endo-tert-butyl (1R,5S)-3-[(3-nitropyridin-2-yl)amino]-8-azabicyclo[3.2.1]octane-8-carboxylate | 716359-09-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: endo-tert-butyl (1R,5S)-3-[(3-nitropyridin-2-yl)amino]-8-azabicyclo[3.2.1]octane-8-carboxylate
• CAS: 716359-09-0
• 化学式: C₁₇H₂₄N₄O₄
• 分子量: 348.402
• InChiKey: GFNUBVFAFCFFRF-CLLJXQQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.33
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  97.6
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  endo-tert-butyl (1R,5S)-3-[(3-nitropyridin-2-yl)amino]-8-azabicyclo[3.2.1]octane-8-carboxylate 在 palladium 10% on activated carbon 、 氢气 、 camphor-10-sulfonic acid 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 19.0h， 生成 endo-tert-butyl (1R,5S)-3-(2-methyl-3H-imidazo[4,5-b]pyridin-3-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate
  参考文献：
  名称：

  Novel 4,4-Disubstituted Piperidine-Based C–C Chemokine Receptor-5 Inhibitors with High Potency against Human Immunodeficiency Virus-1 and an Improved human Ether-a-go-go Related Gene (hERG) Profile

  摘要：

  We recently described (J. Med. Chem. 2008, 51, 6538-6546) a novel class of CCR5 antagonists with strong anti-HIV potency. Herein, we detail SAR converting leads 1 and 2 to druglike molecules. The pivotal structural motif enabling this transition was the secondary sulfonamide substituent. Further fine-tuning of the substituent pattern in the sulfonamide paved the way to enhancing potency and bioavailability and minimizing hERG inhibition, resulting in discovery of clinical compound 122 (GSK163929).

  DOI：

  10.1021/jm200279v
• 作为产物：
  描述：

  1,1-dimethylethyl endo-3-[(phenylmethyl)amino]-8-azabicyclo[3.2.1]octane-8-carboxylate 在 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 、 甲醇 为溶剂， 反应 16.0h， 生成 endo-tert-butyl (1R,5S)-3-[(3-nitropyridin-2-yl)amino]-8-azabicyclo[3.2.1]octane-8-carboxylate
  参考文献：
  名称：

  Novel 4,4-Disubstituted Piperidine-Based C–C Chemokine Receptor-5 Inhibitors with High Potency against Human Immunodeficiency Virus-1 and an Improved human Ether-a-go-go Related Gene (hERG) Profile

  摘要：

  We recently described (J. Med. Chem. 2008, 51, 6538-6546) a novel class of CCR5 antagonists with strong anti-HIV potency. Herein, we detail SAR converting leads 1 and 2 to druglike molecules. The pivotal structural motif enabling this transition was the secondary sulfonamide substituent. Further fine-tuning of the substituent pattern in the sulfonamide paved the way to enhancing potency and bioavailability and minimizing hERG inhibition, resulting in discovery of clinical compound 122 (GSK163929).

  DOI：

  10.1021/jm200279v

文献信息

• [EN] PIPERIDINE DERIVATIVES AS CCR5 ANTAGONISTS<br/>[FR] ANTAGONISTES DE CCR5 UTILES COMME AGENTS THERAPEUTIQUES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004054974A3

  公开（公告）日：2004-09-02
• US7645771B2
  申请人：——

  公开号：US7645771B2

  公开（公告）日：2010-01-12