(S)-2-amino-1-(4-(4-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-6-morpholino-1,3,5-triazin-2-yl)piperazin-1-yl)-3-phenylpropan-1-one | 1416956-33-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-amino-1-(4-(4-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-6-morpholino-1,3,5-triazin-2-yl)piperazin-1-yl)-3-phenylpropan-1-one
• 英文别名: MIPS-9922；(2S)-2-amino-1-[4-[4-[2-(difluoromethyl)benzimidazol-1-yl]-6-morpholin-4-yl-1,3,5-triazin-2-yl]piperazin-1-yl]-3-phenylpropan-1-one
• CAS: 1416956-33-6
• 化学式: C₂₈H₃₁F₂N₉O₂
• 分子量: 563.61
• InChiKey: VOPWCDJBVPMVLJ-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  41
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  tert-butyl 4-(4-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-6-morpholino-1,3,5-triazin-2-yl)piperazine-1-carboxylate 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.66h， 生成 (S)-2-amino-1-(4-(4-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-6-morpholino-1,3,5-triazin-2-yl)piperazin-1-yl)-3-phenylpropan-1-one
  参考文献：
  名称：

  l-Aminoacyl-triazine Derivatives Are Isoform-Selective PI3Kβ Inhibitors That Target Nonconserved Asp862 of PI3Kβ

  摘要：

  A series of aminoacyl-triazine derivatives based upon the pan-PI3K inhibitor ZSTK474 were identified as potent and isoform-selective inhibitors of PI3K beta. The compounds showed selectivity based upon stereochemistry with L-amino acyl derivatives preferring PI3K beta, while their D-congeners favored PI3K delta. The mechanistic basis of this inhibition was studied using site-directed mutants. One Asp residue, D862, was identified as a critical participant in binding to the PI3K beta-selective inhibitors, distinguishing this class from other reported PI3K beta-selective inhibitors. The compounds show strong inhibition of cellular Akt phosphorylation and growth of PTEN-deficient MD-MBA-468 cells.

  DOI：

  10.1021/ml300336j

文献信息

• [EN] PHOSPHOINOSITIDE 3-KINASE (PI3K) INHIBITORS<br/>[FR] INHIBITEURS DE PHOSPHOINOSITIDE 3-KINASE (PI3K)
  申请人：UNIV MONASH

  公开号：WO2014005182A1

  公开（公告）日：2014-01-09

  The invention relates to compounds, and uses of the compounds, that are inhibitors of the enzyme phosphoinositide 3-kinase (PI3K). More particularly the compounds are selective inhibitors of one or more isoforms of PI3K. In particular embodiments the compounds are selective inhibitors of one isoform of PI3K.

  这项发明涉及一种抑制酶磷脂酰肌醇3-激酶（PI3K）的化合物及其用途。更具体地说，这些化合物是PI3K的一个或多个亚型的选择性抑制剂。在特定实施例中，这些化合物是PI3K的一个亚型的选择性抑制剂。
• Discovery and antiplatelet activity of a selective PI3Kβ inhibitor (MIPS-9922)
  作者：Zhaohua Zheng、Jo-Anne Pinson、Simon J. Mountford、Stephanie Orive、Simone M. Schoenwaelder、David Shackleford、Andrew Powell、Erin M. Nelson、Justin R. Hamilton、Shaun P. Jackson、Ian G. Jennings、Philip E. Thompson

  DOI：10.1016/j.ejmech.2016.06.010

  日期：2016.10

  A series of amino-substituted triazines were developed and examined for PI3K13 inhibition and anti platelet function. Structural adaptations of a morpholine ring of the prototype pan-PI3K inhibitor ZSTK474 yielded PI3K beta selective compounds, where the selectivity largely derives from an interaction with the non-conserved Asp862 residue, as shown by site directed mutagenesis. The most PI3K beta selective inhibitor from the series was studied in detail through a series of in vitro and in vivo functional studies. MIPS-9922, 10 potently inhibited ADP-induced washed platelet aggregation. It also inhibited integrin alpha(IIb)beta(3) activation and alpha(IIb)beta(3) dependent platelet adhesion to immobilized vWF under high shear. It prevented arterial thrombus formation in the in vivo electrolytic mouse model of thrombosis without inducing prolonged bleeding or excess blood loss. (C) 2016 Elsevier Masson SAS. All rights reserved.
• <scp>l</scp>-Aminoacyl-triazine Derivatives Are Isoform-Selective PI3Kβ Inhibitors That Target Nonconserved Asp862 of PI3Kβ
  作者：Jo-Anne Pinson、Zhaohua Zheng、Michelle S. Miller、David K. Chalmers、Ian G. Jennings、Philip E. Thompson

  DOI：10.1021/ml300336j

  日期：2013.2.14

  A series of aminoacyl-triazine derivatives based upon the pan-PI3K inhibitor ZSTK474 were identified as potent and isoform-selective inhibitors of PI3K beta. The compounds showed selectivity based upon stereochemistry with L-amino acyl derivatives preferring PI3K beta, while their D-congeners favored PI3K delta. The mechanistic basis of this inhibition was studied using site-directed mutants. One Asp residue, D862, was identified as a critical participant in binding to the PI3K beta-selective inhibitors, distinguishing this class from other reported PI3K beta-selective inhibitors. The compounds show strong inhibition of cellular Akt phosphorylation and growth of PTEN-deficient MD-MBA-468 cells.