US2004116399A1PendingUtilityA1
Inhibitors of factor Xa
Est. expirySep 17, 2019(expired)· nominal 20-yr term from priority
C07D 213/75C07C 311/16C07C 311/46C07C 317/40C07C 317/44C07D 213/81C07D 213/82C07D 217/22C07D 231/12C07D 231/14C07D 233/56C07D 249/08C07D 277/56C07D 333/38C07D 401/04C07D 401/06C07D 401/12C07D 401/14C07D 403/04C07D 403/06C07D 403/12C07D 403/14C07D 405/12C07D 409/12C07D 409/14C07D 417/04C07D 417/12C07D 417/14C07D 471/04C07D 487/04
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Claims
Abstract
Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed. The compounds are useful in vitro or in vivo for preventing or treating coagulation disorders.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of the formula (I):
A-Q-D-E-G-J-X
wherein:
A is selected from the group consisting of:
—C 1-6 alkyl and —C 3-8 cycloalkyl;
phenyl, which is substituted with 0-2 R 1 groups;
naphthyl, which is substituted with 0-2 R 1 groups; and
a 3-10 membered aromatic or non-aromatic heterocyclic ring system which may be a monocyclic ring system or a fused bicyclic ring system, wherein the heterocyclic ring system contains 1-4 heteroatoms selected from N, O and S and is substituted with 0-2 R 1 groups;
R 1 is independently selected from the group consisting of:
Halo, —CN, —C(═O)—N(R 2 , R 3 ), —NO 2 , —SO 2 N(R 2 , R 3 ), —SO 2 R 2 , —(CH 2 ) m NR 2 R 3 , —(CH 2 ) m —C(═NR 3 )—R 2 , —(CH 2 ) m —C(═NR 2 )N(R 2 ,R 3 ), —(CH 2 ) m —N(R 2 )—C(═NR 2 ) N(R 2 ,R 3 ), —(CH 2 ) m NR 2 —C 3-6 heterocyclics, C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 scycloalkyl, C 0-4 alkylC 3-8 cycloalkyl, —CF 3 , —OR 2 , and a 5-6 membered heterocyclic system containing from 1-4 heteroatoms selected from N, O and S, wherein from 1-4 hydrogen atoms on the heterocyclic system may be independently replaced with a member selected from the group consisting of halo, C 1 C 4 -alkyl, —CN C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C O-4 alkylC 3-8 cycloalkyl and —NO 2 ;
R 2 and R 3 are independently selected from the group consisting of: —H, —C 1-6 alkyl, —C 1-6 alkyloxy, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-6 alkylC 3-8 cycloalkyl and —C 0-6 alkyl-(carbocyclic aryl), wherein from 0-4 hydrogen atoms on the ring atoms of the carbocyclic aryl moiety may be independently replaced with a member selected from the group consisting of halo, —C 1-4 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-4 alkylC 3-8 cycloalkyl, —S(═O) 2 —OH, —CN, —CF 3 and —NO 2 ;
m is an integer of 0-2;
Q is selected from the group consisting of:
a direct link, divalent —C 1-4 alkyl, divalent —C 2-4 alkenyl, divalent —C 2-4 alkynyl, —C(═O)—, —C(═NH)—, —C(═NMe)—, —NH—C(═NH)—, —NH—C(═NMe)—, —N(—R 4 )—, —N(—R 4 )—CH 2 —, —C(═O)—N(—R 4 )—, —N(—R 4 )—C(═O)—, —S(═O) 2 —, —O—, —S(═O) 2 —N(—R 4 )— and —N(—R 4 )—S(═O) 2 —, wherein one or more hydrogens on each of the divalent C 1-4 alkyl, divalent C 2-4 alkenyl and divalent C 2-4 alkynyl moieties can be replaced with a —R 4 group;
R 4 is selected from the group consisting of:
—H, —C 1-6 alkyl, —C 1-6 alkyloxy, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-6 alkylC 3-8 cycloalkyl and —C 0-6 alkyl-(carbocyclic aryl), wherein from 0-4 hydrogen atoms on the ring atoms of the carbocyclic aryl moiety may be independently replaced with a member selected from the group consisting of halo, —C 1-4 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 scycloalkyl, —C 0-4 alkylC 3-8 cycloalkyl, —S(═O) 2 —OH, —CN, —CF 3 and —NO 2 ;
D is selected from the group consisting of:
a direct link;
phenyl, which is substituted with 0-2 R 1a groups; and a 5-10 membered aromatic or non-aromatic heterocyclic ring system which may be a monocyclic ring system or a fused bicyclic ring system, wherein the heterocyclic ring system contains 1-4 heteroatoms selected from N, O and S and the ring system is substituted with 0-2 R 1a groups;
R 1a is independently selected from the group consisting of:
halo, —C 1-6 alkyl, —C 1-6 alkyloxy, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-6 alkylC 3-8 cycloalkyl, —S(═O) 2 —OH, —CN, —NO 2 , (CH 2 ) n —N(—R 2a , —R 3a ), S(═O) 2 N(—R 2a , R 3a ), —S(═O) 2 —R 2a , —CF 3 , —(CH 2 ) n —OR 2a , —C(═O)—O—R 2a , —C(═O)—N(—R 2a , —R 3a ), —C(═NH)—N(—R 2a , R 3a ), —C(═NMe)—N(—R 2a , —R 3a ), 2-imidazolin-2-yl, 1-methyl-2-imidazolin-2-yl and a 5-6 membered aromatic heterocyclic ring containing 1-4 heteroatoms selected from N, O and S and —C 0-6 alkyl-(carbocyclic aryl), wherein from 0-4 hydrogen atoms on the ring atoms of the aromatic heterocyclic ring and the carbocyclic aryl moiety may be independently replaced with a member selected from the group consisting of halo, —C 1-4 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-4 alkylC 3-8 cycloalkyl, —CN, —CF 3 and —NO 2 ;
