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US 7,402,595 B2Granted
JNK inhibitor
AssigneeTakeda Pharmaceutical Company Limited
InventorsFumio Itoh, Hiroyuki Kimura, Hideki Igata, Tomohiro Kawamoto, Mitsuru Sasaki, Shuji Kitamura
Life of this patent
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Abstract
A JNK inhibitor containing a compound having an isoquinolinone skeleton or a salt thereof, such as a compound represented by the formula wherein ring A and ring B are each an optionally substituted benzene ring, X is —O—, —N═, —NR3— or —CHR3—, R2 is an acyl group, an optionally esterified or thioesterified carboxyl group, an optionally substituted carbamoyl group or an optionally substituted amino group and the like, a broken line shows a single bond or a double bond, and R1 is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and the like, and the like.
Claims29
A compound represented by the formula
- wherein
- ring B′ is a benzene ring optionally having not more than two substituent(s);
- X′ is —CH2—:
- R1′ is
- a phenyl group optionally substituted by substituent(s) selected from substituent group B or
- a heterocyclic group bonded via a ring-constituting carbon atom and optionally substituted by substituent(s) selected from the substituent group B;
- R2 is
- a hydrocarbon group optionally having substituent(s) selected from the group consisting of a hydroxy group optionally substituted by a substituent selected from substituent group C,
- a thiol group optionally substituted by a substituent selected from the substituent group C,
- a sulfinyl group substituted by a substituent selected from the group consisting of
- 1) a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- 2) an amino optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C,
- 3) a 3 to 8-membered cyclic amino group,
- 4) a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B, and
- 5) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- a sulfonyl group substituted by a substituent selected from the group consisting of
- 1) a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- 2) an amino optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C,
- 3) a 3 to 8-membered cyclic amino group,
- 4) a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B, and
- 5) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- and
- an optionally esterified carboxyl group,
- RACO wherein RA is a hydrogen atom, a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B or a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- RASO2 wherein RA is as defined above,
- RASO wherein RA is as defined above,
- RAOPO(ORB) wherein RA is as defined above and RB is a hydrogen atom or a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B,
- an optionally esterified or thioesterified carboxyl group,
- a carbamoyl group optionally N-mono- or N,N-di-substituted by subsuituent(s) selected from the group consisting of
- i) a hydrocarbon group optionally substituted by substituent(s) selected from substituent group B,
- ii) RACO wherein wherein RA is as defined above,
- iii) RASO2 wherein RA is as defined above,
- iv) RASO wherein RA is as defined above,
- v) RAOPO(ORB) wherein each symbol is as defined above,
- vi) an alkoxycarbonyl optionally substituted by substituent(s) selected from substituent group A,
- vii) a carbamoyl optionally N-mono- or N,N-di-substituted by 1 or 2 substituent(s) selected from the group consisting of a lower(C1-6)alkyl group and phenyl group,
- viii) a 3 to 8-membered cyclic aminocarbonyl,
- ix) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- x) an amino optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C,
- xi) a 3 to 8-membered cyclic amino group, and
- xii) a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- a 3 to 8-membered cyclic aminocarbonyl,
- an amino group optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C, or
- a 3to 8-membered cyclic amino group;
- R4 is
- a hydrogen atom,
- a halogen atom,
- a cyano group,
- a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B,
- a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- a thiol group optionally substituted by a substituent selected from the substituent group C,
