(3S,5S)-3-isopropyl-5-[(2S)-1-(2-nitrobenzenesulfonyl)aziridine-2-yl]dihydrofuran-2-one | 1000045-31-7

• 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: (3S,5S)-3-isopropyl-5-[(2S)-1-(2-nitrobenzenesulfonyl)aziridine-2-yl]dihydrofuran-2-one
• 英文别名: (3S,5S)-3-isopropyl-5-[(S)-1-(2-nitrobenzenesulfonyl)aziridin-2-yl]tetrahydrofuran-2-one；(3S,5S)-5-[(2S)-1-(2-nitrophenyl)sulfonylaziridin-2-yl]-3-propan-2-yloxolan-2-one
• CAS: 1000045-31-7
• 化学式: C₁₅H₁₈N₂O₆S
• 分子量: 354.384
• InChiKey: RWINRAVYWPZOIK-MSOSYJBYSA-N

物化性质

• 沸点：
  561.8±60.0 °C(Predicted)
• 密度：
  1.443±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  118
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3S,5S)-3-isopropyl-5-[(2S)-1-(2-nitrobenzenesulfonyl)aziridine-2-yl]dihydrofuran-2-one 在 二甲基氯化铝 、 caesium carbonate 、 苯硫酚 、 三乙胺 、 三氟乙酸 作用下， 以 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 23.08h， 生成 (2S,4S,5S)-5-amino-6-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-4-hydroxy-2-isopropyl-N-(pyridin-3-yl)hexanamide fumarate
  参考文献：
  名称：

  Lead optimization of 5-amino-6-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)-4-hydroxyhexanamides to reduce a cardiac safety issue: Discovery of DS-8108b, an orally active renin inhibitor

  摘要：

  With the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. Extensive structure-activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (DS-8108b) as a potent renin inhibitor with reduced potential cardiac risk. Oral administration of single doses of 3 and 10 mg/kg of 56 in cynomolgus monkeys pre-treated with furosemide led to significant reduction of mean arterial blood pressure for more than 12 h. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.022
• 作为产物：
  描述：

  (S)-3-(3-甲基丁酰基)-4-苄基-2-恶唑烷酮 在 盐酸 、 N,N-二甲基丙烯基脲 、 Oxone 、 sodium azide 、 Shi's ketone 、 lithium hydroxide monohydrate 、 palladium 10% on activated carbon 、 氢气 、 双氧水 、 四丁基硫酸氢铵 、 sodium hexamethyldisilazane 、 edetate disodium 、 potassium carbonate 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 正己烷 、 二氯甲烷 、 水 、 甲苯 、 乙腈 为溶剂， 反应 114.92h， 生成 (3S,5S)-3-isopropyl-5-[(2S)-1-(2-nitrobenzenesulfonyl)aziridine-2-yl]dihydrofuran-2-one
  参考文献：
  名称：

  Lead optimization of 5-amino-6-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)-4-hydroxyhexanamides to reduce a cardiac safety issue: Discovery of DS-8108b, an orally active renin inhibitor

  摘要：

  With the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. Extensive structure-activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (DS-8108b) as a potent renin inhibitor with reduced potential cardiac risk. Oral administration of single doses of 3 and 10 mg/kg of 56 in cynomolgus monkeys pre-treated with furosemide led to significant reduction of mean arterial blood pressure for more than 12 h. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.022

文献信息

• CYCLIC AMINE COMPOUND
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP2036896B1

  公开（公告）日：2012-03-14
• Design and optimization of novel (2S,4S,5S)-5-amino-6-(2,2-dimethyl-5-oxo-4-phenylpiperazin-1-yl)-4-hydroxy-2-isopropylhexanamides as renin inhibitors
  作者：Yuji Nakamura、Chie Sugita、Masaki Meguro、Shojiro Miyazaki、Kazuhiko Tamaki、Mizuki Takahashi、Yoko Nagai、Takahiro Nagayama、Mikio Kato、Hiroshi Suemune、Takahide Nishi

  DOI：10.1016/j.bmcl.2012.05.092

  日期：2012.7

  Introduction of the 2,2-dimethyl-4-phenylpiperazin-5-one scaffold into the P-3-P-1 portion of the (2S,4S,5S)-5-amino-6-dialkylamino-4-hydroxy-2-isopropylhexanamide backbone dramatically increased the renin inhibitory activity without using the interaction to the S-3(sp) pocket. Compound 31 exhibited >10,000-fold selectivity over other human proteases, and 18.5% oral bioavailability in monkey. (C) 2012 Elsevier Ltd. All rights reserved.
• Efficient Synthesis of 5-Amino-6-dialkylamino-4-hydroxypentanamide Derivatives for Renin Inhibitors
  作者：Yuji Nakamura、Chie Suzuki、Teppei Fujimoto、Shojiro Miyazaki、Kazuhiko Tamaki、Takahide Nishi、Hiroshi Suemune

  DOI：10.3987/com-11-12224

  日期：——

  We report an efficient synthetic method for 5-amino-6-dialkylamino-4-hydroxypentanamide derivatives using Shi Asymmetric Epoxidation and the ring opening of N-(2-nitrobenzenesulfonyl)aziridine with hindered secondary amine as key steps.
• US8158790B2
  申请人：——

  公开号：US8158790B2

  公开（公告）日：2012-04-17