Parallel solid-phase synthesis of a model library of 7alpha-alkylamide estradiol derivatives as potential estrogen receptor antagonists.
The C17-THP derivative of 7alpha-(11-azidoundecanyl)-estradiol (4) was synthesized and coupled to an aminomethyl resin via a photolabile o-nitrobenzyl linker. Reduction of the azide by the Staudinger reaction to its corresponding amine followed by acylation using four activated NFmoc protected amino acids gave a first level of diversity. Subsequent deprotection of the Fmoc followed by a second acylation with five activated carboxylic acids produced, after photocleavage, a model library of twenty antiestrogen-related 7alpha-alkylamide estradiol derivatives in acceptable overall yields and very good purities.
Tremblay
M R
MR
Medicinal Chemistry Division, Laboratory of Molecular Endocrinology, Laval University Medical Research Center, Quebec, Canada.
Simard
J
J
Poirier
D
D
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D053284:Polyunsaturated Alkamides; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D000577:Amides; D020847:Estrogen Receptor Modulators; D053284:Polyunsaturated Alkamides; D011960:Receptors, Estrogen; D004958:Estradiol; C051781:ICI 164384