n is an integer of 0-2;
R 2a and R 3a are independently selected from the group consisting of:
—H, —C 1-6 alkyl, —C 1-6 alkyloxy, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-6 alkylC 3-8 cycloalkyl and —C 0-6 alkyl-(carbocyclic aryl), wherein from 0-4 hydrogen atoms on the ring atoms of the carbocyclic aryl moiety may be independently replaced with a member selected from the group consisting of halo, —C 1-4 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-4 alkylC 3-8 cycloalkyl, —S(═O) 2 —OH, —CN, —CF 3 and —NO 2 ;
E is selected from the group consisting of:
a direct link, —(CH 2 ) q —C(═O)—, (CH 2 ) q —N(—R 5 )—C(═O)—(CH 2 ) x —, —(CH 2 ) q —C(═O)—N(—R 5 )—(CH 2 ) x —, —(CH 2 ) q —N(—R 5 )—(CH 2 ) x —, , —(CH 2 ) q —N(R 5 )CO—NR 6 (CH 2 ) x and —SO 2 —;
q and x are independently an integer of 0-2;
R 5 and R 6 are, independently selected from the group consisting of:
—H, —C 1-6 alkyl, —C 1-6 alkyloxy, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-6 alkylC 3-8 cycloalkyl, —C 1-4 alkyl-C(═O)—OH, —C 0-6 alkyl-(carbocyclic aryl), —C 0-4 alkyl-(monocyclic heteroaryl) and —C 1-4 alkyl-C(═O)—O—C 1-4 alkyl, wherein from 0-4 hydrogen atoms on the ring atoms of the carbocyclic aryl moiety and the monocyclic heteroaryl moieties may be independently replaced with a member selected from the group consisting of halo, —C 1-4 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-4 alkylC 3-8 cycloalkyl, —S(═O) 2 —OH, —CN, —CF 3 and —NO 2 ;
G is selected from the group consisting of:
phenyl, which is substituted with 0-2 R 1b groups; and
a 5-6 membered aromatic heterocyclic ring containing 1-4 hetero atoms selected from N, O and S wherein the heterocyclic ring is substituted with 0-2 R 1b groups;
R 1b is independently selected from the group consisting of:
halo, —C 1-6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-6 alkylC 3-8 cycloalkyl, —C 1-4 alkyl-C(═O)—OH, —CN, —NO 2 , —S(═O) 2 —OH, —N(—R 2b , R 3b ), —C(═O)—N(—R 2b , R 3b )—S(═O) 2 —N(—R 2b , R 3b ) S(═O) 2 R 2b , —CF 3 , —O—R 2b , —O—CH 2 —CH 2 —O—R 2b , —O—CH 2 —C(═O)—O—R 2b , —N(—R 2b )—CH 2 —CH 2 —O—R 2b , —N(—CH 2 —CH 2 —O—R 2b ) 2 , —N(—R 2b )—C(═O)R 3b , —N(—R 2b )—S(═O) 2 R 3b , and a 5-6 membered heterocyclic ring containing 1-4 heteroatoms selected from N, O and S substituted with 0-4 R 1b′ groups;
alternatively, when two R 1b may be present on adjacent ring atoms of G and combine to form a benzene ring substituted with 0-4 R 1b′ groups or a 5-6 membered aromatic or non—aromatic heterocyclic ring having 1-3 heteroatoms selected from N, O and S substituted with 0-4 R 1b′ groups;
in a second alternative, one of the R 1b groups of G can cylize with the —N—R 5 group of E to form a 5-7 membered heterocyclic ring containing 1-4 heteroatoms selected from N, O and S, which is subtituted with 0-4 R 1b′ groups, wherein two of the R 1b′ groups attached to the same ring carbon may form a (═O) group;
R 2b and R 3b are independently selected from the group consisting of:
—H, —C 1-6 alkyl, —C 1-6 alkyloxy, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-6 alkylC 3-8 cycloalkyl and —C 0-6 alkyl-(carbocyclic aryl), wherein from 0-4 hydrogen atoms on the ring atoms of the carbocyclic aryl moiety may be independently replaced with a member selected from the group consisting of halo, —C 1-4 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-4 alkylC 3-8 cycloalkyl, —S(═O) 2 —O − , —CN, —CF 3 and —NO 2 ;
R 1b′ is independently selected from the group consisting of:
halo, —C 1-6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-6 alkylC 3-8 cycloalkyl, —C 1-4 alkyl-C(═O)—OH, —CN, —NO 2 , —S(═O) 2 —OH, —N(—R 2b′ , R 3b′ ), —C(═O)—N(—R 2b′ , —R 3b′ ), —S(═O) 2 —N(—R 2b′ , R 3b′ ), —S(═O) 2 —R 2b′ , —CF 3 , —O—R 2b′ , —O—CH 2 —CH 2 —O—R 2b′ , —O—CH 2 —C(═O)O—R 2b′ , —N(—R 2b′ )—CH 2 —CH 2 —O—R 2b′ , —N(—CH 2 —CH 2 —O—R 2b′ ) 2 , —N(—R 2b′ )—C(═O)—R 3b′ and —N(—R 2b′ )—S(═O) 2 —R 3b′ ;
R 2b′ and R 3b′ are independently selected from the group consisting of:
—H, —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-6 alkylC 3-8 cycloalkyl and —C 0-6 alkyl-(carbocyclic aryl), wherein from 0-4 hydrogen atoms on the ring atoms of the carbocyclic aryl moiety may be independently replaced with a member selected from the group consisting of halo, —C 1-4 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloakyl, —C 0-4 alkylC 3-8 cycloalkyl, —S(═O) 2 —OH, —CN, —CF 3 and —NO 2 ;
