3-methyl-11-(2-(pyrrolidin-1-yl)ethoxy)-14,20-dioxa-5,7,22,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene | 1083181-85-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-methyl-11-(2-(pyrrolidin-1-yl)ethoxy)-14,20-dioxa-5,7,22,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene
• 英文别名: (16E)-3-methyl-11-(2-pyrrolidin-1-ylethoxy)-14,20-dioxa-5,7,22,27-tetrazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2(27),3,5,8(26),9,11,16,21,23-decaene
• CAS: 1083181-85-4
• 化学式: C₂₈H₃₃N₅O₃
• 分子量: 487.602
• InChiKey: DWMYQJBUFRLTQG-GORDUTHDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  36
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  81.6
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-(2-氯乙氧基)-5-硝基苯甲醛 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 四丁基碘化铵 盐酸 、 甲醇 、 氢氧化钾 、 sodium tetrahydroborate 、 水 、 sodium hydride 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 水 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 5.5h， 生成 3-methyl-11-(2-(pyrrolidin-1-yl)ethoxy)-14,20-dioxa-5,7,22,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene
  参考文献：
  名称：

  WO2008/140419

  摘要：

  公开号：

文献信息

• Discovery of the Macrocycle (9<i>E</i>)-15-(2-(Pyrrolidin-1-yl)ethoxy)-7,12,25-trioxa-19,21,24-triaza-tetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2,4,9,14(26),15,17,20,22-nonaene (SB1578), a Potent Inhibitor of Janus Kinase 2/Fms-LikeTyrosine Kinase-3 (JAK2/FLT3) for the Treatment of Rheumatoid Arthritis
  作者：Anthony D. William、Angeline C.-H. Lee、Anders Poulsen、Kee Chuan Goh、Babita Madan、Stefan Hart、Evelyn Tan、Haishan Wang、Harish Nagaraj、Dizhong Chen、Chai Ping Lee、Eric T. Sun、Ramesh Jayaraman、Mohammad Khalid Pasha、Kantharaj Ethirajulu、Jeanette M. Wood、Brian W. Dymock

  DOI：10.1021/jm201454n

  日期：2012.3.22

  Herein, we describe the synthesis and SAR of a series of small molecule macrocycles that selectively inhibit JAK2 kinase within the JAK family and FLT3 kinase. Following a multiparameter optimization of a key aryl ring of the previously described SB1518 (pacritinib), the highly soluble 141 was selected as the optimal compound. Oral efficacy in the murine collagen-induced arthritis (CIA) model for rheumatoid arthritis (RA) supported 141 as a potential treatment for autoimmune diseases and inflammatory disorders such as psoriasis and RA. Compound 141 (SB1578) was progressed into development and is currently undergoing phase 1 clinical trials in healthy volunteers.
• [EN] PYRIDYL SUBSTITUTED PYRIMIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE PYRIMIDINE À SUBSTITUTION PYRIDYLE
  申请人：S BIO PTE LTD

  公开号：WO2008140419A2

  公开（公告）日：2008-11-20

  [EN] The present invention relates to pyridyl substituted pyrimidine compounds that are useful as agents for the treatment of kinase related disorders such as proliferative disorders. More particularly, the present invention relates to oxygen linked and pyridyl substituted pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of kinase related disorders such as proliferative disorders including tumours and cancers as well as other disorders or conditions related to or associated with kinases.
  [FR] La présente invention porte sur des composés de pyrimidine à substitution pyridyle qui sont utiles en tant qu'agents pour le traitement de troubles liés à la kinase, tels que des troubles prolifératifs. Plus particulièrement, la présente invention porte sur des composés de pyrimidine liés à l'oxygène et à substitution pyridyle, sur des procédés pour leur préparation, sur des compositions pharmaceutiques contenant ces composés et sur des utilisations de ces composés dans le traitement de troubles prolifératifs. Ces composés peuvent être utiles en tant que médicaments pour le traitement d'un certain nombre de troubles liés à la kinase, tels que des troubles prolifératifs comprenant les tumeurs et les cancers ainsi que d'autres troubles ou états liés ou associés aux kinases.