Conformational analysis of ticagrelor: effect of noncovalent interaction on conformational population

被引：4

作者：

Fan, Qiangwen ^{[1
]}

Tan, Hongbo ^{[2
]}

Wang, Yeming ^{[3
]}

Song, Xiuqing ^{[1
]}

Yan, Hong ^{[1
]}

机构：

[1] Beijing Univ Technol, Coll Life Sci & Bioengn, 100 Ping Le Yuan, Beijing 100124, Peoples R China

[2] Chongqing Univ Arts & Sci, Int Acad Targeted Therapeut & Innovat, 319 Honghe Ave, Chongqing 402160, Peoples R China

[3] Beijing Tide Pharmaceut Co Ltd, Beijing Econ Technol Dev Area BDA, 8 East Rongjing St, Beijing 100176, Peoples R China

来源：

STRUCTURAL CHEMISTRY | 2018年 / 29卷 / 06期

关键词：

Ticagrelor; Variable-temperature NMR (VT-NMR); Molecular mechanics (MM) stimulations; Quantum mechanics (QM) calculations; Noncovalent interaction (NCI) topological analysis; ACUTE CORONARY SYNDROMES; PLATELET INHIBITION; CH/PI INTERACTION; PI INTERACTIONS; CLOPIDOGREL; CONFIGURATION; RING;

D O I：

10.1007/s11224-018-1143-z

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

In order to track the source of duplicated peaks in the H-1-NMR spectrum of Ticagrelor, variable-temperature NMR (VT-NMR) experiment was carried out with temperature increasing from 300 to 343K. The result showed that the phenomenon was brought forth by coexistence of conformational isomers. Subsequently, conformational search was carried out by molecular mechanics (MM) stimulations associating with quantum mechanics (QM) calculations. The results revealed that the isomers resulting in duplicated proton peaks were introduced by the rotation of 2,4-diflurophenyl group on C(3')position of cyclopropyl. Finally, noncovalent interaction (NCI) topological analysis of the conformers exhibited that CH- interactions and H-bonds play important roles in controlling the population of conformers of ticagrelor.

引用

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页码：1663 / 1670

页数：8

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