3-(1-ethyl-1,2,3,4-tetrahydro-1-naphthalenyl)-1,1,1-trifluoro-2-propanone | 875796-76-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 3-(1-ethyl-1,2,3,4-tetrahydro-1-naphthalenyl)-1,1,1-trifluoro-2-propanone
• 英文别名: 3-(1-ethyl-3,4-dihydro-2H-naphthalen-1-yl)-1,1,1-trifluoropropan-2-one
• CAS: 875796-76-2
• 化学式: C₁₅H₁₇F₃O
• 分子量: 270.295
• InChiKey: PLSSBFVRQCNNPT-UHFFFAOYSA-N

物化性质

• 沸点：
  304.8±37.0 °C(Predicted)
• 密度：
  1.126±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(1-ethyl-1,2,3,4-tetrahydro-1-naphthalenyl)-1,1,1-trifluoro-2-propanone 在 lithium aluminium tetrahydride 、 cesium fluoride 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  Non-steroidal glucocorticoid agonists—The discovery of aryl pyrazoles as A-ring mimetics

  摘要：

  Starting from an established series of non-steroidal glucocorticoid receptor (GR) agonists, a large array was designed where a metabolically labile benzoxazinone moiety was replaced. Initial hits bound to GR but lacked agonist activity. Following two further iterations, potent GR agonists were discovered with 20D1E1 having NF kappa B agonism pIC(50) 8-8 (103%). Other analogues such as 23D1E1 display a dissociated profile (NF kappa B pIC(50) 8.1 (103%), MMTV pEC(50) 7.02 (36%)). The tetrahydronaphthalene moiety can also be replaced with substituted aryls such as 24E1 and 25E1. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.06.066
• 作为产物：
  描述：

  (1,2,3,4-四氢-1-亚萘基)丙二腈 在 氢氧化钾 、 copper(l) iodide 、 双(三甲基硅烷基)氨基钾 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙二醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 生成 3-(1-ethyl-1,2,3,4-tetrahydro-1-naphthalenyl)-1,1,1-trifluoro-2-propanone
  参考文献：
  名称：

  Non-steroidal glucocorticoid agonists—The discovery of aryl pyrazoles as A-ring mimetics

  摘要：

  Starting from an established series of non-steroidal glucocorticoid receptor (GR) agonists, a large array was designed where a metabolically labile benzoxazinone moiety was replaced. Initial hits bound to GR but lacked agonist activity. Following two further iterations, potent GR agonists were discovered with 20D1E1 having NF kappa B agonism pIC(50) 8-8 (103%). Other analogues such as 23D1E1 display a dissociated profile (NF kappa B pIC(50) 8.1 (103%), MMTV pEC(50) 7.02 (36%)). The tetrahydronaphthalene moiety can also be replaced with substituted aryls such as 24E1 and 25E1. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.06.066

文献信息

• [EN] TETRAHYDRO-NAPHTHALENE DERIVATIVES AS GLUCOCORTICOID RECEPTOR MODULATORS<br/>[FR] DÉRIVÉS DE TÉTRAHYDRONAPHTHALÈNE SERVANT DE MODULATEURS DU RÉCEPTEUR DES GLUCOCORTICOÏDES
  申请人：GLAXO GROUP LTD

  公开号：WO2006015870A1

  公开（公告）日：2006-02-16

  The present invention is directed to compounds of formula (I): wherein R represents a methyl or an ethyl group X represents N, C-H or C-CH3 when X represents C-H or C-CH3, Y represents N when X represents N, Y represents C-H and physiologically functional derivatives thereof, pharmaceutical compositions comprising the compounds, the use of the compounds for the manufacture of medicaments particularly for the treatment of inflammatory and/or allergic conditions, processes for the preparation of the compounds, and chemical intermediates in the processes for the manufacture of the compounds.

