(5-氨基苯并[b]噻吩-2-基)-1-哌啶基甲酮 | 832102-94-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: (5-氨基苯并[b]噻吩-2-基)-1-哌啶基甲酮
• 英文名称: [2-(1-piperidinylcarbonyl)-1-benzothien-5-yl]amine
• 英文别名: Piperidine, 1-[(5-aminobenzo[b]thien-2-yl)carbonyl]-；(5-amino-1-benzothiophen-2-yl)-piperidin-1-ylmethanone
• CAS: 832102-94-0
• 化学式: C₁₄H₁₆N₂OS
• mdl: MFCD16363398
• 分子量: 260.36
• InChiKey: RZJDNTBSGPAANZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.357
• 拓扑面积：
  74.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5-氨基苯并[b]噻吩-2-基)-1-哌啶基甲酮 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 间氯过氧苯甲酸 作用下， 以 吡啶 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 N-(1,1-dioxido-2-(piperidine-1-carbonyl)benzo[b]thiophen-5-yl)benzamide
  参考文献：
  名称：

  Novel 2-Carbonylbenzo[b]thiophene 1,1-Dioxide Derivatives as Potent Inhibitors of STAT3 Signaling Pathway

  摘要：

  Signal transducer and activator of transcription 3 (STAT3) is considered to be an attractive therapeutic target for cancer therapy. In this study, a series of 2-carbonylbenzo[b]thiophene 1,1-dioxide derivatives (CBT) were designed to inhibit the STAT3 SH2 domain phosphorylation site Try 705. We demonstrated that incorporation of basic flexible groups through amide bond linkage to benzo[b]thiophene 1,1-dioxide (BTP) achieved compounds with higher antiproliferative potency than BTP itself. The most potent compound 6o, as indicated from luciferase reporter gene assay, inhibited the STAT3 pathway by decreasing the phosphorylation level of STAT3 Tyr705, while the phosphorylation level of other upstream tyrosine kinases in this pathway was not significantly inhibited. Compound 6o was also shown to trigger ROS generation and accumulation, thus consequently attributed partially to the observed cell apoptosis. This study provided important structural information for the development of inhibitors targeting the STAT3 pathway.

  DOI：

  10.1021/acsmedchemlett.5b00228
• 作为产物：
  描述：

  2-氯-5-硝基苯甲醛 在 Pd/C 氢氧化钾 、 lithium hydroxide 、 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、275.79 kPa 条件下， 反应 37.0h， 生成 (5-氨基苯并[b]噻吩-2-基)-1-哌啶基甲酮
  参考文献：
  名称：

  6-(4-Chlorophenyl)-3-substituted-thieno[3,2-d]pyrimidin-4(3H)-one-Based Melanin-Concentrating Hormone Receptor 1 Antagonist

  摘要：

  Genetic manipulation studies in mice at both the MCH receptor 1 (MCHR1) as well as the MCH peptide levels have implicated MCHR1 as a key player in energy homeostasis. The phenotype exhibited by these studies, that is, increased metabolic rate, resistance to high fat diet, and subsequent weight loss, has spurred considerable efforts to develop antagonists of MCHR1. In continuation of efforts directed toward this goal, the present work capitalizes on the putative binding mode of an MCH antagonist, resulting in the identification of several novel chemotypes that are potent and selective MCHR1 antagonists. In addition, the favorable pharmacokinetics of representative examples has allowed for the evaluation of an MCHR1 antagonist in a high fat diet-induced obese rodent model of obesity. The tolerability of the right-hand side of the template for diverse chemotypes accompanied by favorable effects on weight loss enhances the attractiveness of this template in the pursuit toward development of effective anti-obesity agents.

  DOI：

  10.1021/jm060814b

文献信息

• [EN] HETEROCYCLIC MCHR1 ANTAGONISTS<br/>[FR] ANTAGONISTES HETEROCYCLIQUES DE MCHR1
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004092181A9

  公开（公告）日：2005-01-27

  [EN] This invention relates to novel heterocycles which are antagonists at the melanin-concentrating hormone receptor 1 (MCHR1), also referred to as 11CBy, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in medicines. Compounds of the invention have formula (I).
  [FR] L'invention concerne des dérivés de benzopyrane substitués, des stéréoisomères et des sels pharmaceutiquement acceptables desdits composés, ainsi que des procédés appropriés pour les préparer. Les composés de la présente invention s'utilisent comme agonistes du récepteur beta des oestrogènes. De tels agonistes s'utilisent dans le traitement d'affections induites par le récepteur beta des oestrogènes, telles que le cancer de la prostate ou l'hyperplasie prostatique bénigne (HPB).
• Novel 2-Carbonylbenzo[<i>b</i>]thiophene 1,1-Dioxide Derivatives as Potent Inhibitors of STAT3 Signaling Pathway
  作者：Peng Ji、Xin Xu、Shuhua Ma、Junchao Fan、Qiang Zhou、Xinliang Mao、Chunhua Qiao

  DOI：10.1021/acsmedchemlett.5b00228

  日期：2015.9.10

  Signal transducer and activator of transcription 3 (STAT3) is considered to be an attractive therapeutic target for cancer therapy. In this study, a series of 2-carbonylbenzo[b]thiophene 1,1-dioxide derivatives (CBT) were designed to inhibit the STAT3 SH2 domain phosphorylation site Try 705. We demonstrated that incorporation of basic flexible groups through amide bond linkage to benzo[b]thiophene 1,1-dioxide (BTP) achieved compounds with higher antiproliferative potency than BTP itself. The most potent compound 6o, as indicated from luciferase reporter gene assay, inhibited the STAT3 pathway by decreasing the phosphorylation level of STAT3 Tyr705, while the phosphorylation level of other upstream tyrosine kinases in this pathway was not significantly inhibited. Compound 6o was also shown to trigger ROS generation and accumulation, thus consequently attributed partially to the observed cell apoptosis. This study provided important structural information for the development of inhibitors targeting the STAT3 pathway.
• 6-(4-Chlorophenyl)-3-substituted-thieno[3,2-<i>d</i>]pyrimidin-4(3<i>H</i>)-one-Based Melanin-Concentrating Hormone Receptor 1 Antagonist
  作者：Francis X. Tavares、Kamal A. Al-Barazanji、Michael J. Bishop、Christy S. Britt、David L. Carlton、Joel P. Cooper、Paul L. Feldman、Dulce M. Garrido、Aaron S. Goetz、Mary K. Grizzle、Donald L. Hertzog、Diane M. Ignar、Daniel G. Lang、Maggie S. McIntyre、Ronda J. Ott、Andrew J. Peat、Hui-Qiang Zhou

  DOI：10.1021/jm060814b

  日期：2006.11.30

  Genetic manipulation studies in mice at both the MCH receptor 1 (MCHR1) as well as the MCH peptide levels have implicated MCHR1 as a key player in energy homeostasis. The phenotype exhibited by these studies, that is, increased metabolic rate, resistance to high fat diet, and subsequent weight loss, has spurred considerable efforts to develop antagonists of MCHR1. In continuation of efforts directed toward this goal, the present work capitalizes on the putative binding mode of an MCH antagonist, resulting in the identification of several novel chemotypes that are potent and selective MCHR1 antagonists. In addition, the favorable pharmacokinetics of representative examples has allowed for the evaluation of an MCHR1 antagonist in a high fat diet-induced obese rodent model of obesity. The tolerability of the right-hand side of the template for diverse chemotypes accompanied by favorable effects on weight loss enhances the attractiveness of this template in the pursuit toward development of effective anti-obesity agents.