Hallinan E A, Hagen T J, Tsymbalov S, Husa R K, Lee A C, Stapelfeld A, Savage M A
Department of Chemistry, Searle, Skokie, Illinois 60077, USA.
J Med Chem. 1996 Jan 19;39(2):609-13. doi: 10.1021/jm950454k.
8-Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4-pyridinyl)propyl]hydrazide, monohydrochloride (1, SC-51089) is a functional PGE2 antagonist selective for the EP1 receptor subtype with antinociceptive activity. During metabolism in cultured rat hepatocytes, SC-51089, which contains a diacylhydrazine moiety, has been shown to release hydrazine. Analogs of SC-51089, in which the diacylhydrazine functionality has been replaced by isosteric and isoelectronic groups, have been synthesized and have been shown to be analgesics and PGE2 antagonists of the EP1 subtype. This report discusses the structure-activity relationships within these series.
8-氯二苯并[b,f][1,4]恶唑嗪-10(11H)-羧酸2-[1-氧代-3-(4-吡啶基)丙基]酰肼盐酸盐（1，SC-51089）是一种对EP1受体亚型具有选择性的功能性前列腺素E2拮抗剂，具有抗伤害感受活性。在培养的大鼠肝细胞代谢过程中，含有二酰肼部分的SC-51089已被证明会释放肼。已合成了SC-51089的类似物，其中二酰肼官能团已被等排和等电子基团取代，并且已证明它们是EP1亚型的镇痛药和前列腺素E2拮抗剂。本报告讨论了这些系列中的构效关系。
