Patent ID: 6100266
Filing Date: 2000-08-08
Classification: A61P,C07C

Abstract:
A method for treating a condition associated with matrix metalloproteinases or that is mediate by TNF.alpha. or enzymes involved in the shedding of L-selectin, CD23, the TNF receptors, IL-1 receptors, or IL-6 receptors, wherein said method comprises the administration of an effective amount a composition comprising a compound of formula (I)B--X--(CH.sub.2).sub.m --(CR.sup.1 R.sup.2).sub.n --W--COY (I)whereinm=0-2;n=1-2, provided that when m=0, then n=2;X is S(O).sub.0-2 ;Y is H;W is N--OR.sup.8 ;R.sup.1 is H or a substituent (optionally substituted with R.sup.7) selected from the group consisting of C.sub.1-6 alkyl, C.sub.2-6 alkenyl, aryl, C.sub.1-6 alkyl-aryl, heteroaryl, C.sub.1-6 alkyl-heteroaryl, heterocycloalkyl, C.sub.1-6 alkyl-heterocycloalkyl, cycloalkyl, and C.sub.1-6 alkyl-cycloalkyl;R.sup.2 is H or C.sub.1-6 alkyl, provided that (CR.sup.1 R.sup.2).sub.n is not (CH.sub.2).sub.n ;or CR.sup.1 R.sup.2 is a cycloalkyl or heterocycloalkyl ring optionally substituted with R.sup.7 or a group (optionally substituted with R.sup.7) selected from the group consisting of C.sub.1-6 alkyl, aryl, C.sub.1-6 alkyl-aryl, heteroaryl, and C.sub.1-6 alkyl-heteroaryl;B is selected from the group consisting of C.sub.1-6 alkyl-aryl, C.sub.1-6 alkyl, cycloalkyl, C.sub.1-6 alkyl-cycloalkyl, cycloalkenyl, heterocycloalkenyl, C.sub.1-6 alkyl-heteroaryl, heterocycloalkyl, C.sub.1-6 alkyl-heterocycloalkyl, aryl, and heteroaryl, any of which groups can optionally be substituted by a substituent selected from the group consisting of R.sup.3, C.sub.1-6 alkyl-R.sup.3, C.sub.2-6 alkenyl-R.sup.3, aryl (optionally substituted with R.sup.3), aryl-C.sub.1-6 alkyl-R.sup.3, C.sub.1-6 alkyl-aryl (optionally substituted with R.sup.3), C.sub.1-6 alkyl-heteroaryl (optionally substituted with R.sup.3), aryl-C.sub.2-6 alkenyl-R.sup.5, heteroaryl (optionally substiatuted with R.sup.3), heteroaryl-C.sub.1-6 alkyl-R.sup.3, cycloalkyl (optionally substituted with R.sup.3), and heterocycloalkyl (optionally substituted with R.sup.3);R.sup.3 is selected from the group consisting of C.sub.1-6 alkyl, halogen, CN, NO.sub.2, N(R.sup.4).sub.2, OR.sup.4, COR.sup.4, C(.dbd.NOR.sup.6)R.sup.4, CO.sub.2 R.sup.8, CON(R.sup.4).sub.2, NR.sup.4 R.sup.5, S(O).sub.0-2 R.sup.6, and SO.sub.2 N(R.sup.4).sub.2 ;R.sup.4 is H or a substituent selected from the group consisting of C.sub.1-6 alkyl, aryl, C.sub.1-6 alkyl-aryl, heteroaryl, C.sub.1-6 alkyl-heteroaryl, cycloalkyl, C.sub.1-6 alkyl-cycloalkyl, heterocycloalkyl, and C.sub.1-6 alkyl-heterocycloalkyl, wherein said substituent is optionally substituted with R.sup.6, COR.sup.6, SO.sub.0-2 R.sup.6, CO.sub.2 R.sup.6, OR.sup.6, CONR.sup.8 R.sup.6, NR.sup.8 R.sup.6, halogen, CN, SO.sub.2 NR.sup.8 R.sup.6, or NO.sub.2, and for each case of N(R.sup.4).sub.2, The R.sup.4 groups are the same or different, or N(R.sup.4).sub.2 is heterocycloalkyl optionally substituted with R.sup.6, COR.sup.6, SO.sub.0-2 R.sup.6, CO.sub.2 R.sup.6, OR.sup.6, CONR.sup.8 R.sup.6, NR.sup.8 R.sup.6, halogen, CN, SO.sub.2 NR.sup.8 R.sup.6, or NO.sub.2 ;R.sup.5 is selected from the group consisting of COR.sup.4, CON(R.sup.4).sub.2, CO.sub.2 R.sup.6, and SO.sub.2 R.sup.6 ;R.sup.6 is selected from the group consisting of C.sub.1-6 alkyl, aryl, C.sub.1-6 alkyl-aryl, heteroaryl, and C.sub.1-6 alkyl-heteroaryl;R.sup.7 is selected from the group consisting of OR.sup.4, COR.sup.4, CO.sub.2 R.sup.8, CON(R.sup.4).sub.2, NR.sup.4 R.sup.5, S(O).sub.0-2 R.sup.6, SO.sub.2 N(R.sup.4).sub.2, halogen, CN, and cycloimidyl (optionally substituted with R.sup.8); andR.sup.8 is H or C.sub.1-6 alkyl;or a salt, solvate, hydrate, N-oxide or protected amino, protected carboxy, or proteted hydroxamic acid derivative thereof.