title: Structure-activity relationships of C-17-substituted estratriene-3-O-sulfamates as anticancer agents.
abstract: The synthesis and antiproliferative activities of analogues of 2-substituted estradiol-3,17-O,O-bis-sulfamates (E2bisMATEs) are discussed. Modifications of the C-17 substituent confirm that an H-bond acceptor is essential for high activity; its optimal linkage to C-17 and the local environment in which it resides are defined. In the non-sulfamoylated series 17β-acyl substitution delivers 48b, the most potent compound identified to date. In the sulfamate series a number of permutations of linker and H-bond acceptor deliver excellent activity, with 55, 61, 65, 49a, and 49b proving especially promising. The in vivo potential of these compounds was explored in the NCI hollow fiber assay and also in a mouse Matrigel model of antiangiogenesis in which 49 and 55 show significant inhibitory activity.
authors: Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, UK.
authors: Fabrice
authors: F
authors: Jourdan
authors: Mathew P
authors: MP
authors: Leese
authors: Wolfgang
authors: W
authors: Dohle
authors: Eric
authors: E
authors: Ferrandis
authors: Simon P
authors: SP
authors: Newman
authors: Surinder
authors: S
authors: Chander
authors: Atul
authors: A
authors: Purohit
authors: Barry V L
authors: BV
authors: Potter