- a sulfinyl group substituted by a substituent selected from the group consisting of
- 1) a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- 2) an amino optionally N-mono- or N,N-di-substituted by substituent(s) selected from the subsutuent group C,
- 3) a 3 to 8-membered cyclic amino group,
- 4) a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B, and
- 5) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- a sulfonyl group substituted by a substituent selected from the group consisting of
- 1) a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- 2) an amino optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C,
- 3) a 3 to 8-membered cyclic amino group,
- 4) a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B, and
- 5) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- an amino group optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C,
- a 3 to 8-membered cyclic amino group,
- a carbamoyl group optionally N-mono- or N,N-di-substituted by substituent(s) selected from the group consisting of
- i) a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B,
- ii) RACO wherein wherein RA is as defined above,
- iii) RASO, wherein RA is as defined above,
- iv) RASO wherein RA is as defined above,
- v) RAOPO(ORB) wherein each symbol is as defined above,
- vi) an alkoxycarbonyl optionally substituted by substituent(s) selected from the substituent group A,
- vii) a carbamoyl optionally substituted by 1 or 2 substituent(s) selected from the group consisting of a lower(C1-6)alkyl group and phenyl group,
- viii) a 3 to 8-membered cyclic aminocarbonyl,
- ix) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- x) an amino optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C,
- xi) a 3 to 8-membered cyclic amino group, and
- xii) a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- a 3 to 8-membered cyclic aminocarbonyl, or
- an optionally esterified carboxyl group;
- the substituent group A consists of
- (1) a nitro group,
- (2) a hydroxy group,
- (3) an oxo group,
- (4) a cyano group,
- (5) a carbamoyl group,
- (6) a mono- or di-C1-4 alkyl-carbamoyl group,
- (7) a mono- or di-C2-4 alkenyl-carbamoyl group,
- (8) a mono- or di-phenyl-carbamoyl group,
- (9) a mono- or di-benzyl-carbamoyl group,
- (10) a C1-4 alkoxy-carbonyl-carbamoyl group,
- (11) a C1-4 alkylsulfonyl-carbamoyl group,
- (12) a C1-4 alkoxy-carbamoyl group,
- (13) an amino-carbamoyl group,
- (14) a mono- or di-C1-4 alkylamino-carbamoyl group,
- (15) a mono- or di-phenylamino-carbamoyl group,
- (16) a carboxyl group,
- (17) a C1-4 alkoxy-carbonyl group,
- (18) a sulfo group,
- (19) a halogen atom,
- (20) an optionally halogenated C1-4 alkoxy group,
- (21) a C1-4 alkoxy group optionally substituted by hydroxy group,
- (22) a C1-4 alkoxy group optionally substituted by carboxyl group,
- (23) a C1-4 alkoxy group optionally substituted by C1-4 alkoxy-carbonyl group,
- (24) a C1-4 alkoxy-C1-4 alkoxy group,
- (25) a C1-4 alkoxy-C1-4 alkoxy-C1-4 alkoxy group,
- (26) a phenoxy group,
- (27) a phenoxy-C1-4 alkyl group,
- (28) a phenoxy-C1-4 alkoxy group,
- (29) a C1-4 alkylcarbonyl-oxy group,
- (30) a carbamoyloxy group,
- (31) a mono- or di-C1-4 alkyl-carbamoyloxy group,
- (32) an optionally halogenated phenyl group,
- (33) an optionally hatogenated phenyl-C1-4 alkyl group,
- (34) an optionally halogenated phenyl-C2-4 alkenyl group,
- (35) an optionally halogenated phenoxy group,
- (36) a pyridyloxy group,
- (37) a C3-10 cycloalkyl group,
- (38) a C3-10 cycloalkyl-C1-4 alkoxy group,
- (39) a C3-10 cycloalkyl-C1-4 alkyl group,
- (40) an optionally halogenated C1-4 alkyl group,
- (41) an optionally halogenated C2-6 alkenyl group,
- (42) an optionally halogenated C1-4 alkylthio group,
- (43) a C1-4 alkyl group optionally substituted by hydroxy group,
- (44) a C1-4 alkylthio group optionally substituted by hydroxy group,
- (45) a mercapto group,
- (46) a thioxo group,
- (47) a benzyloxy group or benzylthio group optionally substituted by a substituent(s) selected from a halogen atom, carboxyl group and C1-4 alkoxy-carbonyl group,
- (48) an optionally halogenated phenylthio group,
- (49) a pyridylthio group,
- (50) a phenylthio-C1-4 alkyl group,
- (51) a pyridylthio C1-4 alkyl group,
