Synthesis and biological evaluation of 2-amino-3-(3', 4', 5'-trimethoxy-phenylsulfonyl)-5-aryl thiophenes as a new class of antitubulin agents.
Bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents. Bioisosteres are substituents or groups that have chemical or physical similarities and that produce broadly similar biological effects. The sulfone moiety is recognized as a nonclassical bioisostere for replacement of the carbonyl group. When sulfonyl derivatives 5a-e were compared with carbonyl compounds 4a-e, the sulfone substitution dramatically decreased the antiproliferative activity of the series.
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Via Fossato di Mortara 17-19, I-44100 Ferrara, Italy. rmr@unife.it
Romeo
R
Romagnoli
Pier Giovanni
PG
Baraldi
Vincent
V
Remusat
Maria Dora
MD
Carrion
Carlota Lopez
CL
Cara
Olga
O
Cruz-Lopez
Delia
D
Preti
Francesca
F
Fruttarolo
Mojgan Aghazadeh
MA
Tabrizi
Jan
J
Balzarini
Ernest
E
Hamel
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D013329:Structure-Activity Relationship; D013450:Sulfones; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000494:pharmacology
D000970:Antineoplastic Agents; D013450:Sulfones; D013876:Thiophenes; D050257:Tubulin Modulators