US 9,808,445 B2
Factor IXa inhibitors
Isao Sakurada, Gotemba (JP); Tomokazu Hirabayashi, Gotemba (JP); Yoshitaka Maeda, Gotemba (JP); Hiroshi Nagasue, Gotemba (JP); Takashi Mizuno, Gotemba (JP); Jiayi Xu, Marlboro, NJ (US); Ting Zhang, Princeton Junction, NJ (US); Cameron Smith, Montgomery Village, MD (US); and Dann Parker, Cranford, NJ (US)
Assigned to Merck Sharp & Dohme Corp., Rahway, NJ (US); and Mochida Pharmaceutical Co., Ltd., Tokyo (JP)
Appl. No. 15/303,322
Filed by Merck Sharp & Dohme Corp., Rahway, NJ (US); and Mochida Pharmaceutical Co., Ltd., Tokyo (JP)
PCT Filed Apr. 10, 2015, PCT No. PCT/US2015/025219
§ 371(c)(1), (2) Date Oct. 11, 2016,
PCT Pub. No. WO2015/160634, PCT Pub. Date Oct. 22, 2015.
Claims priority of provisional application 61/980,358, filed on Apr. 16, 2014.
Prior Publication US 2017/0027916 A1, Feb. 2, 2017
Int. Cl. A61K 31/501 (2006.01); A61K 31/439 (2006.01); C07D 413/14 (2006.01); C07D 261/20 (2006.01); C07D 413/04 (2006.01); C07D 498/04 (2006.01); C07D 209/52 (2006.01); C07D 519/00 (2006.01); A61K 31/444 (2006.01); A61K 31/506 (2006.01); A61K 45/06 (2006.01)
CPC A61K 31/439 (2013.01) [A61K 31/444 (2013.01); A61K 31/501 (2013.01); A61K 31/506 (2013.01); A61K 45/06 (2013.01); C07D 209/52 (2013.01); C07D 261/20 (2013.01); C07D 413/04 (2013.01); C07D 413/14 (2013.01); C07D 498/04 (2013.01); C07D 519/00 (2013.01)] 19 Claims
 
1. A compound of the Formula (I):

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof;
wherein: n is an integer of 0 or 1; p is an integer of 0 to 5; q is an integer of 0 to 4; r is an integer of 0 to 4; X is a nitrogen atom or CH; Y is an oxygen atom, a sulfur atom or NH (when n=0), Y is a nitrogen atom or CH (when n=1);
Z1, Z2, Z3, and Z4 are each independently a nitrogen atom or CH;
each R1 is a halogen atom, a cyano group, a C1-6 alkyl group, a halogenated C1-6 alkyl group, a hydroxyl C1-6 alkyl group, a C3-12 cycloalkyl group, a C1-6 alkoxy group, a halogenated C1-6 alkoxy group, a C2-7 alkanoyl group, or a group of —NRARB;
RA and RB are each independently a hydrogen atom, a C1-6 alkyl group, a halogenated C1-6 alkyl group or a C2-7 alkanoyl group;
each R2 is independently a halogen atom, a cyano group, a C1-6 alkyl group, a halogenated C1-6 alkyl group, a C3-12 cycloalkyl group, a C1-6 alkoxy group, or a halogenated C1-6 alkoxy group;
each R3 is independently a halogen atom, a cyano group, a C1-6 alkyl group, a C3-12 cycloalkyl group, a halogenated C1-6 alkyl group, a hydroxy C1-6 alkyl group, a cyanated C1-6 alkyl group, a C1-6 alkoxy group, a C1-6 alkoxy C1-6 alkyl group, a halogenated C1-6 alkoxy group, a C2-7 alkanoyl group, a C1-6 alkylthio group, a C1-6 alkylsulfonyl group, or a group of —NRARB, or oxo;
a dotted line in a bicyclic substructure of Formula (I) represented by Formula (II):

OG Complex Work Unit Drawing
represents a single bond when n is 0, or a double bond when n is 1;
a substructure of ring A represented by Formula (III):

OG Complex Work Unit Drawing
is a non aromatic heterocyclic group selected from:

OG Complex Work Unit Drawing
is heteroaryl.