1-(2-((allyloxy)methyl)-4-nitrophenyl)-4-methylpiperazine | 1083182-38-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(2-((allyloxy)methyl)-4-nitrophenyl)-4-methylpiperazine
• 英文别名: 1-Methyl-4-[4-nitro-2-[(2-propen-1-yloxy)methyl]phenyl]piperazine；1-methyl-4-[4-nitro-2-(prop-2-enoxymethyl)phenyl]piperazine
• CAS: 1083182-38-0
• 化学式: C₁₅H₂₁N₃O₃
• 分子量: 291.35
• InChiKey: MXRLNGCPTCYRSG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  61.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-((allyloxy)methyl)-4-nitrophenyl)-4-methylpiperazine 在 盐酸 、 铁粉 、 氯化铵 作用下， 以 乙醇 、 水 、 正丁醇 为溶剂， 反应 8.0h， 生成 [3-allyloxymethyl-4-(4-methylpiperazin-1-yl)phenyl]-[4-(3-allyloxymethylphenyl)pyrimidin-2-yl]amine
  参考文献：
  名称：

  Discovery of the Macrocycle 11-(2-Pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a Potent Janus Kinase 2/Fms-Like Tyrosine Kinase-3 (JAK2/FLT3) Inhibitor for the Treatment of Myelofibrosis and Lymphoma

  摘要：

  Discovery of the activating mutation V617F in Janus Kinase 2 (JAK2(V617F)), a tyrosine kinase critically involved in receptor signaling, recently ignited interest in JAK2 inhibitor therapy as a treatment for myelofibrosis (ME). Herein, we describe the design and synthesis of a series of small molecule 4-aryl-2-aminopyrimidine macrocycles and their biological evaluation against the JAK family of kinase enzymes and FLT3. The most promising leads were assessed for their in vitro ADME properties culminating in the discovery of 21c, a potent JAK2 (IC50 = 23 and 19 nM for JAK2(WT) and JAK2(V617F), respectively) and FLT3 (IC50 = 22 nM) inhibitor with selectivity against JAK1 and JAK3 (IC50 = 1280 and 520 nM, respectively). Further profiling of 21c in preclinical species and mouse xenograft and allograft models is described. Compound 21c (SB1518) was selected as a development candidate and progressed into clinical trials where it is currently in phase 2 for ME and lymphoma.

  DOI：

  10.1021/jm200326p
• 作为产物：
  描述：

  2-氯-5-硝基苯甲醛 在 sodium tetrahydroborate 、 四丁基硫酸氢铵 、 potassium carbonate 、 potassium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 1-(2-((allyloxy)methyl)-4-nitrophenyl)-4-methylpiperazine
  参考文献：
  名称：

  Discovery of the Macrocycle 11-(2-Pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a Potent Janus Kinase 2/Fms-Like Tyrosine Kinase-3 (JAK2/FLT3) Inhibitor for the Treatment of Myelofibrosis and Lymphoma

  摘要：

  Discovery of the activating mutation V617F in Janus Kinase 2 (JAK2(V617F)), a tyrosine kinase critically involved in receptor signaling, recently ignited interest in JAK2 inhibitor therapy as a treatment for myelofibrosis (ME). Herein, we describe the design and synthesis of a series of small molecule 4-aryl-2-aminopyrimidine macrocycles and their biological evaluation against the JAK family of kinase enzymes and FLT3. The most promising leads were assessed for their in vitro ADME properties culminating in the discovery of 21c, a potent JAK2 (IC50 = 23 and 19 nM for JAK2(WT) and JAK2(V617F), respectively) and FLT3 (IC50 = 22 nM) inhibitor with selectivity against JAK1 and JAK3 (IC50 = 1280 and 520 nM, respectively). Further profiling of 21c in preclinical species and mouse xenograft and allograft models is described. Compound 21c (SB1518) was selected as a development candidate and progressed into clinical trials where it is currently in phase 2 for ME and lymphoma.

  DOI：

  10.1021/jm200326p

文献信息

• WO2008/140419
  申请人：——

  公开号：——

  公开（公告）日：——
• [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.
• WO2024088189A1
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of the Macrocycle 11-(2-Pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a Potent Janus Kinase 2/Fms-Like Tyrosine Kinase-3 (JAK2/FLT3) Inhibitor for the Treatment of Myelofibrosis and Lymphoma
  作者：Anthony D. William、Angeline C.-H. Lee、Stéphanie Blanchard、Anders Poulsen、Ee Ling Teo、Harish Nagaraj、Evelyn Tan、Dizhong Chen、Meredith Williams、Eric T. Sun、Kee Chuan Goh、Wai Chung Ong、Siok Kun Goh、Stefan Hart、Ramesh Jayaraman、Mohammed Khalid Pasha、Kantharaj Ethirajulu、Jeanette M. Wood、Brian W. Dymock

  DOI：10.1021/jm200326p

  日期：2011.7.14

  Discovery of the activating mutation V617F in Janus Kinase 2 (JAK2(V617F)), a tyrosine kinase critically involved in receptor signaling, recently ignited interest in JAK2 inhibitor therapy as a treatment for myelofibrosis (ME). Herein, we describe the design and synthesis of a series of small molecule 4-aryl-2-aminopyrimidine macrocycles and their biological evaluation against the JAK family of kinase enzymes and FLT3. The most promising leads were assessed for their in vitro ADME properties culminating in the discovery of 21c, a potent JAK2 (IC50 = 23 and 19 nM for JAK2(WT) and JAK2(V617F), respectively) and FLT3 (IC50 = 22 nM) inhibitor with selectivity against JAK1 and JAK3 (IC50 = 1280 and 520 nM, respectively). Further profiling of 21c in preclinical species and mouse xenograft and allograft models is described. Compound 21c (SB1518) was selected as a development candidate and progressed into clinical trials where it is currently in phase 2 for ME and lymphoma.