Synthesis and antiinflammatory activity of some 2-arylamino-2-thiazoline-4-ones.
A mild and efficent method of synthesis of 2-arylamino-2-thiazoline-4-ones was established using 2-carboethoxymethylthio-2-thiazolin-4-one (II) as a key intermediate. Reaction of 2-carboethoxymethylthio-2-thiazolin-4-one with m- or p-aminophenole afforded 2-(3-or4-oxyphenylamino)-2-thiazoline-4-ones (V, XV). Condensation of V, XV with aromatic aldehydes, according to the Knoevenagel, gives respective 5-arylidene derivatives V-XIII, XVI-XXIX, which were obtained alternatively using m- or p-oxyarylthioureas. 5-Carboxymethylderivatives XIV, XXX were synthesized by condensation of arylthioureas and maleic anhydride in acetic acid. Quantum-chemical calculations were made to confirm the possibility of dynamic amino-imino tautomerism of synthesized compounds. Structure and tautomerism of the obtained substances were confirmed by UV, IR, MS and NMR spectra. Biological activity prediction using the computer program PASS C&T has been made. According to these prediction results, some compounds were tested in vivio for their antiinflammatory activity. 5-[2-Chloro-3-(4-nitrophenyl)-2-propenilidene]-2-(3-hydroxyanilino-2-thiazoline-4-one (XII) possess significant antiinflammatory effect in comparison with diclofenac sodium, aspirin, acetaminofen and phenylbutazone.
Lesyk
Roman
R
Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv State Medical University, 69 Pekarska Str., Lviv-10, 79010, Ukraine.
Zimenkovsky
Boris
B
Subtelna
Ivanna
I
Nektegayev
Igor
I
Kazmirchuk
Gennadij
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D005260:Female; D008297:Male; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013844:Thiazoles