Synthesis, Reactions, and Pharmacological Screening of Heterocyclic Derivatives Using Nicotinic Acid as a Natural Synthon |
| |
Authors: | Nehad A Abd El-Latif Abd El-Galil E Amr Alhusain A Ibrahiem |
| |
Institution: | (1) National Research Center, Natural Compounds Chemistry Department, Cairo, Dokki, Egypt;(2) National Research Center, Applied Organic Chemistry Department, Cairo, Dokki, Egypt |
| |
Abstract: | Summary. 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-β-(3-indolyl)acryloylpyridine, which was reacted with hydroxylamine hydrochloride in pyridine or acetic acid in the presence
of sodium acetate to afford 3-β-(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-β-(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? and Carbamazepine? as reference drugs. |
| |
Keywords: | , Nicotinic acid, Indole-3-carboxaldehyde, Thioxopyrimidine, Analgesics, Anticonvulsants, |
本文献已被 SpringerLink 等数据库收录! |
|