Open AccessAddition of Fluorine and a Late-Stage Functionalization (LSF) of the Oral SERD AZD9833
Author(s) -
James S. Scott,
Tom Moss,
Bernard Barlaam,
Paul Davey,
Gary Fairley,
Eric Gangl,
Ryan Greenwood,
Holia HatoumMokdad,
Andrew Lister,
David Longmire,
Radosław Polański,
Stephen Stokes,
Michael Tucker,
Jeffrey Varnes,
Bin Yang
Publication year - 2020
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.0c00505
Subject(s) - lipophilicity , surface modification , cascade , fluorine , combinatorial chemistry , chemistry , computer science , stereochemistry , organic chemistry , chromatography
Herein we describe our efforts using a late stage functionalization together with more traditional synthetic approaches to generate fluorinated analogues of the clinical candidate AZD9833. The effects of the addition of fluorine on the lipophilicity, permeability, and metabolism are discussed. Many of these changes were tolerated in terms of pharmacology and resulted in high quality molecules which reached advanced stages of profiling in the testing cascade.