3-(thiophen-2-ylthio)-1-(4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)propan-1-one | 1432445-18-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 3-(thiophen-2-ylthio)-1-(4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)propan-1-one
• 英文别名: 3-Thiophen-2-ylsulfanyl-1-[4-[4-(trifluoromethyl)phenyl]piperazin-1-yl]propan-1-one；3-thiophen-2-ylsulfanyl-1-[4-[4-(trifluoromethyl)phenyl]piperazin-1-yl]propan-1-one
• CAS: 1432445-18-5
• 化学式: C₁₈H₁₉F₃N₂OS₂
• 分子量: 400.489
• InChiKey: SAHNIRKFADWSCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  77.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  对氯三氟甲苯 在 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.75h， 生成 3-(thiophen-2-ylthio)-1-(4-(4-(trifluoromethyl)phenyl)piperazin-1-yl)propan-1-one
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of aryl piperazines with potential as antidiabetic agents via the stimulation of glucose uptake and inhibition of NADH:ubiquinone oxidoreductase

  摘要：

  The management of blood glucose levels and the avoidance of diabetic hyperglycemia are common objectives of many therapies in the treatment of diabetes. An aryl piperazine compound 3a (RTC1) has been described as a promoter of glucose uptake, in part through a cellular mechanism that involves inhibition of NADH:ubiquinone oxidoreductase. We report herein the synthesis of 41 derivatives of 3a (RTC1) and a systematic structure-activity-relationship study where a number of compounds were shown to effectively stimulate glucose uptake in vitro and inhibit NADH:ubiquinone oxidoreductase. The hit compound 3a (RTC1) remained the most efficacious with a 2.57 fold increase in glucose uptake compared to vehicle control and micromolar inhibition of NADH:ubiquinone oxidoreductase (IC50 = 27 mu M). In vitro DMPK and in vivo PK studies are also described, where results suggest that 3a (RTC1) would not be expected to provoke adverse drug-drug interactions, yet be readily metabolised, avoid rapid excretion, with a short half-life, and have good tissue distribution. The overall results indicate that aryl piperazines, and 3a (RTC1) in particular, have potential as effective agents for the treatment of diabetes. (C) 2020 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2020.112416

文献信息

• [EN] N-ACYL-N'-PHENYLPIPERAZINE DERIVATIVES AS SRBP MODULATORS FOR USE IN THE TREATMENT OF DIABETES AND OBESITY<br/>[FR] DÉRIVÉS DE N-ACYL-N'-PHÉNYLPIPÉRAZINE UTILISÉS COMME MODULATEURS DE LA SRBP DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DU DIABÈTE ET DE L'OBÉSITÉ
  申请人：NAT UNIVERSITY OF IRELAND MAYNOOTH

  公开号：WO2013060860A1

  公开（公告）日：2013-05-02

  The present invention relates to compounds having the general formula (I) as described herein; methods of preparing said compounds; and their use in treating Type 1 and/or Type 2 Diabetes Mellitus. The compounds were assayed for binding to serum retinol binding protein (sRBP) and for disruption of the sRBP:transthyretin (TTR) and sRBP:sRBP receptor interaction. The compounds were also assayed for their ability to induce glucose uptake into mouse muscle cells. Also described is a pharmaceutical composition comprising a compound according to the first aspect of the present invention, and use thereof in treating Type 1 and Type 2 Diabetes.

  本发明涉及具有如下所述的一般式（I）的化合物；制备该化合物的方法；以及它们在治疗1型和/或2型糖尿病中的应用。对这些化合物进行了与血清视黄醇结合蛋白（sRBP）的结合和对sRBP：甲状腺素转运蛋白（TTR）和sRBP：sRBP受体相互作用的破坏的测定。这些化合物还被检测其促进小鼠肌肉细胞中葡萄糖摄取的能力。还描述了包含根据本发明第一方面的化合物的药物组合物，以及其在治疗1型和2型糖尿病中的用途。
• Design, synthesis, and biological evaluation of aryl piperazines with potential as antidiabetic agents via the stimulation of glucose uptake and inhibition of NADH:ubiquinone oxidoreductase
  作者：R. Devine、M. Kelada、S. Leonard、D.S.D. Martin、J.M.D. Walsh、C.J. Breen、R.B. Driver、G.K. Kinsella、J.B.C. Findlay、J.C. Stephens

  DOI：10.1016/j.ejmech.2020.112416

  日期：2020.9

  The management of blood glucose levels and the avoidance of diabetic hyperglycemia are common objectives of many therapies in the treatment of diabetes. An aryl piperazine compound 3a (RTC1) has been described as a promoter of glucose uptake, in part through a cellular mechanism that involves inhibition of NADH:ubiquinone oxidoreductase. We report herein the synthesis of 41 derivatives of 3a (RTC1) and a systematic structure-activity-relationship study where a number of compounds were shown to effectively stimulate glucose uptake in vitro and inhibit NADH:ubiquinone oxidoreductase. The hit compound 3a (RTC1) remained the most efficacious with a 2.57 fold increase in glucose uptake compared to vehicle control and micromolar inhibition of NADH:ubiquinone oxidoreductase (IC50 = 27 mu M). In vitro DMPK and in vivo PK studies are also described, where results suggest that 3a (RTC1) would not be expected to provoke adverse drug-drug interactions, yet be readily metabolised, avoid rapid excretion, with a short half-life, and have good tissue distribution. The overall results indicate that aryl piperazines, and 3a (RTC1) in particular, have potential as effective agents for the treatment of diabetes. (C) 2020 Elsevier Masson SAS. All rights reserved.