one 5-Bromo-4-iodopyridin-2-amine (27.0 g, 90.33 mmol) was dissolved in sulfuric acid (500 mL). Sodium nitrite (12.50 g, 181.1 mmol) in water (54 mL) was added dropwise to the reaction mixture at 0 °C. The reaction mixture was stirred at room temperature for 2 hours. TLC (5:5 hexane / ethyl acetate) showed no residual SM. The resulting mixture was cooled to 0 °C and quenched by the dropwise addition of ammonia solution to give a pale yellow precipitate, which was filtered. The resulting solid was dried under vacuum at 50 °C overnight (21 g, 77.52%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.19 min, m / z = 299.8 [M+H] + HPLC: (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 3.50 min 1H NMR: (400 MHz, DMSO) δ 11.99 (br s, 1H), 7.80 (s, 1H), 7.13 (s, 1H). Preparation 27: 5-Bromo-4-iodo-1-methylpyridin-2(1H)-one 5-Bromo-4-iodopyridin-2(1H)-one (22.0 g, 90.33 mmol) was dissolved in DMF (220 mL) under nitrogen. Cesium carbonate (28.77 g, 181.1 mmol) was added to the reaction mixture, followed by dropwise addition of methyl iodide (13.74 mL) at 0 °C. The reaction mixture was stirred at room temperature for 1 h. TLC (5:5 hexane / ethyl acetate) showed no residual SM. The resulting mixture was quenched by the addition of water (100 mL). After stirring the mixture for 5 min, the phases were separated. The aqueous phase was extracted with ethyl acetate (3 × 100 mL). The combined organics were washed with brine (2 × 50 ml) and dried over Na SO . The fractions were concentrated to give a sticky oil, which was triturated with a mixture of n-pentane / diethyl ether to give a pale yellow solid (13 g, 56.62%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.31 min, m / z = 313.8 [M+H] + HPLC: (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 6.10 min 1H NMR: (400 MHz, DMSO) δ 8.13 (s, 1H), 7.13 (s, 1H), 3.33 (s, 3H). Preparation 28: Ethyl 4-(5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate 5-Bromo-4-iodo-1-methylpyridin-2(1H)-one (3.0 g, 9.615 mmol) was dissolved in dioxane (48 mL) and water (12 mL) at room temperature. Ethyl 6-methyl-7-oxo-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate (5.76 g, 11.53 mmol) was added to the reaction, followed by sodium carbonate (2.03 g, 19.23 mmol) at room temperature. The reaction mixture was purged with argon for 30 minutes. Tetrakis (0.556 g, 0.480 mmol) was added to the reaction mixture, which was then stirred at 95°C for 16 hours. TLC (9.5:0.5 DCM\MeOH) showed no residual SM. The resulting mixture was slowly poured into cold water to give a white precipitate, which was filtered. The solid was dried under vacuum to give the pure product (3.1 g, 92.26%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.879 min, m / z = 560.1 [M+H] + . 1H NMR: (400 MHz, DMSO) δ 8.33 (d, J=8.4 Hz, 2H), 8.22 (s, 1H), 7.70 (s, 1H), 7.52 (d, J=8.2 Hz, 2H), 6.89 (s, 1H), 6.48 (s, 1H), 4.38-4.32 (m, 2H), 3.50 (s, 3H), 3.47 (s, 3H), 2.44 (s, 3H), 1.30 (t, J= 7.2 Hz, 3H). Preparation 29: Ethyl 6-methyl-4-(1-methyl-2-oxo-5-phenyl-1,2-dihydropyridin-4-yl)-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine e-2-carboxylate Ethyl 4-(5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate (0.5 g, 0.894 mmol) was dissolved in toluene (8.0 mL) and water (2.0 mL) at room temperature. 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane (0.218 g, 1.788 mmol) was added to the reaction mixture, followed by potassium phosphate (0.569 g, 2.683 mmol) at room temperature. The reaction mixture was purged with argon for 30 minutes. S-Phos (0.036 g, 0.089 mmol) and Pd2(dba)3 (0.04 g, 0.0447 mmol) were added to the reaction mixture. The resulting mixture was heated at 95 °C for 1 h. TLC (9:1 DCM\methanol) showed no residual SM. The reaction mixture was quenched with water and extracted with EtOAc (3 × 50 mL). The combined organic layers were dried (Na2SO4), filtered, and evaporated. The resulting residue was purified by flash column chromatography using EtOAc\methanol eluting with a zero gradient of neat ethyl acetate. Solvent reduction gave a cream-colored solid (0.3 g, 60.30%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.937 min, m / z = 557.16 [M+H] + . 1H NMR: (400 MHz, DMSO) δ 8.22 (d, J = 8.4 Hz, 2H), 7.88 (s, 1H), 7.59 (s, 1H), 7.49 (d, J=8.4 Hz, 2H), 7.20 - 7.12 (m, 5H), 6.46 (d, J= 8.7 Hz, 2H), 4.30 - 4.24 (m, 2H), 3.53 (s, 3H), 3.42 (s, 3H), 2.42 (s, 3H), 1.27 (t, J = 14.4 Hz, 3H). Preparation 30: 2-(hydroxymethyl)-6-methyl-4-(1-methyl-2-oxo-5-phenyl-1,2-dihydropyridin-4-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Ethyl 6-methyl-4-(1-methyl-2-oxo-5-phenyl-1,2-dihydropyridin-4-yl)-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carboxylate (0.75 g, 1.34 mmol) was dissolved in DCM (180 mL) under argon, and the reaction mixture was cooled to -20 °C. DIBAL-H (28.2 mL, 28.2 mmol) was added dropwise to the reaction mixture at -20 °C over 6 h. TLC (9:1 DCM:methanol) showed no residual SM. The mixture was diluted with DCM (240 mL) and quenched by the addition of sodium hydroxide solution (300 mL). The resulting mixture was filtered through a Celite pad. The mixture was separated, and the aqueous layer was re-extracted with DCM (240 mL). The combined organics were dried (Na2SO4), filtered and evaporated. The residue was purified on silica eluting with 3:97 methanol:DCM. Solvent reduction gave an off-light yellow solid (0.2g, 28%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.537 min, m / z = 516.17 [M+H] + 1H NMR: (400 MHz, DMSO) δ 7.93 (d, J = 8.4Hz, 2H), 7.86 (s, 1H), 7.49 (d, J = 8.4Hz, 2H), 7.31 (s, 1H), 7.20 - 7.17(m, 3H) 7.12 7.10 (m, 2H), 6.40 (s, 1H), 6.18 (s, 1H), 5.45 (t, 1H), 4.75 (d, J = 5.2Hz, 2H), 3.53 (s, 3H), 3.28 (s, 3H), 2.37 (s, 3H). Preparation 31: 6-methyl-4-(1-methyl-2-oxo-5-phenyl-1,2-dihydropyridin-4-yl)-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carbaldehyde 2-(Hydroxymethyl)-6-methyl-4-(1-methyl-2-oxo-5-phenyl-1,2-dihydropyridin-4-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.47 g, 0.91 mmol) was dissolved in DCM (47 mL). Manganese oxide (0.47 g, 5.47 mmol) was added to the reaction mixture, which was then heated to 50 °C for 4 h. TLC (9:1 DCM:MeOH) showed no residual SM. The mixture was filtered through a Celite pad and concentrated. Solvent reduction afforded a pale yellow solid (0.28 g, 59%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.823 min, m / z = 514.07 [M+H] + 1H NMR: (400 MHz, DMSO) δ 10.08 (s, 1H), 8.12 (d, J = 8.4Hz, 2H), 7.89 (s, 1H), 7.62 (s, 1H), 7.47(d, J = 8.0Hz, 2H) 7.17 - 7.13(m, 5H), 6.63 (s, 1H), 6.48 (s, 1H), 3.53 (s, 3H), 3.42 (s, 3H), 2.42 (s, 3H) Preparation 32: 6-methyl-2-(5-methyl-1H-imidazol-2-yl)-4-(1-methyl-2-oxo-5-phenyl-1,2-dihydropyridin-4-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 6-Methyl-4-(1-methyl-2-oxo-5-phenyl-1,2-dihydropyridin-4-yl)-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-2-carbaldehyde (0.22 g, 0.428 mmol) was dissolved in methanol (4.5 mL) under nitrogen. Ammonium carbonate (0.411 g, 4.288 mmol) was added to the reaction mixture and stirred at room temperature for 30 minutes. 2-Oxopropanal (0.15 g, 0.428 mmol) was added to the reaction mixture. The reaction mixture was heated at 50°C for 5 hours. TLC (9.5:0.5 DCM:methanol) showed no residual sulfonyl methylcellulose. The resulting solution was directly concentrated under reduced pressure in vacuo. The residue was purified by flash column chromatography, and the product was eluted with 2% methanol in DCM. Solvent reduction gave the pure product as a white solid (0.05 g, 20%) LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 1.256 min, m / z = 566.11 [M+H] Preparation 33: 6-methyl-2-(5-methyl-1H-imidazol-2-yl)-4-(1-methyl-2-oxo-5-phenyl-1,2-dihydropyridin-4-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 6-Methyl-2-(5-methyl-1H-imidazol-2-yl)-4-(1-methyl-2-oxo-5-phenyl-1,2-dihydropyridin-4-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.200 g, 0.35 mmol) was dissolved in 1 M TBAF (5 mL, 7.07 Vol) at room temperature. The resulting solution was stirred at room temperature for 16 hours. TLC (9.5:0.5 DCM / methanol) showed no residual SM. The reaction mixture was concentrated under reduced pressure to give the crude material. The residue was purified by preparative HPLC purification (instrument A, column A) eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. Lyophilization gave an off-white solid (0.0028 g, 1.79%). LCMS: (Waters Acquity UPLC with QDA mass detector, acidic, 4.0 min): 5.772 min, m / z = 412.41 [M+H] + 1H NMR: (400 MHz, DMSO) δ 11.98 (s, 1H), 11.84(s, 1H) 7.87 (s, 1H), 7.39 (t, J = 14Hz, 1H), 7.17 - 7.12 (m, 3H), 7.06 - 6.99(m, 2H), 6.90 (br s, 1H), 6.65 (br s, 1H), 6.48 (br s, 1H), 3.55 (s, 3H), 3.40 (s, 3H), 2.19 - 2.11 (m, 3H) Example 6: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 34: 4-Bromo-2-chloro-7-methoxy-1-tosyl-1H-pyrrolo[2,3-c]pyridine 4-Bromo-7-methoxy-1-tosyl-1H-pyrrolo[2,3-c]pyridine (80 g, 210.5 mmol) was dissolved in anhydrous THF (1200 mL) under argon. LDA (1 M in THF / heptane) (273.6 mL, 273.6 mmol) was added dropwise to the reaction mixture at −78° C. over 30 minutes. The orange solution was stirred at ambient temperature for 2 hours. Hexachloroethane (82.33 g, 347.33 mmol) in anhydrous tetrahydrofuran (400 mL) was added dropwise to the reaction mixture at −78° C. TLC (9.5:0.5 hexane / EtOAc) after 2 hours showed no residual SM. The reaction mixture was quenched by the dropwise addition of saturated NH4Cl (2400 mL). After stirring the mixture for 5 minutes, the phases were separated. The aqueous phase was extracted with ethyl acetate (2 × 800 mL). The combined organics were washed (brine), dried (Na2SO4), filtered and evaporated to an oil which was triturated with EtOAc to give a pale yellow solid (76g, 87%). LCMS: (Waters, acidic, 4.0 min): 2.753 min, m / z = 414.7 [M+H] + 1 H NMR: (400 MHz, DMSO) δ 8.08 (s, 1H), 7.95 (d, J=8.4, 2H), 7.53 (d, J=8, 2H), 7.05 (s, 1H), 3.87 (s, 3H), 2.42 (s, 3H). Preparation 35: 2-chloro-6-methyl-1-tosyl-4-(tributylstannyl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 1,4-Dioxane (50 mL) was degassed with argon for 30 minutes. 4-Bromo-2-chloro-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (5.0 g, 1.20 mmol) and hexabutylditin (11.6 mL, 22.9 mmol) were added to the reaction mixture, followed by tetrakis (1.4 g, 1.20 mmol) at room temperature. The resulting mixture was stirred at 130 °C for 3 hours, at which time TLC (3:7 ethyl acetate / hexane) showed no residual SM. The resulting solution was filtered through a Celite pad, and the filtrate was diluted with water (50 mL) and ethyl acetate (50 mL). The combined organics were dried over Na SO , filtered, and concentrated. The resulting residue was purified by normal phase chromatography eluting with (30:70) ethyl acetate / hexane to give 2-chloro-6-methyl-1-tosyl-4-(tributylstannyl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one as an off-white solid (2.5 g, 28%). 1 H NMR: (400 MHz, DMSO) δ 8.14 (d, J=8 Hz, 2H), 7.48 (d, J=8 Hz, 2H), 7.22 (s,1H), 6.58 (s,1H), 3.45 (s, 3H), 2.40 (s, 3H), 1.50-1.43 (m, 6H), 1.32-1.22 (m, 6H), 1.11-1.06 (m, 6H), 0.87 (t, J=8 Hz, 9H). Preparation 36: 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 2-Chloro-6-methyl-1-tosyl-4-(tributylstannyl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (2.6 g, 4.15 mmol) and 4-bromo-5-(2,6-dimethylphenoxy)-1-methylpyridin-2(1H)-one (1.27 g, 4.15 mmol) were dissolved in toluene (24 mL). The reaction mixture was purged with argon for 30 minutes. Tetrakis (0.47 g, 0.41 mmol) was added to the reaction mixture, and the resulting mixture was stirred at 120 °C for 3 hours. TLC (0.5:9.5 MeOH / DCM) after 3 hours indicated that SM had been consumed. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (50 mL). The combined organics were dried over Na SO , filtered, and evaporated. The residue was purified by reverse-phase chromatography eluting with acetonitrile / water (60:40) to give 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one as an off-white solid (0.95 g, 46%). LCMS R :(Water, acidic, 4.0 min):2.171 min, m / z =563.9 [M+H] + . 1 H NMR: (400 MHz, DMSO) δ 8.14 (d, J=8.0 Hz, 2H), 7.80 (s, 1H), 7.47 (d, J=8.0 Hz, 2H), 7.11-7.02 (m, 3H), 6.78 (s, 1H), 6.68 (s, 1H), 6.47 (s, 1H), 3.52 (s, 3H), 3.33 (s, 3H), 2.39 (s, 3H), 2.05 (s, 6H). Preparation 37: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 2-Chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was dissolved in dioxane (1.5 mL) under argon. 1-Isopropyl-3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.13 g, 0.53 mmol) was added to the reaction mixture, followed by sodium carbonate (0.084 g, 0.79 mmol) and water (0.3 mL) at room temperature. The suspension was degassed for 30 minutes. PdCl2(dppf).DCM (0.021 g, 0.026 mmol) was added to the reaction mixture. The dark solution was heated at 140 °C for 1 h. TLC (9.5:0.5 DCM:methanol) showed no residual SM. The reaction mixture was cooled to 0 °C. Sodium hydroxide (0.053 g, 1.33 mmol) was added to the reaction mixture. The dark solution was stirred at 140 °C for 40 min. TLC (9.5:0.5 DCM:methanol) showed complete deprotection. The resulting solution was directly concentrated under reduced pressure, and ethyl acetate was added. The mixture was filtered, and the filtrate was evaporated to an oil. The crude material was purified by preparative HPLC purification using Instrument: A, Column: B, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction yielded an off-white solid (0.010 g, 8.0%). LCMS R (Water, acidic, 4.0 min): 1.630 min, m / z =498.1 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 6.763 min 1H NMR: (400 MHz, DMSO) δ 12.01 (s, 1H), 8.36 (s, 1H), 7.46 (s, 1H), 7.11-7.04 (m, 2H), 6.66 (s, 1H), 6.53 (s, 1H), 6.34 (s, 1H), 5.76 (s, 1H), 4.43-4.37 (m, 1H), 3.59 (s, 3H), 3.32 (s, 3H), 2.32 (s, 3H), 2.10 (s, 6H), 1.43 (d, J=6.8 Hz, 6H). Example 7: 2-(1,3-dimethyl-1H-pyrazol-5-yl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 38: 2-(1,3-dimethyl-1H-pyrazol-5-yl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with 1,3-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.088 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument A, Column C, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave a white solid (0.027 g, 22%). LCMS tR(Waters, acidic, 4.0 min): 1.529 min, m / z = 470.0 [M+H] + HPLC tR (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 6.376 min 1H NMR: (400 MHz, DMSO) δ 12.46 (s, 1H), 7.52 (s, 1H), 7.09 -7.06 (m, 3H), 6.67 (s, 1H), 6.57 (s, 2H), 6.54 (s, 1H), 3.88 (s, 3H), 3.60 (s, 3H), 3.32 (s, 3H), 2.16 (s, 3H), 2.08 (s, 6H). Example 8: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-phenyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 39: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-phenyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with phenylboronic acid (0.064 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument B, Column A, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.032 g, 27%). LCMS R (Waters, acidic, 4.0 min): 1.78 min, m / z = 452.0 [M+H] + HPLC R(Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 7.641 min 1 H NMR: (400 MHz, DMSO) δ 12.47 (s, 1H), 7.95 (d, J= 7.6 Hz, 2H), 7.51 (s, 1H), 7.42 (apparent t, J=7.4 Hz, 2H), 7.32 (apparent t, J=7.2 Hz, 1H), 7.11-7.02 (m, 3H), 6.81 (s, 1H), 6.67 (s, 1H), 6.56 (s, 1H), 3.61 (s, 3H), 3.33 (s, 3H), 2.10 (s, 6H). Example 9: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(pyridin-3-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one. TFA [ka] Preparation 40: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(pyridin-3-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with pyridin-3-ylboronic acid (0.065 g, 0.399 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument A, Column C, eluting with a gradient of 0.05% trifluoroacetic acid in water and acetonitrile. The lyophilized