Zwitterionic uracil derivatives as potent GnRH receptor antagonists with improved pharmaceutical properties

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4503-7. doi: 10.1016/j.bmcl.2008.07.059. Epub 2008 Jul 17.

Authors

Colin F Regan¹, Zhiqiang Guo, Yongsheng Chen, Charles Q Huang, Mi Chen, Wanlong Jiang, Jaimie K Rueter, Timothy Coon, Chen Chen, John Saunders, Michael S Brown, Steve F Betz, R Scott Struthers, Chun Yang, Jenny Wen, Ajay Madan, Yun-Fei Zhu

Affiliation

¹ Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12780 El Camino Real, San Diego, CA 92130, USA.

PMID: 18667310
DOI: 10.1016/j.bmcl.2008.07.059

Abstract

A novel series of potent zwitterionic uracil GnRH antagonists were discovered that showed reduced liability for CYP3A4 enzyme inhibition.

MeSH terms

Chemistry, Pharmaceutical / methods*
Cytochrome P-450 CYP3A / chemistry*
Drug Design
Gonadotropin-Releasing Hormone / chemistry
Humans
Ions*
Kinetics
Models, Chemical
Molecular Structure
Peptides / chemistry
Receptors, LHRH / antagonists & inhibitors*
Stereoisomerism
Structure-Activity Relationship
Uracil / analogs & derivatives*
Uracil / chemistry

Substances

Ions
Peptides
Receptors, LHRH
Gonadotropin-Releasing Hormone
Uracil
Cytochrome P-450 CYP3A
CYP3A4 protein, human