- (52) an optionally halogenated C1-4 alkylsulfinyl group,
- (53) a phenylsulfinyl group,
- (54) a phenylsulfinyl-C1-4 alkyl group,
- (55) an optionally halogenated C1-4 alkylsulfonyl group,
- (56) a phenylsulfonyl group,
- (57) a phenylsulfonyl-C1-4 alkyl group,
- (58) an amino group,
- (59) an arninosulfonyl group,
- (60) a mono- or di-C1-4 alkylaminosulfonyl group wherein said alkyl group is optionally substituted by halogen atom, hydroxy group or C1-4 alkoxy group,
- (61) a C1-6 alkanoylamino wherein said C1-6 alkanoyl is optionally substituted by halogen atom, hydroxy group or carboxyl group,
- (62) a benzoylamino wherein said benzoyl is optionally substituted by halogen atom, hydroxy group, carboxyl group,
- (63) a C1-6 alkylsulfonylamino wherein said C1-6 alkylsulfonyl is optionally substituted by halogen atom, hydroxy group or carboxyl group,
- (64) a C6-10 arylsulfonylamino wherein said C6-10 arylsulfonyl is optionally substituted by halogen atom, hydroxy group or carboxyl group,
- (65) a benzyloxycarbonylamino,
- (66) an optionally halogenated C1-6 alkoxycarbonylamino,
- (67) a carbamoylamino group,
- (68) a mono- or di-C1-4 alkylcarbamoylamino group,
- (69) a mono- or di-C1-4 alkylamino group wherein said alkyl group is optionally substituted by halogen atom, hydroxy group or C1-4 alkoxy group and the like,
- (70) phenylamino,
- (71) benzylamino,
- (72) a 4 to 6-membered cyclic amino group,
- (73) a 4 to 6-membered cyclic amino-carbonyl group,
- (74) a 4 to 6-membered cyclic amino-carbonyl-oxy group,
- (75) a 4 to 6-membered cyclic amino-carbonyl-amino group,
- (76) a 4 to 6-membered cyclic amino-sulfonyl group,
- (77) a 4 to 6-membered cyclic amino-C1-4 alkyl group,
- (78) a formyl,
- (79) a C2-6 alkanoyl group optionally substituted by a substituent(s) selected from halogen atom, carboxyl group and C1-4 alkoxy-carbonyl group,
- (80) a benzoyl group,
- (81) a benzoyl group optionally substituted by halogen atom,
- (82) a 5 to 10-membered heterocyclic group wherein said heterocyclic group is optionally substituted by C1-4 alkyl group,
- (83) a 5 to 10-membered heterocycle-carbonyl group wherein said heterocyclic group is optionally substituted by C1-4 alkyl group,
- (84) a hydroxyimino group,
- (85) a C1-4 alkoxyimino group,
- (86) an aryl group, and
- (87) an optionally halogenated linear or branched C1-4 alkylenedioxy group;
- the substituent group B consists of
- (1) the substituent group A,
- (2) a C1-10 alkyl group,
- (3) a C2-10 alkenyl group,
- (4) a phenyl-C2-4 alkenyl group,
- (5) a mono- or di-C1-6 alkenyl-carbamoyl group,
- (6) a C6-14 aryl group,
- (7) a C7-20 aralkyl group, and
- (8) a styryl group;
- and
- the substituent group C consists of
- (1) a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B,
- (2) RACO wherein wherein RA is as defined above,
- (3) RASO2 wherein RA is as defined above,
- (4) RASO wherein RA is as defined above,
- (5) RAOPO(ORB) wherein each symbol is as defined above,
- (6) an alkoxycarbonyl optionally substituted by substituent(s) selected from the substituent group A,
- (7) a carbamoyl optionally N-mono- or N,N-di-substituted by substituent(s) selected from the group consisting of
- i) a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B,
- ii) RACO wherein wherein RA is as defined above,
- iii) RASO2 wherein RA is as defined above,
- iv) RASO wherein RA is as defined above,
- v) RAOPO(ORB) wherein each symbol is as defined above,
- vi) an alkoxycarbonyl optionally substituted by substituent(s) selected from the substituent group A,
- vii) a carbamoyl optionally N-mono- or N,N-di-substituted by 1 or 2 substituent(s) selected from the group consisting of a lower(C1-6)alkyl group and phenyl group,
- viii) a 3 to 8-membered cyclic aminocarbonyl,
- ix) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- x) an amino optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C,
- xi) a 3 to 8-membered cyclic amino group, and
- xii) a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- (8) a 3 to 8-membered cyclic aminocarbonyl, and
- (9) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B;
- or a salt thereof,
- provided that 2-benzyl-1-oxo-4-phenyl-1,2-dihydro-isociuinoline-3-carboxamide is excluded.
