(1S,2S)-1-[(tert-butoxycarbonyl)amino]-2,3-dihydro-1H-inden-2-yl methanesulfonate | 845269-22-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (1S,2S)-1-[(tert-butoxycarbonyl)amino]-2,3-dihydro-1H-inden-2-yl methanesulfonate
• 英文别名: [(1S,2S)-1-[(2-methylpropan-2-yl)oxycarbonylamino]-2,3-dihydro-1H-inden-2-yl] methanesulfonate
• CAS: 845269-22-9
• 化学式: C₁₅H₂₁NO₅S
• 分子量: 327.401
• InChiKey: CGXCOKLWNSZOMM-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  90.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1S,2S)-1-[(tert-butoxycarbonyl)amino]-2,3-dihydro-1H-inden-2-yl methanesulfonate 在 palladium on activated charcoal N-甲基吗啉 、 sodium azide 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications

  摘要：

  We previously reported a series of enantiopure cis-(1 R,2S)-cyclopentyldiamine derivatives as potent and selective inhibitors of Factor Xa (FXa). Herein, we describe our approach to improve the metabolic stability of this series via core modifications. Multiple resulting series of compounds demonstrated similarly high FXa potency and improved metabolic stability in human liver microsomes compared with the cyclopentyldiamide 1. (3R,4S)-Pyrrolidinyldiamide 31 was the best overall compound with human FXa K; of 0.50 nM, PT EC2x of 2.1 mu M in human plasma, bioavailability of 25% and t z of 2.7 h in dogs. Further biochemical characterization of compound 31 is also presented. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.020
• 作为产物：
  描述：

  [(1S,2R)-2-羟基-2,3-二氢-1H-茚-1-基]氨基甲酸叔丁酯 在 sodium methylate 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (1S,2S)-1-[(tert-butoxycarbonyl)amino]-2,3-dihydro-1H-inden-2-yl methanesulfonate
  参考文献：
  名称：

  Enantiopure five-membered cyclicdiamine derivatives as potent and selective inhibitors of factor Xa. Improving in vitro metabolic stability via core modifications

  摘要：

  We previously reported a series of enantiopure cis-(1 R,2S)-cyclopentyldiamine derivatives as potent and selective inhibitors of Factor Xa (FXa). Herein, we describe our approach to improve the metabolic stability of this series via core modifications. Multiple resulting series of compounds demonstrated similarly high FXa potency and improved metabolic stability in human liver microsomes compared with the cyclopentyldiamide 1. (3R,4S)-Pyrrolidinyldiamide 31 was the best overall compound with human FXa K; of 0.50 nM, PT EC2x of 2.1 mu M in human plasma, bioavailability of 25% and t z of 2.7 h in dogs. Further biochemical characterization of compound 31 is also presented. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.020

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

  公开号：WO2005013975A1

  公开（公告）日：2005-02-17

  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)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); 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.

  化合物的化学式（1）或药用盐，其中，例如，A是苯基或杂环芳基；Y选自-C（O）R2，-C（O）OR2，-C（O）NR2R3，-(1-4C)烷基[可选择性取代]，-(2-4C)烯基，-SO2NR2R3 和-S（O）CR2（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相关的疾病状态中具有价值。描述了制备化合物和含有它们的药物组合物的方法。
• Indan-Amide Derivatives with Glycogen Phosphorylase Inhibitory Activity
  申请人：Birch Alan Martin

  公开号：US20090124682A1

  公开（公告）日：2009-05-14

  A compound of the formula (1) or a pharmaceutically-acceptable salt: (A chemical formula should be inserted here—please see paper copy enclosed herewith) (1) 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.

  化合物的化学式（1）或其药学上可接受的盐：（化学式请参见随附的纸质副本）（1）具有糖原磷酸化酶抑制活性，因此对于治疗与糖原磷酸化酶活性增加相关的疾病状态具有价值。本文描述了制备化合物和含有它们的制药组合物的过程。
• Chemical Compounds
  申请人：Birch Alan Martin

  公开号：US20100137397A1

  公开（公告）日：2010-06-03

  A compound of the formula (1) or a pharmaceutically-acceptable salt: possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity such as 2 diabetes. Processes for the manufacture of compounds and pharmaceutical compositions containing them are described.

  公式（1）的化合物或药学上可接受的盐：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，如2型糖尿病方面具有价值。本文描述了制备这些化合物和含有它们的制药组合物的过程。
• 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。