N,N-dicyclopropyl-4-(1,3-dimethyl-1H-pyrazol-5-ylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide

• 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: N,N-dicyclopropyl-4-(1,3-dimethyl-1H-pyrazol-5-ylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide
• 英文别名: N,N-dicyclopropyl-7-[(2,5-dimethylpyrazol-3-yl)amino]-10-ethyl-3-methyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaene-11-carboxamide
• 化学式: C₂₃H₂₈N₈O
• 分子量: 432.528
• InChiKey: BIAKCAIUXMWBPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  85.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide 在 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 N,N-二环丙基-4-[(1,5-二甲基-1H-吡唑-3-基)氨基]-6-乙基-1,6-二氢-1-甲基-咪唑并[4,5-d]吡咯并[2,3-b]吡啶-7-甲酰胺 、 N,N-dicyclopropyl-4-(1,3-dimethyl-1H-pyrazol-5-ylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide
  参考文献：
  名称：

  Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms

  摘要：

  JAK2 kinase inhibitors are a promising new class of agents for the treatment of myeloproliferative neoplasms and have potential for the treatment of other diseases possessing a deregulated JAK2-STAT pathway. X-ray structure and ADME guided refinement of C-4 heterocycles to address metabolic liability present in dialkylthiazole 1 led to the discovery of a clinical candidate, BMS-911543 (11), with excellent kinome selectivity, in vivo PD activity, and safety profile.

  DOI：

  10.1021/acsmedchemlett.5b00226

文献信息

• Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms
  作者：Honghe Wan、Gretchen M. Schroeder、Amy C. Hart、Jennifer Inghrim、James Grebinski、John S. Tokarski、Matthew V. Lorenzi、Dan You、Theresa Mcdevitt、Becky Penhallow、Ragini Vuppugalla、Yueping Zhang、Xiaomei Gu、Ramaswamy Iyer、Louis J. Lombardo、George L. Trainor、Stefan Ruepp、Jonathan Lippy、Yuval Blat、John S. Sack、Javed A. Khan、Kevin Stefanski、Bogdan Sleczka、Arvind Mathur、Jung-Hui Sun、Michael K. Wong、Dauh-Rurng Wu、Peng Li、Anuradha Gupta、P. N. Arunachalam、Bala Pragalathan、Sankara Narayanan、Nanjundaswamy K.C.、Prakasam Kuppusamy、Ashok V. Purandare

  DOI：10.1021/acsmedchemlett.5b00226

  日期：2015.8.13

  JAK2 kinase inhibitors are a promising new class of agents for the treatment of myeloproliferative neoplasms and have potential for the treatment of other diseases possessing a deregulated JAK2-STAT pathway. X-ray structure and ADME guided refinement of C-4 heterocycles to address metabolic liability present in dialkylthiazole 1 led to the discovery of a clinical candidate, BMS-911543 (11), with excellent kinome selectivity, in vivo PD activity, and safety profile.