1-[1-(methylsulfonyl)piperidin-4-yl]-3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-2(1H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 1-[1-(methylsulfonyl)piperidin-4-yl]-3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-2(1H)-one
• 英文别名: 3-(1-Methylsulfonylpiperidin-4-yl)-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,6,8,11-tetraen-4-one
• 化学式: C₁₄H₁₇N₅O₃S
• 分子量: 335.387
• InChiKey: AGSPYTHTZIURIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-氯-1H-吡咯并[2,3-b]吡啶-5-羧酸乙酯 在 盐酸 、 叠氮磷酸二苯酯 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 、 正丁醇 为溶剂， 反应 11.58h， 生成 1-[1-(methylsulfonyl)piperidin-4-yl]-3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-2(1H)-one
  参考文献：
  名称：

  Discovery of 3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-2(1H)-one derivatives as novel JAK inhibitors

  摘要：

  Because Janus kinases (JAKs) play a crucial role in cytokine-mediated signal transduction, JAKs are an attractive target for the treatment of organ transplant rejection and autoimmune diseases such as rheumatoid arthritis (RA). To identify JAK inhibitors, we focused on the 1H-pyrrolo[2,3-b]pyridine derivative 3, which exhibited moderate JAK3 and JAK1 inhibitory activities. Optimization of 3 identified the tricyclic imidazo-pyrrolopyridinone derivative 19, which exhibited potent JAK3 and JAK1 inhibitory activities (IC50 = 1.1 nM, 1.5 nM, respectively) with favorable metabolic stability. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.028

文献信息

• HETEROCYCLIC JANUS KINASE 3 INHIBITORS
  申请人：Inoue Takayuki

  公开号：US20090264399A1

  公开（公告）日：2009-10-22

  The invention relates to compound of the formula (I) or its salt, wherein —R 1 , —R 2 , —R 3 , —R 4 , —R 5 , -M-, —X— and —Y═ are as defined in the description, their use of as, medicament, the process for their preparation and use for the treatment of JAK3 mediated diseases.

  本发明涉及公式（I）的化合物或其盐，其中-R1，-R2，-R3，-R4，-R5，-M-，-X-和-Y═如描述中所定义，它们的用途作为药物，制备它们的过程以及用于治疗JAK3介导的疾病的用途。
• Heterocyclic Janus kinase 3 inhibitors
  申请人：Astellas Pharma Inc.

  公开号：EP2251341A1

  公开（公告）日：2010-11-17

  The invention relates to compound of the formula (I) or its salt, wherein -R1, -R2, -R3, -R4, -R5, -M-, -X- and -Y= are as defined in the description, their use of as medicament, the process for their preparation and use for the treatment of JAK3 mediated diseases.

  本发明涉及式 (I) 的化合物或其盐，其中 -R1、-R2、-R3、-R4、-R5、-M-、-X- 和 -Y= 如描述中所定义；本发明还涉及其作为药物的用途、制备工艺以及用于治疗 JAK3 介导的疾病。
• US8163767B2
  申请人：——

  公开号：US8163767B2

  公开（公告）日：2012-04-24
• Discovery of 3,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridin-2(1H)-one derivatives as novel JAK inhibitors
  作者：Hiroaki Yamagishi、Shohei Shirakami、Yutaka Nakajima、Akira Tanaka、Fumie Takahashi、Hisao Hamaguchi、Keiko Hatanaka、Ayako Moritomo、Masamichi Inami、Yasuyuki Higashi、Takayuki Inoue

  DOI：10.1016/j.bmc.2015.05.028

  日期：2015.8

  Because Janus kinases (JAKs) play a crucial role in cytokine-mediated signal transduction, JAKs are an attractive target for the treatment of organ transplant rejection and autoimmune diseases such as rheumatoid arthritis (RA). To identify JAK inhibitors, we focused on the 1H-pyrrolo[2,3-b]pyridine derivative 3, which exhibited moderate JAK3 and JAK1 inhibitory activities. Optimization of 3 identified the tricyclic imidazo-pyrrolopyridinone derivative 19, which exhibited potent JAK3 and JAK1 inhibitory activities (IC50 = 1.1 nM, 1.5 nM, respectively) with favorable metabolic stability. (C) 2015 Elsevier Ltd. All rights reserved.