Patent ID: 6130231
Filing Date: 2000-10-10
Classification: A61P,C07D

Abstract:
A compound of Formula I: ##STR44## including stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, or pharmaceutically acceptable salt forms thereof wherein:R.sup.1 is selected from: ##STR45## D is --N(R.sup.12)-- or --S--; J is --C(R.sup.2)-- or --N--;K, L and M are independently --C(R.sup.2)-- or --C(R.sup.3)--;R.sup.2 and R.sup.3 are independently selected from:H, C.sub.1 -C.sub.4 alkoxy, NR.sup.11 R.sup.12, halogen, NO.sub.2, CN, CF.sub.3, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 alkenyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.7 cycloalkyl(C.sub.1 -C.sub.4 alkyl), aryl(C.sub.1 -C.sub.6 alkyl)-, (C.sub.1 -C.sub.6 alkyl)carbonyl, (C.sub.1 -C.sub.6 alkoxy)carbonyl, arylcarbonyl, and aryl substituted with 0-4 R.sup.7,alternatively, when R.sup.2 and R.sup.3 are substituents on adjacent atoms, they can be taken together with the carbon atoms to which they are attached to form a 5-7 membered carbocyclic or 5-7 membered heterocyclic aromatic or nonaromatic ring system, said carbocyclic or heterocyclic ring being substituted with 0-2 groups selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, cyano, amino, CF.sub.3 and NO.sub.2 ;R.sup.2a is selected from:H, C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.3 -C.sub.7 cycloalkyl(C.sub.1 -C.sub.4 alkyl), aryl, aryl(C.sub.1 -C.sub.4 alkyl)-, (C.sub.2 -C.sub.7 alkyl)carbonyl, arylcarbonyl, (C.sub.2 -C.sub.10 alkoxy)carbonyl, C.sub.3 -C.sub.7 cycloalkoxycarbonyl, C.sub.7 -C.sub.11 bicycloalkoxycarbonyl, aryloxycarbonyl, aryl(C.sub.1 -C.sub.10 alkoxy)carbonyl, C.sub.1 -C.sub.6 alkylcarbonyloxy(C.sub.1 -C.sub.4 alkoxy)carbonyl, arylcarbonyloxy(C.sub.1 -C.sub.4 alkoxy)carbonyl, and C.sub.3 -C.sub.7 cycloalkylcarbonyloxy(C.sub.1 -C.sub.4 alkoxy)carbonyl;R.sup.4 is selected from:H, C.sub.1 -C.sub.10 alkyl, (C.sub.1 -C.sub.10 alkyl)carbonyl, aryl, aryl(C.sub.1 -C.sub.4 alkyl)-, C.sub.3 -C.sub.11 cycloalkyl, and C.sub.3 -C.sub.11 cycloalkyl(C.sub.1 -C.sub.4 alkyl)-;U is selected from:--(CH.sub.2).sub.n --, --(CH.sub.2).sub.n O(CH.sub.2).sub.m --, --(CH.sub.2).sub.n N(R.sup.12)(CH.sub.2).sub.m --, --N(H)(CH.sub.2).sub.n --, --(CH.sub.2).sub.n C(.dbd.O)(CH.sub.2).sub.m --, --(CH.sub.2).sub.n S(O).sub.p (CH.sub.2).sub.m --, --(CH.sub.2).sub.n NHNH(CH.sub.2).sub.m --, --N(R.sup.10)C(.dbd.O)--, --NHC(.dbd.O)(CH.sub.2).sub.n --, --C(.dbd.O)N(R.sup.10)--, and --N(R.sup.10)S(O).sub.p --;W is --C(.dbd.O)--N(R.sup.10)--(C.sub.2 -C.sub.3 alkylene)-, in which the alkylene group is substituted by R.sup.8 and by R.sup.9 :R.sup.8 and R.sup.9 are independently selected from:H, CO.sub.2 R.sup.18b, C(.dbd.O)R.sup.18b, CONR.sup.17 R.sup.18b,hydroxy, C.sub.5 -C.sub.10 alkoxy, nitro, --N(R.sup.10)R.sup.11, --N(R.sup.16)R.sup.17, aryl(C.sub.0 -C.sub.6 alkyl)carbonyl, aryl(C.sub.3 -C.sub.6 alkyl), heteroaryl(C.sub.1 -C.sub.6 alkyl), CONR.sup.18a R.sup.20, SO.sub.2 R.sup.18a, SO.sub.2 NR.sup.18a R.sup.20,C.sub.1 -C.sub.10 alkyl substituted with 0-1 R.sup.6,C.sub.5 -C.sub.10 alkenyl substituted with 0-1 R.sup.6,C.sub.5 -C.sub.10 alkynyl substituted with 0-1 R.sup.6,C.sub.3 -C.sub.8 cycloalkyl substituted with 0-1 R.sup.6,C.sub.5 -C.sub.6 cycloalkenyl substituted with 0-1 R.sup.6,C.sub.1 -C.sub.10 alkylcarbonyl,C.sub.3 -C.sub.10 cycloalkyl(C.sub.1 -C.sub.4 alkyl)-,phenyl substituted with 1-3 R.sup.6,naphthyl substituted with 0-3 R.sup.6,a 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R.sup.7, andC.sub.5 -C.sub.10 alkyl substituted with 0-3 R.sup.7,providing that any of the above alkyl, cycloalkyl, aryl or heteroaryl groups may be unsubstituted or substituted independently with 1-2 R.sup.7 ;R.sup.6 is selected from:H, C.sub.1 -C.sub.10 alkyl, hydroxy, C.sub.1 -C.sub.10 alkoxy, nitro, C.sub.1 -C.sub.10 alkylcarbonyl, --N(R.sup.11)R.sup.12, cyano, halo, CF.sub.3, CHO, CO.sub.2 R.sup.18b, C(.dbd.O)R.sup.18b, CONR.sup.17 R.sup.18b, OC(.dbd.O)R.sup.10, OR.sup.10, OC(.dbd.O)NR.sup.10 R.sup.11, NR.sup.10 C(.dbd.O)R.sup.10, NR.sup.10 C(.dbd.O)OR.sup.21, NR.sup.10 C(.dbd.O)NR.sup.10 R.sup.11, NR.sup.10 SO.sub.2 NR.sup.10 R.sup.11, NR.sup.10 SO.sub.2 R.sup.21, S(O).sub.p R.sup.11, SO.sub.2 NR.sup.10 R.sup.11,aryl substituted with 0-3 groups selected from halogen, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkyl, CF.sub.3, S(O).sub.m Me, and --NMe.sub.2,aryl(C.sub.1 -C.sub.4 alkyl)-, said aryl being substituted with 0-3 groups selected from halogen, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkyl, CF.sub.3, S(O).sub.p Me, and --NMe.sub.2, anda 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 R.sup.7 ;R.sup.7 is selected from:H, hydroxy, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, aryl, aryl(C.sub.1 -C.sub.4 alkyl)-, (C.sub.1 -C.sub.4 alkyl)carbonyl, CO.sub.2 R.sup.18a, SO.sub.2 R.sup.11, SO.sub.2 NR.sup.10 R.sup.11, OR.sup.10, and N(R.sup.11)R.sup.12 ;R.sup.10 is selected from:H, C.sub.3 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, aryl, (C.sub.3 -C.sub.11 cycloalkyl)methyl, aryl(C.sub.1 -C.sub.4 alkyl), and C.sub.1 -C.sub.10 alkyl substituted with 0-2 R.sup.6 ;R.sup.11 is selected from:H, hydroxy, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, (C.sub.3 -C.sub.11 cycloalkyl)methyl, C.sub.1 -C.sub.6 alkoxy, benzyloxy, aryl, heteroaryl, heteroaryl(C.sub.1 -C.sub.4 alkyl)-, aryl(C.sub.1 -C.sub.4 alkyl), adamantylmethyl, and C.sub.1 -C.sub.10 alkyl substituted with 0-2 R.sup.4,alternatively, when R.sup.10 and R.sup.11 are both substituents on the same nitrogen atom (as in --NR.sup.10 R.sup.11) they may be taken together with the nitrogen atom to which they are attached to form a heterocycle selected from:3-azabicyclononyl, 1,2,3,4-tetrahydro-1-quinolinyl, 1,2,3,4-tetrahydro-2-isoquinolinyl, 1-piperidinyl, 1-morpholinyl, 1-pyrrolidinyl, thiamorpholinyl, thiazolidinyl, and 1-piperazinyl;said heterocycle being substituted with 0-3 groups selected from: C.sub.1 -C.sub.6 alkyl, aryl, heteroaryl, aryl(C.sub.1 -C.sub.4 alkyl)-, (C.sub.1 -C.sub.6 alkyl)carbonyl, (C.sub.3 -C.sub.7 cycloalkyl)carbonyl, (C.sub.1 -C.sub.6 alkoxy)carbonyl, aryl(C.sub.1 -C.sub.4 alkoxy)carbonyl, C.sub.1 -C.sub.6 alkylsulfonyl, and arylsulfonyl;R.sup.12 is selected from:H, C.sub.1 -C.sub.6 alkyl, triphenylmethyl, methoxymethyl, methoxyphenyldiphenylmethyl, trimethylsilylethoxymethyl, (C.sub.1 -C.sub.6 alkyl)carbonyl, (C.sub.1 -C.sub.6 alkoxy)carbonyl, (C.sub.1 -C.sub.6 alkyl)aminocarbonyl, C.sub.3 -C.sub.6 alkenyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.7 cycloalkyl(C.sub.1 -C.sub.4 alkyl)-, aryl, heteroaryl(C.sub.1 -C.sub.6 alkyl)carbonyl, heteroarylcarbonyl, aryl(C.sub.1 -C.sub.6 alkyl)-, (C.sub.1 -C.sub.6 alkyl)carbonyl, arylcarbonyl, C.sub.1 -C.sub.6 alkylsulfonyl, arylsulfonyl, aryl(C.sub.1 -C.sub.6 alkyl)sulfonyl, heteroarylsulfonyl, heteroaryl(C.sub.1 -C.sub.6 alkyl)sulfonyl, aryloxycarbonyl, and aryl(C.sub.1 -C.sub.6 alkoxy)carbonyl, wherein said aryl groups are substituted with 0-2 substituents selected from the group consisting of C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, CF.sub.3, and nitro;R.sup.14 is selected from H, C.sub.1 -C.sub.4 alkyl, and phenyl(C.sub.1 -C.sub.4 alkyl);R.sup.16 is selected from:--C(.dbd.O)OR.sup.18a, --C(.dbd.O)R.sup.18b, --C(.dbd.O)N(R.sup.18b).sub.2, --C(.dbd.O)NHSO.sub.2 R.sup.18a, --C(.dbd.O)NHC(.dbd.O)R.sup.18b, --C(.dbd.O)NHC(.dbd.O)OR.sup.18a, --C(.dbd.O)NHSO.sub.2 NHR.sup.18b, --SO.sub.2 R.sup.18a, --SO.sub.2 N(R.sup.18b).sub.2, and --SO.sub.2 NHC(.dbd.O)OR.sup.18b ;R.sup.17 is selected from:H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.7 cycloalkyl(C.sub.1 -C.sub.4 alkyl)-, aryl, aryl(C.sub.1 -C.sub.6 alkyl)-, and heteroaryl(C.sub.1 -C.sub.6 alkyl);R.sup.18a is selected from:C.sub.7 -C.sub.8 alkyl, C.sub.3 -C.sub.11 cycloalkyl,aryl(C.sub.1 -C.sub.6 alkyl)-, said aryl substituted with 0-4 R.sup.19,heteroaryl(C.sub.1 -C.sub.6 alkyl)-, said heteroaryl substituted with 0-4 R.sup.19,(C.sub.1 -C.sub.6 alkyl)heteroaryl, said heteroaryl substituted with 0-4 R.sup.19,heteroaryl substituted with 0-4 R.sup.19,phenyl substituted with 3-4 R.sup.19, andnaphthyl substituted with 0-4 R.sup.19 ;R.sup.18b is H or R.sup.18a ;R.sup.19 is selected from:H, halogen, CF.sub.3, CO.sub.2 H, CN, NO.sub.2, --NR.sup.11 R.sup.12, OCF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, C.sub.3 -C.sub.11 cycloalkyl, C.sub.3 -C.sub.7 cycloalkyl(C.sub.1 -C.sub.4 alkyl)-, aryl(C.sub.1 -C.sub.6 alkyl)-, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.4 alkoxycarbonyl, aryl, aryl-O--, aryl-SO.sub.2 --, heteroaryl, and heteroaryl-SO.sub.2 --, wherein said aryl and heteroaryl groups are substituted with 0-4 groups selected from hydrogen, halogen, CF.sub.3, C.sub.1 -C.sub.3 alkyl, and C.sub.1 -C.sub.3 alkoxy;R.sup.20 is selected from:hydroxy, C.sub.1 -C.sub.10 alkyloxy, C.sub.3 -C.sub.11 cycloalkyloxy,aryloxy, aryl(C.sub.1 -C.sub.4 alkyl)oxy,C.sub.2 -C.sub.10 alkylcarbonyloxy(C.sub.1 -C.sub.2 alkyl)oxy-,C.sub.2 -C.sub.10 alkoxycarbonyloxy(C.sub.1 -C.sub.2 alkyl)oxy-,C.sub.2 -C.sub.10 alkoxycarbonyl(C.sub.1 -C.sub.2 alkyl)oxy-,C.sub.3 -C.sub.10 cycloalkylcarbonyloxy(C.sub.1 -C.sub.2 alkyl)oxy-,C.sub.3 -C.sub.10 cycloalkoxycarbonyloxy(C.sub.1 -C.sub.2 alkyl)oxy-,C.sub.3 -C.sub.10 cycloalkoxycarbonyl(C.sub.1 -C.sub.2 alkyl)oxy-,aryloxycarbonyl(C.sub.1 -C.sub.2 alkyl)oxy-,aryloxycarbonyloxy(C.sub.1 -C.sub.2 alkyl)oxy-,arylcarbonyloxy(C.sub.1 -C.sub.2 alkyl)oxy-,C.sub.1 -C.sub.5 alkoxy(C.sub.1 -C.sub.5 alkyl)carbonyloxy(C.sub.1 -C.sub.2 alkyl)oxy-,(5-(C.sub.1 -C.sub.5 alkyl)-1,3-dioxa-cyclopenten-2-one-yl)methyloxy,(5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, and(R.sup.10)(R.sup.11)N--(C.sub.1 -C.sub.10 alkoxy)-;R.sup.21 is selected from:C.sub.1 -C.sub.8 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.11 cycloalkyl, (C.sub.3 -C.sub.11 cycloalkyl)methyl, aryl, aryl(C.sub.1 -C.sub.4 alkyl)-, and C.sub.1 -C.sub.10 alkyl substituted with 0-2 R.sup.7 ;Y is selected from:--COR.sup.20, --SO.sub.3 H, --PO.sub.3 H;m is 0-2;n is 0-4;p is 0-2;with the following provisos:(1) n and m are chosen such that the number of atoms connecting R.sup.1 and Y is in the range of 8-14;(2) in W, the alkylene group is substituted with at least one R.sup.8 or R.sup.9 which is not H;(3) in the definition of W, when there is only one non-hydrogen substituent on the alkylene group, such substituent may not be an unsubstituted pyridyl radical.