(3S,4S)-4-甲基-3-(甲基-7H-吡咯并[2,3-d]嘧啶-4-氨基)-beta-氧代-1-哌啶丙腈 | 1092578-47-6

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: (3S,4S)-4-甲基-3-(甲基-7H-吡咯并[2,3-d]嘧啶-4-氨基)-beta-氧代-1-哌啶丙腈
• 中文别名: (3S,4S)-4-甲基-3-(甲基-7H-吡咯并[2,3-D]嘧啶-4-氨基)-BETA-氧代-1-哌啶丙腈；(3S,4S)-4-甲基-3-(甲基-7H-吡咯并[2,3-D]嘧啶-4-氨基)-β-氧代-1-哌啶丙腈
• 英文名称: tofacitinib
• 英文别名: (3S,4S)-Tofacitinib；3-[(3S,4S)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3-oxopropanenitrile
• CAS: 1092578-47-6
• 化学式: C₁₆H₂₀N₆O
• 分子量: 312.374
• InChiKey: UJLAWZDWDVHWOW-WCQYABFASA-N

物化性质

• 密度：
  1.296
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  88.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-methyl-N-((3S,4S)-4-methylpiperidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine 、 氰乙酸 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 (3S,4S)-4-甲基-3-(甲基-7H-吡咯并[2,3-d]嘧啶-4-氨基)-beta-氧代-1-哌啶丙腈
  参考文献：
  名称：

  Examining the Chirality, Conformation and Selective Kinase Inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550)

  摘要：

  Here, we examine the significance that stereochemistry plays within the clinically relevant Janus kinase 3 (Jak3) inhibitor 1 (CP-690,550). A synthesis of all four enantiopure stereoisomers of the drug was carried out and an examination of each compound revealed that only the enantiopure 3R,4R isomer was capable of blocking Stat5 phosphorylation (Jak3 dependent). Each compound was profiled across a panel of over 350 kinases, which revealed a high level of selectivity for the Jak family kinases for these related compounds. Each stereoisomer retained a degree of binding to Jak3 and Jak2 and the 3R,4S and 3S,4R stereoisomers were further revealed to have binding affinity for selected members of the STE7 and STE20 subfamily of kinases. finally, an appraisal of the minimum energy conformation of each stereoisomer and molecular docking at Jak3 was performed in an effort to better understand each compounds selectivity and potency profiles.

  DOI：

  10.1021/jm801142b

文献信息

• [EN] SUBSTITUTED (7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)AMINO COMPOUNDS USEFUL AS JAK1 INHIBITORS<br/>[FR] COMPOSÉS (7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)AMINO SUBSTITUÉS UTILES COMME INHIBITEURS DE JAK1
  申请人：CHEMWERTH INC

  公开号：WO2021041392A1

  公开（公告）日：2021-03-04

  The disclosure provides compounds and pharmaceutically acceptable salts thereof of Formula (I) The variables, R, R!-R3 and the A-ring are described herein. A can be a cyclohexyl ring. The compounds are inhibitors of JAK1 Kinase and are useful in methods of treating an allergic, inflammatory, or autoimmune disorders, in a patient, comprising administering a therapeutically effective amount of compound of Formula I or salt thereof, to the patient. The disclosure also provides pharmaceutical formulations containing a compound of Formula I.

  该披露提供了公式（I）的化合物及其药用盐。变量R、R1-R3和A环在此处描述。A可以是一个环己烷环。这些化合物是JAK1激酶的抑制剂，可用于治疗过敏、炎症或自身免疫性疾病的方法，包括向患者施用公式I的化合物或其盐的治疗有效量。该披露还提供了含有公式I化合物的药物配方。
• [EN] CODRUG THAT DISINTEGRATES IN INTESTINE, PREPARATION THEREFOR, AND USE THEREOF<br/>[FR] CO-MÉDICAMENT SE DÉSINTÉGRANT DANS L'INTESTIN, SA PRÉPARATION ET SON UTILISATION<br/>[ZH] 一类肠道裂解型共药及其制备和用途
  申请人：ENNOVABIO ZHEJIANG PHARMACEUTICALS CO LTD

  公开号：WO2022012693A1

  公开（公告）日：2022-01-20

  本发明涉及一类肠道裂解型共药（Codrug）及其制备和用途，具体地，本发明提供了一种如式I所示的共药化合物。本发明还提供了使用这类化合物治疗胃肠道自身免疫性疾病、炎症性疾病和癌症的方法；以及用于制备这类化合物的方法和中间物。
• Examining the Chirality, Conformation and Selective Kinase Inhibition of 3-((3<i>R</i>,4<i>R</i>)-4-methyl-3-(methyl(7H-pyrrolo[2,3-<i>d</i>]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550)
  作者：Jian-kang Jiang、Kamran Ghoreschi、Francesca Deflorian、Zhi Chen、Melissa Perreira、Marko Pesu、Jeremy Smith、Dac-Trung Nguyen、Eric H. Liu、William Leister、Stefano Costanzi、John J. O’Shea、Craig J. Thomas

  DOI：10.1021/jm801142b

  日期：2008.12.25

  Here, we examine the significance that stereochemistry plays within the clinically relevant Janus kinase 3 (Jak3) inhibitor 1 (CP-690,550). A synthesis of all four enantiopure stereoisomers of the drug was carried out and an examination of each compound revealed that only the enantiopure 3R,4R isomer was capable of blocking Stat5 phosphorylation (Jak3 dependent). Each compound was profiled across a panel of over 350 kinases, which revealed a high level of selectivity for the Jak family kinases for these related compounds. Each stereoisomer retained a degree of binding to Jak3 and Jak2 and the 3R,4S and 3S,4R stereoisomers were further revealed to have binding affinity for selected members of the STE7 and STE20 subfamily of kinases. finally, an appraisal of the minimum energy conformation of each stereoisomer and molecular docking at Jak3 was performed in an effort to better understand each compounds selectivity and potency profiles.
• METHODS OF TREATING MYELOPROLIFERATIVE NEOPLASMS
  申请人：Kartos Therapeutics, Inc.

  公开号：EP3801476A2

  公开（公告）日：2021-04-14
• 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.