2-{4-[1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl]phenoxymethyl}quinoline

• ChemBase编号: 6003
• 分子式: C25H20N4O
• 平均质量: 392.4525
• 单一同位素质量: 392.16371128
• SMILES: c1cc(ccc1c1c(cn(C)n1)c1ccncc1)OCc1ccc2c(cccc2)n1
• Canonical SMILES: Cn1nc(c(c1)c1ccncc1)c1ccc(cc1)OCc1ccc2c(n1)cccc2
• InChI: InChI=1S/C25H20N4O/c1-29-16-23(18-12-14-26-15-13-18)25(28-29)20-7-10-22(11-8-20)30-17-21-9-6-19-4-2-3-5-24(19)27-21/h2-16H,17H2,1H3
• InChIKey: AZEXWHKOMMASPA-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 2-{4-[1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl]phenoxymethyl}quinoline
• IUPAC传统名: 2-{4-[1-methyl-4-(pyridin-4-yl)pyrazol-3-yl]phenoxymethyl}quinoline
• 别名: PF-2545920; 2-{[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxy]methyl}quinoline

登记号

• CAS号: 1292799-56-4
• PubChem SID: 160969428; 99444858
• PubChem CID: 11581936

理论计算性质

JChem

• 质子受体: 4
• 质子供体: 0
• LogD (pH = 5.5): 4.645283
• LogD (pH = 7.4): 4.669347
• Log P: 4.669663
• 摩尔折射率: 127.1798 cm^3
• 极化性: 48.825813 Å^3
• 极化表面积: 52.83 Å^2
• 可自由旋转的化学键: 5
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 5.01
• LOG S: -5.42
• 溶解度: 1.49e-03 g/l

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

• 成盐信息: Free Base

详细说明

DrugBank - DB08387

Drug information: experimental

Selleck Chemicals - S2687

Research Area

• Description: Schizophrenia

Biological Activity

• Description: PF-2545920 is a potent and selective PDE10A inhibitor with IC50 of 0.37 nM.
• Targets: PDE10A
• IC50: 0.37 nM ^[2]
• In Vitro: MP-10 shows excellent potency and selectivity of PDE10A with IC50 of 1.26 nM. ^[1]
• In Vivo: MP-10 intraperitoneally administrated at dose of 0.3, 3, and 5 mg/kg in male CF-1 mice causes striking increases in GluR1 phosphorylation levels of 3-, 5.4-, and 4.1-fold , respectively. MP-10 at concentration of 1 μM treats Rat striatal slices for 30 min, the level of GluR1S845 phosphorylation at the cell surface is significantly increased 2-fold, without change the level of total GluR1 on the cell surface. MP-10 intraperitoneally administrated at dose of 0.3, 3, and 5 mg/kg in male CF-1 mice results in robust, statistically significant increases in CREBS133 phosphorylation of 3-, 4-, and 2.6-fold, respectively. MP-10 intraperitoneally administrated at dose of 3 mg/kg increases both enkephalin and substance-P mRNA levels in striatum of CF-1 mice. MP-10 intraperitoneally administrated at dose of 0.3–1 mg/kg decreases avoidance responding with a significant treatment effect in the mouse CAR model. Mice treated with MP-10 at dose of 0.03 mg/kg spents more time in the empty than social side in the mice, MP-10 also dose-dependently decreased locomotor activity. ^[1] PDE10A subcutaneously administrated at dose of 1 mg/kg elevates striatal cGMP about 3 fold in male CD-1 mice, while PDE10A subcutaneously administrated at dose of 3.2 mg/kg displays a maximal elevation of striatal cGMP approximately a 5-fold increase in male CD-1 mice. PDE10A intravenous injected at a dose of 0.1 mg/kg in Sprague-Dawley rats displays clearance of 36 ml/min/Kg, DE10A intravenous injected at a dose of 0.3 mg/kg in Dog Beagle displays clearance of 7.2 ml/min/Kg in vivo clearance with a moderate volume of distribution, DE10A intravenous injected at a dose of 0.03 mg/kg in Monkey Cynomolgus displays clearance of 13.9 ml/min/Kg in vivo clearance with a moderate volume of distribution. PDE10A is active with an ED50 of 1 mg/kg at a significantly lower total plasma exposure (115 nM) in the conditioned avoidance response assay (CAR) in Sprague-Dawley rats. ^[2]

References

• References: [1] Grauer SM, et al. J Pharmacol Exp Ther, 2009, 331(2), 574-590.
• References: [2] Verhoest PR, et al. J Med Chem, 2009, 52(16), 5188-5196.

参考文献

• Grauer SM, et al. J Pharmacol Exp Ther, 2009, 331(2), 574-590.
• Verhoest PR, et al. J Med Chem, 2009, 52(16), 5188-5196.