2-[(1R,4R,5S)-1-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-5-methyl-3,7-dioxo-6-oxa-2-azabicyclo[3.2.0]heptan-4-yl]ethyl 5-(dimethylamino)naphthalene-1-sulfonate | 1073241-49-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-[(1R,4R,5S)-1-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-5-methyl-3,7-dioxo-6-oxa-2-azabicyclo[3.2.0]heptan-4-yl]ethyl 5-(dimethylamino)naphthalene-1-sulfonate
• CAS: 1073241-49-2
• 化学式: C₂₇H₃₂N₂O₇S
• 分子量: 528.626
• InChiKey: KHUBMJSUZYEULF-PDIKNTFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (1R,4R,5S)-1-((S)-((S)-cyclohex-2-en-1-yl)(hydroxy)methyl)-4-(2-hydroxyethyl)-5-methyl-6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione 、 丹酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 42.0h， 以55.3%的产率得到2-[(1R,4R,5S)-1-[(S)-[(1S)-cyclohex-2-en-1-yl]-hydroxymethyl]-5-methyl-3,7-dioxo-6-oxa-2-azabicyclo[3.2.0]heptan-4-yl]ethyl 5-(dimethylamino)naphthalene-1-sulfonate
  参考文献：
  名称：

  PROTEASOME INHIBITORS

  摘要：

  本文披露了包含磺酸酯、酯或醚基团的化合物(I)。化合物(I)可以包含在药物组合物中，并可用于治疗和/或改善疾病或症状，如癌症、微生物疾病和/或炎症。

  公开号：

  US20090298906A1

文献信息

• Leaving Groups Prolong the Duration of 20S Proteasome Inhibition and Enhance the Potency of Salinosporamides
  作者：Rama Rao Manam、Katherine A. McArthur、Ta-Hsiang Chao、Jeffrey Weiss、Janid A. Ali、Vito J. Palombella、Michael Groll、G. Kenneth Lloyd、Michael A. Palladino、Saskia T. C. Neuteboom、Venkat R. Macherla、Barbara C. M. Potts

  DOI：10.1021/jm800548b

  日期：2008.11.13

  Salinosporamide A (1 (NPI-0052)) is a potent, monochlorinated 20S proteasome inhibitor in clinical trials for the treatment of cancer. To elucidate the role of the chlorine leaving group (LG), we synthesized analogues with a range of LG potentials and determined their IC50 values for inhibition of chymotrypsin-like (CT-L) trypsin-like (T-L), and caspase-like (C-L) activities of 20S proteasomes. Proteasome activity was also determined before and after attempted removal of the inhibitors by dialysis. Analogues bearing substituents with good LG potential exhibited the greatest potency and prolonged duration of proteasome inhibition, with no recovery after 24 h of dialysis. In contrast, activity was restored after : 12 h in the case of non-LG analogues. Intermediate results were observed for fluorosalinosporamide, with poor LG potential. Kinetic studies indicate that 1 acts as a classical slow, tight inhibitor of the CT-L, T-L, and C-L activities and that inhibition occurs via a two-step mechanism involving reversible recognition followed by rate-limiting formation of a covalent enzyme-inhibitor complex.
• US7910616B2
  申请人：——

  公开号：US7910616B2

  公开（公告）日：2011-03-22
• US8227503B2
  申请人：——

  公开号：US8227503B2

  公开（公告）日：2012-07-24
• US8389564B2
  申请人：——

  公开号：US8389564B2

  公开（公告）日：2013-03-05
• [EN] SALINOSPORAMIDE DERIVATIVES AS PROTEASOME INHIBITORS<br/>[FR] DÉRIVÉS DE SALINOSPORAMIDE À UTILISER EN TANT QU'INHIBITEURS DES PROTÉASOMES
  申请人：NEREUS PHARMACEUTICALS INC

  公开号：WO2009140287A1

  公开（公告）日：2009-11-19

  Disclosed herein are 6-oxa-2-azabicyclo[3.2.0]heptane-3,7-dione or heterobicyclic γ-lactam-β-lactone derivatives of formula (I) that include a sulfonate ester, ester or ether group in the substituent at the 4-position as proteasome inhibitors. These Salinosporamide derivatives of formula (I) can be included in pharmaceutical compositions and can be used for treating or ameliorating a disease or condition such as cancer, a microbial disease or inflammation.