N-[(2S)-2-[5-[1-(2-azabicyclo[2.2.2]octan-2-yl)-2-methyl-1-oxopropan-2-yl]-2-(3,5-dimethylphenyl)-1H-indol-3-yl]propyl]-2,4-dinitrobenzenesulfonamide | 380227-90-7

• 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: N-[(2S)-2-[5-[1-(2-azabicyclo[2.2.2]octan-2-yl)-2-methyl-1-oxopropan-2-yl]-2-(3,5-dimethylphenyl)-1H-indol-3-yl]propyl]-2,4-dinitrobenzenesulfonamide
• CAS: 380227-90-7
• 化学式: C₃₆H₄₁N₅O₇S
• 分子量: 687.817
• InChiKey: GFWWSDYYIYTHBV-MNEVETPYSA-N

物化性质

• 沸点：
  879.8±75.0 °C(Predicted)
• 密度：
  1.325±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  49
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  182
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-[(2S)-2-[5-[1-(2-azabicyclo[2.2.2]octan-2-yl)-2-methyl-1-oxopropan-2-yl]-2-(3,5-dimethylphenyl)-1H-indol-3-yl]propyl]-2,4-dinitrobenzenesulfonamide 在 palladium on activated charcoal 正丙胺 、 甲酸铵 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 甲醇 、 二氯甲烷 、 苯 为溶剂， 生成
  参考文献：
  名称：

  2-Arylindoles as gonadotropin releasing hormone (GnRH) antagonists: optimization of the tryptamine side chain

  摘要：

  A series of 2-arylindoles containing novel heteroaromatic substituents on the tryptamine tether, based on compound 1, was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) antagonists. Successful modifications of 1 included chain length variation (reduction) and replacement of the pyridine with heteroaromatic groups. These alterations culminated in the discovery of compound 27kk which had excellent in vitro potency and oral efficacy in rodents. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00026-4
• 作为产物：
  描述：

  (S)-2-[3-(2-tert-butoxycarbonylamino-1-methylethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-2-methylpropionic acid 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 碳酸氢钠 、 苯甲醚 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-[(2S)-2-[5-[1-(2-azabicyclo[2.2.2]octan-2-yl)-2-methyl-1-oxopropan-2-yl]-2-(3,5-dimethylphenyl)-1H-indol-3-yl]propyl]-2,4-dinitrobenzenesulfonamide
  参考文献：
  名称：

  Orally bioavailable, indole-based nonpeptide GnRH receptor antagonists with high potency and functional activity

  摘要：

  Stereospecific introduction of a methyl group to the indole-3-side chain enhanced activity in our tryptamine-derived series of GnRH receptor antagonists. Further improvements were achieved by variation of the bicyclic amino moiety of the tertiary amide and by adjustment of the tether length to a pyridine or pyridone terminus. These modifications culminated in analogue 24, which had oral activity in a rat model and acceptable oral bioavailability and half-life in dogs and monkeys. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00512-1

文献信息

• Modification of the pyridine moiety of non-peptidyl indole GnRH receptor antagonists
  作者：Joseph P Simeone、Robert L Bugianesi、Mitree M Ponpipom、Yi Tien Yang、Jane-Ling Lo、Joel B Yudkovitz、Jisong Cui、George R Mount、Rena Ning Ren、Mellissa Creighton、An-Hua Mao、Stella H Vincent、Kang Cheng、Mark T Goulet

  DOI：10.1016/s0960-894x(02)00751-5

  日期：2002.11

  The synthesis of a number of indole GnRH antagonists is described. Oxidation of the pyridine ring nitrogen, combined with alkylation at the two position, led to a compound with an excellent in vitro activity profile as well as oral bioavailability in both rats and dogs. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Orally bioavailable, indole-based nonpeptide GnRH receptor antagonists with high potency and functional activity
  作者：Wallace T. Ashton、Rosemary M. Sisco、Gerard R. Kieczykowski、Yi Tien Yang、Joel B. Yudkovitz、Jisong Cui、George R. Mount、Rena Ning Ren、Tsuei-Ju Wu、Xiaolan Shen、Kathryn A. Lyons、An-Hua Mao、Josephine R. Carlin、Bindhu V. Karanam、Stella H. Vincent、Kang Cheng、Mark T. Goulet

  DOI：10.1016/s0960-894x(01)00512-1

  日期：2001.10

  Stereospecific introduction of a methyl group to the indole-3-side chain enhanced activity in our tryptamine-derived series of GnRH receptor antagonists. Further improvements were achieved by variation of the bicyclic amino moiety of the tertiary amide and by adjustment of the tether length to a pyridine or pyridone terminus. These modifications culminated in analogue 24, which had oral activity in a rat model and acceptable oral bioavailability and half-life in dogs and monkeys. (C) 2001 Elsevier Science Ltd. All rights reserved.
• 2-Arylindoles as gonadotropin releasing hormone (GnRH) antagonists: optimization of the tryptamine side chain
  作者：Jonathan R. Young、Song X. Huang、Thomas F. Walsh、Matthew J. Wyvratt、Yi Tien Yang、Joel B. Yudkovitz、Jisong Cui、George R. Mount、Rena Ning Ren、Tsuei-Ju Wu、Xiaolan Shen、Kathryn A. Lyons、An-Hua Mao、Josephine R. Carlin、Bindhu V. Karanam、Stella H. Vincent、Kang Cheng、Mark T. Goulet

  DOI：10.1016/s0960-894x(02)00026-4

  日期：2002.3

  A series of 2-arylindoles containing novel heteroaromatic substituents on the tryptamine tether, based on compound 1, was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) antagonists. Successful modifications of 1 included chain length variation (reduction) and replacement of the pyridine with heteroaromatic groups. These alterations culminated in the discovery of compound 27kk which had excellent in vitro potency and oral efficacy in rodents. (C) 2002 Elsevier Science Ltd. All rights reserved.