Patent ID: 6297258
Filing Date: 2001-10-02
Classification: C07D

Abstract:
A compound of Formula 1 having the structure: ##STR44##wherein:X is cycloalkyl of 3 to 7 carbon atoms, which may be optionally substituted with one or more alkyl of 1 to 6 carbon atom groups; or is a pyridinyl, pyrimidinyl, or phenyl ring wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono- di-, or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalky of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 2-9 carbon atoms, N,N-dialkylaminoalkoxy of 3-10 carbon atoms, mercapto, methylmercapto, and benzoylamino;Z is --NH--, --O--, --S--, or --NR--;R is alkyl of 1-6 carbon atoms, or carboalkyl of 2-7 carbon atoms;G.sub.1, G.sub.2, R.sub.1, and R.sub.4 are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-6 carbon atoms, hydroxymethyl, halomethyl, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkenoyloxymethyl of 4-9 carbon atoms, alkynoyloxymethyl of 4-9 carbon atoms, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulphonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, hydroxy, trifluoromethyl, trifluoromethoxy, cyano, nitro, carboxy, carboalkoxy of 2-7 carbon atoms, carboalkyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzyl, amino, hydroxyamino, alkoxyamino of 1-4 carbon atoms, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, ##STR45##R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.k --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.g --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.k --Y--, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.k --Y--with the proviso that either G.sub.1 or G.sub.2 or both G.sub.1 and G.sub.2 must be a radical selected from the group ##STR46##R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.k --Y--, R'.sub.7 --(C(R.sub.6).sub.2).sub.g --Y--, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.k --Y--, Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.k --Y--, or ##STR47##Y is a divalent radical selected from the group consisting of ##STR48##R.sub.7 is --NR.sub.6 R.sub.6, --J, --OR.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6 (OR.sub.6);R'.sub.7 is --N(OR.sub.6), --N(R.sub.6).sub.3.sup.+, alkenoxy of 1-6 carbon atoms, alkynoxy of 1-6 carbon atoms,N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms,N-alkyl-N-alkynylamino of 4 to 12 carbon atoms, N-alkenyl-N-alkynylamino of 4 to 12 carbon atoms, or N,N-dialkynylamino of 6-12 carbon atoms with the proviso that the alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom;M is >NR.sub.6, --O--, >N--(C(R.sub.6).sub.2).sub.p NR.sub.6 R.sub.6, or >N--(C(R.sub.6).sub.2).sub.p --OR.sub.6 ;W is >NR.sub.6, --O-- or is a bond;Het is a heterocycle selected from the group consisting of morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, pyridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, thiazole, thiazolidine, tetrazole, piperazine, furan, thiophene, tetrahydrothiophene, tetrahydrofuran, dioxane, 1,3-dioxolane, tetrahydropyran, and ##STR49##wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R.sub.6, optionally mono- or di-substituted on carbon with hydroxy, --N(R.sub.6).sub.2, or --OR.sub.6, optionally mono or di-substituted on carbon with the mono-valent radicals --(C(R.sub.6).sub.2).sub.S OR.sub.6 or --(C(R.sub.6).sub.2).sub.S N(R.sub.6).sub.2, or optionally mono or di-substituted on a saturated carbon with divalent radicals --O-- or --O(C(R.sub.6).sub.2).sub.S O--;R.sub.6 is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, carboalkyl of 2-7 carbon atoms, carboxyalkyl (2-7 carbon atoms), phenyl, or phenyl optionally substituted with one or more halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, carboalkoxy of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, or alkyl of 1-6 carbon atoms;R.sub.2, is selected from the group consisting of ##STR50## ##STR51##R.sub.3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR52##R.sub.7 --(C(R.sub.6).sub.2).sub.s --, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.r --, R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.r --, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.r --;with the proviso that at least one of the R.sub.3 groups is selected from the group ##STR53##R'.sub.7 --(C(R.sub.6).sub.2).sub.s --, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.r --, R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.r --, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.r --;with the proviso that for said at least one R.sub.3 group the moiety Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2)r-- cannot be morpholino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, piperidino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, N-alkyl piperidino-N-alkyl wherein either alkyl group is 1-6 carbon atoms, or azacycloalkyl-N-alkyl of 3-11 carbon atoms;R.sub.5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms, ##STR54##R.sub.7 --(C(R.sub.6).sub.2).sub.s --, R.sub.7 --(C(R.sub.6).sub.2).sub.p --M--(C(R.sub.6).sub.2).sub.r --, R.sub.8 R.sub.9 --CH--M--(C(R.sub.6).sub.2).sub.r --, or Het-(C(R.sub.6).sub.2).sub.q --W--(C(R.sub.6).sub.2).sub.r --;R.sub.8, and R.sub.9 are each, independently, --(C(R.sub.6).sub.2).sub.r NR.sub.6 R.sub.6, or --(C(R.sub.6).sub.2).sub.r OR.sub.6 ;J is independently hydrogen, chlorine, fluorine, or bromine;Q is alkyl of 1-6 carbon atoms or hydrogen;a=0 or 1;g=1-6;k=0-4;n is 0-1;p=2-4;q=0-4;r=1-4;s=1-6;u 0-4 and v=0-4, wherein the sum of u+v is 2-4;or a pharmaceutically acceptable salt thereof,provided thatwhen R.sub.6 is alkenyl of 2-7 carbon atoms or alkynyl of 2-7 carbon atoms, such alkenyl or alkynyl moiety is bound to a nitrogen or oxygen atom through a saturated carbon atom;and further provided thatwhen Y is --NR.sub.6 -- and R.sub.7 is --NR.sub.6 R.sub.6, --N(R.sub.6).sub.3.sup.+, or --NR.sub.6 (OR.sub.6), then g 2-6;when M is --O-- and R.sub.7 is --OR.sub.6, then p=1-4;when Y is --NR.sub.6 --, then k=2-4;when Y is --O-- and M or W is --O--, then k=1-4;when W is not a bond with Het bonded through a nitrogen atom, then q=2-4;and when W is a bond with Het bonded through a nitrogen atom and Y is --O-- or --NR.sub.6 --, then k=2-4.