title: Synthesis, biological evaluation and molecular modeling study of 5-trifluoromethyl-Δ²-pyrazoline and isomeric 5/3-trifluoromethylpyrazole derivatives as anti-inflammatory agents.
abstract: Searching for new anti-inflammatory agents, we have prepared a series of potential COX-2 inhibitors, 1-(4,6-dimethylpyrimidin-2-yl)-5-hydroxy-5-trifluoromethyl-Δ(2)-pyrazolines (3) and 1-(4,6-dimethylpyrimidin-2-yl)-3-trifluoromethylpyrazoles (4), by refluxing 2-hydrazino-4,6-dimethylpyrimidine (1) with a number of trifluoromethyl-β-diketones (2) in ethanol. Further dehydration of compounds (3) to the corresponding 1-(4,6-dimethylpyrimidin-2-yl)-5-trifluoromethylpyrazoles (5) was also achieved. Fifteen of these compounds were screened for their anti-inflammatory activity using the carrageenan-induced rat paw edema assay. While all the compounds exhibited significant anti-inflammatory activity (47-76%) as compared to indomethacin (78%), 3-trifluoromethylpyrazoles (4) were found to be the most effective agents (62-76%). To rationalize this anti-inflammatory activity, docking experiments molecular dynamics simulations were performed to study the ability of these compounds to bind into the active site of the COX-2 enzyme.
authors.affiliation: Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana 136 119, India. Electronic address: ranjana67in@yahoo.com.
authors.forename: Ranjana
authors.initials: R
authors.lastname: Aggarwal
authors.forename: Anshul
authors.initials: A
authors.lastname: Bansal
authors.forename: Isabel
authors.initials: I
authors.lastname: Rozas
authors.forename: Brendan
authors.initials: B
authors.lastname: Kelly
authors.forename: Pawan
authors.initials: P
authors.lastname: Kaushik
authors.forename: Dhirender
authors.initials: D
authors.lastname: Kaushik
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D002351:Carrageenan; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008958:Models, Molecular; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C000591462:5-trifluoromethyl-delta2-pyrazoline; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D006845:Hydrocarbons, Fluorinated; D011720:Pyrazoles; D002351:Carrageenan; D051546:Cyclooxygenase 2
keywords: 3-Trifluoromethylpyrazoles; 5-Trifluoromethyl-Δ(2)-pyrazolines; 5-Trifluoromethylpyrazoles; Anti-inflammatory activity; COX-2; Docking