N-{3-[(3,5-dimethylphenyl)sulfonyl]-5-chloro-1H-indole-2-carbonyl}-D,L-alanine | 742106-26-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-{3-[(3,5-dimethylphenyl)sulfonyl]-5-chloro-1H-indole-2-carbonyl}-D,L-alanine
• 英文别名: 2-[[5-chloro-3-(3,5-dimethylphenyl)sulfonyl-1H-indole-2-carbonyl]amino]propanoic acid
• CAS: 742106-26-9
• 化学式: C₂₀H₁₉ClN₂O₅S
• 分子量: 434.9
• InChiKey: JGVVSEUJKIEJTA-UHFFFAOYSA-N

物化性质

• 沸点：
  761.9±60.0 °C(Predicted)
• 密度：
  1.434±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  125
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-{3-[(3,5-dimethylphenyl)sulfonyl]-5-chloro-1H-indole-2-carbonyl}-D,L-alanine 在 ammonium hydroxide 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 75.0h， 生成 5-Chloro-3-(3,5-dimethyl-benzenesulfonyl)-1H-indole-2-carboxylic acid [1-(carbamoylmethyl-carbamoyl)-ethyl]-amide
  参考文献：
  名称：

  磺酰吲哚羧酰胺（L-737,126）的简单，短肽衍生物在体外对HIV-1野生型和携带非核苷类逆转录酶抑制剂耐药突变的变体具有活性。

  摘要：

  通过在L-737,126的苯磺酰基部分的3和5位上引入两个甲基并将1至3个甘氨酰胺/丙氨酰胺单元与其羧基酰胺偶联，可以获得对NNRTI抗性突变体有活性的非核苷逆转录酶抑制剂（NNRTIs）。功能。在基于细胞的测定中，新衍生物显示出对HIV-1野生型和NNRTI耐药突变体[Y181C，K103N-Y181C和对依非韦伦高度耐药的三重突变体（K103R，V179D，P225H）的活性优于父本的活性。吲哚衍生物1。

  DOI：

  10.1021/jm031147e
• 作为产物：
  描述：

  N-{3-[(3,5-dimethylphenyl)sulfonyl]-5-chloro-1H-indole-2-carbonyl}-D,L-alanine ethyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以97%的产率得到N-{3-[(3,5-dimethylphenyl)sulfonyl]-5-chloro-1H-indole-2-carbonyl}-D,L-alanine
  参考文献：
  名称：

  磺酰吲哚羧酰胺（L-737,126）的简单，短肽衍生物在体外对HIV-1野生型和携带非核苷类逆转录酶抑制剂耐药突变的变体具有活性。

  摘要：

  通过在L-737,126的苯磺酰基部分的3和5位上引入两个甲基并将1至3个甘氨酰胺/丙氨酰胺单元与其羧基酰胺偶联，可以获得对NNRTI抗性突变体有活性的非核苷逆转录酶抑制剂（NNRTIs）。功能。在基于细胞的测定中，新衍生物显示出对HIV-1野生型和NNRTI耐药突变体[Y181C，K103N-Y181C和对依非韦伦高度耐药的三重突变体（K103R，V179D，P225H）的活性优于父本的活性。吲哚衍生物1。

  DOI：

  10.1021/jm031147e

文献信息

• Chiral Indolylarylsulfone Non-Nucleoside Reverse Transcriptase Inhibitors as New Potent and Broad Spectrum Anti-HIV-1 Agents
  作者：Valeria Famiglini、Giuseppe La Regina、Antonio Coluccia、Domiziana Masci、Andrea Brancale、Roger Badia、Eva Riveira-Muñoz、José A. Esté、Emmanuele Crespan、Alessandro Brambilla、Giovanni Maga、Myriam Catalano、Cristina Limatola、Francesca Romana Formica、Roberto Cirilli、Ettore Novellino、Romano Silvestri

