Patent ID: 6514988
Filing Date: 2003-02-04
Classification: A61P,C07D

Abstract:
A method for controlling pregnancy in a mammal in need thereof, comprising administering to said mammal an gonadotropin-releasing hormone antagonistic amount of a pharmaceutical composition comprising a compound of the formula: whereinR1 is a group of the formula: R9â€”(CH2)mâ€”, wherein R9 is a group bonded through a nitrogen atom of the formula: â€”NR22R23; m is 0 to 3; R2 is a group of the formula: R10â€”Aâ€”wherein R10 is phenyl which may be substituted by 1 to 5 substituents selected from the group consisting of (i) halogen, (ii) C1-8 alkyl which may be substituted by 1 to 3 of halogen, (iii) C1-8 alkoxy which may be substituted by 1 to 3 of halogen, (iv) C1-8 alkylthio which may be substituted by 1 to 3 of halogen, (v) C1-8 aralkyloxy, (vi) hydroxy, (vii) carboxy, (vii) C1-6 alkoxy-carbonyl, (ix) cyano, (x) nitro, (xi) amido, and (xii) mono- or di-C1-6 alkylcarbamoyl; A is (i) a chemical bond, (ii) C1-4 alkylene, (iii) vinylene, (iv) butadienylene, (v) a group of the formula: â€”(CH2)cNR24â€” wherein c is 0 to 3; R24 is hydrogen or C1-6 alkyl, (vi) â€”COâ€”, (vii) a group of the formula: â€”CONR22, (viii) â€”Oâ€”(ix) â€”Sâ€”, or (x) a group of the formula: â€”NR22S(O)eâ€” wherein e is 0 to 2; wherein R22 is (1â€²) hydrogen, (2â€²) C1-6 alkyl, (3â€²) C3-6 cycloalkyl, (4â€²) C6-14 aryl, (5â€²) a 5-membered cyclic group selected from the group consisting of 2- or 3-thienyl, 2- or 3-furyl, 2- or 3-pyrrolyl, 2-, 3- or 4-pyridyl, 2-, 4- or 5-oxazolyl, 2-, 4- or 5-thiaxolyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-imidazolyl, 3-, 4- or 5-isoxazolyl, 3-, 4- or 5-isothiazol, 3- or 5-(1,2,4-oxadiazolyl), 1,3,4-oxadiazolyl, 3- or 5-(1,2,4-thiadiazolyl), 1,3,4-thiadiazolyl, 4- or 5-(1,2,3-thiadiazolyl), 1,2,5-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl and 1H- or 2H-tetrazolyl, (6â€²) a 6-membered cyclic group selected from the group consisting of N-oxido-2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, N-oxido-2-, 4- or 5-pyrimidinyl, 2- or 3-thiomorpholinyl, 2- or 3-morpholinyl, oxoimidazinyl, dioxotriazinyl, pyrrolidinyl, piperidinyl, pyranyl, thiopyranyl, 1,4-oxazinyl, 1,4-thiazinyl, 1,3-thiazinyl, 2- or 3-piperazinyl, triazinyl, oxotriazinyl, 3- or 4-pyridazinyl, pyrazinyl and N-oxido-3- or 4-pyridazinyl, or (7â€²) a 5- to 8-membered cyclic group or condensed ring thereof, selected from the group consisting of benzofuryl, benzothiazolyl, benzoxazolyl, tetrazolo[1,5-b]pyridazinyl, triazolo[4,5-b]pyridazinyl, benzoimidazolyl, quinolyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, indolizinyl, quinolizinyl, 1,8-naphthylizinyl, purinyl, pteridinyl, dibenzofuranyl, carbazolyl, acrydinyl, phenanthridinyl, chromanyl, benzoxazinyl, phenazinyl, phenothiazinyl and phenoxazinyl; R23 is hydrogen or C1-6 alkyl; or R22 and R23 form, taken together with the adjacent nitrogen atom, 1H-1-pyrrolyl, 1-imidazolyl, pyrazolyl, indolyl, 1H-1-indazolyl, 7-purinyl, 1-pyrrolidinyl, 1-pyrrolinyl, 1-imidazolidinyl, pyrazolidinyl, piperazinyl, pyrazolidinyl, 