title: The crystal structure, absolute configuration, and phosphodiesterase inhibitory activity of (+)-1-(4-bromobenzyl)-4-(3-(cyclopentyloxy)- 4-methoxyphenyl)-pyrrolidin-2-one.
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.
authors.affiliation: Department of Physical and Structural Chemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
authors.forename: P W
authors.initials: PW
authors.lastname: Baures
authors.forename: D S
authors.initials: DS
authors.lastname: Eggleston
authors.forename: K F
authors.initials: KF
authors.lastname: Erhard
authors.forename: L B
authors.initials: LB
authors.lastname: Cieslinski
authors.forename: T J
authors.initials: TJ
authors.lastname: Torphy
authors.forename: S B
authors.initials: SB
authors.lastname: Christensen
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001593:Benzyl Compounds / Q000737:chemistry* / Q000494:pharmacology*; D002417:Cattle; D018360:Crystallography, X-Ray; D008968:Molecular Conformation; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000737:chemistry* / Q000494:pharmacology*; D020889:Rolipram; D013237:Stereoisomerism
chemical_list: D001593:Benzyl Compounds; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C084127:1-(4-bromobenzyl)-4-(3-(cyclopentyloxy)-4-methoxyphenyl)pyrrolidin-2-one; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D020889:Rolipram