Details for Patent: 6,686,368

Title:	Inhibitors of factor Xa
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.
Inventor(s):	Zhu; Bing-Yan (Belmont, CA), Jia; Zhaozhong Jon (So. San Francisco, CA), Huang; Wenrong (Cupertino, CA), Song; Yonghong (Foster City, CA), Kanter; James (So. San Francisco, CA), Scarborough; Robert M. (Half Moon Bay, CA)
Assignee:	Millennium Pahrmaceuticals, Inc. (Cambridge, MA)
Filing Date:	Mar 12, 2003
Application Number:	10/387,927
Claims:	1. A compound of the formula (I): wherein: A is phenyl, which is independently substituted with 0-2 R.sup.1 substituents; R.sup.1 is selected from halo, --CN, --C(.dbd.O)--N(R.sup.2, R.sup.3), --NO.sub.2, --SO.sub.2 N(R.sup.2, R.sup.3), --SO.sub.2 R.sup.2, --(CH.sub.2).sub.m NR.sup.2 R.sup.3, --(CH.sub.2).sub.m --C(.dbd.NR.sup.3)--R.sup.2, --(CH.sub.2).sub.m --C(.dbd.NR.sup.2)--N(R.sup.2,R.sup.3), --(CH.sub.2).sub.m --N(R.sup.2)--C(.dbd.NR.sup.2)--N(R.sup.2,R.sup.3), --(CH.sub.2).sub.m NR.sup.2 --C.sub.3-6 heterocyclics, C.sub.1-4 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.0-4 alkylC.sub.3-8 cycloalkyl, --CF.sub.3, --OR.sup.2, and a 5-6 membered heterocyclic system having from 1-4 heteroatoms each independently a member selected from the group consisting of 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.sub.1-4 alkyl-CN, C.sub.1-4 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.0-4 alkylC.sub.3-8 cycloalkyl and --NO.sub.2 ; each of R.sup.2 and R.sup.3 is independently a member selected from the group consisting of --H, --OR.sup.a, --N(--R.sup.a, --R.sup.b), --C.sub.1-4 alkyl, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalkyl, --C.sub.0-4 alkylC.sub.3-8 cycloalkyl, --C.sub.0-4 alkylphenyl and --C.sub.0-4 alkylnaphthyl, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, C.sub.1-4 alkyl-CN, --C.sub.1-4 alkyl, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalkyl, --C.sub.0-4 alkylC.sub.3-8 cycloalkyl, --CN and --NO.sub.2 ; or R.sup.2 and R.sup.3 are taken together to form a 3-8 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and having from 1-4 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein from 1-4 hydrogen atoms on the heterocyclic ring system may be independently replaced with a member selected from the group consisting of halo, C.sub.1-4 alkyl-CN, --C.sub.1-4 alkyl, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalkyl, --C.sub.0-4 alkylC.sub.3-8 cycloalkyl and --NO.sub.2 ; each of R.sup.a and R.sup.b is independently a member selected from the group consisting of --C.sub.1-4 alkyl, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalkyl, --C.sub.0-4 alkylC.sub.3-8 cycloalkyl can be taken together with a nitrogen atom to which they are attached to form a 3-8 heterocyclic ring system having 1-4 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein from 1-4 hydrogen atoms on the heterocyclic ring system may be independently replaced with a member selected from the group consisting of halo, --CN, --C.sub.1-4 alkyl, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalkyl, --C.sub.0-4 alkylC.sub.3-8 cycloalkyl and --NO.sub.2 ; m is an integer of 0-2; Q is a direct link; D is a monocyclic heterocyclic ring system having from 5 to 6 ring atoms, wherein 1-3 ring atoms of the ring system are N, and wherein the ring system may be substituted from 0-2 R.sup.1a substituents; each R.sup.1a is independently a member selected from the group consisting of halo, C.sub.1-4 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.0-4 alkylC.sub.3-8 cycloalkyl, --CN, --NO.sub.2, (CH.sub.2).sub.n NR.sup.2a R.sup.3a, SO.sub.2 NR.sup.2a