4-morpholinyl or 4-thiomorpholinyl, and the above group of â€”NR22R23 is optionally substituted by 1 to 6 substituents selected from the group consisting of(1â€²) C1-6 alkyl, (2â€²) C2-6 alkenyl, (3â€²) C2-6 alkynyl, (4â€²) C3-6 cycloalkyl, (5â€²) C5-7 cycloalkenyl, (6â€²) C7-11 aralkyl, (7â€²) C6-14 aryl, (8â€²) C1-6 alkoxy, (9â€²) C6-14 aryloxy, (10â€²) C1-6 alkanoyl, (11â€²) C6-14 aryl-carbonyl, (12â€²) C1-6 alkanoyloxy, (13â€²) C6-14 aryl-carbonyloxy, (14â€²) carboxy, (15â€²) C1-6 alkoxy-carbonyl, (16â€²) carbamoyl, (17â€²) N-mono-C1-4 alkylcarbamoyl, (18â€²) N,N-di-C1-4 alkylcarbamoyl, (19â€²) cyclic aminocarbonyl selected from the group consisting of 1-aziridinylcarbonyl, 1-azetidinylcarbonyl, 1-pyrrolidinylcarbonyl, 1-piperidinylcarbonyl, N-methylpiperazinylcarbonyl and morpholinocarbonyl, (20â€²) halogen, (21â€²) mono- to tri-halogeno-C1-4 alkyl, (22â€²) oxo, (23â€²) amidino, (24â€²) imino, (25â€²) amino, (26â€²) mono- or di-C1-4 alkylamino, (27â€²) 3- to 6-membered cyclic amino selected from the group consisting of aziridinyl, azetidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, imidazolyl, pyrazolyl, imidazolidinyl, piperidino, morpholino, dihydropyridyl, N-methylpiperazinyl and N-ethylpiperazinyl, (28â€²) C1-6 alkanoylamino, (29â€²) benzamido, (30â€²) carbamoylamino, (31â€²) N-C1-4 alkylcarbamoylamino, (32â€²) N,N-di-C1-4 alkylcarbamoylamino, (33â€²) C1-3 alkylenedioxy, (34â€²) â€”B(OH)2, (35â€²) hydroxy, (36â€²) epoxy, (37â€²) nitro, (38â€²) cyano, (39â€²) mercapto, (40â€²) sulfo, (41â€²) sulfino, (42â€²) phosphono, (43â€²) sulfamoyl, (44â€²) C1-6 alkylsulfamoyl, (45â€²) di-C1-6 alkylsulfamoyl, (46â€²) C1-6 alkylthio, (47â€²) phenylthio, (48â€²) C1-6 alkylsulfinyl, (49â€²) phenylsulfinyl, (50â€²) C1-6 alkylsulfonyl, and (51â€²) phenylsulfonyl,R3 is a group of the formula: wherein R7 is (i) hydrogen, (ii) a group bonded through a carbon atom selected from the group consisting of (1) C1-6 alkyl, (2) C3-6 cycloalkyl, (3) C1-3 alkoxy-C1-6 alkyl, (4) hydroxy-C1-6 alkyl, (5) C2-6 alkenyl, (6) formyl, (7) carboxyl, (8) C1-6 alkoxycarbonyl, (9) cyano, (10) amido, (11) mono- or di-C1-6 alkylcarbamoyl, (12) amidino, (13) C6-14 aryl, (14) C7-20 aralkyl, (15) a 5-membered cyclic group selected from the group consisting of 2- or 3-thienyl, 2- or 3-furyl, 2- or 3-pyrrolyl, 2-, 3- or 4-pyridyl, 2-, 4- or 5-oxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-imidazolyl, 3-, 4- or 5-isoxazolyl, 3-, 4- or 5-isothiazolyl, 3- or 5-(1,2,4-oxadiazolyl), 1,3,4-oxadiazolyl, 3- or 5-(1,2,4-thiadiazolyl), 1,3,4-thiadiazolyl, 4- or 5-(1,2,3-thiadiazolyl), 1,2,5-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl and 1H- or 2H-tetrazolyl, (16) a 6-membered cyclic group selected from the group consisting of N-oxido-2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, N-oxido-2-, 4- or 5-pyrimidinyl, 2- or 3-thiomorpholinyl, 2- or 3-morpholinyl, oxoimidazinyl, dioxotriazinyl, pyrrolidinyl, piperidinyl, pyranyl, thiopyranyl, 1,4-oxazinyl, 1,4-thiazinyl, 1,3-thiazinyl, 2- or 3-piperazinyl, triazinyl, oxotriazinyl, 3- or 4-pyridazinyl, pyrazinyl