200 more elements
A compound selected from the group consisting of 2-(benzo[1 ,3]dioxol-5-ylmethyl)-6-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester, 6-bromo-1-oxo-4-phenyl-2-(4-sulfamoylbenzyl)-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester, 6-bromo-2-(4-methanesulfonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester, 6-bromo-2-(2,3-dihydrobenzofuran-5-ylmethyl)-1 -oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester, 6-bromo-2-(4-carboxybenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester, 2-(1 -acetylpiperidine-4-ylmethyl)-6-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester, 6-bromo-2-[4-(3-carboxypropionylamino)benzyl]-1 -oxo-4-phenyl-1 ,2-dihydroisoquinoline-3-carboxylic acid methyl ester, 6-bromo-2-(4-carbamoylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxyl ic acid methyl ester, 2-(benzo[1,3]dioxol-5-ylmethyl)-6-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester, 6-amino-2-(benzo[1 ,3]dioxol-5-ylmethyl)-1 -oxo-4-phenyl-1 ,2-dihydroisoquinoline-3-carboxylic acid methyl ester, 2-(benzo[1,3]dioxol-5-ylmethyl)-6-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic acid pyridin-3-ylmethyl ester, N,N-dimethyl-2-(benzo[1,3]dioxol-5-ylmethyl)-6-bromo-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxamide, 6-bromo-2-(4-methanesulfonylbenzyl)-4-phenyl-3-propionyl-2H-isoquinolin-1 -one, 3-butyryl-6-chloro-2-(4-methanesulfonylbenzyl)-4-phenyl-2H-isoquinolin-1-one, 2-(4-carboxybenzyl)-6-chloro-4-(3-hydroxymethylphenyl) -1-oxo-1,2-dihydroisoqu inoline-3-carboxyl ic acid methyl ester, 6-bromo-2-[4-(N′,N′-diethylhydrazinocarbonyl)benzyl]-1-oxo-4-phenyl-1,2-dihydroisoquinol ine-3-carboxylic acid methyl ester, 4-(6-chloro-3-butyryl-1-oxo-4-phenyl-1H-isoquinolin-2-ylmethyl)benzenesulfonamide, 4-(6-bromo-1-oxo-4-phenyl-3-propionyl-1H-isoquinolin-2-ylmethyl)benzoic acid, 4-(6-chloro-1-oxo-4-phenyl-3-propionyl-1H-isoquinolin-2-ylmethyl)benzoic acid, 6-bromo-4-phenyl-3-propionyl-2-[4-(1H-tetrazol-5-yl)benzyl]-2H -isoquinolin-1-one, 3-[(2Z)-3-aminobut-2-enoyl]-6-bromo-2-(4-methanesulfonylbenzyl)-4-phenyl-2H-isoquinolin-1-one, 3-[(2Z)-3-aminopent-2-enoyl]-6-bromo-2-(4-methanesulfonylbenzyl)-4-phenyl-2H-isoquinolin-1-one, 3-amino-2-(benzo[1,3]dioxol-5-ylmethyl)-6-bromo-4-phenyl-2H-isoquinolin-1-one, and 6-bromo-2-(4-methanesulfonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbothioic acid S-pyridin-2-yl ester, or a salt thereof.
