3,3,3-trifluoro-1-{(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-propan-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3,3,3-trifluoro-1-{(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-propan-1-one
• 英文别名: 3,3,3-trifluoro-1-[(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]propan-1-one
• 化学式: C₁₆H₂₀F₃N₅O
• 分子量: 355.363
• InChiKey: MTRMACOHLXKTOY-PWSUYJOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  65.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3,3,3-三氟丙酸 、 N-methyl-N-((3S,4S)-4-methylpiperidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3,3,3-trifluoro-1-{(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-propan-1-one
  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

• Method of treatment of atherosclerosis
  申请人：Changelian S. Paul

  公开号：US20050113395A1

  公开（公告）日：2005-05-26

  A method of treating or preventing atherosclerosis comprising administering a compound of the formula wherein R 1 , R 2 and R 3 are as defined above.

  一种治疗或预防动脉粥样硬化的方法，包括给予一个符合以下公式的化合物，其中R1、R2和R3如上定义。
• Method of treatment of transplant rejection
  申请人：Pfizer Inc

  公开号：US20040116449A1

  公开（公告）日：2004-06-17

  A method of treating or preventing chronic organ transplant rejection comprising administering a compound of the formula 1 wherein R 1 , R 2 and R 3 are as defined above.

  一种治疗或预防器官移植慢性排异反应的方法，包括给予以下式子中R1、R2和R3如上定义的化合物1。
• Chiral salt resolution
  申请人：——

  公开号：US20030073719A1

  公开（公告）日：2003-04-17

  A method for resolving enantiomers of a compound containing the structure of the formula: 1 wherein R 4 or R 5 may contain one or more asymmetric centers, by mixing a racemic mixture of enantiomers of a compound, containing the structure of said formula; in a solvent, with a resolving compound having a defined stereospecificity, to form a solution and with said resolving agent being capable of binding with at least one but not all of said enantiomers to form a precipitate, containing said at least one of said enantiomers in stereospecific form and collecting either the precipitate and purifying it or collecting the solution with contained other of said enantiomers and recrystallizing the enantiomer contained in said solution.

  一种用于分离具有公式1结构的化合物的对映体的方法，其中R4或R5可能包含一个或多个不对称中心，通过将具有公式所述化合物的对映体的混合物与具有定义的立体特异性的分离剂在溶剂中混合，形成溶液，并且所述分离剂能够与至少一个但不是全部的对映体结合形成沉淀，其中所述沉淀包含所述至少一个对映体的立体特异性形式，并收集沉淀并纯化它或收集溶液和所含的其他对映体并重结晶所含的对映体。
• [EN] METHOD OF TREATMENT OF TRANSPLANT REJECTION<br/>[FR] METHODE POUR TRAITER LE REJET DE GREFFE
  申请人：PFIZER PROD INC

  公开号：WO2005060972A2

  公开（公告）日：2005-07-07

  A method of treating or preventing chronic organ transplant rejection comprising administering a compound of the formula (I) wherein R1, R2 and R3 are as defined above.

  一种治疗或预防慢性器官移植排斥的方法，包括给予式(I)中R1、R2和R3如上定义的化合物。
• Method treatment of transplant rejection
  申请人：Changelian S. Paul

  公开号：US20050159433A1

  公开（公告）日：2005-07-21

  A method of treating or preventing chronic organ transplant rejection comprising administering a compound of the formula wherein R 1 , R 2 and R 3 are as defined above.

  一种治疗或预防慢性器官移植排斥的方法，包括给予上述式中R1、R2和R3定义的化合物。