• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

奥他米班的对映体表征与结构解析

Enantiomeric characterization and structure elucidation of Otamixaban.

作者信息

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

机构信息

Sanofi, 1041 Route 202-206, Bridgewater, NJ 08807, United States.

Sanofi, Industriepark Hoechst Bldg., D-65926 Frankfurt, Germany.

出版信息

J Pharm Anal. 2014 Jun;4(3):197-204. doi: 10.1016/j.jpha.2013.10.001. Epub 2013 Nov 26.

DOI:10.1016/j.jpha.2013.10.001
PMID:29403883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5761123/
Abstract

Otamixaban is a potent (Ki=0.5 nM) fXa inhibitor currently in late-stage clinical development 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 (,).

摘要

奥他米班是一种强效（Ki = 0.5 nM）的Xa因子抑制剂，赛诺菲公司目前正处于急性冠脉综合征治疗的后期临床开发阶段。由于难以获得合适的奥他米班晶体，因此利用振动圆二色光谱（VCD）完成了所需的对映体表征。通过光谱相似性指数进行筛选，发现几个高能构象体的计算光谱与观测光谱匹配良好。还确定了这些构象体的特征红外波段，并归因于溶剂化效应。结合中间体的单晶X射线衍射结果和质子核磁共振研究，明确确定奥他米班的绝对构型为（，）。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/cd2fed477a81/fx00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/3e64dc0b2458/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/d87ab3f65f7b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/9f76115b4ef1/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/dd36cb922dc6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/b61e15946c31/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/125a10731a5f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/80955c497183/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/cd2fed477a81/fx00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/3e64dc0b2458/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/d87ab3f65f7b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/9f76115b4ef1/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/dd36cb922dc6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/b61e15946c31/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/125a10731a5f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/80955c497183/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/302a/5761123/cd2fed477a81/fx00.jpg

相似文献

1
Enantiomeric characterization and structure elucidation of Otamixaban.奥他米班的对映体表征与结构解析
J Pharm Anal. 2014 Jun;4(3):197-204. doi: 10.1016/j.jpha.2013.10.001. Epub 2013 Nov 26.
2
Enantiomeric characterization and structure elucidation of LH601A using vibrational circular dichroism spectroscopy.使用振动圆二色光谱法对LH601A进行对映体表征和结构解析。
Spectrochim Acta A Mol Biomol Spectrosc. 2018 Mar 5;192:312-317. doi: 10.1016/j.saa.2017.11.033. Epub 2017 Nov 21.
3
Absolute configuration determination and conformational analysis of (-)-(3S,6S)-3alpha,6beta-diacetoxytropane using vibrational circular dichroism and DFT techniques.使用振动圆二色性和 DFT 技术测定 (-)-(3S,6S)-3alpha,6beta-二乙酰氧基托烷的绝对构型和构象分析。
Chirality. 2010 Feb;22(2):234-41. doi: 10.1002/chir.20734.
4
Vibrational circular dichroism enantiomeric similarity index improvement for absolute configuration discrimination using individual infrared scaling factors.利用个体红外比例因子提高振动圆二色性对映体相似度指数以进行绝对构型判别。
Chirality. 2022 Mar;34(3):559-570. doi: 10.1002/chir.23411. Epub 2022 Jan 10.
5
Interplay of Exciton Coupling and Large-Amplitude Motions in the Vibrational Circular Dichroism Spectrum of Dehydroquinidine.脱氢奎尼丁振动圆二色光谱中激子耦合与大幅度运动的相互作用
Chemistry. 2016 Jan 11;22(2):704-15. doi: 10.1002/chem.201503250. Epub 2015 Nov 27.
6
The discovery of the Factor Xa inhibitor otamixaban: from lead identification to clinical development.凝血因子Xa抑制剂奥米沙班的发现：从先导化合物识别到临床开发
Curr Med Chem. 2007;14(23):2471-81. doi: 10.2174/092986707782023659.
7
Vibrational circular dichroism and single crystal X-Ray diffraction analyses of [Ir(bzq)(phen)] (bzq = benzo[h]quinoline; phen = 1,10-phenanthroline): absolute configuration and role of CH-π interaction in molecular packing.[Ir(bzq)(phen)]（bzq = 苯并[h]喹啉；phen = 1,10-菲咯啉）的振动圆二色性和单晶X射线衍射分析：绝对构型及CH-π相互作用在分子堆积中的作用
Dalton Trans. 2017 Mar 27;46(13):4397-4402. doi: 10.1039/c7dt00606c.
8
Absolute configuration and conformation analysis of 1-phenylethanol by matrix-isolation infrared and vibrational circular dichroism spectroscopy combined with density functional theory calculation.通过基质隔离红外光谱和振动圆二色光谱结合密度泛函理论计算对1-苯乙醇进行绝对构型和构象分析
J Phys Chem A. 2007 Sep 6;111(35):8598-605. doi: 10.1021/jp068448v. Epub 2007 Aug 8.
9
Absolute configuration assignment of (+)-fluralaner using vibrational circular dichroism.利用振动圆二色性对(+)-氟虫腈进行绝对构型归属
Chirality. 2017 Dec;29(12):854-864. doi: 10.1002/chir.22770. Epub 2017 Oct 5.
10
Absolute configuration of natural diastereoisomers of 6beta-hydroxyhyoscyamine by vibrational circular dichroism.通过振动圆二色性确定6β-羟基莨菪碱天然非对映异构体的绝对构型
J Nat Prod. 2006 Sep;69(9):1335-40. doi: 10.1021/np060133j.

