US 12,115,154 B2
Compounds for the modulation of proprotein convertase subtilisin/kexin type 9 (PCSK9)
Simeon Bowers, Oakland, CA (US); Mark Karbarz, Burlingame, CA (US); Jiang Zhu, Palo Alto, CA (US); Thomas E. Barta, Carrboro, NC (US); Jonathan William Bourne, Fairport, NY (US); and Anjali Pandey, Fremont, CA (US)
Assigned to SRX Cardio, LLC, Pittsford, NY (US)
Filed by SRX Cardio, LLC, Pittsford, NY (US)
Filed on Dec. 16, 2020, as Appl. No. 17/124,357.
Prior Publication US 2022/0193058 A1, Jun. 23, 2022
Int. Cl. C07D 211/14 (2006.01); A61K 31/451 (2006.01); A61K 31/4545 (2006.01); A61P 3/06 (2006.01); C07D 401/04 (2006.01)
CPC A61K 31/451 (2013.01) [A61K 31/4545 (2013.01); A61P 3/06 (2018.01); C07D 211/14 (2013.01); C07D 401/04 (2013.01)] 7 Claims
 
1. A compound of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, prodrug, deuterated analog, stereoisomer, or mixture of stereoisomers thereof,
wherein:
Ring A is a six-membered aromatic ring; X1, X4 and X5 are independently CH or CR1, X2 is CH or CR2, and X3 is CR3, provided that at least one of X2 and X3 is other than CH;
Ring B is a six-membered non-aromatic ring; Z1 is CH2, CHR9, CR9R9, or S; Z2 is N; and Z3 is CHR7 or CR7R9;
each of R1 and R9 are independently C1-C6 alkyl, heterocyclyl, heteroaryl, halo, OH, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, CN, or NH2;
m is 0, 1, 2, 3 or 4, and is not inclusive of R9 groups at Z1 or Z3;
R3 is C3-C6 cycloalkyl, phenyl, heteroaryl, or heterocyclyl;
R2 is H, C1-C6 alkyl, halo, OH, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, CN, NH2, C3-C6 cycloalkyl, phenyl, heteroaryl, or heterocyclyl, wherein each of the C3-C6 cycloalkyl, phenyl, heteroaryl, or heterocyclyl of R2 and R3 is monocyclic and further wherein each of which is optionally substituted with one to five R4;
each R4 is independently selected from C1-C6 alkyl, halo, OH, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, and CN;
R6 is H, halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, OH, CN, or NH2;
R7 is H, halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, OH, CN, or NH2;
R8 is C3-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, heterocyclyl, aryl, heteroaryl, C3-C6 cycloalkyl-C1-C6 alkyl, heteroaryl-C1-C6 alkyl, or heterocyclyl-C1-C6 alkyl; each of which is optionally substituted with one to four substituents independently selected from C1-C6 alkyl, C1-C6 alkoxy, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, halo, =NR11, CN, NH2 and OH; or
R8 and R7 together with the atoms to which they are attached form Ring C, which is a C3-C6 cycloalkyl or heterocyclyl ring fused with Ring B, wherein Ring C is optionally substituted with one to four R12;
R11 is H or C1-C6 alkyl;
each R12 is independently selected from the group consisting of C1-C6 alkyl, halo, OH, C1-C6 alkoxy, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, NH2 and CN; or two R12 together with the atoms to which they are attached form Ring D, which is C3-C6 cycloalkyl or heterocyclyl fused with Ring C; or two R12 on a same carbon atom form=O or =NR11.