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Discovery of 3-aryloxy-lactam analogs as potent androgen receptor full antagonists for treating castration resistant prostate cancer.

Abstract：

:High throughput cell-based screening led to the identification of 3-aryloxy lactams as potent androgen receptor (AR) antagonists. Refinement of these leads to improve the ADME profile and remove residual agonism led to the discovery of 12, a potent full antagonist with greater oral bioavailability. Improvements in the ADME profile were realized by designing more ligand-efficient molecules with reduced molecular weights and lower lipophilicities.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Guo C,Kephart S,Ornelas M,Gonzalez J,Linton A,Pairish M,Nagata A,Greasley S,Elleraas J,Hosea N,Engebretsen J,Fanjul AN

doi

10.1016/j.bmcl.2011.11.068

subject

Has Abstract

pub_date

2012-01-15 00:00:00

pages

1230-6

issue

2

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)01612-X

journal_volume

22

pub_type

杂志文章

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