97134-50-4

Upstream product

• 74991-35-8 (1R,2R)-1-(4-(benzyloxy)phenyl)-2-(4-benzylpiperidin-1-yl)propan-1-ol 
• 35081-45-9 1-<4-(benzyloxy)phenyl>-2-bromo-1-propanone 
• 74991-35-8 (1R,2S)-1-(4-Benzyloxy-phenyl)-2-(4-benzyl-piperidin-1-yl)-propan-1-ol 
• 74991-32-5 (RS)-2-(4-benzylpiperidin-1-yl)-1-(4-hydroxyphenyl)propan-1-one 
• 53946-87-5 2-bromo-(4'-hydroxyphenyl)-propan-1-one 
• 108-95-2 phenol 
• 35133-39-2 1-(4-(benzyloxy)phenyl)-2-(4-benzylpiperidin-1-yl)propan-1-one 
• 31252-42-3 4-benzylpyperidine 

Relevant academic research and scientific papers

Ifenprodil Stereoisomers: Synthesis, Absolute Configuration, and Correlation with Biological Activity

Ifenprodil (1) is a potent GluN2B-selective N-methyl-d-aspartate (NMDA) receptor antagonist that is used as a cerebral vasodilator and has been examined in clinical trials for the treatment of drug addiction, idiopathic pulmonary fibrosis, and COVID-19. To correlate biological data with configuration, all four ifenprodil stereoisomers were prepared by diastereoselective reduction and subsequent separation of enantiomers by chiral HPLC. The absolute configuration of ifenprodil stereoisomers was determined by X-ray crystal structure analysis of (1R,2S)-1a and (1S,2S)-1d. GluN2B affinity, ion channel inhibitory activity, and selectivity over α, σ, and 5-HT receptors were evaluated. (1R,2R)-Ifenprodil ((1R,2R)-1c) showed the highest affinity toward GluN2B-NMDA receptors (Ki = 5.8 nM) and high inhibition of ion flux in two-electrode voltage clamp experiments (IC50 = 223 nM). Whereas the configuration did not influence considerably the GluN2B-NMDA receptor binding, (1R)-configuration is crucial for elevated inhibitory activity. (1R,2R)-Configured ifenprodil (1R,2R)-1c exhibited high selectivity for GluN2B-NMDA receptors over adrenergic, serotonergic, and σ1 receptors.

Separation of α1 Adrenergic and N-Methyl-D-aspartate Antagonist Activity in a Series of Ifenprodil Compounds

Ifenprodil (1) represents a new class of N-methyl-D-aspartate (NMDA) antagonist.This drug also possesses potent activity at several other brain receptors (most notably α1 adrenergic receptors).We have prepared the enantiomers and diastereomers of ifenprodil along with a series of partial structures in order to explore the basic structure activity relations within this class of compounds.From this study, it is clear that α1 adrenergic and NMDA receptor activities may be separated by selection of the threo relative stereochemistry.Examination of the optical isomers of threo-ifenprodil (2) reveals that no further improvement in receptor selectivity is gained from either antipode.Individual removal of most of the structural fragments from the ifenprodil molecule generally results in less active compounds although fluorinated derivative 9 with threo relative stereochemistry is somewhat more potent and substantially more selective for the NMDA receptor.Finally a minimum structure for activity in this series (14) has been identified.This stripped-down version of ifenprodil possesses nearly equivalent affinity for the NMDA receptor with no selectivity over α1 adrenergic receptors.

THE STEREOSELECTIVE REDUCTION OF α-AMINOPROPIOPHENONE DERIVATIVES WITH SODIUM BOROHYDRIDE

The ratio of erythro and threo products from the sodium borohydride reduction of the hydrochlorides, and other acid salts, of α-aminopropiophenone derivatives was determined.It was found that this procedure resulted in stereoselective formation of erythro-2-amino-1-phenylpropanols in contrast to sodium borohydride reduction of the corresponding free bases.The method was successfully applied to the synthesis of dl-erythro-2-(4-benzylpiperidino)-1-(4-hydroxyphenyl)propanol which has been used as a vasodilator.