Patent ID: 6326372
Filing Date: 2001-12-04
Classification: A61P,C07D

Abstract:
A compound of formula: ##STR87##wherein A is ##STR88## ##STR89##E is CR.sup.a R.sup.b or NR.sup.c ;R.sup.1 is hydrogen, C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, fluorinated C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.20 alkylcycloalkyl, or C.sub.4 -C.sub.20 cycloalky1a lkyl;R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as follows:(i) R.sup.2 and R.sup.3 are each independently selected from hydrogen, cyano, C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, fluorinated C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.20 alkylcycloalkyl, C.sub.4 -C.sub.20 cycloalkylalkyl, fluorinated C.sub.4 -C.sub.20 alkylcycloalkyl, fluorinated C.sub.4 -C.sub.20 cycloalkylalkyl, (CH.sub.2).sub.0-4 CO.sub.2 R.sup.d, (CH2).sub.0-4 OR.sup.d, and (CH.sub.2).sub.0-4 CON(R.sup.d).sub.2 ; and R.sup.4 and R.sup.5 are each independently selected from hydrogen, C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, fluorinated C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.20 alkylcycloalkyl, C.sub.4 -C.sub.20 cycloalkylalkyl, and (CH.sub.2).sub.0-4 OR.sup.d ;(ii) R.sup.2 and R.sup.3 together with the carbon atom to which they are attached form C.sub.4 -C.sub.6 cycloalkyl or substituted C.sub.4 -C.sub.6 cycloalkyl, wherein the each of the substituents on substituted cycloalkyl is hydrogen, halogen, cyano, C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, fluorinated C.sub.1 -C.sub.6 alkoxy, CO.sub.2 R.sup.d, C.sub.2 -C.sub.8 alkoxyalkyl, or fluorinated C.sub.2 -C.sub.8 alkoxyalkyl; and R.sup.4 and R.sup.5 are as defined in (i); or(iii) R.sup.2 and R.sup.4 together with the carbon atoms to which each is attached form C.sub.4 -C.sub.6 cycloalkyl or substituted C.sub.4 -C.sub.6 cycloalkyl, wherein the each of the substituents on the substituted cycloalkyl is hydrogen, halogen, cyano, C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, fluorinated C.sub.1 -C.sub.6 alkoxy, CO.sub.2 R.sup.d, C.sub.2 -C.sub.8 alkoxyalkyl, or fluorinated C.sub.2 -C.sub.8 alkoxyalkyl; and R.sup.3 and R.sup.5 are as defined in (i);R.sup.6 is hydrogen, cyano, hydroxy, CO.sub.2 R.sup.e, CON(R.sup.e).sub.2, aryl, or substituted aryl;R.sup.7 is aryl, substituted aryl, heterocyclic, or substituted heterocyclic;R.sup.8 is hydrogen or C.sub.1 -C.sub.4 alkyl;R.sup.9 and R.sup.10 are each independently selected from hydrogen, C.sub.1 -C.sub.6 alkyl, and C.sub.3 -C.sub.8 cycloalkyl;each R.sup.11 is a substituent connected to a ring atom other than CR.sup.6 R.sup.7 or N and is independently hydrogen or C.sub.1 -C.sub.4 alkyl;R.sup.12 is hydrogen, C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, fluorinated C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.20 alkylcycloalkyl, or C.sub.4 -C.sub.20 cycloalkylalkyl;R.sup.14 is hydrogen or OR.sup.e ;each R.sup.16 is a substituent connected to a ring atom other than N or the carbon to which R.sup.14 is attached and is independently hydrogen or C.sub.1 -C.sub.4 alkyl;each R.sup.18 is a substituent connected to a ring atom other than N or spiro subsituted carbon and is independently hydrogen or C.sub.1 -C.sub.4 alkyl;D.sup.1 is a benzene ring, or a substituted benzene, wherein each of the substituents on the substituted benzene is independently halogen, cyano, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, fluorinated C.sub.1 -C.sub.8 alkyl, fluorinated C.sub.3 -C.sub.8 cycloalkyl, C.sub.1 -C.sub.6 alkoxy, fluorinated C.sub.1 -C.sub.6 alkoxy, C.sub.2 -C.sub.8 alkoxyalkyl, or fluorinated C.sub.2 -C.sub.8 alkoxyalkyl;D.sup.2 independently has the same definition as set forth for D.sup.1 ;Q is absent, [C(R.sup.a 'R.sup.b ')].sub.1-4, O[C(R.sup.a 'R.sup.b ')].sub.1-2, [C(R.sup.a 'R.sup.b ')].sub.1-2 O, C(R.sup.a ').dbd.C(R.sup.b '), C(R.sup.a 'R.sup.b ').dbd.C(R.sup.a ').dbd.C(R.sup.b '), or C(R.sup.a ').dbd.C(R.sup.b ')--C(R.sup.a 'R.sup.b ');T is absent, C(.dbd.O), C(.dbd.O)O, N(SO.sub.2 R.sup.c ')C(R.sup.a 'R.sup.b '), N(R.sup.c ')C.dbd.O, or N(R.sup.c ')C(.dbd.O)O, provided that (i) when T is absent, Q is [C(R.sup.a 'R.sup.b ')].sub.2-4, O[C(R.sup.a 'R.sup.b ')].sub.1-2, [C(R.sup.a 'R.sup.b ')].sub.1-2 O, C(R.sup.a ').dbd.C(R.sup.b '), C(R.sup.a 'R.sup.b ')--C(R.sup.a ').dbd.C(R.sup.b '), or C(R.sup.a ').dbd.C(R.sup.b ')--C(R.sup.a 'R.sup.b '); (ii) when T is C(.dbd.O) or C(.dbd.O)O, Q is C(R.sup.a 'R.sup.b ') or C(R.sup.a 'R.sup.b ')C(R.sup.a 'R.sup.b '); and (iii) when T is N(SO.sub.2 R.sup.c ')C(R.sup.a 'R.sup.b '), N(R.sup.c ')C.dbd.O, or N(R.sup.c ')C(.dbd.O)O, Q is absent or C(R.sup.a 'R.sup.b ');each X is independently hydrogen, halogen, cyano, C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, fluorinated C.sub.1 -C.sub.6 alkoxy, (CH.sub.2).sub.0-4 CO.sub.2 R.sup.d, C.sub.2 -C.sub.8 alkoxyalkyl, or fluorinated C.sub.2 -C.sub.8 alkoxyalkyl;each Y.sup.1 is independently hydrogen, halogen, cyano, C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, fluorinated C.sub.1 -C.sub.6 alkoxy, (CH.sub.2).sub.0-4 CO.sub.2 R.sup.d, C.sub.2 -C.sub.8 alkoxyalkyl, or fluorinated C.sub.2 -C.sub.8 alkoxyalkyl;Z is absent, O, S, SO, SO.sub.2, NR.sup.h, C.dbd.O, NR.sup.h C(.dbd.O), C(.dbd.O)NR.sup.h, NR.sup.h SO.sub.2, SO.sub.2 NR.sup.h, C(R.sup.f R.sup.g), C(R.sup.f R.sup.g)C(R.sup.f R.sup.g), C(R.sup.f).dbd.C(R.sup.g), C(R.sup.f R.sup.g)S, SC(R.sup.f R.sup.g), C(R.sup.f R.sup.g)SO, SOC(R.sup.f R.sup.g), C(R.sup.f R.sup.g)NR.sup.h, NR.sup.h C(R.sup.f R.sup.g), C(R.sup.f R.sup.g)C(.dbd.O), or C(.dbd.O)C(R.sup.f R.sup.g);R.sup.a and R.sup.b are each independently selected from hydrogen, C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, fluorinated C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.20 alkylcycloalkyl and C.sub.4 -C.sub.20 cycloalkylalkyl;R.sup.c is hydrogen, C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, fluorinated C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.20 alkylcycloalkyl, C.sub.4 -C.sub.20 cycloalkylalkyl, or CHR.sup.k1 R.sup.k2 ;R.sup.a ', R.sup.b 'and R.sup.c 'are each independently selected from hydrogen, C.sub.1 -C.sub.4 alkyl, and fluorinated C.sub.1 -C.sub.4 alkyl;R.sup.d is hydrogen, C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, fluorinated C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.20 alkylcycloalkyl, or C.sub.4 -C.sub.20 cycloalkylalkyl;R.sup.e is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, or fluorinated C.sub.1 -C.sub.6 alkyl;R.sup.f and R.sup.g are each independently selected from hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, fluorinated C.sub.1 -C.sub.6 alkyl, phenyl, and substituted phenyl, wherein each of the substituents on substituted phenyl is independently halo, C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, fluorinated C.sub.1 -C.sub..notident. alkoxy, (CH.sub.2).sub.0-4 CO.sub.2 R.sup.d, C.sub.2 -C.sub.8 alkoxyalkyl, or fluorinated C.sub.2 -C.sub.8 alkoxyalkyl;R.sup.h is hydrogen, C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, fluorinated C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.20 alkylcycloalkyl, or C.sub.4 -C.sub.20 cycloalkylalkyl;R.sup.k1 is hydrogen or C.sub.1 -C.sub.6 alkyl;R.sup.k2 is phenyl or substituted phenyl, wherein each of the substituents on substituted phenyl is halogen, cyano, C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, fluorinated C.sub.1 -C.sub.6 alkoxy, (CH.sub.2).sub.0-4 CO.sub.2 R.sup.d, C.sub.2 -C.sub.8 alkoxyalkyl, or fluorinated C.sub.2 -C.sub.8 alkoxyalkyl;m is an integer from 0 to 4;n is an integer from 2 to 6;p and q are 1;u and v are independently 0 or 1;s1 is an integer from 0 to 5;s2 is an integer from 0 to 4;t is an integer from 0 to 3, provided that when t is zero, R.sup.14 is hydrogen;w is an integer from 0 to 4; andprovided that when A is of formula (a1), thenR.sup.1 is hydrogen;R.sup.2 and R.sup.3 are each independently selected from hydrogen, methyl, ethyl, and cyclopropyl; or R.sup.2 and R.sup.3 together with the carbon atom to which they are attached form C.sub.4 -C.sub.6 cycloalkyl;R.sup.4 and R.sup.5 are each independently selected from hydrogen, methyl, and ethyl;R.sup.6 is hydrogen or cyano;R.sup.7 is phenyl, substituted phenyl, or pyridyl; wherein each of the substituents on substituted phenyl is independently halogen or cyano;R.sup.9 and R.sup.10 are both hydrogen;each X is independently hydrogen or fluorine;R.sup.a and R.sup.b are each independently selected from hydrogen, methyl, and ethyl;R.sup.c is hydrogen, methyl, ethyl, benzyl, or .alpha.-methylbenzyl;m is zero;n is 3; ands1 is an integer from 0 to 2;or a pharmaceutically acceptable salt thereof.