US 12,404,274 B2
Macrocycles as factor xia inhibitors
James R. Corte, Yardley, PA (US); Tianan Fang, Newtown, PA (US); Carl P. Decicco, New Hope, PA (US); Donald J.P. Pinto, Churchville, PA (US); Karen A. Rossi, Newtown, PA (US); Zilun Hu, Jamison, PA (US); Yoon Jeon, Belle Mead, NJ (US); Mimi L Quan, Yardley, PA (US); Joanne M. Smallheer, Yardley, PA (US); Yufeng Wang, Belle Mead, NJ (US); and Wu Yang, Princeton Junction, NJ (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Filed by Bristol-Myers Squibb Company, Princeton, NJ (US)
Filed on Oct. 4, 2021, as Appl. No. 17/493,516.
Application 17/493,516 is a division of application No. 16/691,099, filed on Nov. 21, 2019, granted, now 11,136,327.
Application 16/691,099 is a division of application No. 15/718,431, filed on Sep. 28, 2017, granted, now 10,487,086, issued on Nov. 26, 2019.
Application 15/718,431 is a division of application No. 14/578,846, filed on Dec. 22, 2014, granted, now 9,802,939, issued on Oct. 31, 2017.
Application 14/578,846 is a division of application No. 13/024,544, filed on Feb. 10, 2011, granted, now 8,940,720, issued on Jan. 27, 2015.
Claims priority of provisional application 61/405,338, filed on Oct. 21, 2010.
Claims priority of provisional application 61/303,423, filed on Feb. 11, 2010.
Prior Publication US 2023/0058729 A1, Feb. 23, 2023
Int. Cl. C07D 471/18 (2006.01); C07D 471/14 (2006.01); C07D 487/04 (2006.01); C07D 487/06 (2006.01); C07D 487/08 (2006.01); C07D 487/14 (2006.01); C07D 487/16 (2006.01); C07D 487/18 (2006.01); C07D 498/04 (2006.01); C07D 498/06 (2006.01); C07D 498/08 (2006.01)
CPC C07D 487/04 (2013.01) [C07D 471/14 (2013.01); C07D 471/18 (2013.01); C07D 487/06 (2013.01); C07D 487/08 (2013.01); C07D 487/14 (2013.01); C07D 487/16 (2013.01); C07D 487/18 (2013.01); C07D 498/04 (2013.01); C07D 498/06 (2013.01); C07D 498/08 (2013.01)] 8 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, or a solvate thereof, wherein:
ring A is phenyl;
ring B is a 6-membered heteroaryl comprising: carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p;
ring C is a 6-membered heteroaryl comprising: carbon atoms and 1-4 heteroatoms selected from N, O, and S(O)p;
L1 is —CR5═CR5—;
L is C3-8 alkylene; wherein said alkylene is substituted with 0-2 R7;
Y is —CONH—;
R1 is, independently at each occurrence, selected from the group consisting of: halogen, C1-6 alkyl, C1-4 alkoxy, C1-4 alkylthio, and C1-4 haloalkyl;
R2 is independently a 5- to 7-membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, NH, N (C1-4 alkyl), O, and S(O)p, wherein said heterocycle is substituted with 0-2 R2a;
R2a is, independently at each occurrence, selected from the group consisting of: halogen, C1-4 alkyl, —CH2OH, C1-4 alkoxy, OH, CF3, OCF3, CN, NH2, CO2H, CO2(C1-4 alkyl), COC1-4 alkyl, —CONH2, —CONH (C1-4 alkyl), —CON(C1-4 alkyl)2, —SO2(C1-4 alkyl), —SO2NH2, —SO2NH(C1-4 alkyl), and —SO2N(C1-4 alkyl)2;
R3 is independently selected from the group consisting of: H, halogen, and CN;
R4 is independently selected from the group consisting of: H, and C1-4 alkyl;
R5 is, independently at each occurrence, selected from the group consisting of: H, halogen, OH, and C1-4 alkyl;
R6 is, independently at each occurrence, selected from the group consisting of: halogen, C1-4 alkyl, CN, OH, and CF3;
R7 is, independently at each occurrence, selected from the group consisting of: halogen, C1-4 haloalkyl, OCH2F, OCHF2, OCF3, and C1-4 alkoxy; and
p is, independently at each occurrence, selected from the group consisting of: 0, 1, and 2.
 
7. A pharmaceutical composition comprising one or more compounds of claim 1 and a pharmaceutically acceptable carrier or diluent.