3-(hydroxymethyl)-1,4-dihydrocinnolin-4-one | 1342948-21-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3-(hydroxymethyl)-1,4-dihydrocinnolin-4-one
• 英文别名: 3-(hydroxymethyl)-4-oxo-1,4-dihydrocinnoline；3-hydroxymethyl-1H-cinnolin-4-one；3-(hydroxymethyl)-4(1H)-Cinnolinone；3-(hydroxymethyl)-1H-cinnolin-4-one
• CAS: 1342948-21-3
• 化学式: C₉H₈N₂O₂
• 分子量: 176.175
• InChiKey: FQPOVTLQIPNNSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  61.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(hydroxymethyl)-1,4-dihydrocinnolin-4-one 在 ammonium cerium (IV) nitrate 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 28.0h， 生成 1-(3-methylbenzoyl)-3-[(tetrahydro-2H-pyran-2-yloxy)-methyl]cinnolin-4(1H)-one
  参考文献：
  名称：

  Cinnoline derivatives as human neutrophil elastase inhibitors

  摘要：

  Compounds that can effectively inhibit the proteolytic activity of human neutrophil elastase (HNE) represent promising therapeutics for treatment of inflammatory diseases. We present here the synthesis, structure-activity relationship analysis, and biological evaluation of a new series of HNE inhibitors with a cinnoline scaffold. These compounds exhibited HNE inhibitory activity but had lower potency compared to N-benzoylindazoles previously reported by us. On the other hand, they exhibited increased stability in aqueous solution. The most potent compound, 18a, had a good balance between HNE inhibitory activity (IC50 value = 56 nM) and chemical stability (t(1/2) = 114 min). Analysis of reaction kinetics revealed that these cinnoline derivatives were reversible competitive inhibitors of HNE. Furthermore, molecular docking studies of the active products into the HNE binding site revealed two types of HNE inhibitors: molecules with cinnolin-4(1H)-one scaffold, which were attacked by the HNE Ser195 hydroxyl group at the amido moiety, and cinnoline derivatives containing an ester function at C-4, which is the point of attack of Ser195.

  DOI：

  10.3109/14756366.2015.1057718
• 作为产物：
  描述：

  3-(2-氨基苯基)-2-丙炔-1-醇 在 盐酸 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 18.0h， 以42%的产率得到3-(hydroxymethyl)-1,4-dihydrocinnolin-4-one
  参考文献：
  名称：

  [EN] MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)
  [FR] MODULATEURS DU STIMULATEUR DES GÈNES DE L'INTERFÉRON (SING)

  摘要：

  本发明涉及式(I)化合物及其作为STING（干扰素基因刺激剂）调节剂的盐、立体异构体、互变异构体或N-氧化物。本发明进一步涉及式(I)化合物作为药物的应用以及包含该化合物的药物组合物。

  公开号：

  WO2019238786A1

文献信息

• [EN] MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)<br/>[FR] MODULATEURS DU STIMULATEUR DES GÈNES DE L'INTERFÉRON (SING)
  申请人：RYVU THERAPEUTICS S A

  公开号：WO2019238786A1

  公开（公告）日：2019-12-19

  The present invention relates to compounds of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof that are useful as modulators of STING (Stimulator of Interferon Genes). The present invention further relates to the compounds of formula (I) for use as a medicament and to a pharmaceutical composition comprising said compounds.

  本发明涉及式(I)化合物及其作为STING（干扰素基因刺激剂）调节剂的盐、立体异构体、互变异构体或N-氧化物。本发明进一步涉及式(I)化合物作为药物的应用以及包含该化合物的药物组合物。
• A convenient and efficient protocol for the synthesis of 4(1H)-cinnolones, 1,4-dihydrocinnolines, and cinnolines in aqueous medium: application for detection of nitrite ions
  作者：Raju Dey、Brindaban C. Ranu

  DOI：10.1016/j.tet.2011.09.016

  日期：2011.11

  3-Aryl/alkyl-4(1H)-cinnolones are obtained in one step from 2-aryl/alkylethynyl aniline by reaction with sodium nitrite and dilute hydrochloric acid via Richter cyclization. The alkyl cinnolones on reduction with Sn/HCl furnish 1,4-dihydro-3-alkylcinnolines, which are converted to 3-alkylcinnolines by treatment with NaNO2/HCl/KI. The whole process is carried out in aqueous medium at ambient temperature within a short reaction period. The reaction of 2-phenylethynyl aniline exhibits yellow color with UV absorbance at 391 nm and has been successfully tested for the detection of nitrite ions in water at parts per million concentration. (C) 2011 Elsevier Ltd. All rights reserved.
• MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)
  申请人：Ryvu Therapeutics S.A.

  公开号：EP3807264A1

  公开（公告）日：2021-04-21
• Cinnoline derivatives as human neutrophil elastase inhibitors
  作者：Maria Paola Giovannoni、Igor A. Schepetkin、Letizia Crocetti、Giovanna Ciciani、Agostino Cilibrizzi、Gabriella Guerrini、Andrei I. Khlebnikov、Mark T. Quinn、Claudia Vergelli

  DOI：10.3109/14756366.2015.1057718

  日期：2016.7.3

  Compounds that can effectively inhibit the proteolytic activity of human neutrophil elastase (HNE) represent promising therapeutics for treatment of inflammatory diseases. We present here the synthesis, structure-activity relationship analysis, and biological evaluation of a new series of HNE inhibitors with a cinnoline scaffold. These compounds exhibited HNE inhibitory activity but had lower potency compared to N-benzoylindazoles previously reported by us. On the other hand, they exhibited increased stability in aqueous solution. The most potent compound, 18a, had a good balance between HNE inhibitory activity (IC50 value = 56 nM) and chemical stability (t(1/2) = 114 min). Analysis of reaction kinetics revealed that these cinnoline derivatives were reversible competitive inhibitors of HNE. Furthermore, molecular docking studies of the active products into the HNE binding site revealed two types of HNE inhibitors: molecules with cinnolin-4(1H)-one scaffold, which were attacked by the HNE Ser195 hydroxyl group at the amido moiety, and cinnoline derivatives containing an ester function at C-4, which is the point of attack of Ser195.