The crystal structure, absolute configuration, and phosphodiesterase inhibitory activity of (+)-1-(4-bromobenzyl)-4-(3-(cyclopentyloxy)- 4-methoxyphenyl)-pyrrolidin-2-one

P W Baures; D S Eggleston; K F Erhard; L B Cieslinski; T J Torphy; S B Christensen

doi:10.1021/jm00074a007

The crystal structure, absolute configuration, and phosphodiesterase inhibitory activity of (+)-1-(4-bromobenzyl)-4-(3-(cyclopentyloxy)- 4-methoxyphenyl)-pyrrolidin-2-one

J Med Chem. 1993 Oct 29;36(22):3274-7. doi: 10.1021/jm00074a007.

Authors

P W Baures¹, D S Eggleston, K F Erhard, L B Cieslinski, T J Torphy, S B Christensen

Affiliation

¹ Department of Physical and Structural Chemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.

PMID: 8230117
DOI: 10.1021/jm00074a007

Abstract

Chiral HPLC resolution of the phosphodiesterase IV (PDE IV) inhibitor rolipram (1) provided (-)-1, and this enantiomer was converted into its 1-(4-bromobenzyl) derivative, (+)-2. X-ray structural analysis of (+)-2 established the absolute configuration as R, which provides the first direct evidence for a previously assumed assignment of configuration. The crystal structure of (+)-2 and the PDE inhibitory activity of both enantiomers of 2 are discussed in the context of a previously proposed topological model.

MeSH terms

3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
Animals
Benzyl Compounds / chemistry*
Benzyl Compounds / pharmacology*
Cattle
Crystallography, X-Ray
Molecular Conformation
Muscle, Smooth / drug effects
Muscle, Smooth / enzymology
Phosphodiesterase Inhibitors / chemistry*
Phosphodiesterase Inhibitors / pharmacology*
Pyrrolidinones / chemistry*
Pyrrolidinones / pharmacology*
Rolipram
Stereoisomerism

Substances

Benzyl Compounds
Phosphodiesterase Inhibitors
Pyrrolidinones
1-(4-bromobenzyl)-4-(3-(cyclopentyloxy)-4-methoxyphenyl)pyrrolidin-2-one
3',5'-Cyclic-AMP Phosphodiesterases
Rolipram