J is selected from the group consisting of:
a direct link, —S(═O) 2 —, —C(═O)—, —N(—R 7 )—S(═Q) 2 —, —C(═O)—N(—R 7 )—S(═O) 2 —, —C(═O)—N(—R 7 )—(CH 2 ) y —, —S(═O) 2 —N(—R 7 ) —(CH 2 ) y —, and —N(—R 7 )—C(═O)—(CH2) y ;
y is an integer of 0-2;
R 7 is selected from the group consisting of:
—H, —C 2-4 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-6 alkylC 3-8 cycloalkyl, —C 1-6 alkyl-C(═O)—OH, —C 1-6 alkyl-OH, —C 1-6 alkyl-O—C 1-4 alkyl, —C 0-4 alkyl-(carbocyclic aryl), —C 0-4 alkyl-(monocyclic or bicyclic heterocyclic ring system having from 0-4 heteroatoms selected from the group consisting of N, O and S), —CH 2 —C(═O)—O—C 1-4 alkyl and —CH 2 —C(═O)—O—C 1-4 alkyl-(carbocyclic aryl), wherein from 0-4 hydrogen atoms on the ring atoms of the carbocyclic aryl moiety or the heterocyclic ring system may be independently replaced with a member selected from the group consisting of halo, —C 1-4 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-4 alkylC 38 cycloalkyl, —S(═O) 2 —OH, —CN, —CF 3 and —NO 2 ;
X is a member selected from the group consisting of:
phenyl, which is substituted with 0-3 R 1c groups;
naphthyl, which is substituted with 0-3 R 1c groups;
a 6-membered heteroaromatic ring containing from 1-2 nitrogen atoms, wherein the ring is substituted with 0-3 R 1c groups; and
a fused heterobicyclic ring system, wherein the ring system contains 1-3 heteroatoms selected from N, O and S and is substituted with 0-3 R 1c groups;
R 1c is independently selected from the group consisting of:
halo, —CF 3 , —C 1-6 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-6 alkylC 3-8 cycloalkyl, —C 1-4 alkyl-C(═O)—OH, —CF 3 , —CN, —NO 2 , (CH 2 ) z —N(—R 2c , —R 3c ), —C(═O)—N(—R 2c , —R 3c , —C(═NH)—N(—R 2c , —R 3c ), —C(═NMe)—N(—R 2c , —R 3c ), —S(═O) 2 —N(—R 2c , —R 3c , —S(═O) 2 —R 2c ), —S(═O) 2 —OH, —CF 3 , —R 2c , —O(—CH 2 ) z —O—R 2c , —O(—CH 2 ) z —C(═O)—O—R 2c , —N(—R 2c , —O(—CH 2 ) z —O—R 2c , —N[(—CH 2 ) z —O—R 2c ] 2 , —(CH 2 ) z —N(—R 2c )—C(═O)R 3c , —(CH 2 ) z —N(—R 2c )—S(═O) 2 —R 3c , and a 5-6 membered heterocyclic ring containing 1-4 heteroatoms selected from N, O and S;
z is an integer of 0-4;
R 2c and R 3c are independently selected from the group consisting of:
—H, —C 1-6 alkyl, —C 1-6 alkyloxy, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-6 alkylC 3-8 cycloalkyl and —C 0-6 alkyl-(carbocyclic aryl), wherein from 0-4 hydrogen atoms on the ring atoms of the carbocyclic aryl moiety may be independently replaced with a member selected from the group consisting of halo, —C 1-4 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-8 cycloalkyl, —C 0-4 alkylC 3-8 cycloalkyl, —S(═O) 2 —OH, —CN, —CF 3 and —NO 2 ;
and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives thereof.
2 . A compound of claim 1 , wherein:
A is selected from the group consisting of:
—C 1-6 alkyl and —C 3-8 cycloalkyl;
phenyl, which is substituted with 0-2 R 1 groups;
naphthyl, which is substituted with 0-2 R 1 groups; and
a 3-10 membered aromatic or non-aromatic heterocyclic ring system which may be a monocyclic ring system or a fused bicyclic ring system, wherein the heterocyclic ring system contains 1-4 heteroatoms selected from N, O and S and is substituted with 0-2 R 1 groups;
R 1 is independently selected from the group consisting of:
halo, —C 1-4 alkyl, —CN, —NO 2 , —(CH 2 ) m —N(—R 2 ,—R 3 ), —C(═O)—N(—R 2 ,—R 3 ), —S(═O) 2 —N(—R 2 ,—R 3 ), —S(═O) 2 —R 2 , —(CH 2 ) m —C(═NR 3 )—R 2 , —(CH 2 ) m —C(═NR 2 )—N(R 2 ,R 3 ), (CH 2 ) m —N(R 2 )—C(═NR 2 )—N(R 2 ,R 3 ), —CF 3 , —(CH 2 ) m —O—R 2 and a 5-6 membered aromatic heterocyclic ring containing 1-4 heteroatoms selected from N, O and S;
R 2 and R 3 are independently selected from the group consisting of:
—H, —C 1-4 alkyl and —C 0-4 alkyl-(carbocyclic aryl);
m is an integer of 0-2; Q is selected from the group consisting of:
a direct link, —C 1-4 alkyl, —C 2-4 alkenyl, —C 2-4 alkynyl, —C(═O)—, —C(═NH)—, —C(═NMe)—, —N(—R 4 )—, —N(—R 4 )—CH 2 —, —C(═O)—N(—R 4 )—, —N(—R 4 )—C(═O)—, —S(═O) 2 —, —O—, —S(═O) 2 —N(—R 4 )— and —N(—R 4 )—S(═O) 2 —;
R 4 is selected from the group consisting of:
—H, —C 1-4 alkyl and —C 0-4 alkyl-(carbocyclic aryl);
D is selected from the group consisting of:
a direct link;
phenyl, which is substituted with 0-2 R 1a groups; and
a 5-10 membered aromatic or non-aromatic heterocyclic ring system which may be a monocyclic ring system or a fused bicyclic ring system, wherein the heterocyclic ring system contains 1-4 heteroatoms selected from N, O and S and the ring system is substituted with 0-2 R 1a groups;
R 1a is independently selected from the group consisting of:
