N-(3-trifluoromethylphenyl)guanidine nitrate | 71198-38-4

• 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: N-(3-trifluoromethylphenyl)guanidine nitrate
• 英文别名: [3-(trifluoromethyl)phenyl]-Guanidine nitrate；N-[3-(trifluoromethyl)phenyl]guanidinium nitrate；3-Trifluoromethyl-phenylguanidine nitrate；nitric acid;2-[3-(trifluoromethyl)phenyl]guanidine
• CAS: 71198-38-4
• 化学式: C₈H₈F₃N₃*HNO₃
• 分子量: 266.18
• InChiKey: VVIBNGXNJXFWCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.26
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(3-trifluoromethylphenyl)guanidine nitrate 在 吗啉 、 potassium carbonate 作用下， 以 乙二醇甲醚 为溶剂， 反应 14.0h， 生成 3-[2-(3-Trifluoromethyl-phenylamino)-pyrimidin-4-yl]-pyrazolo[1,5-b]pyridazin-6-ol
  参考文献：
  名称：

  N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as Potent and Selective Inhibitors of Glycogen Synthase Kinase 3 with Good Cellular Efficacy

  摘要：

  Glycogen synthase kinase 3 regulates glycogen synthase, the rate-determining enzyme for glycogen synthesis. Liver and muscle glycogen synthesis is defective in type 2 diabetics, resulting in elevated plasma glucose levels. Inhibition of GSK-3 could potentially be an effective method to control plasma glucose levels in type 2 diabetics. Structure-activity studies on a N-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine series have led to the identification of potent and selective compounds with good cellular efficacy. Molecular modeling studies have given insights into the mode of binding of these inhibitors. Since the initial leads were also potent inhibitors of CDK-2/CDK-4, an extensive SAR was performed at various positions of the pyrazolo[1,5-b]pyridazin core to afford potent GSK-3 inhibitors that were highly selective over CDK-2. In addition, these inhibitors also exhibited very good cell efficacy and functional response. A representative example was shown to have good oral exposure levels, extending their utility in an in vivo setting. These inhibitors provide a viable lead series in the discovery of new therapies for the treatment of type 2 diabetes.

  DOI：

  10.1021/jm040063i
• 作为产物：
  描述：

  氰胺 、 间氨基三氟甲苯 在 硝酸 作用下， 以 乙醇 、 水 为溶剂， 生成 N-(3-trifluoromethylphenyl)guanidine nitrate
  参考文献：
  名称：

  Pharmacologically active pyridine derivatives and processes for the

  摘要：

  式I的N-苯基-2-嘧啶胺衍生物，其中取代基如权利要求1中定义的那样，式I的衍生物可以用于例如治疗肿瘤疾病。

  公开号：

  US05728708A1

文献信息

• Phenylamino-Pyrimidine (PAP) Derivatives: A New Class of Potent and Selective Inhibitors of Protein Kinase C (PKC)
  作者：Jürg Zimmermann、Giorgio Caravatti、Helmut Mett、Thomas Meyer、Marcel Müller、Nicholas B. Lydon、Doriano Fabbro

  DOI：10.1002/ardp.19963290707

  日期：——

  Phenylamino‐pyrimidines represent a novel class of inhibitors of the protein kinase C with a high degree of selectivity versus other serine/threonine and tyrosine kinases. Steady state kinetic analysis of N‐(3‐[1‐imidazolyl]‐phenyl)‐4‐(3‐pyridyl)‐2‐pyrimidinamine (5), which showed potent inhibitory activity, revealed competitive kinetics relative to ATP. The adjacent H‐bond acceptor of the pyrimidine

  苯氨基嘧啶是一类新型的蛋白激酶 C 抑制剂，与其他丝氨酸/苏氨酸和酪氨酸激酶相比具有高度选择性。N-(3-[1-咪唑基]-苯基)-4-(3-吡啶基)-2-嘧啶胺(5)的稳态动力学分析显示出有效的抑制活性，揭示了相对于ATP的竞争动力学。发现与苯胺的 H 键供体相邻的嘧啶部分的相邻 H 键受体对抑制活性至关重要。N-(3-Nitro-phenyl)-4-(3-pyridyl)-2-pyrimidinamine (7) 优先抑制 PKC-α (IC50 = 0.79 μM) 而不是其他测试的亚型。PKC-α 的抑制常数与对 T24 人膀胱癌细胞的抗增殖作用呈定性相关，但也有一些例外。
• Pharmacologically active pyrimidineamine derivatives and processes for
  申请人：Novartis Corporation