  本发明涉及以下式（I）的化合物：其中R代表甲基或乙基基团，X代表N、C-H或C-CH3，当X代表C-H或C-CH3时，Y代表N，当X代表N时，Y代表C-H以及其生理功能衍生物，包括该化合物的药物组合物，该化合物用于制备药物，特别用于治疗炎症和/或过敏症状，该化合物的制备方法以及用于制备该化合物的化学中间体。
• Tetrahydro-Naphthalene Derivatives as Glucocorticoid Receptor Modulators
  申请人：Edwards Christine

  公开号：US20070224130A1

  公开（公告）日：2007-09-27

  The present invention is directed to compounds of formula (I): wherein R represents a methyl or an ethyl group X represents N, C—H or C—CH 3 when X represents C—H or C—CH 3 , Y represents N when X represents N, Y represents C—H and physiologically functional derivatives thereof, pharmaceutical compositions comprising the compounds, the use of the compounds for the manufacture of medicaments particularly for the treatment of inflammatory and/or allergic conditions, processes for the preparation of the compounds, and chemical intermediates in the processes for the manufacture of the compounds.

  本发明涉及化合物公式(I)：其中R代表甲基或乙基基团，X代表N、C-H或C-CH3，当X代表C-H或C-CH3时，Y代表N，当X代表N时，Y代表C-H及其生理功能衍生物，包括该化合物的制药组合物，用于制造药物的化合物，特别是用于治疗炎症和/或过敏症状的药物，制备该化合物的过程以及制造该化合物的化学中间体。
• Tetrahydro-naphthalene derivatives as glucocorticoid receptor modulators
  申请人：Glaxo Group Limited

  公开号：US07902224B2

  公开（公告）日：2011-03-08

  The present invention is directed to compounds of formula (I): wherein R represents a methyl or an ethyl group X represents N, C—H or C—CH3 when X represents C—H or C—CH3, Y represents N when X represents N, Y represents C—H and physiologically functional derivatives thereof, pharmaceutical compositions comprising the compounds, the use of the compounds for the manufacture of medicaments particularly for the treatment of inflammatory and/or allergic conditions, processes for the preparation of the compounds, and chemical intermediates in the processes for the manufacture of the compounds.

  本发明涉及以下式子的化合物(I)：其中，R代表甲基或乙基基团，X代表N、C-H或C-CH3，当X代表C-H或C-CH3时，Y代表N；当X代表N时，Y代表C-H，以及其生理功能衍生物，包含该化合物的制药组合物，使用该化合物制造药物，特别是用于治疗炎症和/或过敏症的药物，制备该化合物的过程以及制造该化合物的化学中间体。
• Nonsteroidal Glucocorticoid Agonists: Tetrahydronaphthalenes with Alternative Steroidal A-Ring Mimetics Possessing Dissociated (Transrepression/Transactivation) Efficacy Selectivity
  作者：Keith Biggadike、Mohamed Boudjelal、Margaret Clackers、Diane M. Coe、Derek A. Demaine、George W. Hardy、Davina Humphreys、Graham G. A. Inglis、Michael J. Johnston、Haydn T. Jones、David House、Richard Loiseau、Deborah Needham、Philip A. Skone、Iain Uings、Gemma Veitch、Gordon G. Weingarten、Iain M. McLay、Simon J. F. Macdonald

  DOI：10.1021/jm070778w

  日期：2007.12.27

  The synthesis and biological activity of tetrahydronaphthalene derivatives coupled to various heterocycles are described. These compounds are potent glucocorticoid receptor agonists with efficacy selectivity in an NF kappa B glucocorticoid receptor (GR) agonist assay (representing transrepression effects) over an MMTV GR agonist assay (representing transactivation effects). Quinolones, indoles, and C- and N-linked quinolines are some of the heterocycles that provide efficacy selectivity. For example, the isoquinoline 49D1E2 has NF kappa B agonism with pIC(50) of 8.66 (89%) and reduced efficacy in MMTV agonism (6%), and the quinoline 55D1E1 has NF kappa B agonism with pIC(50) of 9.30 (101%) and reduced efficacy in MMTV agonism with pEC(50) of 8.02 (47%). A description of how a compound from each class is modeled in the active site of the receptor is given.
• TETRAHYDRO-NAPHTHALENE DERIVATIVES AS GLUCOCORTICOID RECEPTOR MODULATORS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1776119A1

  公开（公告）日：2007-04-25