R.sup.3a, SO.sub.2 R.sup.2a, CF.sub.3, OR.sup.2a, and a 5-6 membered aromatic heterocycl system having from 1-4 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein from 1-4 hydrogen atoms on the aromatic heterocyclic system may be independently replaced with a member selected from the group consisting of halo, C.sub.1-4 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.0-4 alkylC.sub.3-8 cycloalkyl, --CN and --NO.sub.2 ; each of R.sup.2a and R.sup.3a is independently a member selected from the group consisting of --H, C.sub.1-4 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.0-4 alkylC.sub.3-8 cycloalkyl, C.sub.0-4 alkylphenyl and C.sub.0-4 alkylnaphthyl, wherein from 1-4 hydrogen atoms on the ring atoms of the phenyl and naphthyl moieties may be independently replaced with a member selected from the group consisting of halo, C.sub.1-4 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.0-4 alkylC.sub.3-8 cycloalkyl, --CN and --NO.sub.2 ; n is an integer of 0-2; E is --N(--R.sup.5)--C(.dbd.O)--; R.sup.5 is a member selected from the group consisting of H, --C.sub.1-6 alkyl, --C.sub.1-6 alkyloxy, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalkyl, --C.sub.0-6 alkylC.sub.3-8 cycloalkyl, --C.sub.1-4 alkyl-C(.dbd.O)--OH, --C.sub.0-6 alkyl-(carbocyclic aryl), --C.sub.0-4 alkyl-(monocyclic heteroaryl) and --C.sub.1-4 alkyl-C(.dbd.O)--O--C.sub.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.sub.1-4 alkyl, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalkyl, --C.sub.0-4 alkylC.sub.3-8 cycloalkyl, --S(.dbd.O).sub.2 --OH, --CN, --CF.sub.3 and --NO.sub.2 ; G is a pyrazolyl substituted with 0-2 R.sup.1b groups; each R.sup.1b is independently a member selected from the group consisting of halo, --C.sub.1-6 alkyl, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalkyl, --C.sub.0-6 alkylC.sub.3-8 cycloalkyl, --C.sub.1-4 alkyl-C(.dbd.O)--OH, --CN, --COOR.sup.2b, --CONR.sup.2b R.sup.3b, --NO.sub.2, --S(.dbd.O).sub.2 --OH, --N(--R.sup.2b, --R.sup.3b), --C(.dbd.O)--N(--R.sup.2b, --R.sup.3b), --S(.dbd.O).sub.2 --N(--R.sup.2b, --R.sup.3b), --S(.dbd.O).sub.2 --R.sup.2b, --CF.sub.3, --O--R.sup.2b, --O--CH.sub.2 --CH.sub.2 --O--R.sup.2b, --O--CH.sub.2 --C(.dbd.O)--O--R.sup.2b, --N(--R.sup.2b)CH.sub.2 --CH.sub.2 --O--R.sup.2b, --N(--CH.sub.2 --CH.sub.2 --O--R.sup.2b).sub.2, --N(--R.sup.2b)--C(.dbd.O)--R.sup.3b, --N(--R.sup.2b)--S(.dbd.O).sub.2 --R.sup.3b, and a 5-6 membered heterocyclic ring having 1-4 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein said heterocyclic ring is substituted with 0-4 R.sup.1b' groups; alternatively, two R.sup.1b may be present on adjacent ring atoms of G and combine to form a benzene ring substituted with 0-4 R.sup.1b' groups or a 5-6 membered aromatic or non-aromatic heterocyclic ring having 1-3 heteroatoms each independently a member selected from the group consisting of N, O and S, and substituted with 0-4 R.sup.1b' groups; each of R.sup.2b and R.sup.3b is independently a member selected from the group consisting of --H, --C.sub.1-6 alkyl, --C.sub.1-6 alkyloxy, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalkyl, --C.sub.0-6 alkylC.sub.3-8 cycloalkyl and --C.sub.