4-[(7-氯-2-甲基喹啉-4-基)氨基]-2-(二乙基氨基甲基)苯酚 | 102374-64-1

• 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
• 中文名称: 4-[(7-氯-2-甲基喹啉-4-基)氨基]-2-(二乙基氨基甲基)苯酚
• 英文名称: 4-(7-chloro-2-methylquinolin-4-ylamino)-2-((diethylamino)methyl)phenol
• 英文别名: 4-[(7-Chloro-2-methylquinolin-4-yl)amino]-2-(diethylaminomethyl)phenol
• CAS: 102374-64-1
• 化学式: C₂₁H₂₄ClN₃O
• 分子量: 369.894
• InChiKey: PEASJFIJLUGKGU-UHFFFAOYSA-N

物化性质

• 熔点：
  183-184 °C
• 沸点：
  478.7±45.0 °C(Predicted)
• 密度：
  1.236±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  48.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[(7-氯-2-甲基喹啉-4-基)氨基]-2-(二乙基氨基甲基)苯酚 、 对硝基苯磺酰氯 在 N,N-二异丙基乙胺 作用下， 以 丙酮 为溶剂， 反应 3.0h， 以76%的产率得到N-(7-chloro-2-methylquinolin-4-yl)-N-(3-((diethylamino)methyl)-4-hydroxyphenyl) 4-nitrobenzenesulfonamide
  参考文献：
  名称：

  Novel, potent, orally bioavailable and selective mycobacterial ATP synthase inhibitors that demonstrated activity against both replicating and non-replicating M. tuberculosis

  摘要：

  The mycobacterial F0F1-ATP synthase (ATPase) is a validated target for the development of tuberculosis (TB) therapeutics. Therefore, a series of eighteen novel compounds has been designed, synthesized and evaluated against Mycobacterium smegmatis ATPase. The observed ATPase inhibitory activities (IC50) of these compounds range between 0.36 and 5.45 mu M. The lead compound 9d [N-(7-chloro-2-methylquinolin-4-yl)-N-(34(diethylamino)methyl)-4-hydroxyphenyl)-2,3-dichlorobenzenesulfonamidel with null cytotoxicity (CC50 >300 mu g/mL) and excellent anti-mycobacterial activity and selectivity (mycobacterium ATPase IC50 = 0.51 mu M, mammalian ATPase IC50 >100 mu M, and selectivity >200) exhibited a complete growth inhibition of replicating Mycobacterium tuberculosis H37Rv at 3.12 mu g/mL. In addition, it also exhibited bactericidal effect (approximately 2.4 log(10) reductions in CFU) in the hypoxic culture of nonreplicating M. tuberculosis at 100 mu g/mL (32-fold of its MIC) as compared to positive control isoniazid [approximately 0.2 log(10) reduction in CFU at 5 mu g/mL (50-fold of its MIC)]. The pharmacokinetics of 9d after p.o. and IV administration in male Sprague Dawley rats indicated its quick absorption, distribution and slow elimination. It exhibited a high volume of distribution (V-ss, 0.41 L/kg), moderate clearance (0.06 L/h/kg), long half-life (4.2 h) and low absolute bioavailability (1.72%). In the murine model system of chronic TB, 9d showed 2.12 log(10) reductions in CFU in both lung and spleen at 173 mu mol/kg dose as compared to the growth of untreated control group of Balb/C male mice infected with replicating M. tuberculosis H37Rv. The in vivo efficacy of 9d is at least double of the control drug ethambutol. These results suggest 9d as a promising candidate molecule for further preclinical evaluation against resistant TB strains. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.060
• 作为产物：
  描述：

  4'-甲氧基乙酰苯胺 在 盐酸 、 三溴化硼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 4-[(7-氯-2-甲基喹啉-4-基)氨基]-2-(二乙基氨基甲基)苯酚
  参考文献：
  名称：

  Novel, potent, orally bioavailable and selective mycobacterial ATP synthase inhibitors that demonstrated activity against both replicating and non-replicating M. tuberculosis

  摘要：

  The mycobacterial F0F1-ATP synthase (ATPase) is a validated target for the development of tuberculosis (TB) therapeutics. Therefore, a series of eighteen novel compounds has been designed, synthesized and evaluated against Mycobacterium smegmatis ATPase. The observed ATPase inhibitory activities (IC50) of these compounds range between 0.36 and 5.45 mu M. The lead compound 9d [N-(7-chloro-2-methylquinolin-4-yl)-N-(34(diethylamino)methyl)-4-hydroxyphenyl)-2,3-dichlorobenzenesulfonamidel with null cytotoxicity (CC50 >300 mu g/mL) and excellent anti-mycobacterial activity and selectivity (mycobacterium ATPase IC50 = 0.51 mu M, mammalian ATPase IC50 >100 mu M, and selectivity >200) exhibited a complete growth inhibition of replicating Mycobacterium tuberculosis H37Rv at 3.12 mu g/mL. In addition, it also exhibited bactericidal effect (approximately 2.4 log(10) reductions in CFU) in the hypoxic culture of nonreplicating M. tuberculosis at 100 mu g/mL (32-fold of its MIC) as compared to positive control isoniazid [approximately 0.2 log(10) reduction in CFU at 5 mu g/mL (50-fold of its MIC)]. The pharmacokinetics of 9d after p.o. and IV administration in male Sprague Dawley rats indicated its quick absorption, distribution and slow elimination. It exhibited a high volume of distribution (V-ss, 0.41 L/kg), moderate clearance (0.06 L/h/kg), long half-life (4.2 h) and low absolute bioavailability (1.72%). In the murine model system of chronic TB, 9d showed 2.12 log(10) reductions in CFU in both lung and spleen at 173 mu mol/kg dose as compared to the growth of untreated control group of Balb/C male mice infected with replicating M. tuberculosis H37Rv. The in vivo efficacy of 9d is at least double of the control drug ethambutol. These results suggest 9d as a promising candidate molecule for further preclinical evaluation against resistant TB strains. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.060

文献信息

• [EN] N-(3-((DIETHYLAMINO) METHYL)-4-HYDROXYPHENYL)-N-(QUINOLIN-4-YL) SULFONAMIDES FOR THE TREATMENT OF TUBERCULOSIS AND PROCESS OF PREPARATION THEREOF<br/>[FR] SULFAMIDES N-(3-((DIÉTHYLAMINO) MÉTHYL)-4-HYDROXYPHÉNYL)-N-(QUINOLIN-4-YL) UTILES POUR LE TRAITEMENT DE LA TURBERCULOSE ET PROCÉDÉ DE PRÉPARATION DE CES DERNIERS
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2013102936A4

  公开（公告）日：2013-09-12
• Sen; Basu, Journal of the Indian Chemical Society, 1957, vol. 34, p. 836
  作者：Sen、Basu

  DOI：——

  日期：——