4-(octahydro-1H-indol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine | 1259403-97-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-(octahydro-1H-indol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: 4-(2,3,3a,4,5,6,7,7a-octahydroindol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine
• CAS: 1259403-97-8
• 化学式: C₁₄H₁₈N₄
• 分子量: 242.324
• InChiKey: JKLNAJIHZIIHPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  44.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  八氢吲哚(混旋) 、 4-氯吡咯并嘧啶 以 叔丁醇 为溶剂， 生成 4-(octahydro-1H-indol-1-yl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Discovery of CP-690,550: A Potent and Selective Janus Kinase (JAK) Inhibitor for the Treatment of Autoimmune Diseases and Organ Transplant Rejection

  摘要：

  There is a critical need for safer and more convenient treatments for organ transplant rejection and autoimmune disorders such as rheumatoid arthritis. Janus tyrosine kinases (JAK1, JAK3) are expressed in lymphoid cells and are involved in the signaling of multiple cytokines important for various T cell functions. Blockade of the JAK1/JAK3-STAT pathway with a small molecule was anticipated to provide therapeutic immunosuppression/immunomodulation. The Pfizer compound library was screened against the catalytic domain of JAK3 resulting in the identification of a pyrrolopyrimidine-based series of inhibitors represented by CP-352,664 (2a). Synthetic analogues of 2a were screened against the JAK enzymes and evaluated in an IL-2 induced T cell blast proliferation assay. Select compounds were evaluated in rodent efficacy models of allograft rejection and destructive inflammatory arthritis. Optimization within this chemical series led to identification of CP-690,550 1, a potential first-in-class JAK inhibitor for treatment of autoimmune diseases and organ transplant rejection.

  DOI：

  10.1021/jm1004286

文献信息

• Discovery of CP-690,550: A Potent and Selective Janus Kinase (JAK) Inhibitor for the Treatment of Autoimmune Diseases and Organ Transplant Rejection
  作者：Mark E. Flanagan、Todd A. Blumenkopf、William H. Brissette、Matthew F. Brown、Jeffrey M. Casavant、Chang Shang-Poa、Jonathan L. Doty、Eileen A. Elliott、Michael B. Fisher、Michael Hines、Craig Kent、Elizabeth M. Kudlacz、Brett M. Lillie、Kelly S. Magnuson、Sandra P. McCurdy、Michael J. Munchhof、Bret D. Perry、Perry S. Sawyer、Timothy J. Strelevitz、Chakrapani Subramanyam、Jianmin Sun、David A. Whipple、Paul S. Changelian

  DOI：10.1021/jm1004286

  日期：2010.12.23

  There is a critical need for safer and more convenient treatments for organ transplant rejection and autoimmune disorders such as rheumatoid arthritis. Janus tyrosine kinases (JAK1, JAK3) are expressed in lymphoid cells and are involved in the signaling of multiple cytokines important for various T cell functions. Blockade of the JAK1/JAK3-STAT pathway with a small molecule was anticipated to provide therapeutic immunosuppression/immunomodulation. The Pfizer compound library was screened against the catalytic domain of JAK3 resulting in the identification of a pyrrolopyrimidine-based series of inhibitors represented by CP-352,664 (2a). Synthetic analogues of 2a were screened against the JAK enzymes and evaluated in an IL-2 induced T cell blast proliferation assay. Select compounds were evaluated in rodent efficacy models of allograft rejection and destructive inflammatory arthritis. Optimization within this chemical series led to identification of CP-690,550 1, a potential first-in-class JAK inhibitor for treatment of autoimmune diseases and organ transplant rejection.