化合物 T28434 | 326823-27-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 化合物 T28434
• 英文名称: PNU 292137
• 英文别名: N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(naphthalen-2-yl)acetamide；N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-(2-naphthyl)acetamide；PNU0292137；N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-naphthalen-2-ylacetamide
• CAS: 326823-27-2
• 化学式: C₁₈H₁₇N₃O
• 分子量: 291.352
• InChiKey: RIGZCVNCFXYBEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  57.8
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  5-硝基-3-环己基-1-氢-吡唑-1-羧酸叔丁酯 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 化合物 T28434
  参考文献：
  名称：

  3-Acylaminopyrazole derivatives via a regioselectively N-protected 3-nitropyrazole

  摘要：

  A simple procedure for the selective protection of the enclocyclic 1-N of 3-aminopyrazoles as tert-butoxycarbamate (Boc) in good yield is described. A 3-nitropyrazole derivative represents the key intermediate with the nitro substituent determining the regiochemistry of the obtained protected Compound. Subsequent acylation at the exocyclic amino group gave rise, after Bee removal, to a series of 3-acylaminopyrazoles in high yields and purities. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2004.12.054

文献信息

• 3-Aminopyrazole Inhibitors of CDK2/Cyclin A as Antitumor Agents. 1. Lead Finding
  作者：Paolo Pevarello、Maria Gabriella Brasca、Raffaella Amici、Paolo Orsini、Gabriella Traquandi、Luca Corti、Claudia Piutti、Pietro Sansonna、Manuela Villa、Betsy S. Pierce、Maurizio Pulici、Patrizia Giordano、Katia Martina、Edward L. Fritzen、Richard A. Nugent、Elena Casale、Alexander Cameron、Marina Ciomei、Fulvia Roletto、Antonella Isacchi、GianPaolo Fogliatto、Enrico Pesenti、Wilma Pastori、Aurelio Marsiglio、Karen L. Leach、Paula M. Clare、Francesco Fiorentini、Mario Varasi、Anna Vulpetti、Martha A. Warpehoski

  DOI：10.1021/jm031145u

  日期：2004.6.1

  targeting complexes between cyclin-dependent kinases (CDK) and cyclins, such as CDK2/cyclin A and CDK2/cyclin E, and inhibiting their kinase activity are regarded as promising antitumor agents to complement the existing therapies. From a high-throughput screening effort, we identified a new class of CDK2/cyclin A/E inhibitors. The hit-to-lead expansion of this class is described. X-ray crystallographic

  由正常细胞周期机制的破坏介导的异常增殖实际上是所有癌细胞的标志。靶向针对细胞周期蛋白依赖性激酶（CDK）与细胞周期蛋白之间的复合物（例如CDK2 / cyclin A和CDK2 / cyclin E）并抑制其激酶活性的化合物被认为是有前途的抗肿瘤药物，可补充现有疗法。通过高通量筛选工作，我们确定了一类新的CDK2 / cyclin A / E抑制剂。描述了此类的从头到尾的扩展。该系列中早期化合物的X射线晶体学数据以及为快速达到体内功效而进行的体外试验，导致了CDK2 / cyclin A（N-（5-环丙基-1H-吡唑-3- yl）-2-（2-萘基）乙酰胺（41），PNU-292137，IC50 = 37 nM），具有体内抗肿瘤活性（TGI>
• [EN] 3(5)-AMINO-PYRAZOLE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS ANTITUMOR AGENTS<br/>[FR] DERIVES DE 3(5)-AMINO-PYRAZOLE, LEUR PROCEDE DE FABRICATION ET LEUR EMPLOI COMME AGENTS ANTI-TUMORAUX
  申请人：PHARMACIA & UPJOHN SPA

  公开号：WO2001012189A1

  公开（公告）日：2001-02-22

  Compounds which are 3-amino-pyrazole derivatives represented by formula (I) wherein R is C3-C6 cycloalkyl group optionally substituted by a straight or branched C1-C6 alkyl or arylalkyl group; R1 is a straight or branched C1-C6 alkyl, C2-C4 alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, arylalkyl, arylcarbonyl, aryloxyalkyl or arylalkenyl group, each of which may be optionally further substituted as indicated in the description; or a pharmaceutically acceptable salt thereof. The compounds are useful for the treatment of cancer, cell proliferative disorders, Alzheimer's disease, viral infections, auto-immune diseases or neurodegenerative diseases.

  化合物是由式（I）表示的3-氨基吡唑衍生物，在该式中，R是C3-C6环烷基，可以选择性地被直链或支链的C1-C6烷基或芳基烷基取代；R1是直链或支链的C1-C6烷基，C2-C4烯基，环烷基，环烯基，杂环烷基，芳基，芳基烷基，芳基羰基，芳氧基烷基或芳基烯基基团，每个基团可以选择性地进一步按照说明中所示取代；或其药学上可接受的盐。这些化合物可用于治疗癌症、细胞增殖性疾病、阿尔茨海默病、病毒感染、自身免疫性疾病或神经退行性疾病。
• Synthesis of aminopyrazole analogs and their evaluation as CDK inhibitors for cancer therapy
  作者：Sandeep Rana、Yogesh A. Sonawane、Margaret A. Taylor、Smitha Kizhake、Muhammad Zahid、Amarnath Natarajan

  DOI：10.1016/j.bmcl.2018.10.020

  日期：2018.12

  We synthesized a library of aminopyrazole analogs to systematically explore the hydrophobic pocket adjacent to the hinge region and the solvent exposed region of cyclin dependent kinases. Structure-activity relationship studies identified an optimal substitution for the hydrophobic pocket and analog 24 as a potent and selective CDK2/5 inhibitor.
• 3(5)-AMINO-PYRAZOLE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS ANTITUMOR AGENTS
  申请人：Pharmacia Italia S.p.A.

  公开号：EP1202733A1

  公开（公告）日：2002-05-08
• EP1202733A4
  申请人：——

  公开号：EP1202733A4

  公开（公告）日：2003-05-14