[4-(4-allyloxymethylfuran-2-yl)pyrimidin-2-yl]-[3-allyloxymethyl-4-(2-pyrrolidin-1-ylethoxy)phenyl]amine | 1364123-99-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [4-(4-allyloxymethylfuran-2-yl)pyrimidin-2-yl]-[3-allyloxymethyl-4-(2-pyrrolidin-1-ylethoxy)phenyl]amine
• CAS: 1364123-99-8
• 化学式: C₂₈H₃₄N₄O₄
• 分子量: 490.602
• InChiKey: VCSQJMXQFMLAEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.36
• 重原子数：
  36.0
• 可旋转键数：
  15.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  81.88
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  [4-(4-allyloxymethylfuran-2-yl)pyrimidin-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49%的产率得到15-(2-(pyrrolidin-1-yl)ethoxy)-3,7,12-trioxa-19,21,24-triazatetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2(25),4,9,14(26),15,17,20,22-nonaene
  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：

  5-(2-chloropyrimidin-4-yl)furan-3-carbaldehyde 在 盐酸 、 甲醇 、 sodium tetrahydroborate 、 水 、 四丁基硫酸氢铵 、 potassium hydroxide 作用下， 以 四氢呋喃 、 正丁醇 为溶剂， 反应 24.0h， 生成 [4-(4-allyloxymethylfuran-2-yl)pyrimidin-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