halo, —C 1-4 alkyl, —CN, —NO 2 , —(CH 2 ) n —N(—R 2a , —R 3a ), —S(═O) 2 —N(—R 2a , —R 3a ), —S(═O) 2 —R 2a , —CF 3 , —(CH 2 ) n —O—R 2a , C(═O)—O—R 2a , —C(═O)—N(—R 2a , R 3a ) and a 5-6 membered aromatic heterocyclic ring containing 1-4 heteroatoms selected from N, O and S;
n is an integer of 0-2; R 2a and R 3a are independently selected from the group consisting of:
—H, —C 1-4 alkyl, and —C 1-4 alkyl-(carbocyclic aryl);
E is selected from the group consisting of:
a direct link, —(CH 2 ) q —C(═O)—, —(CH 2 ) q —N(R 5 )—C(═O)—(CH 2 ) x —, —(CH 2 ) q —C(═O)—N(—R 5 )—(CH 2 ) x —, —(CH 2 )q—N(—R 5 )—(CH 2 ) x —, —(CH 2 ) q —N(R 5 )CO—NR 6 (CH 2 ) x — and —SO 2 —;
q and x are independently an integer of 0-2; R 5 and R 6 are independently selected from the group consisting of:
—H, —C 1-4 alkyl, —C 0-4 alkyl-(carbocyclic aryl), —C 0-4 alkyl-(monocyclic heteroaryl), —C 1-4 alkyl-C(═O)—OH and —C 1-4 alkyl-C(═O)—O—C 1-4 alkyl;
G is selected from the group consisting of:
phenyl, which is substituted with 0-2 R 1b groups; and
a 5-6 membered aromatic heterocyclic ring containing 1-4 hetero atoms selected from O, S and N, wherein the heterocyclic ring is substituted with 0-2 R 1b groups;
R 1b is independently selected from the group consisting of:
halo, —C 1-4 alkyl, —CN, —NO 2 , N(R 2b , R 3b ), C(═O)—N(R 2b , R 3b ), —S(═O) 2 —N(R 2b , —R 3b ), —S(═O) 2 —R 2b , —CF 3 , —O—CH 2 —CH 2 —O—R 2b , —O—CH 2 —C(═O)—O—R 3b , —N(—R 2b )—CH 2 —CH 2 —O—R 2b , —N(—CH 2 —CH 2 —CH—R 2b ) 2 , —N(—R 2b )—C(═O)—R 3b , —N(—R 2b )—S(═O) 2 —R 3b and a 5-6 membered heterocyclic ring containing 1-4 heteroatoms selected from N, O and S;
alternatively, when two R 1b may be present on adjacent ring atoms of G and combine to form a benzene ring substituted with 0-4 R 1b′ groups or a 5-6 membered aromatic or non-aromatic heterocyclic ring having 1-3 heteroatoms selected from N, O and S substituted with 0-4 R 1b′ groups; in a second alternative, one of the R 1b groups of G can cylize with the —N—R 5 group of E to form a 5-7 membered saturated, unsaturated or partially unsaturated heterocyclic ring containing 1-4 heteroatoms selected from N, O and S, which is substituted with 0-4 R 1b′ groups, wherein two of the R 1b′ groups attached to the same ring carbon may form a (═O) group;
R 2b and R 3b are independently selected from the group consisting of:
—H, —C 1-4 alkyl and —C 1-4 alkyl-(carbocyclic aryl);
R 1b′ is independently selected from the group consisting of:
halo, —C 1-4 alkyl, —CN, —NO 2 , N(R 2b′ , R 3b′ ), C(═O)—N(R 2b′ , R 3b′ ), —S(═O) 2 —N(—R 2b′ , —R 3b′ ), —S(═O) 2 —R 2b′ , —CF 3 , —O—R 2b′ , —O—CH 2 —CH 2 —O—R 2b′ , —O—CH 2 —C(═O)—O—R 2b′ , —N(—R 2b′ )—CH 2 —CH 2 —O—R 2b′ , —N(—CH 2 —CH 2 —O—R 2b′ ) 2 , —N(—R 2b′ )—C(═O)—R 3b′ , —N(—R 2b′ )—S (═O) 2 —R 3b′ ;
R 2b′ and R 3b′ are independently selected from the group consisting of:
—H, —C 1-4 alkyl and —C 1-4 alkyl-(carbocyclic aryl);
J is selected from the group consisting of:
a direct link, —S(═O) 2 —, —C(═O)—, —N(—R 7 )—S(═0) 2 —, —C(═O)—N(—R 7 )—S(═O) 2 —, —C(═O)—N(—R 7 )—(CH 2 ) y , —S(═O) 2 —N(—R 7 )—, —(CH 2 ) y — and —N(—R 7 )—C(═O)—(CH 2 ) y —;
y is an integer of 0-2; R 7 is selected from the group consisting of:
—H, —C 1-4 alkyl, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 0-4 alkyl-(carbocyclic aryl), —C 0-4 alkyl-(heterocyclic ring system), —CH 2 —C(═O)—O—C 1-4 alkyl and —CH 2 —C(═O)—O—C 1-4 alkyl-(carbocyclic aryl);
X is selected from the group consisting of:
phenyl, which is substituted with 0-3 R 1c groups;
naphthyl, which is substituted with 0-3 R 1c groups;
a 6-membered heteroaromatic ring containing from 1-2 nitrogen atoms, wherein the ring is substituted with 0-3 R 1c groups; and
a fused heterobicyclic ring system, wherein the ring system contains 1-3 heteroatoms selected from N, O and S and is substituted with 0-3 R 1c groups;
R 1c is independently selected from the group consisting of:
halo, —C 1-4 alkyl, —CN, —NO 2 , —(CH 2 ) z —N(—R 2c , —R 3c ), —C(═O)—N(—R 2c , —R 3c ), —C(═NH)—N(—R 2c , R 3c ), —C(═NMe)—N(—R 2c , —R 3c ), —S(═O) 2 —N(—R 2c , —R 3c ), —S(═O) 2 —R 2c , —S(═O) 2 —O − , —CF 3 , —O—R 2c , —O—CH 2 —CH 2 —O—R 2c , —O—CH 2 —C(═O)—O—R 2c , —N(—R 2c )—CH 2 —CH 2 —O—R 2c , —N(—CH 2 —CH 2 —O—R 2c ) 2 , —(CH 2 ) z —N(—R 2c )—C(═O)—R 3c , —(CH 2 ) z —N(—R 2c )—S(═O) 2 —R 3c , and a 5-6 membered heterocyclic ring containing 1-4 heteroatoms selected from N, O and S;
z is an integer of 0-2; R 2c and R 3c are independently selected from the group consisting of:
—H, —C 1-4 alkyl and —C 1-4 alkyl-(carbocyclic aryl);
and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives, thereof.
