Novel diarylalkene derivatives and novel diarylalkane derivatives

Diarylalkene derivatives or diarylalkane derivatives of the following general formula (1-A), or pharmaceutically acceptable salts thereof:

• 119
• wherein A represents —CH═CH—, —CH2—CH2— or —S—;
• B represents —(CH2)v—CHR21 wherein v represents 0 to 3, R21 represents H, a lower alkyl, an aryl, a hydroxyl-lower alkyl, —(CH2)w—COOR29 or —(CH2)w—NR29R30 wherein R29 and R30 each independently represent hydrogen atom or a lower alkyl group and w represents 0 to 4;
• G represents —(CO)— or a covalent bond;
• m represents 0 to 6;
• and
• R7 and R8 each independently represent H, a lower alkyl, an aryl, —(CO)R18a wherein R18a represents H, a lower alkyl, an aryl or a cycloalkyl group which may contain a hetero atom in the ring, or —(CO)OR20 wherein R20 represents an alkyl group having 1 to 12 carbon atoms, an aryl or a cycloalkyl group which may have a hetero atom in the ring.

A method for treating diseases selected from pain, brain injury caused by ischemia at the acute stage after the onset of cerebral infarction or cerebral hemorrhage, Alzheimer's disease, AIDS related dementia, Parkinson's disease, progressive neurodegenerative diseases, neuropathy caused by head injury, bronchial asthma, unstable angina, irritable colitis or withdrawal symptoms after addiction to drugs, which comprises administrating a diarylalkene derivative or a diarylalkane derivative of the following general formula (1), (2), (3) or (4), or a pharmaceutically acceptable salt thereof as the active ingredient to a patient in need of such treatment:

• 124 125
• wherein A represents —CH═CH—, —CH2—CH2—, —S—, —CH2—S—, —S—CH2—, —O—, —CH2—O—, —O—CH2—, —N(R17)—CH2—, —CH2—N(R17)—, —CH═CH—CH2—, —CH2—CH═CH—, —CH2—CH2—CH2—, —N(R17)—(CO)—, —(CO)—N(R17)—, —(CO)—, —(SO)—, —C(R18R19)— wherein R17 represents H, a lower alkyl or an aryl, and R18 and R19 are each independently selected from the group consisting of H, a lower alkyl, an aryl and —C(O)OR15 wherein R15 represents a lower alkyl or an aryl;
• a, b, c and d are each independently selected from the group consisting of CR1 and CR2;
• or one of a, b, c and d is N;
• R1, R2, R3 and R4 each independently represent H, a halogen, —CF3, —OR14, —COR14, —SR14, —S(O)t R15, —N(R14)2, —NO2, —OC(O)R14, —CO2R14, —OCO2R14, —CN, —NR14COOR15, —SR15C(O)OR15 or —SR15N(R16)2 wherein R14 represents H, a lower alkyl, an aryl or an aryl-lower alkyl group, R15 represents a lower alkyl or an aryl group, R16 is independently selected from the group consisting of H and —C(O)OR15, and t represents 1 or 2;
• V—W represents C═C, CH—CH, CH—N or N—CH;
• Z is selected from the group consisting of C, CH and N (with the proviso that when Z is C, the bond represented by a dotted line represents a double bond and when Z is CH or N, the bond represented by the dotted line represents a single bond;
• n represents 0 to 3;
• R5 and R6 each represent H, a halogen, —CF3, a lower alkyl or an aryl;
• or R5 and R6 together represent ═O or ═S;
• Y1 represents O or S;
• B represents NR17a, —NR17a(CH2) vCHR21—, —(CH2)vCHR21— wherein v represents 0 to 3, R17a represents H, a lower alkyl or an aryl, R21 represents H, a lower alkyl, an aryl, a hydroxyl-lower alkyl, —CH2SH, —CH2CH2SCH3, —CH2(CO)NH2, —CH2CH2(CO)NH2, —(CH2)w—COOR29, —(CH2)w—NR29R30 wherein R29 and R30 each independently represent hydrogen atom or a lower alkyl group, and w represents 0 to 4, —(CH2)3NHC(NH2)═NH, benzyl, 4-hydroxybenzyl, 3-indoylmethyl or 5 -imidazoylmethyl;
• G represents —(CO)—, —(SO)—, —(SO2)— or a covalent bond;
• m represents 0 to 6;
• Y2 represents C or S;
• p and q are each independently selected from the group consisting of 1, 2 and 3;
• R7 and R8 each independently represent H, a lower alkyl, an aryl, —(CO)R18a, —(CS)R18a, —(CO)NR18aR19a, —(CS)NR18aR19a wherein R18a represents H, a lower alkyl, an aryl or a cycloalkyl group which may have a hetero atom in the ring, R19a represents H, a lower alkyl or an aryl;
• or R18a and R19a together form a cycloalkyl which may have a halogen, —CF3, a lower alkyl or an aryl as a substituent, —(CO)OR20 or —(CS)OR20 wherein R20 represents an alkyl group having 1 to 12 carbon atoms, an aryl, a cycloalkyl group which may have a hetero atom in the ring, an aryl-lower alkyl group, or a group of the following general formula (5):
• 126
• wherein Y4 and Y3 each represent O or S;
• s represents 0 to 6;
• E represents NR22 or CHR23 wherein R22 represents H, a lower alkyl or an aryl;
• and R23 represents H, a lower alkyl, an aryl, a hydroxyl-lower alkyl, —CH2SH, —CH2CH2SCH3, —CH2(CO)NH2, —CH2CH2(CO)NH2, —CH2COOH, —CH2CH2COOH, —(CH2)4NH2, —(CH2)3NHC(NH2)═NH, benzyl, 4-hydroxybenzyl, 3-indoylmethyl or 5-imidazoylmethyl;
• R24 represents H, a lower alkyl or an aryl;
• R25 represents H, a lower alkyl, an aryl, —OR18a, —(CO)R18a, —(CS)R18a, —(CO)NR18aR19a, —(CS)NR18aR19a, —(CO)OR20 or —(CS)OR20 wherein R18a, R19a and R20 are as defined above,
• R9 represents H, a lower alkyl, an aryl, —(CO)R18a, —(CS)R18a, —(CO)NR18aR19a, —(CS)NR18aR19a, —(CO)OR20 or —(CS)OR20 wherein R18a, R19a and R20 are as defined above;
• R10 represents H, a lower alkyl or an aryl;
• R11 represents H, a lower alkyl or an aryl;
• R12 represents H, a lower alkyl, an aryl, —(CO)R18a, —(CS)R18a, —(CO)NR18aR19a, —(CS)NR18aR19a, —(CO)OR20 or —(CS)OR20 wherein R18a, R19a and R20 are as defined above, or a substituent represented by the following general formula (6):
• 127
• wherein s1 represents 1 to 6;
• Y3 represents O or S,
• R26 represents H, a lower alkyl or an aryl;
• R27 represents H, a lower alkyl, an aryl, —OR18a, —(CO)R18a, —(CS)R18a, —(CO)NR18aR19a, —(CS)NR18aR19a, —(CO)OR20 or —(CS)OR20 wherein R18a, R19a and R20 are as defined above;
• or R11 and R12 form a substituent represented by the following general formula (7) together with the nitrogen atom:
• 128
• wherein Y3 represents O or S, and R27 represents a group described above.