3,3'-Bi-[1,3-thiazolidine-4-one] system. VII. Synthesis and SARS of some 2-heteroaryl derivatives with antiinflammatory and related activities.
In pursuing the research on the SARs of chiral 3,3'-Bi-[1,3-thiazolidine-4-one] system derivatives, two new structural modifications were explored, both having on chiral C atoms thienyl or 2/3 pyridyl groups which have been found to improve antiinflammatory and related activities in the previously studied 3,3'-(1,2-ethanediyl)bisthiazolidinones. In particular a trimetylene chain was introduced between N-3 and N-3' thus obtaining the 3,3'-(1,3-propanediyl) derivatives [type Ic compounds], whereas by elimination of a thiazolidinone ring the 2-heteroaryl-3-[2'(heteroarylidenamino) ethyl]-1,3-thiazolidine-4-one derivatives (type II compounds) were prepared. The new compounds were explored in vivo for their antiinflammatory, analgesic, antipyretic activities, as well as for acute toxicity and ulcerogenic effects. The results obtained don't allow us to draw any reliable SAR except that, by increasing the distance between thiazolidinonic rings, in Ic compounds, the pharmacological profile is not improved with respect to (1,2-ethanediyl) inferior homologs. Among compounds II, only the thienyl derivative 5 appears to have antiinflammatory and analgesic activities.
Previtera
T
T
Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università di Messina, Italy.
Vigorita
M G
MG
Fenech
G
G
Zappala
C
C
Giordano
A
A
Monforte
M T
MT
Forestieri
A M
AM
D000085:Acetates; D019342:Acetic Acid; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001169:Arthritis, Experimental / Q000188:drug therapy; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010146:Pain / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013055:Spectrophotometry, Infrared; D013276:Stomach Ulcer / Q000139:chemically induced; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D013844:Thiazoles; D002351:Carrageenan; D019342:Acetic Acid