Synthesis and antihistamine evaluations of novel loratadine analogues

Bioorg Med Chem Lett. 2011 Aug 1;21(15):4454-6. doi: 10.1016/j.bmcl.2011.06.012. Epub 2011 Jun 16.

Abstract

A series of loratadine analogues containing hydroxyl group and chiral center were synthesized. The effect of the synthesized compounds on the histamine-induced contractions of guinea-pig ileum muscles was studied. In addition, the in vivo asthma-relieving effect of the analogues in the histamine induced asthmatic reaction in guinea-pigs was determined. Most of the compounds exhibited definite H(1) antihistamine activity. The S-enantiomers, compounds 2, 4 and 8, are more potent than the R-enantiomers, compounds 1, 3 and 7. Compound 6 was the most active one among the eight synthesized compounds.

MeSH terms

  • Animals
  • Anti-Allergic Agents / chemical synthesis*
  • Anti-Allergic Agents / pharmacology
  • Anti-Allergic Agents / therapeutic use
  • Asthma / drug therapy
  • Guinea Pigs
  • Histamine / chemistry*
  • Histamine / metabolism
  • Histamine Antagonists / chemical synthesis*
  • Histamine Antagonists / pharmacology
  • Histamine Antagonists / therapeutic use
  • Ileum / drug effects
  • Loratadine / analogs & derivatives*
  • Loratadine / chemical synthesis
  • Loratadine / pharmacology
  • Loratadine / therapeutic use
  • Stereoisomerism

Substances

  • Anti-Allergic Agents
  • Histamine Antagonists
  • Loratadine
  • Histamine