4-chloro-2,6-dimethyl-8-quinolinecarboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-chloro-2,6-dimethyl-8-quinolinecarboxamide
• 英文别名: 4-Chloro-2,6-dimethylquinoline-8-carboxamide；4-chloro-2,6-dimethylquinoline-8-carboxamide
• 化学式: C₁₂H₁₁ClN₂O
• 分子量: 234.685
• InChiKey: KNKMDXCWCRDYMF-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：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  56
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,6-二甲基苄胺 、 4-chloro-2,6-dimethyl-8-quinolinecarboxamide 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 以36%的产率得到4-{[(2,6-dimethylphenyl)methyl]amino}-2,6-dimethyl-8-quinolinecarboxamide
  参考文献：
  名称：

  Discovery of 4-Amino-8-quinoline Carboxamides as Novel, Submicromolar Inhibitors of NAD-Hydrolyzing Enzyme CD38

  摘要：

  Starting from the micromolar 8-quinoline carboxamide high-throughput screening hit la, a systematic exploration of the structure activity relationships (SAR) of the 4-, 6-, and 8-substituents of the quinoline ring resulted in the identification of approximately 10-100-fold more potent human CD38 inhibitors. Several of these molecules also exhibited pharmacokinetic parameters suitable for in vivo animal studies, including low clearances and decent oral bioavailability. Two of these CD38 inhibitors, 1ah and 1ai, were shown to elevate NAB tissue levels in liver and muscle in a diet-induced obese (DIO) C57BL/6 mouse model. These inhibitor tool compounds will enable further biological studies of the CD38 enzyme as well as the investigation of the therapeutic implications of NAD enhancement in disease models of abnormally low NAD.

  DOI：

  10.1021/acs.jmedchem.5b00992
• 作为产物：
  描述：

  5-溴氨基苯甲酸甲酯 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 氨 、 caesium carbonate 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 1.0h， 生成 4-chloro-2,6-dimethyl-8-quinolinecarboxamide
  参考文献：
  名称：

  Discovery of 4-Amino-8-quinoline Carboxamides as Novel, Submicromolar Inhibitors of NAD-Hydrolyzing Enzyme CD38

  摘要：

  Starting from the micromolar 8-quinoline carboxamide high-throughput screening hit la, a systematic exploration of the structure activity relationships (SAR) of the 4-, 6-, and 8-substituents of the quinoline ring resulted in the identification of approximately 10-100-fold more potent human CD38 inhibitors. Several of these molecules also exhibited pharmacokinetic parameters suitable for in vivo animal studies, including low clearances and decent oral bioavailability. Two of these CD38 inhibitors, 1ah and 1ai, were shown to elevate NAB tissue levels in liver and muscle in a diet-induced obese (DIO) C57BL/6 mouse model. These inhibitor tool compounds will enable further biological studies of the CD38 enzyme as well as the investigation of the therapeutic implications of NAD enhancement in disease models of abnormally low NAD.

  DOI：

  10.1021/acs.jmedchem.5b00992

文献信息

• COMPOUNDS WHICH SPECIFICALLY BIND TO CD38 FOR USE IN THE TREATMENT OF NEURODEGENERATIVE AND INFLAMMATORY DISEASES
  申请人：ENCEFA

  公开号：EP3658586A1

  公开（公告）日：2020-06-03
• [EN] COMPOUNDS WHICH SPECIFICALLY BIND TO CD38 FOR USE IN THE TREATMENT OF NEURODEGENERATIVE AND INFLAMMATORY DISEASES<br/>[FR] COMPOSÉS SE LIANT DE MANIÈRE SPÉCIFIQUE À CD38 POUR UNE UTILISATION DANS LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES ET INFLAMMATOIRES
  申请人：ENCEFA

  公开号：WO2019020643A1

  公开（公告）日：2019-01-31

  The present invention relates to a compound, which specifically binds to CD38, for use as a medicament in the prevention and/or treatment of a neurodegenerative disease and/or an inflammatory disease, by the opening of NAADP receptors Two Pore Channels TPC and/or TPC2, wherein said compound activates the opening of NAADP receptors Two Pore Channels TPC1 and/or TPC2.
• Discovery of 4-Amino-8-quinoline Carboxamides as Novel, Submicromolar Inhibitors of NAD-Hydrolyzing Enzyme CD38
  作者：J. David Becherer、Eric E. Boros、Tiffany Y. Carpenter、David J. Cowan、David N. Deaton、Curt D. Haffner、Michael R. Jeune、Istvan W. Kaldor、J. Chuck Poole、Frank Preugschat、Tara R. Rheault、Christie A. Schulte、Barry G. Shearer、Todd W. Shearer、Lisa M. Shewchuk、Terrence L. Smalley、Eugene L. Stewart、J. Darren Stuart、John C. Ulrich

  DOI：10.1021/acs.jmedchem.5b00992

  日期：2015.9.10

  Starting from the micromolar 8-quinoline carboxamide high-throughput screening hit la, a systematic exploration of the structure activity relationships (SAR) of the 4-, 6-, and 8-substituents of the quinoline ring resulted in the identification of approximately 10-100-fold more potent human CD38 inhibitors. Several of these molecules also exhibited pharmacokinetic parameters suitable for in vivo animal studies, including low clearances and decent oral bioavailability. Two of these CD38 inhibitors, 1ah and 1ai, were shown to elevate NAB tissue levels in liver and muscle in a diet-induced obese (DIO) C57BL/6 mouse model. These inhibitor tool compounds will enable further biological studies of the CD38 enzyme as well as the investigation of the therapeutic implications of NAD enhancement in disease models of abnormally low NAD.