N-(3-chloro-4-fluorophenyl)-8-methyl-6-(1,3-thiazol-5-yl)-4-quinazolinamine

• 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: N-(3-chloro-4-fluorophenyl)-8-methyl-6-(1,3-thiazol-5-yl)-4-quinazolinamine
• 英文别名: N-(3-chloro-4-fluorophenyl)-8-methyl-6-(1,3-thiazol-5-yl)quinazolin-4-amine
• 化学式: C₁₈H₁₂ClFN₄S
• 分子量: 370.837
• InChiKey: BIFSNDSAGPUPAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  78.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氨基-5-溴-3-甲基苯甲酸 在 bis-triphenylphosphine-palladium(II) chloride 、 四乙基氯化铵一水合物 、 potassium carbonate 、 N,N-二甲基甲酰胺 作用下， 以 氯化亚砜 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 32.0h， 生成 N-(3-chloro-4-fluorophenyl)-8-methyl-6-(1,3-thiazol-5-yl)-4-quinazolinamine
  参考文献：
  名称：

  Discovery, Synthesis, and Biological Evaluation of Thiazoloquin(az)olin(on)es as Potent CD38 Inhibitors

  摘要：

  A series of thiazoloquin(az)olinones were synthesized and found to have potent inhibitory activity against CD38. Several of these compounds were also shown to have good pharmacokinetic properties and demonstrated the ability to elevate NAD levels in plasma, liver, and muscle tissue. In particular, compound 78c was given to diet induced obese (DIO) C57Bl6 mice, elevating NAD > 5-fold in liver and >1.2-fold in muscle versus control animals at a 2 h time point. The compounds described herein possess the most potent CD38 inhibitory activity of any small molecules described in the literature to date. The inhibitors should allow for a more detailed assessment of how NAD elevation via CD38 inhibition affects physiology in NAD deficient states.

  DOI：

  10.1021/jm502009h

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, Synthesis, and Biological Evaluation of Thiazoloquin(az)olin(on)es as Potent CD38 Inhibitors
  作者：Curt D. Haffner、J. David Becherer、Eric E. Boros、Rodolfo Cadilla、Tiffany Carpenter、David Cowan、David N. Deaton、Yu Guo、Wallace Harrington、Brad R. Henke、Michael R. Jeune、Istvan Kaldor、Naphtali Milliken、Kim G. Petrov、Frank Preugschat、Christie Schulte、Barry G. Shearer、Todd Shearer、Terrence L. Smalley、Eugene L. Stewart、J. Darren Stuart、John C. Ulrich

  DOI：10.1021/jm502009h

  日期：2015.4.23

  A series of thiazoloquin(az)olinones were synthesized and found to have potent inhibitory activity against CD38. Several of these compounds were also shown to have good pharmacokinetic properties and demonstrated the ability to elevate NAD levels in plasma, liver, and muscle tissue. In particular, compound 78c was given to diet induced obese (DIO) C57Bl6 mice, elevating NAD > 5-fold in liver and >1.2-fold in muscle versus control animals at a 2 h time point. The compounds described herein possess the most potent CD38 inhibitory activity of any small molecules described in the literature to date. The inhibitors should allow for a more detailed assessment of how NAD elevation via CD38 inhibition affects physiology in NAD deficient states.