A production method of a compound represented by the formula
- wherein
- ring B′ is a benzene ring optionally having not more than two substituent(s):
- X′ is —CH2—;
- R1′ is
- a phenyl group optionally substituted by substituent(s) selected from the substituent group B or
- a heterocyclic group bonded via a ring-constituting carbon atom and optionally substituted by substituent(s) selected from substituent group B;
- R2 is
- a hydrocarbon group optionally having substituent(s) selected from the group consisting of
- a hydroxy group optionally substituted by a substituent selected from substituent group C,
- a thiol group optionally substituted by a substituent selected from the substituent group C,
- a sulfinyl group substituted by a substituent selected from the group consisting of
- 1) a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- 2) an amino optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C,
- 3) a 3 to 8-membered cyclic amino group,
- 4) a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B, and
- 5) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- a sulfonyl group substituted by a substituent selected from the group consisting of
- 1) a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- 2) an amino optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C,
- 3) a 3 to 8-membered cyclic amino group,
- 4) a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B, and
- 5) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- and
- an optionally esterified carboxyl group,
- RACO wherein RA is a hydrogen atom, a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B or a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- RASO2 wherein RA is as defined above,
- RASO wherein RA is as defined above,
- RAOPO(ORB) wherein RA is as defined above and RB is a hydrogen atom or a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B,
- an optionally esterified or thioesterified carboxyl group,
- a carbamoyl group optionally N-mono- or N,N-di-substituted by substituent(s) selected from the group consisting of
- i) a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B,
- ii) RACO wherein wherein RA is as defined above,
- iii) RASO2 wherein RA is as defined above,
- iv) RASO wherein RA is as defined above,
- v) RAOPO(ORB) wherein each symbol is as defined above,
- vi) an alkoxycarbonyl optionally substituted by substituent(s) selected from substituent group A,
- vii) a carbamoyl optionally N-mono- or N,N-di-substituted by 1 or 2 substituent(s) selected from the group consisting of a lower(C1-6)alkyl group and phenyl group,
- viii) a 3 to 8-membered cyclic aminocarbonyl,
- ix) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- x) an amino optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C,
- xi) a 3 to 8-membered cyclic amino group, and
- xii) a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- a 3 to 8-membered cyclic aminocarbonyl,
- an amino group optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C, or
- a 3 to 8-membered cyclic amino group;
- R4 is
- a hydrogen atom,
- a halogen atom,
- a cyano group,
- a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B,
- a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- a thiol group optionally substituted by a substituent selected from the substituent group C,
- a sulfinyl group substituted by a substituent selected from the group consisting of
- 1) a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- 2) an amino optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C,
- 3) a 3 to 8-membered cyclic amino group,
- 4) a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B, and
- 5) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- a sulfonyl group substituted by a substituent selected from the group consisting of
- 1) a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- 2) an amino optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C,
- 3) a 3 to 8-membered cyclic amino group,
- 4) a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B, and
- 5) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- an amino group optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C,
- a 3 to 8-membered cyclic amino group,
- a carbamoyl group optionally N-mono- or N,N-di-substituted by substituent(s) selected from the group consisting of
- i) a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B,
- ii) RACO wherein wherein RA is as defined above,
- iii) RASO2 wherein RA is as defined above,
