Enantiomeric characterization and structure elucidation of Otamixaban

作     者：Jian Shen Jiping Yang Winfried Heyse Harald Schweitzer Norbert Nagel Doris Andert Chengyue Zhu Vincent Morrison Gregory A.Nemeth Teng-Man Chen Zhicheng Zhao Timothy A.Ayers Yong-Mi Choi 

作者机构：Sanofi1041 Route 202-206BridgewaterNJ 08807United States SanofiIndustriepark Hoechst Bldg.D-65926 FrankfurtGermany 

出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)

年 卷 期：2014年第4卷第3期

页      面：197-204页

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：acknowledgments the authors thank drs. b. vanasse and p  agrawala for reviewing the manuscript  and dr y. he of biotools for performing comparevoa calculation 

主　　题：Vibrational circular dichroism DFT IR Absolute configuration Vicinal proton-proton coupling scXRD 

摘      要：Otamixaban is a potent （Ki=0.5 nM） fXa inhibitor currently in late-stage clinical develop-ment at Sanofi for the management of acute coronary syndrome. Being unproductive in obtaining a suitable crystal of Otamixaban, the required enantiomeric characterization has been accomplished using vibrational circular dichroism （VCD） spectroscopy. Selected by a spectrum similarity index, the calculated spectra of several higher energy conformers were found to match well with the observed spectra. The characteristic IR bands of these conformers were also identified and attributed to the solvation effect. Combined with both the single crystal x-ray diffraction results for an intermediate and the proton NMR study, the absolute configuration of Otamixaban is unambiguously determined to be （R,R）.