3 . A compound of claim 1 , wherein:
A is selected from the group consisting of: Q is selected from the group consisting of:
a direct link, —C(═NH), —C(═NMe)—, —C(═O)—, —CH 2 —, —NH—, —N(—CH 3 )—, —O—, —NH—CH 2 —, —CH 2 —NH—, —N(—CH 3 )—CH 2 —, and —CH 2 —N(—CH 3 )—;
D is selected from the group consisting of: E is selected from the group consisting of:
a direct link, —NH—C(═O)—, —N(—CH 3 )—C(═O)—, —N(—CH 2 CO 2 H)—C(═O)—, —C(═O)—NH—, —C(═O)—N(—CH 3 )—, —NH—CH 2 — and —CH 2 —NH—;
G is a member selected from the group consisting of: R 1b is selected from the group consisting of:
—H, —Me, —CF 3 , —F, —Cl, —Br, —SO 2 Me, —CN, —CONH 2 , —CONMe 2 , —NH 2 , —NO 2 , —NHCOMe, —NHSO 2 Me, —CH 2 NH 2 and —CO 2 H;
J is selected from the group consisting of:
a direct link, —NH—, —O—, —S(═O) 2 —, —S(═O) 2 —NH, —NH—S(═O) 2 —, —C(═O)—, —NH—C(═O)— and —C(═O)—NH—;
X is selected from the group consisting and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives, thereof.
4 . A compound of claim 1 , wherein:
A is selected from the group consisting of:
phenyl, which is substituted with 0-2 R 1 groups;
naphthyl, which is substituted with 1 R 1 group; and
a 5-7 membered aromatic or non—aromatic monocyclic heterocyclic ring, wherein the heterocyclic ring contains 1-2 heteroatoms selected from N, O and S and is substituted with 0-1 R 1 groups;
R 1 is selected from the group consisting of:
—S(═O) 2 —N(—R 2 , —R 3 ), —S(═O) 2 —R 2 , —CH 2 N(—R 2 , —R 3 ), —CN and halo.
R 2 and R 3 are independently selected from the group consisting of:
—H and —Cl 4 alkyl;
Q is selected from the group consisting of:
a direct link, —C(═NH), —C(═NMe)—, —C(═O)—, —CH 2 —, —NH—, and —N(—CH 3 )—;
D is selected from the group consisting of:
a direct link;
phenyl, which is substituted with 0-2 R 1a groups; and
a 5-6 membered aromatic heterocyclic ring, wherein the heterocyclic ring contains 1-2 heteroatoms selected from N and S and is substituted with 0-1 R 1a groups;
R 1a is selected from the group consisting of:
—H and halo;
E is selected from the group consisting of:
a direct link, —NH—C(═O)—and —C(═O)—NH—;
G is selected from the group consisting of:
Pyrazole, pyrazoline, triazole and tertrazole, which are substituted with 0-2 R 1b groups; and
a 5-membered aromatic heterocyclic ring, wherein the heterocyclic ring contains 2 heteroatoms selected from N, O and S and is substituted with 0-1 R 1b groups and;
R 1b is selected from the group consisting of:
—Me, —Et, —CF 3 , —C(═O)—NH 2 , —NH 2 , —NH—C(═O)—Me, —NH—S(═O) 2 —Me, —SMe, —S(═O) 2 —Me and halo;
alternatively, when two R 1b groups may be present on adjacent ring atoms of and combine to form a benzene ring;
in a second alternative, one of the R 1b groups of G can cyclize with the NH group of E to form a 5-6 membered non-aromatic heterocyclic ring containing 1-2 nitrogen atoms and which is substituted with 0-2 C═O groups;
J is selected from the group consisting of:
a direct link, —NH—C(═O)— and —C(═O)—NH—;
X is selected from the group consisting of:
phenyl, which is substituted with 1-3 R 1c groups;
naphthyl, which is substituted with 0-3 R 1c groups;
pyridinyl, which is substituted with 1-3 R 1c groups; and
a 9-10 membered fused bicyclic aromatic ring, wherein the aromatic ring contains 0-2 heteroatoms selected from N and O and is substituted with 0-3 R 1c groups;
R 1c is independently selected from the group consisting of:
—H, halo, —Me, —CF 3 , —OH, —OMe, —NH 2 , —CN, —NO 2 , —CH 2 —R 2c , —C(═O)—N(—R 2c , —R 3c ), —S(═O) 2 —R 2c , —S(═O) 2 —N(—R 2c , —R 2c ), —S(═O) 2 —OH, —C(═NH)—N(—R 2c , —R 3c ), 2-imidazolin-2-yl and 1-methyl-2-imidazolin-2-yl;
R 2c and R 3c are independently selected from the group consisting of:
—H, —OH, —NH 2 and —C 1-4 alkyl;
and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives, thereof.
