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Bioorg Med Chem Lett. 2008 Jun 1;18(11):3344-9. doi: 10.1016/j.bmcl.2008.04.029. Epub 2008 Apr 15.

5-Aryluracils as potent GnRH antagonists-Characterization of atropisomers.

Author information

1
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92129, USA.

Abstract

Optimization of a series of uracils bearing a 2-fluoro- or 2-chloro-3-methoxyphenyl group at the 5-position resulted in compounds such as 3d and 3f with subnanomolar binding affinity at the human GnRH receptor. While the 2-fluoro-3-methoxyphenyl compound 3a was characterized as a mixture of interchangeable atropisomers, the diastereoisomers of 2-chloro-3-methoxyphenyl analogs were separated. It was found that the aR-atropisomer was much more potent than the aS-isomer based on the X-ray crystal structure of 3h-II.

PMID:
18442905
DOI:
10.1016/j.bmcl.2008.04.029
[Indexed for MEDLINE]

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