Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H1 antagonize activities

Feng Li; Qinlong Xu; Qihua Zhu; Zhaoxing Chu; Gaofeng Lin; Jiajia Mo; Yan Zhao; Jiaming Li; Guangwei He; Yungen Xu

doi:10.1016/j.bmcl.2019.126712

Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H₁ antagonize activities

Bioorg Med Chem Lett. 2019 Dec 15;29(24):126712. doi: 10.1016/j.bmcl.2019.126712. Epub 2019 Oct 15.

Authors

Feng Li¹, Qinlong Xu², Qihua Zhu³, Zhaoxing Chu¹, Gaofeng Lin⁴, Jiajia Mo⁴, Yan Zhao⁴, Jiaming Li⁵, Guangwei He⁴, Yungen Xu⁶

Affiliations

¹ Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; Hefei Institute of Pharmaceutical Industry Co., Ltd., Hefei 230088, China.
² Hefei Institute of Pharmaceutical Industry Co., Ltd., Hefei 230088, China; Anhui University of Chinese Medicine, Hefei 230031, China.
³ Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
⁴ Hefei Institute of Pharmaceutical Industry Co., Ltd., Hefei 230088, China.
⁵ Anhui University of Chinese Medicine, Hefei 230031, China.
⁶ Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China. Electronic address: xu_yungen@hotmail.com.

PMID: 31679973
DOI: 10.1016/j.bmcl.2019.126712

Abstract

To improve the anti-inflammatory activity of desloratadine, we designed and synthesized a series of novel desloratadine derivatives. All compounds were evaluated for their anti-inflammatory and H₁ antagonistic activities. Among them, compound 2c showed the strongest H₁ antagonistic and anti-inflammatory activity. It also exhibited promising pharmacokinetic profiles and low toxicity. All these results suggest that compound 2c as a novel anti-allergic agent is worthy of further investigation.

Keywords: Anti-allergic; Anti-inflammatory; Desloratadine; H(1) antagonize.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Inflammatory Agents / pharmacology
Anti-Inflammatory Agents / therapeutic use*
Histamine H1 Antagonists / pharmacology
Histamine H1 Antagonists / therapeutic use*
Humans
Loratadine / analogs & derivatives*
Loratadine / chemical synthesis
Loratadine / chemistry
Structure-Activity Relationship

Substances

Anti-Inflammatory Agents
Histamine H1 Antagonists
Loratadine
desloratadine