Tricyclic compound

A pharmaceutical composition comprising the compound of the formula (I):

• wherein A ring, B ring and C ring are each independently optionally substituted aromatic carbocycle or optionally substituted 5- or 6-membered heterocycle which may fuse with benzene ring,
• W1, W2 and/or W3 represents a single bond when A ring, B ring and/or C ring is optionally substituted 5-membered heterocycle,
• X is —O—, —CH2—, —NR1— wherein R1 is hydrogen, optionally substituted lower alkyl, lower alkenyl, lower alkylcarbonyl or optionally substituted lower alkoxycarbonyl or —S(O)p— wherein p is an integer of 0 to 2,
• Y is hydrogen, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted lower alkoxycarbonyl, optionally substituted sulfamoyl, optionally substituted amino, optionally substituted aryl or optionally substituted 5- or 6-membered heterocycle,
• Y may be optionally substituted lower alkoxy when X is —CH2—,
• Y may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or —NR1—,
• one of V1 and V2 is a single bond and the other is a single bond, an —O— bond, an —NH— bond, an —OCH2— bond, a —CH2O— bond, a —CH═CH— bond, a —C≡C— bond, a —CH(OR2)— bond, wherein R2 is hydrogen or lower alkyl, a —CO— bond, or an —NHCHR3— bond, wherein R3 is hydrogen or hydroxy, and
• at least one of A ring, B ring and C ring is optionally substituted aromatic carbocycle and at least another one is optionally substituted 5- or 6-membered heterocycle which may fuse with benzene ring when both of V1 and V2 are single bonds,
• excluding
• (i) a compound wherein B ring is optionally substituted imidazole ring, optionally substituted furan ring, optionally substituted thiophene ring, optionally substituted pyrrole ring, optionally substituted oxazole ring, or optionally substituted thiazole ring and
• (ii) a compound wherein one of A ring and C ring is optionally substituted oxadiazole ring or optionally substituted tetrazole ring,
• salt or hydrate thereof and a pharmaceutically acceptable carrier.

A compound of the formula (Ib′):

• wherein C ring is optionally substituted 5- or 6-membered heterocycle which contains one or two hetero atoms, W3 represents a bond when C ring is 5-membered heterocycle,
• X and X′ are each independently —O—, —CH2—, —NR1— (wherein R1 is hydrogen, optionally substituted lower alkyl, lower alkenyl, lower alkylcarbonyl or optionally substituted lower alkoxycarbonyl) or —S(O)p— wherein p is an integer of 0 to 2,
• Y and Y′ are each independently optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted lower alkoxycarbonyl, optionally substituted amino, optionally substituted sulfamoyl, optionally substituted aryl or optionally substituted 5- or 6-membered heterocycle,
• R1, taken together with Y or Y′, may form —(CH2)m—, —(CH2)2—Q—(CH2)2— (wherein Q is CH2, O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—, —N═CH—N═CH—, —C(═O)—O(CH2)n—, —C(═O) —NR′—(CH2)n— or —C(═O)—NR′—N═CH— wherein m is 4 or 5, n is 2 or 3, R′ is hydrogen, lower alkyl or lower alkenyl,
• Y may be optionally substituted lower alkoxy when X is —CH2—,
• Y′ may be optionally substituted lower alkoxy when XI is —CH2—,
• Y may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or —NR1—,
• Y′ may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X′ is —O— or —NR1—,
• Y may be hydrogen or halogen when X is —CH2— or —NR1—,
• Y′ may be hydrogen or halogen when X′ is —CH2— or —NR1—,
• R4, R5, R6, R7, R8, R9, R10 and R11 are each independently hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted lower alkenyl, optionally substituted lower alkenyloxy, optionally substituted cycloalkyloxy, optionally substituted RC(O)—O wherein R is hydrogen, alkyl, cycloalkyl or aryl, carboxy, optionally substituted lower alkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl, optionally substituted lower alkylthio, optionally substituted lower alkenylthio, optionally substituted amino, optionally substituted carbamoyl, guanidino, nitro, optionally substituted lower alkylsulfonyl, optionally substituted lower alkylsulfonyloxy, optionally substituted arylsulfonyl or optionally substituted arylsulfonyloxy,
• excluding
• (i) a compound wherein all of R8, R9, R10 and R11 are selected from hydrogen and halogen,
• (ii) a compound wherein C ring is optionally substituted pyrimidine ring, and at least one of —X—Y and —X′—Y′ is unsubstituted lower alkyl, unsubstituted lower alkoxy, unsubstituted alkanoyloxy or unsubstituted lower alkylamino, and
• (iii) a compound wherein one of A ring and C ring is substituted with optionally substituted phenylaminocarbonyl or optionally substituted benzoylamino,
• salt or hydrate thereof.