5 . The following compounds are claimed by the present invention:
wherein:
R 1 is selected from the group consisting of:
—SO 2 NH 2 , —SO 2 Me, —CH 2 NH 2 and —CH 2 NMe 2 ;
R 1a is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1c1 is selected from the group consisting of:
—H, —F, —Cl, —Br, —NH 2 , —OH, —SO 2 Me, —SO 2 Et, —SO 2 NH 2 , —NO 2 , —CH 2 NH 2 , —CN, —CONH 2 , —CH 2 OH;
R 1c2 is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1c3 is selected from the group consisting of:
—H, —F, —Cl and —Br;
G is selected from the group consisting of:
wherein:
R 1b1 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b2 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b3 is selected from the group consisting of —Cl, —NH 2 , —CH 3 and —CF 3 .
6 . The following compounds are claimed by the present invention:
wherein:
R 1 is selected from the group consisting of:
—SO 2 NH 2 , —SO 2 Me, —CH 2 NH 2 and —CH 2 NMe 2 ;
R 1a is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1c1 is selected from the group consisting of:
—H, —F, —Cl, —Br, —NH 2 , —OH, —SO 2 Me, —SO 2 Et, —SO 2 NH 2 , —NO 2 , —CH 2 NH 2 , a CN, —CONH 2 , —CH 2 OH;
R 1c2 is selected from the group consisting of:
—H, —F, —Cl, —Br and —OMe;
R 1c3 is selected from the group consisting of:
—H, —F, —Cl, —Br, —OCH 3 , —NH 2 , —CH 2 NH 2 , —CONH 2 , —CONHMe, —CONMe 2
G is selected from the group consisting of:
wherein:
R 1b1 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b2 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b3 is selected from the group consisting of —Cl, —NH 2 , —CH 3 and —CF 3 .
7 . The following compounds are claimed by the present invention:
wherein:
R 1 is selected from the group consisting of:
—SO 2 NH 2 , —SO 2 CH 3 , —CN, —CONH 2 , —CONH(CH 3 ), —CON(CH 3 ) 2 , —CH 2 NH 2 , —CH 2 NH(CH 3 ), —CH 2 N(CH 3 ) 2 ;
R 1a is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1c1 is selected from the group consisting of:
—H, —F, —Cl, —Br, —CN, —CH 2 NH 2 , —CH 2 OH, —CONH 2 , —C(═NH)NH 2 , —CO 2 H, CO 2 Me, —SO 2 Me, —SO 2 NH 2 , —OH, —NH 2 , and —NO 2 ;
R 1c2 is selected from the group consisting of:
—H, —F, —Cl, —Br, and —OCH 3 ;
R 1c3 is selected from the group consisting of:
—H, —F, —Cl, —Br, —OCH 3 , —NH 2 , —CH 2 NH 2 , —CONH 2 , —CONHMe, —CONMe 2 ;
G is selected from the group consisting of:
wherein:
R 1b1 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b2 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b3 is selected from the group consisting of —Cl, —NH 2 , —CH 3 and —CF 3 .
8 . The following compounds are claimed by the present invention:
wherein:
R 1 is selected from the group consisting of:
—SO 2 NH 2 , —SO 2 Me, —CH 2 NH 2 and —CH 2 NMe 2 ;
R 1a is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1c is selected from the group consisting of:
—H, —F, —Cl, —Br, —NH 2 , —OH, —SO 2 Me, —SO 2 Et, —SO 2 NH 2 , —NO 2 , —CH 2 NH 2 , CN, —CONH 2 , —CH 2 OH;
G is selected from the group consisting of:
wherein:
R 1b1 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b2 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b3 is selected from the group consisting of —Cl, —NH 2 , —CH 3 and —CF 3 .
9 . The following compounds are claimed by the present invention:
wherein:
R 1 is selected from the group consisting of:
—SO 2 NH 2 , —SO 2 Me, —CH 2 NH 2 and —CH 2 NMe 2 ;
R 1a is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1c1 is selected from the group consisting of:
—H, —F, —Cl, —Br, —NH 2 , —OH, —SO 2 Me, —SO 2 Et, —SO 2 NH 2 , —NO 2 , —CH 2 NH 2 , —CN, —CONH 2 , —CH 2 OH;
R 1c2 is selected from the group consisting of:
—H, —F, —Cl and —Br;
G is selected from the group consisting of:
wherein:
R 1b1 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b2 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b3 is selected from the group consisting of —Cl, —NH 2 , —CH 3 and —CF 3 .
10 . The following compounds are claimed by the present invention:
wherein:
A-Q is selected from the group consisting of:
wherein:
A is selected from the group consisting of:
R 1a is selected from the group consisting of —H, —F, —Cl and —Br;
R 1c1 is selected from the group consisting of:
—H, —F, —Cl, —Br, —NH 2 , —OH, —SO 2 Me, —SO 2 Et, —SO 2 NH 2 , —NO 2 , —CH 2 NH 2 , CN, —CONH 2 , —CH 2 OH;
R 1c2 is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1c3 is selected from the group consisting of:
—H, —F, —Cl and —Br;
G is selected from the group consisting of:
wherein:
R 1b1 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b2 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b3 is selected from the group consisting of —Cl, —NH 2 , —CH 3 and —CF 3 .
11 . The following compounds are claimed by the present invention:
wherein:
A-Q is selected from the group consisting of:
wherein:
A is selected from the group consisting of:
R 1a is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1b is selected from the group consisting of:
—CH 3 , —CF 3 , —CH 2 CH 3 , —SO 2 Me, —CONH 2 and —NHSO 2 Me;
R 1d is selected from the group consisting of:
—H, —F, —Cl, —Br, —NH 2 , —OH, —SO 2 Me, —SO 2 Et, —SO 2 NH 2 , —NO 2 , —CH 2 NH 2 , CN, —CONH 2 , —CH 2 OH;
R 1c2 is selected from the group consisting of:
—H, —F, —Cl, —Br and —OMe;
R 1c3 is selected from the group consisting of:
—H, —F, —Cl, —Br, —OH, —OCH 3 , —NH 2 , —CONH 2 , —CH 2 NH 2 ;
G is selected from the group consisting of:
wherein:
R 1b1 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b2 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b3 is selected from the group consisting of —Cl, —NH 2 , —CH 3 and —CF 3 .
