Patent ID: 6403595
Filing Date: 2002-06-11
Classification: A61P,C07D

Abstract:
A compound of the formula: wherein R1 is a hydrocarbon group selected from the group consisting of C1-10 alkyl group, C2-6 alkenyl group, C2-6 alkynyl group, C3-9 cycloalkyl group, C3-6 cycloalkenyl group, C4-6 cycloalkanedienyl group and C6-14 aryl group, said hydrocarbon group being unsubstituted or substituted with 1 to 5 substituents selected from the group consisting of the LIST O; the ring A may have 1 to 3 substituents selected from the group consisting of the LIST P; Xâ€² and X are independently (1) a chemical bond or (2) straight-chain C1-6 alkylene which may be substituted with 1 to 3 substituents selected from the group consisting of (A) C1-6 alkyl group unsubstituted or substituted with 1 to 5 substituents selected from the group consisting of the LIST M, (B) a carbamoyl group, (C) a carbamoyl group substituted with one substituent selected from the group consisting of the LIST E, (D) a carbamoyl group, substituted with one substituent selected from the group consisting of the LIST E and substituted with another substituent selected from the group consisting of the LIST J wherein two substituents of the carbamoyl group may form a cyclic carbamoyl group selected from the group consisting of the LIST K which may have at the 4-position a C1-6 alkyl group, C7-10 aralkyl group or C6-10 aryl group, (E) cyano group, (F) a halogen atom, (G) hydroxy group, (H) C1-6 alkoxy-carbonyl group, (I) C7-12 aryloxy-carbonyl group unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of the LIST D and (J) C7-10 aralkyloxy-carbonyl group unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of the LIST D; Y is a divalent cyclic group selected from the group consisting (1) a divalent group formed by removing a hydrogen atom at an optional position from a C3-9 cycloalkyl group, C3-6 cycloalkenyl group, C4-6 cycloalkanedienyl group or C6-10 aryl group, (2) a 5- to 6-membered divalent aromatic heterocyclic group which contains, besides carbon atoms, 1 to 3 hetero-atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom, and (3) a 5- to 6-membered divalent saturated or unsaturated non-aromatic heterocyclic group which contains, besides carbon atoms, 1 to 3 hetero-atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom, said divalent cyclic group being unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of the LIST P; Z is a nitrogen-containing heterocyclic group selected from the group consisting of (1) a 5-6 membered aromatic monocyclic nitrogen-containing heterocyclic group and (2) a 5-6 membered non-aromatic monocyclic nitrogen-containing heterocyclic group, which contains, besides carbon atoms, 1 to 3 ring nitrogen atoms and may contain 1 to 3 hetero-atoms selected from the group consisting of oxygen atom and sulfur atom, and wherein said ring nitrogen may be oxidized, said nitrogen-containing heterocyclic group being unsubstituted or substituted with 1 to 5 substituents selected from the group consisting of the LIST O; wherein said LIST A is (i) C1-6 alkoxy group, (ii) a halogen atom, (iii) C1-6 alkyl group, (iv) C2-6 alkenyl group, (v) C2-6 alkynyl group, (vi) an amino group unsubstituted or substituted with a substituent selected from the group consisting of LIST B, (vii) a hydroxyl group unsubstituted or substituted with a substituent selected from the group consisting of LIST C, (viii) a cyano group and (ix) an amidino group unsubstituted or substituted with a substituent selected from the group consisting of LIST C; wherein said LIST B is (a) C1-6 alkyl group, (b) C1-6 alkanoyl group, (c) benzoyl group, (d) an unhalogenated or halogenated C1-6 alkoxy-carbonyl group, (e) a heterocyclic group which contains, besides carbon atoms, 1 to 4 hetero-atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom and which is selected from the group consisting of 5- to 6-membered aromatic monocyclic heterocyclic group, 8- to 12-membered aromatic fused heterocyclic group, 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and non-aromatic heterocyclic group wherein a part or all of the double bonds in said aromatic monocyclic heterocyclic group or said aromatic fused heterocyclic group are saturated, (f) an imidoyl group, (g) C1-6 alkylimidoyl group, (h) C1-6 alkanoylimidoyl group, (i) an amidino group and (j) an amino group unsubstituted or substituted with 1-2 C1-6 alkyl groups, wherein two substituents of the amino group may form a cyclic amino group selected from the group consisting of 1-azetidinyl, 1-pyrrolidinyl, piperidino, morpholino, 1-piperazinyl and 1-piperazinyl which may have at the 4-position a C1-6 alkyl group, C7-10 