Patent ID: 6114367
Filing Date: 2000-09-05
Classification: A61K,A61P,C07D

Abstract:
A method of inhibiting production of TNF (tumor necrosis factor) in a mammal in need thereof which method comprises administering to said mammal an effective amount of a compound selected from the group consisting of compounds of the formula (I) ##STR40## the racemic, racemic-diastereomeric mixtures and optical isomers of said compounds, and the pharmaceutically acceptable salts thereof, whereinX.sup.1 is --(CH.sub.2).sub.q OH, --CHOHR.sup.5 or --(CH.sub.2).sub.m CON(R.sup.6)(OH);wherein q and m are each independently 0 or an integer from 1 to 5; R.sup.5 is (C.sub.1 -C.sub.4)alkyl; and R.sup.6 is hydrogen or (C.sub.1 -C.sub.3)alkyl;n is 0, 1, 2 or 3;Y.sup.1 and Y.sup.2 are independently selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6)alkyl, optionally substituted phenylalkyl having 1 to 6 carbons in the alkyl portion, optionally substituted phenoxyalkyl having 1 to 6 carbons in the alkyl portion, (C.sub.3 -C.sub.7)cycloalkyl, difluoromethyl, trifluoromethyl, fluoro, chloro, bromo, iodo, --OR.sup.1 and --OR.sup.2 ;wherein the aromatic portion of the optionally substituted phenylalkyl, and the aromatic portion of the optionally substituted phenoxyalkyl are optionally independently substituted with (C.sub.1 -C.sub.4)alkyl, (C.sub.1 -C.sub.4)alkoxy, halogen or CF.sub.3 ;R.sup.1 is (C.sub.1 -C.sub.5)alkyl, phenylalkyl having one to four carbon atoms in the alkyl portion, fluoromethyl, difluoromethyl, trifluoromethyl, or --(CH.sub.2).sub.r -quinoline wherein r is 0 or an integer from 1 to 5;R.sup.2 is (C.sub.1 -C.sub.3)alkyl, (C.sub.3 -C.sub.7)cycloalkyl, alkoxyalkyl having 3 to 7 carbons in the alkoxy portion and 2 to 4 carbons in the alkyl portion, optionally substituted phenoxyalkyl having 2 to 6 carbons in the alkyl portion, optionally substituted phenylalkyl having 1 to 6 carbons in the alkyl portion, bicycloalkyl having 6 to 9 carbons or optionally substituted indanyl;wherein the aromatic portion of the optionally substituted phenylalkyl, the aromatic portion of the optionally substituted phenoxyalkyl and the optionally substituted indanyl are optionally substituted with (C.sub.1 -C.sub.4)alkyl, (C.sub.1 -C.sub.4)alkoxy, halogen or CF.sub.3 ;R.sup.3 is hydrogen, (C.sub.1 -C.sub.3)alkyl, fluoro(C.sub.1 -C.sub.3)alkyl having 1 to 3 fluoro atoms, mono-hydroxyalkyl having 1 to 3 carbons or alkoxyalkyl having 1 to 3 carbons in the alkyl portion and 1 to 3 carbons in the alkoxy portion;R.sup.4 is hydrogen, (C.sub.1 -C.sub.5)alkyl, fluoro(C.sub.1 -C.sub.5)alkyl having 1 to 3 fluoro atoms, mono-hydroxyalkyl having 1 to 3 carbons, phenyl, alkoxyalkyl having 1 to 3 carbons in the alkyl portion and 1 to 3 carbons in the alkoxy portion, aminoalkyl having 1 to 3 carbons, ##STR41## wherein X.sup.2 is (C.sub.1 -C.sub.3)alkyl and t is an integer from 1 to 3, N-alkylaminoalkyl having 1 to 3 carbons in the alkylamino portion and 1 to 3 carbons in the alkyl portion, (C.sub.3 -C.sub.7)cycloalkyl or N,N-dialkylaminoalkyl having a total of 2 to 6 carbons in the dialkylamino portion and 1 to 3 carbons in the alkyl portion;or R.sup.3 and R.sup.4 are taken together with the carbon atoms to which they are attached and form a carbocyclic ring having 4 to 7 carbon atoms.