(3R,3aR,6aR)-(9H-fluoren-9-yl)methyl 3-hydroxytetrahydro-2H-furo[3,2-b]pyrrole-4(5H)-carboxylate | 1001592-21-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (3R,3aR,6aR)-(9H-fluoren-9-yl)methyl 3-hydroxytetrahydro-2H-furo[3,2-b]pyrrole-4(5H)-carboxylate
• 英文别名: (3R,3aR,6R)-(9H-fluoren-9-yl)methyl 3-hydroxytetrahydro-2H-furo[3,2-]pyrrole-4(5H)-carboxylate；9H-fluoren-9-ylmethyl (3R,3aR,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]pyrrole-4-carboxylate
• CAS: 1001592-21-7
• 化学式: C₂₁H₂₁NO₄
• 分子量: 351.402
• InChiKey: IERRNOMWBQHFED-XUVXKRRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R,3aR,6aR)-(9H-fluoren-9-yl)methyl 3-hydroxytetrahydro-2H-furo[3,2-b]pyrrole-4(5H)-carboxylate 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 1.25h， 以100%的产率得到(-)-(3aS,6aR)-3-oxo-hexahydrofuro[3,2-b]pyrrole-4-carboxylic acid 9H-fluoren-9-ylmethyl ester
  参考文献：
  名称：

  WO2008/7130

  摘要：

  公开号：
• 作为产物：
  描述：

  异山梨醇 在 palladium 10% on activated carbon 吡啶 、 盐酸 、 氨 、 氢气 、 双氧水 、 三乙基硼氢化锂 、 sodium carbonate 、 氯化铵 、 lithium bromide 、 锌 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 水 、 二甲基亚砜 、 异丙醇 、 乙腈 为溶剂， 反应 287.02h， 生成 (3R,3aR,6aR)-(9H-fluoren-9-yl)methyl 3-hydroxytetrahydro-2H-furo[3,2-b]pyrrole-4(5H)-carboxylate
  参考文献：
  名称：

  WO2008/7103

  摘要：

  公开号：

文献信息

• Furo[3,2-B]pyrrol-3-one derivatives and their use as cysteinyl proteinase inhibitors
  申请人：Amura Therapeutics Limited

  公开号：US07846935B2

  公开（公告）日：2010-12-07

  The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: X is CH or N; and R4 is optionally substituted C3-8 alkyl or optionally substituted C3-8 cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

  本发明涉及公式（I）的化合物及其药学上可接受的盐，其中：X为CH或N；以及R4为可选择取代的C3-8烷基或可选择取代的C3-8环烷基。本发明还涉及包含公式（I）化合物的制药组合物，以及在治疗骨质疏松症、帕盖特病、查加斯病、疟疾、牙龈疾病、高血钙症、代谢性骨病、涉及基质或软骨降解的疾病以及骨癌疾病如骨转移和相关疼痛中使用这种化合物的用途。
• Furo[3, 2-b] pyrrol derivatives
  申请人：Amura Therapeutics Limited

  公开号：US07737150B2

  公开（公告）日：2010-06-15

  The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: R3 is tert-butylmethyl, sec-butyl or tert-butyl; X is CH or N; and R4 is optionally substituted C1-8 alkyl or optionally substituted C3-8 cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

  本发明涉及式(I)的化合物及其药学上可接受的盐，其中：R3为叔丁基甲基、仲丁基或叔丁基；X为CH或N；R4为可选取代的C1-8烷基或可选取代的C3-8环烷基。本发明还涉及含有式(I)化合物的制药组合物，以及在治疗从骨质疏松症、帕盖特病、恶性贫血、疟疾、牙龈疾病、高钙血症、代谢性骨病、涉及基质或软骨降解的疾病以及骨癌性疾病如骨转移和相关疼痛方面使用这些化合物的方法。
• FURO[3. 2-B] PYRROL DERIVATIVES
  申请人：Quibell Martin

