4-((trifluoromethyl)sulfonyl)benzylamine hydrochloride | 578028-97-4

• 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: 4-((trifluoromethyl)sulfonyl)benzylamine hydrochloride
• 英文别名: [4-(trifluoromethylsulfonyl)phenyl]methanamine;hydrochloride
• CAS: 578028-97-4
• 化学式: C₈H₈F₃NO₂S*ClH
• 分子量: 275.679
• InChiKey: BFCOVWYLVYATCC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.86
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  68.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(3-Undecyl-1,2,4-oxadiazol-5-yl)benzaldehyde 、 4-((trifluoromethyl)sulfonyl)benzylamine hydrochloride 生成 N-{4-[(trifluoromethyl)sulfonyl]benzyl}-N-[4-(3-undecyl-1,2,4-oxadiazol-5-yl)benzyl]amine
  参考文献：
  名称：

  Substituted methylene amide derivatives as modulators of protein tyrosine phosphatases(ptps)

  摘要：

  本发明涉及公式（I）的取代亚甲基酰胺衍生物及其用于治疗和/或预防由胰岛素抵抗或高血糖引起的代谢障碍，包括1型和/或2型糖尿病、不足的葡萄糖耐受性、胰岛素抵抗、高脂血症、高三酰甘油血症、高胆固醇血症、肥胖症、多囊卵巢综合症（PCOS）。特别是，本发明涉及使用公式（I）的取代亚甲基酰胺衍生物来调节，尤其是抑制PTP的活性。本发明还涉及一种治疗2型糖尿病、肥胖症和调节哺乳动物食欲的方法。此外，本发明还涉及新的取代亚甲基酰胺衍生物及其制备方法。公式（I）。

  公开号：

  US20050124656A1
• 作为产物：
  描述：

  4-(三氟甲基磺酰基)苯甲腈 在 盐酸 、 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 96.0h， 生成 4-((trifluoromethyl)sulfonyl)benzylamine hydrochloride
  参考文献：
  名称：

  Isoindolinone Inhibitors of the Murine Double Minute 2 (MDM2)-p53 Protein−Protein Interaction: Structure−Activity Studies Leading to Improved Potency

  摘要：

  Inhibition of the MDM2-p53 interaction has been shown to produce an antitumor effect, especially in MDM2 amplified tumors.. The isoindolinone scaffold has proved to be versatile for the discovery of MDM2-p53 antagonists. Optimization of previously reported inhibitors, for example, NU8231 (7) and NU8165 (49), was guided by MDM2 NMR titrations, which indicated key areas of the binding interaction to be explored. Variation of the 2-N-benzyl and 3-alkoxy substituents resulted in the identification of 3-(4-nitrobenzyl)-3-((1-(hydroxymethyl)cyclopropyl)methoxy)-2-(4-nitrobenzyl)isoindolin-1-one (74) as a potent MDM2-p53 inhibitor (IC(50) = 0.23 +/- 0.01 mu M). Resolution of the enantiomers of 74 showed that potent MDM2-p53 activity primarily resided with the (+)R-enantiomer (74a; IC(50) = 0.17 +/- 0.02 mu M). The cellular activity of key compounds has been examined in cell lines with defined p53 and MDM2 status. Compound 74a activates p53, MDM2, and p21 transcription in MDM2 amplified cells and shows moderate selectivity for wild-type p53 cell lines in growth inhibition assays.

  DOI：

  10.1021/jm1011929

文献信息

• Substituted methylene amide derivatives as modulators of protein tyrosine phosphatases(ptps)
  申请人：Swinnen Dominique

  公开号：US20050124656A1

  公开（公告）日：2005-06-09

  The present invention is related to substituted methylene amide derivatives of formula (I) and use thereof for the treatment and/or prevention of metabolic disorders mediated by insulin resistance or pyperglycemia, comprising diabetes type I and/or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, obesity, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of substituted methylene amide derivatives of formula (I) to modulate, notably to inhibit the activity of PTPs. Also the present invention relates to a method of treating diabetes type II, obesity and to regulate the appetite of mammals. The present invention is furthermore related to novel substituted methylene amide derivatives and method of preparation thereof. Formula (I).

