(2S,3aS,7aS)-1-[(2S)-2-[(1-ethoxy-1-oxopentan-2-yl)amino]propanoyl]-octahydro-1H-indole-2-carboxylic acid; 2-methylpropan-2-amine

• ChemBase编号: 72715
• 分子式: C23H43N3O5
• 平均质量: 441.60462
• 单一同位素质量: 441.32027149
• SMILES: CCCC(N[C@H](C(=O)N1[C@@H]2[C@H](C[C@H]1C(=O)O)CCCC2)C)C(=O)OCC.C(C)(N)(C)C
• Canonical SMILES: CC(N)(C)C.CCCC(C(=O)OCC)N[C@H](C(=O)N1[C@H]2CCCC[C@H]2C[C@H]1C(=O)O)C
• InChI: InChI=1S/C19H32N2O5.C4H11N/c1-4-8-14(19(25)26-5-2)20-12(3)17(22)21-15-10-7-6-9-13(15)11-16(21)18(23)24;1-4(2,3)5/h12-16,20H,4-11H2,1-3H3,(H,23,24);5H2,1-3H3/t12-,13-,14?,15-,16-;/m0./s1
• InChIKey: IYNMDWMQHSMDDE-VUDKHQNUSA-N

名称和登记号

名称

• IUPAC标准名: (2S,3aS,7aS)-1-[(2S)-2-[(1-ethoxy-1-oxopentan-2-yl)amino]propanoyl]-octahydro-1H-indole-2-carboxylic acid; 2-methylpropan-2-amine
• IUPAC传统名: (2S,3aS,7aS)-1-[(2S)-2-[(1-ethoxy-1-oxopentan-2-yl)amino]propanoyl]-octahydroindole-2-carboxylic acid; erbumine
• 别名: Perindopril; Coversyl; Aceon; Perindopril Erbumine

登记号

• CAS号: 107133-36-8
• PubChem SID: 162037636
• PubChem CID: 46705389

理论计算性质

• Acid pKa: 3.7860548
• 质子受体: 5
• 质子供体: 2
• LogD (pH = 5.5): 0.4626669
• LogD (pH = 7.4): -0.8469951
• Log P: 0.63074386
• 摩尔折射率: 95.6928 cm^3
• 极化性: 38.332016 Å^3
• 极化表面积: 95.94 Å^2
• 可自由旋转的化学键: 9
• 里宾斯基五规则: true

分子性质

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: RAAS

产品相关信息

• 成盐信息: t-Butylamine

详细说明

Selleck Chemicals - S1506

Research Area

• Description: Cardiovascular Disease

Biological Activity

• Description: Perindopril Erbumine (Aceon) is a potent ACE) inhibitor with IC50 of 1.05 nM.
• Targets: ACE
• IC50: 1.05 nM ^[1]
• In Vitro: Perindopril Erbumine displays a higher binding affinity for the bradykinin binding sites than the angiotensin I binding sites of the angiotensin-converting enzyme (ACE) with bradykinin/angiotensin I selectivity ratio of 1.44. ^[1] Perindopril Erbumine inhibits the angiotensin- and Aβ42-to-Aβ40-converting activity of mutated ACE containing two active domains (F-ACE) with IC50 of 0.03-0.1 μM, and 0.01-0.03 μM, respectively. ^[2] Perindopril Erbumine (~2 μM) displays no significant cytotoxicity towards SCC-VII and KB cells, but can significantly reduce the production of angiotensin II and the transcription of VEGF in KB cells in a concentration-dependent manner. ^[3]
• In Vivo: Oral administration of Perindopril Erbumine at 2 mg/kg/day has a significant inhibitory effect on SCC-VII tumor growth, and reduces blood vessel formation surrounding the tumors in vivo due to the suppression of VEGF-induced angiogenesis. ^[3] Administration of Perindopril Erbumine at 2 mg/kg/day displays a strong inhibitory effect of the BNL-HCC tumor growth in rats similar to that of 20 mg/kg/day and in contrast to the AT1-R antagonist candesartan or losartan which at the dose of 20 mg/kg/day has no inhibitory effect. ^[4] Administration of Perindopril Erbumine at 3 mg/kg/day significantly inhibits LPS-induced apoptosis by 6.4% in RAECs in vivo than that of ramipril by 3.2%. ^[5] Administration of Perindopril Erbumine (1 mg/kg/day) significantly suppresses the hippocampal ACE activity, and prevents cognitive impairment and brain injury in rats with Alzheimer’s disease (AD). ^[6]
• Clinical Trials: A Phase III study to evaluate the efficacy and safety of a fixed-dose combination of Perindopril Arginine plus Amlodipine Besylate versus Perindopril Erbumine and Amlodipine Besylate in subjects with essential hypertension is currently recruiting participants.

Protocol

• Protocol: Kinase Assay ^[1]
• ACE inhibitor binding assay: The binding assay is based on the competitive displacement of [^125I]351A by Perindopril Erbumine and performed on whole endothelial cells. Subconfluent HUVECs in 6-well plates are rinsed with 2 mL binding buffer (140 mM NaCl, 2.7 mM KCl, 1.8 mM CaCl₂, 1.03 mM MgCl₂, 0.42 mM NaH₂PO₄, 10 mM HEPES, 2 mM sodium pyruvate, 5 mM glucose, pH 7.4), and the culture medium is replaced with 2.5 mL fresh binding buffer containing 5% fetal bovine serum (FBS). A set concentration of Perindopril Erbumine (2.5–12.5 μL, 0.1–50 nM) is added to the binding buffer. A saturating amount of [^125I]351A (10 μL, typically 10^6 cpm) is then added to each sample and the plates are incubated at 37 °C for 2 hours in a thermostatic bath. The cells are then rinsed twice with 1.5 mL binding buffer. Finally, the cells are extracted with 0.5 mL NaOH 1 N, incubated for 5 minutes, and the radioactivity is counted with a gamma counter. The radioactivity, which is due to [^125I]351A binding, is inversely related to Perindopril Erbumine's affinity for endothelial ACE. The concentration of Perindopril Erbumine that displaces 50% of the bound radioligand is calculated from the competition curve.
• Protocol: Animal Study ^[3]
• Animal Models: Female BALB/c nude mice injected with SCC-VII cells
• Formulation: Dissolved in DMSO, and diluted in saline
• Doses: 1 or 2 mg/kg/day
• Administration: Orally

References

• References: [1] Ceconi C, et al. Eur J Pharmacol, 2007, 577(1-3), 1-6.
• References: [2] Zou K, et al. J Biol Chem, 2009, 284(46), 31914-31920.
• References: [3] Yasumatsu R, et al. J Cancer Res Clin Oncol, 2004, 130(10), 567-573.
• References: [4] Yoshiji H, et al. Clin Cancer Res, 2001, 7(4), 1073-1078.
• References: [5] Ceconi C, et al. Cardiovasc Drugs Ther, 2007, 21(6), 423-429.
• References: [6] Dong YF, et al. FASEB J, 2011, 25(9), 2911-2920.

参考文献

• Ceconi C, et al. Eur J Pharmacol, 2007, 577(1-3), 1-6.
• Zou K, et al. J Biol Chem, 2009, 284(46), 31914-31920.
• Yasumatsu R, et al. J Cancer Res Clin Oncol, 2004, 130(10), 567-573.
• Yoshiji H, et al. Clin Cancer Res, 2001, 7(4), 1073-1078.
• Ceconi C, et al. Cardiovasc Drugs Ther, 2007, 21(6), 423-429.
• Dong YF, et al. FASEB J, 2011, 25(9), 2911-2920.