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J Med Chem. 2004 Jan 29;47(3):519-29.

Structural analysis and optimization of NK(1) receptor antagonists through modulation of atropisomer interconversion properties.

Author information

1
CNS Discovery Research, AstraZeneca Pharmaceuticals LP, 1800 Concord Pike, P.O. Box 15437, Wilmington, Delaware 19850-5437, USA. jeffrey.albert@astrazeneca.com

Abstract

We have previously described a series of antagonists that showed high potency and selectivity for the NK(1) receptor. However, these compounds also had the undesirable property of existing as a mixture of interconverting rotational isomers. Here we show that alteration of the 2-naphthyl substituent can modulate the rate of isomer exchange. Comparisons of the NK(1) receptor affinity for the various conformational forms has facilitated the development of a detailed NK(1) pharmacophore model.

PMID:
14736234
DOI:
10.1021/jm030197g
[Indexed for MEDLINE]

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