A compound of the formula (Ia′):

• wherein B ring is optionally substituted 5- or 6-membered ring which contains one or two hetero atoms (wherein the substituent is halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted lower alkenyl, optionally substituted lower alkenyloxy, optionally substituted acyloxy, carboxy, optionally substituted lower alkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl, optionally substituted alkylthio, optionally substituted lower alkenylthio, optionally substituted amino, guanidino, nitro, optionally substituted lower alkylsulfonyl, optionally substituted lower alkylsulfonyloxy, optionally substituted arylsulfonyl or optionally substituted arylsulfonyloxy, excluding a compound wherein B ring is substituted with only halogen(s)), and
• W2 represents a bond when B ring is 5-membered heterocycle,
• X and X′ are each independently —O—, —CH2—, —NR1— (wherein R1 is hydrogen, optionally substituted lower alkyl, lower alkenyl, lower alkylcarbonyl or optionally substituted lower alkoxycarbonyl) or —S(O)p— wherein p is an integer of 0 to 2,
• Y and Y′ are each independently optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted lower alkoxycarbonyl, optionally substituted amino, optionally substituted sulfamoyl, optionally substituted aryl or optionally substituted 5- or 6-membered heterocycle,
• R1, taken together with Y or Y′, may form —(CH2)m, —(CH2)2—Q—(CH2)2— (wherein Q is CH2, O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—, —N═CH—N═CH—, —C(═O)—O(CH2)n—, —C(═O)—NR′—(CH2)n— or —C(═O)—NR′—N═CH— wherein m is 4 or 5, n is 2 or 3, R′ is hydrogen, lower alkyl or lower alkenyl,
• Y may be optionally substituted lower alkoxy when X is —CH2—,
• Y′ may be optionally substituted lower alkoxy when X′ is —CH2—,
• Y may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or —NR1—,
• Y′ may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X′ is —O— or —NR1—,
• Y may be hydrogen or halogen when X is —CH2— or —NR1,
• Y′ may be hydrogen or halogen when X′ is —CH2— or —NR1—,
• R4, R5, R6, R7, R12, R13, R14 and R15 are each independently hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted lower alkenyl, optionally substituted lower alkenyloxy, optionally substituted acyloxy, carboxy, optionally substituted lower alkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl, optionally substituted lower alkylthio, optionally substituted lower alkenylthio, optionally substituted amino, optionally substituted carbamoyl, guanidino, nitro, optionally substituted lower alkylsulfonyl, optionally substituted lower alkylsulfonyloxy, optionally substituted arylsulfonyl or optionally substituted arylsulfonyloxy,
• excluding
• (i) a compound wherein Y and Y′ are simultaneously hydrogen,
• (ii) a compound wherein at least one of Y and Y′ is optionally substituted acyl,
• (iii) a compound wherein at least one of —X—Y and —X′—Y′ is unsubstituted lower alkoxy, and
• (iv) a compound wherein —X—Y and —X′—Y′ are simultaneously optionally substituted lower alkoxy or amino substituted with phenyl,
• salt or hydrate thereof.

