Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors.

ABSTRACT: Novel 2- or 4-phosphonated 13α-estrone derivatives were synthesized via the Hirao reaction. Bromo regioisomers (2- or 4-) of 13α-estrone and its 3-benzyl or 3-methyl ether were reacted with diethyl phosphite or diphenylphosphine oxide using Pd(PPh₃)₄ as catalyst under microwave irradiation. The influence of the new compounds on the transport function of the organic anion transporting polypeptide OATP2B1 was investigated by measuring Cascade Blue uptake. Derivatives bearing a 3-benzyl ether function displayed substantial submicromolar OATP2B1 inhibitory activity. The inhibitory effects of the compounds on human placental steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated by in vitro radiosubstrate incubation methods

SUBMITTER: Jojart R 

PROVIDER: S-EPMC6244214 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature