N-(2,3-dihydro-1H-inden-4-yl)-3-iodo-4-methylbenzamide | 913067-79-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: N-(2,3-dihydro-1H-inden-4-yl)-3-iodo-4-methylbenzamide
• CAS: 913067-79-5
• 化学式: C₁₇H₁₆INO
• 分子量: 377.225
• InChiKey: YQQGTSSFBVCIBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-(2,3-dihydro-1H-inden-4-yl)-3-iodo-4-methylbenzamide 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 8.0h， 生成 N-Indan-4-yl-4-methyl-3-(2-methylamino-quinazolin-6-yl)-benzamide
  参考文献：
  名称：

  Discovery of Aminoquinazolines as Potent, Orally Bioavailable Inhibitors of Lck:  Synthesis, SAR, and in Vivo Anti-Inflammatory Activity

  摘要：

  The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and natural killer (NK) cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disease. Screening of our kinase-preferred collection identified aminoquinazoline 1 as a potent, nonselective inhibitor of Lck and T cell proliferation. In this report, we describe the synthesis and structure-activity relationships of a series of novel aminoquinazolines possessing in vitro mechanism-based potency. Optimized, orally bioavailable compounds 32 and 47 exhibit anti-inflammatory activity (ED50 of 22 and 11 mg/kg, respectively) in the anti-CD3-induced production of interleukin-2 (IL-2) in mice.

  DOI：

  10.1021/jm0605482
• 作为产物：
  描述：

  4-氨基茚满 、 3-碘-4-甲基苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.5h， 生成 N-(2,3-dihydro-1H-inden-4-yl)-3-iodo-4-methylbenzamide
  参考文献：
  名称：

  Discovery of Aminoquinazolines as Potent, Orally Bioavailable Inhibitors of Lck:  Synthesis, SAR, and in Vivo Anti-Inflammatory Activity

  摘要：

  The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and natural killer (NK) cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. Selective inhibition of Lck is expected to offer a new therapy for the treatment of T-cell-mediated autoimmune and inflammatory disease. Screening of our kinase-preferred collection identified aminoquinazoline 1 as a potent, nonselective inhibitor of Lck and T cell proliferation. In this report, we describe the synthesis and structure-activity relationships of a series of novel aminoquinazolines possessing in vitro mechanism-based potency. Optimized, orally bioavailable compounds 32 and 47 exhibit anti-inflammatory activity (ED50 of 22 and 11 mg/kg, respectively) in the anti-CD3-induced production of interleukin-2 (IL-2) in mice.

  DOI：

  10.1021/jm0605482

文献信息

• Aryl nitrogen-containing bicyclic compounds and methods of use
  申请人：Patel F. Vinod

  公开号：US20070054916A1

  公开（公告）日：2007-03-08

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I wherein A 1 , A 2 , A 3 , B, R 1 , R 2 , R 3 and R 4 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.

  这项发明涉及一类新的化合物，用于预防和治疗蛋白激酶介导的疾病，包括炎症、癌症和相关疾病。这些化合物具有一般的化学式I，其中A1、A2、A3、B、R1、R2、R3和R4在此有定义。因此，该发明还涉及包括该发明的化合物的药物组合物，使用该发明的化合物和组合物预防和治疗激酶介导的疾病的方法，以及用于制备该发明的化合物的中间体和方法。
• HETEROARYL-SUBSTITUTED ALKYNE COMPOUNDS AND METHOD OF USE
  申请人：Chaffee Stuart C.

  公开号：US20100160283A1

  公开（公告）日：2010-06-24

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I wherein A 1 , A 2 , A 3 , A 4 , R 1 and R 2 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, 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，用于预防和治疗蛋白激酶介导的疾病，包括炎症、癌症和相关疾病。该化合物具有一般式I，其中A1、A2、A3、A4、R1和R2的定义如本文所述。因此，本发明还涉及包括本发明化合物的制药组合物，使用本发明化合物和组合物预防和治疗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。
• ARYL NITROGEN-CONTAINING BICYCLIC COMPOUNDS AND THEIR USE AS KINASE INHIBITORS
  申请人：AMGEN INC.

  公开号：EP1836174B2

  公开（公告）日：2019-10-02
• US7776869B2
  申请人：——

  公开号：US7776869B2

  公开（公告）日：2010-08-17
• US8557996B2
  申请人：——

  公开号：US8557996B2

  公开（公告）日：2013-10-15