Stereoselective synthesis of desloratadine derivatives as antagonist of histamine

Bioorg Med Chem. 2010 Feb 15;18(4):1626-32. doi: 10.1016/j.bmc.2009.12.061. Epub 2010 Jan 4.

Abstract

A series of desloratadine derivatives were stereoselectively synthesized and evaluated for H(1) antihistamine activity. For the evaluation of H(1) antihistamine activity, the in vitro histamine-induced contraction of the guinea-pig ileum assay (HC) was used. The synthesized desloratadine derivatives 7, 8 and 9 are structurally related to rupatadine and were generated by replacement of the 5-methyl-3-pyridine group of rupatadine with gamma-alkylidene butenolide. Their H(1) antihistamine activities have shown a high dependence on the exact nature of the substituent in the lactone ring. Optimum structures 7, 8a and 8g display potent activity inhibiting histamine-induced effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Guinea Pigs
  • Histamine H1 Antagonists, Non-Sedating / chemical synthesis*
  • Histamine H1 Antagonists, Non-Sedating / chemistry
  • Histamine H1 Antagonists, Non-Sedating / pharmacology
  • In Vitro Techniques
  • Loratadine / analogs & derivatives*
  • Loratadine / chemical synthesis
  • Loratadine / chemistry
  • Loratadine / pharmacology
  • Male
  • Models, Molecular
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Infrared
  • Stereoisomerism

Substances

  • Histamine H1 Antagonists, Non-Sedating
  • Loratadine
  • desloratadine