and N-oxido-3- or 4-pyridazinyl, and (17) a 5- to 8-membered cyclic group or condensed ring thereof, selected from the group consisting of benzofuryl, benzothiazolyl, benzoxazolyl, tetrazolo[1,5-b]pyridazinyl, triazolo[4,5-b]pyridazinyl, benzoimidazolyl, quinolyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, indolizinyl, quinolizinyl, 1,8-naphthylizinyl, purinyl, pteridinyl, dibenzofuranyl, carbazolyl, acrydinyl, phenanthridinyl, chromanyl, benzoxazinyl, phenazinyl, phenothiazinyl and phenoxazinyl, each of which (1) to (17) is optionally substituted by 1 to 6 substituents selected from the group consisting of (a) C6-14 aryl which optionally substituted by 1 to 4 substituents selected from the group consisting of hydroxy, amino, mono- or di-C1-6 alkylamino, C1-6 alkoxy and halogen, (b) mono- or di-C1-6 alkylamino, (c) C1-4 acylamino, (d) hydroxy, (e) carboxy, (f) nitro, (g) C1-6 alkoxy, (h) C1-6 alkyl-carbonyloxy, (i) halogen and (j) a group of the formula: â€”NR22R23; wherein R22 and R23 areas defined above, (iii) a group bonded through a nitrogen atom, of the formula: â€”NR22R23 wherein R22 and R23 are as defined above, (iv) a group bonded through an oxygen atom selected from the group consisting of (a) hydroxy, (b) C1-6 alkoxy, (c) C3-6 cycloalkoxy, (d) C6-14 aryloxy, (e) C7-11 aralkyloxy, (f) hydroxy substituted by a 5-membered cyclic group selected from the group consisting of 2- or 3-thienyl, 2- or 3-furyl, 2- or 3-pyrrolyl, 2-, 3- or 4-pyridyl, 2-, 4- or 5-oxazolyl, 2-, 4- or 5-thiazolyl 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-imidazolyl, 3-, 4- or 5-isoxazolyl, 3-, 4- or 5-isothiazolyl, 3- or 5-(1,2,4-oxadiazolyl), 1,3,4-oxadiazolyl, 3- or 5-(1,2,4-thiadiazolyl), 1,3,4-thiadiazolyl, 4- or 5-(1,2,3-thiadiazolyl), 1,2,5-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl and 1H- or 2H-tetrazolyl, (g) hydroxy substituted by a 6-membered cyclic group selected from the group consisting of N-oxido-2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, N-oxido-2-, 4- or 5-pyrimidinyl, 2- or 3-thiomorpholinyl, 2- or 3-morpholinyl, oxoimidazinyl, dioxotriazinyl, pyrrolidinyl, piperidinyl, pyranyl, thiopyranyl, 1,4-oxazinyl, 1,4-thiazinyl, 1,3-thiazinyl, 2- or 3-piperazinyl, triazinyl, oxotriazinyl, 3- or 4-pyridazinyl, pyrazinyl and N-oxido-3- or 4-pyridazinyl, or (h) hydroxy substituted by a 5- to 8-membered cyclic group or a condensed ring thereof, selected from the group consisting of benzofuryl, benzothiazolyl, benzoxazolyl, tetrazolo[1,5-b]pyridazinyl, triazolo[4,5-b]pyridazinyl, benzoimidazolyl, quinolyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, indolizinyl, quinolizinyl, 1,8-naphthylizinyl, purinyl, pteridinyl, dibenzofuranyl, carbazolyl, acrydinyl, phenanthridinyl, chromanyl, benzoxazinyl, phenazinyl, phenothiazinyl and phenoxazinyl, each of which (b) to (h) is optionally substituted by 1 to 6 substituents selected from the group consisting of (1) C1-6 alkyl, (2) C2-6 alkenyl, (3) C2-6 alkynyl, (4) C3-6 cycloalkyl, (5) C5-7 cycloalkenyl, (6) C7-11 aralkyl, (7) C6-14 aryl, (8) C1-6 alkoxy, (9) C6-14 