5-(4,4,4-trifluorobutoxy)-1-indanone | 521079-63-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 5-(4,4,4-trifluorobutoxy)-1-indanone
• 英文别名: 5-(4,4,4-trifluorobutoxy)-2,3-dihydro-1H-inden-1-one；5-(4,4,4-trifluorobutyloxy)-1-indanone；5-(4,4,4-trifluorobutoxy)-2,3-dihydroinden-1-one
• CAS: 521079-63-0
• 化学式: C₁₃H₁₃F₃O₂
• 分子量: 258.24
• InChiKey: NXDUCJHCTJGKBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(4,4,4-trifluorobutoxy)-1-indanone 在 selenium(IV) oxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以76%的产率得到5-(4,4,4-trifluorobutyloxy)ninhydrin
  参考文献：
  名称：

  Synthesis and inhibition study of monoamine oxidase, indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase by 3,8-substituted 5H-indeno[1,2-c]pyridazin-5-one derivatives

  摘要：

  Previous studies on 5H-indeno[1,2-c]pyridazin-5-one derivatives as inhibitors of MAO-B revealed that it was possible to increase the MAO-B inhibitory potency of 5H-indeno[1,2-c]pyridazin-5-ones by substituting the central heterocycle in the 3-position or C-8 with lipophilic groups which occupy the substrate cavity or the entrance of the binding site, respectively. Here, four new 5H-indeno[1,2-c]pyridazin-5-one derivatives containing lipophilic groups at both positions were synthesized and their inhibitory potency against human monoamine oxidase A and B were evaluated. Selectivity of these compounds against IDO and TDO, two enzymes sharing substrate similarity with MAO and involved in the serotonergic and kynurenine pathways was also studied. All compounds showed higher activity and selectivity against MAO-B, the most effective one being 3-methyl-8-meta-chlorobenzyloxy-5H-indeno [1,2-c]pyridazin-5-one (9a) which was shown to be a competitive inhibitor with a K-i value of 0.11 mu M. Replacing the methyl group in the 3-position with a meta-CF3-phenyl group (7a, 7b and 7c) abolished the inhibitory potency against MAO-B. Indeed, the substitution of the 5H-indeno[1,2-c]pyridazin-5-one core in the 3-position dramatically influences the MAO-inhibiting properties of these compounds. Molecular docking studies of 9a within MAO-B suggest that the 5H-indeno[1,2-c]pyridazin-5-one scaffold is well stabilized into the substrate cavity with the meta-chlorobenzyloxy side chain extending towards a rather hydrophobic pocket at the entrance cavity. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.09.042
• 作为产物：
  描述：

  5-甲氧基-1H-茚-1-酮 在 二甲基二硒醚 、 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.0h， 生成 5-(4,4,4-trifluorobutoxy)-1-indanone
  参考文献：
  名称：

  Synthesis, Structural Reassignment, and Biological Activity of Type B MAO Inhibitors Based on the 5H-Indeno[1,2-c]pyridazin-5-one Core

  摘要：

  The synthesis and enzyme inhibitor properties of reversible type B monoamine oxidase inhibitors are described. These compounds belong to the 5H-indeno[ 1,2-c] pyridazine family and possess a hydrophobic benzyloxy or 4,4,4-trifluorobutoxy side chain which, in contrast to a previous assignment, has been unambiguously located at C( 8) of the heterocyclic moiety. Investigation of the regioisomeric structures establishes that substitution of the 5H-indeno[ 1,2-c] pyridazin-5-one core at C( 7) vs C( 8) dramatically influences the MAO-inhibiting properties of these compounds.

  DOI：

  10.1021/jm051091j

文献信息

• [EN] SUBSTITUTED HETEROCYCLIC DERIVATIVES AS GPR AGONISTS AND USES THEREOF<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES SUBSTITUÉS EN TANT QU'AGONISTES DE GPR ET LEURS UTILISATIONS
  申请人：PIRAMAL ENTPR LTD

  公开号：WO2015028960A1

  公开（公告）日：2015-03-05

  The present invention generally relates to substituted heterocyclic derivatives (the compounds of Formula (I)), processes for their preparation, pharmaceutical compositions containing said compounds, their use as G-protein coupled receptor (GPR) agonists, particularly as GPR40 agonists and methods of using these compounds in the treatment of GPR40 mediated diseases or conditions such as Type 2 diabetes, obesity, dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.

  本发明通常涉及取代杂环衍生物（式（I）化合物），其制备方法，含有所述化合物的药物组合物，它们作为G-蛋白偶联受体（GPR）激动剂的用途，特别是作为GPR40激动剂，并且使用这些化合物治疗GPR40介导的疾病或症状，如2型糖尿病、肥胖症、血脂异常、高脂血症、高胆固醇血症和高甘油三酯血症的方法。
• Rational approaches towards reversible inhibition of type B monoamine oxidase. Design and evaluation of a novel 5H-Indeno[1,2-c]pyridazin-5-one derivative
  作者：Frédéric Ooms、Raphaël Frédérick、François Durant、Jacobus P Petzer、Neal Castagnoli、Cornelis J Van der Schyf、Johan Wouters

  DOI：10.1016/s0960-894x(02)00838-7

  日期：2003.1

  The stereoelectronic properties of several potent reversible monoamine oxidase B (MAO-B) inhibitors were studied with a view to develop a pharmacophore model for reversible MAO-B inhibition. This study suggested that important specific H-bond and hydrophobic interactions are required for potent and selective MAO-B inhibition. These requirements were applied in the design and synthesis of a novel reversible and selective MAO-B inhibitor, 3-methyl-8-(4,4,4-trifluoro-butoxy)indeno[1,2-c]pyridazin5-one, that is ca. 7000 times more selective as an inhibitor for MAO-B than for MAO-A, with Ki(MAO-B) in the low nanomolar range. (C) 2002 Elsevier Science Ltd. All rights reserved.