509-60-4

Usage

Uses

Dihydromorphine is a metabolite of Hydromorphone (H714650).

InChI:InChI=1/C17H21NO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2,4,10-11,13,16,19-20H,3,5-8H2,1H3/t10-,11+,13-,16-,17-/m0/s1

Upstream product

• 52-26-6 morphine hydrochloride 
• 57-27-2 MORPHIN 
• 125-29-1 Hydrocodone 
• 23095-84-3 [3H]-Morphine 3-sulfate 
• 107-15-3 ethylenediamine 
• 466-99-9 hydromorphone 
• 509-71-7 Dihydroheroin 
• 509-60-4 dihydromorphine 
• 699533-76-1 ent-4,5α-epoxy-17-methyl-morphinane-3,6α-diol 
• 76-57-3 codeine 
• 33049-61-5 (-)-tetrahydrothebaine 
• 125-28-0 dihydrocodeine 
• 503441-35-8 neopine methyl ether 

Downstream Products

• 466-99-9 hydromorphone 
• 509-60-4 dihydromorphine 
• 57366-19-5 4,5α-epoxy-17-methyl-3-(1-phenyl-1H-tetrazol-5-yloxy)-morphinan-6α-ol 
• 22222-98-6 3-acetoxy-6-β-acetylthiodihydromorphine 
• 58752-60-6 3-O-acetyldihydromorphine 
• 302965-12-4 4,5-epoxy-17-methyl-(5α,6α)-morphinan-3,6-diol 3-benzoate 
• 1403776-94-2 4,5-epoxy-17-methyl-(5α,6α)-morphinan-3,6-diol 3,6-dibenzoate 
• 1403776-86-2 4,5-epoxy-17-methyl-(5α,6α)-morphinan-3,6-diol 3-benzoate 6-acetate 
• 130178-43-7 6-β-<5-nitro-2-pyridinesulfenyl>thio-dihydromorphine 
• 302965-08-8 C₄₃H₅₃NO₁₃ 
• 70001-26-2 Dihydromorphine 6-β-D-glucuronide 

Relevant academic research and scientific papers

Stereoselective reduction method of morphinone compounds

The invention discloses a stereoselective reduction method of morphinone compounds. The stereoselective reduction method comprises the step as follows: the morphinone compounds and tetramethylammonium triacetoxyborohydride are subjected to a reaction in an organic solvent in the presence of acid. A reducing agent, namely, tetramethylammonium triacetoxyborohydride, used in the method is convenient to prepare, low in cost, easy to store and non-corrosive to equipment, besides, reaction yield can basically reach about 99%, and de value can reach 98% or higher.

General, Simple, and Chemoselective Catalysts for the Isomerization of Allylic Alcohols: The Importance of the Halide Ligand

Remarkably simple IrIIIcatalysts enable the isomerization of primary and sec-allylic alcohols under very mild reaction conditions. X-ray absorption spectroscopy (XAS) and mass spectrometry (MS) studies indicate that the catalysts, with the general formula [Cp*IrIII], require a halide ligand for catalytic activity, but no additives or additional ligands are needed.

On the selection of an opioid for local skin analgesia: Structure-skin permeability relationships

Recent studies demonstrated that post-herpetical and inflammatory pain can be locally managed by morphine gels, empirically chosen. Aiming to rationalize the selection of the most suitable opioid for the cutaneous delivery, we studied the in vitro penetration through human epidermis of eight opioids, evidencing the critical modifications of the morphinan core. Log P, log D, solid-state features and solubility were determined. Docking simulations were performed using supramolecular assembly made of ceramide VI. The modifications on position 3 of the morphinan core resulted the most relevant in determining both physicochemical characteristics and diffusion pattern. The 3-methoxy group weakened the cohesiveness of the crystal lattice structure and increased the permeation flux (J). Computational studies emphasized that, while permeation is essentially controlled by molecule apolarity, skin retention depends on a fine balance of polar and apolar molecular features. Moreover, ChemPLP scoring the interactions between the opioids and ceramide, correlated with both the amount retained into the epidermis (Qret) and J. The balance of the skin penetration properties and the affinity potency for μ-receptors evidenced hydromorphone as the most suitable compound for the induction of local analgesia.

Preparation of benzoate esters of morphine and its derivatives

Sustained analgesia is crucial for patients suffering from long-acting pain. Ester derivatives of morphine could enhance the lipophilicity of morphine; consequently its transdermal delivery as well as its duration of action are also increased. Therefore, twenty-one 3-O-, 6-O-, and 14-Obenzoate esters of morphine and their derivatives were synthesized in order to elaborate different synthetic methods suitable for esterification of these widely used compounds. Schotten-Baumann reaction was applied with sodium hydrogen carbonate, triethylamine, or pyridine in methylene chloride or 1,2-dichloroethane as solvents. The presence of 4-dimethylaminopyridine catalyst was also successfully utilized mainly in the case of tertiary alcohols. A novel synthesis of dihydromorphine via diacetyl morphine free of by-products is also presented. Structures of all synthesized compounds were elucidated by 1H nuclear magnetic resonance (NMR), 13CNMR, high-resolution mass spectrometry (HRMS), and electron ionizationmass spectrometry (EI-MS). The log D (pH 7.4) values of the synthesized compounds were determined by a reversed-phase high-performance liquid chromatography (HPLC)-MS-based method, and calculated hydrolysis rate constants are also provided. The synthesized benzoate esters are potential prodrugs of the parent morphine with enhanced lipophilicity, derivatives which can also be used in transdermal drug delivery as prospective long-acting narcotic analgesics.

