Patent ID: 6316437
Filing Date: 2001-11-13
Classification: A61K,A61P,C07D

Abstract:
A compound of formula: ##STR78##wherein Q is ##STR79##R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each independently selected from hydrogen, fluorine, C.sub.1 -C.sub.6 alkyl, and C.sub.3 -C.sub.8 cycloalkyl;R.sup.5 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, (CH.sub.2).sub.1-4 CO.sub.2 R.sup.d, (CH.sub.2).sub.1-4 C(.dbd.O)N(R.sup.d).sub.2, C.sub.2 -C.sub.8 alkoxyalkyl, or fluorinated C.sub.2 -C.sub.8 alkoxyalkyl;each R.sup.6 is a substituent connected to a ring atom other than C(R.sup.7 R.sup.8), spiro substituted carbon, or N and is independently hydrogen or C.sub.1 -C.sub.4 alkyl;R.sup.7 is hydrogen, cyano, hydroxy, CO.sub.2 R.sup.d, CON(R.sup.d).sub.2, aryl, or substituted aryl; wherein each of the substituents on substituted aryl is independently halo, cyano, hydroxy, 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.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;R.sup.8 is aryl, substituted aryl, heteroaryl, or substituted heteroaryl; wherein each of the substituents on substituted aryl is independently halo, cyano, hydroxy, 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.1 -C.sub.6 alkoxy, fluorinated C.sub.1 -C.sub.6 alkoxy, (CH.sub.2).sub.1-4 CO.sub.2 R.sup.d, (CH.sub.2).sub.0-4 C(.dbd.O)N(R.sup.d).sub.2, (CH.sub.2).sub.0-4 SO.sub.2 R.sup.d, C.sub.2 -C.sub.8 alkoxyalkyl, or fluorinated C.sub.2 -C.sub.8 alkoxyalkyl; and wherein each of the substitutents on substituted heteroaryl is independently halogen, cyano, N(R.sup.d).sub.2, (CH.sub.2).sub.0-4 C(.dbd.O)N(R.sup.d).sub.2, (CH.sub.2).sub.0-4 SO.sub.2 N(R.sup.d).sub.2, (CH.sub.2).sub.0-4 SO.sub.2 R.sup.d, phenyl, 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.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;R.sup.10 is hydrogen, C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, or fluorinated C.sub.3 -C.sub.8 cycloalkyl;R.sup.12 is hydrogen or C.sub.1 -C.sub.4 alkyl;each X.sup.1 is independently hydrogen, halogen, cyano, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, fluorinated C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.3 -C.sub.8 cycloalkyl, (CH.sub.2).sub.0-4 CO.sub.2 R.sup.d, (CH.sub.2).sub.0-4 C(.dbd.O)N(R.sup.d).sub.2, 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;Y is 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), C(R.sup.a).dbd.C(R.sup.b)--C(R.sup.a R.sup.b), [C(R.sup.a R.sup.b)].sub.1-3, or ##STR80##Z is absent, C(R.sup.a R.sup.b), O, S, SO, SO.sub.2, or N(R.sup.c); provided that (i) when Z is absent, Y is 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), C(R.sup.a).dbd.C(R.sup.b)--C(R.sup.a R.sup.b), or ##STR81##and (ii) when Z is C(R.sup.a R.sup.b), O, S, SO, SO.sub.3, or N(R.sup.c), Y is [C(R.sup.a R.sup.b)].sub.1-3 or ##STR82##D is absent, [C(R.sup.a R.sup.b)].sub.1-4, O[C(R.sup.a)].sub.1-2, [C(R.sup.a)].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);E 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 E is absent, D 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 E is C(.dbd.O) or C(.dbd.O)O, D 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 E 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, D is absent or C(R.sup.a R.sup.b);each X.sup.2 is independently hydrogen, halogen, cyano, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, fluorinated C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.3 -C.sub.8 cycloalkyl, (CH.sub.2).sub.0-4 CO.sub.2 R.sup.d, (CH.sub.2).sub.0-4 C(.dbd.O)N(R.sup.d).sub.2, 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;each X.sup.3 is independently hydrogen, halogen, cyano, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, fluorinated C.sub.1 -C.sub.6 alkyl, fluorinated C.sub.3 -C.sub.8 cycloalkyl, (CH.sub.2).sub.0-4 CO.sub.2 R.sup.d, (CH.sub.2).sub.0-4 C(.dbd.O)N(R.sup.d).sub.2, 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;R.sup.a and R.sup.b are each independently hydrogen, C.sub.1 -C.sub.4 alkyl, and fluorinated C.sub.1 -C.sub.4 alkyl;R.sup.c is hydrogen, C.sub.1 -C.sub.4 alkyl, or fluorinated C.sub.1 -C.sub.4 alkyl;R.sup.d is hydrogen, C.sub.1 -C.sub.6 alkyl, or fluorinated C.sub.1 -C.sub.6 alkyl;m is an integer from 1 to 4;p and q are each independently integers from 0 to 3;s1 is an integer from 0 to 4;s2 is an integer from 0 to 4;s3 is an integer from 0 to 4; andt is an integer from 0 to 4;and provided that when Q is of formula (a1), Z is O, Y is [C(R.sup.a R.sup.b)].sub.1-3, and R.sup.8 is aryl, then R.sup.7 is cyano, CO.sub.2 R.sup.d, CON(R.sup.d).sub.2, or substituted aryl;or a pharmaceutically acceptable salt thereof.