tert-butyl (1R,3r,5S)-3-(benzylamino)-8-azabicyclo[3.2.1]octane-8-carboxylate | 207564-70-3

• 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: tert-butyl (1R,3r,5S)-3-(benzylamino)-8-azabicyclo[3.2.1]octane-8-carboxylate
• 英文别名: tert-butyl 3-(benzylamino)-endo-8-azabicyclo[3.2.1]octane-8-carboxylate；1,1-dimethylethyl 3-[(phenylmethyl)amino]-8-azabicyclo[3.2.1]octane-8-carboxylate
• CAS: 207564-70-3
• 化学式: C₁₉H₂₈N₂O₂
• 分子量: 316.444
• InChiKey: SFSGQPRQMNUZTA-OSYLJGHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.71
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  41.57
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (1R,3r,5S)-3-(benzylamino)-8-azabicyclo[3.2.1]octane-8-carboxylate 在 盐酸 、 palladium hydroxide on carbon 、 氢气 、 甲酸铵 、 三乙酰氧基硼氢化钠 、 铁粉 、 potassium carbonate 、 溶剂黄146 作用下， 以 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 20.0~140.0 ℃ 、400.01 kPa 条件下， 反应 170.0h， 生成 3-endo-(8-azabicyclo[3.2.1]oct-3-yl)-5-benzyl-2-methyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridine
  参考文献：
  名称：

  An Imidazopiperidine Series of CCR5 Antagonists for the Treatment of HIV: The Discovery of N-{(1S)-1-(3-Fluorophenyl)-3-[(3-endo)-3-(5-isobutyryl-2-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]propyl}acetamide (PF-232798)

  摘要：

  Preventing entry of HIV into human host cells has emerged as an attractive approach to controlling viral replication Maraviroc 1 is an approved antagonist of the human CCR5 receptor which prevents the entry of HIV Herein, we report the design and discovery of a series of imidazopiperidine CCR5 antagonists which retain the attractive antiviral profile and window over hERG activity of maraviroc 1, combined with improved absorption profiles in rat and dog Furthermore, this series of compounds has been shown to retain activity against a laboratory generated maraviroc-resistant HIV-1 strain, which indicates an alternative resistance profile to that of maraviroc 1 Compound 41f (PF-232798) was selected as a clinical candidate from the imidazopiperidine series and is currently in phase II clinical trials

  DOI：

  10.1021/jm100978n
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 palladium hydroxide on carbon 、 氢气 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 20.0 ℃ 、269.0 kPa 条件下， 反应 20.0h， 生成 tert-butyl (1R,3r,5S)-3-(benzylamino)-8-azabicyclo[3.2.1]octane-8-carboxylate
  参考文献：
  名称：

  An Imidazopiperidine Series of CCR5 Antagonists for the Treatment of HIV: The Discovery of N-{(1S)-1-(3-Fluorophenyl)-3-[(3-endo)-3-(5-isobutyryl-2-methyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]propyl}acetamide (PF-232798)

  摘要：

  Preventing entry of HIV into human host cells has emerged as an attractive approach to controlling viral replication Maraviroc 1 is an approved antagonist of the human CCR5 receptor which prevents the entry of HIV Herein, we report the design and discovery of a series of imidazopiperidine CCR5 antagonists which retain the attractive antiviral profile and window over hERG activity of maraviroc 1, combined with improved absorption profiles in rat and dog Furthermore, this series of compounds has been shown to retain activity against a laboratory generated maraviroc-resistant HIV-1 strain, which indicates an alternative resistance profile to that of maraviroc 1 Compound 41f (PF-232798) was selected as a clinical candidate from the imidazopiperidine series and is currently in phase II clinical trials

  DOI：

  10.1021/jm100978n

文献信息

• Tropane derivatives useful in therapy
  申请人：Pfizer Inc.

  公开号：US20040014742A1

  公开（公告）日：2004-01-22

  The present invention provides compounds of formula (I) 1 wherein X, Y, R 1 , R 2 and R 3 are as defined hereinabove. The compounds of the present invention are modulators, especially antagonists, of the activity of chemokine CCR5 receptors. Modulators of the CCR5 receptor may be useful in the treatment of various inflammatory diseases and conditions, and in the treatment of infection by HIV and genetically related retroviruses.

  本发明提供了式(I)中的化合物，其中X、Y、R1、R2和R3如上文所定义。本发明的化合物是化学趋化因子CCR5受体的调节剂，特别是拮抗剂。CCR5受体的调节剂可能在治疗各种炎症性疾病和症状以及治疗HIV和遗传相关逆转录病毒感染方面有用。
• HETEROARYL-SUBSTITUTED SULFONAMIDE COMPOUNDS AND THEIR USE AS SODIUM CHANNEL INHIBITORS
  申请人：Xenon Pharmaceuticals Inc.

  公开号：US20200071313A1

  公开（公告）日：2020-03-05

  This invention is directed to heteroaryl-substituted sulfonamide compounds, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment of diseases or conditions associated with voltage-gated sodium channels, such as epilepsy.

  这项发明涉及杂环取代磺酰胺化合物，包括其立体异构体、对映异构体、互变异构体或其混合物；或其药用可接受盐、溶剂合物或前药，用于治疗与电压门控钠通道相关的疾病或症状，如癫痫。
• [EN] IMIDAZOPYRIDINE SUBSTITUTED TROPANE DERIVATIVES WITH CCR5 RECEPTOR ANTAGONIST ACTIVITY FOR THE TREATMENT OF HIV AND INFLAMMATION<br/>[FR] DERIVES DE TROPANE A SUBSTITUTION IMIDAZOPYRIDINE EN TANT QU'ANTAGONISTES DES RECEPTEURS CCR5 POUR LE TRAITEMENT DU VIH ET DE L'INFLAMMATION
  申请人：PFIZER LTD

  公开号：WO2005033107A1

  公开（公告）日：2005-04-14

  The present invention provides compounds of formula (I) wherein R1 and R2 are as defined hereinabove. The compounds of the present invention are modulators, especially antagonists, of the activity of chemokine CCR5 receptors. Modulators of the CCR5 receptor may be useful in the treatment of various inflammatory diseases and conditions, and in the treatment of infection by HIV and genetically related retroviruses.

  本发明提供了式（I）中R1和R2如上所定义的化合物。本发明的化合物是化学因子CCR5受体的调节剂，特别是拮抗剂。CCR5受体的调节剂可能在治疗各种炎症性疾病和状况以及治疗HIV和遗传相关逆转录病毒感染方面有用。
• PIPERAZINO DERIVATIVES AS NEUROKININ ANTAGONISTS
  申请人：SCHERING CORPORATION

  公开号：EP0937069B1

  公开（公告）日：2006-05-03