  公开号：US20100216811A1

  公开（公告）日：2010-08-26

  The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein: R 3 is tert-butylmethyl, sec-butyl or tert-butyl; X is CH or N; and R 4 is optionally substituted C 1-8 alkyl or optionally substituted C 3-8 cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

  本发明涉及式（I）的化合物及其药学上可接受的盐，其中：R3是叔丁基甲基、仲丁基或叔丁基；X是CH或N；R4是可选取代的C1-8烷基或可选取代的C3-8环烷基。本发明还涉及包含式（I）的化合物的药物组合物，以及将这些化合物用于治疗从骨质疏松症、帕盖特病、查加斯病、疟疾、牙龈疾病、高钙血症、代谢性骨病、涉及基质或软骨降解的疾病，以及骨癌疾病，如骨转移和相关疼痛。
• Furo[3,2-B] pyrrol-3-one derivatives and their use as cysteinyl proteinase inhibitors
  申请人：Amura Therapeutics Limited

  公开号：US07846934B2

  公开（公告）日：2010-12-07

  The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof (I), wherein: R3 is cyclopentyl or cyclohexyl; X is CH or N; and R4 is optionally substituted C1-8 alkyl or optionally substituted C3-8 cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

  本发明涉及公式（I）的化合物及其药学上可接受的盐（I），其中：R3为环戊基或环己基；X为CH或N；R4为可选取取代的C1-8烷基或可选取取代的C3-8环烷基。本发明还涉及包含公式（I）化合物的制药组合物，以及在治疗骨质疏松症、帕盖特病、查加斯病、疟疾、牙龈疾病、高钙血症、代谢性骨病、涉及基质或软骨降解的疾病以及骨癌等疾病的治疗中使用这些化合物的用途。
• Tetrahydrofuro(3,2-B) pyrrol-3-one derivatives as inhibitors of cysteine proteinases
  申请人：Amura Therapeutics Limited

  公开号：US07799791B2

  公开（公告）日：2010-09-21

  A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, wherein: one of R1 and R2 is H, and the other is selected from OR6, SR6, NR6R7, N3, Me, Et, CF3, SOR8 and SO2R8; or R1 and R2 are both H; one of R3 and R4 is H, and the other is selected from tert-butylmethyl, iso-propylmethyl, sec-butyl, tert-butyl, cyclopentyl and cyclohexyl; or R3 and R4 are joined together with the adjacent backbone carbon atom to form a spiro-C5-C6 cycloalkyl group; R6 and R7 are each independently selected from H, C1-8-alkyl and C3-8-cycloalkyl; or R6 and R7 are linked to form a cyclic group together with the nitrogen to which they are attached; R8 is C1-8-alkyl or C3-8-cycloalkyl; R9 is a para-substituted 6-membered monocyclic aryl or heteroaryl ring which includes up to five heteroatoms. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

  化合物的式子（I），或其药学上可接受的盐，水合物，复合物或前药，其中： - R1和R2中的一个是H，另一个被选择自OR6，SR6，NR6R7，N3，Me，Et，CF3，SOR8和SO2R8之中；或者 - R1和R2都是H； - R3和R4中的一个是H，另一个被选择自叔丁基甲基，异丙基甲基，仲丁基，叔丁基，环戊基和环己基之中；或者 - R3和R4与相邻的主干碳原子结合形成螺旋C5-C6环烷基团； - R6和R7各自独立地被选择自H，C1-8-烷基和C3-8-环烷基；或者 - R6和R7与它们所连接的氮一起形成一个环状基团； - R8是C1-8-烷基或C3-8-环烷基； - R9是一个带有最多五个杂原子的对位取代的6元单环芳基或杂芳基环。 本发明还涉及包括式子（I）化合物的药物组合物，以及在治疗骨质疏松症，帕盖特病，查加斯病，疟疾，牙龈疾病，高钙血症，代谢性骨病，涉及基质或软骨降解的疾病，以及骨癌疾病如骨转移和相关疼痛时使用这种化合物的用途。