Discovery and SAR study of 3-(tert-butyl)-4-hydroxyphenyl benzoate and benzamide derivatives as novel farnesoid X receptor (FXR) antagonists

Bioorganic & Medicinal Chemistry
Kebiao SongLihong Hu

Abstract

3-(tert-Butyl)-4-hydroxyphenyl 2,4-dichlorobenzoate (1) was discovered in our in-house high throughput screening as a moderate FXR antagonist. To improve the potency and the stability of the hit 1, forty derivatives were synthesized and SAR was systematically explored. The results turn out that replacing the 2,4-dichlorophenyl with 2,6-dichloro-4-amidophenyl shows great improvement in potency, replacing the benzoate with benzamide shows improvement in stability and slight declining of potency and 3-(tert-butyl)-4-hydroxyphenyl unit is essential in obtaining the FXR antagonistic activity.

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Citations

Feb 16, 2016·Journal of Medicinal Chemistry·Yanping Xu
Jan 26, 2018·Pharmacological Reports : PR·Yuichiro AmanoRyuichi Tozawa
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Somruedee JansongsaengTanatorn Khotavivattana

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