3,5-diamino-4-(4-carboxy)phenylazo-pyrazole | 140651-21-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3,5-diamino-4-(4-carboxy)phenylazo-pyrazole
• CAS: 140651-21-4
• 化学式: C₁₀H₁₀N₆O₂
• 分子量: 246.228
• InChiKey: NCWCSLXGDWIAIT-BUHFOSPRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.69
• 重原子数：
  18.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  142.74
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  4-[2-(Dicyanomethylidene)hydrazinyl]benzoic acid 在 一水合肼 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 3,5-diamino-4-(4-carboxy)phenylazo-pyrazole
  参考文献：
  名称：

  4-Arylazo-3,5-diamino-1H-pyrazole CDK Inhibitors:  SAR Study, Crystal Structure in Complex with CDK2, Selectivity, and Cellular Effects

  摘要：

  In a routine screening of our small-molecule compound collection we recently identified 4-arylazo-3,5-diamino-1H-pyrazoles as a novel group of ATP antagonists with moderate potency against CDK2-cyclin E. A preliminary SAR study based on 35 analogues suggests ways in which the pharmacophore could be further optimized, for example, via substitutions in the 4-aryl ring. Enzyme kinetics studies with the lead compound and X-ray crystallography of an inhibitor-CDK2 complex demonstrated that its mode of inhibition is competitive. Functional kinase assays confirmed the selectivity toward CDKs, with a preference for CDK9cyclin T1. The most potent inhibitor, 4-[(3,5-diamino-1H-pyrazol-4-yl) diazenyl] phenol 31b (CAN508), reduced the frequency of S-phase cells of the cancer cell line HT-29 in antiproliferation assays. Further observed cellular effects included decreased phosphorylation of the retinoblastoma protein and the C-terminal domain of RNA polymerase II, inhibition of mRNA synthesis, and induction of the tumor suppressor protein p53, all of which are consistent with inhibition of CDK9.

  DOI：

  10.1021/jm0605740

文献信息

• [EN] 4-ARYLAZO-3,5-DIAMINO-PYRAZOLE COMPOUNDS AND USE THEREOF<br/>[FR] COMPOSES DE 4-ARYLAZO-3,5-DIAMINO-PYRAZOLE ET LEUR UTILISATION
  申请人：INST OF EX BOTANY OF THE ACADE

  公开号：WO2006024858A1

  公开（公告）日：2006-03-09

  A series of mono- and binuclear 4-arylazo-3,5-diamino-pyrazoles which are useful for inhibition of cyclin-dependent kinases (preferably CDK9). Hence they can be used as antimitotic-, pro-apoptotic and antünflammatory drugs, in particular, in chemotherapy of cancer and asthma, therapy of psoriasis and parasitoses as those caused by fungi or protists, treatment of Alzheimer's disease or as antineurodegenerative drugs, or to suppress immunostimulation. These compounds are useful in a variety of utilities, including as intermediates in the preparation of flame-retardants, diagnostic reagents and therapeutics, including antivirals and immunosuppressors.

  一系列单核和双核的4-芳基偶氮-3,5-二氨基吡唑醇，可用于抑制细胞周期依赖性激酶（优选为CDK9）。因此，它们可以用作抗有丝分裂、促凋亡和抗炎药物，特别是在癌症和哮喘化疗、牛皮癣和由真菌或原生动物引起的寄生虫病的治疗中，阿尔茨海默病的治疗或作为抗神经退行性药物，或用于抑制免疫刺激。这些化合物在各种用途中都很有用，包括作为制备阻燃剂、诊断试剂和治疗药物的中间体，包括抗病毒药物和免疫抑制剂。
• 4-ARYLAZO-3,5-DIAMINO-PYRAZOLE COMPOUNDS AND USE THEREOF
  申请人：INSTITUTE OF EXPERIMENTAL BOTANY ASCR

  公开号：EP1786779A1

  公开（公告）日：2007-05-23
• 4-Arylazo-3,5-Diamino-Pyrazole Compounds and Use Thereof
  申请人：Cankar Petr

  公开号：US20080312238A1

  公开（公告）日：2008-12-18

  A series of mono- and binuclear 4-arylazo-3,5-diamino-pyrazoles which are useful for inhibition of cyclin-dependent kinases (preferably CDK9). Hence they can be used as antimitotic-, pro-apoptotic and antiinflammatory drugs, in particular, in chemotherapy of cancer and asthma, therapy of psoriasis and parasitoses as those caused by fungi or protists, treatment of Alzheimer's disease or as anti neurodegenerative drugs, or to suppress immunostimulation. These compounds are useful in a variety of utilities, including as intermediates in the preparation of flame-retardants, diagnostic reagents and therapeutics, including antivirals and immunosuppressors.
• US8357673B2
  申请人：——

  公开号：US8357673B2

  公开（公告）日：2013-01-22
• 4-Arylazo-3,5-diamino-1<i>H</i>-pyrazole CDK Inhibitors:  SAR Study, Crystal Structure in Complex with CDK2, Selectivity, and Cellular Effects
  作者：Vladimír Kryštof、Petr Cankař、Iveta Fryšová、Jan Slouka、George Kontopidis、Petr Džubák、Marián Hajdúch、Josef Srovnal、Walter F. de Azevedo、Martin Orság、Martina Paprskářová、Jakub Rolčík、Aleš Látr、Peter M. Fischer、Miroslav Strnad

  DOI：10.1021/jm0605740

  日期：2006.11.1

  In a routine screening of our small-molecule compound collection we recently identified 4-arylazo-3,5-diamino-1H-pyrazoles as a novel group of ATP antagonists with moderate potency against CDK2-cyclin E. A preliminary SAR study based on 35 analogues suggests ways in which the pharmacophore could be further optimized, for example, via substitutions in the 4-aryl ring. Enzyme kinetics studies with the lead compound and X-ray crystallography of an inhibitor-CDK2 complex demonstrated that its mode of inhibition is competitive. Functional kinase assays confirmed the selectivity toward CDKs, with a preference for CDK9cyclin T1. The most potent inhibitor, 4-[(3,5-diamino-1H-pyrazol-4-yl) diazenyl] phenol 31b (CAN508), reduced the frequency of S-phase cells of the cancer cell line HT-29 in antiproliferation assays. Further observed cellular effects included decreased phosphorylation of the retinoblastoma protein and the C-terminal domain of RNA polymerase II, inhibition of mRNA synthesis, and induction of the tumor suppressor protein p53, all of which are consistent with inhibition of CDK9.