(3R,4S,5S,6R)-4,5-bis(2-methoxyethoxymethoxy)-3,6-bis(phenoxymethyl)-1,2,7-thiadiazepane 1,1-dioxide | 185450-20-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (3R,4S,5S,6R)-4,5-bis(2-methoxyethoxymethoxy)-3,6-bis(phenoxymethyl)-1,2,7-thiadiazepane 1,1-dioxide
• CAS: 185450-20-8
• 化学式: C₂₆H₃₈N₂O₁₀S
• 分子量: 570.661
• InChiKey: XCBSTSXJLIUURD-XPGKHFPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  39
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  140
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (3R,4S,5S,6R)-4,5-bis(2-methoxyethoxymethoxy)-3,6-bis(phenoxymethyl)-1,2,7-thiadiazepane 1,1-dioxide 在 盐酸 、 palladium diacetate 、 sodium tetrahydroborate 、 sodium hydride 、 potassium carbonate 、 lithium chloride 作用下， 以 甲醇 、 乙醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-{3-[(3R,4S,5S,6R)-7-[3-(2-Hydroxy-ethyl)-benzyl]-4,5-bis-(2-methoxy-ethoxymethoxy)-1,1-dioxo-3,6-bis-phenoxymethyl-1λ⁶-[1,2,7]thiadiazepan-2-ylmethyl]-phenyl}-ethanol
  参考文献：
  名称：

  C（2）对称HIV-1蛋白酶的抑制剂：对称的环硫酰胺与P2 / P2'侧链中的酮肟基团的非对称结合。

  摘要：

  已经制备了在环状的P2 / P2'位置被官能团取代的对称环状环硫酰胺，该官能团被认为优先与HIV-1蛋白酶的S2 / S2'亚位结合。尽管已努力促进对称结合，但从最有效的抑制剂之一的X射线晶体结构分析推论，磺酰胺似乎倾向于不对称结合，在P2 / P2'侧链上具有酮肟基。从头算计算表明，环状磺酰胺支架的非对称构象比相应的对称环状脲样构象具有更低的能量。

  DOI：

  10.1021/jm991054q
• 作为产物：
  描述：

  (2R,3S,4S,5R)-3,4-Bis-(2-methoxy-ethoxymethoxy)-1,6-diphenoxy-hexane-2,5-diamine 在 磺酰胺 作用下， 以 吡啶 为溶剂， 反应 16.0h， 生成 (3R,4S,5S,6R)-4,5-bis(2-methoxyethoxymethoxy)-3,6-bis(phenoxymethyl)-1,2,7-thiadiazepane 1,1-dioxide
  参考文献：
  名称：

  Cyclic HIV-1 Protease Inhibitors Derived from Mannitol:  Synthesis, Inhibitory Potencies, and Computational Predictions of Binding Affinities

  摘要：

  Ten C-2-symmetric cyclic urea and sulfamide derivatives have been synthesized from L-mannonic gamma-lactone and D-mannitol. The results of experimental measurement of their inhibitory potencies against HIV-1 protease were compared to calculated free energies of binding derived from molecular dynamics (MD) simulations. The compounds were selected, firstly, to enable elucidation of the role of stereochemistry for binding affinity (1a-d) and, secondly, to allow evaluation of the effects of variation in the link to the P1 and P1' phenyl groups on affinity (la and 2-5). Thirdly, compounds with hydrogen bond-accepting or -donating groups attached to the phenyl groups in the P2 and P2' side chains (6 and 7) were selected. Binding free energies were estimated by a linear response method, whose predictive power for estimating binding affinities from MD simulations was demonstrated.

  DOI：

  10.1021/jm960728j

文献信息

• Inhibitors of the <i>C</i>₂-Symmetric HIV-1 Protease:  Nonsymmetric Binding of a Symmetric Cyclic Sulfamide with Ketoxime Groups in the P2/P2‘ Side Chains
  作者：Johan Hultén、Hans O. Andersson、Wesley Schaal、Helena U. Danielson、Björn Classon、Ingemar Kvarnström、Anders Karlén、Torsten Unge、Bertil Samuelsson、Anders Hallberg

  DOI：10.1021/jm991054q

  日期：1999.10.1

  Symmetric cyclic sulfamides, substituted in the P2/P2' position with functional groups foreseen to bind preferentially to the S2/S2' subsites of HIV-1 protease, have been prepared. Despite efforts to promote a symmetric binding, the sulfamides seemed prone to bind nonsymmetrically, as deduced from X-ray crystal structure analysis of one of the most potent inhibitors, possessing ketoxime groups in the

  已经制备了在环状的P2 / P2'位置被官能团取代的对称环状环硫酰胺，该官能团被认为优先与HIV-1蛋白酶的S2 / S2'亚位结合。尽管已努力促进对称结合，但从最有效的抑制剂之一的X射线晶体结构分析推论，磺酰胺似乎倾向于不对称结合，在P2 / P2'侧链上具有酮肟基。从头算计算表明，环状磺酰胺支架的非对称构象比相应的对称环状脲样构象具有更低的能量。
• Cyclic HIV-1 Protease Inhibitors Derived from Mannitol:  Synthesis, Inhibitory Potencies, and Computational Predictions of Binding Affinities
  作者：Johan Hultén、Nicholas M. Bonham、Ulrika Nillroth、Tomas Hansson、Guido Zuccarello、Abderrahim Bouzide、Johan Åqvist、Björn Classon、U. Helena Danielson、Anders Karlén、Ingemar Kvarnström、Bertil Samuelsson、Anders Hallberg

  DOI：10.1021/jm960728j

  日期：1997.3.1

  Ten C-2-symmetric cyclic urea and sulfamide derivatives have been synthesized from L-mannonic gamma-lactone and D-mannitol. The results of experimental measurement of their inhibitory potencies against HIV-1 protease were compared to calculated free energies of binding derived from molecular dynamics (MD) simulations. The compounds were selected, firstly, to enable elucidation of the role of stereochemistry for binding affinity (1a-d) and, secondly, to allow evaluation of the effects of variation in the link to the P1 and P1' phenyl groups on affinity (la and 2-5). Thirdly, compounds with hydrogen bond-accepting or -donating groups attached to the phenyl groups in the P2 and P2' side chains (6 and 7) were selected. Binding free energies were estimated by a linear response method, whose predictive power for estimating binding affinities from MD simulations was demonstrated.