Patent ID: 6022861
Filing Date: 2000-02-08
Classification: A61K,C07K

Abstract:
A pharmaceutical composition comprising a therapeutically effective carrier and a therapeutically effective amount of a compound having the formula: ##STR26## wherein: m is 0, 1, 2, 3, or 4;n is 0, 1, 2, 3, or 4;Y is NH, S, O, CH.sub.2, CH--OH, CH.sub.2 CH.sub.2, or C=0;A is piperidinyl, pyrrolidinyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, or C.sub.3-6 heteroaryl, or A is absent;R.sub.1 is H or C.sub.1-3 alkyl;J is O or H.sub.2 ;R.sub.2 is H or C.sub.1-3 alkyl;D is N, CH, NCH.sub.2, NCH.sub.2 CH.sub.2, or CHCH.sub.2 ;R.sub.3 is H or C.sub.1-3 alkyl;E is O or H.sub.2 ;R.sub.4 is H or CH.sub.3 ;M is N, NH, N--CH.sub.3, O, S, SO, SO.sub.2, or CH.sub.2 or M is absent;Q is piperidinyl, pyrrolidynyl, C.sub.3-8 cycloalkyl, phenyl, substituted phenyl, naphthyl, or pyridyl, or Q is absent;G is N, CH, or H;R.sub.5 is H or C.sub.1-3 alkyl or R.sub.5 is absent if G is H;R.sub.6 is H or CH.sub.3 ;U is selected from a group consisting of ##STR27## where n is an integer from 0 to 4; R.sub.7 and R.sub.8 are independently selected from a group consisting of H, C.sub.1-10 alkyl, aryl, arylalkyl, halogen, nitro, an amino group of formula --NR.sub.9 R.sub.10, an acylamino group of formula --NHCOR.sub.11, hydroxy, an acyloxy group of formula --OCOR.sub.12, C.sub.1-4 alkyloxy, C.sub.1-4 alkyl, trifluoromethyl, carboxy, cyano, phenyl, aromatic heterocyclic group, C.sub.1-4 alkyloxycarbonyl, an aminocarbonyl group of formula CONR.sub.13 R.sub.14, sulfo, sulfonamido of formula SO.sub.2 NR.sub.15 R.sub.16 and C.sub.1-6 hydroxyalkyl; wherein R.sub.9, R.sub.10, R.sub.11, R.sub.12, R.sub.13, R.sub.14, R.sub.15, R.sub.16 are the same or different and are H, C.sub.1-6 alkyl, arylC.sub.1-3 alkyl or aryl, andif M is absent, U is: ##STR28## K is C or N; W is H, arylacyl, heteroarylacyl, arylC.sub.1-3 alkylsulfonyl, arylsulfonyl, substituted arylsulfonyl, arylC.sub.1-4 alkenylsulfonyl, C.sub.1-8 alkylsulfonyl, heteroaryl-C.sub.1-3 alkylsulfonyl, heteroarylsulfonyl, aryloxycarbonyl, C.sub.1-6 alkyloxycarbonyl, arylC.sub.1-3 alkyloxycarbonyl, arylaminocarbonyl, C.sub.1-6 alkylaminocarbonyl, arylC.sub.1-3 alkylaminocarbonyl, or HOOC--C.sub.0-3 alkylcarbonyl, or W is absent if G is H;X is NR'R"", NH--C(NR'R"").dbd.NH, NH--C(NHR').dbd.NR"", NH--C(R').dbd.NR"", S--C(NR'R"").dbd.NH, S--C(NHR').dbd.NR"", C(NR'R"").dbd.NH, C(NHR').dbd.NR"" and CR'=NR""; where: R',R"" are the same or different and are H, C.sub.1-6 alkyl, arylC.sub.1-3 alkyl, or aryl, or R'R"" taken together represent (CH.sub.2).sub.p where p is an integer from 2 to 5, to form a 3 to 7 membered heterocycle;Z is NR'R"", NH--C(NR'R"").dbd.NH, NH--C(NHR').dbd.NR"", NH--C(R').dbd.NR"", S--C(NR'R"").dbd.NH, S--C(NHR').dbd.NR"", C(NR'R"").dbd.NH, C(NHR').dbd.NR"" and CR'=NR""; where: R',R"" are the same or different and are H, C.sub.1-6 alkyl, arylC.sub.1-3 alkyl, or aryl, or R'R"" taken together represent (CH.sub.2).sub.p where p is an integer from 2 to 5, to form a 3 to 7 membered heterocycle;or a pharmaceutically acceptable isomer, salt, hydrate, or solvate thereof, wherein said compound is a selective Factor Xa inhbitor and has an IC.sub.50 of less than about 0.5 .mu.M for Factor Xa.