(1R,2R)-2-[(tert-butoxycarbonyl)amino]indane-1-carboxylic acid | 845268-98-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (1R,2R)-2-[(tert-butoxycarbonyl)amino]indane-1-carboxylic acid
• 英文别名: (1R,2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-2,3-dihydro-1H-indene-1-carboxylic acid
• CAS: 845268-98-6
• 化学式: C₁₅H₁₉NO₄
• 分子量: 277.32
• InChiKey: GFHYZWUGRYLPCL-VXGBXAGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,2R)-2-[(tert-butoxycarbonyl)amino]indane-1-carboxylic acid 在 盐酸 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 (1R,2R)-2-amino-N,N-dimethyl-2,3-dihydro-1H-indene-1-carboxamide
  参考文献：
  名称：

  Identification and Pharmacological Profile of an Indane Based Series of Ghrelin Receptor Full Agonists

  摘要：

  Cachexia and muscle wasting are very common among patients suffering from cancer, chronic obstructive pulmonary disease, and other chronic diseases. Ghrelin stimulates growth hormone secretion via the ghrelin receptor, which subsequently leads to increase of IGF-1 plasma levels. The activation of the GH/IGF-1 axis leads to an increase of muscle mass and functional capacity. Ghrelin further acts on inflammation, appetite, and adipogenesis and for this reason was considered an important target to address catabolic conditions. We report the synthesis and properties of an indane based series of ghrelin receptor full agonists; they have been shown to generate a sustained increase of IGF-1 levels in dog and have been thoroughly investigated with respect to their functional activity.

  DOI：

  10.1021/acs.jmedchem.8b00322
• 作为产物：
  描述：

  tert-butyl [(1R,2R)-1-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl]carbamate 在 ruthenium trichloride sodium periodate 作用下， 以 四氯化碳 、 水 、 乙腈 为溶剂， 反应 3.0h， 以100%的产率得到(1R,2R)-2-[(tert-butoxycarbonyl)amino]indane-1-carboxylic acid
  参考文献：
  名称：

  [EN] HETEROCYCLIC AMIDE DERIVATIVES WHICH POSSESS GLYCOGEN PHOSPHORYLASE INHIBITORY ACTIVITY
  [FR] DERIVES D'AMIDE HETEROCYCLIQUES PRESENTANT UNE ACTIVITE INHIBITRICE DE LA GLYCOGENE PHOSPHORYLASE

  摘要：

  该化合物的结构式（1）或其药用可接受的盐或前药；其中，例如，Z为CH或氮，R4和R5一起是-S-C（R6）=C（R7）-或-C（R7）=C（R6）-S-；R6和R7分别选自氢，卤素，硝基，氰基，羟基，氟甲基，二氟甲基，三氟甲基，三氟甲氧基，羧基和氨基；A为苯基或杂环芳基；n为0，1或2；r为1或2；R1为卤素，氰基或羧基；Y选自-C（O）R2，-C（O）OR2，-C（O）NR2R3，-(1-4C)烷基[可选择取代]-(2-4C)烯基，-SO2NR2R3和-S（O）cR2（其中c为0，1或2）；R2和R3分别选自氢，-O（1-4C）烷基，-S（1-4C）烷基，-N（1-4C）烷基，杂环烷基，芳基和（1-4C）烷基[可选择取代]；具有糖原磷酸化酶抑制活性，因此在治疗与糖原磷酸化酶活性增加相关的疾病状态中具有价值。描述了制备该化合物和含有它们的药物组合物的方法。

  公开号：

  WO2005013981A1

文献信息

• [EN] HETEROCYCLIC AMIDE DERIVATIVES WHICH POSSESS GLYCOGEN PHOSPHORYLASE INHIBITORY ACTIVITY<br/>[FR] DERIVES D'AMIDE HETEROCYCLIQUES PRESENTANT UNE ACTIVITE INHIBITRICE DE LA GLYCOGENE PHOSPHORYLASE
  申请人：ASTRAZENECA AB

  公开号：WO2005013981A1

  公开（公告）日：2005-02-17

  A compound of the formula (1) or a pharmaceutically-acceptable salt, or pro-drug thereof; wherein, for example, Z is CH or nitrogen, R4 and R5 together are either -S-C(R6)=C(R7)- or -C(R7)=C(R6)-S- ; R6 and R7 are independently selected from hydrogen, halo, nitro, cyano, hydroxy, fluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, carboxy and carbamoyl; A is phenylene or heteroarylene; n is 0, 1 or 2; r is 1 or 2; R1 is halo, cyano or carboxy; Y is selected from -C(O)R2 , -C(O)OR2, -C(O)NR2R3, -(1-4C)alkyl [optionally substituted] -(2-4C)alkenyl, -SO2NR2R3, and -S(O)cR2 (wherein c is 0, 1 or 2); R2 and R3 are independently selected from hydrogen, -O(1-4C)alkyl, -S(1-4C)alkyl, -N(1-4C)alkyl, heterocyclyl, aryl, and (1-4C)alkyl [optionally substituted]; possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of compounds and pharmaceutical compositions containing them are described.

