7-Chloro-1,2,3,4-tetrahydronaphthalen-2-amine

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 7-Chloro-1,2,3,4-tetrahydronaphthalen-2-amine
• 化学式: C₁₀H₁₂ClN
• mdl: MFCD06739162
• 分子量: 181.665
• InChiKey: YGTHAPVEIKCPDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  7-氯-5-甲基-2-(三氟甲基)-[1,2,4]噻唑并[1,5-a]嘧啶 、 7-Chloro-1,2,3,4-tetrahydronaphthalen-2-amine 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(7-chloro-1,2,3,4-tetrahydronaphthalen-2-yl)-5-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine 、 N-(7-chloro-1,2,3,4-tetrahydronaphthalen-2-yl)-5-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
  参考文献：
  名称：

  Tetrahydro-2-naphthyl and 2-Indanyl Triazolopyrimidines Targeting Plasmodium falciparum Dihydroorotate Dehydrogenase Display Potent and Selective Antimalarial Activity

  摘要：

  Malaria persists as one of the most devastating global infectious diseases. The pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH) has been identified as a new malaria drug target, and a triazolopyrimidine-based DHODH inhibitor I (DSM265) is in clinical development. We sought to identify compounds with higher potency against Plasmodium DHODH while showing greater selectivity toward animal DHODHs. Herein we describe a series of novel triazolopyrimidines wherein the p-SF5-aniline was replaced with substituted 1,2,3,4-tetrahydro-2-naphthyl or 2-indanyl amines. These compounds showed strong species selectivity, and several highly potent tetrahydro-2-naphthyl derivatives were identified. Compounds with halogen substitutions displayed sustained plasma levels after oral dosing in rodents leading to efficacy in the P. falciparum SCID mouse malaria model. These data suggest that tetrahydro-2-naphthyl derivatives have the potential to be efficacious for the treatment of malaria, but due to higher metabolic clearance than 1, they most likely would need to be part of a multidose regimen.

  DOI：

  10.1021/acs.jmedchem.6b00275

文献信息

• Tetrahydro-2-naphthyl and 2-Indanyl Triazolopyrimidines Targeting <i>Plasmodium falciparum</i> Dihydroorotate Dehydrogenase Display Potent and Selective Antimalarial Activity
  作者：Sreekanth Kokkonda、Xiaoyi Deng、Karen L. White、Jose M. Coteron、Maria Marco、Laura de las Heras、John White、Farah El Mazouni、Diana R. Tomchick、Krishne Manjalanagara、Kakali Rani Rudra、Gong Chen、Julia Morizzi、Eileen Ryan、Werner Kaminsky、Didier Leroy、María Santos Martínez-Martínez、Maria Belen Jimenez-Diaz、Santiago Ferrer Bazaga、Iñigo Angulo-Barturen、David Waterson、Jeremy N. Burrows、Dave Matthews、Susan A. Charman、Margaret A. Phillips、Pradipsinh K. Rathod

  DOI：10.1021/acs.jmedchem.6b00275

  日期：2016.6.9

  Malaria persists as one of the most devastating global infectious diseases. The pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH) has been identified as a new malaria drug target, and a triazolopyrimidine-based DHODH inhibitor I (DSM265) is in clinical development. We sought to identify compounds with higher potency against Plasmodium DHODH while showing greater selectivity toward animal DHODHs. Herein we describe a series of novel triazolopyrimidines wherein the p-SF5-aniline was replaced with substituted 1,2,3,4-tetrahydro-2-naphthyl or 2-indanyl amines. These compounds showed strong species selectivity, and several highly potent tetrahydro-2-naphthyl derivatives were identified. Compounds with halogen substitutions displayed sustained plasma levels after oral dosing in rodents leading to efficacy in the P. falciparum SCID mouse malaria model. These data suggest that tetrahydro-2-naphthyl derivatives have the potential to be efficacious for the treatment of malaria, but due to higher metabolic clearance than 1, they most likely would need to be part of a multidose regimen.