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.sub.1-4 alkyl, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalky --C.sub.0-4 alkylC.sub.3-8 cycloalkyl, --S(.dbd.O).sub.2 --OH, --CN, --CF.sub.3 and --NO.sub.2 ; each R.sup.1b' is independently a member selected from the group consisting of halo, --C.sub.1-6 alkyl, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalkyl, --C.sub.0-6 alkylC.sub.3-8 cycloalkyl, --C.sub.1-4 alkyl-C(.dbd.O)--OH, --CN, --NO.sub.2, --S(.dbd.O).sub.2 --OH, --N(--R.sup.2b', --R.sup.3b'), --C(.dbd.O)--N(--R.sup.2b', --R.sup.3b'), --S(.dbd.O).sub.2 --N(--R.sup.2b', --R.sup.3b'), --S(.dbd.O).sub.2 --R.sup.2b', --CF.sub.3, --O--R.sup.2b', --O--CH.sub.2 --CH.sub.2 --R.sup.2b', --O--CH.sub.2 --C(.dbd.O)--O--R.sup.2b', --N(--R.sup.2b')--CH.sub.2 --CH.sub.2 --O--R.sup.2b', --N(--CH.sub.2 --CH.sub.2 --O--R.sup.2b').sub.2, --N(--R.sup.2b')--C(.dbd.O)--R.sup.3b' and --N(--R.sup.2b')--S(.dbd.O).sub.2 --R.sup.3b' ; each of R.sup.2b' and R.sup.3b' is independently a member selected from the group consisting of --H, --C.sub.1-6 alkyl, --C.sub.1-6 alkoxy, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalkyl, --C.sub.0-6 alkylC.sub.3-8 cycloalkyl and --C.sub.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.sub.1-4 alkyl, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloakyl, --C.sub.0-4 alkylC.sub.3-8 cycloalkyl, --S(.dbd.O).sub.2 --OH, --CN, --CF.sub.3 and --NO.sub.2 ; J is a direct link; X is naphthyl, which is substituted with 0-3 R.sup.1c groups; each R.sup.1c is independently a member selected from the group consisting of halo, --CF.sub.3, --C.sub.1-6 alkyl, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalkyl, --C.sub.0-6 alkylC.sub.3-8 cycloalkyl, --C.sub.1-4 alkyl-C(.dbd.O)--OH, --CF.sub.3, --CN, --NO.sub.2, --(CH.sub.2).sub.z --N(--R.sup.2c, --R.sup.3c), --C(.dbd.O)--N(--R.sup.2c, --R.sup.3c), --C(.dbd.NH)--N(--R.sup.2c, --R.sup.3c), --C(.dbd.NMe)--N(--R.sup.2c, --R.sup.3c), --S(.dbd.O).sub.2 --N(--R.sup.2c, --R.sup.3c), --S(.dbd.O).sub.2 --R.sup.2c, --S(.dbd.O).sub.2 --OH, --CF.sub.3, --O--R.sup.2c, --O(--CH.sub.2).sub.z --O--R.sup.2c, --O(--CH.sub.2).sub.z --C(.dbd.O)--O--R.sup.2c, --N(--R.sup.2c), --O(--CH.sub.2).sub.z --O--R.sup.2c, --N[(--CH.sub.2).sub.z --OR.sup.2c ].sub.2, --(CH.sub.2).sub.z --N(--R.sup.2c)--C(.dbd.O)--R.sup.3c, --(CH.sub.2).sub.z --N(--R.sup.2c)--S(.dbd.O).sub.2 --R.sup.3c, and a 5-6 membered heterocyclic ring having 1-4 heteroatoms each independently a member selected from the group consisting of N, O and S; z is an integer of 0-4; each of R.sup.2c and R.sup.3c is independently a member selected from the group consisting of --H, --C.sub.1-6 alkyl, --C.sub.1-6 alkyloxy, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalkyl, --C.sub.0-6 alkylC.sub.3-8 cycloalkyl and --C.sub.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.sub.1-4 alkyl, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalky --C.sub.0-4 alkylC.sub.3-8 cycloalkyl, --S(.dbd.O).sub.2 --OH, --CN, --CF.sub.3 and --NO.sub.2 ; or all pharmaceutically acceptable diastereoisomers, enantiomers or mixtures thereof, salts, hydrates or solvates thereof. 2. The compound of claim 1, wherein: A is phenyl, which is substituted with 0-2 R.sup.1 groups; each R.sup.1 is independently a member selected from the group consisting of halo, --C.sub.1-4 alkyl, --CN, --NO.sub.2, --(CH.sub.2).sub.m --N(--R.sup.2, --R.sup.3), --C(.dbd.O)--N(--R.sup.2, --R.sup.3), --S(.dbd.O).sub.2 --N(--R.sup.2, --R.sup.3), --S(.dbd.O).sub.2 --R.sup.2, --(CH.sub.2).sub.m --C(.dbd.NR.sup.3)--R.sup.2, --(CH.sub.2).sub.m --C(.dbd.NR.sup.2)--N(R.sup.2, R.sup.3), --(CH.sub.2).sub.m --N(R.sup.2)--C(.dbd.NR.sup.2)--N(R.sup.2, R.sup.3), --CF.sub.3, --(CH.sub.2).sub.m --O--R.sup.2 and a 5-6 membered aromatic heterocyclic ring having 1-4 heteroatoms each independently a member selected from the group consisting of N, O and S; each of R.sup.2 and R.sup.3 is independently a member selected from the group consisting of --H and --C.sub.1-4 alkyl; or R.sup.2 and R.sup.3 are taken