CAS: 1034616-18-6; 1-(2-Hydroxyethyl)-8-((5-(4-Methylpiperazin-1-yl)-2-(Trifluoromethoxy)Phenyl)Amino)-4,5-Dihydro-1H-Pyrazolo[4,3-H]Quinazoline-3-Carboxamide
化学文摘社编号1034616-18-6所鉴定的一种化学化合物,主要被确认为是三-K酶(PI3K)的选择性抑制剂,该酶在各种细胞过程,包括生长,扩散和存活过程中起着关键作用;该化合物由于潜在的治疗应用,在癌症研究领域引起了注意,特别是针对显示异常PI3K信号的特定癌症类型.NMS-P937的特点是独特的分子结构,它促进了它与PI3K酶的相互作用,从而抑制了它的活动.这一抑制作用可导致肿瘤生长减少,并改进某些恶性肿瘤的结果.此外,正在进行的研究正在探索其药理学,功效和安全概况,这对于确定其作为治疗选择的可行性至关重要.由于研究的进展,NMS-P937可能有助于发展有目标的肿瘤疗法,从而突显了解其化学特性和生物影响的重要性.
- 英文名称1-(2-Hydroxyethyl)-8-((5-(4-Methylpiperazin-1-yl)-2-(Trifluoromethoxy)Phenyl)Amino)-4,5-Dihydro-1H-Pyrazolo[4,3-H]Quinazoline-3-Carboxamide
- 中文名称4,5-二氢-1-(2-羟基乙基)-8-[[5-(4-甲基-1-哌嗪基)-2-(三氟甲氧基)苯基]氨基]-1H-吡唑并[4,3-h]喹唑啉-3-甲酰胺
- IUPAC名称1-(2-hydroxyethyl)-8-((5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl)amino)-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
- CAS编号1034616-18-6
- MFCD编号:MFCD26793840
- FDA UNII编号:67RM91WDHQ
- 分子式:C24H27F3N8O3分子量:532.53
- 产品CID: 69282
- 同类组份化合物CAS1034616-18-6 (free base)1263293-37-3 (fumarate)
- 产品分类生物化工 → 抑制剂 → 细胞周期(Cell Cycle)
物理性质
- 沸点757.8±70.0 °C(预测)
- 密度1.57±0.1 g/cm3(预测)
- pKa:14.29±0.10(预测)
- PSA:135.65
- LogP:2.884
- 溶解性Insoluble In H2O; Insoluble In Etoh; ≥13.33 mg/mL In DMSO
- 外观形态类白色至淡黄色固体
- 储存条件储存在 -20°C
- 产品应用该化合物是一种口服活性,选择性的POLO类血酶1(PLK1)抑制剂,其IC50抗体为2纳米,在PL K2/PLK3中显示有超过5000倍的选择性,PL2/PLCK3.它表明在体外对各种固态肿瘤,白血病和淋巴细胞线存在广泛的抗增生活动.NMS/P927在A2780细胞中有效诱发肾细胞循环阻塞,导致吸附.在体内,它显示人类HCT116肝癌的老鼠乳腺细胞模型(90毫克/千克/天,I.V.或P.O.)以及HT29,COLO205色切癌和A278的卵巢癌XEGRAFTS中,肿瘤生长严重抑制肿瘤,并在与核准的细胞毒剂结合时延长存活期.
MSDS等安全信息
上下游产品
potassium 1-(2-hydroxy-ethyl)-8-[5-(4-methyl-piperazin-1-yl)-2-trifluoromethoxy-phenylamino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxylate 1-methyl-piperazine 8-{[5-(4-methylpiperazin-1-yl)-2-(trifluoromethoxy)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide 29H35F3N8O4C29H35F3N8O41-(2-hydroxy-ethyl)-8-[2-trifluoromethoxy-5-(4-methyl-4-oxy-piperazin-1-yl)-phenylamino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide 1-(2-hydroxyethyl)-8-[5-(4-methylpiperazin-1-yl)-2-trifluoromethoxyphenylamino]-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide fumarate合成工艺路线路线简述
📜8-[5-Bromo-2-Trifluoromethoxy-Phenylamino]-4,5-Dihydro-1H-Pyrazolo[4,3-H]Quinazoline-3-Carboxamide置于tris-(Dibenzylideneacetone)Dipalladium(0),Caesium Carbonate,对甲苯磺酸,Lithium Hexamethyldisilazane,2-二环己膦基-2'-(N,N-二甲胺)-联苯体系中,用 四氢呋喃,乙醇,N,N-二甲基甲酰胺 用作溶剂,化学反应生成4,5-二氢-1-(2-羟基乙基)-8-[[5-(4-甲基-1-哌嗪基)-2-(三氟甲氧基)苯基]氨基]-1H-吡唑并[4,3-H]喹唑啉-3-甲酰胺
参考文献:Nms-P937,A 4,5-Dihydro-1H-Pyrazolo[4,3-H]Quinazoline Derivative As Potent And Selective Polo-Like Kinase 1 Inhibitor
标题:Nms-P937,A 4,5-Dihydro-1H-Pyrazolo[4,3-H]Quinazoline Derivative As Potent And Selective Polo-Like Kinase 1 Inhibitor
摘要:As Part Of Our Drug Discovery Effort,We Identified And Developed 4,5-Dihydro-1H-Pyrazolo[4,3-H]Quinazoline Derivatives As Plk1 Inhibitors. We Now Report The Optimization Of This Class That Led To The Identification Of Nms-P937,A Potent,Selective And Orally Available Plk1 Inhibitor. Also,In Order To Understand The Source Of Plk1 Selectivity,We Determined The Crystal Structure Of Plk1 With Nms-P937. The Compound Was Active In Vivo In Hct116 Xenograft Model After Oral Administration And Is Presently In Phase I Clinical Trials Evaluation. (C) 2011 Elsevier Ltd. All Rights Reserved.
Doi:10.1016/j.Bmcl.2011.03.054
海关参考信息
- 2905199090-其他饱和一元醇
2905399099-其他二元醇
2905499000-其他多元醇
2905590090-其他无环醇的卤化、磺化等衍生物 - 💡 提示：海关信息按照顺序优先匹配，如需确认的海关信息，请参考相关资料。
- 详情请参考：📖 海关编码查询和海关进出口税则
供应商参考报价(招募中)
品牌试剂参考报价(招募中)
📌 第三方产品分析报告
主要参考文献
1: Zhang G, Pannucci A, Ivanov AA, Switchenko J, Sun SY, Sica GL, Liu Z, Huang Y, Schmitz JC, Owonikoko TK. Polo-like Kinase 1 Inhibitors Demonstrate In Vitro and In Vivo Efficacy in Preclinical Models of Small Cell Lung Cancer. Cancers (Basel). 2025 Jan 28;17(3):446. doi: 10.3390/cancers17030446.
2: Petrella S, Colombo M, Marabese M, Grasselli C, Panfili A, Chiappa M, Sancisi V, Craparotta I, Barbera MC, Cassanmagnago GA, Bolis M, Damia G. Onvansertib and Navitoclax Combination as a New Therapeutic Option for Mucinous Ovarian Carcinoma. Int J Mol Sci. 2025 Jan 8;26(2):472. doi: 10.3390/ijms26020472.
3: Kim DE, Oh HJ, Kim HJ, Kim YB, Kim ST, Yim H. Synergistic two-step inhibition approach using a combination of trametinib and onvansertib in KRAS and TP53-mutated colorectal adenocarcinoma. Biomed Pharmacother. 2025 Jan;182:117796. doi: 10.1016/j.biopha.2024.117796. Epub 2024 Dec 28. 43(1):113. doi: 10.1200/JCO-24-02458. Epub 2024 Nov 19. Erratum for: J Clin Oncol. 2025 Mar;43(7):840-851. doi: 10.1200/JCO-24-01266. 43(7):840-851. doi: 10.1200/JCO-24-01266. Epub 2024 Oct 30. Erratum in: J Clin Oncol. 2025 Jan;43(1):113. doi: 10.1200/JCO-24-02458.
合成参考文献
参考文献:10.1038/s41587-023-01706-x
摘要:People. Nat Biotechnol. 2023 Mar;41(3):432. doi: 10.1038/s41587-023-01706-x.
参考文献:10.1124/mol.119.115964
摘要:Lee TD, Lee OW, Brimacombe KR, Chen L, Guha R, Lusvarghi S, Tebase BG, Klumpp-Thomas C, Robey RW, Ambudkar SV, Shen M, Gottesman MM, Hall MD. A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Molecular Pharmacology. 2019 Nov;96(5):629–40. doi: 10.1124/mol.119.115964.
参考文献:10.1007/s12247-025-10362-4
摘要:Afiadenyo M, Hamidu S, Obiri-Yeboah D, Amponsah SK, Dankwah K, Adams L. Structure-Guided Discovery of Potent Polo-Like Kinase 1 Inhibitors for Breast Cancer Therapy. J Pharm Innov. 2026 Jan 24;21(2). doi: 10.1007/s12247-025-10362-4.
参考文献:10.1158/1535-7163.mct-11-0765
摘要:Valsasina B, Beria I, Alli C, Alzani R, Avanzi N, Ballinari D, Cappella P, Caruso M, Casolaro A, Ciavolella A, Cucchi U, De Ponti A, Felder E, Fiorentini F, Galvani A, Gianellini LM, Giorgini ML, Isacchi A, Lansen J, Pesenti E, Rizzi S, Rocchetti M, Sola F, Moll J. NMS-P937, an orally available, specific small-molecule polo-like kinase 1 inhibitor with antitumor activity in solid and hematologic malignancies. Mol Cancer Ther. 2012 Apr;11(4):1006–16. doi: 10.1158/1535-7163.mct-11-0765.
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