IMPROVED PROCESS FOR THE PREPARATION OF 6-ALPHA-HYDROXY-N-ALKYLATED OPIATES

The present invention is directed to the conversion of a 6-keto morphinan to a 6-alpha-hydroxy morphinan in the presence of a ruthenium, rhodium, or iridium asymmetric catalyst and a hydrogen source.

Practical and high-yield syntheses of dihydromorphine from tetrahydrothebaine and efficient syntheses of (8S)-8-bromomorphide

A practical method for the conversion of tetrahydrothebaine to dihydromorphine in 92% yield is described. The procedure should allow more efficient production of opium products and may be easily modified for large-scale synthesis. The conversion of codeine to (8S)-8-bromomorphide, a potentially valuable intermediate to 6-demethoxyoripavine and derivatives, is also described. The absolute configuration of (8S)-8-bromomorphide was determined by a single-crystal X-ray diffraction study of the hydrobromide salt.

Affinities of dihydrocodeine and its metabolites to opioid receptors.

Dihydrocodeine is metabolized to dihydromorphine, dihydrocodeine-6-O-, dihydromorphine-3-O- and dihydromorphine-6-O-glucuronide, and nordihydrocodeine. The current study was conducted to evaluate the affinities of dihydrocodeine and its metabolites to mu-, delta- and kappa-opioid receptors. Codeine, morphine, d,1-methadone and levomethadone were used as controls. Displacement binding experiments were carried out at the respective opioid receptor types using preparations of guinea pig cerebral cortex and the specific opioid agonists [5H]DAMGO (mu-opioid receptor), [3H]DPDPE (delta-opioid receptor) and [3H]U69,593 (K-opioid receptor) as radioactive ligands at concentrations of 0.5, 1.0 and 1.0 nmol/l, respectively. All substances had their greatest affinity to the mu-opioid receptor. The affinities of dihydromorphine and dihydromorphine-6-O-glucuronide were at least 70 times greater compared with dihydrocodeine (Ki 0.3 micromol/l), whereas the other metabolites yielded lower affinities. For the delta-opioid receptor, the order of affinities was similar with the exception that dihydrocodeine-6-O-glucuronide revealed a doubled affinity in relation to dihydrocodeine (Ki 5.9 micromol/l). In contrast, for the K-opioid receptor, dihydrocodeine-6-O- and dihydromorphine-6-O-glucuronide had clearly lower affinities compared to the respective parent compounds. The affinity of nordihydrocodeine was almost identical to that of dihydrocodeine (Ki 14 micromol/l), whereas dihydromorphine had a 60 times higher affinity. These results suggest that dihydromorphine and its 6-O-glucuronide may provide a relevant contribution to the pharmacological effects of dihydrocodeine. The O-demethylation of dihydrocodeine to dihydromorphine is mediated by the polymorphic cytochrome P-450 enzyme CYP2D6, resulting in different metabolic profiles in extensive and poor metabolizers. About 7% of the caucasian population which are CYP2D6 poor metabolizers thus may experience therapeutic failure after standard doses.

Hydromorphone metabolites: Isolation and identification from pooled urine samples of a cancer patient

1. Hydromorphone-3-glucuronide, dihydromorphine, dihydroisomorphine, dihydromorphine-3-glucuronide and dihydroisomorphine-3-glucuronide were isolated from a cancer patient's urine and identified as metabolites of hydromorphone by comparison with synthetic standards using LC/MS/MS with gradient elution. 2. The relative urinary recovery of dihydroisomorphine-3-glucuronide was estimated to be 17-fold higher than previously reported. 3. Three new metabolites, including hydromorphone-3-sulphate, norhydromorphone and nordihydroisomorphine, were tentatively identified.

Morphine-6-sulfate analogues and their use for the treatment of pain

3-O-Acetylmorphine-6-sulfate analogues are potent, centrally-acting morphine derivatives. The compounds are useful for the treatment of pain.

L-Selectride as a general reagent for the O-demethylation and N- decarbomethoxylation of opium alkaloids and derivatives

L-Selectride was shown to be an efficient and general O-demethylating agent for the opium alkaloids and their derivatives and also an efficient reagent for the cleavage of methyl carbamates, thus offering a convenient method for the N-demethylation of opioids. Further, it was shown that by choice of reaction conditions it is possible to achieve both N- decarbomethoxylation and O-demethylation in one pot, or only render N- decarbomethoxylation in high yield without accompanying O-demethylation.