845-69-2

Usage

Uses

Used in Pharmaceutical Industry:
Nordihydrocodeine is used as an active pharmaceutical ingredient for the development of pain relief medications. It is utilized in the formulation of drugs that target the management of moderate to severe pain, providing an alternative to other opioid analgesics.
Used in Research and Development:
In the field of pharmaceutical research and development, nordihydrocodeine serves as a key compound for studying the metabolism and pharmacokinetics of Dihydrocodeine. This helps in understanding the drug's efficacy, safety, and potential side effects, ultimately contributing to the improvement of pain management therapies.
Used in Regulatory Compliance:
As a controlled substance, nordihydrocodeine is used in regulatory compliance and monitoring efforts to ensure the responsible distribution, prescription, and use of opioid analgesics. This helps in preventing the misuse and abuse of these potent pain relievers, safeguarding public health and addressing the ongoing opioid crisis.
Used in Toxicology and Forensic Analysis:
Nordihydrocodeine plays a role in toxicology and forensic analysis, where it is identified and quantified in biological samples to determine the presence and levels of Dihydrocodeine and its metabolites. This is crucial in cases of drug overdose, poisoning, or substance abuse investigations, aiding in the legal and medical assessment of such incidents.

InChI:InChI=1/C17H21NO3/c1-20-13-5-2-9-8-11-10-3-4-12(19)16-17(10,6-7-18-11)14(9)15(13)21-16/h2,5,10-12,16,18-19H,3-4,6-8H2,1H3/t10?,11-,12+,16?,17+/m1/s1

Upstream product

• 467-15-2 norcodeine 
• 3861-72-1 dihydrocodeine-6-O-acetate 
• 125-28-0 dihydrocodeine 
• 5083-62-5 Norhydrocodone 

Relevant academic research and scientific papers

Synthesis of Potential Haptens with Morphine Skeleton and Determination of Protonation Constants

Vaccination could be a promising alternative warfare against drug addiction and abuse. For this purpose, so-called haptens can be used. These molecules alone do not induce the activation of the immune system, this occurs only when they are attached to an immunogenic carrier protein. Hence obtaining a free amino or carboxylic group during the structural transformation is an important part of the synthesis. Namely, these groups can be used to form the requisite peptide bond between the hapten and the carrier protein. Focusing on this basic principle, six nor-morphine compounds were treated with ethyl acrylate and ethyl bromoacetate, while the prepared esters were hydrolyzed to obtain the N-carboxymethyl- and N-carboxyethyl-normorphine derivatives which are considered as potential haptens. The next step was the coupling phase with glycine ethyl ester, but the reactions did not work or the work-up process was not accomplishable. As an alternative route, the normorphine-compounds were N-alkylated with N-(chloroacetyl)glycine ethyl ester. These products were hydrolyzed in alkaline media and after the work-up process all of the derivatives contained the free carboxylic group of the glycine side chain. The acid-base properties of these molecules are characterized in detail. In the N-carboxyalkyl derivatives, the basicity of the amino and phenolate site is within an order of magnitude. In the glycine derivatives the basicity of the amino group is significantly decreased compared to the parent compounds (i.e., morphine, oxymorphone) because of the electron withdrawing amide group. The protonation state of the carboxylate group significantly influences the basicity of the amino group. All of the glycine ester and the glycine carboxylic acid derivatives are currently under biological tests.

PROCESS FOR REDUCING THE 6-KETO GROUP OF A MORPHINAN ALKALOID TO THE 6-HYDROXY GROUP BY HYDROGENATION

The present invention relates to a process for the reduction of a 6-keto group in a morphinan alkaloid to the corresponding 6-hydroxy group, comprising hydrogenating the 6-keto group using gaseous hydrogen in the presence of a heterogeneous catalyst and a solvent, to yield the 6-hydroxy morphinan alkaloid, wherein the reduction is carried out at a pH in the range of about 5 to about 7, and the 6-hydroxy morphinan alkaloid has an α:β ratio of > 85: 15.

Oxidative metabolism of dihydrocodeine in Dark-Agouti and Sprague-Dawley rat liver microsomes

The oxidative metabolism of dihydrocodeine to nordihydrocodeine and dihydromorphine was studied in liver microsomes of female Dark-Agouti (cytochrome P450 2D1 (CYP2D1) deficient) and Sprague-Dawley rats. Evaluation of microsomal metabolism in these two rat strains is a useful in-vitro model to test possible substrates of polymorphic human cytochrome P450 2D6 (CYP2D6). Nordihydrocodeine formation rates were similar in both strains. Analysis of the Michaelis-Menten kinetics of dihydromorphine formation showed a significant difference (P -1 g-1) and intrinsic clearance (0.986; 19.5 mL min-1 g-1). In Sprague-Dawley liver microsomes, dihydromorphine formation was suppressed by the CYP2D1 inhibitors, quinine and quinidine, at concentrations which had no effect on nordihydrocodeine formation. These in-vitro findings indicate that in rat liver microsomes the cytochrome P450 system is involved in dihydrocodeine metabolism to dihydromorphine and nordihydrocodeine and that CYP2D1 is involved in the O-demethylation to dihydromorphine but not the N-demethylation to nordihydrocodeine. The results of this study are in agreement with recent in-vivo studies of dihydrocodeine metabolism in man which indicate CYP2D6 is the predominant enzyme catalysing dihydromorphine formation.

Metabolism and pharmacokinetics of dihydrocodeine in dog

The metabolism and pharmacokinetics of dihydrocodeine have been studied in dog. Urinary metabolites after oral administration of dihydrocodeine were identified using hplc with diode-array and ms. In urine, dihydronorcodeine, dihydromorphine and dihydrocodeine glucuronide were identified in comparison with their authentic standards, and dihydronorcodeine 6-glucuronide also appeared to be excreted as a metabolite. The major urinary metabolite was dihydrocodeine glucuronide, recovered as 49% of the dose, and other metabolites were found to be 0.1-3%, 24h after 3 mg/kg oral administration of dihydrocodeine. Plasma concentrations of unchanged dihydrocodeine were significantly lower after oral rather than intramuscular administration, the maximum concentrations were 40 and 549 ng/ml after oral and intramuscular administration, respectively. This suggests that dihydrocodeine was metabolized via a hepatic first-pass effect after oral administration. Overall, our results indicate that the metabolic pathways of dihydrocodeine in dog were similar to that of codeine metabolism in animals and man.