aralkyl group or C6-10 aryl group; wherein said LIST C is (a) C1-6 alkyl group, (b) C1-6 alkanoyl group, (c) benzoyl group, (d) an unhalogenated or halogenated C1-6 alkoxy-carbonyl group and (e) a heterocyclic group which contains, besides carbon atoms, 1 to 4 hetero-atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom and which is selected from the group consisting of 5- to 6-membered aromatic monocyclic heterocyclic group, 8- to 12-membered aromatic fused heterocyclic group, 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and non-aromatic heterocyclic group wherein a part or all of the double bonds in said aromatic monocyclic heterocyclic group or said aromatic fused heterocyclic group are saturated; wherein said LIST D is (a) a hydroxy group, (b) an amino group which may have 1 to 2 substituents selected from the group consisting of C1-6 alkyl group, C1-6 alkanoyl group, benzoyl group, a carboxyl group and C1-6 alkoxy-carbonyl group, (c) a halogen atom, (d) a nitro group, (e) a cyano group, (f) C1-6 alkyl group unsubstituted or substituted with 1 to 5 halogen atoms and (g) C1-6 alkoxy group unsubstituted or substituted with 1 to 5 halogen atoms; wherein said LIST E is (i) C1-6 alkyl group which may be substituted with 1 to 3 substituents selected from the group consisting of said LIST D, (ii) C2-6 alkenyl group which may be substituted with 1 to 3 substituents selected from the group consisting of said LIST D, (iii) C3-6 cycloalkyl group which may be substituted with 1 to 3 substituents selected from the group consisting of said LIST D, (iv) C6-10 aryl group which may be substituted with 1 to 3 substituents selected from the group consisting of said LIST D, (v) C7-10 aralkyl group which may be substituted with 1 to 3 substituents selected from the group consisting of said LIST D, (vi) C8-10 arylalkenyl group which may be substituted with 1 to 3 substituents selected from the group consisting of said LIST D and (vii) a heterocyclic group which contains, besides carbon atoms, 1 to 4 hetero-atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom, which is selected from the group consisting of 5- to 6-membered aromatic monocyclic heterocyclic group, 8- to 12-membered aromatic fused heterocyclic group, 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and non-aromatic heterocyclic group wherein a part or all of the double bonds in said aromatic monocyclic heterocyclic group or said aromatic fused heterocyclic group are saturated, and which may be substituted with 1 to 3 substituents selected from the group consisting of said LIST D; wherein said LIST F is (i) a halogen atom, (ii) a phenyl group unsubstituted or substituted with LIST G and (iii) a naphthyl group unsubstituted or substituted with LIST G; wherein said LIST G is (a) a halogen atom, (b) C1-6 alkyl group, (c) C1-6 alkoxy group, (d) a hydroxyl group unsubstituted or substituted with a substituent selected from the group consisting of said LIST C, (e) a thiol group unsubstituted or substituted with a substituent selected from the group consisting of said LIST C, (f) an amino group unsubstituted or substituted with a substituent selected from the group consisting of said LIST B, (g) C1-6 alkoxy-carbonyl group, (h) C7-12 aryloxy-carbonyl group unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of said LIST D and (i) C7-10 aralkyloxy-carbonyl group unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of said LIST D; wherein said LIST H is (A) C1-6 alkyl group which may be substituted with said LIST F, (B) C1-6 alkoxy-carbonyl group, (C) C7-12 aryloxy-carbonyl group unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of said LIST D, (D) C7-1 aralkyloxy-carbonyl group unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of said LIST D, (E) a carbamoyl group, (F) a carbamoyl group substituted with one substituent selected from the group consisting of said LIST E, (G) a carbamoyl group substituted with one substituent selected from the group consisting of said LIST E and substituted with another substituent selected from the group consisting of LIST J wherein two substituents of the carbamoyl group may form a cyclic carbamoyl group selected from the group consisting of LIST K which may have at the 4-position a C1-6 alkyl group, C7-10 arallyl group or C6-10 aryl group, (H) a thiocarbamoyl group, (I) a thiocarbamoyl group substituted with one substituent selected from the group consisting of said LIST E, (J) a thiocarbamoyl group substituted with one substituent selected from the group consisting of said LIST E and substituted with another substituent selected from the group consisting of LIST J wherein two substituents of the