  该化合物的结构式（1）或其药用可接受的盐或前药；其中，例如，Z为CH或氮，R4和R5一起是-S-C（R6）=C（R7）-或-C（R7）=C（R6）-S-；R6和R7分别选自氢，卤素，硝基，氰基，羟基，氟甲基，二氟甲基，三氟甲基，三氟甲氧基，羧基和氨基；A为苯基或杂环芳基；n为0，1或2；r为1或2；R1为卤素，氰基或羧基；Y选自-C（O）R2，-C（O）OR2，-C（O）NR2R3，-(1-4C)烷基[可选择取代]-(2-4C)烯基，-SO2NR2R3和-S（O）cR2（其中c为0，1或2）；R2和R3分别选自氢，-O（1-4C）烷基，-S（1-4C）烷基，-N（1-4C）烷基，杂环烷基，芳基和（1-4C）烷基[可选择取代]；具有糖原磷酸化酶抑制活性，因此在治疗与糖原磷酸化酶活性增加相关的疾病状态中具有价值。描述了制备该化合物和含有它们的药物组合物的方法。
• Indolamide derivatives which possess glycogen phosphorylase inhibitory activity
  申请人：Birch Martin Alan

  公开号：US20060211760A1

  公开（公告）日：2006-09-21

  A compound of the formula (1) or a pharmaceutically-acceptable salt wherein, for example, A is phenylene or heteroarylene; Y is selected from —C(O)R 2 , —C(O)OR 2 , —C(O)NR 2 R 3 , -(1-4C)alkyl [optionally substituted]-(2-4C)alkenyl, —SO 2 NR 2 R 3 , and —S(O) c R 2 (wherein c is 0, 1 or 2); compounds which possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of compounds and pharmaceutical compositions containing them are described.

  式 (1) 的化合物或药学上可接受的盐 其中，例如，A 是亚苯基或杂芳基；Y 选自-C(O)R 2 、-C(O)OR 2 、-C(O)NR 2 R 3 -(1-4C)烷基[任选取代的]-(2-4C)烯基，-SO 2 NR 2 R 3 和 -S(O) c R 2 (其中 c 为 0、1 或 2）；这些化合物具有糖原磷酸化酶抑制活性，因此在治疗与糖原磷酸化酶活性增加有关的疾病方面具有价值。本文介绍了化合物的生产工艺以及含有这些化合物的药物组合物。
• INDOLAMIDE DERIVATIVES WHICH POSSESS GLYCOGEN PHOSPHORYLASE INHIBITORY ACTIVITY
  申请人：AstraZeneca AB

  公开号：EP1658067B1

  公开（公告）日：2008-11-12
• HETEROCYCLIC AMIDE DERIVATIVES WHICH POSSESS GLYCOGEN PHOSPHORYLASE INHIBITORY ACTIVITY
  申请人：AstraZeneca AB

  公开号：EP1658069B1

  公开（公告）日：2008-07-30
• Heterocyclic Amide Derivatives Which Possess Glycogen Phosphorylase Inhibitory Activity
  申请人：Birch Alan Martin

  公开号：US20080064691A1

  公开（公告）日：2008-03-13

  A compound of the formula (1) or a pharmaceutically-acceptable salt, or pro-drug thereof; wherein, for example, Z is CH or nitrogen, R 4 and R 5 together are either —S—C(R 6 )═C(R7)— or —C(R 7 )═C(R 6 )—S—; R 6 and R 7 are independently selected from hydrogen, halo, nitro, cyano, hydroxy, fluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, carboxy and carbamoyl; A is phenylene or heteroarylene; n is 0, 1 or 2; r is 1 or 2; R 1 is halo, cyano or carboxy; Y is selected from —C(O)R 2 , —C(O)OR 2 , —C(O)NR 2 R 3 , -(1-4C)alkyl [optionally substituted] -(2-4C)alkenyl, —SO 2 NR 2 R 3 , and —S(O) c R 2 (wherein c is 0, 1 or 2); R 2 and R 3 are independently selected from hydrogen, —O(1-4C)alkyl, —S(1-4C)alkyl, —N(1-4C)alkyl, heterocyclyl, aryl, and (1-4C)alkyl [optionally substituted]; possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of compounds and pharmaceutical compositions containing them are described.