1-甲基-1,3-二氢-2H-吡咯并[2,3-b]吡啶-2-酮 | 156136-84-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 中文名称: 1-甲基-1,3-二氢-2H-吡咯并[2,3-b]吡啶-2-酮
• 英文名称: 1-methyl-1H-pyrrolo[2,3-b]pyridin-2(3H)-one
• 英文别名: 1-methyl-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one；7-aza-N-methyloxindole；1-methyl-7-aza-2-indolinone；1-methyl-1H,2H,3H-pyrrolo[2,3-b]pyridin-2-one；1-methyl-3H-pyrrolo[2,3-b]pyridin-2-one
• CAS: 156136-84-4
• 化学式: C₈H₈N₂O
• 分子量: 148.164
• InChiKey: PIKWRIBNROHTRO-UHFFFAOYSA-N

物化性质

• 沸点：
  391.3±37.0 °C(Predicted)
• 密度：
  1.241±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-甲基-1,3-二氢-2H-吡咯并[2,3-b]吡啶-2-酮 在 tetraphosphorus decasulfide 、 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 以73%的产率得到1-甲基-1,3-二氢-2H-吡咯并[2,3-b]吡啶-2-硫酮
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 3. Structure-Activity Relationships for Inhibition of Protein Tyrosine Kinases by Nuclear-Substituted Derivatives of 2,2'-Dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamide)

  摘要：

  A series of indole-substituted 2,2'-dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamides) were prepared and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and the nonreceptor pp60(v-src) tyrosine kinase. The compounds were synthesized by conversion of appropriate 1-methyloxindoles to 1-methyl-2-indolinethiones with P2S5 followed by subsequent reaction with NaH and phenyl isocyanate and oxidative dimerization of the resulting 2,3-dihydro-N-phenyl-2-thioxo-1H-indole-3-carboxamides. The parent compound and many of the substituted analogues were moderately potent inhibitors of both kinase enzymes, but no clear relationships were seen between substitution on the indole ring and inhibitory activity, While 4-substituted compounds were generally inactive, 5-substituted derivatives with electron-withdrawing groups showed inhibitory activity. However, none of the substituted compounds showed significantly better activity than the unsubstituted parent compound. There was generally a good correlation between activity against the EGFR and pp60(v-src) kinases, but several compounds did show some specificity (>20-fold) of inhibition; 5-Cl and 5-Br derivatives preferentially inhibited pp60(v-src), while the 5-CF3 compound preferentially inhibited EGFR. Selected compounds from the series were found to inhibit the growth of Swiss 3T3 fibroblasts with IC(50)s in the range 2-25 mu M, the most active being 4-substituted derivatives. The compounds inhibited bFGF-mediated protein tyrosine phosphorylation in intact cells more effectively than EGFR- or PDGF-mediated phosphorylation.

  DOI：

  10.1021/jm00039a016
• 作为产物：
  描述：

  2-(2-氯吡啶-3-基)乙酸乙酯 在 三甲基铝 、 palladium diacetate 、 caesium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 3.08h， 生成 1-甲基-1,3-二氢-2H-吡咯并[2,3-b]吡啶-2-酮
  参考文献：
  名称：

  含有特权吖嗪的双环片段的多样性导向合成

  摘要：

  为基于片段的药物发现 (FBDD) 计划开发了一种创新且高效的基于试剂和支架的片段集的多样性导向合成 (DOS)。通过围绕三个优先的吖嗪核心采用方便的合成工具包，可以快速访问十二种不同的功能化双环支架，以有效调节生物分子。这些结构的特征在于通过氢键与不同生物靶标相互作用的关键基序和用于后续片段优化的有用生长点。

  DOI：

  10.1016/j.bmcl.2018.11.046

文献信息

• FUSED HETEROCYCLIC COMPOUNDS
  申请人：TANIGUCHI Takahiko

  公开号：US20110319394A1

  公开（公告）日：2011-12-29

  The present invention provides a compound which has the effect of PDE inhibition, and which is useful as an agent for preventing or treating schizophrenia. The compound is represented by the formula (I): wherein the symbols are defined in the specification.

