ethyl 2-[N-[5-chloro-3-[(3,5-dimethylphenyl)sulfonyl]-1H-indole-2-carboxamido]]acetate | 473257-55-5

• 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: ethyl 2-[N-[5-chloro-3-[(3,5-dimethylphenyl)sulfonyl]-1H-indole-2-carboxamido]]acetate
• 英文别名: N-{3-[(3,5-dimethylphenyl)sulfonyl]-5-chloro-1H-indole-2-carbonyl}glycine ethyl ester；2-{N-[5-chloro-3-(3,5-dimethylphenylsulfonyl)-indol-2-carboxy-amido]}-acetic acid ethyl ester；ethyl 2-[[5-chloro-3-(3,5-dimethylphenyl)sulfonyl-1H-indole-2-carbonyl]amino]acetate
• CAS: 473257-55-5
• 化学式: C₂₁H₂₁ClN₂O₅S
• 分子量: 448.927
• InChiKey: YDLCMNQKDDESGX-UHFFFAOYSA-N

物化性质

• 沸点：
  714.2±60.0 °C(Predicted)
• 密度：
  1.368±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-[N-[5-chloro-3-[(3,5-dimethylphenyl)sulfonyl]-1H-indole-2-carboxamido]]acetate 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以98%的产率得到N-{3-[(3,5-dimethylphenyl)sulfonyl]-5-chloro-1H-indole-2-carbonyl}glycine
  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：

  1-(3,5-dimethylphenylthio)pyrrolidine-2,5-dione 在 lithium hydroxide 、 三氟化硼乙醚 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 101.0h， 生成 ethyl 2-[N-[5-chloro-3-[(3,5-dimethylphenyl)sulfonyl]-1H-indole-2-carboxamido]]acetate
  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

• [EN] SUBSTITUTED PHENYLINDOLES FOR THE TREATMENT OF HIV<br/>[FR] PHENYLINDOLES SUBSTITUES DE TRAITEMENT DU VIH
  申请人：IDENIX CAYMAN LTD

  公开号：WO2004014364A1

  公开（公告）日：2004-02-19

  This invention is in the area of phenylindoles that are useful for the treatment of HIV infection, and, in particular, phenylindoles that exhibit significant activity against resistant strains of HIV. The phenylindoles have at least two substituents other than hydrogen on the benzo ring of the indole function, preferably at the 4' and 5', 5' and 6' or the 5' and 7' positions, optionally in combination with disubstitution at positions 3' and 5' on the phenyl ring of the compound, and carboxamide containing moieties at position-2 on the indole group of the compound. Methyl is a preferred group for substitution on the phenyl ring. Preferred substituents for the benzo ring of the indole function include but are not limited to chlorine, fluorine, bromine, iodine, CF3, methoxy, CN, and NO2­.

  这项发明涉及苯基吲哚领域，用于治疗HIV感染，特别是对抗HIV耐药菌株具有显著活性的苯基吲哚。这些苯基吲哚在吲哚功能的苯环上至少有两个取代基，除了氢，最好在4'和5'、5'和6'或5'和7'位置，可选地与化合物的苯环上的3'和5'位置二取代结合，并且在化合物的吲哚基团的2号位置含有羧酰胺基团。甲基是苯环上取代的首选基团。吲哚功能的苯环的首选取代基包括但不限于氯、氟、溴、碘、CF3、甲氧基、CN和NO2。
• Indolylarylsulfones Bearing Natural and Unnatural Amino Acids. Discovery of Potent Inhibitors of HIV-1 Non-Nucleoside Wild Type and Resistant Mutant Strains Reverse Transcriptase and Coxsackie B4 Virus
  作者：Francesco Piscitelli、Antonio Coluccia、Andrea Brancale、Giuseppe La Regina、Anna Sansone、Cesare Giordano、Jan Balzarini、Giovanni Maga、Samantha Zanoli、Alberta Samuele、Roberto Cirilli、Francesco La Torre、Antonio Lavecchia、Ettore Novellino、Romano Silvestri

  DOI：10.1021/jm801470b

  日期：2009.4.9

  New potent indolylarylsulfone (IAS) HIV-I NNRTIs were obtained by coupling natural and unnatural amino acids to the 2-carboxamide and introducing different electron-withdrawing substituents at position 4 and 5 of the indole nucleus. The new IASs inhibited the HIV-1 replication in human T-lymphocyte (CEM) cells at low/subnanomolar concentration and were weakly cytostatic. Against the mutant L100I, K103N, and Y181C RT HIV-1 strains in CEM cells, sulfones 3, 4, 19, 27, and 31 were comparable to EFV. The new IASs were inhibitors to Coxsackie B4 virus at low micromolar (2-9 mu M) concentrations. Superimposition of PLANTS docked conformations of IASs 19 and 9 revealed different hydrophobic interactions of the 3,5-dimethylphenyl group, for which a staking interaction with Tyr181 aromatic side chain was observed. The binding mode of 19 was not affected by the L100I mutation and was consistent with the interactions reported for the WT strain.
• 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。