N-(6-(2-(4-methylphenylthio)pyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide | 1112979-56-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: N-(6-(2-(4-methylphenylthio)pyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide
• 英文别名: N-(6-(2-((4-methylphenyl)sulfanyl)-4-pyrimidinyl)-1,3-benzothiazol-2-yl)acetamide；N-[6-[2-(4-methylphenyl)sulfanylpyrimidin-4-yl]-1,3-benzothiazol-2-yl]acetamide
• CAS: 1112979-56-2
• 化学式: C₂₀H₁₆N₄OS₂
• 分子量: 392.505
• InChiKey: MPHAVQZPYRQKGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-(6-溴苯并[d]噻唑-2-基)乙酰胺 在 四(三苯基膦)钯 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 sodium hydride 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.33h， 生成 N-(6-(2-(4-methylphenylthio)pyrimidin-4-yl)benzo[d]thiazol-2-yl)acetamide
  参考文献：
  名称：

  Discovery and Optimization of a Series of Benzothiazole Phosphoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitors

  摘要：

  Phosphoinositide 3-kinase alpha (Pi3K alpha) is a lipid kinase that plays a key regulatory role in several cellular processes. The mutation or amplification of this kinase in humans has been implicated in the growth of multiple tumor types. Consequently, PI3K alpha has become a target of intense research for drug discovery. Our studies began with the identification of benzothiazole compound 1 from a high throughput screen. Extensive SAR studies led to the discovery of sulfonamide 45 as an early lead, based on its in vitro cellular potency. Subsequent modifications of the central pyrimidine ring dramatically improved enzyme and cellular potency and led to the identification of chloropyridine 70. Further arylsulfonamide SAR studies optimized in vitro clearance and led to the identification of 82 as a potent dual inhibitor of PI3K and mTOR This molecule exhibited potent enzyme and cell activity, low clearance, and high oral bioavailability. In addition, compound 82 demonstrated tumor growth inhibition in U-87 MG, A549, and HCT116 tumor xenograft models.

  DOI：

  10.1021/jm1014605

文献信息

• PI3 kinase modulators and methods of use
  申请人：Booker Shon

  公开号：US20090054405A1

  公开（公告）日：2009-02-26

  The present invention comprises a new class of compounds capable of modulating the activity of PI3 kinase and, accordingly, useful for treatment of PI3 kinase mediated diseases, including melanomas, carcinomas and other cancer-related conditions. The compounds have a general Formula I wherein each of A 1 , A 2 , A 3 , A 4 , X, R 1 and R 2 are defined herein. The invention further comprises pharmaceutical compositions, methods for treatment of PI3 kinase mediated diseases, and intermediates and processes useful for the preparation of compounds of the invention.

  本发明涉及一类新的化合物，能够调节PI3激酶的活性，因此对于治疗PI3激酶介导的疾病，包括黑色素瘤、癌瘤和其他与癌症相关的疾病非常有用。这些化合物具有通式I，其中A1、A2、A3、A4、X、R1和R2均在此定义。本发明还涉及制药组合物、治疗PI3激酶介导的疾病的方法，以及用于制备本发明化合物的中间体和过程。
• PI3 KINASE MODULATORS AND METHODS OF USE
  申请人：Amgen, Inc

  公开号：EP2183232A2

  公开（公告）日：2010-05-12
• US7928140B2
  申请人：——

  公开号：US7928140B2

  公开（公告）日：2011-04-19
• [EN] PI3 KINASE MODULATORS AND METHODS OF USE<br/>[FR] MODULATEUR DE LA PI3 KINASE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2009017822A2

  公开（公告）日：2009-02-05

  The present invention comprises a new class of compounds capable of modulating the activity of PI3 kinase and, accordingly, useful for treatment of PI3 kinase mediated diseases, including melanomas, carcinomas and other cancer-related conditions. The compounds have a general Formula I wherein each of A1, A2, A3, A4, X, R1 and R2 are defined herein. The invention further comprises pharmaceutical compositions, methods for treatment of PI3 kinase mediated diseases, and intermediates and processes useful for the preparation of compounds of the invention.
• Discovery and Optimization of a Series of Benzothiazole Phosphoinositide 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Dual Inhibitors
  作者：Noel D. D’Angelo、Tae-Seong Kim、Kristin Andrews、Shon K. Booker、Sean Caenepeel、Kui Chen、Derin D’Amico、Dan Freeman、Jian Jiang、Longbin Liu、John D. McCarter、Tisha San Miguel、Erin L. Mullady、Michael Schrag、Raju Subramanian、Jin Tang、Robert C. Wahl、Ling Wang、Douglas A. Whittington、Tian Wu、Ning Xi、Yang Xu、Peter Yakowec、Kevin Yang、Leeanne P. Zalameda、Nancy Zhang、Paul Hughes、Mark H. Norman

  DOI：10.1021/jm1014605

  日期：2011.3.24

  Phosphoinositide 3-kinase alpha (Pi3K alpha) is a lipid kinase that plays a key regulatory role in several cellular processes. The mutation or amplification of this kinase in humans has been implicated in the growth of multiple tumor types. Consequently, PI3K alpha has become a target of intense research for drug discovery. Our studies began with the identification of benzothiazole compound 1 from a high throughput screen. Extensive SAR studies led to the discovery of sulfonamide 45 as an early lead, based on its in vitro cellular potency. Subsequent modifications of the central pyrimidine ring dramatically improved enzyme and cellular potency and led to the identification of chloropyridine 70. Further arylsulfonamide SAR studies optimized in vitro clearance and led to the identification of 82 as a potent dual inhibitor of PI3K and mTOR This molecule exhibited potent enzyme and cell activity, low clearance, and high oral bioavailability. In addition, compound 82 demonstrated tumor growth inhibition in U-87 MG, A549, and HCT116 tumor xenograft models.