CP-352664 | 1097883-05-0

• 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: CP-352664
• 英文别名: 9-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2,3,4,4a,9,9a-hexahydro-1H-carbazole；9-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2,3,4,4a,9a-hexahydrocarbazole
• CAS: 1097883-05-0
• 化学式: C₁₈H₁₈N₄
• 分子量: 290.368
• InChiKey: QKYQEWXQVQGDJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 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：

  2,3,4,4a,9,9a-hexahydro-1H-carbazole hydrobromide 、 4-氯吡咯并嘧啶 在 吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以28%的产率得到CP-352664
  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

• Pyrrolo[2,3-d]pyrimidine compounds
  申请人：Pfizer inc.

  公开号：US20040058922A1

  公开（公告）日：2004-03-25

  A compound of the formula 1 wherein R 1 , R 2 and R 3 are as defined above, which are inhibitors of the enzyme protein tyrosine kinases such as Janus Kinase 3 and as such are useful therapy as immunosuppressive agents for organ transplants, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other autoimmune diseases.

  该化合物的化学式为1，其中R1、R2和R3如上所定义，是蛋白酪氨酸激酶的抑制剂，例如Janus Kinase 3，因此可作为免疫抑制剂用于器官移植、狼疮、多发性硬化症、类风湿性关节炎、银屑病、1型糖尿病及糖尿病并发症、癌症、哮喘、特应性皮炎、自身免疫性甲状腺疾病、溃疡性结肠炎、克罗恩病、阿尔茨海默病、白血病和其他自身免疫性疾病的治疗。
• PYRROLO 2,3-d]PYRIMIDINE COMPOUNDS
  申请人：Pfizer Products Inc.

  公开号：EP1087971B1

  公开（公告）日：2004-07-07
• US6635762B1
  申请人：——

  公开号：US6635762B1

  公开（公告）日：2003-10-21
• US7569569B2
  申请人：——

  公开号：US7569569B2

  公开（公告）日：2009-08-04
• [EN] PYRROLO[2,3-d]PYRIMIDINE COMPOUNDS<br/>[FR] COMPOSES DE PYRROLO[2,3-d]PYRIMIDINE
  申请人：PFIZER PRODUCTS INC.

  公开号：WO1999065909A1

  公开（公告）日：1999-12-23

  (EN) A compound of formula (I) wherein R1, R2 and R3 are as defined in the formula which are inhibitors of the enzyme protein tyrosine kinases such as Janus Kinase 3 and as such are useful therapy as immunosuppresive agents for organ transplants, lupus, multiple sclesoris, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other autoimmune diseases.(FR) La présente invention concerne des composés de formule, dans laquelle R1, R2 et R3 sont tels que définis dans la description. Ces composés sont des inhibiteurs d'enzymes tyrosine kinases, telle que la Janus Kinase 3, et en tant que tels, sont des traitements utiles comme agents immunosuppresseurs en cas de transplantations d'organes, de lupus, de sclérose en plaques, d'arthrite rhumatoïde, de psoriasis, de diabète de type I et de complications diabétiques, de cancer, d'asthme, de dermatite atopique, de troubles thyroïdiens auto-immuns, de colites ulcérantes, de maladie de Crohn et de maladie d'Alzheimer, de leucémie et d'autres maladies auto-immunes.