Design and synthesis of some substituted 1H-pyrazolyl-oxazolidines or 1H-pyrazolyl-thiazolidines as anti-inflammatory-antimicrobial agents.
Four series of 1 H-pyrazole derivatives have been synthesized. The first series was synthesized starting with the reaction of 3-(5-bromo-2-thienyl)-1-phenyl-1 H-pyrazole-4-carboxaldehyde 1 with L-serine, L-cysteine, or L-penicillamine, followed by N-protection using (Boc)(2)O to provide compounds 2. The latter compounds could be N-deprotected by 4N HCl/dioxane to afford the second series 3 or reacted with NH(4)OH in the presence of DCC/HOBt to give the corresponding amides 4 followed by N-deprotection giving rise to compounds 5. The newly synthesized compounds were evaluated for their anti-inflammatory-antimicrobial activities. In addition, the ulcerogenic and acute toxicity profiles were determined. Compound 5b (2RS, 4R)-2-[3-(5-bromo-2-thienyl)-1-phenyl-1H-pyrazol-4-yl]-5-methylthiazolidine-4-carboxamide, proved to be the most active anti-inflammatory-antimicrobial agent in the present study with a good safety margin and no ulcerogenic effect.
Bekhit
Adnan A
AA
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt. adnbekit@hotmail.com
Fahmy
Hesham T Y
HT
D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects; D007263:Infusions, Parenteral; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013211:Staphylococcus aureus / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D023382:Toxicity Tests, Acute
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010080:Oxazoles; D011720:Pyrazoles; D013844:Thiazoles