title: Synthesis and antihormonal properties of novel 11β-benzoxazole-substituted steroids.
abstract: Early studies led to the identification of 11β-aryl-4',5'-dihydrospiro[estra-4,9-diene-17β,4'-oxazole] analogs with potent and more selective antiprogestational activity compared to antiglucocorticoid activity than mifepristone. In the present study, we replaced the 4'-dimethylaminophenyl group of mifepristone with the benzoxazol group to give 5a-d. We also prepared the 17β-formamido analogs 6a,b using a new synthetic strategy via the intermediate epoxide 21. These compounds were evaluated for their antagonist hormonal properties using the T47D cell-based alkaline phosphatase assay and the A549 cell-based functional assay. Compound 5c showed potent antagonist activity at GR with better selectivity for GR versus PR than mifepristone and is a promising lead for further development.
authors.affiliation: Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, NC 27709-2194, USA. cjin@rti.org
authors.forename: Chunyang
authors.initials: C
authors.lastname: Jin
authors.forename: Scott E
authors.initials: SE
authors.lastname: Fix
authors.forename: John A
authors.initials: JA
authors.lastname: Kepler
authors.forename: C Edgar
authors.initials: CE
authors.lastname: Cook
mesh_terms: D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D006727:Hormone Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015735:Mifepristone / Q000737:chemistry; D015394:Molecular Structure; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors*; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013379:Substrate Specificity / Q000187:drug effects
chemical_list: D001583:Benzoxazoles; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D013256:Steroids; D015735:Mifepristone