together to form a 3-8 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and having from 1-4 heteroatoms each independently a member selected from the group consisting of N, O and S, wherein from 1-4 hydrogen atoms on the heterocyclic ring system may be independently replaced with a member selected from the group consisting of halo, C.sub.1 -C.sub.4 -alkyl-CN, --C.sub.1-4 alkyl, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalkyl, --C.sub.0-4 alkylC.sub.3-8 cycloalkyl and --NO.sub.2 ; m is an integer of 0-2; Q is a direct link; D is a 6 membered aromatic heterocyclic ring system, wherein the heterocyclic ring system has 1-2 N heteroatoms, substituted with 0-2 R.sup.1a groups; each R.sup.1a is independently a member selected from the group consisting of halo, --C.sub.1-4 alkyl, --CN, --NO.sub.2, --(CH.sub.2).sub.n --N(--R.sup.2a, --R.sup.3a), --S(.dbd.O).sub.2 --N(R.sup.2a, --R.sup.3a), --S(.dbd.O).sub.2 --R.sup.2a, --CF.sub.3, --(CH.sub.2).sub.n --OR.sup.2a, --C(.dbd.O)--O--R.sup.2a, --C(.dbd.O)--N(--R.sup.2a, --R.sup.3a) and a 5-6 membered aromatic heterocyclic ring having 1-4 heteroatoms each independently a member selected from the group consisting of N, O and S; n is an integer of 0-2; each of R.sup.2a and R.sup.3a is independently a member selected from the group consisting of --H, --CF.sub.3 and --C.sub.1-4 alkyl; E is --N(--R.sup.5)--C(.dbd.O)--; R.sup.5 is a member selected from the group consisting of H, --C.sub.1-4 alkyl, --C.sub.2-6 alkenyl, --C.sub.2-6 alkynyl, --C.sub.3-8 cycloalkyl and --C.sub.0-4 alkylC.sub.3-8 cycloalkyl; G is a pyrazolyl substituted with 0-2 R.sup.1b groups; each R.sup.1b is independently a member selected from the group consisting of halo, --C.sub.1-4 alkyl, --CN, --NO.sub.2, --N(R.sup.2b, R.sup.3b), --C(.dbd.O)--N(--R.sup.2b, --R.sup.3b), --S(.dbd.O).sub.2 --N(--R.sup.2b, --R.sup.3b), --S(.dbd.O).sub.2 --R.sup.2b, --CF.sub.3, --O--R.sup.2b, --O--CH.sub.2 --CH.sub.2 --O--R.sup.2b, --O--CH.sub.2 --C(.dbd.O)--O--R.sup.2b, --N(--R.sup.2b)--CH.sub.2 --CH.sub.2 --O--R.sup.2b, --N(--CH.sub.2 --CH.sub.2 --O--R.sup.2b).sub.2, --N(--R.sup.2b)--C(.dbd.O)--R.sup.3b, --N(--R.sup.2b)--S(.dbd.O).sub.2 --R.sup.3b and a 5-6 membered heterocyclic ring having 1-4 heteroatoms each independently a member selected from the group consisting of N, O and S; alternatively, two R.sup.1b may be present on adjacent ring atoms of G and combine to form a benzene ring substituted with 0-4 R.sup.1b' groups or a 5-6 membered aromatic or non-aromatic heterocyclic ring having 1-3 heteroatoms each independently a member selected from the group consisting of N, O and S substituted with 0-4 R.sup.1b' groups; each of R.sup.2b and R.sup.3b is independently a member selected from the group consisting of --H, --CF.sub.3, --C.sub.1-4 alkyl and --C.sub.1-4 alkyl-(carbocyclic aryl); each R.sup.1b' is independently a member selected from the group consisting of halo, --C.sub.1-4 alkyl, --CN, --NO.sub.2, --N(--R.sup.2b', --R.sup.3b'), --C(.dbd.O)--N(--R.sup.2b', R.sup.3b'), --S(.dbd.O).sub.2 --N(--R.sup.2b', --R.sup.3b'), --S(.dbd.O).sub.2 --R.sup.2b', --CF.sub.3, --O--R.sup.2b', --O--CH.sub.2 --CH.sub.2 --O--R.sup.2b', --O--CH.sub.2 --C(.dbd.O)--O--R.sup.2b', --N(--R.sup.2b')--CH.sub.2 --CH.sub.2 --O--R.sup.2b', --N(--CH.sub.2 --CH.sub.2 --O--R.sup.2b').sub.2, --N(--R.sup.2b')--C(.dbd.O)--R.sup.3b' and --N(--R.sup.2b')--S(.dbd.O).sub.2 R.sup.3b' ; each of R.sup.2b' and R.sup.3b' is independently a member selected from the group consisting of --H, --C.sub.1-4 alkyl and --C.sub.1-4 alkyl-(carbocyclic aryl); J is a direct link; X is naphthyl, which is substituted with 0-3 R.sup.1c groups; each R.sup.1c is independently a member selected from the group consisting of halo, --C.sub.1-4 alkyl, --CN, --NO.sub.2, --(CH.sub.2), --N(--R.sup.2c, --R.sup.3c), --C(.dbd.O)--N(R.sup.2c, R.sup.3c), C(.dbd.NH)--N(--R.sup.2c, --R.sup.3c), --C(.dbd.NMe)--N(--R.sup.2c, --R.sup.3c), --S(.dbd.O).sub.2 --N(--R.sup.2c, R.sup.3c), --S(.dbd.O).sub.2 --R.sup.2c, --S(.dbd.O).sub.2 --O.sup.