thiocarbamoyl group may form a cyclic thiocarbamoyl group selected from the group consisting of LIST L which may have at the 4-position a C1-6 alcyl group, C7-10 aralkyl group or C6-10 aryl group, (K) a sulfamoyl group, (L) a sulfonyl group having one substituent selected from the group consisting of said LIST E and (M) a carbonyl group having a hydrogen atom or one substituent selected from the group consisting of said LIST E; wherein said LIST I is (A) C1-6 alkyl group which may have 1 to 3 substituents selected from the group consisting of said LIST A, (B) a carbamoyl group, (C) a carbamoyl group substituted with one substituent selected from the group consisting of said LIST E, (D) a carbamoyl group substituted with one substituent selected from the group consisting of said LIST E and substituted with another substituent selected from the group consisting of LIST J wherein two substituents of the carbamoyl group may form a cyclic carbamoyl group selected from the group consisting of LIST K which may have at the 4-position a C1-6 alkyl group, C7-10 aralkyl group or C6-10 aryl group, (E) a thiocarbamoyl group, (F) a thiocarbamoyl group substituted with one substituent selected from the group consisting of said LIST E, (G) a thiocarbamoyl group substituted with one substituent selected from the group consisting of said LIST E and substituted with another substituent selected from the group consisting of LIST J wherein two substituents of the thiocarbamoyl group may form a cyclic thiocarbamoyl group selected from the group consisting of LIST L which may have at the 4-position C1-6 alkyl group, C7-10 aralkyl group or C6-10 aryl group, (H) a sulfamoyl group, (I) C1-6 alkoxy-carbonyl group, (J) C7-12 aryloxy-carbonyl group unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of said LIST D, (K) C7-10 aralkyloxy-carbonyl group group unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of said LIST D, (L) a sulfonyl group having one substituent selected from the group consisting of said LIST E and (M) a carbonyl group having a hydrogen atom or one substituent selected from the group consisting of said LIST E; wherein said LIST J is (i) C1-6 alkyl group, (ii) C3-6 cycloalkyl group and (iii) C7-10 aralkyl group; wherein said LIST K is 1-azetidinylcarbonyl, 1-pyrrolidinylcarbonyl, piperidinocarbonyl, morpholinocarbonyl and 1-piperazinylcarbonyl; wherein said LIST L is 1-azetidinylthiocarbonyl, 1-pyrrolidinylthiocarbonyl, piperidinothiocarbonyl, morpholino-thiocarbonyl and 1-piperazinylthiocarbonyl; wherein said LIST M is (i) a halogen atom, (ii) an amino group, (iii) a carboxyl group, (iv) hydroxy group, (v) C6-10 aryl and (vi) C6-10 aryloxy; wherein said LIST N is (i) a halogen atom, (ii) an amino group, (iii) a carboxyl group and (iv) a hydroxy group; wherein said LIST O is (1) C1-6 alkyl group which may have 1 to 3 substituents selected from the group consisting of said LIST A, (2) C2-6 alkenyl group which may have 1 to 3 substituents selected from the group consisting of said LIST A, (3) C2-6 alkynyl group which may have 1 to 3 substituents selected from the group consisting of said LIST A, (4) C6-14 aryl group which may have 1 to 3 substituents selected from the group consisting of said LIST A, (5) C3-7 cycloalkyl group which may have 1 to 3 substituents selected from the group consisting of said LIST A, (6) C3-6 cycloalkenyl group which may have 1 to 3 substituents selected from the group consisting of said LIST A, (7) a heterocyclic group which contains, besides carbon atoms, 1 to 4 hetero-atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom and which is selected from the group consisting of 5- to 6-membered aromatic monocyclic heterocyclic group, 8- to 12-membered aromatic fused heterocyclic group, 3- to 8-membered saturated or unsaturated non-aromatic heterocyclic group and non-aromatic heterocyclic group wherein a part or all of the double bonds in said aromatic monocyclic heterocyclic group or said aromatic fused heterocyclic group are saturated, said heterocyclic group being unsubstituted or substituted with a substituent selected from the group consisting of (i) C1-6 alkyl group (ii) C2-6 alkenyl group, (iii) C2-6 alkynyl group, (iv) C1-6 alkanoyl group, (v) benzoyl group, (vi) an amino group unsubstituted or substituted with a substituent selected from the group consisting of said LIST B, (vii) a hydroxyl group unsubstituted or substituted with a substituent selected from the group consisting of said LIST C, (viii) a halogen, (ix) an imidoyl group unsubstituted or substituted with a substituent selected from the group consisting of said LIST C and (x) an amidino group unsubstituted or