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SUBSTITUTED AROMATIC COMPOUNDS AS c.AMP PHOSPHODIESTERASE- AND TNF-INHIBITORS

机译:替代的芳香族化合物,如c.AMP磷酸酯酶和TNF抑制剂

摘要

This invention is directed to compounds of formula (I), wherein R1 is an optionally substituted lower alkyl group; R2 is an optionally substituted oxaaliphatic group; R3 is an optionally substituted aryl group or an optionally substituted heteroaryl group; Q?1, Q2 and Q3¿ are independently nitrogen, CX or CH; Z1 is oxygen or sulfur; Z2 is -CH=CH-, -C C-, -CH¿2?-CZ-, -CZCH2-, -CZ-CZ-, -CH2-NH-, -CH2-O-, -CH2-S-, -CX2-O-, -CZNH-, -NH-CH2-, -O-CH2_, -SCH2-, -SOCH2-, -SO2CH2-, -O-CX2-, -O-CZ-, -NH-CZ-, -N=N-, -NH-SO2-, -SO2-NH-, -CZ-CZ-NH-, -NH-CO-O-, -O-CO-NH- or -NH-CO-NH-; Z is oxygen or sulfur; and X is halo; or an N-oxide thereof or a pharmaceutically acceptable salt thereof, which possess useful pharmaceutical properties. They are especially useful for inhibiting the production or physiological effects of TNF and inhibit cyclic AMP. The present invention is also directed to their pharmaceutical use, pharmaceutical compositions containing the compounds, and methods for their preparation.
机译:本发明涉及式(I)的化合物,其中R 1是任选取代的低级烷基; R 2是任选取代的草脂族基团; R 3为任选取代的芳基或任选取代的杂芳基; Q 1,Q 2和Q 3分别是氮,CX或CH; Z1是氧或硫; Z 2是-CH = CH-,-CC-,-CH 2?-CZ-,-CZCH2-,-CZ-CZ-,-CH2-NH-,-CH2-O-,-CH2-S-, -CX2-O-,-CZNH-,-NH-CH2-,-O-CH2 _,-SCH2-,-SOCH2-,-SO2CH2-,-O-CX2-,-O-CZ-,-NH-CZ- ,-N = N-,-NH-SO2-,-SO2-NH-,-CZ-CZ-NH-,-NH-CO-O-,-O-CO-NH-或-NH-CO-NH- ; Z是氧或硫; X是光环;或其有用的药物特性的N-氧化物或其N-氧化物或其药学上可接受的盐。它们对于抑制TNF的产生或生理作用并抑制环状AMP特别有用。本发明还涉及它们的药物用途,包含所述化合物的药物组合物及其制备方法。

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