title: 3D QSAR studies based in silico screening of 4,5,6-triphenyl-1,2,3,4-tetrahydropyrimidine analogs for anti-inflammatory activity.
abstract: The 3D QSAR studies based on generation of common pharmacophore hypotheses (CPHs) were performed separately for the series of 1,2,3,4-tetrahydropyrimidin-5-yl-acetic acid and 2-(4-sulfonylphenyl)pyrimidine analogs for their in-vivo anti-inflammatory activity and in-vitro COX-2 inhibitory activity respectively. The main idea of selecting two different series was to develop two 3D QSAR models for same scaffold (1,2,3,4-tetrahydropyrimidine/pyrimidine) for same target, but with different aspects of activity. The aim of study was to screen designed compounds and select new compounds with increased COX-2 selectivity. The best 3D QSAR model from both group was employed as 3D search query to screen the designed 4,5,6-triphenyl-1,2,3,4-tetrahydropyrimidine derivatives. The new compounds showing good predicted activity were selected for experimental studies. Among the synthesized compounds, 5c and 5f showed highest anti-inflammatory activity.
authors.affiliation: Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004, M.S., India.
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Lokwani
authors.affiliation: Dr. Rafiq Zakaria Campus, Y.B. Chavan College of Pharmacy, Aurangabad 431001, M.S., India.
authors.forename: Santosh N
authors.initials: SN
authors.lastname: Mokale
authors.affiliation: Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004, M.S., India. Electronic address: dbsdeepak10@rediffmail.com.
authors.forename: Devanand B
authors.initials: DB
authors.lastname: Shinde
mesh_terms: D000818:Animals; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D015195:Drug Design; D004487:Edema / Q000188:drug therapy; D005260:Female; D008297:Male; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013871:Thiones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C000592147:4-(4-(dimethylamino)phenyl)-6-(4-(methylsulfonyl)phenyl)-5-phenyl-3,4-dihydropyrimidin-2(1H)-one; C000592148:6-(4-(methylsulfonyl)phenyl)-4,5-diphenyl-3,4-dihydropyrimidine-2(1H)-thione; D052246:Cyclooxygenase 2 Inhibitors; D011743:Pyrimidines; D011744:Pyrimidinones; D013450:Sulfones; D013871:Thiones
keywords: 1,2,3,4-Tetrahydropyrimidine; 3D QSAR; Anti-inflammatory; COX-2; Common Pharmacophore Hypotheses (CPHs)