Computer-aided Design, Synthesis, and Biological Evaluation of 5- Substituted Aminomethylenepyrimidine-2,4,6-Triones as H₁ Antihistaminic Agents (Part2)

Title:Computer-aided Design, Synthesis, and Biological Evaluation of 5- Substituted Aminomethylenepyrimidine-2,4,6-Triones as H₁ Antihistaminic Agents (Part2)

Volume: 10 Issue: 1

Author(s): Rasha Y. Elbayaa

Affiliation:

Keywords: Synthesis, aminomethylenepyrimidine-2, 4, 6-triones, antihistaminic, pharmacophore modeling, docking.

Abstract: As a part of a research project pertaining to the synthesis of novel candidates as nonsedating, nonclassic H₁ histaminergic (H₁) blockers with low toxicity profiles, some new 5-substituted aminomethylenepyrimidine-2,4,6-triones were designed based on the H1 histaminic receptor pharmacophore model. The interactions between the designed compounds and the H₁ receptor were studied using molecular docking on the homology model of H₁ receptor. The designed compounds were synthesized and biologically evaluated for H₁-blocking activity; using isolated segments of guinea pig ileum. Compounds 15,18,19 and 21 exhibited comparable activities to acrivastine (22) as reference nonsedating drug. The C log P of designed compounds revealed lower values in reference to acrivastine (22) which might indicate decreased tendency for crossing the blood brain barrier.

Cite this article as:

Elbayaa Y. Rasha, Computer-aided Design, Synthesis, and Biological Evaluation of 5- Substituted Aminomethylenepyrimidine-2,4,6-Triones as H₁ Antihistaminic Agents (Part2), Medicinal Chemistry 2014; 10 (1) . https://dx.doi.org/10.2174/15734064113099990032