US 7,524,863 B2
Sulfonylaminovalerolactams and derivatives thereof as factor Xa inhibitors
Joanne M. Smallheer, Yardley, Pa. (US); Donald J. Pinto, Kennett Square, Pa. (US); Shuaige Wang, West Chester, Pa. (US); Jennifer X. Qiao, Princeton, N.J. (US); Wei Han, Yardley, Pa. (US); and Zilun Hu, Thornton, Pa. (US)
Assigned to Bristol-Myers Squibb Company, Princeton, N.J. (US)
Filed on Jun. 21, 2006, as Appl. No. 11/472,825.
Application 11/472825 is a division of application No. 10/429461, filed on May 05, 2003, granted, now 7,157,470.
Claims priority of provisional application 60/378313, filed on May 06, 2002.
Prior Publication US 2006/0247243 A1, Nov. 02, 2006
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/45 (2006.01); A61K 31/433 (2006.01); A61K 31/4196 (2006.01); A61K 31/405 (2006.01); A61K 31/381 (2006.01); C07D 211/76 (2006.01); C07D 285/12 (2006.01); C07D 249/12 (2006.01); C07D 209/04 (2006.01); C07D 409/00 (2006.01)
U.S. Cl. 514—318  [514/363; 514/384; 514/415; 514/444; 546/193; 548/136; 548/262.6; 548/469; 549/59] 14 Claims
 
1. A compound of formula Ic:

OG Complex Work Unit Drawing
or a stereoisomer or pharmaceutically acceptable salt thereof, wherein;
G is a group of formula IIa or IIb:

OG Complex Work Unit Drawing
ring D, including the two atoms of ring E to which it is attached, is a 5-6 membered ring consisting of: carbon atoms and 0-2 heteroatoms selected from the group consisting of N, O, and S(O)p;
ring D is substituted with 0-2 R and there are 0-3 ring double bonds;
E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, and pyridazinyl, and is substituted with 1-3 R;
alternatively, ring D is absent, and ring E is selected from phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, triazolyl, thienyl, and thiazolyl, and ring E is substituted with 1-3 R;
alternatively, ring D is absent, ring E is selected from phenyl, phenyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, triazolyl, thienyl, and thiazolyl, and ring E is substituted with 1 R and with a 5-6 membered heterocycle consisting of: carbon atoms and 1-4 heteroatoms selected from the group consisting of N, O, and S(O)p, wherein the 5-6 membered heterocycle is substituted with 0-2 carbonyls and 1-2 R and has 0-3 ring double bonds;
R is selected from H, C1-4 alkyl, F, Cl, Br, I, OH, OCH3, OCH2CH3, OCH(CH3)2, OCH2CH2CH3, CN, C(═NR8)NR7R9, NHC(═NR8)NR7R9, NR8CH(═NR7), NH2, NH(C1-3 alkyl), N(C1-3 alkyl)2, C(═NH)NH2, CH2NH2, CH2NH(C1-3 alkyl), CH2N(C1-3 alkyl)2, CH2CH2NH2, CH2CH2NH(C1-3 alkyl), CH2CH2N(C1-3 alkyl)2, C(O)H, C(O)R2c, NR7R8, C(O)NR7R8, NR7C(O)R7, OR3, S(O)pNR7R8, NR7S(O)pR7, SR3, S(O)R3, S(O)2R3, and OCF3;
A is selected from one of the following carbocyclic and heterocyclic groups which are substituted with 0-2 R4;
cyclohexyl, phenyl, pyridyl, and pyrimidyl;
B is selected from the group consisting of:

OG Complex Work Unit Drawing
R2, at each occurrence, is selected from H, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2CH2CH2CH3, and CH2CH(CH3)2;
R2a, at each occurrence, is selected from H, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2CH2CH2CH3, and CH2CH(CH3)2;
R2c, at each occurrence, is selected from OH, C1-4 alkoxy, CH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CH2CH2CH2CH3, CH2CH(CH3)2, CH(CH3)CH2CH3, and C(CH3)3;
R3, at each occurrence, is selected from H, CH3, and CH2CH3;
R3a, at each occurrence, is selected from H, CH3, and CH2CH3;
R4, at each occurrence, is selected from H, OR2, F, Cl, Br, C1-4 alkyl, CN, NO2, NR2R2a;
R7, at each occurrence, is selected from H, OH, C1-6 alkyl, C1-6 alkyl-C(O)—, C1-6 alkyl-O—, (CH2)n-phenyl, C1-4 alkyl-OC(O)—, C6-10 aryl-O—, C6-10 aryl-OC(O)—, C6-10 aryl-CH2—C(O)—, C1-4 alkyl-C(O)O—C1-4 alkyl-OC(O)—, C6-10 aryl-C(O)O-C1-4 alkyl-OC(O)—, C1-6 alkyl-NH2-C(O)—, phenyl-NH2—C(O)—, and phenyl C1-4 alkyl-C(O)—;
R8, at each occurrence, is selected from H, C1-6 alkyl, and (CH2)n-phenyl;
R9, at each occurrence, is selected from H, C1-6 alkyl, and (CH2)n-phenyl;
n, at each occurrence, is selected from 0, 1, 2, and 3; and
p, at each occurrence, is selected from 0, 1, and 2.