G. Reddy, Κ. Rao
2008
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Journal
Heterocyclic Communications
Abstract
A series of methyl [6-(2-aminothiazol-4-yl)-3-oxo-l,4-benzoxazin-2yl]acetates (3-5) have been synthesized and tested for COX-2 (Cyclooxygenase) / 5-LOX (Lipoxygenase) inhibitory activity. Some of the compounds exhibited notable 5-LOX inhibitory activity. Introduction The introduction of Celecoxib and Rofecoxib as antiinflammatory agents with better gastric tolerance has created interest in the development of selective COX-2 inhibitors'. Aminothiazole ring system has broad application in the treatment of allergies, hypertension, inflammation, schizophrenia , bacterial and HIV infections. Fanetizole (4-phenyl-2-phenethylaminothiazole) is an antiinflammatory agent under phase II clinical trials for the treatment of rheumatoid arthritis. Recently, compounds with pyridylaminothiazole as core unit have been reported as anticancer agents, KDR Kinase inhibitors, CNS, mood disorder, brain tumour, epilepsy, anxiety, depression and Alzheimeirs disease. A number of 1,4-benzoxazine derivatives have been reported as 11 19 ι -3 smooth muscle relaxants , anticoagulants and antibacterial agents . Furthermore, several aryl and heteroaryl acetic acids represented by indomethacin, diclofenac, sulindac, fentiazac and Lonazolac enjoy clinical status as antiinflammatory agents'. Prompted by these observations and in continuation of our work on new benzoxazines we report herein the synthesis and COX-2 / 5-LOX inhibitory activity of some new aminothaizolylbenzoxazinyl acetates. Methyl a-(3,4-dihydro-3-oxo-2H-l,4-benzoxazin-2-yl)acetate (1) required as starting material in the present work, was prepared by the reaction of 2-aminophenol with maleic anhydride in refluxing methanol in the presence of triethylamine according to procedure described earlier. The reaction of 1 with chloroacetyl chloride in the presence of aluminium chloride under Friedel-Crafts reaction conditions gave the hitherto unreported 6-chloroacetylbenzoxazin-2-ylacetate 2 in good yields. 'H NMR spectra of 2 exhibited signals at δ 2.9 (m, 2H, CH2C02CH3), 3.61(s, 3H, CH2C02CH3), 5.17 (m, 3H, OCH & CH2CO) and 10.02 (bs, NH) apart from three aromatic protons. IR spectra of 2 exhibited characteristic absorption bands around 1738 cm" (C02CH3), 1714 & 1716 cm" (C=0).