(3-allyloxyphenyl)-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-yl]amine | 937273-28-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (3-allyloxyphenyl)-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-yl]amine
• 英文别名: (3-allyloxyphenyl)-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-yl]-amine；4-(3-but-3-enoxyphenyl)-N-(3-prop-2-enoxyphenyl)pyrimidin-2-amine
• CAS: 937273-28-4
• 化学式: C₂₃H₂₃N₃O₂
• 分子量: 373.455
• InChiKey: YMWLUQOYZRIHFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  56.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3-allyloxyphenyl)-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-yl]amine 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 盐酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 5.0h， 以51%的产率得到(15E)-13,19-dioxa-5,7,26-triazatetracyclo[18.3.1.12,6.18,12]hexacosa-1(24),2(26),3,5,8(25),9,11,15,20,22-decaene
  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：

  1-allyloxy-3-nitro-benzene 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-allyloxyphenyl)-[4-(3-but-3-enyloxyphenyl)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

文献信息

• OXYGEN LINKED PYRIMIDINE DERIVATIVES
  申请人：Blanchard Stephanie

  公开号：US20120196855A1

  公开（公告）日：2012-08-02

  The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to oxygen linked and 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 proliferative disorders including tumours and cancers as well as other disorders or conditions related to or associated with kinases.

  本发明涉及嘧啶化合物，其作为抗增殖剂具有用处。更具体地说，本发明涉及氧连接和取代的嘧啶化合物，其制备方法，含有这些化合物的制药组合物以及这些化合物在治疗增殖性疾病方面的用途。这些化合物可用作治疗许多增殖性疾病，包括肿瘤和癌症以及与激酶相关或相关的其他疾病或病况的药物。
• Oxygen linked pyrimidine derivatives
  申请人：CTI BIOPHARMA CORP.

  公开号：US11135227B2

  公开（公告）日：2021-10-05

  The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to oxygen linked and 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 proliferative disorders including tumours and cancers as well as other disorders or conditions related to or associated with kinases.

  本发明涉及可用作抗增殖剂的嘧啶化合物。 更具体地说，本发明涉及氧连接和取代的嘧啶化合物、其制备方法、含有这些化合物的药物组合物以及这些化合物在治疗增殖性疾病中的用途。 这些化合物可用作治疗多种增殖性疾病的药物，包括肿瘤和癌症以及与激酶有关或相关的其他疾病或病症。
• US8153632B2
  申请人：——

  公开号：US8153632B2

  公开（公告）日：2012-04-10
• US8415338B2
  申请人：——

  公开号：US8415338B2

  公开（公告）日：2013-04-09
• US9573964B2
  申请人：——

  公开号：US9573964B2

  公开（公告）日：2017-02-21