Substituted biphenyl derivatives as phosphodiesterase inhibitors

摘要

A compound of the following structure: wherein, when R8=H: R1=alkyl, cycloalkyl, arylalkyl, aryl; R2=cycloalkyl, aryl, C3-C10 alkyl; X,Y=O, S(O)n, NH; Z=CHO, CO2R3, CONHR4R5, CN, COR6, H, halo, HCN, NHCONR4R5, CONR4OR5, CONR4NR5R6, 1-tetrazole, S(O)nOH, S(O)nNR3R4, C=NOH, C(=N(OH)NH2, OCONR7R6, P(O)(OR4)2, C(=N(YR3))R4, NH2, SH, OH, OS(O)2R3, C(=NYC(=O)R3)R4, C(O)CO2R3, C(O)CONR3R4, CH(OH)CO2R3, CHFCO2R3, CF2CO2R3, CH(OH)CONR3R4, CF2CONR3R4, C=NNH2, C(=NOC(=O)R3)R4, C(=NNHC(=O)R3)R4, C(=NOH)R3, C(=NNR3)R4, NHC(=O)R6 or C(O)CONH2; R3, R4, R5, R6, R7=hydrogen, alkyl, aryl, aryalkyl, cycloalkyl, or fluoroalkyl; or a compound of Structure I, as just defined, wherein: X,Y=CH2, O, S(O)n, or NH; Z and R8=CO2R3, CONR3, or R8 and Z are concatenated such that R8Z=C(O)NHNHC(O), (CH2)mC(=W), V(CH2)mC(=W), or VnCH=CH(CH2)nC(=W); where V=O, S(O)n, NH; W=O, NOH, NHNH2, NOC(O)CH3, or NNHC(O)CH3; n=0-2; and m=2-4 or pharmaceutically acceptable salts thereof, useful in the treatment of asthma, and allergic and inflammatory diseases, as well as methods of treatment and pharmaceutical compositions utilizing the same.