tert-butyl (3S,6R,8aR)-6-acetamido-6-benzyl-5-oxo-1,2,3,7,8,8a-hexahydroindolizine-3-carboxylate | 162284-68-6

• 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: tert-butyl (3S,6R,8aR)-6-acetamido-6-benzyl-5-oxo-1,2,3,7,8,8a-hexahydroindolizine-3-carboxylate
• CAS: 162284-68-6
• 化学式: C₂₂H₃₀N₂O₄
• 分子量: 386.491
• InChiKey: PMPJQMFVQIHGOR-KGVIQGDOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (3S,6R,8aR)-6-acetamido-6-benzyl-5-oxo-1,2,3,7,8,8a-hexahydroindolizine-3-carboxylate 在 N-甲基吗啉 、 lithium aluminium tetrahydride 、 三氟乙酸 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 ({(S)-3-[((3S,6R,8aR)-6-Acetylamino-6-benzyl-5-oxo-octahydro-indolizine-3-carbonyl)-amino]-2-hydroxy-piperidin-1-yl}-imino-methyl)-carbamic acid benzyl ester
  参考文献：
  名称：

  Design and synthesis of conformationally constrained arginal thrombin inhibitors

  摘要：

  A series of conformationally constrained arginal thrombin inhibitors was prepared starting from 5,6 or 5,7 bicyclic lactamic structures, that an indirect approach of X-ray structure-based drug design indicated as D-Phe-Pro dipeptide mimetics. The tetrahydroquinolyl sulfonamido derivative Ig (LR-D/009) displayed the best inhibitory potency (IC50=0.018 mu m), with good selectivity over plasmin and trypsin. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00403-4
• 作为产物：
  描述：

  N-acetamido cinnamic acid 在 4-二甲氨基吡啶 、 偶氮二异丁腈 、 三正丁基氢锡 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 sodium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 、 苯 为溶剂， 生成 tert-butyl (3S,6R,8aR)-6-acetamido-6-benzyl-5-oxo-1,2,3,7,8,8a-hexahydroindolizine-3-carboxylate
  参考文献：
  名称：

  Design and synthesis of conformationally constrained arginal thrombin inhibitors

  摘要：

  A series of conformationally constrained arginal thrombin inhibitors was prepared starting from 5,6 or 5,7 bicyclic lactamic structures, that an indirect approach of X-ray structure-based drug design indicated as D-Phe-Pro dipeptide mimetics. The tetrahydroquinolyl sulfonamido derivative Ig (LR-D/009) displayed the best inhibitory potency (IC50=0.018 mu m), with good selectivity over plasmin and trypsin. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00403-4

文献信息

• Conformationally constrained dipeptides: Synthesis of 7,5- and 6,5-fused bicyclic lactams by stereoselective radical cyclizations
  作者：Lino Colombo、Marcello Di Giacomo、Carlo Scolastico、Leonardo Manzoni、Laura Belvisi、Valentina Molteni

  DOI：10.1016/0040-4039(94)02319-7

  日期：1995.1

  A study of radical cyclizations of β-substituted α-N-acetyl acrylamide have been performed: high level of regio- and stereoselectivity was obtained.

  已经进行了对β-取代的α-N-乙酰基丙烯酰胺的自由基环化的研究：获得了高水平的区域选择性和立体选择性。
• Colombo, Lino; Giacomo, Marcello Di; Belvisi, Laura, Gazzetta Chimica Italiana, 1996, vol. 126, # 8, p. 543 - 554
  作者：Colombo, Lino、Giacomo, Marcello Di、Belvisi, Laura、Manzoni, Leonardo、Scolastico, Carlo、Salimbeni, Aldo

  DOI：——

  日期：——
• [EN] BICYCLIC LACTAM DERIVATIVES AS THROMBIN INHIBITORS<br/>[FR] DERIVES LACTAMES BICYCLIQUES UTILISES COMME INHIBITEURS DE THROMBINE
  申请人：A. MENARINI INDUSTRIE FARMACEUTICHE RIUNITE S.R.L.

  公开号：WO1997005160A1

  公开（公告）日：1997-02-13

  (EN) Bicyclic lactams containing an arginine residue, which can be of use in therapy as thrombin inhibitors, are disclosed.(FR) L'invention porte sur des lactames bicycliques contenant un reste arginine qui peuvent être utilisés, dans un traitement, comme inhibiteurs de thrombine.
• Design and synthesis of conformationally constrained arginal thrombin inhibitors
  作者：Aldo Salimbeni、Fabio Paleari、Renato Canevotti、Marco Criscuoli、Marco Criscuoli、Annalisa Lippi、Mauro Angiolini、Laura Belvisi、Carlo Scolastico、Lino Colombo

  DOI：10.1016/s0960-894x(97)00403-4

  日期：1997.9

  A series of conformationally constrained arginal thrombin inhibitors was prepared starting from 5,6 or 5,7 bicyclic lactamic structures, that an indirect approach of X-ray structure-based drug design indicated as D-Phe-Pro dipeptide mimetics. The tetrahydroquinolyl sulfonamido derivative Ig (LR-D/009) displayed the best inhibitory potency (IC50=0.018 mu m), with good selectivity over plasmin and trypsin. (C) 1997 Elsevier Science Ltd.