Synthesis of thio-heterocyclic analogues from Baylis-Hillman bromides as potent cyclooxygenase-2 inhibitors

• Published in: Bioorganic & medicinal chemistry letters Vol. 24; no. 8; pp. 1952 - 1957
• Main Authors: Santhoshi, Amlipur, Mahendar, Budde, Mattapally, Saidulu, Sadhu, Partha Sarathi, Banerjee, Sanjay Kumar, Rao, Vaidya Jayathirtha
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier 15.04.2014
• Subjects: Animals; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Benzothiazoles - chemical synthesis; Benzothiazoles - chemistry; Benzothiazoles - pharmacology; Bromides - chemical synthesis; Bromides - chemistry; Bromides - pharmacology; Cells, Cultured; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Cyclooxygenase 2 Inhibitors - chemical synthesis; Cyclooxygenase 2 Inhibitors - chemistry; Cyclooxygenase 2 Inhibitors - pharmacology; Enzyme Activation - drug effects; Heterocyclic Compounds - chemical synthesis; Heterocyclic Compounds - chemistry; Heterocyclic Compounds - pharmacology; Humans; Inhibitory Concentration 50; Life Sciences & Biomedicine; Molecular Structure; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Thiobenzothiazole; Thiobenzotriazole; IDENTIFICATION; Cyclooxygenase; INFLAMMATION; ANTIINFLAMMATORY AGENT; BIOLOGICAL EVALUATION; Baylis-Hillman bromide; Anti-inflammatory; DERIVATIVES; Thiopyrimidine; Thiobenzoxazole; PROSTAGLANDIN SYNTHESIS; Baylis–Hillman bromide
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2014.02.073

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 mu M compared to reference drug whose IC50 is 2.66 mu M. 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. (c) 2014 Elsevier Ltd. All rights reserved.