Synthesis and pharmacological evaluation of 2-substituted benzo[b]thiophenes as anti-inflammatory and analgesic agents

An efficient method for trapping isocyanate 4, generated from the Curtius rearrangement, with ethyl alcohol to afford the carbamate 5 is reported. 5-Nitrobenzo[b]thiophene-2-carboxylic acid 1 is converted to the corresponding hydrazide 2 by the reaction with hydrazine hydrate and then to the azide 3 with nitrous acid, followed by thermal rearrangement, cooling, and trapping in one pot reaction. The carbamate 5 is treated with hydrazine hydrate to afford the desired, Zileuton analogue, 4-(5-nitrobenzo[b]thiophene-2-yl)semicarbazide 6. Also the reactivity of hydrazide 2 towards some carboxyaldehydes and phenylisothiocyanate afforded the corresponding carbohydrazides 7, 8 and phenylthiosemicarbazide 9, respectively. Compounds 9, 2 and 6, respectively, were more potent as anti-inflammatory and anti - noci ceptive agents. (c) 2008 Elsevier Masson SAS. All rights reserved.