pent-4-enoic acid (3-nitrophenyl)amide

• 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: pent-4-enoic acid (3-nitrophenyl)amide
• 英文别名: Pent-4-enoic acid (3-nitro-phenyl)-amide；N-(3-nitrophenyl)pent-4-enamide
• 化学式: C₁₁H₁₂N₂O₃
• mdl: MFCD22381434
• 分子量: 220.228
• InChiKey: SKLKHUWVVPZLNS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  pent-4-enoic acid (3-nitrophenyl)amide 在 甲醇 、 tin(II) chloride dihdyrate 作用下， 以 二氯甲烷 为溶剂， 以96%的产率得到pent-4-enoic acid (3-aminophenyl)amide
  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：

  4-戊烯酸 、 间硝基苯胺 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 生成 pent-4-enoic acid (3-nitrophenyl)amide
  参考文献：
  名称：

  快速构建新型杂环化合物的新合成技术——第 1 部分：Dess - Martin 高碘烷与苯胺和相关化合物的反应

  摘要：

  高价碘试剂 Dess-Martin periodinane 和 IBX 与一系列苯胺的不寻常行为导致仅在一次合成操作中形成复杂的杂环（见方案）。此外，这些转化的底物可从现成的商业构件中一步获得。还探索了这些周期素与苯胺相互作用的机制。这种令人兴奋的新型化学反应是在 CP 分子的全合成过程中发现的，并产生了与化学生物学研究和药物研究相关的化合物。

  DOI：

  10.1002/(sici)1521-3773(20000204)39:3<622::aid-anie622>3.0.co;2-b

文献信息

• Iodine(V) Reagents in Organic Synthesis. Part 1. Synthesis of Polycyclic Heterocycles via Dess−Martin Periodinane-Mediated Cascade Cyclization:  Generality, Scope, and Mechanism of the Reaction
  作者：K. C. Nicolaou、P. S. Baran、Y.-L. Zhong、K. Sugita

  DOI：10.1021/ja012124x

  日期：2002.3.1

  reaction of unsaturated anilides discovered during the total synthesis of the CP-molecules (phomoidrides A and B) are delineated. A plethora of heterocyclic compounds are accessible by employing gamma,delta-unsaturated amides (derived from anilines and carboxylic acids), urethanes, or ureas (derived from isocyanates and allylic alcohols and amines) as substrates. Optimization of the reaction led to room-temperature

  描述了在 CP 分子（phomoidrides A 和 B）的全合成过程中发现的不饱和苯胺的 Dess-Martin periodinane 介导的环化反应的范围、一般性和机制。通过使用γ,δ-不饱和酰胺（衍生自苯胺和羧酸）、氨基甲酸酯或脲（衍生自异氰酸酯和烯丙醇和胺）作为底物，可以获得大量杂环化合物。反应的优化导致室温条件，而同位素标记研究为这种级联反应提供了机械原理。
• 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