Patent ID: 6211154
Filing Date: 2001-04-03
Classification: A61K,C07K

Abstract:
A compound having the formula: ##STR28##wherein.m is 0, 1, 2, 3, or 4;n is 0, 1, 2, 3, or 4;Y is selected from the group consisting of NH, S, O, CH.sub.2, CH--OH, CH.sub.2 CH.sub.2, and C=0;A is piperdinyl, pyrrolidinyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, C.sub.3-6 heteroaryl, or 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 selected from the group consisting of N, CH, NCH.sub.2, NCH.sub.2 CH.sub.2, and CHCH.sub.2 ;R.sub.3 is H or C.sub.1-3 allyl;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, CH.sub.2 or is absent;Q is piperdinyl, pyrrolidynyl, C.sub.3-8 cycloalkyl, naphthyl, pyridyl, phenyl, phenyl substituted with one, two or three substituents selected from the group consisting of loweralkoxy, loweralkyl, lower alkylamino, hydroxy, halogen, cyano, hydroxyl, mercapto, nitro, thioalkoxy, carboxaldehyde, carboxyl, carboalkoxy and carboxamide, or Q is absent;G is selected from the group consisting of N, CH, and H;R.sub.5 is H or C.sub.1-3 alkyl or is absent if G is H;R.sub.6 is H or CH.sub.3 ;U is selected from a group consisting of ##STR29##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, and sulfonamido of formula SO.sub.2 NR.sub.15 R.sub.16 and C.sub.1-6 hydroxyalkyl, and 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.1-4 alkyl, C.sub.1-3 arylalkyl or aryl, andif M is absent, U is: ##STR30##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.1-4 alkylsulfonyl, heteroaryl-C.sub.1-3 alkylsulfonyl, heteroarylsulfonyl, aryloxycarbonyl, C.sub.1-4 alkyloxycarbonyl, arylC.sub.1-3 alkyloxycarbonyl, arylaminocarbonyl, C.sub.1-6 alkylaminocarbonyl, arylC.sub.1-3 alkylaminocarbonyl, HOOC--CO.sub.1-3 alkylcarbonyl, or is absent if G is H;X is selected from the group consisting of H, C.sub.1-3 alkyl, 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'.dbd.NR""; where: R',R"" are the same or different and are H, C.sub.1-6 alkyl, C.sub.1-3 arylalkyl, aryl or where R'R"" forms a cyclic ring containing (CH)p where p is an integer from 2 to 5;Z is selected from the group consisting of H, C.sub.1-3 alkyl, 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'.dbd.NR""; where: R',R"" are the same or different and are H, C.sub.1-6 alkyl, C.sub.1-3 arylalkyl, aryl or where R'R"" forms a cyclic ring containing (CH.sub.2).sub.p where p is an integer from 2 to 5;wherein said compound is a selective Factor Xa inhibitor and has an IC.sub.50 of less than about 0.5 .mu.M for Factor Xa;or a pharmaceutically acceptable isomer, salt, hydrate, or solvate thereof.