新型强效3',5'-环磷酸腺苷磷酸二酯酶III抑制剂：噻唑并[4,5-b][1,6]萘啶-2-酮
Novel and potent adenosine 3',5'-cyclic phosphate phosphodiesterase III inhibitors: thiazolo[4,5-b][1,6]naphthyridin-2-ones.
作者信息
Singh B, Bacon E R, Lesher G Y, Robinson S, Pennock P O, Bode D C, Pagani E D, Bentley R G, Connell M J, Hamel L T
机构信息
Department of Medicinal Chemistry, Sterling Winthrop Pharmaceuticals Research Division, Collegeville, Pennsylvania 19426, USA.
出版信息
J Med Chem. 1995 Jul 7;38(14):2546-50. doi: 10.1021/jm00014a007.
The transformation of 3-bromo-1,6-naphthyridin-2(1H)-ones 8 to thiazolo[4,5-b][1,6]naphthyridin-2(1H)-ones 12 resulted in a 2-9-fold increase in cAMP phosphodiesterase (PDE) III inhibitory potency. Unlike the secondary binding sites on the cAMP PDE III isozyme which interact with the methyl group of milrinone (2) and CI-930 (4), the site which interacts with the 5-substituents of 1,6-naphthyridin-2(1H)-ones and the 8-substituents of thiazolo[4,5-b][1,6]naphthyridin-2(1H)-ones 12 is able to accommodate a diverse group of substituents which have different steric and electronic requirements.
将3-溴-1,6-萘啶-2(1H)-酮8转化为噻唑并[4,5-b][1,6]萘啶-2(1H)-酮12，导致环磷酸腺苷磷酸二酯酶（PDE）III抑制活性提高了2至9倍。与环磷酸腺苷PDE III同工酶上与米力农（2）和CI-930（4）的甲基相互作用的二级结合位点不同，与1,6-萘啶-2(1H)-酮的5-取代基和噻唑并[4,5-b][1,6]萘啶-2(1H)-酮12的8-取代基相互作用的位点能够容纳具有不同空间和电子需求的多种取代基。
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