3-{2-[4-(diphenylmethyl)piperazin-1-yl]ethyl} 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride

• ChemBase编号: 70541
• 分子式: C35H40Cl2N4O6
• 平均质量: 683.6213
• 单一同位素质量: 682.23249038
• SMILES: C1(=C(C(C(=C(N1)C)C(=O)OC)c1cc(ccc1)[N+](=O)[O-])C(=O)OCCN1CCN(CC1)C(c1ccccc1)c1ccccc1)C.Cl.Cl
• Canonical SMILES: COC(=O)C1=C(C)NC(=C(C1c1cccc(c1)[N+](=O)[O-])C(=O)OCCN1CCN(CC1)C(c1ccccc1)c1ccccc1)C.Cl.Cl
• InChI: InChI=1S/C35H38N4O6.2ClH/c1-24-30(34(40)44-3)32(28-15-10-16-29(23-28)39(42)43)31(25(2)36-24)35(41)45-22-21-37-17-19-38(20-18-37)33(26-11-6-4-7-12-26)27-13-8-5-9-14-27;;/h4-16,23,32-33,36H,17-22H2,1-3H3;2*1H
• InChIKey: JINNGBXKBDUGQT-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 3-{2-[4-(diphenylmethyl)piperazin-1-yl]ethyl} 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride
• IUPAC传统名: manidipine dihydrochloride; 3-{2-[4-(diphenylmethyl)piperazin-1-yl]ethyl} 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride
• 别名: 3-(2-(4-Benzhydrylpiperazin-1-yl)ethyl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate dihydrochloride; CV-4093; Manidipine dihydrochloride; Calslot; Manidipine Dihydrochloride

登记号

• CAS号: 89226-75-5
• PubChem SID: 162036256
• PubChem CID: 150762

理论计算性质

• 质子受体: 7
• 质子供体: 1
• LogD (pH = 5.5): 2.3017452
• LogD (pH = 7.4): 4.3359923
• Log P: 5.189972
• 摩尔折射率: 175.1293 cm^3
• 极化性: 66.449524 Å^3
• 极化表面积: 116.93 Å^2
• 可自由旋转的化学键: 12
• 里宾斯基五规则: false

分子性质

安全信息

• 保存条件: -20°C
• 保存注意事项: IRRITANT
• TSCA收录: false

药理学性质

• 生物活性机理: Calcium antagonist

产品相关信息

• 纯度: 95+%
• 成盐信息: 2 HCl; dihydrochloride
• 应用领域: Antihypertensive agent

详细说明

Selleck Chemicals - S2482

Research Area

• Description: Cardiovascular Disease

Biological Activity

• Description: Manidipine HCl is a HCl salt form of Manidipine which is a calcium channel blocker for Ca^2+ current with IC50 of 2.6 nM.
• Targets: Ca^2+ current
• IC50: 2.6 nM ^[1]
• In Vitro: At a holding potential of ?37 mV, Manidipine decreases the Ca^2+ current at concentrations above 0.1 nM, and abolishes it at 100 nM. ^[1] Manidipine concentration-dependently inhibits the calcium concentration response curves. Manidipine inhibits coronay artery and renal artery with pIC50 of 9.3 nM and 9.1 nM, respectively. ^[2] Manidipine partly inhibits sympathetic nerve activity and suppresses the mean arterial pressure response to infused norepinephrine. Manidipine also inhibits aldosterone secretion. Manidipine increases in both urinary calcium and uric acid. ^[3] In addition, Manidipine, at nanomolar concentrations, is efficacious in modulating gene transcriptions that are involved in proinflammatory changes of mesangial cells. ^[4]
• In Vivo: Manidipine (3 mg/kg and 10 mg/kg, p.o.) dose-dependently decreases systolic blood pressure in the three types of hypertensive rats. At the dose of 10 mg/kg, Manidipine decreases the blood pressure to the normotensive level between 1 hour and 3 hours after Manidipine is administered; the antihypertensive effect lasted for at least 8 hours. ^[5] When Manidipine is administered at 10 μg/kg, the hypotensive action is markedly augmented. ^[6] Manidipine potently inhibits the Ca inward current, When the potential is at -60 mV. Manidipine consistently inhibits the Ca current evoked by depolarization to 0 mV. However, a low concentration of Manidipine (1-3 nM) enhances the Ca current evoked by the depolarizing pulse of -20 mV, when the membrane potential is held at -80 mV. Inhibition of the Ca current induced by Manidipine develops slowly and over 10 minutes is required to reach the maximum inhibition. ^[7]

Protocol

• Protocol: Cell Assay ^[4]
• Cell Lines: Mesangial cells
• Concentrations: 10 nM
• Incubation Time: Days 1, 3 and 5
• Methods: The mitogenic effect is measured by the amout of [3H]thymidine incorporated into DNA of human MCs and by assessment of cell proliferation. In brief, 1 × 105 quiescent cells is seeded into a 25-mL cell culture bottle and kept in low serum medium (0.1% FCS). On the following day, the cells are preincubated for 3 hours with Manidipine (10 nM) followed by stimulation with PDGF-BB (10 ng/mL) or incubated with low serum medium abone. The medium is replaced each day, and the cells are counted at days 1, 3 and 5.
• Protocol: Animal Study ^[5]
• Animal Models: Normotensive male Wistar-Kyoto rats and male stroke-prone SHR
• Formulation: Saline
• Doses: 1 mg/kg, 3 mg/kg and 10 mg/kg
• Administration: Administered via p.o.

References

• References: [1] Tohse N, et al. Eur J Pharmacol, 1993, 249(2), 231-233.
• References: [2] Pfaffendorf M, et al. Am Heart J, 1993, 125(2 Pt 2), 571-577.
• References: [3] Iimura O, et al. Am Heart J, 1993, 125(2 Pt 2), 635-641.
• References: [4] Roth M, et al. Proc Natl Acad Sci, 1992, 89(9), 4071-4075.
• References: [5] Kakihana M, et al. Jpn J Pharmacol, 1988, 48(2), 223-228.
• References: [6] Morimoto S, et al. Jpn J Pharmacol, 1989, 51(2), 257-265.
• References: [7] Okabe K, et al. J Pharmacol Exp Ther, 1987, 243(2), 703-710.

参考文献

• Tohse N, et al. Eur J Pharmacol, 1993, 249(2), 231-233.
• Pfaffendorf M, et al. Am Heart J, 1993, 125(2 Pt 2), 571-577.
• Iimura O, et al. Am Heart J, 1993, 125(2 Pt 2), 635-641.
• Roth M, et al. Proc Natl Acad Sci, 1992, 89(9), 4071-4075.
• Kakihana M, et al. Jpn J Pharmacol, 1988, 48(2), 223-228.
• Morimoto S, et al. Jpn J Pharmacol, 1989, 51(2), 257-265.
• Okabe K, et al. J Pharmacol Exp Ther, 1987, 243(2), 703-710.
• Meguro, K. et al., Chem. Pharm. Bull., 1985, 33, 3787, (synth, pharmacol)
• Okabe, K. et al., J. Pharmacol. Exp. Ther., 1987, 243, 703, (pharmacol)
• Nakaya, H. et al., Eur. J. Pharmacol., 1988, 146, 35, (pharmacol)
• Kajino, M. et al., Chem. Pharm. Bull., 1989, 37, 2225, (synth, abs config)
• Cheer, S.M. et al., Drugs, 2001, 61, 1777-1799, (rev)