aryloxy (10) C1-6 alkanoyl, (11) C6-14 aryl-carbonyl, (12) C1-6 alkanoyloxyl, (13) C6-14 aryl-carbonyloxy, (14) carboxy, (15) C1-6 alkoxy-carbonyl, (16) carbamoyl, (17) N-mono-C1-4 alkylcarbamoyl, (18) N,N-di-C1-4 alkylcarbamoyl, (19) cyclic aminocarbonyl selected from the group consisting of 1-aziridinylcarbonyl, 1-azetidinylcarbonyl, 1-pyrrolidinylcarbonyl, 1-piperidinylcarbonyl, N-methylpiperazinylcarbonyl and morpholinocarbonyl, (20) halogen, (21) mono- or tri-halogeno-C1-4 alkyl, (22) oxo, (23) amidino, (24) imino, (25) amino, (26) mono- or di-C1-4 alkylamino, (27) 3 - to 6-membered cyclic amino selected from the group consisting of aziridinyl, azetidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, imidazolyl, pyrazolyl, imidazolidinyl, piperidino, morpholino, dihydropyridyl, N-methylpiperazinyl and N-ethylpiperazinyl, (28) C1-6 alkanoylamino, (29) benzamido, (30) carbamoylamino, (31) N-C1-4 alkylcarbamoylamino, (32) N,N-di-C1-4 alkylcarbamoylamino, (33) C1-3 alkylenedioxy, (34) â€”B(OH)2, (35) hydroxy, (36) epoxy, (37) nitro, (38) cyano, (39) mercapto, (40) sulfo, (41) sulfino, (42) phosphono, (43) sulfamoyl, (44) C1-6 alkylsulfamoyl, (45) di-C1-6 alkylsulfamoyl, (46) C1-6 alkylthio, (47) phenylthio, (48) C1-6 alkylsulfinyl, (49) phenylsulfinyl, (50) C1-6 alkylsulfonyl, and (51) phenylsulfonyl, or (v) a group bonded through a sulfur atom selected from the group consisting of (a) mercapto, (b) C1-6 alkylthio, (c) C3-6 cycloalkylthio, (d) C6-14 arylthio, (e) C7-20 aralkylthio, (f) thio substituted by a 5-membered cyclic group selected from the group consisting of 2- or 3-thienyl, 2- or 3-furyl, 2- or 3-pyrrolyl, 2-, 3- or 4-pyridyl, 2-, 4- or 5-oxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-imidazolyl, 3-, 4- or 5-isoxazolyl, 3-, 4- or 5-isothiazolyl, 3- or 5-(1,2,4-oxadiazolyl), 1,3,4-oxadiazolyl, 3- or 5-(1,2,4-thiadiazolyl), 1,3,4-thiadiazolyl, 4- or 5-(1,2,3-thiadiazolyl), 1,2,5-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl and 1H- or 2H-tetrazolyl, (g) thio substituted by a 6-membered cyclic group selected from the group consisting of N-oxido-2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, N-oxido-2-, 4- or 5-pyrimidinyl, 2- or 3-thiomorpholinyl, 2- or 3-morpholinyl, oxoimidazinyl, dioxotriazinyl, pyrrolidinyl, piperidinyl, pyranyl, thiopyranyl, 1,4-oxazinyl, 1,4-thiazinyl, 1,3-thiazinyl, 2- or 3-piperazinyl, triazinyl, oxotriazinyl, 3- or 4-pyridazinyl, pyrazinyl and N-oxido-3- or 4-pyridazinyl, or (h) thio substituted by a 5- to 8-membered cyclic group or a condensed ring thereof, selected from the group consisting of benzofuryl, benzothiazolyl, benzoxazolyl, tetrazolo[1,5-b]pyridazinyl, triazolo[4,5-b]pyridazinyl, benzoimidazolyl, quinolyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, indolizinyl, quinolizinyl, 1,8-naphthylizinyl, purinyl, pteridinyl, dibenzofuranyl, carbazolyl, acrydinyl, phenanthridinyl, chromanyl, benzoxazinyl, phenazinyl, phenothiazinyl and phenoxazinyl, each of which (b) to (h) is optionally substituted by 1 to 6 substituents selected from the group consisting of (1) C1-6 alkyl, (2) C2-6 alkenyl, (3) C2-6 alkynyl, (4) C3-6 cycloalkyl, (5) C5-7 cycloalkenyl, (6) C7-11 aralkyl, (7) C6-14 aryl, (8) C1-6 alkoxy, (9) C6-14 aryloxy, (10) C1-6 alkanoyl, (11) C6-14 aryl-carbonyl, (12) C1-6 alkanoyloxyl, (13) C6-14 aryl-carbonyloxy, (14) carboxy, (15) C1-6 alkoxy-carbonyl, (16) carbamoyl, (17) N-mono-C1-4 alkylcarbamoyl, (18) N,N-di-C1-4 alkylcarbamoyl, (19) cyclic aminocarbonyl selected from the group consisting of 1-aziridinylcarbonyl, 1-azetidinylcarbonyl, 1-pyrrolidinylcarbonyl, 1-piperidinylcarbonyl, N-methylpiperazinylcarbonyl and morpholinocarbonyl, (20) halogen, (21) mono- or tri-halogeno-C1-4 alkyl, (22) oxo, (23) amidino, (24) imino, (25) amino, (26) mono- or di-C1-4 alkylamino, (27) 3- to 6-membered cyclic amino selected from the group consisting of aziridinyl, azetidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, imidazolyl, pyrazolyl, imidazolidinyl, piperidino, morpholino, dihydropyridyl, N-methylpiperazinyl and N-ethylpiperazinyl, (28) C1-6 alkanoylamino, (29) benzamido, (30) carbamoylamino, (31) N-C1-4 alkylcarbamoylamino, (32) N,N-di-C1-4 alkylcarbamoylamino, (33) C1-3 alkylenedioxy, (34) â€”B(OH)2, (35) hydroxy, (36) epoxy, (37) nitro, (38) cyano, (39) mercapto, (40) sulfo, (41) sulfino, (42) phosphono, (43) sulfamoyl, (44) C1-6 alkylsulfamoyl, (45) di-C1-6 alkylsulfamoyl, (46) C1-6 alkylthio, (47) phenylthio, (48) C1-6 alkylsulfinyl, (49) phenylsulfinyl, (50) C1-6 alkylsulfonyl, and (51) phenylsulfonyl; and R8 is (i) hydrogen, (ii) halogen, (iii) nitro, (iv) cyano, or (v) a hydrocarbon group selected from the group consisting of C1-15 alkyl, C3-8 cycloalkyl, C2-10 alkenyl, C2-10 alkynyl and C1-6 alkoxy, which hydrocarbon group is optionally substituted by 1 to 4 substituents selected from the group consisting of (1) nitro, (2) hydroxy, (3) oxo, (4) thioxo, (5) cyano, (6) carbamoyl, (7) carboxy, (8) C1-4 alkoxy-carbonyl, (9) sulfo, (10) halogen, (11) C1-4 alkoxy, (12) C1-4 alkylthio, (13) amino, (14) C1-6 alkanoylamino, (15) mono- or di-C1-4 alkylamino, (16) C1-4 alkanoyl, (17) 5- or 6-membered heterocyclic group selected from the group consisting of 2- or 3-thienyl, 2- or 3-furyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-imidazolyl, 1,2,3- or 1,2,4-triazolyl, 1H- or 2H-tetrazolyl, 2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidyl, 3- or 4-pyridazinyl, quinolyl, isoquinolyl and indolyl, which heterocyclic group is optionally substituted by 1 to 4 substituents selected from the group consisting of halogen and C1-4 alkyl, and (18) C1-4 haloalkyl; R4 is (i) hydrogen, (ii) formyl, (iii) cyano, (iv) C1-6 alkyl substituted by (1) a group bonded through a sulfur atom as defined above or (2) a hydroxy group which may be substituted by (a) C1-6 alkyl which may be substituted by 1 to 4 substituents selected from the group consisting of halogen, C6-10 aryl, C7-12 aralkyl and nitro, (b) C6-10 aryl which may be substituted by 1 to 4 substituents selected from the group consisting of halogen, C1-6 alkyl and C6-10 aryl, (c) C7-12 aralkyl which may be substituted by 1 to 4 substituents