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

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Abstract

In order to track the source of duplicated peaks in the 1H-NMR spectrum of Ticagrelor, variable-temperature NMR (VT-NMR) experiment was carried out with temperature increasing from 300 to 343 K. 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 C3’position of cyclopropyl. Finally, noncovalent interaction (NCI) topological analysis of the conformers exhibited that CH-π interactions and H-bonds play important roles in controlling the population of conformers of ticagrelor.

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Funding

This work was supported by the Beijing Municipal Natural Science Foundation (CN) (No. KZ201510005004).

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Authors and Affiliations

  1. College of Life Science and Bio-engineering, Beijing University of Technology, 100 Ping Le Yuan, Beijing, 100124, Chaoyang District, China

    Qiangwen Fan, Xiuqing Song & Hong Yan

  2. International Academy of Targeted Therapeutics and Innovation, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan District, Chongqing, 402160, People’s Republic of China

    Hongbo Tan

  3. Beijing Tide Pharmaceutical Co., Ltd, Beijing Economic Technological Development Area (BDA), No. 8 East Rongjing Street, Beijing, 100176, China

    Yeming Wang

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  1. Qiangwen Fan
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  2. Hongbo Tan
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Correspondence to Hong Yan.

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Fan, Q., Tan, H., Wang, Y. et al. Conformational analysis of ticagrelor: effect of noncovalent interaction on conformational population. Struct Chem 29, 1663–1670 (2018). https://doi.org/10.1007/s11224-018-1143-z

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  • DOI: https://doi.org/10.1007/s11224-018-1143-z

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