1-{2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl}-3,3-dimethyl-2,3-dihydro-1H-indol-2-one hydrochloride

• ChemBase编号: 73178
• 分子式: C24H28ClFN2O2
• 平均质量: 430.9427232
• 单一同位素质量: 430.18233405
• SMILES: c1ccc2c(c1)C(C(=O)N2CCN1CCC(CC1)C(=O)c1ccc(cc1)F)(C)C.Cl
• Canonical SMILES: Fc1ccc(cc1)C(=O)C1CCN(CC1)CCN1c2ccccc2C(C1=O)(C)C.Cl
• InChI: InChI=1S/C24H27FN2O2.ClH/c1-24(2)20-5-3-4-6-21(20)27(23(24)29)16-15-26-13-11-18(12-14-26)22(28)17-7-9-19(25)10-8-17;/h3-10,18H,11-16H2,1-2H3;1H
• InChIKey: BOCLFQZPFYNVFD-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 1-{2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl}-3,3-dimethyl-2,3-dihydro-1H-indol-2-one hydrochloride
• IUPAC传统名: 1-{2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl}-3,3-dimethylindol-2-one hydrochloride
• 别名: LY-310762; 3,3-Dimethyl-1-{2-[4-(4-fluorobenzoyl)-1-piperidinyl]-1-ethyl}-1,3-dihydro-2H-indol-2-one hydrochloride; LY-310,762 hydrochloride

登记号

• CAS号: 192927-92-7
• MDL号: MFCD07772272
• PubChem SID: 162038098; 24278114
• PubChem CID: 11957576

理论计算性质

• Acid pKa: 16.566053
• 质子受体: 3
• 质子供体: 0
• LogD (pH = 5.5): 2.2854033
• LogD (pH = 7.4): 3.7963812
• Log P: 4.023813
• 摩尔折射率: 112.2108 cm^3
• 极化性: 42.982872 Å^3
• 极化表面积: 40.62 Å^2
• 可自由旋转的化学键: 5
• 里宾斯基五规则: true

分子性质

理化性质

• 溶解度: DMSO: soluble10 mg/mL (with heating); H2O: insoluble
• 外观: white powder

安全信息

• 保存条件: -20°C
• 欧盟危险性物质标志: 刺激性(Irritant) (Xi)
• 德国WGK号: 3
• 危险公开号: 36/37/38
• 安全公开号: 26-36
• GHS危险品标识: GHS07
• GHS警示词: Warning
• GHS危险声明: H315-H319-H335
• GHS警示性声明: P261-P305 + P351 + P338
• 个人保护装置: dust mask type N95 (US), Eyeshields, Gloves

药理学性质

• 作用靶点: Serotonin receptor
• 相关基因信息: human ... HTR1D(3352)

产品相关信息

• 成盐信息: HCL
• Empirical Formula (Hill Notation): C24H27O2N2F · HCl

详细说明

Selleck Chemicals - S2669

Biological Activity

• Description: LY310762 is a 5-HT_1D antagonist with K_i of ~0.2 μM.
• Targets: 5-HT_1D
• IC50: 0.2 μM (K_i) ^[1]
• In Vitro: LY310762 has a higher affinity for the guinea pig 5-HT1D receptor than for the 5-HT1B receptor. LY310762 potentiates the potassium-induced [^3H]5-HT outflow from guinea pig cortical slices with an EC50 of 30 nM. The maximum potentiation of the potassium-induced outflow which is obtained with LY310762 is about 40%. ^[1] LY310762 blocks the decreased EPSC amplitude induced by Sumatriptan. ^[2]
• In Vivo: Systemic administration of LY310762 (10 mg/kg i.p.) produces a further significant enhancement in the 5-HT response to fluoxetine (20 mg/kg i.p.) when compared to animals receiving a control vehicle injection. In fluoxetine treated animals, levels of 5-HT increases from 312±43% to a maximum of 683% after LY310762. In control animals, levels of 5-HT remains unchanged (250%). LY310762 administered alone also significantly increases basal levels of 5-HT above vehicle controls, reaching a maximum of 258% compared to the pre-injection control. ^[1]

Combination Therapy

• Description: Systemic administration of LY310762 (10 mg/kg i.p.) produces a further significant enhancement in the 5-HT response to fluoxetine (20 mg/kg i.p.) when compared to animals receiving a control vehicle injection. In fluoxetine treated animals, levels of 5-HT increases from 312% to a maximum of 683% after LY310762. In control animals, levels of 5-HT remains unchanged (250%). ^[1]In addition, Sumatriptan fails to decrease glutamatergic EPSCs in the presence of both LY310762 and GR55562 (95.2% of the LY310762 and GR55562 condition). ^[2]

Protocol

• Protocol: Kinase Assay ^[1]
• [3H]-5-HT outflow from guinea pig cortical slices: Male Dunkin Hartley Guinea Pigs (350-400 g) are killed by asphyxiation with CO₂ and their brains rapidly removed. Cortical slices (350 × 350 μm) are prepared, washed once in basal buffer (10 mM HEPES, 133 mM NaCl, 4.8 mM KCl, 1.2 mM KH₂PO₄, 1.2 mM MgSO₄, 1.5 mM CaCl₂, 11.1 mM glucose, 10 μM pargyline pH 7.4) and incubated in basal buffer at 25 mg/mL wet weight with [^3H]5-HT (50 nM) for 30 minutes at 37 °C. The slices are washed three times in basal buffer and transferred to baskets (10 mm i.d. polypropylene tubes with 150 μm nylon mesh bases) at approximately 5 mg wet weight per basket. The baskets are used to transfer the tissue between the washing and release buffers. In order to obtain stable baseline release, the slices are incubated for 11 minutes in basal buffer (0.5 mL), transferred for 4 minutes to a second tube containing basal buffer (0.5 mL) and then, for a further 4 minutes, to basal buffer (0.5 mL) or to a buffer in which NaCl has been substituted with KCl, on an equimolar basis, to give a KCl concentration of 30 mM (release sample). All buffers used in the 11 minutes and the two 4 minutes incubations contained 1 μM paroxetine. Following the incubations, the tissue is digested with Soluene-350 (0.7 mL) and the baskets rinsed with propan-2-ol (0.7 mL). The tritium label in the tissue samples and in the buffers from the three incubation periods is estimated by liquid scintillation spectroscopy. LY310762 being tested is present throughout the three incubation periods and is tested in six replicates. The basal release is measured in four replicates and the control release in eight replicates. The tritium label in the release sample is expressed as the percentage of the total tritium in the tissue at the time the sample is collected (% fractional release). Stimulated release is calculated as the % fractional release produced by the high potassium buffer minus that of basal release. The percentage increase in release produced by LY310762 is calculated as the increase over the control stimulated release, where the control release is 100%. For individual experiments the mean of the replicate data is calculated. The results are the means and standard errors of at least three separate experiments.
• Protocol: Animal Study ^[1]
• Animal Models: Dunkin Hartley guinea pigs weighting 350–400 g
• Doses: 10 mg/kg
• Administration: Administered via i.p.

References

• References: [1] Eur J Pharmacol. 2004, 493(1-3), 85-93.
• References: [2] Choi IS, et al. Br J Pharmacol. 2012.

Sigma Aldrich - L2536

Biochem/physiol Actions
Potent, selective 5-HT1D serotonin receptor antagonist.

参考文献

• Eur J Pharmacol. 2004, 493(1-3), 85-93.
• Choi IS, et al. Br J Pharmacol. 2012.