A compound of the formula (If′):

• wherein one of B ring and C ring is optionally substituted 5- or 6-membered heterocycle which contains one or two hetero atoms and the other is 6-membered heterocycle which contains at least one N atom, excluding a compound wherein every substituent of B ring is selected from cyano and halogen,
• X and X′ are each independently —O—, —CH2—, —NR1— (wherein R1 is hydrogen, optionally substituted lower alkyl, lower alkenyl, lower alkylcarbonyl or optionally substituted lower alkoxycarbonyl) or —S(O)p— wherein p is an integer of 0 to 2,
• Y and Y′ are each independently optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted lower alkoxycarbonyl, optionally substituted amino, optionally substituted sulfamoyl, optionally substituted aryl or optionally substituted 5- or 6-membered heterocycle,
• W2represents a bond when B ring is 5-membered heterocycle, and W3 represents a bond when C ring is 5-membered heterocycle,
• R1, taken together with Y or Y′, may form —(CH2)m—, —C(CH2)2—Q—(CH2)2— (wherein Q is CH2, O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—, —N═CH—N═CH—, —C(═O)—O(CH2)n—, —C(═O)—NR′—(CH2)n— or —C(═O)—NR′—N═CH— wherein m is 4 or 5, n is 2 or 3, R′ is hydrogen, lower alkyl or lower alkenyl,
• Y may be optionally substituted lower alkoxy when X is —CH2—,
• Y′ may be optionally substituted lower alkoxy when X′ is —CH2—,
• Y may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or —NR1—,
• Y′ may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X′ is —O— or —NR1,
• Y may be hydrogen or halogen when X is —CH2— or —NR1,
• Y′ may be hydrogen or halogen when X′ is —CH2— or —NR1—,
• R4, R5, R6 and R7 are each independently hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted lower alkenyl, optionally substituted lower alkenyloxy, optionally substituted cycloalkyloxy, optionally substituted RC(O)—O wherein R is hydrogen, alkyl, cycloalkyl or aryl, carboxy, optionally substituted lower alkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl, optionally substituted lower alkylthio, optionally substituted lower alkenylthio, optionally substituted amino, optionally substituted carbamoyl, guanidino, nitro, optionally substituted lower alkylsulfonyl, optionally substituted lower alkylsulfonyloxy, optionally substituted arylsulfonyl or optionally substituted arylsulfonyloxy, salt or hydrate thereof.

A compound of the formula (Ig′):

• wherein A ring and C ring are each independently optionally substituted 5- or 6-membered which contains one or two hetero atoms,
• W1 represents a bond when A ring is 5-membered heterocycle,
• W3 represents a bond when C ring is 5-membered heterocycle,
• X and X′ are each independently —O—, —CH2—, —NR1— (wherein R1 is hydrogen, optionally substituted lower alkyl, lower alkenyl, lower alkylcarbonyl or optionally substituted lower alkoxycarbonyl) or —S(O)p— wherein p is an integer of 0 to 2,
• Y and Y′ are each independently optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted lower alkoxycarbonyl, optionally substituted amino, optionally substituted sulfamoyl, optionally substituted aryl or optionally substituted 5- or 6-membered heterocycle,
• R1, taken together with Y or Y′, may form —(CH2)m—, —C(CH2)2—Q—(CH2)2— (wherein Q is CH2, O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—, —N═CH—N═CH—, —C(═O)—O(CH2)n—, —C(═O)—NR′—(CH2)n— or —C(═O)—NR′—N═CH— wherein m is 4 or 5, n is 2 or 3, and R′ is hydrogen, lower alkyl or lower alkenyl,
• Y may be optionally substituted lower alkoxy when X is —CH2—,
• Y′ may be optionally substituted lower alkoxy when X′ is —CH2—,
• Y may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or —NR1—,
• Y′ may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X′ is —O— or —NR1—,
• Y may be hydrogen or halogen when X is —NR1—,
• Y′ may be hydrogen or halogen when X′ is —NR1—, R8, R9, R10 and R11 are each independently hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted lower alkenyl, optionally substituted lower alkenyloxy, optionally substituted cycloalkyloxy, optionally substituted RC(O)—O wherein R is hydrogen, alkyl, cycloalkyl or aryl, carboxy, optionally substituted lower alkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl, optionally substituted lower alkylthio, optionally substituted lower alkenylthio, optionally substituted amino, optionally substituted carbamoyl, guanidino, nitro, optionally substituted lower alkylsulfonyl, optionally substituted lower alkylsulfonyloxy, optionally substituted arylsulfonyl or optionally substituted arylsulfonyloxy,
• excluding a compound wherein all of R8, R9, R10 and R11 are selected from hydrogen and halogen, salt or hydrate thereof.