-, --CF.sub.3, --O--R.sup.2c, --O--CH.sub.2 --CH.sub.2 --O--R.sup.2c, --O--CH.sub.2 --C(.dbd.O)--O--R.sup.2c, --N(--R.sup.2c)--CH.sub.2 --CH.sub.2 --O--R.sup.2c, --N(--CH.sub.2 --CH.sub.2 --O--R.sup.2c).sub.2, --(--CH.sub.2).sub.z --N(--R.sup.2c)--C(.dbd.O)R.sup.3c, --(CH.sub.2).sub.z --N(--R.sup.2c)--S(.dbd.O).sub.2 R.sup.3c, and a 5-6 membered heterocyclic ring having 1-4 heteroatoms each independently a member selected from the group consisting of N, O and S; z is an integer of 0-2; each of R.sup.2c and R.sup.3c is independently a member selected from the group consisting of --H, --C.sub.1-4 alkyl and --C.sub.1-4 alkyl-(carbocyclic aryl); or all pharmaceutically acceptable diastereoisomers, enantiomers or mixtures thereof, salts, hydrates or solvates thereof. 3. The compound of claim 1, wherein: A is a member selected from the group consisting of: ##STR701## Q is a direct link; D is a member selected from the group consisting of: ##STR702## E is --NH--C(.dbd.O)--; G is a member selected from the group consisting of: ##STR703## each R.sup.1b is independently a member selected from the group consisting of --H, -Me, --CF.sub.3, --F, --Cl, --Br, --SO.sub.2 Me, --CN, --CONH.sub.2, --CONMe.sub.2, --NH.sub.2, --NO.sub.2, --NHCOMe, --NHSO.sub.2 Me, --CH.sub.2 NH.sub.2 and --CO.sub.2 H; J is a direct link; X is a member selected from the group consisting of: ##STR704## ##STR705## ##STR706## ##STR707## ##STR708## ##STR709## ##STR710## ##STR711## ##STR712## ##STR713## ##STR714## ##STR715## ##STR716## or all pharmaceutically acceptable diastereoisomers, enantiomers or mixtures thereof, salts, hydrates or solvates thereof. 4. The compound of claim 1, wherein: A is phenyl, which is substituted with 0-2 R.sup.1 groups; each R.sup.1 is independently a member selected from the group consisting of --S(.dbd.O).sub.2 --N(--R.sup.2, --R.sup.3), --S(.dbd.O).sub.2 --R.sup.2, --CH.sub.2 N(--R.sup.2, --R.sup.3), --CN and halo; each of R.sup.2 and R.sup.3 is independently a member selected from the group consisting of --H and --C.sub.1-4 alkyl; Q is a direct link; D is a member selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl and pyridazinyl, each substituted with 0-1 R.sup.1a groups; R.sup.1a is a member selected from the group consisting of --H and halo; E is --NH--C(.dbd.O)--; G is pyrazole, substituted with 0-2 R.sup.1b groups; each R.sup.1b is independently a member selected from the group consisting of -Me, --Et, --CF.sub.3, --C(.dbd.O)--NH.sub.2, --NH.sub.2, --NH--C(.dbd.O)-Me, --NH--S(.dbd.O).sub.2 -Me, --SMe, --S(.dbd.O).sub.2 -Me and halo; alternatively, when two R.sup.1b groups may be present on adjacent ring atoms of G and combine to form a benzene ring; J is a direct link; X is naphthyl, which is substituted with 0-3 R.sup.1c groups; each R.sup.1c is independently a member selected from the group consisting of --H, halo, -Me, --CF.sub.3, --OH, --OMe, --NH.sub.2, --CN, --NO.sub.2, --CH.sub.2 --R.sup.2c, --C(.dbd.O)--N(--R.sup.2c, --R.sup.3c), --S(.dbd.O).sub.2 --R.sup.2c, --S(.dbd.O).sub.2 --N(--R.sup.2c, --R.sup.3c), --S(.dbd.O).sub.2 --OH, --C(.dbd.NH)--N(--R.sup.2c, --R.sup.3c), 2-imidazolin-2-yl and 1-methyl-2-imidazolin-2-yl; each of R.sup.2c and R.sup.3c is independently a member selected from the group consisting of --H, --OH, --NH.sub.2 and --C.sub.1-4 alkyl; or all pharmaceutically acceptable diastereoisomers, enantiomers or mixtures thereof, salts, hydrates or solvates thereof. 