911422-95-2

Upstream product

• 143919-32-8 (R)-1,2,3,4-tetrahydro-1,3-dimethyl-4-<3-(1-methylethoxy)phenyl>pyridine 
• 104-53-0 3-phenyl-propionaldehyde 
• 911422-92-9 2-[(1S,4R,5S,7S)-5-(3-isopropoxyphenyl)-2,4-dimethyl-2-azabicyclo[3.3.1]non-7-yl]-1H-isoindole-1,3(2H)-dione 
• 911422-93-0 2-[(1S,4R,5S,7S)-5-(3-isopropoxyphenyl)-4-methyl-2-azabicyclo[3.3.1]non-7-yl]-1H-isoindole-1,3(2H)-dione 
• 911422-94-1 2-[(1S,4R,5S,7S)-5-(3-isopropoxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicyclo[3.3.1]non-7-yl]-1H-isoindole-1,3(2H)-dione 

Downstream Products

• 455311-42-9 (1S,4R,5R,7S)-(+)-5-(3-hydroxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicylo-[3.3.1]nonan-7-amine 

Relevant academic research and scientific papers

Highly potent and selective phenylmorphan-based inverse agonists of the opioid δ receptor

We recently reported the discovery of (+)-5-(3-hydroxyphenyl)-4-methyl-2- (3-phenylpropyl)-2-azabicyclo-[3.3.1]non-7-yl-(1-phenyl-1-cyclopentane) carboxamide [(+)-KF4, (+)-5] as a novel chemotype possessing potent antagonist activity at the δ opioid receptor. Additional SAR studies involving changes to both the 2-amino and 7-amido N-substituents using this same (+)-morphan scaffold have revealed compounds with improved potency and selectivity for the δ opioid receptor. The highly potent and selective 2,2-dimethylphenylacetamide analogue (+)-N-[(1S,4R,5R,7S)-5-(3-hydroxyphenyl)-4- methyl-2-(3-phenylpropyl)-2-azabicyclo[3.3.1]non-7-yl]-2-methyl-2- phenylpropanamide (13d, delmorphan-A) showed picomolar inhibitory potency (Ke = 0.1 nM) in the [35S]GTPγS functional assay with δ opioid receptor selectivity ratios of 103- and 132-fold versus the μ and κ opioid receptors, respectively. The compounds showed no agonist activity at any of the three opioid receptors; however, measurements of δ inverse agonist activity within this series illustrated a broad range of negative efficacy and IC50 values 650-fold more potent than the prototypical δ opioid receptor inverse agonist ICI 174 864 (22).

Discovery of an opioid κ receptor selective pure antagonist from a library of N-substituted 4β-methyl-5-(3-hydroxyphenyl)morphans

A library of compounds biased toward opioid receptor antagonist activity was prepared by incorporating N-phenylpropyl-4β-methyl-5-(3-hydroxyphenyl)morphans as the core scaffold using simultaneous solution phase synthetic methodology. From this library, N-