6,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-ylamine | 173998-64-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 6,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-ylamine
• 英文别名: (-)-6,7-Difluoro-1,2,3,4-tetrahydronaphthalen-2-ylamine；6,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-amine
• CAS: 173998-64-6
• 化学式: C₁₀H₁₁F₂N
• mdl: MFCD18651074
• 分子量: 183.201
• InChiKey: KXUCXETYKQGKKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  13
• 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：
  3

反应信息

• 作为反应物：
  描述：

  6,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-ylamine 、 N,N'-硫羰基二咪唑 在 silica gel 、 二氯甲烷,丙烷-2-酮 作用下， 以 乙酸乙酯 为溶剂， 以gave (-)-6,7-difluoro-2-isothiocyano-1,2,3,4-tetrahydronaphthalene (0.55 g, 2.42 mmol)的产率得到(-)-6,7-difluoro-2-isothiocyano-1,2,3,4-tetrahydronaphthalene
  参考文献：
  名称：

  Benzocycloalkylazolethione derivatives and processes for preparing the

  摘要：

  本发明涉及一种新型苯并环烷基唑硫酮化合物，其为多巴胺β-羟化酶抑制剂，其中化合物的苯并环烷基部分选自吲哚基、1,2,3,4-四氢萘基和6,7,8,9-四氢-5H-苯并环庚基（其中苯并环可以选择性地被一个至三个取代基取代），化合物的唑硫酮部分选自2-硫代-2,3-二氢-1H-咪唑-3-基、5-硫代-4,5-二氢-1H-\x9b1,2,4!三唑-4-基和5-硫代-4,5-二氢-1H-\x9b1,2,4!三唑-1-基（每个可以选择性地被一个至三个取代基取代）；以及这样的苯并环烷基唑硫酮化合物的前药、药学上可接受的盐、单体异构体和异构体混合物以及使用和制备这样的化合物的方法。

  公开号：

  US05719280A1

文献信息

• Benzocycloalkylazolethione derivatives
  申请人：——

  公开号：US05538988A1

  公开（公告）日：1996-07-23

  The present invention relates to novel benzocycloalkylazolethione compounds which are dopamine .beta.-hydroxylase inhibitors in which the benzocycloalkyl portion of the compound is selected from indanyl, 1,2,3,4-tetrahydronaphthalenyl and 6,7,8,9-tetrahydro-5H-benzocycloheptenyl (in which the benzo is optionally substituted with one to three substituents) and the azolethione portion of the compound is selected from 2-thioxo-2,3-dihydro-1H-imidazol-3-yl, 5-thioxo-4,5-dihydro-1H-[1,2,4]triazol-4-yl and 5-thioxo-4,5-dihydro-1H-[1,2,4]triazol-1-yl (each optionally substituted with one to three substituents); and the prodrugs, pharmaceutically acceptable salts, individual isomers and mixtures of isomers and the methods of using and preparing such benzocycloalkylazolethione compounds.

  本发明涉及一种新型苯并环烷基唑硫酮化合物，它们是多巴胺β-羟化酶抑制剂，其中化合物的苯并环烷基部分选自吲哚基、1,2,3,4-四氢萘基和6,7,8,9-四氢-5H-苯并环庚基（其中苯并基可选择性地取代一个到三个取代基），化合物的唑硫酮部分选自2-硫代-2,3-二氢-1H-咪唑-3-基、5-硫代-4,5-二氢-1H-[1,2,4]三唑-4-基和5-硫代-4,5-二氢-1H-[1,2,4]三唑-1-基（每个可选择性地取代一个到三个取代基）；以及这些苯并环烷基唑硫酮化合物的前药、药学上可接受的盐、各个异构体和异构体混合物的使用和制备方法。
• 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.
• BENZOCYCLOALKYLAZOLETHIONE DERIVATIVES
  申请人：SYNTEX (U.S.A.) INC.

  公开号：EP0757677A1

  公开（公告）日：1997-02-12
• BENZOCYCLOHEXYLIMIDAZOLETHIONE DERIVATIVES
  申请人：Syntex (U.S.A.) LLC

  公开号：EP0757677B1

  公开（公告）日：2003-06-18
• US5538988A
  申请人：——

  公开号：US5538988A

  公开（公告）日：1996-07-23