1-methyl-N-(5-nitrobenzo[d]isothiazol-3-yl)-4-oxo-1,4-dihydropyridine-3-carboxamide

• 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: 1-methyl-N-(5-nitrobenzo[d]isothiazol-3-yl)-4-oxo-1,4-dihydropyridine-3-carboxamide
• 英文别名: HIV-1 inhibitor-6；1-methyl-N-(5-nitro-1,2-benzothiazol-3-yl)-4-oxopyridine-3-carboxamide
• 化学式: C₁₄H₁₀N₄O₄S
• 分子量: 330.324
• InChiKey: CPKUAABJFWRBSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  136
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-氯吡啶 在 氯化亚砜 、 水 、 potassium hydrogencarbonate 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 1-methyl-N-(5-nitrobenzo[d]isothiazol-3-yl)-4-oxo-1,4-dihydropyridine-3-carboxamide
  参考文献：
  名称：

  A Parallel Synthesis Approach to the Identification of Novel Diheteroarylamide-Based Compounds Blocking HIV Replication: Potential Inhibitors of HIV-1 Pre-mRNA Alternative Splicing

  摘要：

  A 256-compound library was evaluated in an anti-HIV screen to identify structural "mimics" of the fused tetracyclic indole compound 1 (IDC16) that conserve its anti-HIV activity without associated cytotoxicity. Four diheteroarylamide-type compounds, containing a common 5-nitroisobenzothiazole motif, were identified as active. In subsequent screens, the most potent compound 9 (1C8) was active against wild-type HIV-1(IIIB) (subtype B, X4-tropic) and HIV-1 97USSN54 (subtype A, R5-tropic) with EC50's of 0.6 and 0.9 mu M, respectively. Compound 9 also inhibited HIV strains resistant to drugs targeting HIV reverse transcriptase, protease, integrase, and coreceptor CCRS with EC50's ranging from 0.9 to 1.5 mu M. The CC50 value obtained in a cytotoxicity assay for compound 9 was >100 mu M, corresponding to a therapeutic index (CC50/EC50) of approximately 100. Further comparison studies revealed that, whereas the anti-HIV activity for compound 9 and the parent molecule 1 are similar, the cytotoxic effect for compound 9 was, as planned, markedly suppressed.

  DOI：

  10.1021/acs.jmedchem.5b01357

文献信息

• The Reaction of N-Trimethylsilyl-Substituted Heteroarylamines with Esters and Thioesters: An Efficient Protocol To Access Diheteroarylamides
  作者：Ana Koperniku、Maryam Zamiri、David Grierson

  DOI：10.1055/s-0037-1611435

  日期：2019.4

  representative 4-pyridinone-based carboxylic acid were sufficiently activated to react efficiently in amide coupling reactions with the amide anion generated in situ from the N-trimethylsilyl derivative of different weakly nucleophilic heteroarylamines. In acetonitrile as solvent, the precipitated diheteroarylamide products were isolated in pure form by vacuum filtration. This simple amide bond forming protocol

  抽象的 具有代表性的基于4-吡啶酮的羧酸的S-苄基硫酯和甲酯衍生物被充分活化以在酰胺偶联反应中与从不同的弱亲核性杂芳基胺的N-三甲基甲硅烷基衍生物原位产生的酰胺阴离子有效地反应。在乙腈作为溶剂中，通过真空过滤以纯净的形式分离出沉淀的二杂芳基酰胺产物。这种简单的酰胺键形成方案可以很容易地适应化合物库的平行合成。 具有代表性的基于4-吡啶酮的羧酸的S-苄基硫酯和甲酯衍生物被充分活化以在酰胺偶联反应中与从不同的弱亲核性杂芳基胺的N-三甲基甲硅烷基衍生物原位产生的酰胺阴离子有效地反应。在乙腈作为溶剂中，通过真空过滤以纯净的形式分离出沉淀的二杂芳基酰胺产物。这种简单的酰胺键形成方案可以很容易地适应化合物库的平行合成。
• [EN] BENZISOTHIAZOLE DERIVATIVE COMPOUNDS AS THERAPEUTICS AND METHODS FOR THEIR USE<br/>[FR] COMPOSÉS DÉRIVÉS DE BENZISOTHIAZOLE UTILISÉS COMME AGENTS THÉRAPEUTIQUES ET LEURS MÉTHODES D'UTILISATION
  申请人：UNIV BRITISH COLUMBIA

  公开号：WO2015164956A1

  公开（公告）日：2015-11-05

  This invention provides compound having a structure of Formulas and uses of such compounds for inhibiting HIV infection, adenovirus infection, or for the treatment of colon cancer or spinal muscular atrophy.
• A Parallel Synthesis Approach to the Identification of Novel Diheteroarylamide-Based Compounds Blocking HIV Replication: Potential Inhibitors of HIV-1 Pre-mRNA Alternative Splicing
  作者：Peter K. Cheung、David Horhant、Laura E. Bandy、Maryam Zamiri、Safwat M. Rabea、Stoyan K. Karagiosov、Mitra Matloobi、Steven McArthur、P. Richard Harrigan、Benoit Chabot、David S. Grierson

  DOI：10.1021/acs.jmedchem.5b01357

  日期：2016.3.10

  A 256-compound library was evaluated in an anti-HIV screen to identify structural "mimics" of the fused tetracyclic indole compound 1 (IDC16) that conserve its anti-HIV activity without associated cytotoxicity. Four diheteroarylamide-type compounds, containing a common 5-nitroisobenzothiazole motif, were identified as active. In subsequent screens, the most potent compound 9 (1C8) was active against wild-type HIV-1(IIIB) (subtype B, X4-tropic) and HIV-1 97USSN54 (subtype A, R5-tropic) with EC50's of 0.6 and 0.9 mu M, respectively. Compound 9 also inhibited HIV strains resistant to drugs targeting HIV reverse transcriptase, protease, integrase, and coreceptor CCRS with EC50's ranging from 0.9 to 1.5 mu M. The CC50 value obtained in a cytotoxicity assay for compound 9 was >100 mu M, corresponding to a therapeutic index (CC50/EC50) of approximately 100. Further comparison studies revealed that, whereas the anti-HIV activity for compound 9 and the parent molecule 1 are similar, the cytotoxic effect for compound 9 was, as planned, markedly suppressed.