4(3H)-Quinazolinone, 6-chloro-3-methyl-2-(methylthio)- | 23070-08-8

• 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: 4(3H)-Quinazolinone, 6-chloro-3-methyl-2-(methylthio)-
• 英文别名: 6-chloro-3-methyl-2-methylsulfanylquinazolin-4-one
• CAS: 23070-08-8
• 化学式: C₁₀H₉ClN₂OS
• mdl: MFCD01928010
• 分子量: 240.713
• InChiKey: DAMIMMZCNRKRDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  58
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4(3H)-Quinazolinone, 6-chloro-3-methyl-2-(methylthio)- 、 2-(4-甲氧苯基)乙胺 在 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 24.0h， 生成 6-chloro-2-[2-(4-methoxyphenyl)ethylamino]-3-methyl-3H-quinazolin-4-one
  参考文献：
  名称：

  Identification and optimization of a new series of anti-tubercular quinazolinones

  摘要：

  A high throughput phenotypic screening against Mycobacterium smegmatis led us to the discovery of a new class of bacteriostatic, highly hydrophobic antitubercular quinazolinones that potently inhibited the in vitro growth of either extracellular or intramacrophagic M. tuberculosis (Mtb), via modulation of an unidentified but yet novel target. Optimization of the initial hit compound culminated in the identification of potent but poorly soluble Mtb growth inhibitors, three of which were progressed to in vivo efficacy studies. Despite nanomolar in vitro potency and attractive PK properties, none of these compounds was convincingly potent in our in vivo mouse tuberculosis models. This lack of efficacy may be linked to the poor drug-likeness of the test molecules and/or to the properties of the target.[GRAPHICS](C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.09.043
• 作为产物：
  描述：

  2-氨基-5-氯苯甲酸 在 溶剂黄146 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 29.0h， 生成 4(3H)-Quinazolinone, 6-chloro-3-methyl-2-(methylthio)-
  参考文献：
  名称：

  Identification and optimization of a new series of anti-tubercular quinazolinones

  摘要：

  A high throughput phenotypic screening against Mycobacterium smegmatis led us to the discovery of a new class of bacteriostatic, highly hydrophobic antitubercular quinazolinones that potently inhibited the in vitro growth of either extracellular or intramacrophagic M. tuberculosis (Mtb), via modulation of an unidentified but yet novel target. Optimization of the initial hit compound culminated in the identification of potent but poorly soluble Mtb growth inhibitors, three of which were progressed to in vivo efficacy studies. Despite nanomolar in vitro potency and attractive PK properties, none of these compounds was convincingly potent in our in vivo mouse tuberculosis models. This lack of efficacy may be linked to the poor drug-likeness of the test molecules and/or to the properties of the target.[GRAPHICS](C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.09.043

文献信息

• Ram, Vishnu J.; Kushwaha, Dinesh S., Liebigs Annalen der Chemie, 1990, # 7, p. 701 - 702
  作者：Ram, Vishnu J.、Kushwaha, Dinesh S.

  DOI：——

  日期：——
• Identification and optimization of a new series of anti-tubercular quinazolinones
  作者：Cédric Couturier、Christine Lair、Alain Pellet、Anna Upton、Takushi Kaneko、Corinne Perron、Eric Cogo、Jérome Menegotto、Armin Bauer、Bodo Scheiper、Sophie Lagrange、Eric Bacqué

  DOI：10.1016/j.bmcl.2016.09.043

  日期：2016.11

  A high throughput phenotypic screening against Mycobacterium smegmatis led us to the discovery of a new class of bacteriostatic, highly hydrophobic antitubercular quinazolinones that potently inhibited the in vitro growth of either extracellular or intramacrophagic M. tuberculosis (Mtb), via modulation of an unidentified but yet novel target. Optimization of the initial hit compound culminated in the identification of potent but poorly soluble Mtb growth inhibitors, three of which were progressed to in vivo efficacy studies. Despite nanomolar in vitro potency and attractive PK properties, none of these compounds was convincingly potent in our in vivo mouse tuberculosis models. This lack of efficacy may be linked to the poor drug-likeness of the test molecules and/or to the properties of the target.[GRAPHICS](C) 2016 Elsevier Ltd. All rights reserved.