ethyl 2-[(3S,3aR,6aS)-4-{[(2S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl]carbonyl}-3-methyl-2-oxohexahydropyrrolo[3,2-b]pyrrol-1(2H)-yl]-1,3-benzothiazole-6-carboxylate | 628725-92-8

• 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: ethyl 2-[(3S,3aR,6aS)-4-{[(2S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl]carbonyl}-3-methyl-2-oxohexahydropyrrolo[3,2-b]pyrrol-1(2H)-yl]-1,3-benzothiazole-6-carboxylate
• 英文别名: ethyl 2-[(3aS,6S,6aR)-6-methyl-1-[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carbonyl]-5-oxo-3,3a,6,6a-tetrahydro-2H-pyrrolo[3,2-b]pyrrol-4-yl]-1,3-benzothiazole-6-carboxylate
• CAS: 628725-92-8
• 化学式: C₂₇H₃₄N₄O₆S
• 分子量: 542.656
• InChiKey: GEJHOSCJAJSLNI-LDBRAYGESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  138
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 2-[(3S,3aR,6aS)-4-{[(2S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl]carbonyl}-3-methyl-2-oxohexahydropyrrolo[3,2-b]pyrrol-1(2H)-yl]-1,3-benzothiazole-6-carboxylate 在 三乙胺 作用下， 以 乙腈 为溶剂， 生成 (2S)-2-{[(3aS,6S,6aR)-4-(6-ethylcarboxylate-1,3-benzothiazol-2-yl)-6-methyl-5-oxohexahydropyrrolo[3,2-b]pyrrol-1(2H)-yl]carbonyl}-N-(4-isopropylphenyl)pyrrolidine-1-carboxamide
  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
• 作为产物：
  描述：

  N-苄氧羰基-L-脯氨酸 在 palladium on activated charcoal 氢气 、 potassium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 1-羟基苯并三唑一水物 、 N,N-二异丙基乙胺 、 三氟乙酸 、 copper(l) chloride 作用下， 以 二氯甲烷 、 对二甲苯 、 水 、 异丙醇 、 乙腈 为溶剂， 反应 30.08h， 生成 ethyl 2-[(3S,3aR,6aS)-4-{[(2S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl]carbonyl}-3-methyl-2-oxohexahydropyrrolo[3,2-b]pyrrol-1(2H)-yl]-1,3-benzothiazole-6-carboxylate
  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

文献信息

• Design and Synthesis of Pyrrolidine-5,5‘-<i>trans-</i>Lactams (5-Oxo-hexahydropyrrolo[3,2-<i>b</i>]pyrroles) as Novel Mechanism-Based Inhibitors of Human Cytomegalovirus Protease. 4. Antiviral Activity and Plasma Stability
  作者：Alan D. Borthwick、Dave E. Davies、Peter F. Ertl、Anne M. Exall、Terry M. Haley、Graham J. Hart、Deborah L. Jackson、Nigel R. Parry、Angela Patikis、Naimisha Trivedi、Gordon G. Weingarten、James M. Woolven

  DOI：10.1021/jm030810w

  日期：2003.10.1

  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.