| 摘要 |
Biphenyl derivatives (I) are used in preparation of a drug to prevent and/or treat retinopathy. Biphenyl derivatives of formula (I) and their tautomeric forms, enantiomers, diastereoisomers, epimers and salts are used in preparation of a drug to prevent and/or treat retinopathy. X, Y1, Z = CH or N; m = 0-5; n = 0-4; R1 = C(O)OR, CH2CN, CH2OH or CH2C(O)OR; R = alkyl, alkaryl or (hetero)aryl (all optionally substituted by halo, OH, CN, alkoxy, Ar, OR'>, NO2, NRR', alkaryl or perhaloalkyl) or H; R'> = alkyl (optionally substituted by halo, OR, CN, COOR, NRR' (sic), NO2, (alkyl)aryl or -perhaloalkyl); R2 = halo, OR'>, NO2, NRCOR', (perhalo)alkyl, OH, CN, NRR'>, COOR, alkaryl, heteroaryl, aryl or alkyl (substituted by halo, OR, CN, C(O)OR, NRR'>, NO2, (alkyl)aryl or perhaloalkyl); R3 = halo, (perhalo)alkyl, (perhalo)alkoxy, -S(O)p-alkyl, NRR'>, OR, CN, C(O)OR, NO2, aryl, alkaryl or alkyl (optionally substituted by halo, OR, CN, C(O)OR, NRR'>, NO2, (alkyl)aryl, or perhaloalkyl); and p = 0-2. Independent claims are included for: (1) new biphenyl derivatives of formula (II) subject to provisos such that (2) when X and Y1 = C: (3) R2 = Cl, R1 = CO2H and m = 0; or (4) R2 = Cl, R1 = CO2H, m = 2 and R3 = 2,6-dichloro; (5) R2 = methoxy, R1 = CO2H or CO2CH3, m = 1 and R3 = 4-Cl; or (6) R2 = methoxy, R1 = hydroxymethyl and m = 0; or (7) R2 = methoxy, R1 = CH2CO2H, m = 2 and R3 = 2,3-dimethoxy or 3,4-dimethoxy, or (8) R2 = methoxy, R1 = CH2CO2H, m = 3 and R3 = 2,3,4-trimethoxy; (9) R2 = methyl, R1 = CO2Et and m = 0.; and (10) preparation of (II). [Image] - ACTIVITY : Antidiabetic; Ophthalmological. - MECHANISM OF ACTION : Caspase-10 inhibitor. The ability of (I) to inhibit caspase-10 was tested and results showed that (4-chloro-4'-methoxybiphenyl-2-yl)acetic acid exhibited median inhibitory concentration of 9 mu M. |