fraction gave a brown sticky solid (0.010 g, 10%). LCMS R (Water, acidic, 4.0 min): 1.350 min, m / z = 453.0 [M+H]+ HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 6.290 min 1 H NMR: (400 MHz, DMSO) δ 12.68 (s, 1H), 9.16 (s, 1H), 8.52 (d, J=5.6 Hz, 1H), 8.37 (d, J=8 Hz, 1H), 7.74-7.68 (m, 1H), 7.53 (s, 1H), 7.49-7.46 (m, 1H), 7.23 (s, 1H), 7.10 (d, J=4.4 Hz, 2H), 6.98 (s, 2H), 3.61 (s, 3H), 3.34 (s, 3H), 2.10 (s, 6H). Example 10: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(pyridin-4-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 41: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(pyridin-4-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with pyridin-4-ylboronic acid (0.065 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument A, Column C, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.018 g, 13%). LCMS R(Waters, acidic, 4.0 min): 1.245 min, m / z = 453.1 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 6.278 min 1 H NMR: (400 MHz, DMSO) δ 12.78 (s, 1H), 8.59 (d, J=5.6 Hz 2H), 7.96 (d, J=5.6 Hz 2H), 7.54 (s, 1H), 7.10-7.02 (m, 4H), 6.69 (s, 1H), 6.56 (s, 1H), 3.62 (s, 3H), 3.34 (s, 3H), 2.10 (s, 6H). Example 11: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(1-isopropyl-1H-pyrazol-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 42: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(1-isopropyl-1H-pyrazol-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with 1-isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.125 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument A, Column C, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.026 g, 21%). LCMS R (Waters, acidic, 4.0 min): 1.622 min, m / z = 484.1 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 6.702 min 1 H NMR: (400 MHz, DMSO) δ 12.22 (s, 1H), 8.37 (s, 1H), 8.00 (s, 1H), 7.48 (s, 1H), 7.12-7.03 (m, 3H), 6.67 (s, 1H), 6.54 (d, J=6.4 Hz, 2H), 4.48 (m, 1H), 3.58 (s, 3H), 2.50 (s, 3H), 2.08 (s, 6H), 1.44 (d, J=6.4 Hz, 6H). Example 12: 2-(1,3-dimethyl-1H-pyrazol-4-yl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 43: 2-(1,3-dimethyl-1H-pyrazol-4-yl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with 1,3-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.118 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument: A, Column: A, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.0185 g, 15%). LCMS R (Water, acidic, 4.0 min): 1.474 min, m / z = 470.0 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 6.119 min 1 H NMR: (400 MHz, DMSO) δ 12.09 (s, 1H), 8.20 (s, 1H), 7.47 (s, 1H), 7.11-7.04 (m, 3H), 6.66 (s, 1H), 6.52 (s, 1H), 6.33 (s, 1H), 3.78 (s, 3H), 3.59 (s, 3H), 3.32 (s, 3H), 2.30 (s, 3H), 2.09 (s, 6H). Example 13: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(1-methyl-1H-pyrrol-3-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 44: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(1-methyl-1H-pyrrol-3-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole (0.110 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument A, Column C, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.00671 g, 6%). LCMS R (Waters, acidic, 4.0 min): 1.646 min, m / z = 455.1 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 6.866 min 1 H NMR: (400 MHz, DMSO) δ 11.99 (s, 1H), 7.45 (s, 1H), 7.37 (s, 1H), 7.11 (d, J=7.2 Hz, 2H), 7.06 (m, 1H), 6.72 (s, 1H), 6.64 (s, 1H), 6.53 (s, 2H), 6.37 (s, 1H), 3.62 (s, 3H), 3.57 (s, 3H), 3.32 (s, 3H), 2.10 (s, 6H) Example 14: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(2-fluorophenyl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 45: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(2-fluorophenyl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with (2-fluorophenyl)boronic acid (0.074 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument: A, Column: A, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.040 g, 33%). LCMS R (Water, acidic, 4.0 min): 1.830 min, m / z = 470.0 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 7.739 min 1H NMR: (400 MHz, DMSO) δ 12.49 (s, 1H), 8.11-8.07 (m, 1H), 7.54 (s, 1H), 7.40-7.26 (m, 3H), 7.10 (d, J=8.0 Hz, 2H), 7.06-7.02 (m, 1H), 6.80 (d, J=4.0 Hz, 1H), 6.67 (s, 1H), 6.53(s, 1H), 3.62 (s, 3H), 3.33 (s, 3H), 2.09 (s, 6H) Example 15: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(o-tolyl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 46: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(o-tolyl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with o-tolylboronic acid (0.0720 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument: A, Column: A, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.0245 g, 20%). LCMS R (Water, acidic, 4.0 min): 1.847 min, m / z = 466.1 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 7.817 min 1 H NMR: (400 MHz, DMSO) δ 12.26 (s, 1H), 7.49 (m, 2H), 7.30-7.24 (m, 3H), 7.12-7.03 (m, 3H), 6.65 (s, 1H), 6.55 (s, 1H), 6.42 (s, 1H), 3.60 (s, 3H), 3.32 (s, 3H), 2.39 (s, 3H), 2.08 (s, 6H). Example 16: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(2-fluoro-5-methylphenyl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 47: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(2-fluoro-5-methylphenyl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with (2-fluoro-5-methylphenyl)boronic acid (0.082 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument: A, Column: A, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.076 g, 57%). LCMS R (Water, acidic, 4.0 min): 1.950 min, m / z = 484.0 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 8.203 min 1 H NMR: (400 MHz, DMSO) δ 12.43 (s, 1H), 7.97 (d, J=7.2 Hz, 1H), 7.53 (s, 1H), 7.22-7.18 (m, 2H), 7.11-7.02 (m, 3H), 6.79 (d, J=2.4 Hz, 1H), 6.66 (s, 1H), 6.53 (s, 1H), 3.61 (s, 3H), 3.24 (s, 3H), 2.32 (s, 3H), 2.09 (s, 6H) Example 17: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(2,6-dimethylpyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one. TFA [ka] Preparation 48: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(2,6-dimethylpyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with (2,6-dimethylpyridin-4-yl)boronic acid (0.080 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument: A, Column: A, eluting with a gradient of 0.05% trifluoroacetic acid in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.0278 g, 22%). LCMS R (Waters, acidic, 4.0 min): 1.280 min, m / z = 481.1 [M+H] + HPLC R(Waters Alliance e2695 with 2998 detector, acidic, 17.0 min): 4.953 min 1 H NMR: (400 MHz, DMSO) δ 8.25 (br s, 2H), 7.58 (s, 1H), 7.39 (br s, 1H), 7.10 (d, J=7.2Hz, 3H), 7.06-7.03 (m, 1H), 6.73 (s, 1H), 6.58 (s, 1H), 3.62 (s, 3H), 3.32 (s, 3H), 2.09 (s, 6H), 1.23 (s, 6H). Example 18: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(5-fluoro-2-methylphenyl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 49: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(5-fluoro-2-methylphenyl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with (2,6-dimethylpyridin-4-yl)boronic acid (0.080 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument: A, Column: A, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.044 g, 34.42%). LCMS R (Waters, acidic, 4.0 min): 1.901 min, m / z = 484.1 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 7.948 min 1 H NMR: (400 MHz, DMSO) δ 12.36 (s, 1H), 7.53 (s, 1H), 7.38-7.32 (m, 2H), 7.15-7.02 (m, 4H), 6.66 (s, 1H), 6.55 (s, 1H), 6.51 (d, J=2.4, 1H), 3.61 (s, 3H), 3.32 (s, 3H), 2.38 (s, 3H), 2.08 (s, 6H). Example 19: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(2,5-dimethylphenyl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 50: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(2,5-dimethylphenyl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with (2,5-dimethylphenyl)boronic acid (0.079 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument: A, Column: A, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.026 g, 20%). LCMS R (Water, acidic, 4.0 min): 1.986 min, m / z = 480.1 [M+H]+ HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 8.314 min 1 H NMR: (400 MHz, DMSO) δ 12.21 (s, 1H), 7.51 (s, 1H), 7.34 (s, 1H), 7.18 (d, J=7.6Hz, 1H), 7.12-7.03 (m, 4H), 6.65 (s, 1H), 6.55 (s, 1H), 6.41 (d, J=1.6Hz, 1H), 3.60 (s, 3H), 3.32 (s, 3H), 2.34 (s, 3H), 2.29 (s, 3H), 2.09 (s, 6H). Example 20: 2-(5-chloro-2-methylphenyl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 51: 2-(5-chloro-2-methylphenyl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with (5-chloro-2-methylphenyl)boronic acid (0.090 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument: A, Column: A, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.020 g, 17%). LCMSR (Waters, acidic, 4.0 min): 1.990 min, m / z = 501.6 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 8.516 min 1 H NMR: (400 MHz, DMSO) δ 12.39 (s, 1H), 7.62-7.53 (m, 3H), 7.34 (s, 2H), 7.11-7.02 (m, 2H), 6.66 (s, 1H), 6.55-6.50 (m, 2H), 3.60 (s, 3H), 3.32 (s, 3H), 2.38 (s, 3H), 2.08 (s, 6H) Example 21: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(2-methyl-5-(trifluoromethyl)phenyl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 52: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(2-methyl-5-(trifluoromethyl)phenyl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with (2-methyl-5-(trifluoromethyl)phenyl)boronic acid (0.108 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument: A, Column: A, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.032 g, 22%). LCMS R (Waters, acidic, 4.0 min): 2.055 min, m / z = 534.0 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 8.702 min 1 H NMR: (400 MHz, DMSO) δ 12.51 (s, 1H), 7.85 (s,1H), 7.64 (d, J=8 Hz, 1H), 7.55 (d, J=9.6 Hz, 2H), 7.11 (d, J=8.0 Hz, 2H), 7.05 (d, J=6.4 Hz, 1H), 6.67 (s,1H), 6.56 (s, 2H), 3.61 (s, 3H), 3.30 (s, 3H), 2.32 (s, 3H), 2.08 (s, 6H) Example 22: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(pyrimidin-5-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 53: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(pyrimidin-5-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with pyrimidin-5-ylboronic acid (0.066 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument A, Column C, eluting with a gradient of 0.05% trifluoroacetic acid in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.023 g, 20%). LCMS R (Waters, acidic, 4.0 min): 1.441 min, m / z = 454.0 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 5.974 min 1 H NMR: (400 MHz, DMSO) δ 12.83 (s, 1H), 9.36 (s, 2H), 9.11 (s, 1H), 7.55 (s, 1H), 7.11 (m, 3H), 7.05 (d, J=6.4 Hz, 1H), 6.70 (s, 1H), 6.58 (s, 1H), 3.62 (s, 3H), 3.43 (s, 3H), 2.09 (s, 6H) Example 23: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(p-tolyl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 54: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(p-tolyl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with p-tolylboronic acid (0.072 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument B, Column A, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.023 g, 19%). LCMS R (Water, acidic, 4.0 min): 1.917 min, m / z = 466.0 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 8.151 min 1 H NMR: (400 MHz, DMSO) δ 12.39 (s, 1H), 7.84 (d, J=8.0Hz, 2H), 7.50 (s, 1H), 7.23 (d, J=8.0Hz, 2H), 7.10 (d, J=7.2Hz, 2H), 7.06-7.02 (m, 1H), 6.75 (s, 1H), 6.67 (s, 1H), 6.55 (s, 1H), 3.60 (s, 3H), 3.33 (s, 3H), 2.32 (s, 3H), 2.10 (s, 6H). Example 24: 4-(4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-2-yl)benzonitrile [ka] Preparation 55: 4-(4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-2-yl)benzonitrile Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with (4-cyanophenyl)boronic acid (0.078 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument B, Column A, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.004 g, 4%). LCMS R (Waters, acidic, 4.0 min): 2.145 min, m / z = 477.2 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 7.449 min 1 H NMR: (400 MHz, DMSO) δ 12.70 (br s, 1H), 8.15 (d, J=7.6Hz, 2H), 7.82 (d, J=7.6Hz, 2H), 7.46 (s, 1H), 7.11-6.98 (m, 4H), 6.66 (s, 1H), 6.58 (s, 1H), 3.59 (s, 3H), 3.34 (s, 3H), 2.09 (s, 6H). Example 25: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(4-fluorophenyl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 56: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(4-fluorophenyl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with (4-fluorophenyl)boronic acid (0.074 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument A, Column C, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave a white solid (0.022 g, 22%). LCMS R (Waters Acquity UPLC with QDA Mass Detector, acidic, 4.0 min): 1.82 min, m / z = 470.0 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 7.780 min 1 H NMR: (400 MHz, DMSO) δ 12.51 (s, 1H), 8.02-7.99 (m, 2H), 7.51 (s, 1H), 7.26 (apparent t, J=8.8 Hz, 2H), 7.11-7.02 (m, 3H), 6.79 (s, 1H), 6.67(s, 1H), 6.56 (s, 1H), 3.60 (s, 3H), 3.57 (s, 3H), 2.09 (s, 6H) Example 26: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(4-(methylsulfonyl)phenyl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 57: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(4-(methylsulfonyl)phenyl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with 4,4,5,5-tetramethyl-2-(4-(methylsulfonyl)phenyl)-1,3,2-dioxaborolane (0.150 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument: A, Column: A, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave a white solid (0.0235 g, 17%). LCMS R (Waters, acidic, 4.0 min): 1.627 min, m / z = 529.9 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 6.634 min 1 H NMR: (400 MHz, DMSO) δ 12.74 (br s, 1H), 8.23 ​​(d, J=8.0Hz, 2H), 7.91 (d, J=7.6Hz, 2H), 7.49 (s, 1H), 7.11-6.99 (m, 4H), 6.67 (s, 1H), 6.58 (s, 1H), 3.60 (s, 3H), 3.34 (s, 3H), 3.24 (s, 3H), 2.10 (s, 6H). Example 27: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(pyridazin-4-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 58: 4-(tributylstannyl)pyridazine Pyridazine (3.0 g, 37.4 mmol) was dissolved in THF (30.0 mL) under argon. LDA (2 M, 18.0 mL, 37.4 mmol in THF) was added dropwise to the reaction mixture at -78 °C. The reaction solution was stirred at -78 °C for 30 minutes. Tributyl(chloro)stannane (13.47 g, 41.4 mmol) was added to the reaction mixture. The reaction mixture was warmed to room temperature and stirred for 4 hours. TLC (5.0:5.0 hexane:ethyl acetate) showed no residual SM. The reaction mixture was quenched with cold water, and the mixture was partitioned between water and ethyl acetate. The separated organic layer was concentrated under high vacuum. The product was purified by flash chromatography on silica gel eluting with a hexane / ethyl acetate gradient (0-10%). Fractions corresponding to the product were combined and concentrated to give a brown oil (1.5 g, 11%). LCMS R (Water, acidic, 4.0 min): 2.915 min, m / z = 370.7 [M+H] + Preparation 59: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(pyridazin-4-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 2-Chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.150 g, 0.266 mmol) was dissolved in dioxane (3.0 mL) under argon. The suspension was degassed for 30 minutes. 