  本发明提供了一种具有磷酸二酯酶抑制作用的化合物，可用作预防或治疗精神分裂症的药剂。该化合物由以下式表示（I）： 其中符号在规范中定义。
• 1,3-Dipolar Cycloaddition of Hydrazones with α-Oxo-ketenes: A Three-Component Stereoselective Entry to Pyrazolidinones and an Original Class of Spirooxindoles
  作者：Marc Presset、Kishor Mohanan、Marie Hamann、Yoann Coquerel、Jean Rodriguez

  DOI：10.1021/ol2016669

  日期：2011.8.5

  prepared efficiently by a three-component reaction involving a 1,3-dipolar cycloaddition of azomethine imines obtained from hydrazones with α-oxo-ketene dipolarophiles generated in situ. The reaction allows the creation of four covalent bonds and two contiguous chiral quaternary centers with excellent diastereoselectivity in a single catalyst/additive-free, highly atom-economical transformation. From a

  立体定义的单环，螺双环和双-螺旋三环吡唑并烷-3-酮可通过三组分反应高效制备，该反应涉及从中获得的偶氮甲亚胺与原位生成的α-氧代-乙烯酮双极性亲和剂的1,3-偶极环加成反应。该反应允许在单个催化剂/无添加剂，高度原子经济的转化中以优异的非对映选择性创建四个共价键和两个连续的手性季中心。从基本的观点来看，该反应在1，3-偶极环加成中引入α-氧代-乙烯酮作为有效的偶极亲和性。
• CGRP ANTAGONISTS
  申请人：Gottschling Dirk

  公开号：US20110059954A1

  公开（公告）日：2011-03-10

  The present invention relates to new CGRP-antagonists of general formula I wherein U, V, X, Y, R 1 , R 2 and R 3 are defined as stated hereinafter, the tautomers, the isomers, the diastereomers, the enantiomers, the hydrates, the mixtures thereof and the salts thereof and the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, pharmaceutical compositions containing these compounds, their use and processes for preparing them.

  本发明涉及一般式I的新的CGRP拮抗剂，其中U、V、X、Y、R1、R2和R3如下所述定义，其互变异构体、同分异构体、对映异构体、水合物、混合物及其盐和盐的水合物，特别是其与无机或有机酸或碱的生理上可接受的盐，含有这些化合物的药物组合物，其用途以及制备它们的过程。
• NOVEL COMPOUNDS
  申请人：Gottschling Dirk

  公开号：US20110195954A1

  公开（公告）日：2011-08-11

  The present invention relates to new CGRP-antagonists of general formula I wherein U, V, X, Y, R 1 , R 2 , R 3 and R 4 are defined as mentioned in the description, the tautomers thereof, the isomers thereof, the diastereomers thereof, the enantiomers thereof, the hydrates thereof, the mixtures thereof and the salts thereof as well as the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, medicaments containing these compounds, the use thereof and processes for the preparation thereof.

  本发明涉及一般式I的新CGRP拮抗剂，其中U、V、X、Y、R1、R2、R3和R4如描述中所述定义，其互变异构体、异构体、顺反异构体、对映异构体、水合物、混合物及其盐，以及其盐的水合物，特别是与无机或有机酸或碱形成的生理上可接受的盐，包含这些化合物的药物、其用途以及其制备方法。
• Synthesis of naphthyridin-2(1<i>H</i>)-one derivatives<i>via</i>ring expansion of 3-substituted-1<i>H</i>-pyrrolo[2,3-<i>b</i>]pyridin-2(3<i>H</i>)-one derivatives
  作者：C. Croix、S. Massip、M.-C. Viaud-Massuard

  DOI：10.1039/c8cc01518j

  日期：——

  reaction of 3-substituted 1H-pyrrolo[2,3-b]pyridin-2(3H)-one derivatives with sodium azide or azidotrimethylsilane under microwave irradiation provided 3- and 4-amino-naphthyridin-2(1H)-one derivatives through cycloaddition–ring expansion. The insertion of the azide into the α,β unsaturated carbonyl of 3-substituted pyrrolo[2,3-b]pyridin-2(3H)-one derivatives proceeded via an unusual rearrangement. This

  3-取代的1 H-吡咯并[2,3- b ]吡啶-2（3 H）-one衍生物与叠氮化钠或叠氮三甲基硅烷在微波辐射下的反应提供了3-和4-氨基萘啶2（1 H）通过环加成环扩环得到一个衍生物。将叠氮化物插入3-取代的吡咯并[2，3 - b ]吡啶-2-2（3H）-一衍生物的α，β不饱和羰基中是通过不寻常的重排进行的。该方法提供了39个中高收率的扩环实例。