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.
Romagnoli
Romeo
R
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Via Fossato di Mortara 17-19, I-44100 Ferrara, Italy. rmr@unife.it
Baraldi
Pier Giovanni
PG
Remusat
Vincent
V
Carrion
Maria Dora
MD
Cara
Carlota Lopez
CL
Cruz-Lopez
Olga
O
Preti
Delia
D
Fruttarolo
Francesca
F
Tabrizi
Mojgan Aghazadeh
MA
Balzarini
Jan
J
Hamel
Ernest
E
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