4-(Tributylstannyl)pyridazine (0.295 g, 0.799 mmol) was added to the reaction mixture, followed by TEA (0.074 g, 0.532 mmol). The suspension was degassed for 10 minutes. Bis(triphenylphosphine)palladium chloride (0.037 g, 0.053 mmol) was added to the reaction mixture. The reaction solution was heated at 160° C. for 2 hours. TLC (9.0:1.0 DCM:methanol) showed no residual SM. Sodium hydroxide (0.053 g, 1.33 mmol) was added to the reaction mixture. The dark solution was stirred at 140 °C for 40 min. TLC (9.0:1.0 DCM:methanol) showed no residual SM. The reaction mixture was partitioned between water and DCM. The separated organic layer was concentrated under high vacuum. The product was purified by reverse-phase purification using Instrument: A, Column: B, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction yielded a white solid (0.006 g, 4.9%). LCMS R (Water, acidic, 4.0 min): 1.400 min, m / z = 454.0 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 5.695 min 1H NMR: (400 MHz, DMSO) δ 13.01 (s,1H), 9.81 (s, 1H), 9.32 (d, J=5.2 Hz, 1H), 8.25 (d, J=3.2 Hz, 1H), 8.07 (s, 1H), 7.55 (s, 1H), 7.18-7.02 (m, 3H), 6.71 (s, 1H), 6.57 (s, 1H), 3.62 (s, 3H), 3.34 (s, 3H), 2.18 (s, 6H) Example 28: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(4-(trifluoromethyl)phenyl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 60: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(4-(trifluoromethyl)phenyl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with (4-(trifluoromethyl)phenyl)boronic acid (0.101 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument: A, Column: A, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave a white solid (0.0247 g, 18%). LCMS R (Waters, acidic, 4.0 min): 2.050 min, m / z = 520.0 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 8.568 min 1H NMR: (400 MHz, DMSO) δ 11.05 (br s, 1H), 8.19 (d, J=8.0 Hz, 2H), 7.77 (d, J=8.0 Hz, 2H), 7.54 (s, 1H), 7.11-6.98 (m, 4H), 6.69 (s, 1H), 6.57 (s, 1H), 3.61 (s, 3H), 3.34 (s, 3H), 2.06 (s, 6H). Example 29: 4-(4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-2-yl)benzamide [ka] Preparation 61: 4-(4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-2-yl)benzamide Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with (4-carbamoylphenyl)boronic acid (0.088 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument C, Column B, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave an off-white solid (0.014 g, 11%). LCMS R (Waters, acidic, 4.0 min): 1.452 min, m / z = 494.9 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 5.865 min 1H NMR: (400 MHz, DMSO) δ 12.58 (s, 1H), 8.02 (d, J=12.8 Hz, 2H), 7.92 (s, 2H), 7.52 (s, 1H), 7.38 (s, 1H), 7.07 (d, J=14.8 Hz, 2H), 6.93 (s, 3H), 6.68 (s, 1H), 6.56 (s, 1H), 3.61 (s, 3H), 3.33 (s, 3H), 2.10 (s, 6H). Example 30: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(1H-1,2,3-triazol-5-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 62: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazol-4-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with 2-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-1,2,3-triazole (0.103 g, 0.53 mmol) to give crude material (0.22 g, crude). LCMS R (Waters, acidic, 4.0 min): 1.750 min, m / z =527.0 [M+H] + Preparation 63: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(2H-1,2,3-triazol-4-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one To 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazol-4-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.22 g, 0.26 mmol, crude) was added aqueous HCl (10 mL). The suspension was heated at 70° C. for 2 h. TLC (9.5:0.5 DCM:methanol) showed no residual SM. The reaction mixture was cooled to 0° C. The resulting solution was partitioned between water and dichloromethane, separated, and the organic fraction concentrated under reduced pressure. The mixture was filtered, and the filtrate was evaporated to an oil. The product was purified by reverse-phase chromatography eluting with an acetonitrile / water gradient (0-42%). The fractions corresponding to the product were combined and lyophilized to give an off-white solid (0.045 g, 25%). LCMS R (Waters, acidic, 4.0 min): 1.420 min, m / z = 443.0 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 3.871 min 1 H NMR: (400 MHz, DMSO) δ 15.26 (s, 1H), 12.59 (s, 1H), 8.40 (s, 1H), 7.54 (s, 1H), 7.11 (d, J=7.6Hz, 2H), 7.06-7.03 (m, 1H), 6.80 (s, 1H), 6.68 (s, 1H), 6.53 (s, 1H), 3.61 (s, 3H), 3.33 (s, 3H), 2.10 (s, 6H). Example 31: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(2-methylthiazol-5-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 64: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(2-methylthiazol-5-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 2-Chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was dissolved in dioxane (1.5 mL) under argon. 2-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole (0.119 g, 0.53 mmol) was added to the reaction mixture, followed by potassium phosphate (0.169 g, 0.79 mmol) and water (0.3 mL) at room temperature. The suspension was degassed for 30 minutes. Xphos-Pd-G3 (0.031 g, 0.037 mmol) was added to the reaction mixture. The dark reaction solution was heated at 120°C for 16 hours. TLC (9.5:0.5 DCM:methanol) showed no residual SM. The reaction mixture was cooled to 0°C. Sodium hydroxide (0.031 g, 0.79 mmol) was added to the reaction mixture. The dark reaction solution was stirred at 120°C for 6 hours. TLC (9.5:0.5 DCM:methanol) showed no residual SM. The resulting solution was directly concentrated under reduced pressure, and ethyl acetate was added. The mixture was filtered, and the filtrate was evaporated to give an oil. The product was purified by preparative HPLC purification using Instrument: A, Column: C, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction yielded a white solid (0.027 g, 22%). LCMS R(Waters, acidic, 4.0 min): 1.587 min, m / z = 472.9 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 6.624 min 1 H NMR: (400 MHz, DMSO) δ 12.71 (s, 1H), 8.23 ​​(s, 1H), 7.53 (s, 1H), 7.11-7.02 (m, 3H), 6.67 (s, 1H), 6.52 (d, J= 4.4Hz, 2H), 3.60 (s, 3H), 3.32 (s, 3H), 2.67 (s, 3H), 2.09 (s, 6H). Example 32: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(1H-pyrazol-5-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 65: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(1H-pyrazol-5-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.103 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument B, Column C, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave a brown solid (0.019 g, 16%). LCMS R (Waters, acidic, 4.0 min): 1.480 min, m / z = 442.1 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 6.043 min 1 H NMR: (400 MHz, DMSO) δ 11.70 (m, 2H), 7.70 (s, 1H), 7.52 (s, 1H), 7.11 (d, J= 7.2Hz, 2H), 7.08-7.02 (m, 1H), 6.98 (d, J= 1.2 Hz, 1H), 6.76 (s, 1H), 6.67 (s, 1H), 6.56 (s, 1H), 3.60 (s, 3H), 3.33 (s, 3H), 2.10 (s, 6H). Example 33: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(1-methyl-1H-1,2,3-triazol-5-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 66: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(1-methyl-1H-1,2,3-triazol-5-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one 2-Chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was dissolved in 1,4-dioxane (1.5 mL) under argon. 1-Methyl-5-(tributylstannyl)-1H-1,2,3-triazole (0.118 g, 0.53 mmol) was added to the reaction mixture, followed by triethylamine (0.03 mL, 0.53 mmol) at room temperature. The suspension was degassed for 30 minutes. PdCl(PPh) (0.037 g, 0.052 mmol) was added to the reaction mixture. The dark solution was heated at 160 °C for 1 hour. TLC (9.5:0.5 DCM:methanol) showed no residual SM. The reaction mixture was cooled to 0°C. Sodium hydroxide (0.053 g, 1.33 mmol) was added to the reaction mixture. The dark solution was stirred at 140°C for 40 minutes. TLC (9.5:0.5 DCM:methanol) showed no residual SM. The resulting solution was directly concentrated under reduced pressure, and ethyl acetate was added. The mixture was filtered, and the filtrate was evaporated to give an oil. The crude material was purified by reverse-phase column chromatography, and the product was eluted with 20% acetonitrile in water. Fractions corresponding to the product were combined and lyophilized to give an off-white solid (0.024 g, 21%). LCMS R (Waters, acidic, 4.0 min): 1.442 min, m / z = 456.9 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 5.891 min 1 H NMR: (400 MHz, DMSO) δ 12.76 (s, 1H), 8.09 (s, 1H), 7.44 (s, 1H), 7.06-7.02 (m, 3H), 6.84 (s, 1H), 6.70 (s, 1H), 6.34 (s, 1H), 4.23 (s, 3H), 3.32 (s, 3H), 3.26 (s, 3H), 2.09 (s, 6H). Example 34: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(2-fluoro-5-(trifluoromethyl)phenyl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 67: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(2-fluoro-5-(trifluoromethyl)phenyl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with (2-fluoro-5-(trifluoromethyl)phenyl)boronic acid (0.110 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument A, Column B, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave a white solid (0.031 g, 22%). LCMS R (Waters, acidic, 4.0 min): 2.069 min, m / z = 538.0 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 8.640 min 1 H NMR: (400 MHz, DMSO) δ 12.81 (br s, 1H), 8.63 (br s, 1H), 7.76-7.55 (m, 3H), 7.08-6.91 (m, 4H), 6.67-6.53 (m, 2H), 3.61 (s, 3H), 3.33 (s, 3H), 2.08 (s, 6H). Example 35: 4-(4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-2-yl)benzoic acid [ka] Preparation 68: 4-(4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-2-yl)benzoic acid Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with (4-(ethoxycarbonyl)phenyl)boronic acid (0.103 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument: A, Column: A, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. The lyophilized fraction gave a white solid (0.00599 g, 5%). LCMS R (Waters, acidic, 4.0 min): 1.580 min, m / z = 495.9 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 3.898 min 1 H NMR: (400 MHz, DMSO) δ 12.46 (br s, 2H), 7.87 (s, 4H), 7.51 (s, 1H), 7.11-7.04 (m, 3H), 6.81 (s, 1H), 6.68 (s, 1H), 6.56 (s, 1H), 3.60 (s, 3H), 3.33 (s, 3H), 2.10 (s, 6H). Example 36: 2-(1,5-dimethyl-1H-pyrazol-4-yl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 69: 2-(1,5-dimethyl-1H-pyrazol-4-yl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with 1,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.118 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument C, Column B, eluting with a gradient of 0.1% formic acid in water and acetonitrile. The lyophilized fraction gave a brown solid (0.023 g, 19%). LCMS R (Waters, acidic, 4.0 min): 1.506 min, m / z = 470.1 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 6.205 min 1H NMR: (400 MHz, DMSO) δ 12.15 (s, 1H), 7.92 (s, 1H), 7.48 (s, 1H), 7.11-7.02 (m, 3H), 6.66 (s, 1H), 6.53 (s, 1H), 6.32 (s, 1H), 3.77 (s, 3H), 3.59 (s, 3H), 3.32 (s, 3H), 2.40 (s, 3H), 2.09 (s, 6H). Example 37: 2-(2,6-difluorophenyl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 70: 2-(2,6-difluorophenyl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 37, 2-chloro-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.15 g, 0.26 mmol) was reacted with (2,6-difluorophenyl)boronic acid (0.084 g, 0.53 mmol) to give crude material. The resulting residue was purified by preparative HPLC purification using Instrument C, Column B, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. Lyophilization gave an off-white solid (0.005 g, 4%). LCMS R (Waters, acidic, 4.0 min): 1.790 min, m / z = 487.9 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 7.643 min 1 H NMR: (400 MHz, DMSO) δ 12.40 (br s, 1H), 7.95 (d, J=7.6 Hz, 1H), 7.54-7.40 (m, 2H), 7.34-7.22 (m, 1H), 7.11-7.03 (m, 3H), 6.67-6.53 (m, 3H), 3.61 (s, 3H), 3.36 (s, 3H), 2.08 (s, 6H). Example 38: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(6-methylpyrimidin-4-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 71: 4-Methyl-6-(trimethylstannyl)pyrimidine [ka] Toluene (10 mL, 20 V) was degassed under argon for 30 minutes. 4-Bromo-6-methylpyrimidine (0.50 g, 2.90 mmol) and hexamethylditin (1.20 mL, 5.81 mmol) were added to the reaction mixture, followed by tetrakis(2,4-dimethyl-2,4-diisopropyl-1,4-diisopropyl) (0.167 g, 0.145 mmol) at room temperature. The resulting mixture was stirred at 100 °C for 4 hours. TLC (3:7 ethyl acetate / hexane) showed no residual SM. The resulting solution was filtered through a Celite pad, and the filtrate was directly concentrated under vacuum to give a brown sticky solid (1 g, quantitative). LCMS R (Waters, acidic, 4.0 min): 0.890 min, m / z = 259 [M+H] + . Preparation 72: 4-Bromo-6-methyl-2-(6-methylpyrimidin-4-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] 4-Bromo-2-iodo-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.65 g, 1.29 mmol) and 4-methyl-6-(trimethylstannyl)pyrimidine (1.0 g, 3.87 mmol) were dissolved in DMF (20 mL) under argon. Lithium chloride (0.082 g, 1.93 mmol) was added to the reaction mixture, followed by copper(I) iodide (0.074 g, 0.38 mmol) at room temperature. The suspension was degassed using argon for 30 minutes. Tetrakis(2,3-dichloromethane) (0.074 g, 0.064 mmol) was added to the reaction mixture, and the resulting reaction mixture was stirred at 80 °C for 16 hours. TLC (3:7 ethyl acetate / hexane) showed no residual SM. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (50 mL x 3). The combined organics were dried over sodium sulfate, filtered, and evaporated. The residue was purified by normal phase chromatography eluting with (60:40) ethyl acetate / hexane. Solvent reduction gave a brown gum (0.16 g, 9%). LCMS R (Waters, acidic, 4.0 min): 1.945 min, m / z = 472.7 [M+H] + . Preparation 73: 6-Methyl-2-(6-methylpyrimidin-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] 4-Bromo-6-methyl-2-(6-methylpyrimidin-4-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.12 g, 0.25 mmol) was dissolved in dioxane (10 mL) under argon. The suspension was degassed with argon for 30 minutes. Potassium acetate (0.049 g, 0.50 mmol) was added to the reaction mixture, followed by bis(pinacolato)diboron (0.19 g, 0.76 mmol). Tris(dibenzylideneacetone)dipalladium (0.011 g, 0.012 mmol) and X-Phos (0.012 g, 0.025 mmol) were added to the reaction mixture. The dark reaction solution was heated at 90 °C for 12 hours. TLC (5:5 hexane:ethyl acetate) showed no residual SM. The reaction mixture was diluted with water (40 mL) and extracted with ethyl acetate (40 mL x 3). The combined organics were dried over Na2SO4, filtered and evaporated to give a brown gum (0.13 g, quantitative). LCMS R (Waters, acidic, 4.0 min): 1.477 min, m / z =438.7[M+H] + (boronic acid) and 2.232 min, m / z = 520.8 [M+H] + (boronic acid ester) Preparation 74: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(6-methylpyrimidin-4-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 43, 4-bromo-5-(2,6-dimethylphenoxy)-1-methylpyridin-2(1H)-one (0.114 g, 0.37 mmol) was reacted with 6-methyl-2-(6-methylpyrimidin-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.130 g, 0.29 mmol) to give crude material. The resulting residue was purified by preparative HPLC using Instrument C, Column B, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. Lyophilization gave an off-white solid (0.0044 g, 4%). LCMS R (Waters, acidic, 4.0 min): 1.497 min, m / z = 468.1 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 6.139 min 1 H NMR: (400 MHz, DMSO) δ 12.5 (s, 1H), 9.01 (s, 1H), 8.18 (s, 1H), 7.58 (s, 1H), 7.27 (s, 1H), 7.14-7.02 (m, 3H), 6.69 (s, 1H), 6.56 (s, 1H), 3.61 (s, 3H), 2.67 (s, 3H), 2.33 (s, 3H), 2.10 (s, 6H). Example 39: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(pyrimidin-2-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 75: 4-Bromo-6-methyl-2-(pyrimidin-2-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] 4-Bromo-2-iodo-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.55 g, 1.08 mmol) and 2-(tributylstannyl)pyrimidine (0.80 g, 2.17 mmol) were dissolved in dioxane (22 mL) under argon. Copper(I) iodide (0.010 g, 0.054 mmol) was added to the reaction mixture at room temperature. The suspension was degassed with argon for 15 minutes. Tetrakis(III) (0.062 g, 0.029 mmol) was added to the reaction mixture, and the resulting reaction mixture was stirred at 80 °C for 12 hours. TLC (3:7 ethyl acetate / hexane) showed no residual SM. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (50 mL × 3). The combined organics were dried over Na2SO4, filtered, and evaporated. The residue was purified by normal phase chromatography eluting with (40:60) ethyl acetate / hexanes. Solvent reduction gave a brown solid (0.15 g, 31%). LCMS R :(Waters, acidic, 4.0 min):1.902 min, m / z = 458.7 [M+H] + . Preparation 76: 6-Methyl-2-(pyrimidin-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] According to the procedure of Preparation 73, 4-bromo-6-methyl-2-(pyrimidin-2-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.12 g, 0.26 mmol) was reacted to obtain the title compound as a brown viscous material (0.20 g, quantitative). LCMS R (Waters, acidic, 4.0 min): 1.422 min, m / z =424.8 [M+H] + (boronic acid) and 2.236 min, m / z = 506.9 [M+H] +(boronic acid ester) Preparation 77: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(pyrimidin-2-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 64, 4-bromo-5-(2,6-dimethylphenoxy)-1-methylpyridin-2(1H)-one (0.15 g, 0.48 mmol) was reacted with 6-methyl-2-(pyrimidin-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.20 g, 0.47 mmol) to give crude material. The resulting residue was purified by preparative HPLC using Instrument C, Column B, eluting with a gradient of 0.05% ammonium hydroxide solution in water and acetonitrile. Lyophilization gave an off-white solid (0.021 g, 10%). LCMS R (Waters, acidic, 4.0 min): 1.535 min, m / z = 454 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 6.364 min 1 H NMR: (400 MHz, DMSO) δ 12.4 (br s, 1H), 8.86 (d, J=4.8 Hz, 2H), 7.57 (s, 1H), 7.40 (dd, J=4.8 Hz, J=10 Hz, 1H), 7.21 (s, 1H), 7.11-7.02 (m, 3H), 6.68 (s, 1H), 6.57 (s, 1H), 3.60 (s, 3H), 3.34 (s, 3H), 2.11 (s, 6H). Example 40: 2-(1,5-dimethyl-1H-pyrazol-4-yl)-4-(5-(2,6-dimethylphenoxy)-1-(oxetan-3-yl)-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 78: 4-Bromo-2-(1,5-dimethyl-1H-pyrazol-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] 4-Bromo-2-iodo-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (1.5 g, 2.96 mmol) was dissolved in dioxane (60 mL) under argon. 1,5-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.31 g, 5.93 mmol) was added to the reaction mixture, followed by potassium phosphate (0.125 g, 5.93 mmol) and water (40 mL) at room temperature. The suspension was degassed for 15 minutes. PdCl2(dppf) DCM complex (0.169 g, 0.207 mmol) was added to the reaction mixture. The dark reaction solution was heated at 60 °C for up to 4 hours. TLC (5:5 hexane:ethyl acetate) showed no residual SM. The reaction mixture was diluted with water (150 mL) and extracted with ethyl acetate (150 mL x 3). The combined organics were dried over Na2SO4, filtered, and evaporated. The residue was purified by normal phase chromatography eluting with (50:50) ethyl acetate / hexane. Solvent reduction gave a brown solid (1.0 g, 70%). LCMS R (Waters, acidic, 4.0 min): 1.789 min, m / z = 474.7 [M+H] + 1H NMR: (400 MHz, DMSO) δ 7.88 (s, 1H), 7.71-7.69 (d, J=8.4 Hz, 2H), 7.41-7.37 (m, 3H), 6.38 (s, 1H), 3.78 (s, 3H), 3.42 (s, 3H), 2.38 (s, 3H), 2.16 (s, 3H), Preparation 79: 2-(1,5-dimethyl-1H-pyrazol-4-yl)-6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] 4-Bromo-2-(1,5-dimethyl-1H-pyrazol-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (1.0 g, 2.10 mmol) (0.83 g, 1.75 mmol) was dissolved in dioxane (60 mL) under argon. The suspension was degassed with argon for 15 minutes. Potassium acetate (0.51 g, 5.25 mmol) was added to the reaction mixture, followed by bis(pinacolato)diboron (1.77 g, 7.0 mmol), and the mixture was degassed for 15 minutes. Tris(dibenzylideneacetone)dipalladium(0) (0.080 g, 0.087 mmol) and X-Phos (0.083 g, 0.17 mmol) were added to the reaction mixture. The dark reaction solution was heated at 60° C. for 16 hours. TLC (5:5 hexane:ethyl acetate) showed no residual SM. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (50 mL×3). The combined organic layers were dried over Na2SO4, filtered, and evaporated to give a brown sticky solid (1.20 g, quantitative). LCMS R (Waters, acidic, 4.0 min): 1.336 min, m / z =440.8 [M+H] + (boronic acid) and 2.092 min, m / z = 522.9 [M+H] + (boronic acid ester) Preparation 80: 2-(1,5-dimethyl-1H-pyrazol-4-yl)-4-(5-(2,6-dimethylphenoxy)-1-(oxetan-3-yl)-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] 4-Bromo-5-(2,6-dimethylphenoxy)-1-(oxetan-3-yl)pyridin-2(1H)-one (0.34 g, 0.99 mmol) was dissolved in dioxane (20 mL) under argon. 2-(1,5-dimethyl-1H-pyrazol-4-yl)-6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (1.2 g, 2.29 mmol) was added to the reaction mixture, followed by potassium phosphate (0.42 g, 1.99 mmol) and water (5 mL) at room temperature. The suspension was degassed for 15 minutes. Xphos-PdG3 (0.084 g, 0.099 mmol) was added to the reaction mixture. The dark reaction solution was heated at 60° C. for 6 hours. TLC (9.5:0.5 DCM:methanol) showed no residual SM. The reaction mixture was diluted with water (150 mL) and extracted with ethyl acetate (150 mL×3). The combined organics were dried over Na2SO4, filtered, and evaporated. The residue was purified by normal phase chromatography eluting with (55:45) acetonitrile / water. The fractions corresponding to the product were combined and lyophilized to give a brown solid (0.18 g, 19%). LCMS R (Waters, acidic, 4.0 min): 1.753 min, m / z = 666.10 [M+H] + Preparation 81: 2-(1,5-dimethyl-1H-pyrazol-4-yl)-4-(5-(2,6-dimethylphenoxy)-1-(oxetan-3-yl)-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] 2-(1,5-Dimethyl-1H-pyrazol-4-yl)-4-(5-(2,6-dimethylphenoxy)-1-(oxetan-3-yl)-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.180 g, 0.27 mmol) was dissolved in ethanol (18 mL). Sodium hydroxide (0.075 g, 1.89 mmol) was added, followed by water (2 mL) at room temperature. The resulting solution was heated at 60° C. for 3 hours. TLC (9.5:0.5 DCM:methanol) showed no residual SM. The resulting solution was directly concentrated under reduced pressure in vacuo to give a solid. The crude material was purified by reverse-phase chromatography eluting with acetonitrile / water (70:30). The fractions corresponding to the product were combined and lyophilized to give an off-white solid (0.057 g, 42%). LCMS R (Waters, acidic, 4.0 min): 1.513 min, m / z = 512.1 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 6.15 min 1 H NMR: (400 MHz, DMSO) δ 12.18 (s, 1H), 7.93 (s, 1H), 7.52 (s, 1H), 7.14-7.05 (m, 3H), 6.57 (s, 2H), 6.36 (s, 1H), 5.50 (t, J=6.8Hz, 1H), 4.80 (t, J=7.2 Hz, 2H), 4.44 (t, J=6.8 Hz, 2H), 3.77 (s, 3H), 3.60 (s, 3H), 2.33 (s, 3H), 2.12 (s, 6H). Example 41: 4-(5-(2,6-dimethylphenoxy)-1-(oxetan-3-yl)-2-oxo-1,2-dihydropyridin-4-yl)-2-(2-fluorophenyl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 82: 4-Bromo-2-(2-fluorophenyl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] According to the procedure of Preparation 78, 4-bromo-2-iodo-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (1.5 g, 2.96 mmol) was reacted to give the title compound as a brown solid (0.85 g, 60%). LCMS R :(Waters, acidic, 4.0 min):2.327 min, m / z = 474.7 [M+H] + 1 H NMR: (400 MHz, DMSO) δ 7.99 (s, 1H), 7.85 (d, J=8.4 Hz, 2H), 7.65-7.60 (m, 1H), 7.57-7.52 (m, 1H), 7.39 (d, J=8.4 Hz, 2H), 7.33 (d, J=8 Hz, 2H), 6.67 (s, 1H), 3.40 (s, 3H), 2.38 (s, 3H). Preparation 83: 2-(2-fluorophenyl)-6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] According to the procedure of Preparation 79, 4-bromo-2-(2-fluorophenyl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.8 g, 1.68 mmol) was reacted to give the title compound as a brown sticky solid (1.15 g, quantitative). LCMS R (Waters, acidic, 4.0 min): 1.764 min, m / z =440.8 [M+H] + (boronic acid) and 2.613 min, m / z = 522.9 [M+H] + (boronic acid ester) Preparation 84: 4-(5-(2,6-dimethylphenoxy)-1-(oxetan-3-yl)-2-oxo-1,2-dihydropyridin-4-yl)-2-(2-fluorophenyl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] According to the procedure of Preparation 80, 4-bromo-5-(2,6-dimethylphenoxy)-1-(oxetan-3-yl)pyridin-2(1H)-one (0.401 g, 1.14 mmol) was reacted with 2-(2-fluorophenyl)-6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (1.2 g, 2.29 mmol) to give the title compound as a brown liquid (0.18 g, 12%). LCMS R (Waters, acidic, 4.0 min): 2.111 min, m / z = 666.2 [M+H] + 1H NMR: (400 MHz, DMSO) δ 7.82 (m, 2H), 7.53 (m, 2H), 7.37 (d, J=8 Hz, 2H), 7.32-7.29 (m, 3H), 7.13-7.08 (m, 3H), 6.71 (s, 1H), 6.55 (s, 1H), 6.52 (s, 1H), 5.58-5.54 (m, 1H), 4.78 (dd, J=7.2 Hz, J=14.4 Hz, 2H), 4.40 (dd, J=6.8 Hz, , J=13.2 Hz, 2H), 3.50 (s, 3H), 2.39 (s, 3H), 2.04 (s, 6H). Preparation 85: 4-(5-(2,6-dimethylphenoxy)-1-(oxetan-3-yl)-2-oxo-1,2-dihydropyridin-4-yl)-2-(2-fluorophenyl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Following the procedure of Preparation 81, 4-(5-(2,6-dimethylphenoxy)-1-(oxetan-3-yl)-2-oxo-1,2-dihydropyridin-4-yl)-2-(2-fluorophenyl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.180 g, 0.27 mmol) was reacted with sodium hydroxide (0.075 g, 1.89 mmol) to give the title compound (50.68 mg, 37%). LCMS R (Water, basic, 17 min): 6.62 min, m / z = 512.8 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 7.597 min 1H NMR: (400 MHz, DMSO) δ 12.24 (s, 1H), 8.07 (t, J=7.6 Hz, J=15.6 Hz, 1H), 7.52 (s, 1H), 7.41-7.39 (m, 1H), 7.33-7.29 (m, 2H), 7.20-7.06 (m, 3H), 6.83 (d, J=2.8 Hz, 1H), 6.61 (s, 1H), 6.58 (s, 1H), 5.52 (m, 1H), 4.83 (t, J=7.2 Hz, J=14.4 Hz, 2H), 4.46 (t, J=6.8 Hz, J=13.2 Hz, 2H), 3.63 (s, 3H), 2.14 (s, 6H). Example 42: 4-(1-(azetidin-3-yl)-5-(2,6-dimethylphenoxy)-2-oxo-1,2-dihydropyridin-4-yl)-2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 86: 1-Isopropyl-3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 1-Isopropyl-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole [ka] To 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (5 g, 24.03 mmol) in acetonitrile (120 mL) was added cesium carbonate (31.3 g, 96.12 mmol) at room temperature under nitrogen. Isopropyl iodide (5.04 g, 72.09 mmol) was added to the reaction mixture at room temperature. The resulting reaction mixture was stirred at 90 °C for 12 h. TLC (5:5 hexane:ethyl acetate) showed no residual SM. The resulting solution was directly concentrated under reduced pressure in vacuo, and ethyl acetate was added. The mixture was filtered, and the filtrate was evaporated to give an oil. The product was purified by flash chromatography on silica gel eluting with an ethyl acetate / hexane gradient (0-30%) to give the crude material as a mixture of isomers (3.8 g, 60%). The crude material was used in the next step without further purification. LCMS R (Waters, acidic, 4.0 min): 1.902 min and 1.951 min, m / z = 250.8 [M+H] + Preparation 87: 4-Bromo-2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one and 4-Bromo-2-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] According to the procedure of Preparation 78, 4-bromo-2-iodo-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (2 g, 3.95 mmol) was reacted with a mixture of isomers of 1-isopropyl-3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole and 1-isopropyl-5-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.74 g, 10.99 mmol) to give the title compound as a mixture of isomers (1.5 g, 76%). LCMS R (Waters, acidic, 4.0 min): 1.975 min and 2.002 min, m / z = 502.8 [M+H] + 1 H NMR: (400 MHz, DMSO) δ 7.88 (s, 1H), 7.77 (s, 1H), 7.63 (m, 2H), 7.36 (d, J=8 Hz, 2H), 7.41-7.38 (m, 1H), 3.94 (s, 1H), 3.50 (s, 3H), 2.37 (s, 3H), 2.05 (s, 3H), 1.50 (d, J=6.8Hz, 6H). Preparation 88: 2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one and 2-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] According to the procedure of Preparation 79, 4-bromo-2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (1.5 g, 29.87 mmol) was reacted to give the title compound as a mixture of isomers as a brown sticky solid (3 g, quantitative). LCMS R (Waters, acidic, 4.0 min): 2.314 min and 2.346 min, m / z = 551.0 [M+H] + (boronic acid) and 1.501 min and 1.528 min, m / z = 468.8 [M+H] + (boronic acid ester) Preparation 89: tert-butyl 3-(5-(2,6-dimethylphenoxy)-4-(2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-2-oxopyridin-1(2H)-yl)azetidine-1-carboxylate and tert-butyl 3-(5-(2,6-dimethylphenoxy)-4-(2-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-2-oxopyridin-1(2H)-yl)azetidine-1-carboxylate [ka] Prepare a mixture of tert-butyl 3-(4-bromo-5-(2,6-dimethylphenoxy)-2-oxopyridin-1(2H)-yl)azetidine-1-carboxylate (0.70 g, 1.58 mmol) and 2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1,6-dihydro-7H-pyrazol-4-yl according to the procedure of Preparation 80. -pyrrolo[2,3-c]pyridin-7-one and 2-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (2 g, 3.63 mmol) were reacted to give the title compound as a mixture of isomers as a brown liquid (0.55 g, 20%). LCMS R (Waters, acidic, 4.0 min): 2.236 min and 2.267 min, m / z = 793.2 [M+H] + Preparation 90: Tert-butyl 3-(5-(2,6-dimethylphenoxy)-4-(2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-2-oxopyridin-1(2H)-yl)azetidine-1-carboxylate and tert-butyl 3-(5-(2,6-dimethylphenoxy)-4-(2-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-2-oxopyridin-1(2H)-yl)azetidine-1-carboxylate [ka] According to the procedure of Preparation 81, tert-butyl 3-(5-(2,6-dimethylphenoxy)-4-(2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-2-oxopyridin-1(2H)-yl)azetidine-1-carboxylate and tert-butyl 3 -(5-(2,6-dimethylphenoxy)-4-(2-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-2-oxopyridin-1(2H)-yl)azetidine-1-carboxylate (0.550 g, 0.69 mmol) was reacted to give crude material. The crude material was purified by preparative HPLC purification using instrument A with column C, eluting with 0.05% ammonium hydroxide in water and acetonitrile. Lyophilization gave a yellow liquid (0.38 g) of a mixture of two isomers. This material was purified by SFS purification using Instrument PHP-04 - Agilent 1260 Series Infinity UV Detector and a CHIRALPAK IG, 250 × 10 mm, 5 μm column, eluting with methanol. Solvent reduction of separate fractions gave tert-butyl 3-(5-(2,6-dimethylphenoxy)-4-(2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-2-oxopyridin-1(2H)-yl)azetidine-1-carboxylate (0.001) as an off-white solid. 