Ono Sizuka, Ogawa Kiyoshi, Yamashita Kanako, Yamamoto Tamotsu, Kazuta Yuji, Matsuda Akira, Shuto Satoshi
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Chem Pharm Bull (Tokyo). 2002 Jul;50(7):966-8. doi: 10.1248/cpb.50.966.
(1S,2R)-1-phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide (2b, PPDC), a new class of potent N-methyl-D-aspartic acid (NMDA) receptor antagonist, was designed based on a new method for restricting the conformation of compounds having a cyclopropane ring. The three-dimensional structures of PPDC obtained by the three different methods of X-ray crystallographic analysis, usual MM2-calculations in vacuum, and MM2 calculations based on the nuclear Overhauser effect (NOE) data in D2O are similar, which are in accord with that hypothesized. These results suggest that this conformational restriction method is particularly effective in designing novel biologically active molecules.
(1S,2R)-1-苯基-2-[(S)-1-氨基丙基]-N,N-二乙基环丙烷甲酰胺（2b，PPDC）是一类新型强效N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，它是基于一种限制具有环丙烷环化合物构象的新方法设计而成。通过三种不同方法获得的PPDC的三维结构相似，这三种方法分别是X射线晶体学分析、常规的真空MM2计算以及基于重水（D2O）中核Overhauser效应（NOE）数据的MM2计算，所得结果与推测相符。这些结果表明，这种构象限制方法在设计新型生物活性分子方面特别有效。
