3-amino-N-methyl-4-(methylamino)benzenesulfonamide | 66315-14-8

• 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-amino-N-methyl-4-(methylamino)benzenesulfonamide
• CAS: 66315-14-8
• 化学式: C₈H₁₃N₃O₂S
• mdl: MFCD00025629
• 分子量: 215.276
• InChiKey: BSCVJYVFYUNMQC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  92.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-amino-N-methyl-4-(methylamino)benzenesulfonamide 、 6-chloro-N-(4-chlorophenyl)pyrimidin-4-amine 在 silver trifluoromethanesulfonate 作用下， 以6%的产率得到3-({6-[(4-chlorophenyl)amino]-4-pyrimidinyl}amino)-N-methyl-4-(methylamino)benzenesulfonamide
  参考文献：
  名称：

  取代基对药物-受体氢键相互作用的影响：相关的激酶抑制剂设计有用

  摘要：

  肌钙蛋白I相互作用激酶（TNNI3K）作为治疗心力衰竭的潜在靶点的研究已经产生了一系列取代的N-甲基-3-（嘧啶-4-基氨基）苯磺酰胺抑制剂，它们对广泛的药物具有优异的药效和选择性。蛋白激酶的光谱。与TNNI3K的ATP结合位点结合的原型成员的晶体结构揭示了两个锚定氢键接触：（1）从铰链区酰胺N–H到嘧啶氮和（2）从磺酰胺N–H到关守苏氨酸。不同的评价对-取代的苯磺酰胺定义了由对磺酰胺H键供体强度的调节而产生的对结合亲和力的取代作用。对于铰链NH-嘧啶H-键相互作用出现了相反的电子效应，这在计算的H-键受体强度与各种铰链结合杂环的TNNI3K亲和力的相关性中进一步阐明。这些与药物-受体H键相互作用的基本相关性通常可能是在激酶抑制剂设计中优化效价和选择性的有用工具。

  DOI：

  10.1021/acs.jmedchem.6b01342
• 作为产物：
  描述：

  4-methylamino-3-nitro-benzenesulfonic acid methylamide 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以1.3 g的产率得到3-amino-N-methyl-4-(methylamino)benzenesulfonamide
  参考文献：
  名称：

  Identification of Purines and 7-Deazapurines as Potent and Selective Type I Inhibitors of Troponin I-Interacting Kinase (TNNI3K)

  摘要：

  A series of cardiac troponin I-interacting kinase (TNNI3K) inhibitors arising from 34(9H-purin-6-yl)amino)-N-methyl-benzenesulfonamide (1) is disclosed along with fundamental structure function relationships that delineate the role of each element of 1 for TNNI3K recognition. An X-ray structure of 1 bound to TNNI3K confirmed its Type I binding mode and is used to rationalize the structure activity relationship and employed to design potent, selective, and orally bioavailable TNNI3K inhibitors. Identification of the 7-deazapurine heterocycle as a superior template (vs purine) and its elaboration by introduction of C4-benzenesulfonamide and C7- and C8-7-deazapurine substituents produced compounds with substantial improvements in potency (>1000-fold), general kinase selectivity (10-fold improvement), and pharmacokinetic properties (>10-fold increase in poDNAUC). Optimal members of the series have properties suitable for use in in vitro and in vivo experiments aimed at elucidating the role of TNNI3K in cardiac biology and serve as leads for developing novel heart failure medicines.

  DOI：

  10.1021/acs.jmedchem.5b00931

文献信息

• NOVEL BENZIMIDAZOLE DERIVATIVES AS EP4 ANTAGONISTS
  申请人：BAYER PHARMA AKTIENGESELLSCHAFT

  公开号：US20160214977A1

  公开（公告）日：2016-07-28

  The present invention relates to novel benzimidazole derivatives of the general formula (I), processes for their preparation and their use for the production of pharmaceutical compositions for the treatment of diseases and indications that are connected with the receptor EP4.