0.050 g, 15%) and Tert-butyl 3-(5-(2,6-dimethylphenoxy)-4-(2-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-2-oxopyridin-1(2H)-yl)azetidine-1-carboxylate (0.050 g, 15%). Isomer-1:LCMS t R (Waters, acidic, 4.0 min): 1.991 min, m / z = 639.2 [M+H]+ HPLC t R (Waters Alliance e2695 including 2998 detector, basic, 17.0 min): 8.214 min 1 H NMR: (400 MHz, DMSO) δ 12.06 (s, 1H), 8.36 (s, 1H), 7.51 (s, 1H), 7.12 (d, J = 7.2 Hz, 2H), 7.06 - 7.03 (m, 1H), 6.56 (s, 1H), 6.49 (s, 1H), 6.37 (d, J = 2 Hz, 1H), 5.15 (m, 1H), 4.40 (m, 1H), 4.13 - 4.10 (m, 2H), 3.89 (m, 2H), 3.59 (s, 3H), 2.33 (s, 3H), 2.11 (s, 6H), 1.41 (d, J = 6.8 Hz, 6H), 1.35 (s, 9H). Isomer - 2: LCMS t R (Waters, acidic, 4.0 min): 2.010 min, m / z = 639.3 [M + H] + HPLC t R (Waters Alliance e2695 including 2998 detector, basic, 17.0 min): 8.263 min 1 H NMR: (400 MHz, DMSO) δ 12.17 (s, 1H), 7.98 (s, 1H), 7.52 (s, 1H), 7.12 (d, J = 7.6 Hz, 2H), 7.05 (m, 1H), 6.57 (s, 1H), 6.49 (s, 1H), 6.36 (s, 1H), 5.17 - 5.14 (m, 1H), 4.59 (m, 1H), 4.11 (m, 2H), 3.88 (m, 2H), 3.59 (s, 3H), 2.42 (s, 3H), 2.11 (s, 6H), 1.41 (d, J = 6.8 Hz, 6H), 1.35 (s, 9H). Preparation 91: 4-(1-(azetidin-3-yl)-5-(2,6-dimethylphenoxy)-2-oxo-1,2-dihydropyridin-4-yl)-2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Tert-butyl 3-(5-(2,6-dimethylphenoxy)-4-(2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-2-oxopyridin-1(2H)-yl)azetidine-1-carboxylate (0.050 g, 0.078 mmol) was dissolved in DCM at room temperature under nitrogen. The resulting mixture was cooled to 0° C., and TFA (0.50 mL, 10 V) was added. The reaction mixture was stirred at room temperature for 4 hours. TLC (9:1 DCM:methanol) showed no residual SM. The resulting mixture was concentrated under vacuum to give the crude material. The crude material was triturated with diethyl ether to give the title compound (0.022 g, 8%) as an off-white solid. LCMS R (Water, acidic, 4.0 min): 1.328 min, m / z = 539.1 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 7.298 min 1 H NMR: (400 MHz, DMSO) δ 12.01 (bs, 1H), 8.30 (s, 1H), 7.46 (s, 1H), 7.20-7.061 (m, 3H), 6.67 (s, 1H), 6.45 (s, 1H), 6.36 (s, 1H), 5.13-4.96 (m, 2H), 4.45-4.40 (m, 3H), 4.27-4.22 (m, 2H), 3.61 (s, 3H), 2.34 (s, 3H), 2.12 (s, 6H), 1.45 (d, J=6.4 Hz, 6H). Example 43: 4-(1-(azetidin-3-yl)-5-(2,6-dimethylphenoxy)-2-oxo-1,2-dihydropyridin-4-yl)-2-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 92: 4-(1-(azetidin-3-yl)-5-(2,6-dimethylphenoxy)-2-oxo-1,2-dihydropyridin-4-yl)-2-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one According to the procedure of Preparation 91, Tert-butyl 3-(5-(2,6-dimethylphenoxy)-4-(2-(1-isopropyl-5-methyl-1H-pyrazol-4-yl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)-2-oxopyridin-1(2H)-yl)azetidine-1-carboxylate (0.050 g, 0.078 mmol) was reacted to give the title compound as a pale yellow solid (0.028 g, 10%). LCMS R (Water, acidic, 4.0 min): 1.332 min, m / z = 539.1 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 7.381 min 1H NMR: (400 MHz, DMSO) δ 12.12 (bs, 1H), 8.68 (m, 1H), 7.93 (s, 1H), 7.47 (s, 1H), 7.21-7.04 (m, 3H), 6.67-6.34 (m, 2H), 5.40 (m, 1H), 5.15 (d, J=7.2 Hz, 2H), 4.95 (m, 1H), 4.60 (m, 1H), 4.25 (m, 1H), 3.61 (s, 3H), 2.43 (s, 3H), 2.12 (s, 6H), 1.44 (d, J=6.4 Hz, 6H) Example 44: 4-(5-(2,6-dimethylphenoxy)-1-(oxetan-3-yl)-2-oxo-1,2-dihydropyridin-4-yl)-2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 93: 4-(5-(2,6-dimethylphenoxy)-1-(oxetan-3-yl)-2-oxo-1,2-dihydropyridin-4-yl)-2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] According to the procedure of Preparation 80, 4-bromo-5-(2,6-dimethylphenoxy)-1-(oxetan-3-yl)pyridin-2(1H)-one (0.50 g, 1.43 mmol) was reacted with 2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (1.57 g, 2.86 mmol) to give the title compound as a brown liquid (0.45 g, 24%). LCMS R(Waters, acidic, 4.0 min): 1.882 min and 1.909 min, m / z = 694.2 [M+H] + Preparation 94: 4-(5-(2,6-dimethylphenoxy)-1-(oxetan-3-yl)-2-oxo-1,2-dihydropyridin-4-yl)-2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one Following the procedure of Preparation 81, 4-(5-(2,6-dimethylphenoxy)-1-(oxetan-3-yl)-2-oxo-1,2-dihydropyridin-4-yl)-2-(1-isopropyl-3-methyl-1H-pyrazol-4-yl)-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (0.4 g, 0.57 mmol) was reacted to give crude material. The crude material was purified by preparative HPLC purification using Instrument: A and Column: C, eluting with 0.05% ammonium hydroxide in water and 20% a-line in acetonitrile. Lyophilization gave a yellow liquid as a mixture of two isomers. This material was purified by SFS purification using Instrument PHP-04 - Agilent 1260 Series Infinity UV Detector and a CHIRALPAK IG, 250 × 10 mm, 5 μm column, eluting with 0.1% ammonia in heptane and IPA in acetonitrile. Solvent reduction of separate fractions gave the title compound as an off-white solid (0.012 g, 11%). LCMS R (Waters, acidic, 4.0 min): 1.994 min, m / z = 540.4 [M+H] + HPLC R (Waters Alliance e2695 with 2998 detector, basic, 17.0 min): 7.01 min 1H NMR: (400 MHz, DMSO) δ 12.05 (s, 1H), 8.36 (s, 1H), 7.51 (s, 1H), 7.14-7.05 (m, 3H), 6.57 (d, J=4.8 Hz, 2H), 6.37 (s, 1H), 5.50 (m, 1H), 4.80 (dd, J=7.6 Hz, J=14.8 Hz, 2H), 4.46-4.38 (m, 3H), 3.59 (s, 3H), 2.33 (s, 3H), 2.12 (s, 6H), 1.41 (d, J=6.4 Hz, 6H). Example 45: 4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-2-(2-methylpyridin-4-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 95: 4-Bromo-2-chloro-7-methoxy-1-tosyl-1H-pyrrolo[2,3-c]pyridine [ka] 4-Bromo-7-methoxy-1-tosyl-1H-pyrrolo[2,3-c]pyridine (200 g, 526.3 mmol) was dissolved in anhydrous THF (4000 mL, 20 V) at room temperature. LDA (1 M in THF) (684 mL, 684.2 mmol) was added dropwise to the reaction mixture at −78°C over 30 minutes. The resulting reaction mixture was stirred at −78°C for 2 hours. Hexachloroethane (199.3 g, 842 mmol) in anhydrous THF (1000 mL) was added dropwise to the reaction mixture at −78°C over 15 minutes. The resulting reaction mixture was stirred from −78°C to room temperature for 4 hours. TLC (2:8 ethyl acetate / hexane) indicated that SM was consumed. The reaction mixture was quenched with aqueous NH4Cl (3000 mL) and extracted with ethyl acetate (3 × 2000 mL). The organic fraction was dried over Na2SO4, filtered and evaporated to give 4-bromo-2-chloro-7-methoxy-1-tosyl-1H-pyrrolo[2,3-c]pyridine as a white solid (160 g, 68%). LCMS R (Waters, acidic, 4.0 min): 2.723 min, m / z =416.7 [M+H] + 1H NMR: (400 MHz, DMSO-d6) δ 8.08 (s, 1H), 7.96 - 7.94 (d, J=8.4 Hz, 2H), 7.54 - 7.52 (d, J=8.0 Hz, 2H), 7.05 (s, 1H), 3.87 (s, 3H), 2.42 (s, 3H). Preparation 96: 4-Bromo-2-chloro-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] 4-Bromo-2-chloro-7-methoxy-1-tosyl-1H-pyrrolo[2,3-c]pyridine (320 g, 772.9 mmol) was dissolved in acetonitrile (3200 mL, 10 V) at room temperature. Sodium iodide (173.8, 1159.4 mmol) was added to the reaction mixture and stirred at room temperature for 15 minutes. The resulting solution was cooled to 0°C, and trimethylsilyl chloride (147.2 mL, 1159.4 mmol) was added dropwise. The resulting mixture was stirred at ambient temperature for 1 hour. Water (160 mL, 0.5 V) was added to the reaction mixture and heated at 65°C for 3 hours. TLC (5.0:5.0 hexane:ethyl acetate) indicated that SM was consumed. The resulting mixture was quenched with ice-cold water (3200 mL) and stirred for 30 minutes. The resulting residue was filtered and triturated with n-hexane (320 mL) and diethyl ether (320 mL). The solid was dried under vacuum at 45° C. overnight to give a white solid (295 g, 95%). LCMS R :(Waters, acidic, 4.0 min):2.090 min, m / z = 402.7 [M+H] + 1 H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H), 8.12 - 8.10 (d, J= 8.4 Hz, 2H), 7.50 - 7.48 (d, J=8.0 Hz, 2H), 7.45 (s, 1H), 6.79 (s, 1H), 2.41 (s, 3H) Preparation 97: 4-Bromo-2-chloro-6-methyl-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] 4-Bromo-2-chloro-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (295 g, 737.6 mmol) was dissolved in DMF (5900 mL, 20 V) at room temperature. Potassium carbonate (203 g, 1475 mmol) was added portionwise to the reaction mixture at 0 °C, and the resulting solution was stirred at the same temperature for 30 minutes. Methyl iodide (69.2 mL, 1106.4 mmol) was added dropwise to the reaction mixture at 0 °C, and the mixture was stirred at room temperature for 4 hours. TLC (5:5 ethyl acetate / hexane) after 4 hours indicated that SM had been consumed. The reaction mixture was quenched with ice-cold water (5900 mL), giving a yellow precipitate. The resulting precipitate was filtered and washed with water (3000 mL) and hexane (3000 mL). The solid was dried under vacuum at 45° C. overnight to give a white solid (270 g, 88%). LCMS R (Waters, acidic, 4.0 min): 2.243 min, m / z =416.7[M+H] + . 1H NMR: (400 MHz, DMSO-d6) δ 8.13 (d, J=8.4 Hz, 2H), 7.91 (s, 1H), 7.52 - 7.49 (d, J=8.0 Hz, 2H), 6.81 (s, 1H), 3.43 (s, 3H), 2.42 (s, 3H). Preparation 98: 2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-c]pyridin-7-one [ka] To a stirred mixture of 4-bromo-2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)pyrrolo[2,3-c]pyridin-7-one (10.0 g, 24.1 mmol, 1.00 equiv.) and bis(pinacolato)diboron (36.7 g, 144 mmol, 6.00 equiv.) in THF (150 mL) at room temperature under a nitrogen atmosphere, KOAc (4.72 g, 48.1 mmol, 2.00 equiv.) and Pd(PPh3)2Cl2 (1.69 g, 2.41 mmol, 0.100 equiv.) were added. The resulting mixture was stirred overnight under a nitrogen atmosphere at 60 °C. LCMS showed no residual SM. The reaction was quenched with water. The resulting mixture was extracted with CHCl2 (3 × 150 mL). The combined organic layers were washed with brine and dried over anhydrous NaSO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with PE / EA (3:1) to give the crude product as a yellow solid. The crude product was further purified by reverse-phase flash chromatography under the following conditions: column, C18; mobile phase, MeCN in water (0.1% FA), 50% to 90% gradient in 15 min; detector, UV 254 nm. This resulted in 2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-c]pyridin-7-one (4.30 g, 38.6%) as a pale yellow solid. LCMS m / z = 463 [M+H] + 1H NMR (300 MHz, DMSO-d6) δ 8.14 - 8.08 (m, 2H), 7.82 (s, 1H), 7.52 - 7.47 (m, 2H), 6.84 (s, 1H), 3.48 (s, 3H), 2.42 (s, 3H), 1.29 (s, 12H). Preparation 99: 4-[2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-5-(2,6-dimethylphenoxy)-1-methylpyridin-2-one [ka] To a stirred mixture of 2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-c]pyridin-7-one (1.50 g, 3.24 mmol, 1.00 equiv.) and 4-bromo-5-(2,6-dimethylphenoxy)-1-methylpyridin-2-one (1.20 g, 3.89 mmol, 1.20 equiv.) in DME (1.50 mL) and HO (0.30 mL) at room temperature under a nitrogen atmosphere, NaCO (690 mg, 6.48 mmol, 2.00 equiv.) and Pd(dppf)Cl·CHCl (260 mg, 0.324 mmol, 0.10 equiv.) were added. The resulting mixture was stirred overnight at 60 °C under a nitrogen atmosphere. LCMS showed no residual SM. The mixture was cooled to room temperature and then quenched with water. The resulting mixture was extracted with EtOAc (3 × 30 mL). The combined organic layers were washed with brine and dried over anhydrous NaSO. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with EtOAc / MeOH (12:1) to give 4-[2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-5-(2,6-dimethylphenoxy)-1-methylpyridin-2-one as a yellow solid (910 mg, 50%). LCMS: m / z = 564 [M+H] + Preparation 100: 4-{2-chloro-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl}-5-(2,6-dimethylphenoxy)-1-methylpyridin-2-one [ka] To a mixture of 4-[2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-5-(2,6-dimethylphenoxy)-1-methylpyridin-2-one (910 mg, 1.61 mmol, 1.00 equiv.) in 1,4-dioxane (5.0 mL) and HO (1.0 mL) was added NaOH (645 mg, 16.1 mmol, 10.0 equiv.). The mixture was stirred at 60° C. for 1 hour. LCMS showed no residual SM. The mixture was allowed to cool to room temperature. The reaction was quenched with water at room temperature. The resulting mixture was extracted with EtOAc (3×30.0 mL). The combined organic layers were washed with brine and dried over anhydrous NaSO. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with EtOAc / MeOH (12:1) to give 4-{2-chloro-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl}-5-(2,6-dimethylphenoxy)-1-methylpyridin-2-one as a yellow solid (328 mg, 49.7%). LCMS: m / z = 410 [M+H] + Preparation 101: 5-(2,6-dimethylphenoxy)-1-methyl-4-[6-methyl-2-(2-methylpyridin-4-yl)-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]pyridin-2-one [ka] To a stirred mixture of 4-{2-chloro-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl}-5-(2,6-dimethylphenoxy)-1-methylpyridin-2-one (60.0 mg, 0.146 mmol, 1.00 equiv.) and 2-methylpyridin-4-ylboronic acid (40.1 mg, 0.292 mmol, 2.00 equiv.) in DME (1.00 mL) and HO (0.20 mL) at room temperature under a nitrogen atmosphere, KCO (40.5 mg, 0.292 mmol, 2.00 equiv.) and XPhos Pd G (12.4 mg, 0.0150 mmol, 0.100 equiv.) were added. The resulting mixture was stirred at 100 °C for 4 h. The reaction was quenched with water. The resulting mixture was extracted with EtOAc (3 × 30 mL). The combined organic layers were washed with brine and water and dried over anhydrous NaSO. After filtration, the filtrate was concentrated under reduced pressure. The crude product (60.0 mg) was purified by preparative HPLC (instrument C; column D) eluting with a gradient of 0.1% aqueous FA and acetonitrile and lyophilized to give a white solid (40.0 mg). The product was further treated with HCl (g) in MeOH (1.00 mL, 4.0 N) followed by lyophilization. This gave 5-(2,6-dimethylphenoxy)-1-methyl-4-[6-methyl-2-(2-methylpyridin-4-yl)-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]pyridin-2-one hydrochloride as a yellow solid (35.0 mg, 48%). LCMS tR (Shimadzu LMCS-2020,A,2.80 min): 1.11 min, m / z = 467.05 [M+H] + 1H NMR (400 MHz, DMSO-d6) δ 13.21 (bs, 1H), 8.77 (d, J = 6.4 Hz, 1H), 8.53 (d, J = 1.9 Hz, 1H), 8.44 (dd, J = 6.4, 1.9 Hz, 1H), 7.61 (s, 1H), 7.53 (d, J = 2.3 Hz, 1H), 7.14 - 7.08 (m, 2H), 7.07 - 7.01 (m, 1H), 6.77 (s, 1H), 6.65 (s, 1H), 3.63 (s, 3H), 3.37 (s, 3H), 2.73 (s, 3H), 2.09 (s, 6H). Example 46: 2-(2,5-difluorophenyl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 102: 2-(2,5-difluorophenyl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one According to the procedure of Preparation 101, 4-{2-chloro-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl}-5-(2,6-dimethylphenoxy)-1-methylpyridin-2-one (70.0 mg, 0.171 mmol, 1.00 equiv.) was reacted with 2,5-difluorophenylboronic acid (53.9 mg, 0.342 mmol, 2.00 equiv.) to afford the title compound as a white solid (33.0 mg, 39.6%) after purification by preparative HPLC (Instrument C; Column A) eluting with a gradient of 10 mmol / L NH4HCO3 solution in water and acetonitrile. LCMS tR (Shimadzu LMCS-2020,B,2.80 min): 1.834 min, m / z = 488.20 [M+H] + 1H NMR (300 MHz, DMSO-d6) δ 12.56 (s, 1H), 8.11 - 7.97 (m, 1H), 7.54 (s, 1H), 7.45 - 7.31 (m, 1H), 7.30 - 7.14 (m, 1H), 7.14 - 6.98 (m, 3H), 6.88 (d, J = 3.8 Hz, 1H), 6.67 (s, 1H), 6.53 (s, 1H), 3.62 (s, 3H), 3.32 (s, 3H), 2.09 (s, 6H). Example 47: 2-(2,4-difluorophenyl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 103: 2-(2,4-difluorophenyl)-4-(5-(2,6-dimethylphenoxy)-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one According to the procedure of Preparation 101, 4-{2-chloro-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl}-5-(2,6-dimethylphenoxy)-1-methylpyridin-2-one (70.0 mg, 0.171 mmol, 1.00 equiv.) was reacted with 2,4-difluorophenylboronic acid (53.9 mg, 0.342 mmol, 2.00 equiv.) to afford the title compound as a white solid (26.0 mg, 31.1%) after purification by preparative HPLC (Instrument C; Column A) eluting with a gradient of 0.1% NH3 solution in water and acetonitrile. LCMS R (Shimadzu LMCS-2020,B,3.00 minutes): 1.835 minutes, m / z = 488.25 [M+H] + 1 H NMR (300 MHz, DMSO-d 6) δ 12.48 (s, 1H), 8.25-8.00 (m, 1H), 7.54 (s, 1H), 7.47 - 7.33 (m, 1H), 7.21 (t, J = 8.0 Hz, 1H), 7.15 - 6.99 (m, 3H), 6.76 (d, J = 3.6 Hz, 1H), 6.67 (s, 1H), 6.53 (s, 1H), 3.62 (s, 3H), 3.33 (s, 3H), 2.09 (s, 6H). Example 48: 2-{4-[5-(2,6-dimethylphenoxy)-1-methyl-2-oxopyridin-4-yl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-2-yl}benzonitrile [ka] Preparation 104: 2-{4-[5-(2,6-dimethylphenoxy)-1-methyl-2-oxopyridin-4-yl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-2-yl}benzonitrile According to the procedure of Preparation 101, 4-{2-chloro-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl}-5-(2,6-dimethylphenoxy)-1-methylpyridin-2-one (100 mg, 0.244 mmol, 1.00 equiv.) was reacted with 2-cyanophenylboronic acid (71.7 mg, 0.488 mmol, 2.00 equiv.) to afford the title compound as a white solid (20.0 mg, 17.2%) after purification by preparative HPLC (Instrument C; Column D) eluting with a gradient of 0.1% FA solution in water and acetonitrile. LCMS R (Shimadzu LMCS-2020,B,3.00 minutes): 1.675 minutes, m / z = 477.30 [M+H] + 1 H NMR (300 MHz, DMSO-d 6) δ 12.73 (s, 1H), 7.95 (d, J = 8.0 Hz, 2H), 7.83 - 7.72 (m, 1H), 7.61 - 7.50 (m, 2H), 7.14 - 6.99 (m, 3H), 6.97 (s, 1H), 6.67 (s, 1H), 6.56 (s, 1H), 3.62 (s, 3H), 3.32 (s, 3H), 2.07 (s, 6H). Example 49: 4-{4-[5-(2,6-dimethylphenoxy)-1-methyl-2-oxopyridin-4-yl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-2-yl}-1-isopropylpyrazole-3-carbonitrile [ka] Preparation 105: 4-Bromo-1-isopropylpyrazole-3-carbonitrile [ka] To a solution of 4-bromo-1H-pyrazole-3-carbonitrile (3.00 g, 17.4 mmol, 1.00 equiv) in DMF (20.0 mL) was added NaH (840 mg, 20.9 mmol, 1.20 equiv, 60 wt% in mineral oil). The mixture was stirred at 0° C. for 30 minutes, and then 2-bromopropane (2.45 g, 19.8 mmol, 1.14 equiv) was added. The mixture was warmed to room temperature and stirred overnight. The