121962-99-0Relevant academic research and scientific papers
The Facility of Formation of a Δ6 Bond in Dihydromorphinone and Related Opiates
Nagase, Hiroshi,Abe, Akira,Portoghese, Philip S.
, p. 4120 - 4125 (1989)
Treatment of naltrexone, dihydromorphinone, or related opiates that contain a 6-keto group with acetic anhydride or tert-butyldimethylsilyl chloride under mild conditions afforded enol derivatives having a Δ6 bond.Naltrexone also was found to undergo the Robinson annelation reaction with methyl vinyl ketone with facility and in high yield to give the β-hydroxy ketone 3, whose stereochemistry was determined by means of 2D NMR spectroscopy.Upon acid treatment, 3 was dehydrated to the α,β-unsaturated ketone 4.Acid-catalyzed equilibration of 4 afforded the unconjugated olefin 5.These studies suggest that the Δ6 bond is more stable than one that is exocyclic to ring C of the opiate because it permits ring flattening which may partially relieve torsional ring strain.The Δ6 bond also may relieve an eclipsing interaction between a C-6 exocyclic substituent and the vicinal furan oxygen.
Synthesis and biological activity of the phosphate and sulfate esters of naloxone and naltrexone
Lazar, S.,Jabbouri, S.,Moisand, C.,Noeel-Hocquet, S.,Meunier, J.C.,et al.
, p. 45 - 54 (1994)
Prodrugs of the two opiate antagonists naloxone and naltrexone, in particular the 3-monophosphate, 3-triphosphate, 3-monosulfate and 3,14-disulfate esters, have been synthesized and evaluated for: i) their ability to bind opioid receptors in vitro; and ii) their stability in both space and time upon entrapment into ex vivo human red blood cells (RBC).We find that, unlike the other esters, the mono- and triphosphate esters, of naloxone and naltrexone retain high (in the nmol range) affinities especially for μ- and κ-opioid receptors.Owing to their hydrophilic nature, the two esters could possibly help in certain types of pharmacological experiments.Morover, upon entrapment into human RBC, the triphosphate esters of naloxone and naltrexone display considerable ex vivo intracellular stability. phosphate and sulfate esters of naloxone and naltrexone / opiate antagonists / μ- δ- and κ-opioid receptors / equilibrium binding / encapsulation / red blood cells / metabolic stability
