allylmethyl-[2-(2-diethylaminoethoxy)-5-nitrobenzyl]amine | 937271-59-5

• 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: allylmethyl-[2-(2-diethylaminoethoxy)-5-nitrobenzyl]amine
• 英文别名: Allyl-[2-(2-diethylamino-ethoxy)-5-nitro-benzyl]-methyl-amine；N-[[2-[2-(diethylamino)ethoxy]-5-nitrophenyl]methyl]-N-methylprop-2-en-1-amine
• CAS: 937271-59-5
• 化学式: C₁₇H₂₇N₃O₃
• 分子量: 321.42
• InChiKey: BLEIIQUJKCHUCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 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：

  allylmethyl-[2-(2-diethylaminoethoxy)-5-nitrobenzyl]amine 在 盐酸 、 甲醇 、 tin(II) chloride dihdyrate 作用下， 以 二氯甲烷 、 水 、 正丁醇 为溶剂， 生成 [3-[(allylmethylamino)methyl]-4-(2-diethylaminoethoxy)phenyl]-[4-(3-but-3-enyloxyphenyl)pyrimidin-2-yl]amine
  参考文献：
  名称：

  Discovery of Kinase Spectrum Selective Macrocycle (16E)-14-Methyl-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (SB1317/TG02), a Potent Inhibitor of Cyclin Dependent Kinases (CDKs), Janus Kinase 2 (JAK2), and Fms-like Tyrosine Kinase-3 (FLT3) for the Treatment of Cancer

  摘要：

  Herein, we describe the design, synthesis, and SAR of a series of unique small molecule macrocycles that show spectrum selective kinase inhibition of CDKs, JAK2, and FLT3. The most promising leads were assessed in vitro for their inhibition of cancer cell proliferation, solubility, CYP450 inhibition, and microsomal stability. This screening cascade revealed 26h as a preferred compound with target IC50 of 13, 73, and 56 nM for CDK2, JAK2 and FLT3, respectively. Pharmacokinetic (PK) studies of 26h in preclinical species showed good oral exposures. Oral efficacy was observed in colon (HCT-116) and lymphoma (Ramos) xenograft studies, in line with the observed PK/PD correlation. 26h (SB1317/TG02) was progressed into development in 2010 and is currently undergoing phase 1 clinical trials in advanced leukemias and multiple myeloma.

  DOI：

  10.1021/jm201112g
• 作为产物：
  描述：

  5-硝基水杨醛 在 三乙酰氧基硼氢化钠 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 allylmethyl-[2-(2-diethylaminoethoxy)-5-nitrobenzyl]amine
  参考文献：
  名称：

  Discovery of Kinase Spectrum Selective Macrocycle (16E)-14-Methyl-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (SB1317/TG02), a Potent Inhibitor of Cyclin Dependent Kinases (CDKs), Janus Kinase 2 (JAK2), and Fms-like Tyrosine Kinase-3 (FLT3) for the Treatment of Cancer

  摘要：

  Herein, we describe the design, synthesis, and SAR of a series of unique small molecule macrocycles that show spectrum selective kinase inhibition of CDKs, JAK2, and FLT3. The most promising leads were assessed in vitro for their inhibition of cancer cell proliferation, solubility, CYP450 inhibition, and microsomal stability. This screening cascade revealed 26h as a preferred compound with target IC50 of 13, 73, and 56 nM for CDK2, JAK2 and FLT3, respectively. Pharmacokinetic (PK) studies of 26h in preclinical species showed good oral exposures. Oral efficacy was observed in colon (HCT-116) and lymphoma (Ramos) xenograft studies, in line with the observed PK/PD correlation. 26h (SB1317/TG02) was progressed into development in 2010 and is currently undergoing phase 1 clinical trials in advanced leukemias and multiple myeloma.

  DOI：

  10.1021/jm201112g

文献信息

• HETEROALKYL LINKED PYRIMIDINE DERIVATIVES
  申请人：Blanchard Stephanie

  公开号：US20090258886A1

  公开（公告）日：2009-10-15

  The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to heteroalkyl 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 conditions or disorders associated with kinases.

  本发明涉及用作抗增殖剂的嘧啶化合物。更具体地说，本发明涉及杂原子烷基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在治疗增殖性疾病中使用这些化合物的用途。这些化合物可能作为药物对许多增殖性疾病，包括肿瘤和癌症以及与激酶相关的其他疾病或疾病的治疗有用。
• Heteroalkyl linked pyrimidine derivatives
  申请人：S*BIO Pte Ltd.

  公开号：US08143255B2

  公开（公告）日：2012-03-27

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

  本发明涉及嘧啶化合物，其可用作抗增殖剂。更具体地说，本发明涉及杂环烷基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。这些化合物可能作为药物用于治疗多种增殖性疾病，包括肿瘤和癌症以及与激酶相关的其他疾病或疾病。
• US8143255B2
  申请人：——

  公开号：US8143255B2

  公开（公告）日：2012-03-27
• US9133214B2
  申请人：——

  公开号：US9133214B2

  公开（公告）日：2015-09-15
• [EN] HETEROALKYL LINKED PYRIMIDINE DERIVATIVES<br/>[FR] DERIVES DE PYRIMIDINE A LIAISON HETEROALKYLE
  申请人：S BIO PTE LTD

  公开号：WO2007058628A1

  公开（公告）日：2007-05-24

  [EN] The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to heteroalkyl 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 conditions or disorders associated with kinases.
  [FR] L'invention concerne des composés de pyrimidine utiles comme agents antiprolifératifs. Plus particulièrement, l'invention concerne des composés de pyrimidine à liaison hétéroalkyle et substitués, des procédés de préparation, des compositions pharmaceutiques contenant ces composés et l'utilisation de ceux-ci dans le traitement de troubles prolifératifs. Ces composés, utilisés comme médicaments, sont destinés à traiter des troubles prolifératifs tels que des tumeurs et des cancers ainsi que d'autres troubles ou états pathologiques liés ou associés aux kinases.