Patent ID: 6211235
Filing Date: 2001-04-03
Classification: A61K,C07K

Abstract:
A compound of the formula: ##STR13##wherein R.sup.1 is selected from the group consisting of:(a) aryl group substituted with from 1 to 3 substituents selected from the group consisting of hydroxy, acyl, acyloxy, alkyl, alkoxy, alkenyl, alkynyl, amino, aminoacyl, alkaryl, aryl, aryloxy, carboxyl, carboxylalkyl, carboxylamido, cyano, halo, nitro, heteroaryl, and trihalomethyl provided that at least one of said substituents is selected from acyl, acyloxy, alkenyl, alkynyl, aminoacyl, alkaryl, aryloxy, carboxyl, carboxylalkyl, carboxylamido, fluoro and heteroaryl,(b) a heteroaryl group substituted with 1 to 3 substituents selected from the group consisting hydroxy, acyl, acyloxy, alkyl, alkoxy, alkenyl, alkynyl, amino, aminoacyl, alkaryl, aryl, aryloxy, carboxyl, carboxylalkyl, carboxylamido, cyano, halo, nitro, heteroaryl, and trihalomethyl provided that at least one of said substituents is selected from acyl, acyloxy, alkenyl, alkynyl, aminoacyl, alkaryl, aryloxy, carboxyl, carboxylalkyl, carboxylamido, fluoro and heteroaryl,(c) cycloalkenyl,(d) substituted alkyl provided that the substituent is not aryl and/or heteroaryl groups,(e) substituted alkenyl provided that the substituent is not aralkenyl or heteroaralkenyl,(f) substituted alkynyl provided that the substituent is not aralkynyl or heteroaralkynyl, and(h) heterocyclic;R.sup.2 is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclic;each R.sup.4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocyclic, substituted alkyl, substituted alkenyl and substituted alkynyl;each R.sup.5 is selected from hydrogen and methyl or together with R.sup.4 forms a cycloalkyl group of from 3 to 6 carbon atoms;X is --C(O)Y or --C(S)Y where Y is selected from the group consisting of(a) alkyl or cycloalkyl,(b) substituted alkyl with the proviso that the substitution on said substituted alkyl do not include .alpha.-haloalkyl, .alpha.-diazoalkyl, .alpha.--OC(O)alkyl or .alpha.--OC(O)aryl groups,(c) alkoxy or thioalkoxy,(d) substituted alkoxy or substituted thioalkoxy,(e) hydroxy,(f) aryl,(g) heteroaryl,(h) heterocyclic,(i) --NR'R"" where R' and R"" are independently selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, aryl, heteroaryl, heterocyclic, where one of R' or R"" is hydroxy or alkoxy, and where R' and R"" are joined to form a cyclic group having from 2 to 8 carbon atoms optionally containing 1 to 2 additional heteroatoms selected from oxygen, sulfur and nitrogen and optionally substituted with one or more alkyl, alkoxy or carboxyalkyl groups,(j) --NHSO.sub.2 --R.sup.8 where R.sup.8 is selected from alkyl, substituted alkyl, alkenyl, substituted alkenyl, cycloalkyl, aryl, heteroaryl and heterocyclic,(k) --NR.sup.9 NR.sup.10 R.sup.10 where R.sup.9 is hydrogen or alkyl, and each R.sup.10 is independently selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, cycloalkyl, aryl, heteroaryl, heterocyclic, and(l) --ONR.sup.9 [C(O)O].sub.z R.sup.10 where z is zero or one, R.sup.9 and R.sup.10 are as defined above;X can also be --CR.sup.6 R.sup.6 Y' where each R.sup.6 is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl and heterocyclic and Y' is selected from the group consisting of hydroxyl, amino, thiol, alkoxy, substituted alkoxy, phthalimido, --OC(O)R.sup.7, --SSR.sup.7, --SSC(O)R.sup.7 where R.sup.7 is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, aryl, heteroaryl and heterocyclic,X' is hydrogen, hydroxy or fluoro;X"" is hydrogen, hydroxy or fluoro, or X' and X"" together form an oxo group, andn is an integer equal to 1 or 2;with the proviso excluding the following known compounds:when R.sup.1 is o-fluorophenyl, R.sup.2 is 3,4-dichlorophenyl or ethyl, R.sup.4 and R.sup.5 are hydrogen, X' and X"" are hydrogen, then X is not --C(O)OCH.sub.3 ; andwhen n is 1, R.sup.1 is 5-fluoro-2-nitrophenyl, X' and X"" are hydrogen, R.sup.4 is 3-hydroxy-5-methoxyphenyl or 3-isopropoxy-5-methoxyphenyl, R.sup.5 is hydrogen, and X is --C())OCH.sub.3, then R.sup.2 is not benzyl.