2-[(5-chloro-1,3-benzothiazol-2-yl)thio]pentanoic acid | 1192214-88-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 2-[(5-chloro-1,3-benzothiazol-2-yl)thio]pentanoic acid
• 英文别名: rac-2-[(5-Chloro-1,3-benzothiazol-2-yl)thio]pentanoic Acid；2-[(5-chloro-1,3-benzothiazol-2-yl)sulfanyl]pentanoic acid
• CAS: 1192214-88-2
• 化学式: C₁₂H₁₂ClNO₂S₂
• 分子量: 301.818
• InChiKey: WLSSFLBYJDWBIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  苯磺酰胺 、 2-[(5-chloro-1,3-benzothiazol-2-yl)thio]pentanoic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 生成 2-[(5-chloro-1,3-benzothiazol-2-yl)thio]-N-(phenylsulfonyl)pentanamide
  参考文献：
  名称：

  Benzothiazole-based N-(phenylsulfonyl)amides as a novel family of PPARα antagonists

  摘要：

  The discovery of PPAR antagonists is emerging as an useful tool for elucidating the biological role of the receptor. Here we report the identification of N-(phenylsulfonyl)amides containing the benzothiazole scaffold, a novel class of potent PPAR alpha antagonists obtained from chemical modification of carboxylic acid agonists. In this work, a group of phenylsulfonamides were synthesized and in vitro evaluated against the agonistic effect of GW7647; they showed an inhibitory effect on PPARa activation, with best compounds revealing a dose-dependent antagonistic profile. Some of these antagonists showed also an inhibitory effect on CPT1A pattern expression. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.028
• 作为产物：
  描述：

  2-溴戊酸乙酯 在 乙醇 、 sodium 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 2-[(5-chloro-1,3-benzothiazol-2-yl)thio]pentanoic acid
  参考文献：
  名称：

  Benzothiazole-based N-(phenylsulfonyl)amides as a novel family of PPARα antagonists

  摘要：

  The discovery of PPAR antagonists is emerging as an useful tool for elucidating the biological role of the receptor. Here we report the identification of N-(phenylsulfonyl)amides containing the benzothiazole scaffold, a novel class of potent PPAR alpha antagonists obtained from chemical modification of carboxylic acid agonists. In this work, a group of phenylsulfonamides were synthesized and in vitro evaluated against the agonistic effect of GW7647; they showed an inhibitory effect on PPARa activation, with best compounds revealing a dose-dependent antagonistic profile. Some of these antagonists showed also an inhibitory effect on CPT1A pattern expression. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.028

文献信息

• Fibrate-derived N-(methylsulfonyl)amides with antagonistic properties on PPARα
  作者：Alessandra Ammazzalorso、Alessandra D'Angelo、Antonella Giancristofaro、Barbara De Filippis、Mauro Di Matteo、Marialuigia Fantacuzzi、Letizia Giampietro、Pasquale Linciano、Cristina Maccallini、Rosa Amoroso

  DOI：10.1016/j.ejmech.2012.10.019

  日期：2012.12

  The identification of novel PPAR ligands represents an attractive research to fully understand the complex biological pathways regulated by these receptors. Selective PPAR modulators, inverse agonists and antagonists of three PPAR isoforms could help to clarify biological effects on lipid and glucose homeostasis. Here we describe the identification of a group of N-(methylsulfonyl)amides, derived from PPAR alpha agonist carboxylic acids. Transactivation and FRET assay confirmed an antagonist behaviour on PPAR alpha for some of these compounds, with submicromolar IC50. A preliminary analysis on selectivity alpha/gamma revealed different profiles of inhibition or activation. (C) 2012 Published by Elsevier Masson SAS.
• Synthesis, in vitro evaluation, and molecular modeling investigation of benzenesulfonimide peroxisome proliferator-activated receptors α antagonists
  作者：Alessandra Ammazzalorso、Antonio Carrieri、Fabio Verginelli、Isabella Bruno、Giuseppe Carbonara、Alessandra D'Angelo、Barbara De Filippis、Marialuigia Fantacuzzi、Rosalba Florio、Giuseppe Fracchiolla、Letizia Giampietro、Antonella Giancristofaro、Cristina Maccallini、Alessandro Cama、Rosa Amoroso

