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Chemical Papers

, Volume 73, Issue 4, pp 987–994 | Cite as

Design and synthesis of novel 3,4-diaminobenzoyl derivatives as antithrombotic agents with improved solubility

  • Guangqu Liu
  • Jiabin Yang
  • Bolang Su
  • Ruizhu Liao
  • Wei ZhouEmail author
  • Li ChenEmail author
Original Paper
  • 32 Downloads

Abstract

To obtain a highly selective, direct coagulation factor Xa (FXa) inhibitor with excellent antithrombotic activity and improved solubility, a series of novel 3,4-diaminobenzoyl derivatives were designed and synthesized based on reported structure–activity relationship analysis of FXa inhibitors. Preliminary solubility test showed that the decrease of intramolecular hydrogen bonds and the change of rigid structure could effectively improve physicochemical property of compounds. The synthesized compound 7ab could significantly prolong prothrombin time at a concentration of 40 nM compared with Apixaban. Docking investigation of 7ab with FXa protein revealed that the several groups could form multiple hydrogen bonds with amino acid residues ALA-190, ASP-189 and GLY-216. These results indicated that compound 7ab might serve as a potential anticoagulant agent.

Keywords

Anticoagulant Synthesis Improved solubility FXa inhibitor PT Docking 

Supplementary material

11696_2018_645_MOESM1_ESM.docx (1.9 mb)
Supplementary material 1 (DOCX 1969 kb)

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Copyright information

© Institute of Chemistry, Slovak Academy of Sciences 2018

Authors and Affiliations

  1. 1.Department of PharmaceuticsChina Pharmaceutical UniversityNanjingPeople’s Republic of China
  2. 2.Department of Natural Medicinal Chemistry, School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjingPeople’s Republic of China
  3. 3.Nanjing Zhongrui Pharmaceutical Co., Ltd.NanjingPeople’s Republic of China

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