Patent ID: 6165999
Filing Date: 2000-12-26
Classification: A61P,C07C,C07D

Abstract:
A compound of the formula ##STR115## wherein X is hydrogen; R.sup.1 is methyl;R.sup.3 is a group of the formula ##STR116## wherein n is an integer from zero to four; R.sup.4 is hydrogen or (C.sub.1 -C.sub.6)alkyl;R.sup.5 is hydrogen; (C.sub.1 -C.sub.6)alkyl optionally substituted with one or more substituents independently selected from methylthio, (C.sub.1 -C.sub.6)alkoxy, amino, guanidino, amido, carboxamido, (C.sub.1 -C.sub.6)alkyl-C(O)--O--, (C.sub.1 -C.sub.6)alkyl-HN--C(O)--, di(C.sub.1 -C.sub.6)alkyl-N--C(O)--, di(C.sub.1 -C.sub.6)alkyl-N--C(O)--, (C.sub.1 -C.sub.6)alkyl-C(O)--NH-- ##STR117## (C.sub.1 -C.sub.6)alkyl-O--C(O)--, HC(O)--NH--, and HO--C(O)--; (C.sub.6 -C.sub.10)aryl-(CH.sub.2).sub.h --, wherein h is an integer from zero to three, wherein the (C.sub.6 -C.sub.10)aryl moiety of said (C.sub.6 -C.sub.10)aryl-(CH.sub.2).sub.h group may optionally be substituted with one or more substituents independently selected from halogen, hydroxy, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6)alkylsulfonyl, trihalo(C.sub.1 -C.sub.6)alkyl, amino, cyano, (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkyl-HN--C(O)--, di(C.sub.1 -C.sub.6)alkyl-N--C(O)--, (C.sub.1 -C.sub.6)alkyl-C(O)--NH--, ##STR118## (C.sub.1 -C.sub.6)alkyl-O--C(O)--, HC(O)--NH--, and HO--C(O)--; or (C.sub.3 -C.sub.6)cycloalkyl-(CH.sub.2).sub.j --, wherein j is an integer from zero to three, wherein the (C.sub.3 -C.sub.6)cycloalkyl moiety of said (C.sub.3 -C.sub.6)cycloalkyl-(CH.sub.2).sub.j -- group may optionally be substituted with one or more substituents independently selected from halogen, hydroxy, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6)alkylsulfonyl, trihalo(C.sub.1 -C.sub.6)alkyl, amino, cyano, (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, amido, carboxamido, (C.sub.1 -C.sub.6)alkyl-C(O)--O--, (C.sub.1 -C.sub.6)alkyl-HN--C(O)--, di(C.sub.1 -C.sub.6)alkyl-N--C(O)--, (C.sub.1 -C.sub.6)alkyl-C(O)--NH--, ##STR119## (C.sub.1 -C.sub.6)alkyl-O--C(O)--, HC(O)--NH--, and HO--C(O)--; R.sup.6 is halogen; amino; hydroxylamino; (C.sub.1 -C.sub.12)alkylamino optionally substitued with one or more substituents independently selected from halogen, hydroxy, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6)alkylsulfonyl, trihalo(C.sub.1 -C.sub.6)alkyl, amino, cyano, (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, amido, carboxamido, (C.sub.1 -C.sub.6)alkyl-C(O)--O--, (C.sub.1 -C.sub.6)alkyl-HN--C(O)--, di(C.sub.1 -C.sub.6)alkyl-N--C(O)--, (C.sub.1 -C.sub.6)alkyl-C(O)--NH--, ##STR120## (C.sub.1 -C.sub.6)alkyl-O--C(O)--, HC(O)--NH--, and HO--C(O)--; (C.sub.3 -C.sub.18)cycloalkylamino wherein the (C.sub.3 -C.sub.18)cycloalkyl moiety of said (C.sub.3 -C.sub.18)cycloalkyl amino group may optionally be substituted with one or more substituents independently selected from halogen, hydroxy, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6)alkylsulfonyl, trihalo(C.sub.1 -C.sub.6)alkyl, amino, cyano, (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, amido, carboxamido, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkyl-C(O)--O--, (C.sub.1 -C.sub.6)alkyl-HN--C(O)--, di(C.sub.1 -C.sub.6)alkyl-N--C(O)--, (C.sub.1 -C.sub.6)-alkyl-C(O)--NH--, ##STR121## (C.sub.1 -C.sub.6)alkyl-O--C(O)--, HC(O)--NH--, and HO--C(O)--; and wherein the amino moiety of said (C.sub.3 -C.sub.18)cycloalkylamino group may optionally be substituted with (C.sub.1 -C.sub.6)alkyl; di(C.sub.3 -C.sub.18)cycloalkyl-amino optionally substituted with one or more substituents independently selected from halogen, hydroxy, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6)alkylsulfonyl, trihalo(C.sub.1 -C.sub.6)alkyl, amino, cyano, (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, amido, carboxamido, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkyl-C(O)--O--, (C.sub.1 -C.sub.6)alkyl-HN--C(O)--, di(C.sub.1 -C.sub.6)alkyl-N--C(O)--, (C.sub.1 -C.sub.6)-alkyl-C(O)--NH--, ##STR122## (C.sub.1 -C.sub.6)alkyl-O--C(O)--, HC(O)--NH--, and HO--C(O)--; (C.sub.6 -C.sub.10)aryl-(CH.sub.2).sub.m -amino, wherein m is an integer from zero to three, wherein the (C.sub.6 -C.sub.10)aryl moiety of said (C.sub.6 -C.sub.10)aryl-(CH.sub.2 .sub.m -amino group may optionally be substituted with one or more substituents independently selected from halogen, hydroxy, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6)alkylsulfonyl, trihalo(C.sub.1 -C.sub.6)alkyl, amino, cyano, (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, amido, carboxamido, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkyl-C(O)--O--, (C.sub.1 -C.sub.6)alkyl-HN--C(O)--, di(C.sub.1 -C.sub.6)alkyl-N--C(O)--, (C.sub.1 -C.sub.6)-alkyl-C(O)--NH--, (C.sub.1 -C.sub.6)alkyl-C(O)--N--(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkyl-O--C(O)--, HC(O)--NH--, and HO--C(O)--; di(C.sub.1 -C.sub.8)alkyl-amino optionally substituted with one or more substituents independently selected from halogen, hydroxy, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6)alkylsulfonyl, trihalo(C.sub.1 -C.sub.6)alkyl, amino, cyano, (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, amido, carboxamido, (C.sub.1 -C.sub.6)alkyl-C(O)--O--, (C.sub.1 -C.sub.6)alkyl-HN--C(O)--, di(C.sub.1 -C.sub.6)alkyl-N--C(O)--, (C.sub.1 -C.sub.6)alkyl-C(O)--NH--, ##STR123## (C.sub.1 -C.sub.6)alkyl-O--C(O)--, HC(O)--NH--, and HO--C(O)--; (C.sub.2 -C.sub.10)azacycloalkyl optionally substituted with one or more substituents independently selected from halogen, hydroxy, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkylsulfonyl, trihalo(C.sub.1 -C.sub.6)alkyl, amino, cyano, (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, amido, carboxamido, (C.sub.1 -C.sub.6)alkyl-C(O)--O--, (C.sub.1 -C.sub.6)alkyl-HN--C(O)--, di(C.sub.1 -C.sub.6)alkyl-N--C(O)--, (C.sub.1 -C.sub.6)alkyl-C(O)--NH--, ##STR124## (C.sub.1 -C.sub.6)alkyl-O--C(O)--, HC(O)--NH--, and HO--C(O)--; carboxy(C.sub.1 -C.sub.6)alkylamino; (C.sub.1 -C.sub.6)alkyl-O--C(O)-amino; (C.sub.1 -C.sub.6)alkyl-O--C(O)--(C.sub.1 -C.sub.6)alkylamino; (C.sub.1 -C.sub.6)alkoxyamino; (C.sub.3 -C.sub.8)cycloalkoxyamino; (C.sub.6 -C.sub.10)aryl-(CH.sub.2).sub.t -oxyamino, wherein t is an integer from zero to three, wherein the (C.sub.6 -C.sub.10)aryl moiety of said (C.sub.6 -C.sub.10)aryl-(CH.sub.2).sub.t -oxyamino group may optionally be substituted with one or more substituents independently selected from halogen, (C.sub.1 -C.sub.6)alkoxy, trihalo(C.sub.1 -C.sub.6)alkyl, amino, cyano, (C.sub.1 -C.sub.6)alkylamino, hydroxy, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkylsulfonyl, di(C.sub.1 -C.sub.6)alkylamino, amido, carboxamido, (C.sub.1 -C.sub.6)alkyl-C(O)--O--, (C.sub.1 -C.sub.6)alkyl-HN--C(O)--, di(C.sub.1 -C.sub.6)alkyl-N--C(O)--, (C.sub.1 -C.sub.6)alkyl-C(O)--NH--, ##STR125## (C.sub.1 -C.sub.6)alkyl-O--(O)--, HC(O) --NH--, and HO--C(O)--; or a heterocycle-(CH.sub.2).sub.k -amino group, wherein k is an integer from zero to three, wherein said heterocycle is selected from pyrrolyl, furyl, thienyl, oxazolyl, isoxazolyl, imidazolyl, thiazolyl, isothiazolyl, pyrazolyl, triazolyl, tetrazolyl, 1,3,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,5-thiadiazolyl, 1,2,4-thiadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,2,4-triazinyl, 1,2,3-triazinyl, 1,3,5-triazinyl, 1,2,5-thiadiazinyl, 1,2,5-oxathiazinyl, 1,2,6-oxathiazinyl, benzoxazolyl, benzothiazolyl, benzisothiazolyl, benzisoxazolyl, benzimidazolyl, thianaphthenyl, isothianaphthenyl, benzofuranyl, isobenzofuranyl, chromenyl, isoindolyl, indolyl, indazolyl, isoquinolyl, quinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl and benzoxazinyl; wherein the heterocycle moiety of said heterocycle-(CH.sub.2).sub.k --group may be, where possible, substituted with from one to three substituents independently selected from (C.sub.1 -C.sub.6)alkyl, halogen, hydroxy, cyano, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6 alkylsulfonyl, trihalo(C.sub.1 -C.sub.6)alkyl, amino, (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, amido, carboxamido, (C.sub.1 -C.sub.6)alkyl-C(O)--O--, (C.sub.1 -C.sub.6)alkyl-HN--C(O)--, di(C.sub.1 -C.sub.6)alkyl-N--C(O)--, (C.sub.1 -C.sub.6)alkyl-C(O)--NH--, ##STR126## (C.sub.1 -C.sub.6)alkyl-O--C(O)--, HC(O)--NH--, and HO--(O)--; or R.sup.5 and R.sup.6 taken together may form a --(CH.sub.2).sub.p W(CH.sub.2).sub.q --ring wherein W is selected from ##STR127## --CH.sub.2 --, ##STR128## O, S, and ##STR129## wherein B is selected from hydrogen and (Chd 1--C.sub.3)alkyl, p is an integer from one to three, and q is an integer from one to three;R.sup.7 is hydrogen or (C.sub.1 -C.sub.6) alkyl;R.sup.8 is --CONH.sub.2 or --CONHCH.sub.2 -NR.sup.11 R.sup.12 ;R.sup.9 is hydrogen or (C.sub.1 -C.sub.6)alkyl;R.sup.11 is (C.sub.1 -C.sub.6)alkyl;R.sup.12 is (C.sub.1 -C.sub.6)alkyl; orR.sup.11 and R.sup.12 taken together form a --(CH.sub.2).sub.r --Y--(CH.sub.2).sub.s ring wherein Y is ##STR130## --CH.sub.2 --, ##STR131## oxygen, sulfur or --NOB; wherein B is selected from hydrogen and (C.sub.1 -C.sub.3)alkyl, r is an integer from one to three, and s is an integer from one to three;R.sup.13 is hydrogen, (C.sub.1 -C.sub.6)alkoxy-(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6) alkoxy, (C.sub.3 -C.sub.6)cycloalkyl, (C.sub.3 -C.sub.6)cycloalkylmethyl, or (C.sub.6 -C.sub.10)aryl optionally substituted with one or more substituents independently selected from fluoro, hydroxy, (C.sub.1 -C.sub.6)alkoxy, trihalo(C.sub.1 -C.sub.6)alkyl, amino, cyano, (C.sub.1 -C.sub.6)alkylamino, di(C.sub.1 -C.sub.6)alkylamino, amido, carboxamido, (C.sub.1 -C.sub.6)alkyl-C(O)--O--, (C.sub.1 -C.sub.6)alkyl-HN-C(O)--, di(C.sub.1 -C.sub.6)alkyl-N-C(O)--, (C.sub.1 -C.sub.6)alkyl-C(O)--NH--, ##STR132## (C.sub.1 -C.sub.6)alkyl-O--C(O)--, HC(O)--NH--, and HO--C(O)--; and the pharmacologically acceptable organic and inorganic salts or metal complexes.