(1-ethyl-1,2,3,4-tetrahydro-1-naphthalenyl)propanedinitrile | 951215-50-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (1-ethyl-1,2,3,4-tetrahydro-1-naphthalenyl)propanedinitrile
• 英文别名: 2-(1-ethyl-3,4-dihydro-2H-naphthalen-1-yl)propanedinitrile
• CAS: 951215-50-2
• 化学式: C₁₅H₁₆N₂
• 分子量: 224.305
• InChiKey: DTJLMLLXQQVXSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  47.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1-ethyl-1,2,3,4-tetrahydro-1-naphthalenyl)propanedinitrile 在 氢氧化钾 、 potassium carbonate 作用下， 以 乙二醇 、 丙酮 为溶剂， 生成 methyl (1-ethyl-1,2,3,4-tetrahydro-1-naphthalenyl)acetate
  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 、 乙基溴化镁 在 copper(l) iodide 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 16.5h， 以54%的产率得到(1-ethyl-1,2,3,4-tetrahydro-1-naphthalenyl)propanedinitrile
  参考文献：
  名称：

  Nonsteroidal Glucocorticoid Agonists: Tetrahydronaphthalenes with Alternative Steroidal A-Ring Mimetics Possessing Dissociated (Transrepression/Transactivation) Efficacy Selectivity

  摘要：

  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.

  DOI：

  10.1021/jm070778w

文献信息

• Non-steroidal glucocorticoid agonists—The discovery of aryl pyrazoles as A-ring mimetics
  作者：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、Doug J. Minick、Philip A. Skone、Iain Uings、Iain M. McLay、Simon J.F. Macdonald

  DOI：10.1016/j.bmcl.2007.06.066

  日期：2007.9

  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.
• 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.