Diethylstilbestrol-linked cytotoxic agents: synthesis and binding affinity for estrogen receptors.
The syntheses of diethylstilbestrol derivatives with a C4 side chain at the double bond bearing various functional and potentially alkylating groups (9-25, 38-40, 43, 44) as well as the coupling product with daunorubicin (41) are described. Derivatives with free phenolic groups show easy isomerization to (Z)-stilbenes and styrenes, which could be minimized with silyl protecting groups. Estrogen receptor binding is decreased by polar groups such as carboxylic acids (10) as well as sterically demanding substituents.
Krohn
K
K
Institut für Organische Chemie der Universität Braunschweig, Federal Republic of Germany.
Kulikowski
K
K
Leclercq
G
G
D000478:Alkylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D003630:Daunorubicin; D004054:Diethylstilbestrol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*
D000970:Antineoplastic Agents; D011960:Receptors, Estrogen; D004054:Diethylstilbestrol; D003630:Daunorubicin