Alvimopan

Base Information

• Chemical Name: Alvimopan
• CAS No.: 156053-89-3
• Molecular Formula: C25H32N2O4
• Molecular Weight: 424.54
• Hs Code.: 2933399090
• European Community (EC) Number: 814-137-6
• UNII: Q153V49P3Z
• DSSTox Substance ID: DTXSID60166035
• Nikkaji Number: J605.686E
• Wikipedia: Alvimopan
• Wikidata: Q4738021
• NCI Thesaurus Code: C77377
• RXCUI: 1516803
• Pharos Ligand ID: KN3BKG2Q1YWS
• Metabolomics Workbench ID: 43667
• ChEMBL ID: CHEMBL270190
• Mol file: 156053-89-3.mol

Synonyms:ADL 8-2698;ADL8-2698;alvimopan;alvimopan anhydrous;anhydrous alvimopan;Entereg;LY 246736;LY-246736;LY246736;trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine

Chemical Property of Alvimopan

Chemical Property:

• Melting Point: 210-213oC
• Boiling Point: 684.1 °C at 760 mmHg
• PKA: 3.39±0.10(Predicted)
• Flash Point: 367.5 °C
• PSA: 89.87000
• Density: 1.166 g/cm³
• LogP: 3.38020
• Storage Temp.: 2-8°C
• Solubility.: DMSO (Slightly), Methanol (Slightly, Sonicated, Heated)
• XLogP3: 1.7
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 8
• Exact Mass: 424.23620751
• Heavy Atom Count: 31
• Complexity: 606

Purity/Quality:

99.0%min ^*data from raw suppliers

Alvimopan ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1CN(CCC1(C)C2=CC(=CC=C2)O)CC(CC3=CC=CC=C3)C(=O)NCC(=O)O
• Isomeric SMILES: C[C@H]1CN(CC[C@@]1(C)C2=CC(=CC=C2)O)C[C@H](CC3=CC=CC=C3)C(=O)NCC(=O)O
• Recent ClinicalTrials: Alvimopan as a Rescue Treatment of Postoperative Ileus
• Recent EU Clinical Trials: A Double-Blind, Placebo-Controlled, Multicenter Phase IIb Extension Study to Evaluate the Safety and Efficacy of Multiple Alvimopan Dosage Regimens for the Treatment of Opioid-Induced Bowel Dysfunction in Cancer Pain Subjects.
• Drug Interactions: In vitro studies have shown that this product and its metabolites have no inhibitory effect on CYP1A2, CYP2C9, CYP2C19, CYP3A4, CYP2D6 and CYP2E1 while having no induction effect on CYP1A2, CYP2B6, CYP2C9, CYP2C19 and CYP3A4. Theoretically, there is no effect for drug of CYP enzyme inhibition or induction when being used in combination therapy with the product, but there is no clinical study data supporting this at present. This product and its metabolites are the substrate of the p-glycoprotein. There are still no clinical studies regarding to the combination medication between this product with potent inhibitor of p-glycoprotein (e.g. verapamil, cyclosporine, itraconazole, quinine, diltiazem, bepridil). Population pharmacokinetic analysis has showed that combined application of acid blockers or antibiotics does not affect the pharmacokinetic parameters of the product. This plasma concentration of this product metabolite is relative low and the metabolite has no efficacy, therefore it has no effect. Clinical upon intravenous infusion of morphine, combination with this product has no impact on the pharmacokinetic parameter on the morphine and its metabolites morphine-6 glucuronide.
• Uses: A peripheral μ-opioid receptor antagonist. Gastroprokinetic. flavenoid cytoprotective agent for the treatment of mucosal lesions

Technology Process of Alvimopan

There total 37 articles about Alvimopan 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: 87.0%

(+)-<<2'(S)-<<4(R)-3-(hydroxyphenyl)-3(R),4-dimethyl-1-piperidinyl>methyl>-1-oxo-3-phenylpropyl>amino>acetic acid 2-methylpropyl ester (145603-86-7) → Entereg (156053-89-3,156130-44-8,342639-35-4,342639-02-5)

Guidance literature:

With water; sodium hydroxide; In ethanol; at 25 ℃; for 0.75h;

Reference yield: 53.0%

ethyl N-{(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanoyl}glycinate → Entereg (156053-89-3,156130-44-8,342639-35-4,342639-02-5)

Guidance literature:

ethyl N-{(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanoyl}glycinate; With water; sodium hydroxide; In ethanol; at 25 - 32 ℃;

With hydrogenchloride; In water; at 25 - 32 ℃; pH=5.8 - 6.2;

Reference yield:

N-[(2S)-2-[(3R,4R)-4-(3-triisopropylsilyloxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl-1-oxo-3-phenylpropyl]glycine → Entereg (156053-89-3,156130-44-8,342639-35-4,342639-02-5)

Guidance literature:

With tetrabutyl ammonium fluoride; In tetrahydrofuran; at 20 ℃;

upstream raw materials:

(+)-<<2'(S)-<<4(R)-3-(hydroxyphenyl)-3(R),4-dimethyl-1-piperidinyl>methyl>-1-oxo-3-phenylpropyl>amino>acetic acid 2-methylpropyl ester

2-Benzylacrylic acid ethyl ester

3-[(3R,4R)-3,4-dimethylpiperidin-4-yl]phenol

(S)-2-hydroxymethyl-3-phenylpropionic acid

Refernces

• 1、 Reddy, Beeravalli Ramalinga,Dubey, Manoj Kumar,Ramana Reddy, Ch. Venkata,Bandichhor, Rakeshwar. "Synthesis and characterization of all possible diastereoisomers of alvimopan". . p. 963 - 972. Retrieved 2018/05/28.
• 2、 -. "AN IMPROVED PROCESS FOR THE PREPARATION OF [[2(S)-[[4(R)-(3-HYDROXY PHENYL)-3(R), 4-DIMETHYL-1 -PIPERIDINYL]METHYL]-1 -OXO-3-PHENYLPROPYL] AMINO]ACETIC ACID DIHYDRATE". Page/Page column 12; 14. . Retrieved 2017/10/11.