Discovery of a novel series of nonsteroidal androgen receptor modulators: 5- or 6-oxachrysen-2-ones

Shuo Zhao; Yixing Shen; Arjan van Oeveren; Keith B Marschke; Lin Zhi

doi:10.1016/j.bmcl.2008.03.085

Discovery of a novel series of nonsteroidal androgen receptor modulators: 5- or 6-oxachrysen-2-ones

Bioorg Med Chem Lett. 2008 Jun 1;18(11):3431-5. doi: 10.1016/j.bmcl.2008.03.085. Epub 2008 Apr 8.

Authors

Shuo Zhao¹, Yixing Shen, Arjan van Oeveren, Keith B Marschke, Lin Zhi

Affiliation

¹ Discovery Research, Ligand Pharmaceuticals Inc., 10275 Science Center Drive, San Diego, CA 92121, USA. szhao2005@gmail.com

PMID: 18442912
DOI: 10.1016/j.bmcl.2008.03.085

Abstract

A novel oxachrysenone series (2) of nonsteroidal selective androgen receptor modulators (SARM) was developed based on the 6-aryl-2-quinolinones (1). Synthesis and preliminary SAR results based on in vitro assays are discussed. In the cotransfection assay, lead compound 5d showed AR agonist activity more potent than dihydrotestosterone (DHT), whereas compound 17b was a potent antagonist similar to bicalutamide.

MeSH terms

Androgens*
Anilides / pharmacology*
Combinatorial Chemistry Techniques
Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
Heterocyclic Compounds, 4 or More Rings / chemistry
Heterocyclic Compounds, 4 or More Rings / pharmacology*
Humans
Molecular Structure
Nitriles / pharmacology*
Quinolones / chemistry*
Structure-Activity Relationship
Tosyl Compounds / pharmacology*

Substances

Androgens
Anilides
Heterocyclic Compounds, 4 or More Rings
Nitriles
Quinolones
Tosyl Compounds
bicalutamide