Coumarin congeners as antidepressants.
3-Carboethyl coumarin (I) was converted to coumarin 3-acid hydrazide (II). This on reaction with appropriate aldehyde yielded 3-arylidino amino coumarin (III). Compound III on diazotisation and reaction with ferric chloride yielded the corresponding formazans viz. 3-substituted phenyl azoarylidino, amido coumarins (IVa1-a10) and oxadiazoles viz. 2-aryl-5-(3-coumarinyl)-1,3,4-oxadiazoles (Va1-a3), respectively. Simultaneously 3-carboethyl coumarin on hydrolysis gave 3-carboxy coumarin (VI) which on reaction with aryl amine in methylene chloride yielded 3-(N-aryl)amido coumarin (VIIa1-a3). The compounds were screened for their antidepressant activity against a tricyclic antidepressant (imipramine). Compounds IVa4, IVa5 and IVa9 exhibited activity better than imipramine with no toxicity (ALD50 greater than 1000 mg/kg) but IVa5 showed some side effects.
Singh
V
V
Department of Pharmacology and Therapeutics, King George's Medical College, Lucknow, India.
Srivastava
V K
VK
Palit
G
G
Shanker
K
K
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D003374:Coumarins / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D004357:Drug Synergism; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009422:Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D010862:Pilocarpine / Q000494:pharmacology; D012110:Reserpine / Q000037:antagonists & inhibitors; D012472:Salivation / Q000187:drug effects
D000928:Antidepressive Agents; D003374:Coumarins; D010862:Pilocarpine; D012110:Reserpine; D000661:Amphetamine