reaction was quenched with water. The resulting mixture was extracted with EtOAc (3×30 mL). The combined organic layers were washed with brine and dried over Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with PE / EA (5:1) to give 4-bromo-1-isopropylpyrazole-3-carbonitrile (2.00 g, 54%) as a pale yellow solid. LCMS: m / z = 216 [M+H] + 1H NMR (300 MHz, chloroform-d) δ 7.52 (s, 1H), 4.61–4.43 (m, 1H), 1.51 (d, J = 6.7 Hz, 6H). Preparation 106: 3-Cyano-1-isopropylpyrazol-4-ylboronic acid [ka] To a solution of 4-bromo-1-isopropylpyrazole-3-carbonitrile (500 mg, 2.34 mmol, 1.00 equiv.) in THF (5.00 mL) was added n-BuLi (1.31 mL, 3.27 mmol, 1.40 equiv., 2.50 M / L in hexanes) at −78° C. under a nitrogen atmosphere. The reaction mixture was stirred at −78° C. for 30 minutes, followed by the addition of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (869 mg, 4.67 mmol, 2.00 equiv.). The mixture was allowed to warm to room temperature. The reaction mixture was quenched with saturated NH4Cl. The resulting mixture was extracted with EtOAc (3×20 mL). The combined organic layers were washed with water and brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with PE / EA (5:1) to give 3-cyano-1-isopropylpyrazol-4-ylboronic acid as a pale yellow solid (263 mg, 62.9%). LCMS: m / z = 180 [M+H] + Preparation 107: 4-{4-[5-(2,6-dimethylphenoxy)-1-methyl-2-oxopyridin-4-yl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-2-yl}-1-isopropylpyrazole-3-carbonitrile [ka] According to the procedure of Preparation 101, 3-cyano-1-isopropylpyrazol-4-ylboronic acid (60.0 mg, 0.335 mmol, 1.00 equiv.) was reacted with 4-{2-chloro-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl}-5-(2,6-dimethylphenoxy)-1-methylpyridin-2-one (618 mg, 1.51 mmol, 4.50 equiv.) to give the title compound as a white solid (22.0 mg, 12.9%) after purification by preparative HPLC (instrument C; column D) eluting with a gradient of 0.1% FA solution in water and acetonitrile. LCMS R (Shimadzu LCMS-2020,A,2.80 minutes): 1.599 minutes, m / z = 509 [M+H] + 1 H NMR (300 MHz, methanol-d 4 ) δ 8.37 (s, 1H), 7.55 (s, 1H), 7.17 - 7.02 (m, 3H), 6.92 (s, 1H), 6.79 (s, 1H), 6.69 (s, 1H), 4.74 - 4.63 (m, 1H), 3.75 (s, 3H), 3.49 (s, 3H), 2.17 (s, 6H), 1.59 (d, J = 6.7 Hz, 6H). Example 50: 4-[2-(2,3-difluorophenyl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]-5-(2,6-dimethylphenoxy)-1-methylpyridin-2-one [ka] Preparation 108: 4-[2-(2,3-difluorophenyl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]-5-(2,6-dimethylphenoxy)-1-methylpyridin-2-one According to the procedure of Preparation 101, 4-{2-chloro-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl}-5-(2,6-dimethylphenoxy)-1-methylpyridin-2-one (70.0 mg, 0.171 mmol, 1.00 equiv.) was reacted with 2,3-difluorophenylboronic acid (53.9 mg, 0.342 mmol, 2.00 equiv.) to afford the title compound as a white solid (31.0 mg, 37.1%) after purification by preparative HPLC (Instrument C; Column A) eluting with a gradient of 0.1% NH3 solution in water and acetonitrile. LCMS R (Shimadzu LMCS-2020,B,3.00 minutes):1.824 minutes, m / z = 488 [M+H] + 1 H NMR (300 MHz, DMSO-d 6 ) δ 12.59 (s, 1H), 8.00-7.80 (m, 1H), 7.55 (s, 1H), 7.45-7.35 (m, 1H), 7.35-7.25 (m, 1H), 7.18 - 6.99 (m, 3H), 6.84 (d, J = 3.5 Hz, 1H), 6.67 (s, 1H), 6.54 (s, 1H), 3.62 (s, 3H), 3.32 (s, 3H), 2.10 (s, 6H). Example 51: 5-(2,6-dimethylphenoxy)-1-methyl-4-[6-methyl-2-(1-methyl-6-oxopyridin-3-yl)-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]pyridin-2-one [ka] Preparation 109: 5-(2,6-dimethylphenoxy)-1-methyl-4-[6-methyl-2-(1-methyl-6-oxopyridin-3-yl)-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]pyridin-2-one According to the procedure of Preparation 101, 4-{2-chloro-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl}-5-(2,6-dimethylphenoxy)-1-methylpyridin-2-one (60.0 mg, 0.146 mmol, 1.00 equiv.) was reacted with 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one (51.6 mg, 0.219 mmol, 1.50 equiv.) to afford the title compound as a white solid (11.0 mg, 15.6%) after purification by preparative HPLC (instrument C; column C) eluting with a gradient of 0.1% FA solution in water and acetonitrile. LCMS R (Shimadzu LMCS-2020,C,2.80 minutes): 1.36 minutes, m / z = 483.05 [M+H] + 1 H NMR (300 MHz, methanol-d 4 ) δ 8.27 (d, J = 2.6 Hz, 1H), 8.08 - 7.95 (m, 1H), 7.61 (s, 1H), 7.18 - 7.04 (m, 3H), 6.85 (s, 1H), 6.76 (s, 1H), 6.71 - 6.64 (m, 2H), 3.74 (s, 3H), 3.67 (s, 3H), 3.48 (s, 3H), 2.17 (s, 6H). Example 52: 5-Cyclopentyl-4-[2-(2,5-dimethylpyrazol-3-yl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]-1-methylpyridin-2-one [ka] Preparation 110: 4-Bromo-5-(cyclopent-1-en-1-yl)-1-methylpyridin-2-one [ka] To a stirred mixture of 4-bromo-5-iodo-1-methylpyridin-2-one (5.80 g, 18.5 mmol, 1.00 equiv.) and 2-(cyclopent-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (4.34 g, 22.4 mmol, 1.21 equiv.) in dioxane (20.0 mL) and HO (5.00 mL) was added NaCO (2.04 g, 19.2 mmol, 1.04 equiv.) and Pd(PPh) (7.90 g, 6.84 mmol, 0.370 equiv.) at room temperature under a nitrogen atmosphere. The resulting mixture was stirred at 100 °C overnight. The resulting mixture was extracted with EtOAc (4 × 20.0 mL). The combined organic layers were washed with brine and dried over anhydrous NaSO. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography eluting with PE / EA (1:9) to give 4-bromo-5-(cyclopent-1-en-1-yl)-1-methylpyridin-2-one (2.80 g, 59.6%) as a yellow solid. LCMS: m / z = 256 [M+H] + Preparation 111: 4-Bromo-5-cyclopentyl-1-methylpyridin-2-one [ka] To a solution of 4-bromo-5-(cyclopent-1-en-1-yl)-1-methylpyridin-2-one (2.80 g, 11.0 mmol, 1.00 equiv.) in MeOH (30.0 mL) was added Pt / C (4.30 g, 1.10 mmol, 5 wt%). The mixture was stirred under a hydrogen atmosphere at room temperature for 4 hours. The resulting mixture was filtered, and the filter cake was washed with MeOH. The filtrate was concentrated under reduced pressure. The residue was purified by reverse-phase flash chromatography under the following conditions: column: C18; mobile phase, MeCN in water (0.1% FA), 10% to 50% gradient in 10 min; detector, UV 254 nm. This afforded 4-bromo-5-cyclopentyl-1-methylpyridin-2-one (1.98 g, 67.3%) as a brown solid. LCMS: m / z = 258 [M+H]+ Preparation 112: 5-Cyclopentyl-4-[2-(1-isopropylpyrazol-4-yl)-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methylpyridin-2-one [ka] To a stirred mixture of 2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-c]pyridin-7-one (450 mg, 0.972 mmol, 1.00 equiv.) and 4-bromo-5-cyclopentyl-1-methylpyridin-2-one (373 mg, 1.46 mmol, 1.50 equiv.) in DME (5.00 mL) and HO (1.00 mL) at room temperature under a nitrogen atmosphere, NaCO (206 mg, 1.94 mmol, 2.00 equiv.) and Pd(dppf)ClCHCl (79.2 mg, 0.0970 mmol, 0.100 equiv.) were added. The resulting mixture was stirred at 60 °C for 4 h. The reaction was quenched with water. The resulting mixture was extracted with EtOAc (3 × 10.0 mL). The combined organic layers were washed with brine and dried over anhydrous NaSO. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with EA / MeOH (10:1) to give 4-[2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-5-cyclopentyl-1-methylpyridin-2-one as a pale yellow solid (375 mg, 75.3%). LCMS: m / z = 572 [M+H] + Preparation 113: 5-Cyclopentyl-4-[2-(2,5-dimethylpyrazol-3-yl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]-1-methylpyridin-2-one [ka] To a stirred mixture of 5-cyclopentyl-4-[2-(2,5-dimethylpyrazol-3-yl)-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methylpyridin-2-one (60.0 mg, 0.105 mmol, 1.00 equiv) in dioxane (2.00 mL) and HO (0.400 mL) was added NaOH (42.0 mg, 1.05 mmol, 10.0 equiv) at room temperature. The resulting mixture was stirred at 60° C. for 4 hours. The reaction was quenched with water at room temperature. The resulting mixture was extracted with EtOAc (3×5.00 mL). The combined organic layers were washed with brine and dried over anhydrous NaSO. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by preparative HPLC (instrument C; column A) eluting with a gradient of 10 mmol / L NH4HCO3 in water and acetonitrile to give 5-cyclopentyl-4-[2-(2,5-dimethylpyrazol-3-yl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]-1-methylpyridin-2-one as a white solid (19.0 mg, 42.9%). LCMS R (Shimadzu LMCS-2020,C,2.80 minutes): 1.387 minutes, m / z = 418.15 [M+H] + 1 H NMR (400 MHz, chloroform-d) δ 11.41 (s, 1H), 7.23 (s, 1H), 6.87 (s, 1H), 6.53 (d, J = 5.8 Hz, 2H), 6.23 (d, J = 1.9 Hz, 1H), 3.94 (s, 3H), 3.69 (s, 3H), 3.63 (s, 3H), 2.83 - 2.70 (m, 1H), 2.30 (s, 3H), 1.86 - 1.70 (m, 4H), 1.54 - 1.41 (m, 2H), 1.41 - 1.18 (m, 2H). Example 53: 4-(5-cyclopentyl-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(1-isopropyl-1H-pyrazol-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 114: 4-(5-cyclopentyl-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-2-(1-isopropyl-1H-pyrazol-4-yl)-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one According to the procedure of Preparation 113, 5-cyclopentyl-4-[2-(1-isopropylpyrazol-4-yl)-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methylpyridin-2-one (170 mg, 0.290 mmol, 1.00 equiv) was reacted to give the title compound as a white solid (53.0 mg, 42.3%) after purification by preparative HPLC (Instrument C; Column A) eluting with a gradient of 0.05% NH3 solution in water and acetonitrile. LCMS R (Shimadzu LMCS-2020,D,2.80 minutes): 1.492 minutes, m / z = 432.10 [M+H] + 1 H NMR (400 MHz, DMSO-d 6 ) δ 12.20 (bs, 1H), 8.36 (s, 1H), 8.01 (s, 1H), 7.68 (s, 1H), 7.17 (s, 1H), 6.25 - 6.20 (m, 2H), 4.51 - 4.40 (m, 1H), 3.55 (s, 3H), 3.50 (s, 3H), 2.77 - 2.74 (m, 1H), 1.73 - 1.39 (m, 4H), 1.24 - 1.20 (m, 10H). Example 54: 5-Cyclopentyl-4-[2-(2,6-dimethylpyridin-4-yl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]-1-methylpyridin-2-one [ka] Preparation 115: 5-Cyclopentyl-4-[2-(2,6-dimethylpyridin-4-yl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]-1-methylpyridin-2-one According to the procedure of Preparation 113, 5-cyclopentyl-4-[2-(2,6-dimethylpyridin-4-yl)-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methylpyridin-2-one (170 mg, 0.292 mmol, 1.00 equiv) was reacted to give the title compound as a white solid (52.0 mg, 41.6%) after purification by preparative HPLC (instrument C; column A) eluting with a gradient of 10 mmol / L NH4HCO3 solution in water and acetonitrile. LCMS R (Shimadzu LMCS-2020,E,2.80 minutes): 1.470 minutes, m / z = 429.10 [M+H] + 1 H NMR (400 MHz, DMSO-d 6 ) δ 12.65 (s, 1H), 7.70 - 7.67 (m, 3H), 7.23 (s, 1H), 6.72 (s, 1H), 6.27 (s, 1H), 3.57 (s, 3H), 3.51 (s, 3H), 2.75 - 2.72 (m, 1H), 2.43 (s, 6H), 1.73 - 1.62 (m, 4H), 1.38 - 1.30 (m, 4H). Example 55: 5-Cyclopentyl-1-methyl-4-{6-methyl-7-oxo-2-phenyl-1H-pyrrolo[2,3-c]pyridin-4-yl}pyridin-2-one [ka] Preparation 116: 5-Cyclopentyl-1-methyl-4-{6-methyl-7-oxo-2-phenyl-1H-pyrrolo[2,3-c]pyridin-4-yl}pyridin-2-one According to the procedure of Preparation 113, 5-cyclopentyl-1-methyl-4-[6-methyl-1-(4-methylbenzenesulfonyl)-7-oxo-2-phenylpyrrolo[2,3-c]pyridin-4-yl]pyridin-2-one (150 mg, 0.271 mmol, 1.00 equiv) was reacted to give the title compound as a white solid (42.0 mg, 38.8%) after purification by preparative HPLC (instrument C; column A) eluting with a gradient of 0.05% NH3 solution in water and acetonitrile. LCMS R (Shimadzu LMCS-2020,D,2.80 minutes): 1.444 minutes, m / z = 400.10 [M+H] + 1 H NMR (300 MHz, DMSO-d 6 ) δ 12.48 (s, 1H), 7.96 - 7.93 (m, 2H), 7.69 (s, 1H), 7.42 - 7.28 (s, 3H), 7.22 (s, 1H), 6.50 (s, 1H), 6.28 (s, 1H), 3.57 - 3.51 (m, 6H), 2.81 - 2.76 (m, 1H), 1.74 - 1.63 (m, 4H), 1.38 (s, 4H). Example 56: 5-ethynyl-4-[2-(1-isopropylpyrazol-4-yl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]-1-methylpyridin-2-one [ka] Preparation 117: 4-Bromo-1-methyl-5-[2-(trimethylsilyl)ethynyl]pyridin-2-one [ka] To a stirred mixture of 4-bromo-5-iodo-1-methylpyridin-2-one (17.0 g, 54.2 mmol, 1.00 equiv.) and EtN (16.5 g, 162 mmol, 3.00 equiv.) in THF (170 mL) under a nitrogen atmosphere at room temperature, Pd(dppf)Cl (3.96 g, 5.42 mmol, 0.10 equiv.) and CuI (1.03 g, 5.42 mmol, 0.10 equiv.) were added. To the above mixture, trimethylsilylacetylene (5.85 g, 59.7 mmol, 1.10 equiv.) was added at room temperature. The resulting mixture was stirred at room temperature for an additional 2 hours. LCMS showed no remaining starting material. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with PE / EA (6:1) to give 4-bromo-1-methyl-5-[2-(trimethylsilyl)ethynyl]pyridin-2-one as a brown solid (6.60 g, 42.8%). LCMS: m / z = 286 [M+H] + Preparation 118: 4-Bromo-5-ethynyl-1-methylpyridin-2(1H)-one [ka] A mixture of 4-bromo-1-methyl-5-[2-(trimethylsilyl)ethynyl]pyridin-2-one (6.60 g, 23.2 mmol, 1.00 equiv.) and K2CO3 (9.63 g, 69.7 mmol, 3.00 equiv.) in MeOH (70 mL) was stirred at room temperature overnight. The resulting mixture was filtered, and the filter cake was washed with EtOAc (3 × 100 mL). The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with PE / EA (5:1) to give 4-bromo-5-ethynyl-1-methylpyridin-2-one as a brown solid (2.10 g, 42.6%). LCMS: m / z = 214 [M+H] + Preparation 119: 4-[2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-5-ethynyl-1-methylpyridin-2-one [ka] To a mixture of 2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-c]pyridin-7-one (500 mg, 1.08 mmol, 1.00 equiv.) and 4-bromo-5-ethynyl-1-methylpyridin-2-one (458 mg, 2.16 mmol, 2.00 equiv.) in DME (4.0 mL) and DME (1.0 mL) was added KCO (298 mg, 2.16 mmol, 2.00 equiv.) and Pd(PPh) (125 mg, 0.108 mmol, 0.100 equiv.) at room temperature under a nitrogen atmosphere. The resulting mixture was stirred at 60 °C for 4 hours. The reaction was quenched with water at room temperature. The resulting mixture was extracted with EtOAc (4 × 20.0 mL). The combined organic layers were washed with brine (2 × 10.0 mL) and dried over anhydrous NaSO. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with EtOAc / MeOH (10:1) to give 4-[2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-5-ethynyl-1-methylpyridin-2-one as a pale yellow solid (250 mg, 49.5%). LCMS: m / z = 468 [M+H] + Preparation 120: 5-ethynyl-4-[2-(1-isopropylpyrazol-4-yl)-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methylpyridin-2-one [ka] To a mixture of 4-[2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-5-ethynyl-1-methylpyridin-2-one (250 mg, 0.534 mmol, 1.00 equiv.) and 1-isopropylpyrazol-4-ylboronic acid (165 mg, 1.07 mmol, 2.00 equiv.) in DME (2.00 mL) and HO (0.50 mL) at room temperature under a nitrogen atmosphere, Pd(PPh) (61.7 mg, 0.053 mmol, 0.100 equiv.) and KCO (148 mg, 1.07 mmol, 2.00 equiv.) were added. The resulting mixture was stirred at 80 °C overnight. The reaction was quenched with water at room temperature. The resulting mixture was extracted with EtOAc (4 × 20.0 mL). The combined organic layer was washed with brine (2 × 10.0 mL) and dried over anhydrous NaSO. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with EtOAc / MeOH (10:1) to give 5-ethynyl-4-[2-(1-isopropylpyrazol-4-yl)-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methylpyridin-2-one as a pale yellow solid (90.0 mg, 31.1%). LCMS: m / z = 542 [M+H] + Preparation 121: 5-ethynyl-4-[2-(1-isopropylpyrazol-4-yl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]-1-methylpyridin-2-one [ka] A solution of 5-ethynyl-4-[2-(1-isopropylpyrazol-4-yl)-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methylpyridin-2-one (90.0 mg, 0.166 mmol, 1.00 equiv) and NaOH (66.4 mg, 1.66 mmol, 10.0 equiv) in MeOH (5.00 ml) and HO (1.00 mL) was stirred at 40 °C for 1 h. The reaction was quenched with water at room temperature. The resulting mixture was extracted with EtOAc (4 × 20.0 mL). The combined organic layers were washed with brine (2 × 10.0 mL) and dried over anhydrous NaSO. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by preparative HPLC (instrument C; column E) eluting with a gradient of 10 mmol / L NH4HCO3 in water and acetonitrile to give 5-ethynyl-4-[2-(1-isopropylpyrazol-4-yl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]-1-methylpyridin-2-one as a white solid (7.30 mg, 11.3%). LCMS R (Shimadzu LMCS-2020,D,2.80 minutes):1.240 minutes, m / z = 388.00 [M+H] + 1 H NMR (300 MHz, methanol-d 4 ) δ 8.14 (s, 1H), 8.09 (s, 1H), 7.91 (s, 1H), 7.50 (s, 1H), 6.69 (s, 1H), 6.50 (s, 1H), 4.61 - 4.52 (m, 1H), 3.86 (s, 3H), 3.54 (s, 3H), 3.47 (s, 1H), 1.54 - 1.28 (m, 6H). Example 57: 4-[2-(1-isopropylpyrazol-4-yl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]-1-methyl-5-(prop-1-yn-1-yl)pyridin-2-one [ka] Preparation 122: 4-Bromo-1-methyl-5-(prop-1-yn-1-yl)pyridin-2-one [ka] To a stirred mixture of 4-bromo-5-iodo-1-methylpyridin-2-one (5.00 g, 15.9 mmol, 1.00 equiv.) and 2-butynoic acid (1.61 g, 19.1 mmol, 1.20 equiv.) in DMSO (50.0 mL) at room temperature under a nitrogen atmosphere, DBU (7.27 g, 47.8 mmol, 3.00 equiv.) and Pd(PPh3)2Cl2 (560 mg, 0.796 mmol, 0.05 equiv.) were added. The resulting mixture was stirred at 110 °C for 5 h under a nitrogen atmosphere. The resulting mixture was filtered, and the filter cake was washed with DMSO. The residue was purified by reverse-phase flash chromatography under the following conditions: C18; mobile phase, MeCN in water (0.1% FA), 10% to 40% gradient over 15 min; detector, UV at 254 nm. The resulting mixture was concentrated under reduced pressure. This gave 4-bromo-1-methyl-5-(prop-1-yn-1-yl)pyridin-2-one as a yellow solid (1.70 g, 47.2%). LCMS: m / z = 228 [M+H] + Preparation 123: 4-[2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methyl-5-(prop-1-yn-1-yl)pyridin-2-one [ka] According to the procedure of Preparation 119, 2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-c]pyridin-7-one (524 mg, 1.13 mmol, 1.00 equiv) was reacted with 4-bromo-1-methyl-5-(prop-1-yn-1-yl)pyridin-2-one (512 mg, 2.26 mmol, 2.00 equiv) to give the title compound as a white solid (470 mg, 86.1%). LCMS: m / z = 482 [M+H] + Preparation 124: 4-[2-(1-isopropylpyrazol-4-yl)-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methyl-5-(prop-1-yn-1-yl)pyridin-2-one [ka] According to the procedure of Preparation 112, 4-[2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methyl-5-(prop-1-yn-1-yl)pyridin-2-one (250 mg, 0.519 mmol, 1.00 equiv) was reacted with 1-isopropylpyrazol-4-ylboronic acid (160 mg, 1.04 mmol, 2.00 equiv) to give the title compound as a white solid (100 mg, 34.7%). LCMS: m / z = 556 [M+H] + Preparation 125: 4-[2-(1-isopropylpyrazol-4-yl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]-1-methyl-5-(prop-1-yn-1-yl)pyridin-2-one [ka] According to the procedure of Preparation 113, 4-[2-(1-isopropylpyrazol-4-yl)-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methyl-5-(prop-1-yn-1-yl)pyridin-2-one (100 mg, 0.180 mmol, 1.00 equiv) was reacted to give the title compound as an off-white solid (8.40 mg, 11.6%) after purification by preparative HPLC (instrument C; column A) eluting with a gradient of 10 mmol / L NH4HCO3 solution in water and acetonitrile. LCMSt R(Shimadzu LMCS-2020,D,2.80 minutes): 1.362 minutes, m / z = 402.05 [M+H] + 1 H NMR (400 MHz, methanol-d 4 ) δ 8.15 (s, 1H), 7.92 (d, J = 3.9 Hz, 2H), 7.50 (s, 1H), 6.68 (s, 1H), 6.50 (s, 1H), 4.67 - 4.50 (m, 1H), 3.69 (s, 3H), 3.61 (s, 3H), 1.83 (s, 3H), 1.53 (d, J = 6.6 Hz, 6H). Example 58: 4-[2-(2,6-dimethylpyridin-4-yl)-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methyl-5-(prop-1-yn-1-yl)pyridin-2-one [ka] Preparation 126: 4-[2-(2,6-dimethylpyridin-4-yl)-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methyl-5-(prop-1-yn-1-yl)pyridin-2-one [ka] According to the procedure of Preparation 112, 4-[2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methyl-5-(prop-1-yn-1-yl)pyridin-2-one (270 mg, 0.560 mmol, 1.00 equiv) was reacted with 2,6-dimethylpyridin-4-ylboronic acid (169 mg, 1.12 mmol, 2.00 equiv) to give the title compound as a white solid (70.0 mg, 22.6%). LCMS: m / z = 552 [M+H] + Preparation 127: 4-[2-(2,6-dimethylpyridin-4-yl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]-1-methyl-5-(prop-1-yn-1-yl)pyridin-2-one According to the procedure of Preparation 113, 4-[2-(2,6-dimethylpyridin-4-yl)-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methyl-5-(prop-1-yn-1-yl)pyridin-2-one (70.0 mg, 0.127 mmol, 1.0 equiv) was reacted to give the title compound as a yellow solid (6.50 mg, 12.9%) after purification by preparative HPLC (instrument C; column F) eluting with a gradient of 0.1% FA solution in water and acetonitrile. LCMS R (Shimadzu LMCS-2020,D,2.80 minutes): 1.270 minutes, m / z = 399.05 [M+H] + 1 H NMR (400 MHz, methanol-d 4 ) δ 7.92 (s, 1H), 7.61 - 7.43 (m, 3H), 6.95 (s, 1H), 6.66 (s, 1H), 3.69 (s, 3H), 3.61 (s, 3H), 2.55 (s, 6H), 1.81 (s, 3H). Example 59: 1-Cyclopropyl-5-(2,6-dimethylphenoxy)-4-[2-(2,6-dimethylpyridin-4-yl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]pyridin-2-one [ka] Preparation 128: 2-Bromo-5-(2,6-dimethylphenoxy)pyridine [ka] To a stirred mixture of 2-bromo-5-fluoropyridine (200 g, 1.14 mol, 1.00 equiv.) and 2,6-dimethylphenol (138.9 g, 1.13 mol, 1.0 equiv.) in DMSO (2.0 L) was added CsCO (407.3 g, 1.25 mol, 1.10 equiv.) portionwise at room temperature. The resulting mixture was stirred at 120 °C for 2 h. The desired product could be detected by TLC. The reaction was quenched by adding water / ice (1.0 L) at room temperature. The resulting mixture was extracted with EtOAc (5 × 500 mL). The combined organic layers were washed with brine (3 × 500 mL), dried over anhydrous NaSO, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with PE / EA (12:1) to give 2-bromo-5-(2,6-dimethylphenoxy)pyridine as an off-white solid (248 g, 78.46%). LCMS: m / z = 280.0 [M+H] + 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.03 (d, J = 3.1 Hz, 1H), 7.55 (d, J = 8.7 Hz, 1H), 7.20 - 7.11 (m, 3H), 7.04 (dd, J = 8.7, 3.2 Hz, 1H), 2.07 (s, 6H). Preparation 129: 2-Bromo-5-(2,6-dimethylphenoxy)-4-iodopyridine [ka] To a solution of 2-bromo-5-(2,6-dimethylphenoxy)pyridine (248 g, 0.89 mol, 1.00 equiv) in THF (2.5 L) was added dropwise LDA solution (513 mL, 1.26 mol, 2.0 M / L in THF / hexane) at −78 °C under a N atmosphere. The mixture was stirred at −78 °C for 40 min. To the above mixture was added dropwise a solution of I (1.13 kg, 4.46 mol, 5.0 equiv) in THF (200 mL). The mixture was stirred for an additional 15 min and then warmed to room temperature. The mixture was stirred at room temperature for 1 h. The reaction was quenched with aqueous NaSO (600 mL). The mixture was extracted with EtOAc (3 × 500 mL). The combined organic phase was washed with brine (500 mL), dried over anhydrous NaSO, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with PE / EA (10:1) to give 2-bromo-5-(2,6-dimethylphenoxy)-4-iodopyridine as a white solid (260 g, 72.17%). LCMS: m / z = 405.9 [M+H] + 1 H NMR (300 MHz, DMSO-d 6 ) δ 8.24 (s, 1H), 7.27 - 7.12 (m, 4H), 2.07 (s, 6H). Preparation 130: 5-(2,6-dimethylphenoxy)-4-iodopyridin-2(1H)-one [ka] To a stirred solution of 2-bromo-5-(2,6-dimethylphenoxy)-4-iodopyridine (260 g, 0.64 mol, 1.00 equiv) in t-BuOH (2.6 L) was added KOH (361.0 g, 6.43 mol, 10.0 equiv) portionwise at room temperature. The resulting mixture was stirred in an autoclave at 120 °C for 6 h. The mixture was allowed to cool to room temperature. The reaction was quenched with water / ice at room temperature. The aqueous layer was extracted with CHCl (3 × 500 mL). The combined organic layers were concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with PE / EA (1:4) to give the crude product. The crude product was further purified by trituration with aqueous KCO (2.0 L, 1.0 N) overnight. After filtration, the filter cake was dried to give 5-(2,6-dimethylphenoxy)-4-iodo-1H-pyridin-2-one (90.4 g, 41.18%) as a white solid. LCMS: m / z = 341.9 [M+H] + 1H NMR (400 MHz, DMSO-d6) δ 11.14 (s, 1H), 7.17 - 7.07 (m, 4H), 6.23 (s, 1H), 2.09 (s, 6H). Preparation 131: 1-Cyclopropyl-5-(2,6-dimethylphenoxy)-4-iodopyridin-2-one [ka] To a stirred mixture of 5-(2,6-dimethylphenoxy)-4-iodo-1H-pyridin-2-one (10.0 g, 29.3 mmol, 1.00 equiv.) and cyclopropylboronic acid (5.54 g, 64.5 mmol, 2.20 equiv.) in DCE (400 mL) at room temperature under a nitrogen atmosphere, Cu(OAc) (5.70 g, 31.4 mmol, 1.07 equiv.) and 2,2′-bipyridine (4.90 g, 31.4 mmol, 1.07 equiv.) were added. The resulting mixture was stirred at 70 °C for 3 h. The resulting mixture was extracted with CHCl (3 × 20 mL), dried over anhydrous NaSO, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with PE / EA (1:1) to give 1-cyclopropyl-5-(2,6-dimethylphenoxy)-4-iodopyridin-2-one (1.8 g, 16.11%) as a yellow oil. LCMS: m / z = 382 [M+H] + Preparation 132: 4-[2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-cyclopropyl-5-(2,6-dimethylphenoxy)pyridin-2-one [ka] To a stirred mixture of 2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-c]pyridin-7-one (1.8 g, 3.89 mmol, 1.0 equiv.) and 1-cyclopropyl-5-(2,6-dimethylphenoxy)-4-iodopyridin-2-one (2.22 g, 5.84 mmol, 1.5 equiv.) in DME (20 mL) was added NaCO (820 mg, 7.78 mmol, 2.0 equiv.), Pd(dppf)Cl (0.32 g, 0.389 mmol, 0.1 equiv.), and HO (4 mL) at room temperature under a nitrogen atmosphere. The resulting mixture was stirred overnight at 60 °C under a nitrogen atmosphere. The desired product could be detected by LCMS. The resulting mixture was extracted with EtOAc (3 × 50 mL), dried over anhydrous NaSO, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with EtOAc / MeOH (10:1) to give 4-[2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-cyclopropyl-5-(2,6-dimethylphenoxy)pyridin-2-one (900 mg, 39.21%) as a yellow solid. LCMS: m / z = 590 [M+H] + Preparation 133: 4-{2-chloro-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl}-1-cyclopropyl-5-(2,6-dimethylphenoxy)pyridin-2-one [ka] To a stirred mixture of 4-[2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-cyclopropyl-5-(2,6-dimethylphenoxy)pyridin-2-one (900 mg, 1.53 mmol, 1.0 equiv.) in dioxane (8.0 mL) and HO (2.0 mL), NaOH (610 mg, 15.3 mmol, 10.0 equiv.) was added. The resulting mixture was stirred at 60 °C under a nitrogen atmosphere for 2 hours. The desired product could be detected by LCMS. The resulting mixture was extracted with EtOAc (3 × 20 mL), dried over anhydrous NaSO, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with EA / MeOH (10:1) to give 4-{2-chloro-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl}-1-cyclopropyl-5-(2,6-dimethylphenoxy)pyridin-2-one as a yellow solid (300 mg, 45.12%). LCMS: m / z = 436 [M+H] + Preparation 134: 1-Cyclopropyl-5-(2,6-dimethylphenoxy)-4-[2-(2,6-dimethylpyridin-4-yl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]pyridin-2-one [ka] To a stirred mixture of 4-{2-chloro-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl}-1-cyclopropyl-5-(2,6-dimethylphenoxy)pyridin-2-one (300 mg, 0.688 mmol, 1.0 equiv.) and 2,6-dimethylpyridin-4-ylboronic acid (156 mg, 1.03 mmol, 1.50 equiv.) in DME (5 mL) at room temperature under a nitrogen atmosphere, KCO (190.23 mg, 1.376 mmol, 2 equiv.), XPhos Pd G3 (58.25 mg, 0.069 mmol, 0.1 equiv.), and HO (1.0 mL) were added. The resulting mixture was stirred overnight at 60 °C under a nitrogen atmosphere. The desired product could be detected by LCMS. The resulting mixture was extracted with EtOAc (3 × 20 mL), dried over anhydrous NaSO, filtered, and concentrated under reduced pressure. The crude product was purified by preparative HPLC (instrument C; column G) eluting with a gradient of 0.1% FA solution in water and acetonitrile to give the product, which was further treated with HCl in MeOH (2.0 mL, 4.0 M / L) and lyophilized to give 1-cyclopropyl-5-(2,6-dimethylphenoxy)-4-[2-(2,6-dimethylpyridin-4-yl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]pyridin-2-one hydrochloride as a yellow solid (46 mg, 12.31%). LCMS a t R (Shimadzu LMCS-2020,D,2.80 minutes): 1.41 minutes, m / z = 507.1 [M+H] + 1H NMR (400 MHz, methanol-d4) δ 8.14 (s, 2H), 7.74 (s, 1H), 7.52 (s, 1H), 7.15-7.05(m, 4H), 6.68 (s, 1H), 4.85 (s, 1H), 3.74 (s, 3H), 3.41 (s, 1H), 2.77 (s, 6H), 2.15 (s, 6H), 1.11 (s, 2H), 0.79 (s, 2H). Example 60: 2-(1,3-dimethyl-1H-pyrazol-5-yl)-6-methyl-4-(1-methyl-2-oxo-5-phenyl-1,2-dihydropyridin-4-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] Preparation 135: 4-Bromo-1-methyl-5-phenylpyridin-2-one [ka] To a stirred mixture of 4-bromo-5-iodo-1-methylpyridin-2-one (5.00 g, 15.9 mmol, 1.00 equiv.) and phenylboronic acid (2.72 g, 22.3 mmol, 1.40 equiv.) in DMF (30.0 mL) and HO (3.00 mL) at room temperature under a nitrogen atmosphere, NaCO (3.38 g, 31.9 mmol, 2.00 equiv.) and Pd(PPh) (920 mg, 0.796 mmol, 0.05 equiv.) were added. The resulting mixture was stirred at 100 °C for 6 h. The reaction was quenched with water. The resulting mixture was extracted with EtOAc (3 × 100 mL). The combined organic layers were washed with brine and water and dried over anhydrous NaSO. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with PE / EA (1:1) to give 4-bromo-1-methyl-5-phenylpyridin-2-one as a pale yellow solid (2.00 g, 47.6%). LCMS: m / z = 266 [M+H] + Preparation 136: 2-chloro-6-methyl-4-(1-methyl-2-oxo-5-phenyl-1,2-dihydropyridin-4-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] To a stirred mixture of 2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-c]pyridin-7-one (800 mg, 1.73 mmol, 1.00 equiv.) and 4-bromo-1-methyl-5-phenylpyridin-2-one (548 mg, 2.08 mmol, 1.20 equiv.) in 1,4-dioxane (8.00 mL) and HO (2.00 mL) under a nitrogen atmosphere at room temperature, Pd(PPh) (200 mg, 0.173 mmol, 0.100 equiv.) and NaCO (366 mg, 3.46 mmol, 2.00 equiv.) were added. The resulting mixture was stirred at 60 °C for 4 hours. The reaction was quenched with water at room temperature. The resulting mixture was extracted with EtOAc (4 × 20.0 mL). The combined organic layers were washed with brine and dried over anhydrous NaSO. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with PE / EA (5:1) to give 2-chloro-6-methyl-4-(1-methyl-2-oxo-5-phenyl-1,2-dihydropyridin-4-yl)-1-tosyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one as a pale yellow solid (500 mg, 56.5%). LCMS: m / z = 520 [M+H] + Preparation 137: 4-{2-chloro-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl}-5-phenyl-1H-pyridin-2-one [ka] To a mixture of 4-[2-chloro-6-methyl-1-(4-methylbenzenesulfonyl)-7-oxopyrrolo[2,3-c]pyridin-4-yl]-1-methyl-5-phenylpyridin-2-one (470 mg, 0.904 mmol, 1.00 equiv.) in 1,4-dioxane (5.00 mL) and HO (1.00 mL) was added NaOH (362 mg, 9.04 mmol, 10.0 equiv.) at room temperature. The resulting mixture was stirred at 60 °C for 1 h. The reaction was quenched with water. The resulting mixture was extracted with EtOAc (4 × 20.0 mL). The combined organic layers were washed with brine and dried over anhydrous NaSO. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with EtOAc / MeOH (10:1) to give 4-{2-chloro-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl}-5-phenyl-1H-pyridin-2-one (300 mg, 94.4%) as a white solid. LCMS: m / z = 366 [M+H] + Formulation 138: 2-(1,3-dimethyl-1H-pyrazol-5-yl)-6-methyl-4-(1-methyl-2-oxo-5-phenyl-1,2-dihydropyridin-4-yl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one [ka] To a mixture of 4-{2-chloro-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl}-1-methyl-5-phenylpyridin-2-one (60.0 mg, 0.164 mmol, 1.00 equiv.) and 2,5-dimethylpyrazol-3-ylboronic acid (34.4 mg, 0.246 mmol, 1.50 equiv.) in DME (1.00 mL) and HO (0.200 mL) at room temperature under a nitrogen atmosphere, KCO (45.3 mg, 0.328 mmol, 2.00 equiv.) and XPhos Pd G (13.9 mg, 0.016 mmol, 0.100 equiv.) were added. The resulting mixture was stirred at 60 °C for 1 hour. The reaction was quenched with water at room temperature. The resulting mixture was extracted with EtOAc (4 × 20.0 mL). The combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by preparative HPLC (instrument C;...

