4-pyridylacetic acid N-oxide | 89791-90-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-pyridylacetic acid N-oxide
• 英文别名: 4-pyridine acetic acid N-oxide；4-Pyridineacetic acid 1-oxide；2-(1-oxidopyridin-1-ium-4-yl)acetic acid
• CAS: 89791-90-2
• 化学式: C₇H₇NO₃
• 分子量: 153.137
• InChiKey: JBAPHLHEVPGEIV-UHFFFAOYSA-N

物化性质

• 熔点：
  144-145 °C (decomp)(Solv: ethanol (64-17-5))
• 沸点：
  445.9±20.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  62.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-pyridylacetic acid N-oxide 在 甲烷磺酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 1-[4-(8-chloro-6,6-dioxo-5H-[1]benzothiepino[4,3-b]pyridin-11-ylidene)piperidin-1-yl]-2-(1-oxidopyridin-1-ium-4-yl)ethanone
  参考文献：
  名称：

  Inhibitors of farnesyl protein transferase. synthesis and biological activity of amide and cyanoguanidine derivatives containing a 5,11-dihydro[1]benzthiepin, benzoxepin, and benzazepin [4,3-b]pyridine ring system

  摘要：

  Bioisosteric replacement of the C-6 carbon atom in piperidine I and piperazine II with S, O, and N heteroatoms is described. Amide and cyanoguanidine derivatives of these compounds were evaluated in vitro and found to be good inhibitors of farnesyl-protein transferase. An improved method of preparing the 5,11-dihydro-[1]-benzthiepin nucleus 6 was accomplished in high yield and with excellent regioselectivity using an AlCl3 melt protocol. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00439-9
• 作为产物：
  描述：

  吡啶-4(1H)-硫酮 在 盐酸 、 ammonium hydroxide 、 sodium hydroxide 、 甲基安非他命 、 氯 、 丙酮 作用下， 生成 4-pyridylacetic acid N-oxide
  参考文献：
  名称：

  Naito; Dohmori, Pharmaceutical Bulletin, 1955, vol. 3, p. 38,41

  摘要：

  DOI：

文献信息

• Structure−Activity Relationship of 3-Substituted <i>N</i>-(Pyridinylacetyl)-4- (8-chloro-5,6-dihydro-11<i>H</i>-benzo[5,6]cyclohepta[1,2-<i>b</i>]pyridin-11-ylidene)- piperidine Inhibitors of Farnesyl-Protein Transferase:  Design and Synthesis of in Vivo Active Antitumor Compounds
  作者：F. George Njoroge、Bancha Vibulbhan、Dinananth F. Rane、W. Robert Bishop、Joanne Petrin、Robert Patton、Mathew S. Bryant、K.-J. Chen、Amin A. Nomeir、C.-C. Lin、Ming Liu、Ivan King、Jianping Chen、Suining Lee、Bohdan Yaremko、Janet Dell、Philip Lipari、Michael Malkowski、Zujun Li、Joseph Catino、Ronald J. Doll、V. Girijavallabhan、Ashit K. Ganguly

  DOI：10.1021/jm970464g

  日期：1997.12.1

  Ras farnesyl-protein transferase (FPT) inhibitors are described. A comprehensive structure-activity relationship (SAR) study of compounds arising from substitution at the 3-position of the tricyclic pyridine ring system has been explored. In the case of halogens, the chloro, bromo, and iodo analogues 19, 22, and 28 were found to be equipotent. However, the fluoro analogue 17 was an order of magnitude

  描述了新型三环Ras法呢基蛋白转移酶（FPT）抑制剂。已经探索了由三环吡啶环系统的3位取代产生的化合物的全面构效关系（SAR）研究。对于卤素，发现氯，溴和碘类似物19、22和28等价。但是，氟类似物17的活性降低了一个数量级。较小的烷基取代基（例如甲基）会产生非常有效的FPT抑制剂（SCH 56580），而引入较大的取代基（例如化合物33的叔丁基或化合物29或苯基）会导致FPT抑制剂失活。3位的极性基团（如氨基5，烷基氨基6和羟基12）的活性较低。化合物SCH 44342在体内没有明显的抗肿瘤活性，3-溴取代的吡啶基N-氧化物酰胺类似物38是有效的FPT抑制剂，以50 mpk的qid给药和10 mpk的52％给药时，可使肿瘤生长降低81％。这些化合物是非肽类，不包含巯基。它们选择性抑制FPT，而不抑制香叶基香叶基蛋白转移酶1（GGPT-1）。它们还抑制COS猴肾细胞中的H-Ras加工和Ras转化细胞的软琼脂生长。
• Novel farnesyl protein transferase inhibitors as antitumor agents
  申请人：Schering Corporation

