Duke N E, Codding P W
Department of Chemistry, University of Calgary, Alberta, Canada.
Acta Crystallogr B. 1993 Aug 1;49 ( Pt 4):719-26. doi: 10.1107/s0108768193000576.
Studies of derivatives of the anticonvulsant methaqualone led to the discovery that unsaturation in the 2-substituent produced active but less toxic compounds; accordingly, 2-arylethanone derivatives have been developed. The crystal structures of five 2-arylethanone derivatives of methaqualone were determined to probe structure-activity relationships. Although these compounds display different activities, the solid-state and calculated structures are similar: each compound is observed as the neamine tautomer containing an intramolecular hydrogen bond between the ethanone and the amine N atom and the molecular conformations are the same. These studies conclude that recognition of the anticonvulsants arises from specific binding of an ortho substituent on the N(3) phenyl substituent, rather than from binding of a particular conformation or tautomeric form adopted by the compound containing an ortho substituent, and that such recognition is characteristic of a broad range of anticonvulsant drugs. Crystal data: [see text].
对抗惊厥药甲喹酮衍生物的研究导致发现，2-取代基中的不饱和键产生了活性更高但毒性更低的化合物；因此，已开发出2-芳基乙酮衍生物。测定了五种甲喹酮的2-芳基乙酮衍生物的晶体结构，以探究构效关系。尽管这些化合物表现出不同的活性，但固态结构和计算结构相似：每种化合物均以新霉素互变异构体形式存在，在乙酮和胺N原子之间存在分子内氢键，且分子构象相同。这些研究得出结论，抗惊厥药的识别源于N(3)苯基取代基上邻位取代基的特异性结合，而非源于含邻位取代基化合物所采用的特定构象或互变异构形式的结合，并且这种识别是多种抗惊厥药物的特征。晶体数据：[见正文]
