1,2-dimethyl-4-(4-nitrophenyl)piperazine | 737777-40-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1,2-dimethyl-4-(4-nitrophenyl)piperazine
• 英文别名: 4-(3,4-dimethylpiperazin-1-yl)nitrobenzene
• CAS: 737777-40-1
• 化学式: C₁₂H₁₇N₃O₂
• 分子量: 235.286
• InChiKey: LHVNLXVOVGXVQC-UHFFFAOYSA-N

物化性质

• 沸点：
  373.4±37.0 °C(Predicted)
• 密度：
  1.150±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,2-dimethyl-4-(4-nitrophenyl)piperazine 在 palladium on activated charcoal 对甲苯磺酸 、 一水合肼 作用下， 以 甲醇 为溶剂， 反应 0.33h， 生成 1-{4-[4-(3,4-dimethylpiperazin-1-yl)phenylamino]-2-methylquinolin-3-yl}ethanone
  参考文献：
  名称：

  Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists

  摘要：

  Starting from two acridine compounds identified in a high-throughput screening campaign (1 and 2, Table 1), a series of 4-aminoquinolines was synthesized and tested for their properties on the human alpha(2)-adrenoceptor subtypes (alpha(2A), alpha(2B), and alpha(2C.)). A number of compounds with good antagonist potencies against the alpha(2C)-adrenoceptor and excellent subtype selectivities over the other two subtypes were discovered. For example, (R)-{4-[4-(3,4-dimethylpiperazin-1-yl) phenylamino] quinolin- 3- yl} methanol 6j had an antagonist potency of 8.5 nM against, and a subtype selectivity of more than 200-fold for, the alpha(2C)-adrenoceptor. Investigation of the structure-activity relationship identified a number of structural features, the most critical of which was an absolute need for a substituent in the 3-position of the quinoline ring. The 3-position on the piperazine ring was also found to play an appreciable role, as substitutions in that position exerted a significant and stereospecific beneficial effect on the alpha(2C)-adrenoceptor affinity and potency. Replacing the piperazine ring proved difficult, with 1,4-diazepanes representing the only viable alternative.

  DOI：

  10.1021/jm060262x
• 作为产物：
  描述：

  2-甲基哌嗪 在 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.5h， 生成 1,2-dimethyl-4-(4-nitrophenyl)piperazine
  参考文献：
  名称：

  [EN] PYRIMIDINE DERIVATIVES AS KINASE INHIBITORS AND THEIR THERAPEUTICAL APPLICATIONS
  [FR] DÉRIVÉS DE PYRIMIDINE UTILISÉS EN TANT QU'INHIBITEURS DE KINASE, ET LEURS APPLICATIONS THÉRAPEUTIQUES

  摘要：

  本发明提供了具有抗增殖活性的激酶抑制剂，包括取代嘧啶衍生物及其药用可接受的配方。此外，本发明提供了制备新化合物的方法以及使用这些化合物的方法。

  公开号：

  WO2016138527A1

文献信息

• [EN] PYRIMIDINE DERIVATIVES AS KINASE INHIBITORS AND THEIR THERAPEUTICAL APPLICATIONS<br/>[FR] DÉRIVÉS DE PYRIMIDINE UTILISÉS EN TANT QU'INHIBITEURS DE KINASE, ET LEURS APPLICATIONS THÉRAPEUTIQUES
  申请人：NANTBIOSCIENCE INC

  公开号：WO2016138527A1

  公开（公告）日：2016-09-01

  The present invention provides kinase inhibitors with anti-proliferative activity comprising substituted pyrimidine derivatives and pharmaceutically-acceptable formulations thereof. In addition, the invention provides methods for making novel compounds and methods for using the compounds.

  本发明提供了具有抗增殖活性的激酶抑制剂，包括取代嘧啶衍生物及其药用可接受的配方。此外，本发明提供了制备新化合物的方法以及使用这些化合物的方法。
• [EN] ANTAGONISTS FOR ALPHA-2 ADRENOCEPTORS<br/>[FR] ANTAGONISTES POUR RECEPTEURS ALPHA-2 ADRENERGIQUES
  申请人：JUVANTIA PHARMA LTD OY

  公开号：WO2004067513A1

  公开（公告）日：2004-08-12

  The invention provides a compound of formula (I), wherein Q, Y, A, Ra, Rb, R1 to R4, u and t are as defined in claim 1, or a pharmaceutically acceptable salt or ester thereof, useful as an alpha-2 antagonist. The compounds of formula (I) can be used for the treatment of diseases or conditions where antagonists of alpha-2 adrenoceptors are indicated to be effective.