  DOI：10.1016/j.ejmech.2016.02.064

  日期：2016.5

  Recent evidences suggest a moderate activation of Peroxisome Proliferator-Activated Receptors (PPARs) could be favorable in metabolic diseases, reducing side effects given from full agonists. PPAR partial agonists and antagonists represent, to date, interesting tools to better elucidate biological processes modulated by these receptors. In this work are reported new benzenesulfonimide compounds able to block PPAR alpha, synthesized and tested by transactivation assays and gene expression analysis. Some of these compounds showed a dose-dependent antagonistic behavior on PPAR alpha, submicromolar potency, different profiles of selectivity versus PPAR gamma, and a repressive effect on CPT1A expression. Dockings and molecular dynamics on properly selected benzenesulfonimide derivatives furnished fresh insights into the molecular determinant most likely responsible for PPARa antagonism. (C) 2016 Elsevier Masson SAS. All rights reserved.
• Cytotoxic effect of a family of peroxisome proliferator-activated receptor antagonists in colorectal and pancreatic cancer cell lines
  作者：Alessandra Ammazzalorso、Laura De Lellis、Rosalba Florio、Isabella Bruno、Barbara De Filippis、Marialuigia Fantacuzzi、Letizia Giampietro、Cristina Maccallini、Silvia Perconti、Fabio Verginelli、Alessandro Cama、Rosa Amoroso

  DOI：10.1111/cbdd.13026

  日期：2017.11

  Recent studies report an interesting role of peroxisome proliferator‐activated receptor (PPAR) antagonists in different tumor models, being these compounds able to perturb metabolism and viability in cancer cells. In this work, the identification of a novel PPAR antagonist, showing inhibitory activity on PPARα and a weaker antagonism on PPARγ, is described. The activity of this compound and of a series of chemical analogues was investigated in selected tumor cell lines, expressing both PPARα and PPARγ. Data obtained show a dose‐dependent cytotoxic effect of the novel PPAR antagonist in colorectal and pancreatic cancer models.
• Synthesis and Biological Evaluation of 2-Heteroarylthioalkanoic Acid Analogues of Clofibric Acid as Peroxisome Proliferator-Activated Receptor α Agonists
  作者：Letizia Giampietro、Alessandra Ammazzalorso、Antonella Giancristofaro、Fabio Lannutti、Giancarlo Bettoni、Barbara De Filippis、Marialuigia Fantacuzzi、Cristina Maccallini、Michele Petruzzelli、Annalisa Morgano、Antonio Moschetta、Rosa Amoroso

  DOI：10.1021/jm900878u

  日期：2009.10.22

  A series of 2-heteroarylthioalkanoic acids were synthesized through systematic structural modifications of clofibric acid and evaluated for human peroxisome proliferator-activated receptor alpha (PPAR alpha) transactivation activity, with the aim of obtaining new hypolipidemic compounds. Some thiophene and benzothiazole derivatives showing a good activation of the receptor a were screened for activity against the PPAR gamma isoform. The gene induction of selected compounds was also investigated in the human hepatoma cell line.
• Benzothiazole-based N-(phenylsulfonyl)amides as a novel family of PPARα antagonists
  作者：Alessandra Ammazzalorso、Antonella Giancristofaro、Alessandra D’Angelo、Barbara De Filippis、Marialuigia Fantacuzzi、Letizia Giampietro、Cristina Maccallini、Rosa Amoroso

  DOI：10.1016/j.bmcl.2011.06.028

  日期：2011.8

  The discovery of PPAR antagonists is emerging as an useful tool for elucidating the biological role of the receptor. Here we report the identification of N-(phenylsulfonyl)amides containing the benzothiazole scaffold, a novel class of potent PPAR alpha antagonists obtained from chemical modification of carboxylic acid agonists. In this work, a group of phenylsulfonamides were synthesized and in vitro evaluated against the agonistic effect of GW7647; they showed an inhibitory effect on PPARa activation, with best compounds revealing a dose-dependent antagonistic profile. Some of these antagonists showed also an inhibitory effect on CPT1A pattern expression. (C) 2011 Elsevier Ltd. All rights reserved.