17-MethylnaltrexoneBromide

Base Information

• Chemical Name: 17-MethylnaltrexoneBromide
• CAS No.: 73232-52-7
• Molecular Formula: C21H26BrNO4
• Molecular Weight: 436.346
• Hs Code.: 2934990002
• European Community (EC) Number: 615-932-9
• Wikipedia: Methylnaltrexone
• NCI Thesaurus Code: C80569
• RXCUI: 979111
• Mol file: 73232-52-7.mol

Synonyms:(5alpha)-17-(cyclopropylmethyl)-3,14-dihydroxy-17-methyl-4,5-epoxymorphinan-17-ium-6-one;17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxymorphinanium-6-one;methyl-naltrexone hydrobromide;methylnaltrexone;methylnaltrexone bromide;morphinan-17-ium-6-one, 17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxy-17-methyl-, (5alpha)-;morphinan-17-ium-6-one, 17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxy-17-methyl-, bromide, (5alpha,17R)-;morphinanium, 17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxy-17-methyl-6-oxo-, (5alpha)-;MRZ 2663BR;MRZ-2663;N-methylnaltrexone bromide;naltrexone MB;naltrexone methobromide;naltrexone methylbromide;naltrexonium methiodide;quaternary ammonium naltrexone;relistor

Chemical Property of 17-MethylnaltrexoneBromide

Chemical Property:

• Melting Point: 237-239ºC
• PSA: 69.59000
• LogP: 3.02510
• Storage Temp.: Hygroscopic, -20?C Freezer, Under Inert Atmosphere
• Solubility.: H2O: ≥5mg/mL
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 2
• Exact Mass: 435.10452
• Heavy Atom Count: 27
• Complexity: 664

Purity/Quality:

99% ^*data from raw suppliers

N-MethylNaltrexoneBromide ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T,N
• Hazard Codes: T,N
• Statements: 25-50
• Safety Statements: 45-61

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C[N+]1(CCC23C4C(=O)CCC2(C1CC5=C3C(=C(C=C5)O)O4)O)CC6CC6.[Br-]
• Recent ClinicalTrials: Methylnaltrexone vs Naloxegol in the Treatment of Opioid-Induced Constipation
• Recent EU Clinical Trials: Use of Methylnaltrexone for the Treatment of Opioid Induced Constipation & Gastro-Intestinal Stasis in Intensive Care Patients
• Description: The widespread efficacy of opioids in treating patients with moderate to severe acute and chronic pain is often accompanied by untoward side effects. In particular, opioid-induced bowel dysfunction is one of the more common and debilitating consequences afflicting up to 50% of patients. To counteract the peripherally-mediated adverse effects, opioid antagonists such as naloxone, naltrexone, and nalmephene are sometimes prescribed. The latest market entry exploits a strategic modification of naltrexone to lower its lipid solubility and increase its polarity: quaternization of the amine of naltrexone by methylation (methyl bromide) prevents crossing of the blood–brain barrier thereby creating an effective peripheral antagonist. Despite a loss of potency upon methylation, methylnaltrexone antagonizes opioid binding at m-opioid receptors with an IC50 of 70 nM. Its affinity for k-opioid receptors is approximately eightfold less (IC50＝ 575 nM) with no significant binding to d-opioid, orphanin, or non-opioid receptors. Methylnaltrexone bromide has been approved for the treatment of opioid-induced constipation in patients with advanced illness receiving palliative care.Regarding metabolism, methylnaltrexone bromide is eliminated primarily as intact drug (85% based on administered radioactivity) by slightly more renal than hepatic clearance.The most common adverse events were abdominal pain and flatulence followed by nausea, dizziness, and diarrhea.
• Uses: A metabolite of Naltrexone (N285750). Methylnaltrexone (MNTX), a selective μ-opioid receptor antagonist, functions as a peripherally acting receptor antagonist in tissues of the gastrointestinal tract. Methylnaltrexone bromide has been used as a drug to measure plasma protein binding (PPB), permeability (Pm) and the membrane coefficient (KIAM) for the prediction of blood brain barrier (BBB) penetration. It is also used as a mu-opioid receptor (MOR) antagonist to abrogate morphine tolerance and opioid-induced hyperalgesia (OIH).

Technology Process of 17-MethylnaltrexoneBromide

There total 13 articles about 17-MethylnaltrexoneBromide 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: 99.0%

N-Methylnaltrexone iodide (73232-53-8) → methylnaltrexone bromide (73232-52-7)

Guidance literature:

With bromo-type strongly basic anion exchange resin; In water;

Reference yield: 83.1%

methyl bromide (74-83-9) + 3-O-acetylnaltrexone (111129-14-7) → methylnaltrexone bromide (73232-52-7)

Guidance literature:

methyl bromide; 3-O-acetylnaltrexone; In 1-methyl-pyrrolidin-2-one; at 20.8 - 32.9 ℃; under 103.432 - 206.865 Torr; Inert atmosphere;

With water; hydrogen bromide; In 1-methyl-pyrrolidin-2-one; at 60 - 80 ℃; for 5h; Product distribution / selectivity;

Reference yield:

3-[(tert-butyldimethylsilyl)oxy]-17-(cyclopropylmethyl)-4,5a-epoxy-14-hydroxy-6-(1,3-dioxolan-2-yl)-N-methylmorphinan bromide → methylnaltrexone bromide (73232-52-7)

Guidance literature:

With hydrogen bromide; In methanol; at 50 - 60 ℃; for 3h;

upstream raw materials:

N-methylnaltrexone zwitterion

methyl bromide

Naltrexone

3-O-acetylnaltrexone

Downstream raw materials:

Br^(1-)*C₂₁H₂₆NO₄⁽¹⁺⁾

Br^(1-)*C₂₁H₂₆NO₆⁽¹⁺⁾

Naltrexone

methylnaltrexone-3-sulfate

Refernces

• 1、 -. "Brominated morphinan quaternary ammonium salt preparation method". Paragraph 0066-0068. . Retrieved 2016/10/08.
• 2、 -. "Process for the preparation of quaternary n-alkyl morphinan alkaloid salts". Page/Page column 25. . Retrieved 2010/02/17.