A pharmaceutical composition for use as an immunosuppressant comprising a compound of the formula (Ib′):

• wherein C ring is optionally substituted 5- or 6-membered heterocycle which contains one or two hetero atoms, W3 represents a bond when C ring is 5-membered heterocycle,
• X and X′ are each independently —O—, —CH2—, —NR1— (wherein R1 is hydrogen, optionally substituted lower alkyl, lower alkenyl, lower alkylcarbonyl or optionally substituted lower alkoxycarbonyl), —S(O)p— (wherein p is an integer of 0 to 2) or a single bond,
• Y and Y′ are each independently optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted lower alkoxycarbonyl, optionally substituted amino, optionally substituted sulfamoyl, optionally substituted aryl or optionally substituted 5- or 6-membered heterocycle,
• R1, taken together with Y or Y′, may form —(CH2)m—, —C(CH2)2—Q—(CH2)2— (wherein Q is CH2, O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—, —N═CH—N═CH—, —C(═O)—O(CH2)n—, —C(═O) —NR′—(CH2)n— or —C(═O)—NR′—N═CH— wherein m is 4 or 5, n is 2 or 3, and R1 is hydrogen, lower alkyl or lower alkenyl,
• Y may be optionally substituted lower alkoxy when X is —CH2—,
• Y′ may be optionally substituted lower alkoxy when X′ is —CH2—,
• Y may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or —NR1—,
• Y′ may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X′ is —O— or —NR1—,
• Y may be hydrogen or halogen when X is —CH2— or —NR1—,
• Y′ may be hydrogen or halogen when X′ is —CH2— or NR1—,
• Y′ may be hydrogen, hydroxy, halogen, nitro or oxo when X′ is a single bond,
• R4, R5, R6, R7, R8, R9, R10 and R11 are each independently hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted lower alkenyl, optionally substituted lower alkenyloxy, optionally substituted cycloalkyloxy, optionally substituted RC(O)—O wherein R is hydrogen, alkyl, cycloalkyl or aryl, carboxy, optionally substituted lower alkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl, optionally substituted lower alkylthio, optionally substituted lower alkenylthio, optionally substituted amino, optionally substituted carbamoyl, guanidino, nitro, optionally substituted lower alkylsulfonyl, optionally substituted lower alkylsulfonyloxy, optionally substituted arylsulfonyl or optionally substituted arylsulfonyloxy, excluding a compound wherein all of R8, R9, R10 and R11 are selected from hydrogen and halogen, salt or hydrate thereof.

A pharmaceutical composition for use as an immunosuppressant comprising a compound of the formula (Ia′):

• wherein B ring is optionally substituted 5- or 6- membered heterocycle which contains one or two hetero atoms excluding a compound wherein every substituent of B ring is selected from cyano and halogen,
• W2 represents a bond when B ring is 5-membered heterocycle,
• X and X′ are each independently —O—, —CH2—, —NR1— (wherein R1 is hydrogen, optionally substituted lower alkyl, lower alkenyl, lower alkylcarbonyl or optionally substituted lower alkoxycarbonyl) or —S(O)p— wherein p is an integer of 0 to 2,
• Y and Y′ are each independently optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted lower alkoxycarbonyl, optionally substituted amino, optionally substituted sulfamoyl, optionally substituted aryl or optionally substituted 5- or 6-membered heterocycle,
• R1, taken together with Y or Y′, may form —(CH2)m—, —C(CH2)2—Q—(CH2)2— (wherein Q is CH2, O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—, —N═CH—N═CH—, —C(═O)—O(CH2)n—, —C(═O)—NR′—(CH2)n— or —C(═O)—NR′—N═CH— wherein m is 4 or 5, n is 2 or 3, R′ is hydrogen, lower alkyl or lower alkenyl,
• Y may be optionally substituted lower alkoxy when X is —CH2—,
• Y′ may be optionally substituted lower alkoxy when X′ is —CH2—,
• Y may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or —NR1—,
• Y′ may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X′ is —O— or, —NR1—,
• Y may be hydrogen or halogen when X is —CH2— or —NR1—,
• Y′ may be hydrogen or halogen when X′ is —CH2— or —NR1—,
• R4, R5, R6, R12, R13, R14 and R15 are each independently hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted lower alkenyl, optionally substituted lower alkenyloxy, optionally substituted cycloalkyloxy, optionally substituted RC(O)—O wherein R is hydrogen, alkyl, cycloalkyl or aryl, carboxy, optionally substituted lower alkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl, optionally substituted lower alkylthio, optionally substituted lower alkenylthio, optionally substituted amino, optionally substituted carbamoyl, guanidino, nitro, optionally substituted lower alkylsulfonyl, optionally substituted lower alkylsulfonyloxy, optionally substituted arylsulfonyl or optionally substituted arylsulfonyloxy, excluding
• (i) a compound wherein —X—Y and X′—Y′ are simultaneously unsubstituted lower alkyl, optionally substituted lower alkoxy or unsubstituted acyloxy,
• (ii) a compound wherein one of —X—Y and —X′—Y′ is methyl and the other is methoxy, and
• (iii) a compound wherein —X′—Y′ is hydrogen or halogen and —X—Y is unsubstituted lower alkyl, unsubstituted lower alkoxy or di(lower) alkylamino, salt or hydrate thereof.

