Naltrexone 6-amino

Acamprosate. Acamprosate (calcium acetylhomotaurinate), an amino acid derivative, affects both GABA and excitatory amino acid (i.e., glutamate) neurotransmission (the latter effect most likely being the one that is important for its therapeutic effects in alcoholism). Initially evaluated in a singlecenter trial in France, acamprosate was shown to be twice as effective as placebo in reducing the rate at which alcoholic patients returned to drinking (Lhuin-tre et al. 1985). The safety and efficacy of the medication have been studied most widely in Europe, and three of these studies provided the basis for the recent approval of acamprosate by the FDA for clinical use in the United States. As with naltrexone, there exist a number of meta-analytic studies that provide consistent evidence of the efficacy of the medication in the treatment of alcohol dependence. 

J-CNA can be prepared in two steps from naltrexone. Reductive animation using diethanolamine and sodium cyanoborohydride gave the 6/ -ami-no derivative (16) (the 6a-amino isomer was not formed). The conversion of (16) into (15) was effected by a modification of the triphenylphosphine-CC14 procedure [62] in dimethylformamide. 

NTII was prepared by reacting naltrexone with (4-nitrophenyl)hydrazine to form 5 -nitroindole (142) which was reduced by catalytic hydrogenation over Raney nickel to the 5 -amino derivative (143). Treatment with thio-phosgene yielded NTII [203]. 

Stereochemical studies on medicinal agents. 23. Synthesis and biological evaluation of 6-amino derivatives of naloxone and naltrexone... 

A further patent for the production of codeine, via codeinone, from thebaine has been published. " Codeine has been shown to be oxidized by manganese dioxide to 14-hydroxycodeinone the reaction is presumed to proceed via codeinone since 6-acetylcodeine is not affected by the same reagent. 6-O-Methanesulphonyl-dihydrocodeine has been shown to react with tetra-butylammonium fluoride, lithium chloride, and lithium bromide, with inversion at C-6, to give the related 6-halogeno-dihydrocodides, but when the ester is heated with sodium iodide in dimethylformamide the product is A -deoxycodeine (deoxycodeine-C) (143). Reductive amination of naltrexone with 2,2 -dihy-droxydiethylamine and sodium cyanoborohydride yields the 6-amino-compound (144 R = OH), which can be converted by carbon tetrachloride and tri-... 

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