selected from the group consisting of halogen, C1-6 alkyl, C6-10 aryl, C7-12 aralkyl and nitro, (d) C1-6 alkyl-carbonyl which may be substituted by 1 to 3 substituents selected from the group consisting of formyl, halogen, C1-6 alkyl, C6-10 aryl, C7-12 aralkyl and nitro, (e) C6-10 aryloxy-carbonyl which may be substituted by 1 to 4 substituents selected from the group consisting of halogen, C1-6 alkyl, C6-10 aryl, C7-12 aralkyl and nitro, (f) C6-10 aryl-carbonyl which may be substituted by 1 to 4 substituents selected from the group consisting of halogen, C1-6 alkyl, C6-10 aryl, C7-12 aralkyl and nitro, (g) C7-12 aralkyl-carbonyl which may be substituted by 1 to 4 substituents selected from the group consisting of halogen, C1-6 alkyl, C6-10 aryl, C7-12 aralkyl and nitro, (h) pyranyl which may be substituted by 1 to 4 substituents selected from the group consisting of halogen, C1-6 alkyl, C6-10 aryl, C7-12 aralkyl and nitro, (i) furanyl which may be substituted by 1 to 4 substituents selected from the group consisting of halogen, C1-6 alkyl, C6-10 aryl, C7-12 aralkyl and nitro, (j) tri (C1-4 alkyl)silyl which may be substituted by 1 to 4 substituents selected from the group consisting of halogen, C1-6 alkyl, C6-10 aryl, C7-12 aralkyl and nitro, (v) carbonyl which is substituted by C1-8 alkyl, C3-6 cycloalkyl, C1-3 alkoxy-C1-6 alkyl, C2-6 alkenyl, C6-14 alkyl or C7-20 aralkyl, (vi) carboxy substituted by (1) C1-6 alkyl, (2) C3-6 cycloalkyl, (3) C6-14 aryl, (4) a 5-membered cyclic group selected from the group consisting of 2- or 3-thienyl, 2- or 3-furyl, 2- or 3-pyrrolyl, 2-, 3- or 4-pyridyl, 2-, 4- or 5-oxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-imidazolyl, 3-, 4- or 5-isoxazolyl, 3-, 4- or 5-isothiazolyl, 3- or 5-(1,2,4-oxadiazolyl), 1,3,4-oxadiazolyl, 3- or 5-(1,2,4-thiadiazolyl), 1,3,4-thiadiazolyl, 4- or 5-(1,2,3-thiadiazolyl), 1,2,5-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl and 1H- or 2H-tetrazolyl, (5) a 6-membered cyclic group selected from the group consisting of N-oxido-2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, N-oxido-2-, 4- or 5-pyrimidinyl, 2- or 3-thiomorpholinyl, 2- or 3-morpholinyl, oxoimidazinyl, dioxotriazinyl, pyrrolidinyl, piperidinyl, pyranyl, thiopyranyl, 1,4-oxazinyl, 1,4-thiazinyl, 1,3-thiazinyl, 2- or 3-piperazinyl, triazinyl, oxotriazinyl, 3- or 4-pyridazinyl, pyrazinyl and N-oxido-3- or 4-pyridazinyl, or (6) a 5- to 8-membered cyclic group or condensed ring thereof, selected from the group consisting of benzofuryl, benzothiazolyl, benzoxazolyl, tetrazolo[1,5-b]pyridazinyl, triazolo[4,5-b]pyridazinyl, benzoimidazolyl, quinolyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, indolizinyl, quinolizinyl, 1,8-naphthylizinyl, purinyl, pteridinyl, dibenzofuranyl, carbazolyl, acrydinyl, phenanthridinyl, chromanyl, benzoxazinyl, phenazinyl, phenothiazinyl and phenoxazinyl, or (vii) a group of the formula: â€”CONR22R23 wherein R22 and R23 are as defined above; R5 is (i) hydrogen or (ii) a group bonded through a carbon atom as defined in above R7; n is 0 to 3, or a salt thereof.