A compound of the formula (I):

• wherein A ring and C ring are each independently optionally substituted aromatic carbocycle or optionally substituted 5- or 6-membered heterocycle which may fuse with benzene ring,
• wherein 5- or 6-membered heterocycle is pyrrole ring, imidazole ring, pyridine ring, pyridazine ring, pyrazine ring, triazole ring, triazine ring, isoxazole ring, oxazolo ring, isothiazole ring, thiazole ring, thiadiazole ring, furan ring, thiophene ring, tetrahydropyrane ring, dihydropyridine ring, dihydropyridazine, dihydropyrazine ring, dioxane ring, oxathiorane ring, thiane ring, pyrrolidine ring, pyrroline ring, imidazolidine ring, imidazoline ring, pyrazolidine ring, pyrazoline ring, piperidine ring, piperazine ring or morpholine ring,
• B ring is optionally substituted aromatic carbocycle or optionally substituted 5- or 6-membered heterocycle which may fuse with benzene ring,
• wherein 5- or 6-membered heterocycle is pyrazole ring, pyridine ring, pyridazine ring, pyrazine ring, triazole ring, triazine ring, isoxazole ring, oxadiazole ring, isothiazole ring, thiadiazole ring, tetrahydropyrane ring, dihydropyridine ring, dihydropyridazine, dihydropyrazine ring, dioxane ring, oxathiorane ring, thiane ring, pyrrolidine ring, pyrroline ring, imidazolidine ring, imidazoline ring, pyrazolidine ring, pyrazoline ring, piperdine ring, piperzine ring, morpholine ring,
• W1, W2 and/or W3 represents a single bond when A ring, B ring and/or C ring is optionally substituted 5-membered heterocycle,
• X is —O—, —CH2—, —NR1— wherein R1 is hydrogen, optionally substituted lower alkyl, lower alkenyl, lower alkylcarbonyl or optionally substituted lower alkoxycarbonyl or —S(O)p— wherein p is an integer of 0 to 2,
• Y is hydrogen, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted lower alkoxycarbonyl, optionally substituted sulfamoyl, optionally substituted amino, optionally substituted aryl or optionally substituted 5- or 6-membered heterocycle,
• Y may be optionally substituted lower alkoxy when X is —CH2—,
• Y may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or —NR1—,
• one of V1 and V2 is a single bond and the other is a single bond, an —O— bond, an —NH— bond, an —OCH2— bond, a —CH2O— bond, a —CH═CH— bond, a —C≡C— bond, a —CH(OR2)— bond, wherein R2 is hydrogen or lower alkyl, a —CO— bond, or an —NHCHR3— bond, wherein R3 is hydrogen or hydroxy, and at least one of A ring, B ring and C ring is optionally substituted aromatic carbocycle and at least another one is optionally substituted 5- or 6-membered heterocycle which may fuse with benzene ring when both of V1 and V2 are single bonds, salt or hydrate thereof.

