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

• ChemBase编号: 4425
• 分子式: C25H32N2O4
• 平均质量: 424.53258
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: 2-[(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanamido]acetic acid
• IUPAC传统名: entereg; alvimopan
• 商标名: Entereg
• 别名: 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

登记号

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

理论计算性质

JChem

• Acid pKa: 3.7093873
• 质子受体: 5
• 质子供体: 3
• LogD (pH = 5.5): 0.81727153
• LogD (pH = 7.4): 0.8211437
• Log P: 0.82215357
• 摩尔折射率: 120.5593 cm^3
• 极化性: 46.90431 Å^3
• 极化表面积: 89.87 Å^2
• 可自由旋转的化学键: 8
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 3.25
• LOG S: -4.71
• 溶解度: 8.34e-03 g/l

分子性质

理化性质

• 溶解度: <0.1 mg/mL [FDA]

详细说明

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.

参考文献

• 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)