[(3R)-4-[[4-fluoro-7-(1,2,4-triazol-1-yl)-1H-indol-3-yl]sulfonyl]-3-methyl-piperazin-1-yl]-phenyl-methanone | 1001411-90-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: [(3R)-4-[[4-fluoro-7-(1,2,4-triazol-1-yl)-1H-indol-3-yl]sulfonyl]-3-methyl-piperazin-1-yl]-phenyl-methanone
• 英文别名: [(3R)-4-[[4-fluoro-7-(1,2,4-triazol-1-yl)-1H-indol-3-yl]sulfonyl]-3-methylpiperazin-1-yl]-phenylmethanone
• CAS: 1001411-90-0
• 化学式: C₂₂H₂₁FN₆O₃S
• 分子量: 468.512
• InChiKey: AVJXMYYTKYQQKC-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1H-1,2,4-三唑 、 C₂₀H₁₉BrFN₃O₃S 在 铜 氢氧化钾 作用下， 反应 3.0h， 生成 [(3R)-4-[[4-fluoro-7-(1,2,4-triazol-1-yl)-1H-indol-3-yl]sulfonyl]-3-methyl-piperazin-1-yl]-phenyl-methanone
  参考文献：
  名称：

  Design and Synthesis of Human Immunodeficiency Virus Entry Inhibitors: Sulfonamide as an Isostere for the α-Ketoamide Group

  摘要：

  The crystal structures of many tertiary alpha-ketoamides reveal an orthogonal arrangement of the two carbonyl groups. Based on the hypothesis that the alpha-ketoamide HIV attachment inhibitor BMS 806 (formally BMS378806, 26) might bind to its gp120 target via a similar conformation, we designed and synthesized a series of analogs in which the ketoamide group is replaced by an isosteric sulfonamide group. The most potent of these analogs,. 14i, demonstrated antiviral potency comparable to 26 in the M33 pseudotyped antiviral assay. Flexible overlay calculations of a ketoamide inhibitor with a sulfonamide inhibitor revealed a single conformation of each that gave significantly better overlap of key pharmacophore features than other conformations and thus suggest a possible binding conformation for each class.

  DOI：

  10.1021/jm070650e

文献信息

• Design and Synthesis of Human Immunodeficiency Virus Entry Inhibitors: Sulfonamide as an Isostere for the α-Ketoamide Group
  作者：Rong-Jian Lu、John A. Tucker、Tatiana Zinevitch、Olga Kirichenko、Vitalii Konoplev、Svetlana Kuznetsova、Sergey Sviridov、Jason Pickens、Sagun Tandel、Enugurthi Brahmachary、Yang Yang、Jian Wang、Stephanie Freel、Shelly Fisher、Alana Sullivan、Jiying Zhou、Sherry Stanfield-Oakley、Michael Greenberg、Dani Bolognesi、Brian Bray、Barney Koszalka、Peter Jeffs、Alisher Khasanov、You-An Ma、Cynthia Jeffries、Changhui Liu、Tatiana Proskurina、Tong Zhu、Alexander Chucholowski、Rongshi Li、Connie Sexton

  DOI：10.1021/jm070650e

  日期：2007.12.27

  The crystal structures of many tertiary alpha-ketoamides reveal an orthogonal arrangement of the two carbonyl groups. Based on the hypothesis that the alpha-ketoamide HIV attachment inhibitor BMS 806 (formally BMS378806, 26) might bind to its gp120 target via a similar conformation, we designed and synthesized a series of analogs in which the ketoamide group is replaced by an isosteric sulfonamide group. The most potent of these analogs,. 14i, demonstrated antiviral potency comparable to 26 in the M33 pseudotyped antiviral assay. Flexible overlay calculations of a ketoamide inhibitor with a sulfonamide inhibitor revealed a single conformation of each that gave significantly better overlap of key pharmacophore features than other conformations and thus suggest a possible binding conformation for each class.