Pharmacological characterization of 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-6-[(3′-fluoro-4′-pyridyl)acetamido]morphinan (NFP) as a dual selective MOR/KOR ligand with potential applications in treating opioid use disorder

Systematic Structure–Activity Relationship Study of Nalfurafine Analogues toward Development of Potentially Nonaddictive Pain Management Treatments

“…Warm-water tail immersion (WWTI) assays are often employed to rapidly characterize opioid receptor ligands; this is a technique that we have used for many years. ,,,,− ,,,− Briefly, to assess potential antinociception, a mouse’s tail is dipped into a warm-water bath. The mouse then flicks its tail to remove the thermal stimulus.…”

“…Briefly, 3-dehydroxynaltrexone was first synthesized from naltrexone . Naltrexone and 3-dehydroxynaltrexone were then subjected to four different stereoselective reductive amination methods followed by catalytic hydrogenation under acidic conditions (where applicable) to yield eight different naltrexamines: namely, 6α-naltrexamine, 6α-3-dehydroxynaltrexamine, 6β-naltrexamine, 6β-3-dehydroxynaltrexamine, 6α- N -methyl-naltrexamine, 6α- N -methyl-3-dehydroxynaltrexamine, 6β- N -methyl-naltrexamine, and 6β- N -methyl-3-dehydroxynaltrexamine. − Then primary amines were coupled to carboxylic acids utilizing the EDCI/HOBt coupling reaction while secondary amines were coupled to acyl chlorides under basic conditions. Acyl chlorides were prepared fresh from their carboxylic acid counterparts prior to coupling if they were commercially unavailable .…”