引用本文的文献

1
Impact of conformation and intramolecular interactions on vibrational circular dichroism spectra identified with machine learning.通过机器学习识别构象和分子内相互作用对振动圆二色光谱的影响。
Commun Chem. 2023 Jul 12;6(1):148. doi: 10.1038/s42004-023-00944-z.
2
Enantiomeric characterization and structure elucidation of LH601A using vibrational circular dichroism spectroscopy.使用振动圆二色光谱法对LH601A进行对映体表征和结构解析。
Spectrochim Acta A Mol Biomol Spectrosc. 2018 Mar 5;192:312-317. doi: 10.1016/j.saa.2017.11.033. Epub 2017 Nov 21.
3
Determination of the Absolute Configurations of Chiral Drugs Using Chiroptical Spectroscopy.

本文引用的文献

1
Revisiting Vibrational Circular Dichroism Spectra of (S)-(+)-Carvone and (1S,2R,5S)-(+)-Menthol Using SimIR/VCD Method.使用SimIR/VCD方法重新审视（S）-（+）-香芹酮和（1S，2R，5S）-（+）-薄荷醇的振动圆二色光谱。
J Chem Theory Comput. 2012 Aug 14;8(8):2762-8. doi: 10.1021/ct300110q. Epub 2012 Jul 5.
2
A confidence level algorithm for the determination of absolute configuration using vibrational circular dichroism or Raman optical activity.一种利用振动圆二色性或拉曼光学活性确定绝对构型的置信水平算法。
Chemphyschem. 2011 Jun 6;12(8):1542-9. doi: 10.1002/cphc.201100050. Epub 2011 May 3.
3
A novel computational method for comparing vibrational circular dichroism spectra.
使用旋光光谱法测定手性药物的绝对构型
Molecules. 2016 Aug 12;21(8):1056. doi: 10.3390/molecules21081056.
一种比较振动圆二色光谱的新型计算方法。
Spectrochim Acta A Mol Biomol Spectrosc. 2010 Aug;76(3-4):418-22. doi: 10.1016/j.saa.2010.04.014. Epub 2010 Apr 21.
4
Effects of complex formation on vibrational circular dichroism spectra.络合物形成对振动圆二色光谱的影响。
J Phys Chem A. 2008 Jul 31;112(30):6978-91. doi: 10.1021/jp710201q. Epub 2008 Jul 8.
5
The discovery of the Factor Xa inhibitor otamixaban: from lead identification to clinical development.凝血因子Xa抑制剂奥米沙班的发现：从先导化合物识别到临床开发
Curr Med Chem. 2007;14(23):2471-81. doi: 10.2174/092986707782023659.
6
The determination of the absolute configurations of chiral molecules using vibrational circular dichroism (VCD) spectroscopy.使用振动圆二色性（VCD）光谱法测定手性分子的绝对构型。
Chirality. 2008 May 15;20(5):643-63. doi: 10.1002/chir.20477.
7
An investigation of the absolute configuration of the potent histamine H3 receptor antagonist GT-2331 using vibrational circular dichroism.使用振动圆二色性对强效组胺H3受体拮抗剂GT-2331的绝对构型进行的研究。
Chirality. 2007 Sep;19(9):731-40. doi: 10.1002/chir.20431.
8
Application of chiral technology in a pharmaceutical company. Enantiomeric separation and spectroscopic studies of key asymmetric intermediates using a combination of techniques. Phenylglycidols.手性技术在一家制药公司的应用。使用多种技术组合对关键不对称中间体进行对映体分离和光谱研究。苯基缩水甘油醚。
Chirality. 2007 Sep;19(9):716-30. doi: 10.1002/chir.20368.
9
Spectroscopic investigation of the structures of dialkyl tartrates and their cyclodextrin complexes.酒石酸二烷基酯及其环糊精配合物结构的光谱研究。
J Phys Chem A. 2007 Feb 8;111(5):858-71. doi: 10.1021/jp065847h.
10
Determination of the absolute configuration and solution conformation of the antifungal agents ketoconazole, itraconazole, and miconazole with vibrational circular dichroism.利用振动圆二色性测定抗真菌药物酮康唑、伊曲康唑和咪康唑的绝对构型和溶液构象。
Chirality. 2005;17 Suppl:S101-8. doi: 10.1002/chir.20120.