2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one hydrochloride

• ChemBase编号: 73033
• 分子式: C24H30ClNO3
• 平均质量: 415.9529
• 单一同位素质量: 415.19142151
• SMILES: c1c2c(cc(c1OC)OC)C(=O)C(C2)CC1CCN(CC1)Cc1ccccc1.Cl
• Canonical SMILES: COc1cc2c(cc1OC)CC(C2=O)CC1CCN(CC1)Cc1ccccc1.Cl
• InChI: InChI=1S/C24H29NO3.ClH/c1-27-22-14-19-13-20(24(26)21(19)15-23(22)28-2)12-17-8-10-25(11-9-17)16-18-6-4-3-5-7-18;/h3-7,14-15,17,20H,8-13,16H2,1-2H3;1H
• InChIKey: XWAIAVWHZJNZQQ-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one hydrochloride
• IUPAC传统名: donepezil hydrochloride
• 别名: Aricept; Donepezil hydrochloride

登记号

• CAS号: 120011-70-3
• PubChem SID: 162037953
• PubChem CID: 5741

理论计算性质

• Acid pKa: 17.021936
• 质子受体: 4
• 质子供体: 0
• LogD (pH = 5.5): 1.2351922
• LogD (pH = 7.4): 2.9603515
• Log P: 4.207933
• 摩尔折射率: 112.1147 cm^3
• 极化性: 43.49957 Å^3
• 极化表面积: 38.77 Å^2
• 可自由旋转的化学键: 6
• 里宾斯基五规则: true

分子性质

安全信息

• 保存条件: -20°C

产品相关信息

• 成盐信息: hydrochloride

详细说明

Selleck Chemicals - S2462

Research Area

• Description: Neurological Disease

Biological Activity

• Description: Donepezil is a specific and potent AChE inhibitor for bAChE and hAChE with IC50 of 8.12 nM and 11.6 nM , respectively.
• Targets: bAChE; hAChE
• IC50: 8.12 nM; 11.6 nM ^[1]
• In Vitro: Donepezil inhibits the carbachol-stimulated increase in intracellular Ca^2+ concentration in human SHSY5Y neuroblastoma cells in a concentration dependent manner, indicating that Donepezil have muscarinic antagonist activity. ^[2] A recent study shows that Donepezil can protect human umbilical vein endothelial cells (HUVECs) against H2O2-induced cell injury. This may be useful as a potential therapy for oxidative stress in cardiovascular and cerebrovascular diseases. ^[3]
• In Vivo: Intraperitoneal administration of Donepezil in rats produces a dose dependent increase in salivation and tremor, which are overt cholinergic behavioural signs, with an ED50 of 6 μmol/kg. Donepezil is found to be somewhat less potent with a ED50 of 50 μmol/kg following oral administration. ^[2]. When administered separately in vivo, 5-HT(4) receptor inducer, RS67333 (0.3 and 1 mg/kg) and Donepezil (1 mg/kg) improves recognition performances compared to saline treated mice, while co-administration of subactive doses of RS67333 (0.1mg/kg) and Donepezil (0.3 mg/kg) improves memory. However, this improvement is prevented if a 5-HT(4)R antagonist (GR125487, 10 mg/kg) is also administered. ^[4]
• Clinical Trials: Donepezil is currently being evaluated in Phase III clinical trials for Parkinson' s disease (PD) patients with dementia.

Protocol

• Protocol: Kinase Assay ^[1]
• AChE inhibitory activity: PDGF receptor is immunoprecipitated from BALB/c 3T3 cell extracts with rabbit antiserum (for the murine PDGF receptor) for 2 hours on ice. Protein A-Sepharose beads are used to collect the antigen-antibody complexes. The immunoprecipitates are washed twice with TNET (50 mM Tris, pH 7.5, 140 mM NaCl, 5 mM EDTA, 1% Triton X-100), once with TNE (50 mM Tris, pH 7.5, 140 mM EDTA), and once with kinase buffer (20 mM Tris, pH 7.5,10 mM MgCl2). After stimulation with PDGF (50 ng/ml) at 4 °C for 10 minutes, different concentrations of the drug are added to the reaction mixture. PDGF receptor kinase activity is determined by incubation with 10 μCi [7-32P]-ATP and l μM ATP for 10 minutes at 4 °C. Immune complexes are separated by SDS-PAGE on 7.5% gels.
• Protocol: Animal Study ^[2]
• Animal Models: Male Lister Hooded rats
• Formulation: 0.9% w:v NaCl (saline)
• Doses: 18 μM/kg
• Administration: Administered via i.p. or p.o.

References

• References: [1] Ogura H, et al. Methods Find Exp Clin Pharmacol. 2000, 22(8), 609-613.
• References: [2] Snape MF, et al. Neuropharmacology. 1999, 38(1), 181-193.
• References: [3] Huang ZH, et al. CNS Neurosci Ther. 2012, 18(2), 185-187.
• References: [4] Freret T, et al. Behav Brain Res. 2012 http://dx.doi.org/10.1016/j.bbr.2012.02.012.

参考文献

• Ogura H, et al. Methods Find Exp Clin Pharmacol. 2000, 22(8), 609-613.
• Snape MF, et al. Neuropharmacology. 1999, 38(1), 181-193.
• Huang ZH, et al. CNS Neurosci Ther. 2012, 18(2), 185-187.
• Freret T, et al. Behav Brain Res. 2012 http://dx.doi.org/10.1016/j.bbr.2012.02.012.