N,N-dicyclopropyl-10-ethyl-3-methyl-7-[(5-methyl-1H-pyrazol-3-yl)amino]-3,5,8,10-tetraazatricyclo[7.3.0.0^2,6]dodeca-1(9),2(6),4,7,11-pentaene-11-carboxamide | 1271023-45-0

• 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-10-ethyl-3-methyl-7-[(5-methyl-1H-pyrazol-3-yl)amino]-3,5,8,10-tetraazatricyclo[7.3.0.0^2,6]dodeca-1(9),2(6),4,7,11-pentaene-11-carboxamide
• 英文别名: N,N-dicyclopropyl-6-ethyl-1-methyl-4-(5-methyl-1H-pyrazol-3-ylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide；N,N-dicyclopropyl-10-ethyl-3-methyl-7-[(5-methyl-1H-pyrazol-3-yl)amino]-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaene-11-carboxamide
• CAS: 1271023-45-0
• 化学式: C₂₂H₂₆N₈O
• 分子量: 418.501
• InChiKey: QBMBKEGWVSJZNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  96.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (Z)-N,N-dicyclopropyl-6-ethyl-1-methyl-4-(1-(methylthio)-3-oxobut-1-enylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide 在 肼 作用下， 以 乙醇 为溶剂， 反应 1.5h， 以79%的产率得到N,N-dicyclopropyl-10-ethyl-3-methyl-7-[(5-methyl-1H-pyrazol-3-yl)amino]-3,5,8,10-tetraazatricyclo[7.3.0.0^2,6]dodeca-1(9),2(6),4,7,11-pentaene-11-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

• [EN] JAK2 INHIBITORS AND THEIR USE FOR THE TREATMENT OF MYELOPROLIFERATIVE DISEASES AND CANCER<br/>[FR] INHIBITEURS DE JAK2 ET LEUR UTILISATION POUR LE TRAITEMENT DE MALADIES MYÉLOPROLIFÉRATIVES ET DU CANCER
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2011028864A1

  公开（公告）日：2011-03-10

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof. The formula (I) compounds inhibit tyrosine kinase activity of JAK2, thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.

  本发明提供了式（I）的化合物及其药学上可接受的盐。式（I）的化合物抑制JAK2的酪氨酸激酶活性，因此使它们在作为抗增殖剂治疗癌症和其他疾病时具有用途。
• JAK2 INHIBITORS AND THEIR USE FOR THE TREATMENT OF MYELOPROLIFERATIVE DISEASES AND CANCER
  申请人：Purandare Ashok V.

  公开号：US20110059943A1

  公开（公告）日：2011-03-10

  The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity of JAK2, thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.

  本发明提供了公式I的化合物及其药学上可接受的盐。公式I的化合物抑制JAK2的酪氨酸激酶活性，因此使它们在治疗癌症和其他疾病的抗增殖剂中有用。
• US8202881B2
  申请人：——

  公开号：US8202881B2

  公开（公告）日：2012-06-19
• US8673933B2
  申请人：——

  公开号：US8673933B2

  公开（公告）日：2014-03-18
• 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.