Methyl β-(3,5-dimethyl-4-isoxazolyl)propionate | 154928-90-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: Methyl β-(3,5-dimethyl-4-isoxazolyl)propionate
• 英文别名: methyl 3-(3,5-dimethylisoxazol-4-yl)propanoate；methyl 3-(3,5-dimethyl-1,2-oxazol-4-yl)propanoate
• CAS: 154928-90-2
• 化学式: C₉H₁₃NO₃
• mdl: MFCD08701341
• 分子量: 183.207
• InChiKey: CCJKJNYCQZFBDN-UHFFFAOYSA-N

物化性质

• 沸点：
  276.4±35.0 °C(Predicted)
• 密度：
  1.094±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.555
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P264,P270,P301+P312,P330,P501
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  Methyl β-(3,5-dimethyl-4-isoxazolyl)propionate 在 氢氧化钾 、 草酰氯 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 3-(3,5-dimethyl-4-isoxazolyl)propanoyl chloride
  参考文献：
  名称：

  Metal-Catalyzed, Intramolecular Reactions of .alpha.-Diazo Ketones with Isoxazoles

  摘要：

  DOI：

  10.1021/jo00089a037
• 作为产物：
  描述：

  4-乙酰基-5-羰基己酸甲酯 在 盐酸羟胺 作用下， 以 甲醇 、 水 为溶剂， 反应 12.0h， 以91%的产率得到Methyl β-(3,5-dimethyl-4-isoxazolyl)propionate
  参考文献：
  名称：

  Metal-Catalyzed, Intramolecular Reactions of .alpha.-Diazo Ketones with Isoxazoles

  摘要：

  DOI：

  10.1021/jo00089a037

文献信息

• Hydroxyalkanoylaminolactams and related structures as inhibitors of a beta protein production
  申请人：——

  公开号：US20020052360A1

  公开（公告）日：2002-05-02

  This invention relates to novel lactams having the formula (I): 1 to their pharmaceutical compositions and to their methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of A&bgr;-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to &bgr;-amyloid production such as Alzheimer's disease and Down's Syndrome.

  本发明涉及具有公式(I)的新颖内酰胺：1及其药物组合物及其使用方法。这些新颖化合物抑制淀粉样前体蛋白的加工，更具体地说，抑制Aβ-肽的产生，从而防止神经系统中淀粉样蛋白沉积的形成。更具体地，本发明涉及治疗与β-淀粉样蛋白产生相关的神经系统疾病，如阿尔茨海默病和唐氏综合症。
• Hydroxyalkanoylaminolactams and related structures as inhibitors of A-beta protein production
  申请人：——

  公开号：US20030166636A1

  公开（公告）日：2003-09-04

  This invention relates to novel lactams having the formula (I): 1 to their pharmaceutical compositions and to their methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of A&bgr;-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to &bgr;-amyloid production such as Alzheimer's disease and Down's Syndrome.

  本发明涉及具有公式(I)的新颖内酰胺：及其药物组合物及其使用方法。这些新颖化合物抑制淀粉样前体蛋白的加工，更具体地说，抑制Aβ-肽的产生，从而防止神经性淀粉样蛋白沉积的形成。更具体地说，本发明涉及治疗与β-淀粉样蛋白产生相关的神经障碍，如阿尔茨海默病和唐氏综合症。
• Hydroxyalkanoylaminolactams and related structures as inhibitors of Alphabeta protein production
  申请人：Olson E. Richard

  公开号：US20070027132A1

  公开（公告）日：2007-02-01

  This invention relates to novel lactams having the formula (I): to their pharmaceutical compositions and to their methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of Aβ-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to β-amyloid production such as Alzheimer's disease and Down's Syndrome.

  本发明涉及具有公式（I）的新型内酰胺，其制药组合物以及使用方法。这些新型化合物抑制淀粉样前体蛋白的加工，更具体地抑制Aβ-肽的产生，从而防止神经沉积物的淀粉样蛋白形成。更具体地，本发明涉及与β-淀粉样蛋白产生相关的神经系统疾病的治疗，例如阿尔茨海默病和唐氏综合症。
• HYDROXYALKANOYLAMINOLACTAMS AND RELATED STRUCTURES AS INHIBITORS OF A BETA PROTEIN PRODUCTION
  申请人：Olson Richard E.

  公开号：US20080132482A1

  公开（公告）日：2008-06-05

  This invention relates to novel lactams having the formula (I): to their pharmaceutical compositions and to their methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of Aβ-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to β-amyloid production such as Alzheimer's disease and Down's Syndrome.

  本发明涉及具有公式（I）的新型内酰胺，它们的制药组合物以及它们的使用方法。这些新型化合物抑制淀粉样前体蛋白的处理，更具体地抑制Aβ肽的产生，从而防止神经元中淀粉样蛋白的沉积形成。更具体地，本发明涉及与β-淀粉样蛋白产生相关的神经系统疾病的治疗，例如阿尔茨海默病和唐氏综合症。
• Design and Synthesis of High Affinity Inhibitors of <i>Plasmodium falciparum</i> and <i>Plasmodium vivax N</i>-Myristoyltransferases Directed by Ligand Efficiency Dependent Lipophilicity (LELP)
  作者：Mark D. Rackham、James A. Brannigan、Kaveri Rangachari、Stephan Meister、Anthony J. Wilkinson、Anthony A. Holder、Robin J. Leatherbarrow、Edward W. Tate

  DOI：10.1021/jm500066b

  日期：2014.3.27

  N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both Plasmodium falciparum and P. vivax NMT and displays activity in vivo against a rodent malaria model. Here we describe the discovery of 34c through optimization of a previously described series. Development, guided by targeting a ligand efficiency dependent lipophilicity (LELP) score of less than 10, yielded a 100-fold increase in enzyme affinity and a 100-fold drop in lipophilicity with the addition of only two heavy atoms. 34c was found to be equipotent on chloroquine-sensitive and -resistant cell lines and on both blood and liver stage forms of the parasite. These data further validate NMT as an exciting drug target in malaria and support 34c as an attractive tool for further optimization.