  本发明涉及公式（I）的取代亚甲基酰胺衍生物及其用于治疗和/或预防由胰岛素抵抗或高血糖引起的代谢障碍，包括1型和/或2型糖尿病、不足的葡萄糖耐受性、胰岛素抵抗、高脂血症、高三酰甘油血症、高胆固醇血症、肥胖症、多囊卵巢综合症（PCOS）。特别是，本发明涉及使用公式（I）的取代亚甲基酰胺衍生物来调节，尤其是抑制PTP的活性。本发明还涉及一种治疗2型糖尿病、肥胖症和调节哺乳动物食欲的方法。此外，本发明还涉及新的取代亚甲基酰胺衍生物及其制备方法。公式（I）。
• SUBSTITUTED METHYLENE AMIDE DERIVATIVES AS MODULATORS OF PROTEIN TYROSINE PHOSPHATASES (PTPS)
  申请人：Applied Research Systems ARS Holding N.V.

  公开号：EP1470102A1

  公开（公告）日：2004-10-27
• US7592477B2
  申请人：——

  公开号：US7592477B2

  公开（公告）日：2009-09-22
• [EN] SUBSTITUTED METHYLENE AMIDE DERIVATIVES AS MODULATORS OF PROTEIN TYROSINE PHOSPHATASES PTPS<br/>[FR] DERIVES AMIDES SUBSTITUES METHYLENE EN TANT QUE MODULATEURS DE PROTEINE TYROSINE PHOSPHATASES (PTP)
  申请人：APPLIED RESEARCH SYSTEMS

  公开号：WO2003064376A1

  公开（公告）日：2003-08-07

  The present invention is related to substituted methylene amide derivatives of formula (I) and use thereof for the treatment and/or prevention of metabolic disorders mediated by insulin resistance or pyperglycemia, comprising diabetes type I and/or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, obesity, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of substituted methylene amide derivatives of formula (I) to modulate, notably to inhibit the activity of PTPs. Also the present invention relates to a method of treating diabetes type II, obesity and to regulate the appetite of mammals. The present invention is furthermore related to novel substituted methylene amide derivatives and method of preparation thereof. Formula (I).
• Isoindolinone Inhibitors of the Murine Double Minute 2 (MDM2)-p53 Protein−Protein Interaction: Structure−Activity Studies Leading to Improved Potency
  作者：Ian R. Hardcastle、Junfeng Liu、Eric Valeur、Anna Watson、Shafiq U. Ahmed、Timothy J. Blackburn、Karim Bennaceur、William Clegg、Catherine Drummond、Jane A. Endicott、Bernard T. Golding、Roger J. Griffin、Jan Gruber、Karen Haggerty、Ross W. Harrington、Claire Hutton、Stuart Kemp、Xiaohong Lu、James M. McDonnell、David R. Newell、Martin E. M. Noble、Sara L. Payne、Charlotte H. Revill、Christiane Riedinger、Qing Xu、John Lunec

  DOI：10.1021/jm1011929

  日期：2011.3.10

  Inhibition of the MDM2-p53 interaction has been shown to produce an antitumor effect, especially in MDM2 amplified tumors.. The isoindolinone scaffold has proved to be versatile for the discovery of MDM2-p53 antagonists. Optimization of previously reported inhibitors, for example, NU8231 (7) and NU8165 (49), was guided by MDM2 NMR titrations, which indicated key areas of the binding interaction to be explored. Variation of the 2-N-benzyl and 3-alkoxy substituents resulted in the identification of 3-(4-nitrobenzyl)-3-((1-(hydroxymethyl)cyclopropyl)methoxy)-2-(4-nitrobenzyl)isoindolin-1-one (74) as a potent MDM2-p53 inhibitor (IC(50) = 0.23 +/- 0.01 mu M). Resolution of the enantiomers of 74 showed that potent MDM2-p53 activity primarily resided with the (+)R-enantiomer (74a; IC(50) = 0.17 +/- 0.02 mu M). The cellular activity of key compounds has been examined in cell lines with defined p53 and MDM2 status. Compound 74a activates p53, MDM2, and p21 transcription in MDM2 amplified cells and shows moderate selectivity for wild-type p53 cell lines in growth inhibition assays.