A compound of the formula (I):

• wherein A ring is optionally substituted aromatic carbocycle or optionally substituted- 5- or 6-membered heterocycle which may fuse with benzene ring,
• wherein 5- or 6-membered heterocycle is pyrrole ring, imidazole ring, pyridine ring, pyridazine ring, pyrimidine ring, pyrazine ring, triazole ring, triazine ring, isoxazole ring, oxazole ring, oxadiazole ring, isothiazole ring, thiazole ring, thiadiazole ring, furan ring, thiophene ring, tetrahydropyrane ring, dihydropyridine ring, dihydropyridazine, dihydropyrazine ring, dioxane ring, oxathiorane ring, thiane ring, pyrrolidine ring, pyrroline ring, imidazolidine ring, imidazoline ring, pyrazolidine ring, pyrazoline ring, piperidine ring, piperazine ring or morpholine ring,
• B ring is optionally substituted aromatic carbocycle or optionally substituted 5- or 6-membered heterocycle which may fuse with benzene ring,
• C ring is optionally substituted pyrazole ring,
• W1, W2 and/or W3 represents a single bond when A ring, B ring and/or C ring is optionally substituted 5-membered heterocycle,
• X is —O—, —CH2—, —NR1— wherein R1 is hydrogen, optionally substituted lower alkyl, lower alkenyl, lower alkylcarbonyl or optionally substituted lower alkoxycarbonyl or —S(O)p— wherein p is an integer of 0 to 2,
• Y is hydrogen, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted lower alkoxycarbonyl, optionally substituted sulfamoyl, optionally substituted amino, optionally substituted aryl or optionally substituted 5- or 6-membered heterocycle,
• Y may be optionally substituted lower alkoxy when X is —CH2—,
• Y may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or —NR1—,
• one of V1 and V2 is a single bond and the other is a single bond, an —O— bond, an —NH— bond, an —OCH2— bond, a —CH2O— bond, a —CH═CH— bond, a —C≡C— bond, a —CH(OR2)— bond, wherein R2 is hydrogen or lower alkyl, a —CO— bond, or an —NHCHR3— bond, wherein R3 is hydrogen or hydroxy, and
• at least one of A ring, B ring and C ring is optionally substituted aromatic carbocycle and at least another one is optionally substituted 5- or 6-membered heterocycle which may fuse with benzene ring when both of V1 and V2 are single bonds, salt or hydrate thereof.

A compound of the formula (I):

• wherein A ring and B ring are each independently optionally substituted aromatic carbocycle or optionally substituted 5- or 6-membered heterocycle which may fuse with benzene ring, C ring is optionally substituted pyrimidine ring,
• W1 and/or W2 represents a single bond when A ring and/or B ring is optionally substituted 5-membered heterocycle,
• X is —O—, —CH2—, —NR1— wherein R1 is hydrogen, optionally substituted lower alkyl, lower alkenyl, lower alkylcarbonyl or optionally substituted lower alkoxycarbonyl or —S(O)p— wherein p is an integer of 0 to 2,
• Y is optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted cycloalkyl optionally substituted cycloalkenyl, optionally substituted lower alkoxycarbonyl, optionally substituted sulfamoyl, optionally substituted amino, optionally substituted aryl or optionally substituted 5- or 6-membered heterocycle,
• Y may be optionally substituted lower alkoxy when X is —CH2—,
• Y may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or —NR1—,
• Y may be optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl when X is —NR1—,
• Y may be hydrogen when X is —O— or —S(O)p—,
• one of V1 and V2 is a single bond and the other is a single bond, an —O— bond, an —NH— bond, an —OCH2— bond, a —CH2O— bond, a —CH═CH— bond, a —C≡C— bond, a —CH(OR2)— bond, wherein R2 is hydrogen or lower alkyl, a —CO— bond, or an —NHCHR3— bond, wherein R3 is hydrogen or hydroxy, and
• at least one of A ring, B ring and C ring is optionally substituted aromatic carbocycle and at least another one is optionally substituted 5- or 6-membered heterocycle which may fuse with benzene ring when both of V1 and V2 are single bonds, salt or hydrate thereof.