  该发明提供了一种具有式（I）的化合物，其中Q、Y、A、Ra、Rb、R1至R4、u和t如权利要求1中定义，或其药用可接受的盐或酯，可用作α-2拮抗剂。式（I）的化合物可用于治疗需要α-2肾上腺素受体拮抗剂有效的疾病或症状。
• Compounds, pharmaceutical compositions, and methods for inhibiting cyclin-dependent kinases
  申请人：——

  公开号：US20030220326A1

  公开（公告）日：2003-11-27

  Pharmaceutical compositions containing effective amounts of CDK-inhibiting diaminothiazole compounds of the following formula (where R 1 and R 2 are as defined in the specification) or their salts, or prodrugs or active metabolites of such compounds or salts, are useful for treating disorders and diseases such as cancer: 1 In preferred embodiments, R 1 and R 2 are independently unsubstituted or substituted carbocyclic or heterocyclic aryl ring structures. Compounds where R 2 is ortho-substituted aryl are especially potent inhibitors of CDKs such as CDK4.

  含有以下公式中CDK抑制二氨基噻唑化合物的有效量的药物组合物（其中R1和R2如规范所定义）或其盐，或这些化合物或盐的前药或活性代谢物，可用于治疗癌症等疾病和疾病。在首选实施例中，R1和R2分别是未取代或取代的碳环或杂环芳香环结构。其中R2为邻位取代芳香族的化合物特别是CDKs如CDK4的有效抑制剂。
• 4-Aminothiazole derivatives, their preparation and their use as inhibitors of cyclin-dependent kinases
  申请人：Agouron Pharmaceuticals, Inc.

  公开号：EP1215208A2

  公开（公告）日：2002-06-19

  This invention is directed to aminothiazole compounds of formula (I) wherein R1 is a substituted or unsubstituted group selected from : C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; C1-6-alkoxyl; C1-6-alcohol; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; carbonyl; ether; (C1-6-alkyl)-carbonyl; (C1-6-alkyl)-aryl; (C1-6-alkyl)-cycloalkyl; (C1-6-alkyl)-(C1-6-alkoxyl); aryl-(C1-6-alkoxyl); thioether; thiol; and sulfonyl; wherein when R1 is substituted, each substituent independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol, thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; and R2 is a carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, ring structure having a substituent at the position adjacent to the point of attachment, which ring structure is optionally further substituted, where each substituent of R2 independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol; thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; or a pharmaceutically acceptable salt of a compound of formula (I), or a prodrug or pharmaceutically active metabolite of a compound of formula (I) or pharmaceutically acceptable salt thereof, for inhibiting cyclin-dependent kinases (CDKs), such as CDK1, CDK2, CDK4, and CDK6. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds and to methods of treating malignancies and other disorders by administering effective amounts of such compounds.

  本发明涉及式（I）的氨基噻唑化合物，其中 R1 是一个取代或未取代的基团，选自......：C1-6-烷基；C1-6-烯基；C1-6-炔基；C1-6-烷氧基；C1-6-醇；碳环或杂环、单环或融合或不融合多环、环烷基；碳环或杂环、单环或融合或不融合多环、芳基；羰基；醚；(C1-6-烷基)-羰基；(C1-6-烷基)-芳基；(C1-6-烷基)-环烷基；(C1-6-烷基)-(C1-6-烷氧基)；芳基-(C1-6-烷氧基)；硫醚；硫醇；和磺酰基；其中，当 R1 被取代时，每个取代基独立地为卤素；卤代烷基；C1-6-烷基；C1-6-烯基；C1-6-炔基；羟基；C1-6-烷氧基；氨基；硝基；硫醇、硫醚；亚胺；氰基；氨基；膦酰基；膦；羧基；硫代羰基；磺酰基；磺酰胺；酮；醛；酯；氧；碳环或杂环、单环或有熔合或无熔合多环、环烷基；或碳环或杂环、单环或有熔合或无熔合多环、芳基；和 R2 是碳环或杂环、单环或融合或不融合多环、环状结构，在邻近连接点的位置有一个取代基，该环状结构可选择被进一步取代，其中 R2 的每个取代基独立地是卤素；卤代烷基；C1-6-烷基；C1-6-烯基；C1-6-炔基；羟基；C1-6-烷氧基；氨基；硝基；硫醇；硫醚；亚胺；氰基；氨基；膦酰基；膦；羧基；硫代羰基；磺酰基；磺酰胺；酮；醛；酯；氧；碳环或杂环、单环或有熔合或无熔合多环、环烷基；或碳环或杂环、单环或有熔合或无熔合多环、芳基；或式（I）化合物的药学上可接受的盐，或式（I）化合物或其药学上可接受的盐的原药或药学活性代谢物，用于抑制细胞周期蛋白依赖性激酶（CDKs），如 CDK1、CDK2、CDK4 和 CDK6。本发明还涉及含有此类化合物的药物组合物的治疗或预防用途，以及通过施用有效量的此类化合物治疗恶性肿瘤和其他疾病的方法。
• 4-AMINOTHIAZOLE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS INHIBITORS OF CYCLIN-DEPENDENT KINASES
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：EP1056732A2

  公开（公告）日：2000-12-06