Claims

1. Formula (I): 【Chemical 1】 a compound or a pharmaceutically acceptable salt or N-oxide thereof, wherein Ring A is a 5- or 6-membered heterocyclyl, and X ４ is carbon, and X ５ is carbon or nitrogen; R １ is selected from C １ -C ３ -alkyl, C １ -C ３ -fluoroalkyl, C ３ -C ４ -cycloalkyl, and 4-membered heterocycloalkyl; R ２ is selected from 5-membered heterocyclyl, 6-membered heterocyclyl, and phenyl, each of which may be substituted with 1 to 4 R ２ａ groups; R ２ａ is, independently of one another, =O, =S, halo, nitro, cyano, NR ５ R ６ 、OR ７ 、SR ６ 、SOR ６ 、S(O) ２ R ６ 、SO ２ NR ６ R ６ 、CO ２ R ６ 、C(O)R ６ 、CONR ６ R ６ 、C １ -C ４ -alkyl, C ２ -C ４ -alkenyl, C ２ -C ４ -alkynyl, C １ -C ４ -haloalkyl, C ３ -C ６ cycloalkyl, and 4- to 6-membered heterocyclyl; R ３ is selected from R ３ａ , OR ３ｂ , and NR ６ R ３ｂ ; and is selected from R ３ａ is selected from H, CN, C １ -C ４ -alkyl, C ２ -C ４ -alkenyl, C ２ -C ４ -alkynyl, C １ -C ４ -haloalkyl, C ２ -C ４ -haloalkenyl, and C ０ -C ３ -alkylene-R ３ｃ ; and is selected from R ３ｃ is selected from C ３ -C ８ -cycloalkyl, C ５ -C ８ -cycloalkenyl, 5- to 8-membered heterocycloalkenyl, 3- to 8-membered heterocycloalkyl, phenyl, and 5- or 6-membered heteroaryl, where R ３ｃ when is cycloalkyl, heterocycloalkyl, cycloalkenyl, or heterocycloalkenyl, R ３ｃ may be substituted with 1 to 4 R ８ groups, and when R ３ｃ is phenyl or heteroaryl, R ３ｃ may be substituted with 1 to 5 R9; R ３ｂ is selected from C １ -C ４ -alkyl, C ２ -C ４ -alkylene-O-C １ -C ４ -alkyl, C １ -C ４ -haloalkyl, and C ０ -C ３ -alkylene-R ３ｄ ; and is selected from R ３ｄ is selected from C ３ -C ８ -cycloalkyl, 3- to 8-membered heterocycloalkyl, phenyl, and 5- or 6-membered heteroaryl, where when R ３ｄ is cycloalkyl or heterocycloalkyl, R ３ｄ may be substituted with 1 to 4 R ８ groups, and when R ３ｄ is phenyl or heteroaryl, R ３ｄ may be substituted with 1 to 5 R ９ groups; R ４ is independently =O, =S, halo, nitro, cyano, C ０ -C ４ -alkylene-NR ５ R ６ 、C ０ -C ４ -alkylene-OR ７ 、SR ６ 、SOR ６ 、C ０ -C ４ -alkylene-S(O) ２ R ６ 、SO ２ NR ６ R ６ 、C ０ -C ４ -alkylene-CO ２ R ６ 、C ０ -C ４ -alkylene-C(O)R ６ 、C ０ -C ４ -alkylene-CONR ６ R ６ 、C １ -C ４ -alkyl、C １ -C ４ -alkyl-S(O) ２ R ６ 、C ２ -C ４ -alkenyl、C ２ -C ４ -alkynyl、C １ -C ４ -haloalkyl, cyclopropyl, cyclobutyl, and 4- to 6-membered heterocycloalkyl; R ５ is, independently of each other, H, C １ -C ４ -alkyl, C(O)-C １ -C ４ -alkyl, and S(O) ２ -C １ -C ４ -alkyl, or R ５ and R ６ together with the nitrogen atom to which they are attached, form a C ８ -C ５ -heterocycloalkyl group which may be substituted with 1 to 4 R ８ groups; R ６ is, independently of one another, selected from H and C １ -C ４ -alkyl, or two R ６ groups are bonded to the same nitrogen, and the two R ６ groups, together with the nitrogen atom to which they are bonded, form a C ８ -C ５ -heterocycloalkyl group which may be substituted with 1 to 4 R ８ groups; R ７ is, independently of each other, selected from H, C １ -C ４ -alkyl, C(O)-C １ -C ４ -alkyl, and C １ -C ４ -haloalkyl; R ８ is, independently of each other, =O, =S, fluoro, nitro, cyano, NR ５ R ６ 、OR ７ 、SR ６ 、SOR ６ 、S(O) ２ R ６ 、SO ２ NR ６ R ６ 、CO ２ R ６ 、C(O)R ６ 、CONR ６ R ６ 、C １ -C ４ -alkyl, C ２ -C ４ -alkenyl, C ２ -C ４ -alkynyl, C １ -C ４ -haloalkyl, and cyclopropyl; R ９ is, independently of one another, halo, nitro, cyano, NR ５ R ６ , OR ７ , SR ６ , SOR ６ , S(O) ２ R ６ , SO ２ NR ６ R ６ , CO ２ R ６ , C(O)R ６ , CONR ６ R ６ , C １ -C ４ -alkyl, C ２ -C ４ -alkenyl, C ２ -C ４ -alkynyl, C １ -C ４ -haloalkyl, and cyclopropyl; R ｘ and R ｙ are each independently selected from H, halo, nitro, cyano, NR ５ R ６ , OR ７ , SR ６ , SOR ６ , S(O) ２ R ６ , SO ２ NR ６ R ６ , CO ２ R ６ , C(O)R ６ , CONR ６ R ６ , C １ -C ４ -alkyl, C ２ -C ４ -alkenyl, C ２ -C ４ -alkynyl, C １ -C ４ -haloalkyl, C ３ -C ４ -cycloalkyl, and 4-membered heterocycloalkyl; m is selected from 0, 1, 2, 3, and 4; Any of the above alkyl, alkylene, alkenyl, or cyclopropyl groups, when chemically possible, is independently, if each is C １ -C ４ -alkyl, oxo, fluoro, nitro, cyano, NR ａ R ｂ 、OR ａ 、SR ａ 、CO ２ R ａ 、C(O)R ａ 、CONR ａ R ａ 、S(O)R ａ 、and S(O) ２ Ra, and may be substituted by 1 to 5 substituents selected therefrom, where R ａ is independently H and C １ -C ４ -alkyl, and R ｂ is independently H, C １ -C ４ -alkyl, C(O)-C １ -C ４ -alkyl, and S(O) ２ -C １ -C ４ -alkyl; a compound or a pharmaceutically acceptable salt or N-oxide thereof.

2. R ｘ and R ｙ are each H, the compound according to claim 1 or a pharmaceutically acceptable salt or N-oxide thereof.

3. R １ The compound according to claim 1, or a pharmaceutically acceptable salt or N-oxide thereof, wherein R is methyl.

4. (i) R ２ is 【Chemical 2】 wherein n1 is selected from 0, 1, and 2; (ii) R2 is 【Chemical Formula 3】 wherein n2 is selected from 0, 1, 2, and 3; (iii) R2 is 【Chemical Formula 4】 wherein n3 is selected from 0, 1, and 2; (iv) R2 is 【Chemical Formula 5】 wherein n7 is selected from 0, 1, and 2, and R2b is selected from H, C1-C4-alkyl, C3-C6 cycloalkyl, and 4- to 6-membered heterocyclyl; or (v) R2 is 【Chemical Formula 6】 wherein n8 is selected from 0, 1, 2, and 3, and R2b is selected from H, C1-C4-alkyl, C3-C6 cycloalkyl, and 4- to 6-membered heterocyclyl; a compound or a pharmaceutically acceptable salt or N-oxide thereof according to Claim 1.

5. (i) R ２ is [Chemical Formula 7] wherein n14 is selected from 0, 1, 2, 3, and 4; or (ii) R2 is [Chemical Formula 8] wherein n13 is selected from 0, 1, 2, 3, 4, and 5; a compound or a pharmaceutically acceptable salt or N-oxide thereof according to Claim 1.

6. When ring A is a 5-membered heterocyclyl, it is not pyrrolidone, a compound or a pharmaceutically acceptable salt or N-oxide thereof according to Claim 1.

7. Ring A is a 5-membered heteroaryl, a compound or a pharmaceutically acceptable salt or N-oxide thereof according to Claim 1.

8. Ring A is pyridone, a compound or a pharmaceutically acceptable salt or N-oxide thereof according to Claim 1.

9. Ring A is substituted on its nitrogen with one group selected from C １ -C ４ -alkyl, cyclopropyl, cyclobutyl, and 4-membered heterocycloalkyl, the compound according to claim 8 or a pharmaceutically acceptable salt or N-oxide thereof.

10. Ring A is 【Chemical Formula 9】 and R ４ａ is each independently H, C １ -C ４ -alkyl, cyclopropyl, and 4-membered heterocycloalkyl, a compound according to claim 8 or a pharmaceutically acceptable salt or N-oxide thereof.

11. R ４ａ The compound according to claim 10, or a pharmaceutically acceptable salt or N-oxide thereof, wherein R is selected from methyl, cyclopropyl, oxetane, and azetidine.

12. R ３ is R ３ａ The compound according to claim 1, or a pharmaceutically acceptable salt or N-oxide thereof, wherein

13. R ３ａ The compound or a pharmaceutically acceptable salt or N-oxide thereof according to claim 12, wherein R is phenyl which may be substituted with one, two or three R9 groups.

14. R ３ is OR ３ｂ The compound according to claim 1 or a pharmaceutically acceptable salt or N-oxide thereof.

15. R ３ｂ The compound according to claim 14, or a pharmaceutically acceptable salt or N-oxide thereof, wherein R is phenyl which may be substituted with one, two or three R9 groups.

16. R ３ｂ is C ０ -C ３ -alkylene-R ３ｄ and R ３ｄ is selected from C ３ -C ６ -cycloalkyl, and 4- to 6-membered heterocycloalkyl, where said cycloalkyl or heterocycloalkyl may be substituted with 1 to 4 R ８ groups, and the compound according to claim 14, or a pharmaceutically acceptable salt or N-oxide thereof.

17. The compound of formula (I) is 【Chemical Formula 10】 [Chemical] 【Chem.】 【Chem.】 [Chemical] 【Chem.】 selected from, a compound or a pharmaceutically acceptable salt or N-oxide thereof according to Claim 1.

18. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt or N-oxide thereof according to any one of Claims 1 to 17 and one or more pharmaceutically acceptable excipients.

19. A medicament comprising a compound or a pharmaceutically acceptable salt or N-oxide thereof according to any one of Claims 1 to 17.

20. A composition for use in the treatment of a disease or disorder selected from one or more of an inflammatory disorder, an immune disorder, and an autoimmune disorder, the composition comprising a compound according to any one of claims 1 to 17 or a pharmaceutically acceptable salt or N-oxide thereof.

21. A composition for use in the treatment of cancer, the composition comprising a compound according to any one of claims 1 to 17 or a pharmaceutically acceptable salt or N-oxide thereof.

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