- iv) RASO wherein RA is as defined above,
- v) RAOPO(ORB) wherein each symbol is as defined above,
- vi) an alkoxycarbonyl optionally substituted by substituent(s) selected from the substituent group A,
- vii) a carbamoyl optionally substituted by 1 or 2 substituent(s) selected from the group consisting of a lower(C1-6)alkyl group and phenyl group,
- viii) a 3 to 8-membered cyclic aminocarbonyl,
- ix) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- x) an amino optionally N-mono- or N,N-di-substituted by substituent(s) selected from the substituent group C,
- xi) a 3 to 8-membered cyclic amino group, and
- xii) a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- a 3 to 8-membered cyclic aminocarbonyl, or
- an optionally esterified carboxyl group, or a salt thereof, which comprises (1) reacting a compound represented by the formula
- wherein R2′ is
- an optionally esterified carboxyl group or
- RACO wherein RA is a hydrogen atom, a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B or a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- RASO2 wherein RA is as defined above,
- RASO wherein RA is as defined above, or
- RAOPO(ORB) wherein RA is as defined above and RB is a hydrogen atom or a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B,
- and other symbols are as defined above, or a salt thereof with an amino compound represented by the formula
- H2N—X′—R1′ wherein the symbols in the formula are as defined above, or a salt thereof, or
- (2) reacting a compound represented by the formula
- wherein the symbols in the formula are as defined above, or a salt thereof with a compound represented by the formula L-X′—R1′ wherein L is a leaving group, and other symbols are as defined above, or a salt thereof, or
- (3) subjecting a compound represented by the formula
- wherein the symbols in the formula are as defined above, or a salt thereof to an intramolecular cyclization reaction, or
- (4) reacting a compound represented by the formula
- wherein OTf is a triflate group and other symbols are as defined above, or a salt thereof with a compound represented by the formula
- wherein Y is an atomic group capable of a crosscoupling reaction and other symbols are as defined above, or a salt thereof, wherein
- the substituent group A consists of
- (1) a nitro group,
- (2) a hydroxy group,
- (3) an oxo group,
- (4) a cyano group,
- (5) a carbamoyl group,
- (6) a mono- or di-C1-4 alkyl-carbamoyl group,
- (7) a mono- or di-C2-4 alkenyl-carbamoyl group,
- (8) a mono- or di-phenyl-carbamoyl group,
- (9) a mono- or di-benzyl-carbamoyl group,
- (10) a C1-4 alkoxy-carbonyl-carbamoyl group,
- (11) a C1-4 alkylsulfonyl-carbamoyl group,
- (12) a C1-4 alkoxy-carbamoyl group,
- (13) an amino-carbamoyl group,
- (14) a mono- or di-C1-4 alkylamino-carbamoyl group,
- (15) a mono- or di-phenylamino-carbamoyl group,
- (16) a carboxyl group,
- (17) a C1-4 alkoxy-carbonyl group,
- (18) a sulfo group,
- (19) a halogen atom,
- (20) an optionally halogenated C1-4 alkoxy group,
- (21) a C1-4 alkoxy group optionally substituted by hydroxy group, (22) a C1-4 alkoxy group optionally substituted by carboxyl group,
- (23) a C1-4 alkoxy group optionally substituted by C1-4 alkoxy-carbonyl group,
- (24) a C1-4 alkoxy-C1-4 alkoxy group,
- (25) a C1-4 alkoxy-C1-4 alkoxy-C1-4 alkoxy group,
- (26) a phenoxy group,
- (27) a phenoxy-C1-4 alkyl group,
- (28) a phenoxy-C1-4 alkoxy group,
- (29) a C1-4 alkylcarbonyl-oxy group,
- (30) a carbamoyloxy group,
- (31) a mono- or di-C1-4 alkyl-carbamoyloxy group,
- (32) an optionally halogenated phenyl group,
- (33) an optionally halo genated phenyl-C1-4 alkyl group,
- (34) an optionally halogenated phenyl-C1-4 alkenyl group,
- (35) an optionally halogenated phenoxy group,
- (36) a pyridyloxy group,
- (37) a C3-10 cycloalkyl group,
- (38) a C3-10 cycloalkyl-C1-4 alkoxy group,
- (39) a C3-10 cycloalkyl-C1-4 alkyl group,
- (40) an optionally halogenated C1-4 alkyl group,
- (41) an optionally halogenated C2-6 alkenyl group,
- (42) an optionally halogenated C1-4 alkylthio group,
- (43) a C1-4 alkyl group optionally substituted by hydroxy group,
- (44) a C1-4 alkylthio group optionally substituted by hydroxy group,
- (45) a mercapto group,
- (46) a thioxo group,
- (47) a benzyloxy group or benzylthio group optionally substituted by a substituent(s) selected from a halogen atom, carboxyl group and C1-4 alkoxy-carbonyl group,
- (48) an optionally halogenated phenylthio group,