  本发明涉及通式(I)的新型苯并咪唑衍生物，其制备方法以及它们用于制备治疗与EP4受体相关的疾病和适应症的药物组合物的用途。
• NEUARTIGE BENZIMIDAZOLDERIVATE ALS EP4-ANTAGONISTEN
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：EP2928884B1

  公开（公告）日：2017-05-24
• US9708311B2
  申请人：——

  公开号：US9708311B2

  公开（公告）日：2017-07-18
• Identification of Purines and 7-Deazapurines as Potent and Selective Type I Inhibitors of Troponin I-Interacting Kinase (TNNI3K)
  作者：Brian G. Lawhorn、Joanne Philp、Yongdong Zhao、Christopher Louer、Marlys Hammond、Mui Cheung、Harvey Fries、Alan P. Graves、Lisa Shewchuk、Liping Wang、Joshua E. Cottom、Hongwei Qi、Huizhen Zhao、Rachel Totoritis、Guofeng Zhang、Benjamin Schwartz、Hu Li、Sharon Sweitzer、Dennis A. Holt、Gregory J. Gatto、Lara S. Kallander

  DOI：10.1021/acs.jmedchem.5b00931

  日期：2015.9.24

  A series of cardiac troponin I-interacting kinase (TNNI3K) inhibitors arising from 34(9H-purin-6-yl)amino)-N-methyl-benzenesulfonamide (1) is disclosed along with fundamental structure function relationships that delineate the role of each element of 1 for TNNI3K recognition. An X-ray structure of 1 bound to TNNI3K confirmed its Type I binding mode and is used to rationalize the structure activity relationship and employed to design potent, selective, and orally bioavailable TNNI3K inhibitors. Identification of the 7-deazapurine heterocycle as a superior template (vs purine) and its elaboration by introduction of C4-benzenesulfonamide and C7- and C8-7-deazapurine substituents produced compounds with substantial improvements in potency (>1000-fold), general kinase selectivity (10-fold improvement), and pharmacokinetic properties (>10-fold increase in poDNAUC). Optimal members of the series have properties suitable for use in in vitro and in vivo experiments aimed at elucidating the role of TNNI3K in cardiac biology and serve as leads for developing novel heart failure medicines.
• Substituent Effects on Drug–Receptor H-bond Interactions: Correlations Useful for the Design of Kinase Inhibitors
  作者：Brian G. Lawhorn、Joanne Philp、Alan P. Graves、Dennis A. Holt、Gregory J. Gatto、Lara S. Kallander

  DOI：10.1021/acs.jmedchem.6b01342

  日期：2016.12.8

  o)benzenesulfonamide inhibitors that display excellent potency and selectivity against a broad spectrum of protein kinases. Crystal structures of prototypical members bound to the ATP-binding site of TNNI3K reveal two anchoring hydrogen bond contacts: (1) from the hinge region amide N–H to the pyrimidine nitrogen and (2) from the sulfonamide N–H to the gatekeeper threonine. Evaluation of various para-substituted

  肌钙蛋白I相互作用激酶（TNNI3K）作为治疗心力衰竭的潜在靶点的研究已经产生了一系列取代的N-甲基-3-（嘧啶-4-基氨基）苯磺酰胺抑制剂，它们对广泛的药物具有优异的药效和选择性。蛋白激酶的光谱。与TNNI3K的ATP结合位点结合的原型成员的晶体结构揭示了两个锚定氢键接触：（1）从铰链区酰胺N–H到嘧啶氮和（2）从磺酰胺N–H到关守苏氨酸。不同的评价对-取代的苯磺酰胺定义了由对磺酰胺H键供体强度的调节而产生的对结合亲和力的取代作用。对于铰链NH-嘧啶H-键相互作用出现了相反的电子效应，这在计算的H-键受体强度与各种铰链结合杂环的TNNI3K亲和力的相关性中进一步阐明。这些与药物-受体H键相互作用的基本相关性通常可能是在激酶抑制剂设计中优化效价和选择性的有用工具。