2-[(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanamido]acetic acid

• ChemBase ID: 4425
• Molecular Formular: C25H32N2O4
• Molecular Mass: 424.53258
• Monoisotopic Mass: 424.23620751
• SMILES: Oc1cc([C@]2([C@H](CN(CC2)C[C@H](Cc2ccccc2)C(=O)NCC(=O)O)C)C)ccc1
• Canonical SMILES: OC(=O)CNC(=O)[C@@H](Cc1ccccc1)CN1CC[C@@]([C@H](C1)C)(C)c1cccc(c1)O
• InChI: InChI=1S/C25H32N2O4/c1-18-16-27(12-11-25(18,2)21-9-6-10-22(28)14-21)17-20(24(31)26-15-23(29)30)13-19-7-4-3-5-8-19/h3-10,14,18,20,28H,11-13,15-17H2,1-2H3,(H,26,31)(H,29,30)/t18-,20-,25+/m0/s1
• InChIKey: UPNUIXSCZBYVBB-JVFUWBCBSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-[(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanamido]acetic acid
• IUPAC Traditional name: entereg; alvimopan
• Brand Name: Entereg
• Synonyms: ADL 8-2698; alvimopan; Alvimopan; N-[(2S)-2-[[(3R,4R)-4-(3-Hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-1-oxo-3-phenylpropyl]glycine; LY 246736; Entereg

Database IDs

• CAS Number: 156053-89-3
• PubChem SID: 99443242; 160967857
• PubChem CID: 5488548

CALCULATED PROPERTIES

JChem

• Acid pKa: 3.7093873
• H Acceptors: 5
• H Donor: 3
• LogD (pH = 5.5): 0.81727153
• LogD (pH = 7.4): 0.8211437
• Log P: 0.82215357
• Molar Refractivity: 120.5593 cm^3
• Polarizability: 46.90431 Å^3
• Polar Surface Area: 89.87 Å^2
• Rotatable Bonds: 8
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.25
• LOG S: -4.71
• Solubility (Water): 8.34e-03 g/l

PROPERTIES

Physical Property

• Solubility: <0.1 mg/mL [FDA]

DETAILS

DrugBank - DB06274

• Drug Groups: approved; investigational
• Description: Alvimopan is a peripherally selective opioid antagonist being investigated for the treatment of various gastrointestinal diseases and disorders.
• Indication: Used to accelerate the time to upper and lower gastrointestinal recovery following partial large or small bowel resection surgery with primary anastomosis. Also investigated for use in the treatment of pain (acute or chronic).
• Affected Organisms: Humans and other mammals
• Biotransformation: Alvimopan undergoes no significant hepatic metabolism, but is metabolized by intestinal flora. Gut metabolism produces an active metabolite with no clinically significant contribution to drug effect.
• Absorption: Alvimopan's high affinity for the peripheral mu-receptor results in an absolute oral bioavailability of less than 7%.
• Half Life: 10 to 17 hours (gut metabolite: 10 to 18 hours)
• Protein Binding: 80% to 90% of systemically available alvimopan is bound to plasma protein.
• Elimination: Biliary secretion was considered the primary pathway for alvimopan elimination. Unabsorbed drug and unchanged alvimopan resulting from biliary excretion were then hydrolyzed to its ‘metabolite’ by gut microflora.
• Distribution: * 30±10 L
• Clearance: * 402 +/- 89 mL/min
• References: Buchler MW, Seiler CM, Monson JR, Flamant Y, Thompson-Fawcett MW, Byrne MM, Mortensen ER, Altman JF, Williamson R: Clinical trial: alvimopan for the management of postoperative ileus after abdominal surgery: results of an international randomised, double-blind, multicentre, placebo-controlled clinical study. Aliment Pharmacol Ther. 2008 Mar 28. [Pubmed]
• External Links: Wikipedia; Drugs.com

Toronto Research Chemicals - A575800

A peripheral μ-opioid receptor antagonist. Gastroprokinetic.

REFERENCES

• Buchler MW, Seiler CM, Monson JR, Flamant Y, Thompson-Fawcett MW, Byrne MM, Mortensen ER, Altman JF, Williamson R: Clinical trial: alvimopan for the management of postoperative ileus after abdominal surgery: results of an international randomised, double-blind, multicentre, placebo-controlled clinical study. Aliment Pharmacol Ther. 2008 Mar 28. Pubmed
• Zimmerman, D.M., et al.: J. Med. Chem., 37, 2262 (1994)
• Liu, S.S., et al.: Clin. Pharmacol. Ther., 68, 66 (1994)
• Taguchi, A., et al.: N. Engl. J. Med., 345, 935 (1994)