12 . The following compounds are claimed by the present invention:
wherein:
R 1 is selected from the group consisting of:
—SO 2 NH 2 , —SO 2 CH 3 , —CN, —CONH 2 , —CONH(CH 3 ), —CON(CH 3 ) 2 , —CH 2 NH 2 , —CH 2 NH(CH 3 ), —CH 2 N(CH 3 ) 2 ;
R 1a is selected from the group consisting of:
—H, —F, —Cl and Br;
R 1b is selected from the group consisting of:
—CH 3 and —CF 3 ;
R 1c1 is selected from the group consisting of:
—H, —F, —Cl, —Br, —CN, —CH 2 NH 2 , —CH 2 OH, —CONH 2 , —C(═NH)NH 2 , —CO 2 H, CO 2 Me, —SO 2 Me, —SO 2 NH 2 , —OH, —NH 2 , and —NO 2 ;
R 1c2 is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1c3 is selected from the group consisting of:
—H, —F, —Cl and —Br.
13 . The following compounds are claimed by the present invention:
wherein:
R 1a is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1b is selected from the group consisting of:
—CH 3 , —CF 3 , —CH 2 CH 3 , —SO 2 Me, —CONH 2 and —NHSO 2 Me;
R 1c1 is selected from the group consisting of:
—H, —F, —Cl, —Br, —NH 2 , —OH, —SO 2 Me, —SO 2 Et, —SO 2 NH 2 , —NO 2 , —CH 2 NH 2 , CN, —CONH 2 , —CH 2 OH;
R 1c2 is selected from the group consisting of:
—H, —F, —Cl, —Br and —OCH 3 ;
R 1c3 is selected from the group consisting of:
—H, —F, —Cl, —Br, —OCH 3 , —NH 2 , —CH 2 NH 2 , —CONH 2 , —CONHMe, —CONMe 2 .
14 . The following compounds are claimed by the present invention:
wherein:
A-Q is selected from the group consisting of:
wherein:
A is selected from the group consisting of:
R 1a is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1c1 is selected from the group consisting of:
—H, —F, —Cl, —Br, —CN, —CH 2 NH 2 , —CH 2 OH, —CONH 2 , —C(═NH)NH 2 , —CO 2 H, —CO 2 Me, —SO 2 Me, —SO 2 NH 2 , —OH, —NH 2 , and —NO 2 ;
R 1c2 is selected from the group consisting of:
—H, —l, —Cl, —Br, and —OCH 3 ;
R 1c3 is selected from the group consisting of:
—H, —F, —Cl, —Br, —OCH 3 , —NH 2 , —CH 2 NH 2 , —CONH 2 , —CONHMe, —CONMe 2 ;
G is selected from the group consisting of:
wherein:
R 1b1 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b2 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b3 is selected from the group consisting of —Cl, —NH2, —CH 3 and —CF 3 .
15 . The following compounds are claimed by the present invention:
wherein:
R 1 is selected from the group consisting of:
—SO 2 NH 2 , —SO 2 CH 3 , —CN, —CONH 2 , —CONH(CH 3 ), —CON(CH 3 ) 2 , —CH 2 NH 2 , —CH 2 NH(CH 3 ), —CH 2 N(CH 3 ) 2 ;
R 1a is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1b is selected from the group consisting of:
—H, —CH 3 and —CF 3 ;
R 1c1 is selected from the group consisting of:
—H, —F, —Cl, —Br, —CN, —CH 2 NH 2 , —CH 2 OH, —CONH 2 , —C(═NH)NH 2 , —CO 2 H, —CO 2 Me, —SO 2 Me, —SO 2 NH 2 , —OH, —NH 2 , and —NO 2 ;
R 1c2 is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1c3 is selected from the group consisting of:
—H, —F, —Cl and —Br.
16 . The following compounds are claimed by the present invention:
wherein:
R 1 is selected from the group consisting of:
—SO 2 NH 2 , —SO 2 CH 3 , —CN, —CONH 2 , —CONH(CH 3 ), —CON(CH 3 ) 2 , —CH 2 NH 2 , —CH 2 NH(CH 3 ), —CH 2 N(CH 3 ) 2 ;
R 1a is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1b is selected from the group consisting of:
—H, —CH 3 and —CF 3 ;
R 1c1 is selected from the group consisting of:
—H, —F, —CN, —CH 2 NH 2 , —CONH 2 , —SO 2 Me, —SO 2 NH 2 and —NO 2 ;
R 1c2 is selected from the group consisting of:
—H, —F, —Cl, —Br and —OCH 3 ;
R 1c3 is selected from the group consisting of:
—H, —F, —Cl, —Br, —OCH 3 , —NH 2 , —CH 2 NH 2 , —CONH 2 , —CONHMe, —CONMe 2 .
17 . The following compounds are claimed by the present invention:
wherein:
A-Q is selected from the group consisting of:
wherein:
A is selected from the group consisting of:
R 1a is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1b is selected from the group consisting of:
—H, —CH 3 and —CF 3 ;
R 1c1 is selected from the group consisting of:
—H, —F, —Cl, —Br, —CN, —CH 2 NH 2 , —CH 2 OH, —CONH 2 , —C(═NH)NH 2 , —CO 2 H, —CO 2 Me, —SO 2 Me, —SO 2 NH 2 , —OH, —NH 2 , and —NO 2 ;
R 1c2 is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1c3 is selected from the group consisting of:
—H, —F, —Cl and —Br.
18 . The following compounds are claimed by the present invention:
wherein:
A-Q is selected from the group consisting of:
wherein:
A is selected from the group consisting of:
R 1a is selected from the group consisting of:
—H, —F;—Cl and —Br;
R 1b is selected from the group consisting of:
—H, —CH 3 and —CF 3 ;
R 1c1 is selected from the group consisting of:
—H, —F, —CN, —CH 2 NH 2 , —CONH 2 , —SO 2 Me, —SO 2 NH 2 and —NO 2 ;
R 1c2 is selected from the group consisting of:
—H, —F, —Cl, —Br and —OCH 3 ;
R 1c3 is selected from the group consisting of:
—H, —F, —Cl, —Br, —OCH 3 , —NH 2 , —CH 2 NH 2 , —CONH 2 , —CONHMe, —CONMe 2 .
