Watanabe Y, Usui H, Shibano T, Tanaka T, Kanao M
Daiichi Pharmaceutical Co., Ltd., Research Institute, Tokyo, Japan.
Chem Pharm Bull (Tokyo). 1990 Oct;38(10):2726-32. doi: 10.1248/cpb.38.2726.
New serotonine 2 (5-HT2) antagonists with a monocyclic or bicyclic 2,4(1H,3H)-pyrimidinedione have been prepared and their activities evaluated. In a series of monocyclic compounds, 1-substituted 5-phenyl-2,4(1H,3H)-pyrimidinedione 14 showed potent in vitro activity, and the corresponding 3-substituted 5-phenyl and 6-phenyl derivatives 3, 8 and 20a also showed moderate activity. In the bicyclic compounds, 3-substituted 5,6,7,8-tetrahydro-2,4(1H,3H)-quinazolinedione 33 exhibited the most potent activity among the compounds prepared in this paper. The in vivo antagonist activity of 33 was comparable to that of ketanserin, a typical peripheral 5-HT2 antagonist.
已制备出具有单环或双环2,4(1H,3H)-嘧啶二酮结构的新型血清素2（5-HT2）拮抗剂，并对其活性进行了评估。在一系列单环化合物中，1-取代的5-苯基-2,4(1H,3H)-嘧啶二酮14显示出强大的体外活性，相应的3-取代的5-苯基和6-苯基衍生物3、8和20a也显示出中等活性。在双环化合物中，3-取代的5,6,7,8-四氢-2,4(1H,3H)-喹唑啉二酮33在本文制备的化合物中表现出最强的活性。33的体内拮抗剂活性与典型的外周5-HT2拮抗剂酮色林相当。
