2-methyl-3-(4-phenoxyphenyl)-5,6,7,8-tetrahydroquinolin-4(1H)-one

• 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: 2-methyl-3-(4-phenoxyphenyl)-5,6,7,8-tetrahydroquinolin-4(1H)-one
• 英文别名: MJM170；2-methyl-3-(4-phenoxyphenyl)-5,6,7,8-tetrahydro-1H-quinolin-4-one
• 化学式: C₂₂H₂₁NO₂
• 分子量: 331.414
• InChiKey: SGOVRJBWXWZWSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-羟基-2-甲基喹啉 在 platinum(IV) oxide 、 四(三苯基膦)钯 、 氢溴酸 、 氢气 、 碘 、 potassium carbonate 、 溶剂黄146 、 正丁胺 、 potassium iodide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 118.75h， 生成 2-methyl-3-(4-phenoxyphenyl)-5,6,7,8-tetrahydroquinolin-4(1H)-one
  参考文献：
  名称：

  [EN] COMPOUNDS AND METHODS FOR TREATING, DETECTING, AND IDENTIFYING COMPOUNDS TO TREAT APICOMPLEXAN PARASITIC DISEASES
  [FR] COMPOSÉS ET MÉTHODES DE TRAITEMENT, DE DÉPISTAGE, ET D'IDENTIFICATION DE COMPOSÉS DESTINÉS À TRAITER LES MALADIES PROVOQUÉES PAR DES PARASITES APICOMPLEXES

  摘要：

  本公开的内容包括：用于治疗顶复合体寄生虫相关疾病的新化合物，其使用方法；休眠寄生虫表型的细胞系和非人类动物模型，以及用于识别新药物治疗顶复合体寄生虫相关疾病的方法，以及用于识别由寄生虫引起的疾病及其对治疗的反应的生物标志物。

  公开号：

  WO2017112678A1

文献信息

• [EN] COMPOUNDS AND METHODS FOR TREATING, DETECTING, AND IDENTIFYING COMPOUNDS TO TREAT APICOMPLEXAN PARASITIC DISEASES<br/>[FR] COMPOSÉS ET MÉTHODES DE TRAITEMENT, DE DÉPISTAGE, ET D'IDENTIFICATION DE COMPOSÉS DESTINÉS À TRAITER LES MALADIES PROVOQUÉES PAR DES PARASITES APICOMPLEXES
  申请人：MCLEOD RIMA

  公开号：WO2017112678A1

  公开（公告）日：2017-06-29

  Disclosed herein; are novel compounds for treating apicomplexan parasite related disorders, methods for their use; cell line and non-human animal models of the dormant parasite phenotype and methods for their use in identifying new drugs to teat apicomplexan parasite related disorders, and biomarkers to identify disease due to the parasite and its response to treatment.

  本公开的内容包括：用于治疗顶复合体寄生虫相关疾病的新化合物，其使用方法；休眠寄生虫表型的细胞系和非人类动物模型，以及用于识别新药物治疗顶复合体寄生虫相关疾病的方法，以及用于识别由寄生虫引起的疾病及其对治疗的反应的生物标志物。
• COMPOUNDS AND METHODS FOR TREATING, DETECTING, AND IDENTIFYING COMPOUNDS TO TREAT APICOMPLEXAN PARASITIC DISEASES
  申请人：The University of Chicago

  公开号：EP3394032A1

  公开（公告）日：2018-10-31
• Compounds and Methods for Treating, Detecting, and Identifying Compounds to Treat Apicomplexan Parasitic Diseases
  申请人：The University Of Chicago

  公开号：US20200283391A1

  公开（公告）日：2020-09-10

  Disclosed herein; are novel compounds for treating apicomplexan parasite related disorders, methods for their use; cell line and non-human animal models of the dormant parasite phenotype and methods for their use in identifying new drugs to treat apicomplexan parasite related disorders, and biomarkers to identify disease due to the parasite and its response to treatment.
• Potent Tetrahydroquinolone Eliminates Apicomplexan Parasites
  作者：Martin J. McPhillie、Ying Zhou、Mark R. Hickman、James A. Gordon、Christopher R. Weber、Qigui Li、Patty J. Lee、Kangsa Amporndanai、Rachel M. Johnson、Heather Darby、Stuart Woods、Zhu-hong Li、Richard S. Priestley、Kurt D. Ristroph、Scott B. Biering、Kamal El Bissati、Seungmin Hwang、Farida Esaa Hakim、Sarah M. Dovgin、Joseph D. Lykins、Lucy Roberts、Kerrie Hargrave、Hua Cong、Anthony P. Sinai、Stephen P. Muench、Jitender P. Dubey、Robert K. Prud'homme、Hernan A. Lorenzi、Giancarlo A. Biagini、Silvia N. Moreno、Craig W. Roberts、Svetlana V. Antonyuk、Colin W. G. Fishwick、Rima McLeod

  DOI：10.3389/fcimb.2020.00203

  日期：——

  Apicomplexan infections cause substantial morbidity and mortality, worldwide. New, improved therapies are needed. Herein, we create a next generation anti-apicomplexan lead compound, JAG21, a tetrahydroquinolone, with increased sp3-character to improve parasite selectivity. Relative to other cytochromebinhibitors, JAG21 has improved solubility and ADMET properties, without need for pro-drug. JAG21 significantly reducesToxoplasma gondiitachyzoites and encysted bradyzoitesin vitro, and in primary and established chronic murine infections. Moreover, JAG21 treatment leads to 100% survival. Further, JAG21 is efficacious against drug-resistantPlasmodium falciparum in vitro. Causal prophylaxis and radical cure are achieved afterP. bergheisporozoite infection with oral administration of a single dose (2.5 mg/kg) or 3 days treatment at reduced dose (0.625 mg/kg/day), eliminating parasitemia, and leading to 100% survival. Enzymatic, binding, and co-crystallography/pharmacophore studies demonstrate selectivity for apicomplexan relative to mammalian enzymes. JAG21 has significant promise as a pre-clinical candidate for prevention, treatment, and cure of toxoplasmosis and malaria.