(3S,3aR,6aS)-1-(cyclopropylcarbonyl)-4-[((2S)-1-{[6-(dimethylamino)-1-naphthyl]sulfonyl}pyrrolidin-2-yl)carbonyl]-3-methylhexahydropyrrolo[3,2-b]pyrrol-2(1H)-one | 628725-48-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3S,3aR,6aS)-1-(cyclopropylcarbonyl)-4-[((2S)-1-{[6-(dimethylamino)-1-naphthyl]sulfonyl}pyrrolidin-2-yl)carbonyl]-3-methylhexahydropyrrolo[3,2-b]pyrrol-2(1H)-one
• 英文别名: (3S,3aR,6aS)-1-Cyclopropanecarbonyl-4-[(S)-1-(6-dimethylamino-naphthalene-1-sulfonyl)-pyrrolidine-2-carbonyl]-3-methyl-hexahydro-pyrrolo[3,2-b]pyrrol-2-one；(3aS,6S,6aR)-4-(cyclopropanecarbonyl)-1-[(2S)-1-[6-(dimethylamino)naphthalen-1-yl]sulfonylpyrrolidine-2-carbonyl]-6-methyl-3,3a,6,6a-tetrahydro-2H-pyrrolo[3,2-b]pyrrol-5-one
• CAS: 628725-48-4
• 化学式: C₂₈H₃₄N₄O₅S
• 分子量: 538.668
• InChiKey: AOHAETRTLLGXKQ-XVYJZYCRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-二甲氨基萘-5-磺酰氯 、 (3S,3aR,6aS)-1-(cyclopropylcarbonyl)-3-methyl-4-[(2S)-pyrrolidin-2-ylcarbonyl]hexahydropyrrolo[3,2-b]pyrrol-2(1H)-one hydrochloride 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以64%的产率得到(3S,3aR,6aS)-1-(cyclopropylcarbonyl)-4-[((2S)-1-{[6-(dimethylamino)-1-naphthyl]sulfonyl}pyrrolidin-2-yl)carbonyl]-3-methylhexahydropyrrolo[3,2-b]pyrrol-2(1H)-one
  参考文献：
  名称：

  Design and Synthesis of Pyrrolidine-5,5‘-trans-Lactams (5-Oxo-hexahydropyrrolo[3,2-b]pyrroles) as Novel Mechanism-Based Inhibitors of Human Cytomegalovirus Protease. 4. Antiviral Activity and Plasma Stability

  摘要：

  A series of chiral, (S)-proline-alpha-methylpyrrolidine-5,5-trans-lactam serine protease inhibitors has been developed as antivirals of human cytomegalovirus (HCMV). The SAR of the functionality on the proline nitrogen has shown that derivatives of para-substituted phenyl ureas > para-substituted phenyl sulfonamides > para-substituted phenyl carboxamide for activity against HCMV deltaAla protease, producing para-substituted phenyl ureas with single figure nM potency (K-i) against the viral enzyme. The. SAR of the functionality on the lactam nitrogen has defined the steric and electronic requirements for high human plasma stability while retaining good activity against HCMV protease. The combination of high potency against HCMV deltaAla protease and high human plasma stability has produced compounds with significant in vitro antiviral activity against human cytomegalovirus with the 6-hydroxymethyl benzothiazole derivative 72 being equivalent in potency to ganciclovir. The parent benzothiazole 56 had good pharmacokinetics in dogs with 29% bioavailability and good brain and ocular penetration in guinea pigs.

  DOI：

  10.1021/jm030810w