N-[(1S)-1-(Cyclohexylmethyl)-2-[(3aS,6aR)-hexahydro-3-oxo-4H-furo[3,2-b]pyrrol-4-yl]-2-oxoethyl]benzamide | 443898-19-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[(1S)-1-(Cyclohexylmethyl)-2-[(3aS,6aR)-hexahydro-3-oxo-4H-furo[3,2-b]pyrrol-4-yl]-2-oxoethyl]benzamide
• 英文别名: N-[(2S)-1-[(3aS,6aR)-3-oxo-3a,5,6,6a-tetrahydrofuro[3,2-b]pyrrol-4-yl]-3-cyclohexyl-1-oxopropan-2-yl]benzamide
• CAS: 443898-19-9
• 化学式: C₂₂H₂₈N₂O₄
• 分子量: 384.5
• InChiKey: ZDRBMNHVJWTCNG-DFQSSKMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• 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

文献信息

• INHIBITORS OF CRUZIPAIN AND OTHER CYSTEINE PROTEASES
  申请人：Quibell Martin

  公开号：US20090247471A1

  公开（公告）日：2009-10-01

  Compounds of general formula (I) or general formula (II):— wherein R 1 , P 1 , P 2 , Q, Y, (X) o , (W) n , (V) m , Z and U are as defined in the specification, are inhibitors of cruzipain and other cysteine protease inhibitors and are useful as therapeutic agents, for example in Chagas' disease, or for validating therapeutic target compounds.

  通式(I)或通式(II)的化合物：其中R1、P1、P2、Q、Y、(X)o、(W)n、(V)m、Z和U的定义如规范中所述，是cruzipain和其他半胱氨酸蛋白酶抑制剂，可用作治疗剂，例如在查加斯病中，或用于验证治疗靶点化合物。
• FURO[3, 2-B] PYRR0L-3-ONES AS CATHESPIN S INHIBITORS
  申请人：AMURA THERAPEUTICS LIMITED

  公开号：US20130150345A1

  公开（公告）日：2013-06-13

  A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, wherein: one of R 3 and R 4 is H, and the other is selected from C 1-6 -alkyl, C 1-6 -haloalkyl, C 1-6 -alkoxy, and C 6-12 -aralkyl; or R 3 and R 4 are each independently selected from C 1-6 -alkyl and halo; R 9 is a substituted 5 or 6-membered aryl or heteroaryl group or a 6,5- or 6,6-fused biaryl or heterobiaryl group. Compounds of formula (I) exhibit surprisingly high efficacies for human cathepsin S, excellent selectivity verses other mammalian cathepsins and are useful for treatment of diseases such as rheumatoid arthritis, multiple sclerosis, myasthenia gravis, transplant rejection, diabetes, Sjogrens syndrome, Grave's disease, systemic lupus erythematosis, osteoarthritis, psoriasis, idiopathic thrombocytopenic purpura, allergic rhinitis, asthma, atherosclerosis, obesity, chronic obstructive pulmonary disease and chronic pain.

  本发明的第一个方面涉及公式(I)的化合物，或其药学上可接受的盐、水合物、复合物或前药，其中：R3和R4中的一个为H，另一个选自C1-6-烷基、C1-6-卤代烷基、C1-6-烷氧基和C6-12-芳基烷基; 或R3和R4各自独立地选自C1-6-烷基和卤代基; R9是取代的5或6成员芳基或杂芳基或6,5-或6,6-螺合的双芳基或双杂芳基。公式(I)的化合物表现出对人类卡特普汀S的惊人高效性，对其他哺乳动物卡特普汀具有优异的选择性，并可用于治疗风湿性关节炎、多发性硬化症、重症肌无力、移植排斥、糖尿病、Sjogrens综合症、Grave's病、全身性红斑狼疮、骨关节炎、牛皮癣、特发性血小板减少性紫癜、过敏性鼻炎、哮喘、动脉粥样硬化、肥胖症、慢性阻塞性肺疾病和慢性疼痛等疾病的治疗。
• FURO [3, 2-B] PYRR0L-3-0NES AS CATHESPIN S INHIBITORS
  申请人：Amura Therapeutics Limited

  公开号：US20160015685A1

  公开（公告）日：2016-01-21

  A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, wherein: one of R 3 and R 4 is H, and the other is selected from C 1-6 -alkyl, C 1-6 -haloalkyl, C 1-6 -alkoxy, and C 6-12 -aralkyl; or R 3 and R 4 are each independently selected from C 1-6 -alkyl and halo; R 9 is a substituted 5 or 6-membered aryl or heteroaryl group or a 6,5- or 6,6-fused biaryl or heterobiaryl group. Compounds of formula (I) exhibit surprisingly high efficacies for human cathepsin S, excellent selectivity verses other mammalian cathepsins and are useful for treatment of diseases such as rheumatoid arthritis, multiple sclerosis, myasthenia gravis, transplant rejection, diabetes, Sjogrens syndrome, Grave's disease, systemic lupus erythematosis, osteoarthritis, psoriasis, idiopathic thrombocytopenic purpura, allergic rhinitis, asthma, atherosclerosis, obesity, chronic obstructive pulmonary disease and chronic pain.

