6-[2-(4-methoxyphenyl)-1H-1,3-benzodiazol-6-yl]-5-methyl-2,3,4,5-tetrahydropyridazin-3-one

• ChemBase编号: 72739
• 分子式: C19H18N4O2
• 平均质量: 334.37182
• 单一同位素质量: 334.14297584
• SMILES: c1c2c(ccc1C1=NNC(=O)CC1C)[nH]c(n2)c1ccc(cc1)OC
• Canonical SMILES: COc1ccc(cc1)c1nc2c([nH]1)ccc(c2)C1=NNC(=O)CC1C
• InChI: InChI=1S/C19H18N4O2/c1-11-9-17(24)22-23-18(11)13-5-8-15-16(10-13)21-19(20-15)12-3-6-14(25-2)7-4-12/h3-8,10-11H,9H2,1-2H3,(H,20,21)(H,22,24)
• InChIKey: GLBJJMFZWDBELO-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 6-[2-(4-methoxyphenyl)-1H-1,3-benzodiazol-6-yl]-5-methyl-2,3,4,5-tetrahydropyridazin-3-one; 6-[2-(4-methoxyphenyl)-1H-1,3-benzodiazol-5-yl]-5-methyl-2,3,4,5-tetrahydropyridazin-3-one
• IUPAC传统名: pimobendan
• 别名: 4,5-Dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-6-yl]-5-methyl- 3(2H)-pyridazinone; 4,5Dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-3(2H)-pyridazinone; Pimobendan; UD-CG 115; UD-CG 115BS; dl-Pimobendan; rac Pimobendan; 4,5-dihydro-6-(2-(4-methoxyphenyl)-1h-benzimidazol-5-yl)-5-methyl-3(2h)-pyridazinone; Vetmedin; Acardi; pimobendane; Pimobendan(Vetmedin)

登记号

• CAS号: 74150-27-9
• PubChem SID: 162037660
• PubChem CID: 4823

理论计算性质

• Acid pKa: 11.166092
• 质子受体: 4
• 质子供体: 2
• LogD (pH = 5.5): 2.6294434
• LogD (pH = 7.4): 2.697642
• Log P: 2.6986573
• 摩尔折射率: 104.6832 cm^3
• 极化性: 37.837936 Å^3
• 极化表面积: 79.37 Å^2
• 可自由旋转的化学键: 3
• 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: PDE

产品相关信息

• 纯度: 98%
• 成盐信息: Free Base

详细说明

Selleck Chemicals - S1550

Research Area

• Description: Cardiovascular Disease

Biological Activity

• Description: Pimobendan is a selective inhibitor of PDE3 with IC50 of 0.32 μM.
• Targets: PDE3
• IC50: 0.32 μM ^[1]
• In Vitro: Pimobendan exhibits selective inhibition of PDE III isolated from guinea pig cardiac muscle with IC50 of 0.32 uM compared to the inhibition of PDE I and PDE II (IC50s >30 μM). ^[1] Pimobendan inhibits the activity of cAMP-PDE III with IC50 of 2.4 μM. It also exerts concentration-dependent positive inotropic effects in isolated guinea-pig papillary muscles with a potency (EC50) of 6.0 μM, which is partly due to selective cardiac PDE III inhibition. ^[2] In human atrial cells, 100 μM pimobendan significantly increases the L-type calcium current (I_Ca(L)) (evoked by depolarization to +10 mV from a holding potential of -40 mV) by 250.4% with the half-maximal stimulation (EC50) of 1.13 μM. In rabbit atrial cells, Pimobendan increases I_Ca(L) at +10 mV by 67.4.%, which is significantly lower than that obtained in human atrial cells ^[3]
• In Vivo: Pimobendan shows a beneficial effect on survival in the murine model of EMC virus-induced myocarditis. Administration of Pimobendan significantly increases the final survival rate from 33.6% (control) to 53.3% (0.1 mg/kg) or 66.7% (1 mg/kg). Pimobendan (1 mg/kg) also significantly reduces myocardial cellular infiltration, the level of intracardiac tumor necrosis factor (TNF)-α and interleukin (IL)-1β compared with the control group, which shows no effect on myocardial necrosis, heart weight and body weight. Pimobendan suppresses expression of the intracardiac iNOS gene , causing reduction of intracardiac NO production. ^[4]

Protocol

• Protocol: Kinase Assay ^[1]
• Phosphodiesterase isoenzyme inhibition: The isoenzymes PDE I, PDE II and PDE III are isolated from left ventricular guinea pig muscle. For determination of enzyme inhibition, Pimobendan is preincubated for 5 minutes with PDE in a buffer containing 40 mM Tris HCl, 50 mM MgCl₂, and 10 mM EGTA (PH 8.0). The reaction is initiated at 37 °C by adding 0.3 μM [^3H]cAMP (or 2.5 μM [^3H]cGMP in the case of PDE II). The concentration of PDE is such that only 10% of the substrate is hydrolyzed during the reaction, which is stopped after 20 minutes by heating to 90 °C briefly. The reaction product [^3H]AMP is split to [^3H]adenosine by a phosphatase from king cobra venom. [^3H]adenosine is separated from unhydrolyzed [^3H]cAMP by chromatography and quantified in a scintillation counter. The concentration that produces 50% inhibition of hydrolysis (IC50) is determined from concentration-response curves.
• Protocol: Animal Study ^[4]
• Animal Models: Male DBA/2 mice of viral myocarditis
• Formulation: Prepared as an oral suspension in 0.25% methylcellulose solution, in concentrations of 120 μg/mL and 12 μg/mL
• Doses: 0.1 or 1 mg/kg
• Administration: Orally once daily

References

• References: [1] Beier N, et al. J Cardiovasc Pharmacol, 1991, 18(1), 17-27.
• References: [2] Brunkhorst D, et al. Naunyn Schmiedebergs Arch Pharmacol, 1989, 339(5), 575-583.
• References: [3] Kajimoto K, et al. Br J Pharmacol, 1997, 121(8), 1549-1556.
• References: [4] Iwasaki A, J. Am Coll Cardiol, 1999, 33(5), 1400-1407.

Toronto Research Chemicals - P447500

Pimobendan is a cardiotonic agent. The study of the cardiotonic mechanism of Pimobendan using ventricular muscles from rabbits and guinea pigs suggests that Pimobendan acts by inhibiting phosphodiesterase III and potassium channel. The potent venodilating

参考文献

• Beier N, et al. J Cardiovasc Pharmacol, 1991, 18(1), 17-27.
• Brunkhorst D, et al. Naunyn Schmiedebergs Arch Pharmacol, 1989, 339(5), 575-583.
• Kajimoto K, et al. Br J Pharmacol, 1997, 121(8), 1549-1556.
• Iwasaki A, J. Am Coll Cardiol, 1999, 33(5), 1400-1407.
• Yokota, S. et al.: Yakuri Chiryo, 20, 1143 (1992)
• Yamamoto, M. et al.: Kank. Igaku Ken. Nenpo, 47, 155 (1992)
• Matsumoto, A. et al.: Cardiovas. Drugs Ther., 12, 595 (1992)