title: Synthesis of thio-heterocyclic analogues from Baylis-Hillman bromides as potent cyclooxygenase-2 inhibitors.
abstract: A series of thio-substituted pyrimidine, benzoxazole, benzothiazole and triazole analogues were synthesized from Baylis-Hillman bromides in a clean and efficient way. The synthesized twenty new compounds were subjected to in vitro COX-1 and COX-2 inhibitory activity. Majority of compounds found to be highly selective COX-2 inhibitor. Seven compounds (16e, 16f, 16k, 16l, 16m, 16r and 16s) displayed anti-inflammatory activity at micromolar concentrations with IC50 values for COX-2 inhibition ranging from 2.93 to 5.34 μM compared to reference drug whose IC50 is 2.66 μM. All these seven compounds had very little COX-1 inhibition property and thus are suitable candidates for anti-inflammatory drugs with less gastrointestinal side effect.
authors.affiliation: Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, India.
authors.forename: Amlipur
authors.initials: A
authors.lastname: Santhoshi
authors.affiliation: Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, India.
authors.forename: Budde
authors.initials: B
authors.lastname: Mahendar
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, India.
authors.forename: Saidulu
authors.initials: S
authors.lastname: Mattapally
authors.affiliation: Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, India.
authors.forename: Partha Sarathi
authors.initials: PS
authors.lastname: Sadhu
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, India. Electronic address: skbanerjee@iict.res.in.
authors.forename: Sanjay Kumar
authors.initials: SK
authors.lastname: Banerjee
authors.affiliation: Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, India; AcSIR-IICT, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, India. Electronic address: jrao@iict.res.in.
authors.forename: Vaidya
authors.initials: V
authors.lastname: Jayathirtha Rao
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001965:Bromides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure
chemical_list: D000893:Anti-Inflammatory Agents; D052160:Benzothiazoles; D001965:Bromides; D052246:Cyclooxygenase 2 Inhibitors; D006571:Heterocyclic Compounds; C005465:benzothiazole
keywords: Anti-inflammatory; Baylis–Hillman bromide; Cyclooxygenase; Thiobenzothiazole; Thiobenzotriazole; Thiobenzoxazole; Thiopyrimidine