19 . The following compounds are claimed by the present invention:
wherein:
R 1 is selected from the group consisting of:
—SO 2 NH 2 , —SO 2 Me, —CH 2 NH 2 and —CH 2 NMe 2 ;
R 1a is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1c1 is selected from the group consisting of:
—H, —F, —Cl, —Br, —NH 2 , —OH, —SO 2 Me, —SO 2 Et, —SO 2 NH 2 , —NO 2 , —CH 2 NH 2 , CN, —CONH 2 , —CH 2 OH;
R 1c2 and R 1c3 are independently selected from the group consisting of:
—H, —F, —Cl and —Br;
G is selected from the group consisting of:
wherein:
R 1b1 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b2 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b3 is selected from the group consisting of —Cl, —NH 2 , —CH 3 and —CF 3 .
20 . The following compounds are claimed by the present invention:
wherein:
R 1 is selected from the group consisting of:
—SO 2 NH 2 , —SO 2 Me, —CH 2 NH 2 and —CH 2 NMe 2 ;
R 1a is selected from the group consisting of:
—H, —F, —Cl and —Br;
R 1c1 is selected from the group consisting of:
—H, —F, —Cl, —Br, —NH 2 , —OH, —SO 2 Me, —SO 2 Et, —SO 2 NH 2 , —NO 2 , —CH 2 NH 2 , CN, —CONH 2 , —CH 2 OH;
R 1c2 and R 1c3 are independently selected from the group consisting of:
—H, —F, —Cl and —Br;
G is selected from the group consisting of:
wherein:
R 1b1 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b2 is selected from the group consisting of —H, —CH 3 and —CF 3 ;
R 1b3 is selected from the group consisting of —Cl, —NH 2 , —CH 3 and —CF 3 .
21 . A pharmaceutical composition for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 1 .
22 . A method for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising administering to said mammal a therapeutically effective amount of a compound of claim 1 .
23 . The method of claim 6 , wherein the condition is selected from the group consisting of:
acute coronary syndrome, myocardial infarction, unstable angina, refractory angina, occlusive coronary thrombus occurring post-thrombolytic therapy or post-coronary angioplasty, a thrombotically mediated cerebrovascular syndrome, embolic stroke, thrombotic stroke, transient ischemic attacks, venous thrombosis, deep venous thrombosis, pulmonary embolus, coagulopathy, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, thromboangiitis obliterans, thrombotic disease associated with heparin-induced thrombocytopenia, thrombotic complications associated with extracorporeal circulation, thrombotic complications associated with instrumentation, and thrombotic complications associated with the fitting of prosthetic devices.
24 . A method for inhibiting the coagulation of biological samples, comprising the step of administering a compound of claim 1 .
25 . A pharmaceutical composition for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 2 .
26 . A method for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising administering to said mammal a therapeutically effective amount of a compound of claim 2 .
27 . The method of claim 10 , wherein the condition is selected from the group consisting of:
acute coronary syndrome, myocardial infarction, unstable angina, refractory angina, occlusive coronary thrombus occurring post-thrombolytic therapy or post-coronary angioplasty, a thrombotically mediated cerebrovascular syndrome, embolic stroke, thrombotic stroke, transient ischemic attacks, venous thrombosis, deep venous thrombosis, pulmonary embolus, coagulopathy, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, thromboangiitis obliterans, thrombotic disease associated with heparin-induced thrombocytopenia, thrombotic complications associated with extracorporeal circulation, thrombotic complications associated with instrumentation, and thrombotic complications associated with the fitting of prosthetic devices.
28 . A method for inhibiting the coagulation of biological samples, comprising the step of administering a compound of claim 2 .
29 . A pharmaceutical composition for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 3 .
30 . A method for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising administering to said mammal a therapeutically effective amount of a compound of claim 3 .
31 . The method of claim 30 , wherein the condition is selected from the group consisting of:
acute coronary syndrome, myocardial infarction, unstable angina, refractory angina, occlusive coronary thrombus occurring post-thrombolytic therapy or post-coronary angioplasty, a thrombotically mediated cerebrovascular syndrome, embolic stroke, thrombotic stroke, transient ischemic attacks, venous thrombosis, deep venous thrombosis, pulmonary embolus, coagulopathy, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, thromboangiitis obliterans, thrombotic disease associated with heparin-induced thrombocytopenia, thrombotic complications associated with extracorporeal circulation, thrombotic complications associated with instrumentation, and thrombotic complications associated with the fitting of prosthetic devices.
32 . A method for inhibiting the coagulation of biological samples, comprising the step of administering a compound of claim 3 .
33 . A pharmaceutical composition for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 4 .
34 . A method for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising administering to said mammal a therapeutically effective amount of a compound of claim 4 .
35 . The method of claim 34 , wherein the condition is selected from the group consisting of:
acute coronary syndrome, myocardial infarction, unstable angina, refractory angina, occlusive coronary thrombus occurring post-thrombolytic therapy or post-coronary angioplasty, a thrombotically mediated cerebrovascular syndrome, embolic stroke, thrombotic stroke, transient ischemic attacks, venous thrombosis, deep venous thrombosis, pulmonary embolus, coagulopathy, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, thromboangiitis obliterans, thrombotic disease associated with heparin-induced thrombocytopenia, thrombotic complications associated with extracorporeal circulation, thrombotic complications associated with instrumentation, and thrombotic complications associated with the fitting of prosthetic devices.
36 . A method for inhibiting the coagulation of biological samples, comprising the step of administering a compound of claim 4.Join the waitlist — get patent alerts
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