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-nociceptive agents.
Fakhr
Issa M I
IM
Applied Organic Chemistry Department, National Research Centre, Dokki, Cairo, Egypt.
Radwan
Mohamed A A
MA
el-Batran
Seham
S
Abd el-Salam
Omar M E
OM
el-Shenawy
Siham M
SM
D019342:Acetic Acid / Q000633:toxicity; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D002351:Carrageenan / Q000633:toxicity; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D008099:Liver / Q000201:enzymology; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D017288:Pain Threshold / Q000187:drug effects; D010894:Piroxicam / Q000494:pharmacology; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D013876:Thiophenes; C088015:benzothiophene; D010894:Piroxicam; D002351:Carrageenan; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D019342:Acetic Acid