[4-(1-allyl-1H-indol-6-yl)-5-methylpyrimidin-2-yl]-[3-allyloxymethyl-4-(2-pyrrolidin-1-ylethoxy)phenyl]amine | 1364124-02-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: [4-(1-allyl-1H-indol-6-yl)-5-methylpyrimidin-2-yl]-[3-allyloxymethyl-4-(2-pyrrolidin-1-ylethoxy)phenyl]amine
• CAS: 1364124-02-6
• 化学式: C₃₂H₃₇N₅O₂
• 分子量: 523.678
• InChiKey: UPBWUANQHPFBSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.51
• 重原子数：
  39.0
• 可旋转键数：
  13.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  64.44
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  [4-(1-allyl-1H-indol-6-yl)-5-methylpyrimidin-2-yl]-[3-allyloxymethyl-4-(2-pyrrolidin-1-ylethoxy)phenyl]amine 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 盐酸 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以44%的产率得到19,21-etheno-3-methyl-11-(2-(pyrrolidin-1-yl)ethoxy)-14-oxa-5,7,19,25-tetraazatetracyclo[18.3.1.1(2,6).1(8,12)]hexacosa-1(24),2(25),3,5,8(26),9,11,16,20,22-decaene
  参考文献：
  名称：

  Discovery of the Macrocycle (9E)-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

  摘要：

  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.

  DOI：

  10.1021/jm201454n
• 作为产物：
  描述：

  (2-(2-氯乙氧基)-5-硝基苯基)甲醇 在 盐酸 、 tin(II) chloride dihdyrate 、 水 、 四丁基硫酸氢铵 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 正丁醇 为溶剂， 反应 44.0h， 生成 [4-(1-allyl-1H-indol-6-yl)-5-methylpyrimidin-2-yl]-[3-allyloxymethyl-4-(2-pyrrolidin-1-ylethoxy)phenyl]amine
  参考文献：
  名称：

  Discovery of the Macrocycle (9E)-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

  摘要：

  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.

  DOI：

  10.1021/jm201454n