Synthesis and biological evaluation of five-membered heterocycles fused to cyclopenta[c]thiophene as new antitumor agents.
A series of 10 derivatives 2-6 issued from the fusion of various five-membered heterocycles to cyclopenta[c]thiophene were evaluated for potential anticancer activity in the NCI's in vitro human disease-oriented tumor cell line screening panel that consisted of 60 human tumor cell lines arranged in nine subpanels, representing diverse histologies. Among these tested compounds, four were found to be cytotoxic allowing us to point out some structure-activity relationships. The oxazolidinone derivatives 2a-c displayed further in vivo antitumor activity in the hollow fiber assay and standard xenograft testing developed at the NCI.
Dallemagne
Patrick
P
Centre d'Etudes et de Recherche sur le Médicament de Normandie, U.F.R. des Sciences Pharmaceutiques, Université de Caen, 1, rue Vaubénard 14032 Caen, cedex, France. dallemagne@pharmacie.unicaen.fr
Khanh
Lan Pham
LP
Alsaïdi
Abdellah
A
Varlet
Isabelle
I
Collot
Valérie
V
Paillet
Magalie
M
Bureau
Ronan
R
Rault
Sylvain
S
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D051379:Mice; D009368:Neoplasm Transplantation; D010080:Oxazoles / Q000138:chemical synthesis / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D003517:Cyclopentanes; D006571:Heterocyclic Compounds; D007202:Indicators and Reagents; D010080:Oxazoles; D013876:Thiophenes