N-(2-fluorophenyl)pyridine-2-carbothioamide | 119284-09-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-fluorophenyl)pyridine-2-carbothioamide
• 英文别名: N-(2-fluorophenyl)-2-pyridinecarbothioamide
• CAS: 119284-09-2
• 化学式: C₁₂H₉FN₂S
• 分子量: 232.281
• InChiKey: NWIKPWSEDHOINI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  57
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(2-fluorophenyl)pyridine-2-carbothioamide 在 盐酸 、 potassium carbonate 作用下， 以 异丙醇 、 丙酮 、 正丁醇 为溶剂， 生成 (1S,3r)-3-(4-(2-fluorophenyl)-5-(pyridin-2-yl)-4H-1,2,4-triazol-3-yl)cyclobutan-1-amine dihydrochloride
  参考文献：
  名称：

  Preclinical Lead Optimization of a 1,2,4-Triazole Based Tankyrase Inhibitor

  摘要：

  Tankyrases 1 and 2 are central biotargets in the WNT/beta-catenin signaling and Hippo signaling pathways. We have previously developed tankyrase inhibitors bearing a 1,2,4-triazole moiety and binding predominantly to the adenosine binding site of the tankyrase catalytic domain. Here we describe a systematic structure-guided lead optimization approach of these tankyrase inhibitors. The central 1,2,4-triazole template and trans-cyclobutyl linker of the lead compound 1 were left unchanged, while side-group East, West, and South moieties were altered by introducing different building blocks defined as point mutations. The systematic study provided a novel series of compounds reaching picomolar IC50 inhibition in WNT/beta-catenin signaling cellular reporter assay. The novel optimized lead 13 resolves previous atropisomerism, solubility, and Caco-2 efflux liabilities. 13 shows a favorable ADME profile, including improved Caco-2 permeability and oral bioavailability in mice, and exhibits antiproliferative efficacy in the colon cancer cell line COLO 320DM in vitro.

  DOI：

  10.1021/acs.jmedchem.0c00208
• 作为产物：
  描述：

  N-(2-fluorophenyl)picolinamide 在 劳森试剂 作用下， 以 甲苯 为溶剂， 以89%的产率得到N-(2-fluorophenyl)pyridine-2-carbothioamide
  参考文献：
  名称：

  Preclinical Lead Optimization of a 1,2,4-Triazole Based Tankyrase Inhibitor

  摘要：

  Tankyrases 1 and 2 are central biotargets in the WNT/beta-catenin signaling and Hippo signaling pathways. We have previously developed tankyrase inhibitors bearing a 1,2,4-triazole moiety and binding predominantly to the adenosine binding site of the tankyrase catalytic domain. Here we describe a systematic structure-guided lead optimization approach of these tankyrase inhibitors. The central 1,2,4-triazole template and trans-cyclobutyl linker of the lead compound 1 were left unchanged, while side-group East, West, and South moieties were altered by introducing different building blocks defined as point mutations. The systematic study provided a novel series of compounds reaching picomolar IC50 inhibition in WNT/beta-catenin signaling cellular reporter assay. The novel optimized lead 13 resolves previous atropisomerism, solubility, and Caco-2 efflux liabilities. 13 shows a favorable ADME profile, including improved Caco-2 permeability and oral bioavailability in mice, and exhibits antiproliferative efficacy in the colon cancer cell line COLO 320DM in vitro.

  DOI：

  10.1021/acs.jmedchem.0c00208

文献信息

• 2-pyridinecarbothioamides and pharmaceutical compositions comprising the
  申请人：American Home Products Corporation

  公开号：US04886821A1

  公开（公告）日：1989-12-12

  There are provided gastric antiulcer and cytoprotective substituted N-phenyl-2-pyridinecarbothioamides. The process for their production and formulation is disclosed.

  提供了胃抗溃疡和细胞保护的取代N-苯基-2-吡啶卡博硫胺。公开了它们的生产和制剂过程。
• 2-pyridinecarbothioamides, processes for preparation thereof
  申请人：American Home Products Corporation

  公开号：US04950762A1

  公开（公告）日：1990-08-21

  There are provided gastric antiulcer and cytoprotective substituted N-phenyl-2-pyridinecarbothioamides. The process for their production and formulation is disclosed.

  提供了胃抗溃疡和细胞保护的取代N-苯基-2-吡啶羧硫酰胺。公开了它们的制备和配方过程。
• Preclinical Lead Optimization of a 1,2,4-Triazole Based Tankyrase Inhibitor
  作者：Jo Waaler、Ruben G. G. Leenders、Sven T. Sowa、Shoshy Alam Brinch、Max Lycke、Piotr Nieczypor、Sjoerd Aertssen、Sudarshan Murthy、Albert Galera-Prat、Eddy Damen、Anita Wegert、Marc Nazaré、Lari Lehtiö、Stefan Krauss

  DOI：10.1021/acs.jmedchem.0c00208

  日期：2020.7.9

  Tankyrases 1 and 2 are central biotargets in the WNT/beta-catenin signaling and Hippo signaling pathways. We have previously developed tankyrase inhibitors bearing a 1,2,4-triazole moiety and binding predominantly to the adenosine binding site of the tankyrase catalytic domain. Here we describe a systematic structure-guided lead optimization approach of these tankyrase inhibitors. The central 1,2,4-triazole template and trans-cyclobutyl linker of the lead compound 1 were left unchanged, while side-group East, West, and South moieties were altered by introducing different building blocks defined as point mutations. The systematic study provided a novel series of compounds reaching picomolar IC50 inhibition in WNT/beta-catenin signaling cellular reporter assay. The novel optimized lead 13 resolves previous atropisomerism, solubility, and Caco-2 efflux liabilities. 13 shows a favorable ADME profile, including improved Caco-2 permeability and oral bioavailability in mice, and exhibits antiproliferative efficacy in the colon cancer cell line COLO 320DM in vitro.
• 1,2,4-TRIAZOLE DERIVATIVES AS TANKYRASE INHIBITORS
  申请人：Oslo Universitetssykehus HF

  公开号：EP3810597A1

  公开（公告）日：2021-04-28
• US4886821A
  申请人：——

  公开号：US4886821A

  公开（公告）日：1989-12-12