  公开号：US05705502A1

  公开（公告）日：1998-01-06

  Described are N-phenyl-2-pyrimidineamine derivatives of formula I ##STR1## wherein R.sub.1 is a substituted cyclic radical, the cyclic radical being bonded at a ring carbon atom in each case and being selected from phenyl, pyridyl, pyrazinyl, thiazolyl, pyrimidinyl, pyridazinyl and imidazolyl, and the substituents of the above-mentioned cyclic radical being selected from one or more of the groups halogen, cyano, carbamoyl, --C(.dbd.O)--OR.sub.3, --C(.dbd.O)--R.sub.4, --SO.sub.2 --N(R.sub.5)--R.sub.6, --N(R.sub.7)--R.sub.8, --OR.sub.9 and fluorine-substituted lower alkyl, wherein R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are each independently of the others hydrogen or lower alkyl that is unsubstituted or substituted by mono- or di-lower alkylamino; and R.sub.2 is selected from halogen, cyano, carbamoyl, --C(.dbd.O)--OR.sub.10, --C(.dbd.O)--R.sub.11, --SO.sub.2 --N(R.sub.12)--R.sub.13, --N(R.sub.14)--R.sub.15, --OR.sub.16 and fluorine-substituted lower alkyl, wherein R.sub.10, R.sub.11, R.sub.12, R.sub.13, R.sub.14, R.sub.15 and R.sub.16 are each independently of the others hydrogen or lower alkyl that is unsubstituted or substituted by mono- or di-lower alkylamino. Those compounds can be used, for example, in the treatment of tumour diseases.

  本文描述了式I的N-苯基-2-嘧啶胺衍生物：##STR1## 其中R.sub.1是一个取代的环状基团，在每种情况下与环状基团上的一个环碳原子键合，并且从苯基，吡啶基，吡嗪基，噻唑基，嘧啶基，吡嗪啉基和咪唑基中选择，上述环状基团的取代基从卤素，氰基，氨基甲酰基，--C(.dbd.O)--OR.sub.3，--C(.dbd.O)--R.sub.4，--SO.sub.2--N(R.sub.5)--R.sub.6，--N(R.sub.7)--R.sub.8，--OR.sub.9和氟代的低烷基中选择，其中R.sub.3，R.sub.4，R.sub.5，R.sub.6，R.sub.7，R.sub.8和R.sub.9各自独立地是未取代或取代的低烷基，可以通过单烷基或二烷基氨基进行取代; R.sub.2从卤素，氰基，氨基甲酰基，--C(.dbd.O)--OR.sub.10，--C(.dbd.O)--R.sub.11，--SO.sub.2--N(R.sub.12)--R.sub.13，--N(R.sub.14)--R.sub.15，--OR.sub.16和氟代的低烷基中选择，其中R.sub.10，R.sub.11，R.sub.12，R.sub.13，R.sub.14，R.sub.15和R.sub.16各自独立地是未取代或取代的低烷基，可以通过单烷基或二烷基氨基进行取代。这些化合物可以用于肿瘤疾病的治疗。
• Discovery of novel 1H-imidazol-2-yl-pyrimidine-4,6-diamines as potential antimalarials
  作者：Xianming Deng、Advait Nagle、Tao Wu、Tomoyo Sakata、Kerstin Henson、Zhong Chen、Kelli Kuhen、David Plouffe、Elizabeth Winzeler、Francisco Adrian、Tove Tuntland、Jonathan Chang、Susan Simerson、Steven Howard、Jared Ek、John Isbell、David C. Tully、Arnab K. Chatterjee、Nathanael S. Gray

  DOI：10.1016/j.bmcl.2010.05.095

  日期：2010.7

  A novel family of 1H-imidazol-2-yl-pyrimidine-4,6-diamines has been identified with potent activity against the erythrocyte-stage of Plasmodium falciparum (Pf), the most common causative agent of malaria. A systematic SAR study resulted in the identification of compound 40 which exhibits good potency against both wild-type and drug resistant parasites and exhibits good in vivo pharmacokinetic properties. (C) 2010 Elsevier Ltd. All rights reserved.
• 2-Anilino-4-(thiazol-5-yl)pyrimidine CDK Inhibitors:  Synthesis, SAR Analysis, X-ray Crystallography, and Biological Activity
  作者：Shudong Wang、Christopher Meades、Gavin Wood、Andrew Osnowski、Sian Anderson、Rhoda Yuill、Mark Thomas、Mokdad Mezna、Wayne Jackson、Carol Midgley、Gary Griffiths、Ian Fleming、Simon Green、Iain McNae、Su-Ying Wu、Campbell McInnes、Daniella Zheleva、Malcolm D. Walkinshaw、Peter M. Fischer

  DOI：10.1021/jm0309957

  日期：2004.3.1

  Following the identification through virtual screening of 4-(2,4-dimethyl-thiazol-5-yl)pyrimidin-2-ylamines as moderately potent inhibitors of cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analogue program was initiated. The first aims were to optimize potency and to evaluate the cellular mode of action of lead candidate molecules. Here the synthetic chemistry, the structure-guided design approach, and the structure-activity relationships (SARs) that led to the discovery of 2-anilino-4-(thiazol-5-yl)pyrimidine ATP-antagonistic CDK2 inhibitors, many with very low nM K(i)s against CDK2, are reported. Furthermore, X-ray crystal structures of four representative analogues from our chemical series in complex with CDK2 are presented, and these structures are used to rationalize the observed biochemical SARs. Finally results are reported that show, using the most potent CDK2 inhibitor compound from the current series, that the observed antiproliferative and proapoptotic effects are consistent with cellular CDK2 and CDK9 inhibition.
• KREUTZBERGER A.; TANTAWY A., ARCH. PHARM., 1979, 312, NO 5, 426-431
  作者：KREUTZBERGER A.、 TANTAWY A.

  DOI：——

  日期：——