Substituted 3-cyanoquinolines

A method of treating, inhibiting the growth of, or eradicating a neoplasm in a mammal in need thereof which comprises administering to said mammal an effective amount of a compound of Formula 1 having the structure

• 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;
• G1, G2, R1, and R4 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,
• R8R9—CH—M—(C(R6)2)k—Y—, R7—(C(R6)2)g—Y—, R7—(C(R6)2)p—M—(C(R6)2)k—Y—, or Het-(C(R6)2)q—W—(C(R6)2)k—Y— with the proviso that either G1 or G2 or both G1 and G2 must be a radical selected from the group
• R8R9—CH—M—(C(R6)2)k—Y—, R′7—(C(R6)2)g—Y—, R7—(C(R6)2)p—M—(C(R6)2)k—Y—, Het-(C(R6)2)q—W—(C(R6)2)k—Y—, or
• Y is a divalent radical selected from the group consisting of
• R7 is —NR6R6, -J, —OR6, —N(R6)3+, or —NR6(OR6);
• R′7 is —NR6(OR6), —N(R6)3+, 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 >NR6, —O—, >N—(C(R6)2)pNR6R6, or >N—(C(R6)2)p—OR6;
• W is >NR6, —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
• wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R6, optionally mono- or di-substituted on carbon with hydroxy, —N(R6)2, or —OR6, optionally mono or di-substituted on carbon with the mono-valent radicals —(C(R6)2)sOR6 or —(C(R6)2)sN(R6)2, or optionally mono or di-substituted on a saturated carbon with divalent radicals —O— or —O(C(R6)2)sO—;
• R6 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;
• R2, is selected from the group consisting of
• R3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms,
• R7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—;
• with the proviso that at least one of the R3 groups is selected from the group
• R′7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—;
• with the proviso that for said at least one R3 group the moiety Het-(C(R6)2)q—W—(C(R6)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;
• R5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms,
• R7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—;
• R8, and R9 are each, independently, —(C(R6)2)rNR6R6, or —(C(R6)2)rOR6;
• 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 that
• when R6 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 that
• when Y is —NR6— and R7 is —NR6R6, —N(R6)3+, or —NR6(OR6), then g=2-6;
• when M is —O— and R7 is -OR6, then p=1-4;
• when Y is —NR6—, 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 —NR6—, then k=2-4.

A method of treating, inhibiting the progression of, or eradicating polycystic kidney disease in a mammal in need thereof which comprises administering to said mammal an effective amount of a compound of formula 1 having the structure

• 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;
• G1, G2, R1, and R4 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,
• R8R9—CH—M—(C(R6)2)k—Y—, R7—(C(R6)2)g—Y—, R7—(C(R6)2)p—M—(C(R6)2)k—Y—, or Het-(C(R6)2)q—W—(C(R6)2)k—Y— with the proviso that either G1 or G2 or both G1 and G2 must be a radical selected from the group
• R8R9—CH—M—(C(R6)2)k—Y—, R′7—(C(R6)2)g—Y—, R7—(C(R6)2)p—M—(C(R6)2)k—Y—, Het-(C(R6)2)q—W—(C(R6)2)k—Y—, or R2—NH—;
• Y is a divalent radical selected from the group consisting of
• R7 is —NR6R6, —J, —OR6, —N(R6)3+, or —NR6(OR6),
• R′7 is —NR6(OR6), —N(R6)3+, 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 >NR6, —O—, >N—(C(R6)2)pNR6R6, or >N—(C(R6)2)p—OR6;
• W is >NR6, —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
• wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R6, optionally mono- or di-substituted on carbon with hydroxy, —N(R6)2, or —OR6, optionally mono or di-substituted on carbon with the mono-valent radicals —(C(R6)2)sOR6 or —(C(R6)2)sN(R6)2, or optionally mono or di-substituted on a saturated carbon with divalent radicals —O— or —O(C(R6)2)sO—;
• R6 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;
• R2, is selected from the group consisting of
• R3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms,
• R7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—;
• with the proviso that at least one of the R3 groups is selected from the group
• R′7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—;
• with the proviso that for said at least one R3 group the moiety Het-(C(R6)2)q—W—(C(R6)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;
• R5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms,
• R7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—;
• R8, and R9 are each, independently, —(C(R6)2)rNR6R6, or —(C(R6)2)rOR6;
• 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 that
• when R6 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 that
• when Y is —NR6— and R7 is —NR6R6, —N(R6)3+, or —NR6(OR6), then g=2-6;
• when M is —O— and R7 is —OR6, then p=1-4;
• when Y is —NR6—, 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 —NR6—, then k=2-4.

A pharmaceutical composition which comprises a compound of formula 1 having the structure

• 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;
• G1, G2, R1, and R4 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,
• R8R9—CH—M—(C(R6)2)k—Y—, R7—(C(R6)2)g—Y—, R7—(C(R6)2)p—M—(C(R6)2)k—Y—, or Het-(C(R6)2)q—W—(C(R6)2)k—Y— with the proviso that either G1 or G2 or both G1 and G2 must be a radical selected from the group
• R8R9—CH—M—(C(R6)2)k—Y—, R′7—(C(R6)2)g—Y—, R7—(C(R6)2)p—M—(C(R6)2)k—Y—, Het-(C(R6)2)q—W—(C(R6)2)k—Y—, or
• Y is a divalent radical selected from the group consisting of
• R7 is —NR6R6, -J, —OR6, —N(R6)3+, or —NR6(OR6);
• R′7 is —NR6(OR6), —N(R6)3+, 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 >NR6, —O—, >N—(C(R6)2)pNR6R6, or >N—(C(R6)2)p—OR6,
• W is >NR6, —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
• wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R6, optionally mono- or di-substituted on carbon with hydroxy, —N(R6)2, or —OR6, optionally mono or di-substituted on carbon with the mono-valent radicals —(C(R6)2)sOR6 or —(C(R6)2)sN(R6)2, or optionally mono or di-substituted on a saturated carbon with divalent radicals —O— or —O(C(R6)2)sO—;
• R6 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;
• R2, is selected from the group consisting of
• R3 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms,
• R7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—;
• with the proviso that at least one of the R3 groups is selected from the group
• R′7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—;
• with the proviso that for said at least one R3 group the moiety Het-(C(R6)2)q—W—(C(R6)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;
• R5 is independently hydrogen, alkyl of 1-6 carbon atoms, carboxy, carboalkoxy of 1-6 carbon atoms, phenyl, carboalkyl of 2-7 carbon atoms,
• R7—(C(R6)2)s—, R7—(C(R6)2)p—M—(C(R6)2)r—, R8R9—CH—M—(C(R6)2)r—, or Het-(C(R6)2)q—W—(C(R6)2)r—;
• R8, and R9 are each, independently, —(C(R6)2)rNR6R6, or —(C(R6)2)rOR6;
• 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 that
• when R6 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 that
• when Y is —NR6— and R7 is —NR6R6, —N(R6)3+, or —NR6(OR6), then g=2-6;
• when M is —O— and R7 is -OR6, then p=1-4;
• when Y is —NR6—, 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 —NR6—, then k=2-4.