US 12,459,927 B2
Plasma kallikrein inhibitors
Salman Jabri, Morage, CA (US); Anthony Ken Ogawa, San Mateo, CA (US); Christopher J. Sinz, Walnut Creek, CA (US); Jacqueline D. Hicks, Watchung, NJ (US); Alan C. Cheng, San Francisco, CA (US); Ying-Duo Gao, Middletown, NJ (US); Song Yang, San Francisco, CA (US); Jianming Bao, Princeton, NJ (US); Donna A. A. W. Hayes, San Francisco, CA (US); Simon B. Lang, San Francisco, CA (US); Brandon M. Taoka, San Francisco, CA (US); Maoqun Tian, Forster, CA (US); Galen Paul Shearn-Nance, Tiburon, CA (US); Rongze Kuang, Greenbook, NJ (US); Matthew J. Lombardo, Flemington, NJ (US); Zhicai Wu, Montvale, NJ (US); and Zhiqiang Zhao, Little Neck, NY (US)
Assigned to Merck Sharp & Dohme LLC, Rahway, NJ (US)
Appl. No. 18/007,787
Filed by Merck Sharp & Dohme LLC, Rahway, NJ (US)
PCT Filed Jun. 10, 2021, PCT No. PCT/US2021/036706
§ 371(c)(1), (2) Date Dec. 2, 2022,
PCT Pub. No. WO2021/257353, PCT Pub. Date Dec. 23, 2021.
Claims priority of provisional application 63/039,873, filed on Jun. 16, 2020.
Prior Publication US 2023/0286958 A1, Sep. 14, 2023
Int. Cl. C07D 403/14 (2006.01); A61P 27/00 (2006.01); C07D 471/04 (2006.01)
CPC C07D 403/14 (2013.01) [A61P 27/00 (2018.01); C07D 471/04 (2013.01)] 16 Claims
 
1. A compound of the formula:

OG Complex Work Unit Chemistry
wherein A is selected from

OG Complex Work Unit Chemistry
B is selected from

OG Complex Work Unit Chemistry
V is CH or N;
X is CH or N;
Y is N, NO, NRx or C═O;
Z is NR4 or CR4;
E is N or CH;
Q is N or CH;
G is N or CR7;
J is N or CR7;
L is N or CR7;
M is N or CR8;
R1 is selected from the group consisting of hydrogen, halo, cyano, Rx, ORx and SO2Rx;
R2 is hydrogen or halo;
R3 is hydrogen or halo;
R4 is hydrogen, Rx, C1-3 alkyl-ORx, C1-3 alkyl-O—C3-6 cycloalkyl or CH═CH2;
R5 is hydrogen or C1-3 alkyl, which is optionally substituted with one to three substituents selected from halo and hydroxy;
R6 is hydrogen or C1-3 alkyl;
or R5 and R6 can be taken together with the carbon atom between them to form a C3-6 cycloalkyl group;
each R7 is independently selected from the group consisting of halo, Rx, ORx, C1-3 alkyl-ORx, NH(C═O)ORx and NH2;
R8 is selected from the group consisting of Rx or ORx;
or R7 and R8 can be taken together with the carbon atoms between them to form a 5-membered cycloalkyl or heterocyclyl group;
R9 is hydrogen or C1-3 alkyl;
R10 is hydrogen, hydroxy or C1-3 alkyl;
Rx is hydrogen or C1-6 alkyl, which is optionally substituted with one to four substituents selected from halo and hydroxy;
or a pharmaceutically acceptable salt thereof.