{3-[(allylmethylamino)methyl]phenyl}-[4-(3-allyloxymethylpiperidin-1-yl)pyrimidin-2-yl]amine | 1083089-90-0

• 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: {3-[(allylmethylamino)methyl]phenyl}-[4-(3-allyloxymethylpiperidin-1-yl)pyrimidin-2-yl]amine
• 英文别名: N-(3-((allyl(methyl)amino)methyl)phenyl)-4-(3-(allyloxymethyl)piperidin-1-yl)pyrimidin-2-amine；N-[3-[[methyl(prop-2-enyl)amino]methyl]phenyl]-4-[3-(prop-2-enoxymethyl)piperidin-1-yl]pyrimidin-2-amine
• CAS: 1083089-90-0
• 化学式: C₂₄H₃₃N₅O
• 分子量: 407.559
• InChiKey: BDJXQTFYSAZNKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  53.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  {3-[(allylmethylamino)methyl]phenyl}-[4-(3-allyloxymethylpiperidin-1-yl)pyrimidin-2-yl]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， 生成 、 14-methyl-19-oxa-1,5,7,14,26-pentaazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-2(26),3,5,8(27),9,11,16-heptaene
  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：

  3-哌啶甲醇 在 盐酸 、 水 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 mineral oil 、 正丁醇 为溶剂， 反应 14.0h， 生成 {3-[(allylmethylamino)methyl]phenyl}-[4-(3-allyloxymethylpiperidin-1-yl)pyrimidin-2-yl]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