substituted with a substituent selected from the group consisting of said LIST C, (8) an amino group unsubstituted or substituted with a substituent selected from the group consisting of said LIST B, (9) an imidoyl group unsubstituted or substituted with a substituent selected from the group consisting of said LIST C, (10) an amidino group unsubstituted or substituted with a substituent selected from the group consisting of said LIST C, (11) a hydroxyl group unsubstituted or substituted with a substituent selected from the group consisting of said LIST C, (12) a thiol group unsubstituted or substituted with a substituent selected from the group consisting of said LIST C, (13) C1-6 alkoxy-carbonyl group, (14) C7-12 aryloxy-carbonyl group unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of said LIST D, (15) C7-10 aralkyloxy-carbonyl group unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of said LIST D, (16) a carbamoyl group, (17) a carbamoyl group substituted with one substituent selected from the group consisting of said LIST E, (18) a carbamoyl group substituted with one substituent selected from the group consisting of said LIST E and substituted with another substituent selected from the group consisting of the LIST J wherein two substituents of the carbamoyl group may form a cyclic carbamoyl group selected from the group consisting of the LIST K which may have at the 4-position a C1-6 alkyl group, C7-10 aralkyl group or C6-10 aryl group, (19) a thiocarbamoyl group, (20) a thiocarbamoyl group substituted with one substituent selected from the group consisting of said LIST E, (21) a thiocarbamoyl group substituted with one substituent selected from the group consisting of said LIST E, and substituted with another substituent selected from the group consisting of said LIST J wherein two substituents of the thiocarbamoyl group may form a cyclic thiocarbamoyl group selected from the group consisting of said LIST L which may have at the 4-position a C1-6 alkyl group, C7-10 aralkyl group or C6-10 aryl group, (22) a halogen atom, (23) a cyano group, (24) a nitro group, (25) a sulfonyl group having one substituent selected from the group consisting of said LIST E, (26) a carbonyl group having a hydrogen atom or one substituent selected from the group consisting of said LIST E and (27) an oxo group; and wherein said LIST P is (1) a hydroxy group unsubstituted or substituted with said LIST H, (2) a thiol group, wherein the sulfur atom may be in the form of the formula: S(O)k in which k is an integer of 0 to 2, unsubstituted or substituted with said LIST H, (3) a halogen atom, (4) a nitro group, (5) a cyano group, (6) an amino group unsubstituted or substituted with 1 to 2 substituents selected from the group consisting of said LIST I, (7) C1-6 alkyl group unsubstituted or substituted with 1 to 5 substituents selected from the group consisting of said LIST M, (8) C1-6 alkylidene group unsubstituted or substituted with 1 to 5 substituents selected from the group consisting of said LIST N, (9) C6-10 aryl-C1-4 alkylidene group unsubstituted or substituted with 1 to 5 substituents selected from the group consisting of said LIST N, (10) C1-6 alkoxy group unsubstituted or substituted with 1 to 5 halogen atoms, (11) C1-6 alkoxy-carbonyl group, (12) C7-12 aryloxy-carbonyl group unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of said LIST D, (13) C7-10 aralkyloxy-carbonyl group unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of said LIST D, (14) a carbamoyl group, (15) a carbamoyl group substituted with one substituent selected from the group consisting of said LIST E, (16) a carbamoyl group substituted with one substituent selected from the group consisting of said LIST E and substituted with another substituent selected from the group consisting of said LIST J wherein two substituents of the carbamoyl group may form a cyclic carbamoyl group selected from the group consisting of said LIST K which may have at the 4-position a C1-6 alkyl group, C7-10 aralkyl group or C6-10 aryl group, (17) a thiocarbamoyl group, (18) a thiocarbamoyl group substituted with one substituent selected from the group consisting of said LIST E, (19) a thiocarbamoyl group substituted with one substituent selected from the group consisting of said LIST E and substituted with another substituent selected from the group consisting of said LIST J wherein two substituents of the thiocarbamoyl group may form a cyclic thiocarbamoyl group selected from the group consisting of said LIST L which may have at the 4-position a C1-6 alkyl group, C7-10 aralkyl group or C6-10 aryl group and (20) a sulfamoyl group; or a salt thereof.