Keratinocyte growth inhibitors and hydroxamic acid derivatives

A compound of the general formula (T):

• 31
• or a pharmaceutically acceptable salt thereof, wherein
• Ar1 is any cyclic structure selected from the following formulas (A) to (C):
• 32
• wherein Ar2 is 6-membered aromatic ring which may include 1 to 2 nitrogen atoms, D1 is —(CH2)n— (n is integer of 1 to 3), oxygen atom, sulfur atom, —S(O)—, —S(O)2— or —NR4— (R4 is hydrogen atom, C1-C8 alkyl or C1-C8 acyl), D2 is —(CH)— or nitrogen atom, R2 and R3 may be the same or different, and are hydrogen atom, hydroxyl, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, halogen atom, —NR5R6 (R5 and R6 may be the same or different, and are hydrogen atom, C1-C8 alkyl, C1-C8 acyl, carbamoyl or C1-C4 alkylcarbamoyl), wherein the said C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl may be substituted by halogen atom, heterocycle, C1-C4 alkoxy, C1-C4 acyl, C1-C4 acyloxy, heteroaryloxy, C1-C4 alkylthio, phenyl, phenoxy or NR7R8— (R7 and R8 may be the same or different, and are hydrogen atom, C1-C8 alkyl or C1-C8 acyl);
• R1 is hydrogen atom or methyl;
• W is divalent atomic group of the following formula (IIa) or (IIb):
• 33
• R is hydrogen atom, C1-C8 alkyl or phenyl, wherein the said C1-C8 alkyl and phenyl may be substituted by halogen atom, hydroxyl, nitrile, C1-C4 alkyloxycarbonyl, carboxyl, carbamoyl, C1-C4 alkylcarbamoyl, C2-C4alkenyl, C2-C4alkynyl, heterocycle, C1-C4 alkoxy, C1-C4acyl, C1-C4acyloxy, heteroaryloxy, C1-C4alkylthio, phenyl, biphenyl, phenoxy, C1-C4 alkylsulfonyl, arylsulfonyl, arylaminosulfonyl or NR9R10 (R9 and R10maybe the same or different, and are hydrogen atom, C1-C8 alkyl, C1-C8 acyl, carbamoyl or C1-C4 alkylcarbamoyl);
• X is atomic group of the following formula:
• 34
• wherein cyclic structure Ar3 is benzene ring or 5- or 6-membered heteroaromatic ring including one oxygen atom, one sulfur atom or 1 to 2 nitrogen atoms, B is covalent bond, —(CH2)q— (q is integer of 1 to 4), —CH═CH—, —C(O)—, —CH(OH)— or —NR11—, R11 is hydrogen atom, C1-C8 alkyl, C2-C8 alkenyl or C2-C8 alkynyl, wherein the said C1-C8 alkyl, C2-C8 alkenyl and C2-C8 alkynyl may be substituted by halogen atom, heterocycle, C1-C8 alkoxy, C1-C8 acyl, C1-C8 acyloxy, heteroaryloxy, C1-C8 alkylthio, phenyl, phenoxy or —NR12R13 (R12 and R13 may be the same or different, and are hydrogen atom, C1-C8 alkyl, C1-C8 acyl, carbamoyl or C1-C4 alkylcarbamoyl);
• Z1, Z2 and Z3may be the same or different, and are hydrogen atom, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, phenyl, heterocycle, halogen atom, hydroxyl, C1-C8alkoxy, C1-C8 acyl, C1-C8 acyloxy, phenoxy, heteroaryloxy, C1-C8 alkylthio or —NR14R5 (R4 and R15 may be the same or different, and are hydrogen atom, C1-C8 alkyl, C1-C8 acyl, carbamoyl or C1-C4 alkylcarbamoyl), wherein the said C1-C8 alkyl, phenyl, heterocycle, C2-C8alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, C1-C8 acyl, C1-C8 acyloxy, phenoxy, heteroaryloxy and C1-C8 alkylthio may be substituted by halogen atom, heterocycle, C1-C8 alkoxy, C1-C8 acyl, C1-C4 alkylsulfonyl, cyano, C1-C4 alkoxycarbonyl, hydroxyl, C1-C8 acyloxy, heteroaryloxy, C1-C8 alkylthio, phenyl, phenoxy or amino, or Z1 and Z2 may be combined to represent divalent atomic group —O—CH2—O—.

A compound of the general formula (Ia):

• 35
• or a pharmaceutically acceptable salt thereof, wherein
• R1 is hydrogen atom or methyl, R and R17 may be the same or different, and are hydrogen atom or C1-C4 alkyl, Xa is atomic group of the following formula (D), (E), (F) or (G):
• 36
• 2-propynyl, 2-butynyl, phenyl, halogen, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl, cyano, C1-C4 alkoxycarbonyl, C1-C4 acyloxy or hydroxyl;
• R19 is hydrogen atom or C1-C8 alkyl, wherein the said C1-C8 alkyl may be substituted by C1-C4 alkoxy, R25 is hydrogen atom or C1-C8 alkoxy).

