(S)-2-(2-isocyanato-3,3-dimethylbutyl)-2,3-dihydrobenzo[d]isothiazole 1,1-dioxide | 1144115-04-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: (S)-2-(2-isocyanato-3,3-dimethylbutyl)-2,3-dihydrobenzo[d]isothiazole 1,1-dioxide
• CAS: 1144115-04-7
• 化学式: C₁₄H₁₈N₂O₃S
• 分子量: 294.375
• InChiKey: ZUIRZMBOOXPXNR-CYBMUJFWSA-N

物化性质

• 沸点：
  426.0±55.0 °C(predicted)
• 密度：
  1.24±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.94
• 重原子数：
  20.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  66.81
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl (1R,2S,5S)-3-((S)-2-amino-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate 、 (S)-2-(2-isocyanato-3,3-dimethylbutyl)-2,3-dihydrobenzo[d]isothiazole 1,1-dioxide 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 methyl (1R,2S,5S)-3-((S)-2-(3-((S)-1-(1,1-dioxidobenzo[d]isothiazol-2(3H)-yl)-3,3-dimethylbutan-2-yl)ureido)-3,3-dimethylbutanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate
  参考文献：
  名称：

  Novel potent inhibitors of hepatitis C virus (HCV) NS3 protease with cyclic sulfonyl P3 cappings

  摘要：

  Extensive SAR studies of the P3 capping group led to the discovery of a series of potent inhibitors with sultam and cyclic sulfonyl urea moieties as the P3 capping. The bicyclic thiophene-sultam or phenyl- sultam cappings were selected for further SAR development. Modi. cation at the P3 side chain determined that the tert-butyl group was the best choice at that position. Optimization of P1 residue significantly improved potency and selectivity. The combination of optimal moieties at all positions led to the discovery of compound 33. This compound had the best overall pro. le in potency and PK profile: excellent K-i* of 5.3 nM and activity in replicon (EC90) of 80 nM, extremely high selectivity of 6100, and a good rat PO AUC of 1.43 mu Mh. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.12.111
• 作为产物：
  描述：

  光气 、 (2S)-1-(1,1-dioxo-3H-1,2-benzothiazol-2-yl)-3,3-dimethylbutan-2-amine 在 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 (S)-2-(2-isocyanato-3,3-dimethylbutyl)-2,3-dihydrobenzo[d]isothiazole 1,1-dioxide
  参考文献：
  名称：

  Novel potent inhibitors of hepatitis C virus (HCV) NS3 protease with cyclic sulfonyl P3 cappings

  摘要：

  Extensive SAR studies of the P3 capping group led to the discovery of a series of potent inhibitors with sultam and cyclic sulfonyl urea moieties as the P3 capping. The bicyclic thiophene-sultam or phenyl- sultam cappings were selected for further SAR development. Modi. cation at the P3 side chain determined that the tert-butyl group was the best choice at that position. Optimization of P1 residue significantly improved potency and selectivity. The combination of optimal moieties at all positions led to the discovery of compound 33. This compound had the best overall pro. le in potency and PK profile: excellent K-i* of 5.3 nM and activity in replicon (EC90) of 80 nM, extremely high selectivity of 6100, and a good rat PO AUC of 1.43 mu Mh. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.12.111