title: Computer-aided design, synthesis, and biological evaluation of 5- substituted aminomethylenepyrimidine-2,4,6-triones as H₁ antihistaminic agents (Part2).
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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, 1 Elkhartoum Square, Azarita, Alexandria, Egypt. rashabayaa72@gmail.com.
authors.forename: Rasha Y
authors.initials: RY
authors.lastname: Elbayaa
mesh_terms: D000818:Animals; D017076:Computer-Aided Design; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008956:Models, Chemical; D011485:Protein Binding / Q000187:drug effects; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D006634:Histamine H1 Antagonists; D011744:Pyrimidinones