  本发明的第一个方面涉及公式（I）的化合物，或其药学上可接受的盐、水合物、复合物或前药，其中：R3和R4中的一个是H，另一个被选自C1-6-烷基，C1-6-卤代烷基，C1-6-烷氧基和C6-12-芳基烷基；或R3和R4各自独立地选自C1-6-烷基和卤；R9是取代的5或6元杂环芳基或杂芳基基团或6,5-或6,6-螺合的双芳基或双杂芳基基团。公式（I）的化合物表现出对人类卡特普辛S意外的高效性，对其他哺乳动物卡特普辛具有良好的选择性，并可用于治疗风湿性关节炎、多发性硬化症、重症肌无力、移植排斥反应、糖尿病、Sjogrens综合症、Grave病、系统性红斑狼疮、骨关节炎、牛皮癣、特发性血小板减少性紫癜、过敏性鼻炎、哮喘、动脉粥样硬化、肥胖症、慢性阻塞性肺疾病和慢性疼痛等疾病的治疗。
• FURO[3, 2-B] PYRR0L-3-0NES AS CATHESPIN S INHIBITORS
  申请人：Quibell Martin

  公开号：US20110009386A1

  公开（公告）日：2011-01-13

  A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, wherein: one of R 3 and R 4 is H, and the other is selected from C 1-6 -alkyl, C 1-6 -haloalkyl, C 1-6 -alkoxy, and C 6-12 -aralkyl; or R 3 and R 4 are each independently selected from C 1-6 -alkyl and halo; R 9 is a substituted 5 or 6-membered aryl or heteroaryl group or a 6,5- or 6,6-fused biaryl or heterobiaryl group. Compounds of formula (I) exhibit surprisingly high efficacies for human cathepsin S, excellent selectivity verses other mammalian cathepsins and are useful for treatment of diseases such as rheumatoid arthritis, multiple sclerosis, myasthenia gravis, transplant rejection, diabetes, Sjogrens syndrome, Grave's disease, systemic lupus erythematosis, osteoarthritis, psoriasis, idiopathic thrombocytopenic purpura, allergic rhinitis, asthma, atherosclerosis, obesity, chronic obstructive pulmonary disease and chronic pain.

  本发明的第一个方面涉及化合物式(I)的化合物，或其药学上可接受的盐、水合物、复合物或前药，其中：R3和R4中的一个是H，另一个选自C1-6烷基、C1-6卤代烷基、C1-6烷氧基和C6-12芳基烷基；或者R3和R4各自独立地选自C1-6烷基和卤素；R9是取代的5或6元杂环芳基或杂芳基基团或6,5-或6,6-螺合的双芳基或双杂芳基基团。式(I)的化合物表现出对人类卡特普辛S的惊人高效性，对其他哺乳动物卡特普辛具有良好的选择性，并可用于治疗风湿性关节炎、多发性硬化症、重症肌无力、移植排斥反应、糖尿病、Sjogren综合症、Grave病、系统性红斑狼疮、骨关节炎、牛皮癣、特发性血小板减少性紫癜、过敏性鼻炎、哮喘、动脉硬化、肥胖症、慢性阻塞性肺疾病和慢性疼痛等疾病的治疗。
• COMPOUNDS
  申请人：QUIBELL MARTIN

  公开号：US20110009385A1

  公开（公告）日：2011-01-13

  A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof, wherein: R 3 is selected from cyclopentyl and cyclohexyl; R 9 is a substituted 5 or 6-membered aryl or heteroaryl group or a 6,5- or 6,6-fused biaryl or heterobiaryl group. Compounds of formula (I) exhibit surprisingly high dual efficacies for human cathepsin S and K and are useful for the treatment of rheumatoid arthritis, osteoarthritis, chronic obstructive pulmonary disease (COPD), atherosclerosis, cardiovascular diseases which exhibit significant damage and remodeling of extracellular matrix (ECM) and chronic pain.

  本发明的第一个方面涉及公式（I）的化合物，或其药学上可接受的盐、水合物、复合物或前药，其中：R3选自环戊基和环己基；R9是取代的5或6元杂芳基或杂芳基基团，或6,5-或6,6-融合的双芳基或双杂芳基基团。公式（I）的化合物表现出对人类卡特普辛S和K的惊人的双重功效，并可用于治疗类风湿性关节炎、骨关节炎、慢性阻塞性肺疾病（COPD）、动脉粥样硬化、心血管疾病，其表现出显著的细胞外基质（ECM）的损伤和重塑以及慢性疼痛。