A compound of the general formula (Ib):

• 37
• or a pharmaceutically acceptable salt thereof, wherein
• Ar1 is any cyclic structure selected from the following formulas (A) to (C):
• 38
• wherein Ar is 6-membered aromatic ring which may include 1 to 2 nitrogen atoms, D1 is —(CH2)n— (n is integer of 1 to 3), oxygen atom, sulfur atom, —S(O)—, —S(O)2— or NR4— (R4 is hydrogen atom, C1-C8 alkyl or C1-C8 acyl), D2 is —(CH)— or nitrogen atom, R2 and R3may be the same or different, and are hydrogen atom, hydroxyl, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, halogen atom, —NR5R6 (R5 and R6 may be the same or different, and are hydrogen atom, C1-C8 alkyl, C1-C8 acyl, carbamoyl or C1-C4 alkylcarbamoyl), wherein the said C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl may be substituted by halogen atom, heterocycle, C1-C4 alkoxy, C1-C4 acyl, C1-C4 acyloxy, heteroaryloxy, C1-C4 alkylthio, phenyl, phenoxy or —NR7R8 (R7 and R8 may be the same or different, and are hydrogen atom, C1-C8 alkyl or C1-C8 acyl);
• R is hydrogen atom, C1-C8 alkyl or phenyl, wherein the said C1-C8 alkyl and phenyl may be substituted by halogen atom, hydroxyl, nitrile, C1-C4alkyloxycarbonyl, carboxyl, carbamoyl, C1-C4 alkylcarbamoyl, C2-C4 alkenyl, C2-C4 alkynyl, heterocycle, C1-C4 alkoxy, C1-C4 acyl, C1-C4 acyloxy, heteroaryloxy, C1-C4 alkylthio, phenyl, biphenyl, phenoxy, C1-C4 alkylsulfonyl, arylsulfonyl, arylaminosulfonyl or —NR9R10 (R9 and R10 may be the same or different, and are hydrogen atom, C1-C8 alkyl, C1-C8 acyl, carbamoyl or C1-C4 alkylcarbamoyl);
• Xb is atomic group of the following formula:
• 39
• wherein cyclic structure Ar3 is benzene ring or 5- or 6-membered heteroaromatic ring including one oxygen atom, one sulfur atom or 1 to 2 nitrogen atoms, B is covalent bond, —(CH2)q— (q is integer of 1 to 4), —CH═CH—, —C(O)—, CH(OH)— or NR11—, R11 is hydrogenatom, C1-C8alkyl, C2-C8alkenylor C2-C8alkynyl, wherein the said C1-C8 alkyl, C2-C8 alkenyl and C2-C8 alkynyl may be substituted by halogen atom, heterocycle, C1-C8 alkoxy, C1-C8 acyl, C1-C8 acyloxy, heteroaryloxy, C1-C8 alkylthio, phenyl, phenoxy or NR12R13 (R12 and R13 may be the same or different, and are hydrogen atom, C1-C8 alkyl, C1-C8 acyl, carbamoyl or C1-C4 alkylcarbamoyl);
• Z1, Z2 and Z3 may be the same or different, and are hydrogen atom, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, phenyl, heterocycle, halogenatom, hydroxyl, C1-C8alkoxy, C1-C8 acyl, C1-C8 acyloxy, phenoxy, heteroaryloxy, C1-C8 alkylthio or —NR14R15 (R14 and R15 may be the same or different, and are hydrogen atom, C1-C8 alkyl, C1-C8 acyl, carbamoyl or C1-C4 alkylcarbamoyl), wherein the said C1-C8 alkyl, phenyl, heterocycle, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, C1-C8 acyl, C1-C8 acyloxy, phenoxy, heteroaryloxy and C1-C8 alkylthio may be substituted by halogen atom, heterocycle, C1-C8 alkoxy, C1-C8 acyl, C1-C4 alkylsulfonyl, cyano, C1-C4 alkoxycarbonyl, hydroxyl, C1-C8 acyloxy, heteroaryloxy, C1-C8 alkylthio, phenyl, phenoxy or amino, or Z1 and Z2 may be combined to represent divalent atomic group-O—CH2—O—.

A compound of the general formula (Ic):

• 40
• or a pharmaceutically acceptable salt thereof, wherein
• Xc is atomic group of the following formula (H), (I), (J) or (K):
• 41
• wherein R20 is vinyl, ethynyl, pyridyloxy, pyrazyloxy, C1-C8 alkyl, C1-C8 acyl or C1-C8 alkoxy, wherein the said C1-C8 alkyl, C1-C8 acyl or C1-C8 alkoxy may be substituted by phenyl, halogen atom, C1-C4 alkoxy, C1-C4 alkylthio, C1-C4 alkylsulfonyl, cyano, C1-C4 alkoxycarbonyl, C1-C4acyloxyorhydroxyl;
• R21 and R22 are hydrogen atom or C1-C8alkyl, wherein the said C1-C8alkyl may be substituted by C1-C4 alkoxy.