thiophene-3-carboximidamide | 54610-81-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 杂芳族化合物
• 英文名称: thiophene-3-carboximidamide
• 英文别名: 3-Thiophencarboxamidin；thiophene-3-carboximidic acid amide；thiophen-3-carboximidamide；thiophene-3-carboxamidine
• CAS: 54610-81-0
• 化学式: C₅H₆N₂S
• 分子量: 126.182
• InChiKey: JKCKRNYECSTMLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  78.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  thiophene-3-carboximidamide 在 sodium ethanolate 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 4-Chloro-2-thiophen-3-yl-pyrimidine-5-carboxylic acid ethyl ester
  参考文献：
  名称：

  Novel inhibitors of AP-1 and NF-κB mediated gene expression: structure–activity relationship studies of ethyl 4-[(3-Methyl-2,5-dioxo(3-pyrrolinyl))amino]-2-(trifluoromethyl)pyrimidine-5-carboxylate

  摘要：

  In an effort to identify novel inhibitors of AP-1 and NF-kappa B mediated transcriptional activation, several analogues of ethyl 4-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-2-(trifluoromethyl)pyrimidine-5-carboxylate (1) were synthesized and tested in two in vitro assays. The 2-(2'-thienyl) substituted compound (II) was identified as the most potent in this series. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00312-7
• 作为产物：
  描述：

  methyl 3-thiophenecarboximidate 在 氯化铵 作用下， 以 乙醇 为溶剂， 生成 thiophene-3-carboximidamide
  参考文献：
  名称：

  Discovery of selective PDE4B inhibitors

  摘要：

  In this study the first PDE4B selective inhibitor is described. Optimization of lead 2-arylpyrimidine derivatives afforded a series of potent PDE4B inhibitors with >100-fold selectivity over the PDE4D isozyme. With a good pharmacokinetic profile, a selected compound exhibited potent anti-inflammatory effects in vivo and showed less emesis compared with Cilomilast. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.04.121

文献信息

• Identification of NVP-TNKS656: The Use of Structure–Efficiency Relationships To Generate a Highly Potent, Selective, and Orally Active Tankyrase Inhibitor
  作者：Michael D. Shultz、Atwood K. Cheung、Christina A. Kirby、Brant Firestone、Jianmei Fan、Christine Hiu-Tung Chen、Zhouliang Chen、Donovan N. Chin、Lucian DiPietro、Aleem Fazal、Yun Feng、Pascal D. Fortin、Ty Gould、Bharat Lagu、Huangshu Lei、Francois Lenoir、Dyuti Majumdar、Etienne Ochala、M. G. Palermo、Ly Pham、Minying Pu、Troy Smith、Travis Stams、Ronald C. Tomlinson、B. Barry Touré、Michael Visser、Run Ming Wang、Nigel J. Waters、Wenlin Shao

  DOI：10.1021/jm400807n

  日期：2013.8.22

  Tankyrase 1 and 2 have been shown to be redundant, druggable nodes in the Wnt pathway. As such, there has been intense interest in developing agents suitable for modulating the Wnt pathway in vivo by targeting this enzyme pair. By utilizing a combination of structure-based design and LipE-based structure efficiency relationships, the core of XAV939 was optimized into a more stable, more efficient, but less potent dihydropyran motif 7. This core was combined with elements of screening hits 2, 19, and 33 and resulted in highly potent, selective tankyrase inhibitors that are novel three pocket binders. NVP-TNKS656 (43) was identified as an orally active antagonist of Wnt pathway activity in the MMTV-Wnt1 mouse xenograft model. With an enthalpy-driven thermodynamic signature of binding, highly favorable physicochemical properties, and high lipophilic efficiency, NVP-TNKS656 is a novel tankyrase inhibitor that is well suited for further in vivo validation studies.
• GRONOWITZ S.; LILJEFORS S., ACTA CHEM. SCAND. <ACSA-A4>, 1977, B31, NO 9, 771-780
  作者：GRONOWITZ S.、 LILJEFORS S.

  DOI：——

  日期：——
• Discovery of selective PDE4B inhibitors
  作者：Kenji Naganuma、Akifumi Omura、Naomi Maekawara、Masahiro Saitoh、Naoto Ohkawa、Takashi Kubota、Hiromitsu Nagumo、Toshiyuki Kodama、Masayoshi Takemura、Yuji Ohtsuka、Junji Nakamura、Ryuichi Tsujita、Koh Kawasaki、Hirotsugu Yokoi、Masashi Kawanishi

  DOI：10.1016/j.bmcl.2009.04.121

  日期：2009.6

  In this study the first PDE4B selective inhibitor is described. Optimization of lead 2-arylpyrimidine derivatives afforded a series of potent PDE4B inhibitors with >100-fold selectivity over the PDE4D isozyme. With a good pharmacokinetic profile, a selected compound exhibited potent anti-inflammatory effects in vivo and showed less emesis compared with Cilomilast. (C) 2009 Elsevier Ltd. All rights reserved.
• Novel inhibitors of AP-1 and NF-κB mediated gene expression: structure–activity relationship studies of ethyl 4-[(3-Methyl-2,5-dioxo(3-pyrrolinyl))amino]-2-(trifluoromethyl)pyrimidine-5-carboxylate
  作者：Moorthy S.S Palanki、Paul E Erdman、Anthony M Manning、Arnold Ow、Lynn J Ransone、Cheryl Spooner、Carla Suto、Mark Suto

  DOI：10.1016/s0960-894x(00)00312-7

  日期：2000.8

  In an effort to identify novel inhibitors of AP-1 and NF-kappa B mediated transcriptional activation, several analogues of ethyl 4-[(3-methyl-2,5-dioxo(3-pyrrolinyl))amino]-2-(trifluoromethyl)pyrimidine-5-carboxylate (1) were synthesized and tested in two in vitro assays. The 2-(2'-thienyl) substituted compound (II) was identified as the most potent in this series. (C) 2000 Elsevier Science Ltd. All rights reserved.