Synthesis and pharmacological evaluation of trifluoromethyl containing 4-(2-pyrimidinylamino)benzamides as Hedgehog signaling pathway inhibitors

Bioorganic & Medicinal Chemistry
Min-Hang XinFeng Tang

Abstract

In present study, a series of novel containing trifluoromethyl 4-(2-pyrimidinylamino)benzamide derivatives were designed by the fluorine scan strategy. Their Hh signaling inhibitory activities were evaluated by Gli-luciferase reporter method. The comprehensive SAR was discussed and several derivatives were found to display more potent Hh signaling inhibitory activity than positive drug vismodegib. Compound 13d was the most potent compound with IC50 of 1.44nM against Hh signaling pathway and also exhibited optimal PK properties in the in vivo PK properties study, deserved as an ideal lead compound for further study in future.

References

May 23, 2014·Expert Opinion on Drug Discovery·Upasana Banerjee, Matthew Kyle Hadden
Oct 15, 2014·Trends in Pharmacological Sciences·Mathias Rask-AndersenHelgi B Schiöth
Mar 3, 2015·Expert Opinion on Therapeutic Patents·Minhang Xin

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Citations

Jan 10, 2018·Medicinal Research Reviews·Minhang XinBinghe Wang
Jul 12, 2017·Science Progress·Roderick M Macrae
Nov 30, 2018·Medicinal Research Reviews·Jitender BariwalRam I Mahato
Dec 21, 2017·Skin Pharmacology and Physiology·Ana R FernandesEliana B Souto

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