The crystal structure, absolute configuration, and phosphodiesterase inhibitory activity of (+)-1-(4-bromobenzyl)-4-(3-(cyclopentyloxy)- 4-methoxyphenyl)-pyrrolidin-2-one.
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.
Baures
P W
PW
Department of Physical and Structural Chemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
Eggleston
D S
DS
Erhard
K F
KF
Cieslinski
L B
LB
Torphy
T J
TJ
Christensen
S B
SB
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
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