5. A compound selected from the group consisting of: ##STR717## wherein R.sup.1 is a member selected from the group consisting of --SO.sub.2 NH.sub.2, --SO.sub.2 Me, --CH.sub.2 NH.sub.2 and --CH.sub.2 NMe.sub.2 ; R.sup.1a is a member selected from the group consisting of --H, --F, --Cl and --Br; R.sup.1b is a member selected from the group consisting of --CH.sub.3, --CF.sub.3, --CH.sub.2 CH.sub.3, --SO.sub.2 Me, --CONH.sub.2 and --NHSO.sub.2 Me; R.sup.1c1 is a member selected from the group consisting of --H, --F, --Cl, --Br, --NH.sub.2, --OH, --SO.sub.2 Me, --SO.sub.2 Et, --SO.sub.2 NH.sub.2, --NO.sub.2, --CH.sub.2 NH.sub.2, --CN, --CONH.sub.2 and --CH.sub.2 OH; R.sup.1c2 is a member selected from the group consisting of --H, --F, --Cl and --Br; R.sup.1c3 is a member selected from the group consisting of --H, --F, --Cl and --Br; or all pharmaceutically acceptable diastereoisomers, enantiomers or mixtures thereof, salts, hydrates or solvates thereof. 6. A compound selected from the group consisting of: ##STR718## wherein R.sup.1 is a member selected from the group consisting of --SO.sub.2 NH.sub.2, --SO.sub.2 Me, --CH.sub.2 NH.sub.2 and --CH.sub.2 NMe.sub.2 ; R.sup.1b is a member selected from the group consisting of --CH.sub.3, --CF.sub.3, --CH.sub.2 CH.sub.3, --SO.sub.2 Me, --CONH.sub.2 and --NHSO.sub.2 Me; R.sup.1c1 is a member selected from the group consisting of --H, --F, --Cl, --Br, --NH.sub.2, --OH, --SO.sub.2 Me, --SO.sub.2 Et, --SO.sub.2 NH.sub.2, --NO.sub.2, --CH.sub.2 NH.sub.2, --CN, --CONH.sub.2 and --CH.sub.2 OH; R.sup.1c2 is a member selected from the group consisting of --H, --F, --Cl and --Br; or all pharmaceutically acceptable diastereoisomers, enantiomers or mixtures thereof, salts, hydrates or solvates thereof. 7. A pharmaceutical composition for 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. 8. A method for 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. 9. The method of claim 8, wherein the condition is a member 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. 10. A method for inhibiting the coagulation of biological samples, comprising the step of administering a compound of claim 1. 11. A method for 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. 12. The method of claim 11, wherein the condition is a member 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. 13. A method for inhibiting the coagulation of biological samples, comprising the step of administering a compound of claim 4. 14. A method for treating a condition in a mammal characterized by undesired thrombosis comprising administering to said mammal a therapeutically effective amount of a compound of claim 5. 15. The method of claim 14, wherein the condition is a member 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. 16. A method for inhibiting the coagulation of biological samples, comprising the step of administering a compound of claim 5. 17. A method for treating a condition in a mammal characterized by undesired thrombosis comprising administering to said mammal a therapeutically effective amount of a compound of claim 6. 18. The method of claim 17, wherein the condition is a member 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. 19. A method for inhibiting the coagulation of biological samples, comprising the step of administering a compound of claim 6.