3-(2,4-dichlorophenyl)-3-oxo-2-(4-oxo-1,2,3,4-tetrahydroquinazolin-2-ylidene)propanenitrile

• ChemBase编号: 154756
• 分子式: C17H9Cl2N3O2
• 平均质量: 358.17826
• 单一同位素质量: 357.0071819
• SMILES: c1ccc2c(c1)c(=O)[nH]/c(=C(\C#N)/C(=O)c1ccc(cc1Cl)Cl)/[nH]2
• Canonical SMILES: N#C/C(=c/1\[nH]c(=O)c2c([nH]1)cccc2)/C(=O)c1ccc(cc1Cl)Cl
• InChI: InChI=1S/C17H9Cl2N3O2/c18-9-5-6-10(13(19)7-9)15(23)12(8-20)16-21-14-4-2-1-3-11(14)17(24)22-16/h1-7,21H,(H,22,24)
• InChIKey: SESYPWCSIZUIAS-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 3-(2,4-dichlorophenyl)-3-oxo-2-(4-oxo-1,2,3,4-tetrahydroquinazolin-2-ylidene)propanenitrile
• IUPAC传统名: 3-(2,4-dichlorophenyl)-3-oxo-2-(4-oxo-1,3-dihydroquinazolin-2-ylidene)propanenitrile
• 别名: 2,4-Dichloro-a-(3,4-dihydro-4-oxo-2(1H)-quinazolinylidene)-β-oxo-benzenepropanenitrile; Ciliobrevin A; Hedgehog Pathway Inhibitor 4; HPI-4

登记号

• CAS号: 302803-72-1
• MDL号: MFCD01911757
• PubChem SID: 162248894
• PubChem CID: 6883982

理论计算性质

• Acid pKa: 11.232669
• 质子受体: 4
• 质子供体: 2
• LogD (pH = 5.5): 4.141699
• LogD (pH = 7.4): 4.1416416
• Log P: 4.1417
• 摩尔折射率: 102.7322 cm^3
• 极化性: 34.01831 Å^3
• 极化表面积: 81.99 Å^2
• 可自由旋转的化学键: 2
• 里宾斯基五规则: true

分子性质

理化性质

• 溶解度: DMSO: >20 mg/mL
• 外观: yellow powder

安全信息

• 欧盟危险性物质标志: 环境危害性(Nature polluting) (N); 有害性(Harmful) (Xn)
• 联合国危险货物编号: 3077
• 德国WGK号: 3
• 联合国危险货物等级: 9
• 联合国危险货物包装类别(PG): 3
• 危险公开号: 22-50/53
• 安全公开号: 60-61
• GHS危险品标识: GHS07; GHS09
• GHS警示词: Warning
• GHS危险声明: H302-H410
• GHS警示性声明: P273-P501
• RID/ADR: UN 3077 9/PG 3
• 保存温度: 2-8°C

产品相关信息

• 纯度: ≥98% (HPLC)
• Empirical Formula (Hill Notation): C17H9Cl2N3O2

详细说明

Sigma Aldrich - H4541

Biochem/physiol Actions
HPI-4 is a Hedgehog pathway inhibitor; ciliogenesis inhibitor. The Hedgehog (HH) signaling pathway is targeted for anti-cancer therapeutics. A key signaling molecule in HH pathway, Smoothened (Smo), has been the target of pharmacological intervention, which has resulted in multiple Smo antagonists including Cyclopamine. However, the oncogenic form of Smo is resistant to Cyclopamine, so the identification of inhibitors of downstream effectors, such as the transcription factors Gli1 and Gli2, is important. Four small molecules were identified to inhibit HH downstream of Smo, HPI-1, HPI-2, HPI-3, and HPI-4. HPI-4 blocked HH pathway activation by SAG, decreased Smo ciliary accumulation, decreased HH activity in a consitutively active HH cell line, and decreased Gli1 and Gli2, processing, and stability. HPI-4 inhibited proliferation of cerebellar granula neuron precursor cells, an important model of HH signaling. Cilia in HPI-4-treated cells were either truncated or absent. The mechanism of action of HPI-4 is hypothesized to be directly through perturbation of ciliogenesis, leading to disruption of Gli1/Gli2 activity, which is distinctly different from that of Cyclopamine.