A compound of the formula (Ib′):

• wherein C ring is optionally substituted 5- or 6-membered heterocycle, W3 represents a bond when C ring is 5-membered heterocycle, wherein 5- or 6-heterocycle is pyrrole ring, imidazole ring, pyrazole ring, pyridine ring, pyridazine ring, pyrazine ring, isoxazole ring, oxazole ring, isothiazole ring, thiazole ring, furan ring, thiophene ring, tetrahydropyrane ring, dihydropyridine ring, dihydropyridazine, dihydropyrazine ring, dioxane ring, oxathiorane ring, thiane ring, pyrrolidine ring, pyrroline ring, imidazolidine ring, imidazoline ring, pyrazolidine ring, pyrazoline ring, piperidine ring, piperazine ring or morpholine ring,
• X and X′ are each independently —O—, —CH2—, —NR1— (wherein R1 is hydrogen, optionally substituted lower alkyl, lower alkenyl, lower alkylcarbonyl or optionally substituted lower alkoxycarbonyl) or —S(O)p— wherein p is an integer of 0 to 2,
• Y and Y′ are each independently optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted lower alkoxycarbonyl, optionally substituted amino, optionally substituted sulfamoyl, optionally substituted aryl or optionally substituted 5- or 6-membered heterocycle,
• R1, taken together with Y or Y′, may form —(CH2)m—, —C(CH2)2—Q—(CH2)2— (wherein Q is CH2, O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—, —N═CH—N═CH—, —C(═O)—O(CH2)n—, —C(═O)—NR′—(CH2)n— or —C(═O)—NR′—N═CH— wherein m is 4 or 5, n is 2 or 3, R′ is hydrogen, lower alkyl or lower alkenyl,
• Y may be optionally substituted lower alkoxy when X is —CH2—,
• Y′ may be optionally substituted lower alkoxy when X′ is —CH2—,
• Y may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or —NR1—,
• Y′ may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X′ is —O— or —NR1—,
• Y may be hydrogen or halogen when X is —CH2— or —NR1—,
• Y′ may be hydrogen or halogen when X′ is —CH2— or —NR1—,
• R4, R5, R6, R7, R8, R9, R10 and R11 are each independently hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted lower alkenyl, optionally substituted lower alkenyloxy, optionally substituted cycloalkyloxy, optionally substituted RC(O)O wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, carboxy, optionally substituted lower alkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl, optionally substituted lower alkylthio, optionally substituted lower alkenylthio, optionally substituted amino, optionally substituted carbamoyl, guanidino, nitro, optionally substituted lower alkylsulfonyl, optionally substituted lower alkylsulfonyloxy, optionally substituted arylsulfonyl or optionally substituted arylsulfonyloxy, excluding a compound wherein all of R8, R9, R10 and R11 are selected from hydrogen and halogen, salt or hydrate thereof.

A compound of the formula (Ib′):

• wherein C ring is optionally substituted pyrimidine,
• X and X′ are each independently —O—, —CH2—, —NR1— (wherein R1 is hydrogen, optionally substituted lower alkyl, lower alkenyl, lower alkylcarbonyl or optionally substituted lower alkoxycarbonyl) or —S(O)p— wherein p is an integer of 0 to 2,
• Y and Y′ are each independently optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted cycloalkyl optionally substituted cycloalkenyl, optionally substituted lower alkoxycarbonyl, optionally substituted amino, optionally substituted sulfamoyl, optionally substituted aryl or optionally substituted 5- or 6-membered heterocycle,
• R1, taken together with Y or Y′, may form —(CH2)m—, —C(CH2)2—Q—(CH2)2— (wherein Q is CH2, O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—, —N═CH—N═CH—, —C(═O)—O(CH2)n—, —C(═O)—NR′—(CH2)n— or —C(═O)—NR′—N═CH— wherein m is 4 or 5, n is 2 or 3, R′ is hydrogen, lower alkyl or lower alkenyl,
• Y may be optionally substituted lower alkoxy when X is —CH2—,
• Y′ may be optionally substituted lower alkoxy when X′ is —CH2—,
• Y may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or —NR1—,
• Y′ may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X′ is —O— or —NR1—,
• Y may be halogen when X is —CH2— or —NR1—,
• Y′ may be halogen when X′ is —CH2— or —NR1—,
• Y may be optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl when X is —NR1—,
• Y′ may be optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl when X′ is —NR1—,
• Y may be hydrogen when X is —NR1—,
• Y′ may be hydrogen when X′ is —NR1—,
• R4, R5, R6, R7, R8, R9, R10 and R11 are each independently hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted lower alkenyl, optionally substituted lower alkenyloxy, optionally substituted cycloalkyloxy, optionally substituted RC(O)O wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, carboxy, optionally substituted lower alkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl, optionally substituted lower alkylthio, optionally substituted lower alkenylthio, optionally substituted amino, optionally substituted carbamoyl, guanidino, nitro, optionally substituted lower alkylsulfonyl, optionally substituted lower alkylsulfonyloxy, optionally substituted arylsulfonyl or optionally substituted arylsulfonyloxy, excluding a compound wherein all of R8, R9, R10 and R11 are selected from hydrogen and halogen, salt or hydrate thereof.

