Abstract
A series of substituted pyridine derivatives were prepared from 3-acetylpyridine, which was prepared from the corresponding nicotinic acid as a natural starting material. Reaction of 3-acetylpyridine with indole-3-carboxaldehyde afforded the corresponding 3-beta-(3-indolyl)acryloylpyridine, which was reacted with hydroxylamine hydrochloride in pyridine or acetic acid in the presence of sodium acetate to afford 3-beta-(3-indolyl)acryloylpyridine oxime and oxazole derivatives. The oxime was treated with ethyl isothiocyanate or toluene-3,5-diisocyanate in refluxing dioxane to give the corresponding ethyl thiosemicarbazide and 3,5-bissemicarbazide derivative. 3-beta-(3-Indolyl)acryloylpyridine was condensed with malononitrile in refluxing ethanol in the presence of piperidine as a catalyst to give cyanoaminopyrane, while it was condensed with ethyl cyanoacetate or malononitrile in the presence of ammonium acetate to yield cyanopyridone and cyanoaminopyridine derivatives. Cyclization of acryloylpyridine with o-phenylenediamine in refluxing butanol led to the formation of the corresponding benzodiazipine via the intermediate A. Finally, cycloaddition reaction of acryloylpyridine with thiourea yielded thioxopyrimidine, which was treated with chloroacetic acid to yield thiazolopyrimidine. An arylmethylene derivative was prepared by reacting thiazolopyrimidine with indole-3-carboxaldehyde or by reacting thioxopyrimidine with indole-3-carboxaldehyde and chloroacetic acid in one step. The pharmacological screening showed that many of these obtained compounds have good analgesic and anticonvulsant activities comparable to Valdecoxib (R) and Carbamazepine (R) as reference drugs.