  公开号：US20040122018A1

  公开（公告）日：2004-06-24

  Disclosed are novel tricyclic compounds represented by the formula (1.0): 1 and a pharmaceutically acceptable salt or solvate thereof. The compounds are useful for inhibiting farnesyl protein transferase. Also disclosed are pharmaceutical compositions comprising compounds of formula 1.0. Also disclosed are methods of treating cancer using the compounds of formula 1.0.

  揭示了由式（1.0）表示的新型三环化合物： 1 及其药学上可接受的盐或溶剂。这些化合物对于抑制法尼西基蛋白转移酶是有用的。还揭示了包括式1.0化合物的药物组合物。还揭示了使用式1.0化合物治疗癌症的方法。
• Method of treating cancer using FPT inhibitors and antineoplastic agents
  申请人：Schering Corporation

  公开号：US20040006087A1

  公开（公告）日：2004-01-08

  Disclosed is a method of treating cancer in a patient in need of such treatment comprising administering a therapeutically effective amount of an FPT inhibitor and therapeutically effective amounts of one or more antineoplastic agents. Methods of treating non small cell lung cancer, squamous cell cancer of the head and neck, CML, AML, non-Hodgkin's lymphoma and multiple myeloma are disclosed.

  揭示了一种治疗癌症的方法，包括向需要此类治疗的患者施用治疗有效量的FPT抑制剂和治疗有效量的一种或多种抗肿瘤药物。公开了治疗非小细胞肺癌、头颈部鳞状细胞癌、慢性髓细胞白血病、急性髓细胞白血病、非霍奇金淋巴瘤和多发性骨髓瘤的方法。
• Phenyl-substituted tricyclic inhibitors of farnesyl-protein transferase
  申请人：Schering Corporation

  公开号：US06218401B1

  公开（公告）日：2001-04-17

  Novel phenyl-substituted tricyclic compounds and pharmaceutical compositions are disclosed which are inhibitors of the enzyme, farnesyl protein transferase. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering the novel halo-N-substituted urea compound to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammals such as a human.

  本发明揭示了新型苯基取代的三环化合物和药物组合物，它们是麦角醇蛋白转移酶的抑制剂。还揭示了一种抑制Ras功能从而抑制细胞异常生长的方法。该方法包括向生物系统施用新型卤代-N-取代脲化合物。特别是，该方法抑制了哺乳动物（如人类）中细胞的异常生长。
• Synthesis of C-11 Methyl-Substituted Benzocycloheptapyridine Inhibitors of Farnesyl Protein Transferase
  作者：F. George Njoroge、Bancha Vibulbhan、Jesse K. Wong、Steven K. White、Shing-Chun Wong、Nicholas I. Carruthers、James J. Kaminski、Ronald J. Doll、V. Girijavallabhan、Ashit K. Ganguly

  DOI：10.1021/ol990218u

  日期：1999.11.1

  text] Synthesis of C-11 methyl-substituted benzocycloheptylpyridine tricyclic compounds has been achieved via two different methods. Methylation of C-11 has been effected by treatment of amine 4 with BuLi followed by Mel quenching. In a similar procedure, introduction of a C-11 substituent with concomitant rearrangement of the exocyclic double bond has been carried out. Potent farnesyl protein transferase

  通过两种不同的方法已经完成了C-11甲基取代的苯并环庚基吡啶三环化合物的合成。C-11的甲基化是通过用BuLi处理胺4，然后进行梅尔猝灭来实现的。用相似的方法，引入了带有环外双键的重排的C-11取代基。使用上述方法已经合成了有效的法呢基蛋白转移酶抑制剂。