Ezumi K, Yamakawa M, Narisada M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
J Med Chem. 1990 Apr;33(4):1117-22. doi: 10.1021/jm00166a006.
Conformational analyses on thromboxane A2 (TxA2), its receptor agonist, U-46619, and its receptor antagonist, sulotroban, were carried out by molecular mechanics (MMFF) or molecular orbital (MNDO) methods. Two kinds of putative active conformations of TxA2 and the agonist were proposed on the basis of these results by referring to the hairpin conformation hypothesis. From the superposition of stable conformers of sulotroban on those conformers, the molecular structural requirements for potent TxA2 receptor antagonism were elucidated. S-145 in which these requirements are satisfied was a very potent TxA2 antagonist.
通过分子力学（MMFF）或分子轨道（MNDO）方法，对血栓素A2（TxA2）、其受体激动剂U-46619及其受体拮抗剂舒洛地班进行了构象分析。参照发夹构象假说，基于这些结果提出了TxA2和激动剂的两种假定活性构象。通过将舒洛地班的稳定构象与这些构象进行叠加，阐明了强效TxA2受体拮抗作用的分子结构要求。满足这些要求的S-145是一种非常强效的TxA2拮抗剂。
