Nalfurafine hydrochloride

Base Information

• Chemical Name: Nalfurafine hydrochloride
• CAS No.: 152658-17-8
• Molecular Formula: C₂₈H₃₂N₂O₅*ClH
• Molecular Weight: 513.033
• European Community (EC) Number: 845-923-7
• UNII: 25CC4N0P8J
• DSSTox Substance ID: DTXSID70426071
• Wikidata: Q27253946
• NCI Thesaurus Code: C80586
• Pharos Ligand ID: GAVFYSPDV7NU
• ChEMBL ID: CHEMBL490665
• Mol file: 152658-17-8.mol

Synonyms:17-cyclopropylmethyl-3,14beta-dihydroxy-4,5alpha-epoxy-6beta-(N-methyl-trans-3-(3-furyl)acrylamido)morphinan hydrochloride;nalfurafine;nalfurafine hydrochloride;TRK 820;TRK-820

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Chemical Property of Nalfurafine hydrochloride

Chemical Property:

• Melting Point: 207-217 °C
• PSA: 86.38000
• LogP: 3.82960
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 5
• Exact Mass: 512.2077999
• Heavy Atom Count: 36
• Complexity: 893

Purity/Quality:

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CN(C1CCC2(C3CC4=C5C2(C1OC5=C(C=C4)O)CCN3CC6CC6)O)C(=O)C=CC7=COC=C7.Cl
• Isomeric SMILES: CN([C@@H]1CC[C@]2([C@H]3CC4=C5[C@]2([C@H]1OC5=C(C=C4)O)CCN3CC6CC6)O)C(=O)/C=C/C7=COC=C7.Cl
• Recent ClinicalTrials: A Multi-site Bridging Study of Nalfurafine Hydrochloride Orally Disintegrating Tablet
• Recent EU Clinical Trials: CLINICAL TRIAL NO: EU820UPV01
• Recent NIPH Clinical Trials: Multi-Institutional Joint Research of Health-Related Quality of Life of Patients with Pruritus due to Chronic Liver Disease
• Description: Pruritus (chronic itching) is a common symptom seen in 25-90% of uremic patients, especially those with chronic renal failure requiring hemodialysis. Nalfurafine hydrochloride is a new member of this class that exhibits an improved safety profile as compared with its predecessors in preclinical studies. It is a potent agonist for the κ-opioid receptor (Ki = 0.24 nM, EC50 = 0.008 nM, Imax = 91%), with substantially lower binding and agonism of the - or d-opioid receptors (Ki = 2.24 and 484 nM, EC50 = 1.66 and 21.3 nM, Imax = 53 and 78%, respectively). In vivo, nalfurafine hydrochloride demonstrates potent antipruritic activity against histamine-sensitive as well as histamine-resistant itch in mouse pruritogen-induced scratching models. The most common adverse event associated with nalfurafine hydrochloride was insomnia or sleep disturbance, seen in 10% of the treated patients. Nalfurafine is structurally related to naltrexone (Revia ), an opioid receptor antagonist marketed for treating alcohol dependence. Nalfurafine is synthesized in two steps starting from naltrexone, via reductive amination with methylamine under catalytic hydrogenation conditions, and subsequent acylation with 3(E)-(3-furyl) acryloyl chloride.
• Uses: Nalfurafine hydrochloride was launched on March of 2009 in Japan as the first in class non-narcotic opioid drug for intractable itch caused by hemodialysis. It showed significant opioid κ-agonist activity and induced neither aversion nor preference in rats on the CPP (Conditioned Place Preference) test. A new therapeutic agent for the treatment of uremic pruritus in hemodialysis patients.

Technology Process of Nalfurafine hydrochloride

There total 6 articles about Nalfurafine hydrochloride which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 85.0%

trans-3-(furan-3-yl)acryloyl chloride (81311-96-8) + 6β-N-methylnaltrexamine (102869-99-8) → nalfurafine hydrochloride (152658-17-8)

Guidance literature:

DOI:10.1016/j.bmc.2008.09.011

Reference yield:

17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan (152657-84-6) → nalfurafine hydrochloride (152658-17-8)

Guidance literature:

With hydrogenchloride; In ethanol; water; Product distribution / selectivity;

Reference yield:

(E)-3-furan-3-yl-acrylic acid (39244-10-5,81311-95-7) → nalfurafine hydrochloride (152658-17-8)

Guidance literature:

Multi-step reaction with 3 steps

1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / Inert atmosphere

2: tetrahydrofuran; water / 0.5 h / 20 °C

3: hydrogenchloride / methanol / 0.25 h

With hydrogenchloride; oxalyl dichloride; N,N-dimethyl-formamide; In tetrahydrofuran; methanol; dichloromethane; water;

upstream raw materials:

17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan

trans-3-(furan-3-yl)acryloyl chloride

6β-N-methylnaltrexamine

(E)-3-furan-3-yl-acrylic acid