2. Academic Validation
  3. Synthesis and structure-activity relationship of tricyclic carboxylic acids as novel anti-histamines

Synthesis and structure-activity relationship of tricyclic carboxylic acids as novel anti-histamines

  • Bioorg Med Chem. 2011 May 1;19(9):3005-21. doi: 10.1016/j.bmc.2011.03.003.
Katsumi Kubota 1,  Hirotaka Kurebayashi,  Hirotaka Miyachi,  Masanori Tobe,  Masako Onishi,  Yoshiaki Isobe
Affiliations

Affiliation

  • 1 Dainippon Sumitomo Pharma. Co., Ltd, 3-1-98 Kasagade-naka Konohana-ku Osaka-city, Osaka 554-0022, Japan.
PMID: 21470866 DOI: 10.1016/j.bmc.2011.03.003
Abstract

A series of tricyclic carboxylic acids having 6-amino-pyrimidine-2,4(1H,3H)-dione with piperazino or homopiperazino moiety linked by propylene, were synthesized and evaluated for their affinity toward human histamine H(1) receptor and Caco-2 cell permeability. Selected compounds were further evaluated for their oral anti-histaminic activity in mice, bioavailability in rats, and their anti-inflammatory activity in mice OVA-induced biphasic cutaneous reaction model. Among the compounds tested, dibenzoxazepine carboxylic acid 13b showed both histamine H(1) receptor antagonistic activity and anti-inflammatory activity in vivo. In addition, 13b exhibited low affinity toward α(1) receptor and low occupancy of H(1) receptor in the brain. It is therefore, believed that 13b is a potential candidate for development as 3rd generation anti-histamine.

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