  DOI：10.1021/acs.jmedchem.6b01906

  日期：2017.8.10

  We designed and synthesized a series of chiral indolyarylsulfones (IASs) as new HIV-1 NNRTIs. The new IASs 8-37 showed potent inhibition of the HIV-1 WT NL4-3 strain and of the mutant K103N, Y181C, Y188L, and K103N-Y181C HIV-1 strains. Six racemic mixtures, 8, 23-25, 31, and 33, were separated at semipreparative level into their pure enantiomers. The (R)-8 enantiomer bearing the chiral (alpha-methylbenzyl) was superior to the (S)-counterpart. IAS derivatives bearing the (5) alanine unit, (S)-23, (S,R)-25, (S)-31, and (S)-33, were remarkably more potent than the corresponding (R)-enantiomers. Compound 23 protected hippocampal neuronal cells from the excitotoxic insult, while efavirenz (EFV) did not contrast the neurotoxic effect of glutamate. The present results highlight the chiral IASs as new NNRTIs with improved resistance profile against the mutant HIV-1 strains and reduced neurotoxic effects.
• New indolylarylsulfone non-nucleoside reverse transcriptase inhibitors show low nanomolar inhibition of single and double HIV-1 mutant strains
  作者：Marianna Nalli、Jorge I. Armijos Rivera、Domiziana Masci、Antonio Coluccia、Roger Badia、Eva Riveira-Muñoz、Alessandro Brambilla、Elisabetta Cinquina、Ombretta Turriziani、Francesca Falasca、Myriam Catalano、Cristina Limatola、José A. Esté、Giovanni Maga、Romano Silvestri、Emmanuele Crespan、Giuseppe La Regina

  DOI：10.1016/j.ejmech.2020.112696

  日期：2020.12

  We designed and synthesized 21 new indolylarylsulfones (IASs) as new HIV-1 NNRTIs. Among these, IAS 12 exhibited a remarkable antiviral activity against single and double mutants (K103N EC₅₀ = <0.7 nM; Y181C EC₅₀ = <0.7 nM; Y188L EC₅₀ = 21.3 nM; K103N-Y181C EC₅₀ = 6.2 nM), resulting equally or more active than previuosly reported IAS 6 and some approved anti-HIV-1 drugs. Docking and molecular dynamics simulations of compound 12 in complex with WT, Y181C, Y188L, K103N and K103N-Y181C RTs clarified a general binding mode that was consistent with biological results. Kinetic experiments disclosed that derivative 12 preferentially binds WT and K103N-Y181C RTs to binary and ternary complexes, respectively.
• Simple, Short Peptide Derivatives of a Sulfonylindolecarboxamide (L-737,126) Active in Vitro against HIV-1 Wild Type and Variants Carrying Non-Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations
  作者：Romano Silvestri、Marino Artico、Gabriella De Martino、Giuseppe La Regina、Roberta Loddo、Massimiliano La Colla、Paolo La Colla

  DOI：10.1021/jm031147e

  日期：2004.7.1

  Non-nucleoside reverse transcriptase inhibitors (NNRTIs) active against NNRTI-resistant mutants were obtained by introducing two methyl groups at positions 3 and 5 of the benzenesulfonyl moiety of L-737,126 (1) and coupling one to three glycinamide/alaninamide units to its carboxyamide function. In cell-based assays, the new derivatives showed activities against HIV-1 wild type and NNRTI-resistant

  通过在L-737,126的苯磺酰基部分的3和5位上引入两个甲基并将1至3个甘氨酰胺/丙氨酰胺单元与其羧基酰胺偶联，可以获得对NNRTI抗性突变体有活性的非核苷逆转录酶抑制剂（NNRTIs）。功能。在基于细胞的测定中，新衍生物显示出对HIV-1野生型和NNRTI耐药突变体[Y181C，K103N-Y181C和对依非韦伦高度耐药的三重突变体（K103R，V179D，P225H）的活性优于父本的活性。吲哚衍生物1。