- (49) a pyridylthio group,
- (50) a phenyhhio-C1-4 alkyl group,
- (51) a pyridylthio C1-4 alkyl group,
- (52) an optionally halogenated C1-4 alkylsulfinyl group,
- (53) a phenylsulfinyl group,
- (54) a phenylsulfinyl-C1-4 alkyl group,
- (55) an optionally halogenated C1-4 alkylsulfonyl group,
- (56) a phenylsulfonyl group,
- (57) a phenylsulfonyl-C1-4 alkyl group,
- (58) an amino group,
- (59) an aminosulfonyl group,
- (60) a mono- or di-C1-4 alkylaminosulfonyl group wherein said alkyl group is optionally substituted by halogen atom, hydroxy group or C1-4 alkoxy group,
- (61) a C1-6 alkanoylamino wherein said C1-6 alkanoyl is optionally substituted by halogen atom, hydroxy group or carboxyl group,
- (62) a benzoylamino wherein said benzoyl is optionally substituted by halogen atom, hydroxy group, carboxyl group,
- (63) a C1-6 alkylsulfonylamino wherein said C1-6 alkylsulfonyl is optionally substituted by halogen atom, hydroxy group or carboxyl group,
- (64) a C6-10 aiylsulfonylamino wherein said C6-10 arylsulfonyl is optionally substituted by halogen atom, hydroxy group or carboxyl group,
- (65) a benzyloxycarbonylamino,
- (66) an optionally halogenated C1-6 alkoxycarbonylamino,
- (67) a carbamoylamino group,
- (68) a mono- or di-C1-4 alkylcarbamoylamino group,
- (69) a mono- or di-C1-4 alkylamino group wherein said alkyl group is optionally substituted by halogen atom, hydroxy group or C1-4 alkoxy group and the like,
- (70) phenylamino,
- (71) benzylamino,
- (72) a 4 to 6-membered cyclic amino group,
- (73) a 4 to 6-membered cyclic amino-carbonyl group,
- (74) a 4 to 6-membered cyclic amino-carbonyl-oxy group,
- (75) a 4 to 6-membered cyclic amino-carbonyl-amino group,
- (76) a 4 to 6-membered cyclic amino-sulfonyl group,
- (77) a 4 to 6-membered cyclic amino-C1-4 alkyl group,
- (78) a formyl,
- (79) a C2-6 alkanoyl gruop opionally substituted by a substituent(s) selected from halogen atom, carboxyl group and C1-4 alkoxy-carbonyl group,
- (80) a benzoyl group,
- (81) a benzoyl group optionally substituted by halogen atom,
- (82) a 5 to 10-membered heterocyclic group wherein said heterocyclic group is optionally substituted by C1-4 alkyl group,
- (83) a 5 to 10-membered heterocycle-carbonyl group wherein said heterocyclic group is optionally substituted by C1-4 alkyl group,
- (84) a hydroxyimino group,
- (85) a C1-4 alkoxyirnino group,
- (86) an aryl group, and
- (87) an optionally halogenated linear or branched C1-4 alkylenedioxy group;
- the substituent group B consists of
- (1) the substituent group A,
- (2) a C1-10 alkyl group,
- (3) a C2-10 alkenyl group,
- (4) a phenyl-C2-4 alkenyl group,
- (5) a mono- or di-C1-6 alkenyl-carbamoyl group,
- (6) a C6-14 aryl group,
- (7) a C7-20 aralkyl group, and
- (8) a styryl group;
- and
- the substituent group C consists of
- (1) a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B,
- (2) RACO wherein wherein RA is as defined above,
- (3) RASO2 wherein RA is as defined above,
- (4) RASO wherein RA is as defined above,
- (5) RAOPO(ORB) wherein each symbol is as defined above,
- (6) an alkoxycarbonyl optionally substituted by substituent(s) selected from the substituent group A,
- (7) a carbamoyl optionally N-mono- or N,N-di-substituted by substituent(s) selected from the group consisting of
- a hydrocarbon group optionally substituted by substituent(s) selected from the substituent group B,
- ii) RACO wherein wherein RA is as defined above,
- iii) RASO2 wherein RA is as defined above,
- iv) RASO wherein RA is as defined above,
- v) RAOPO(ORB) wherein each symbol is as defined above,
- vi) an alkoxycarbonyl optionally substituted by substituent(s) selected from the substituent group A,
- vii) a carbamoyl optionally N-mono- or N,N-di-substituted by 1 or 2 substituent(s) selected from the group consisting of a lower(C1-6)alkyl group and phenyl group,
- viii) a 3 to 8-membered cyclic aminocarbonyl,
- ix) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B,
- x) an amino opionally N-mono- or N,N-disubstitued by substituent(s) selected from the substituent group C,
- xi) a 3 to 8-membered cyclic amino group, and
- xii) a hydroxy group optionally substituted by a substituent selected from the substituent group C,
- (8) a 3 to 8-membered cyclic aminocarbonyl, and
- (9) a heterocyclic group optionally substituted by substituent(s) selected from the substituent group B.
213 more elements
Dependencies are inferred from the claim text.