J-113,397
J-113,397 is an opioid drug which was the first compound found to be a highly selective antagonist for the nociceptin receptor, also known as the ORL-1 receptor. It is several hundred times selective for the ORL-1 receptor over other opioid receptors, and its effects in animals include preventing the development of tolerance to morphine, the prevention of hyperalgesia induced by intracerebroventricular administration of nociceptin, as well as the stimulation of dopamine release in the striatum, which increases the rewarding effects of cocaine, but may have clinical application in the treatment of Parkinson's disease.
Synthesis
Patents for treating arrhythmia:Condensation between 1-Benzyl-3-methoxycarbonyl-4-piperidone and O-Phenylenediamine gives . Reaction with boc anhydride followed by treatment with trifluoroacetic acid gives . Reaction with iodoethane in the presence of base alkylates the urea nitrogen giving . Reduction of the enamine by treatment with magnesium metal in methanol solvent occurs to give predominantly the trans isomer, . Catalytic removal of the benzyl group gives . Reductive amination with Cyclooctanecarbaldehyde gives . Lastly, reduction of the ester with lithium aluminium hydride completed the synthesis of J-113397.