A compound of the formula (Ia′):

• wherein B ring is optionally substituted 5- or 6-membered heterocycle (wherein 5- or 6-heterocycle is pyrazole ring, pyridine ring, pyridazine ring, pyrazine ring, isoxazole ring, isothiazole ring, tetrahydropyrane ring, thiane ring, pyrrolidine ring, pyrroline ring, imidazolidine ring, imidazoline ring, pyrazolidine ring, pyrazoline ring, piperidine ring, piperazine ring, morpholine ring, and the substituent is halogen, hydroxy, optionally substituted lower alkyl, optionally substituted acyloxy, optionally substituted lower alkenyl, optionally substituted lower alkenyloxy, optionally substituted RC(Q)Q wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, carboxy, optionally substituted lower alkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl, optionally substituted alkylthio, optionally substituted lower alkenylthio, optionally substituted amino, guanidine, nitro, optionally substituted lower alkylsulfonyl, optionally substituted lower alkylsulfonyloxy, optionally substituted arylsulfonyl or optionally substituted arylsulfonyloxy, excluding a compound wherein B ring is substituted with only halogen(s)), and
• W2 represents a bond when B ring is 5-membered heterocycle,
• X and X′ are each independently —O—, —CH2—, —NR1— (wherein R1 is hydrogen, optionally substituted lower alkyl, lower alkenyl, lower alkylcarbonyl or optionally substituted lower alkoxycarbonyl) or —S(O)p— wherein p is an integer of 0 to 2,
• Y and Y′ are each independently optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted lower alkoxycarbonyl, optionally substituted amino, optionally substituted sulfamoyl, optionally substituted aryl or optionally substituted 5- or 6-membered heterocycle,
• R1, taken together with Y or Y′, may form —(CH2)m, —C(CH2)2—Q—(CH2)2— (wherein Q is CH2, O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—, —N—CH—N═CH—, —C(═O)—O(CH2)n—, —C(═O)—NR′—(CH2)n— or —C(═O)—NR′—N═CH— wherein m is 4 or 5, n is 2 or 3, R′ is hydrogen, lower alkyl or lower alkenyl,
• Y may be optionally substituted lower alkoxy when X is —CH2—,
• Y′ may be optionally substituted lower alkoxy when X′ is —CH2—,
• Y may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or —NR1—,
• Y′ may be optionally substituted lower alkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionally substituted arylsulfonyl when X′ is —O— or —NR1—,
• Y may be hydrogen or halogen when X is —CH2— or —NR1,
• Y′ may be hydrogen or halogen when X′ is —CH2— or —NR1—,
• R4, R5, R6, R7, R12, R13, R14 and R15 are each independently hydrogen, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkoxy, optionally substituted lower alkenyl, optionally substituted lower alkenyloxy, optionally substituted RC(O)O wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, carboxy, optionally substituted lower alkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl, optionally substituted lower alkylthio, optionally substituted lower alkenylthio, optionally substituted amino, optionally substituted carbamoyl, guanidino, nitro, optionally substituted lower alkylsulfonyl, optionally substituted lower alkylsulfonyloxy, optionally substituted arylsulfonyl or optionally substituted arylsulfonyloxy,
• excluding
• (i) a compound wherein Y and Y′ are simultaneously hydrogen,
• (ii) a compound wherein at least one of Y and Y′ is optionally substituted RC(O),
• (iii) a compound wherein at least one of —X—Y and —X′—Y′ is unsubstituted lower alkoxy, and
• (iv) a compound wherein —X—Y and —X′—Y′ are simultaneously optionally substituted lower alkoxy or amino substituted with phenyl,
• salt or hydrate thereof.