5,5-bis[(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)methyl]-3-(1-hydroxyphenylmethyl)-3,4,5-trihydrofuran-2-one | 897397-61-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: 5,5-bis[(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)methyl]-3-(1-hydroxyphenylmethyl)-3,4,5-trihydrofuran-2-one
• 英文别名: 5,5-Bis[[tert-butyl(diphenyl)silyl]oxymethyl]-3-[hydroxy(phenyl)methyl]oxolan-2-one
• CAS: 897397-61-4
• 化学式: C₄₅H₅₂O₅Si₂
• 分子量: 729.076
• InChiKey: HFGFIDDWWQNEFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.18
• 重原子数：
  52
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5,5-bis[(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)methyl]-3-(1-hydroxyphenylmethyl)-3,4,5-trihydrofuran-2-one 在 吡啶 、 四丁基氟化铵 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  [EN] PROTEIN KINASE C AGONISTS
  [FR] AGONISTES DE PROTÉINE KINASE C

  摘要：

  本公开涉及某些二酰基甘油内酯化合物，包括该化合物的药物组合物，以及制备和使用该化合物和药物组合物的方法。本文所披露的化合物和组合物可用于治疗或预防可通过蛋白激酶C（PKC）激动剂，如HIV，可调节的疾病、疾病或感染。

  公开号：

  WO2020176510A1
• 作为产物：
  描述：

  2-hydroxy-2-<<(tert-butyldiphenylsilyl)oxy>methyl>-1-<(tert-butyldiphenylsilyl)oxy>-4-pentene 在 dimethyl sulfide borane 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 70.0h， 生成 5,5-bis[(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)methyl]-3-(1-hydroxyphenylmethyl)-3,4,5-trihydrofuran-2-one
  参考文献：
  名称：

  [EN] PROTEIN KINASE C AGONISTS
  [FR] AGONISTES DE PROTÉINE KINASE C

  摘要：

  本公开涉及某些二酰基甘油内酯化合物，包括该化合物的药物组合物，以及制备和使用该化合物和药物组合物的方法。本文所披露的化合物和组合物可用于治疗或预防可通过蛋白激酶C（PKC）激动剂，如HIV，可调节的疾病、疾病或感染。

  公开号：

  WO2020176510A1

文献信息

• Conformationally Constrained Analogues of Diacylglycerol. 26. Exploring the Chemical Space Surrounding the C1 Domain of Protein Kinase C with DAG-Lactones Containing Aryl Groups at the <i>sn</i>-1 and <i>sn</i>-2 Positions
  作者：Ji-Hye Kang、Samira Benzaria、Dina M. Sigano、Nancy E. Lewin、Yongmei Pu、Megan L. Peach、Peter M. Blumberg、Victor E. Marquez

  DOI：10.1021/jm060011o

  日期：2006.6.1

  Diacylglycerol lactones (DAG-lactones) are known to operate as effective agonists of protein kinase C (PKC), surpassing in potency the activity of natural diacylglycerol (DAG). Localization of activated PKC isozymes in the cell is determined in part by the different cellular scaffolds, the lipid composition of the specific membranes, and the targeting information intrinsic to the individual isoforms bound to DAG. This multifaceted control of diversity suggests that, to develop effective DAG-lactones capable of honing in on a specific cellular target, we need to gain a better understanding of the chemical space surrounding its binding site. Seeking to augment the chemical repertoire of DAG-lactone side chains that could steer the translocation of PKC to specific cellular domains, we report herein the effects of incorporating simple or substituted phenyl residues. A combined series of n-alkyl and phenyl substitutions were used to explore the optimal location of the phenyl group on the side chains. The substantial differences in binding affinity between DAG-lactones with identical functionalized phenyl groups at either the sn-1 or sn-2 position are consistent with the proposed binding model in which the DAG-lactone binds to the C1 domain of PKC with the acyl chain oriented toward the interior of the membrane and the alpha-alkylidene or alpha-arylalkylidene chains directed to the surface of the C1 domain adjacent to the lipid interface. We conclude that DAG-lactones containing alpha-phenylalkylidene side chains at the sn-2 position represent excellent scaffolds upon which to explore further chemical diversity.
• [EN] PROTEIN KINASE C AGONISTS<br/>[FR] AGONISTES DE PROTÉINE KINASE C
  申请人：GILEAD SCIENCES INC

  公开号：WO2020176510A1

  公开（公告）日：2020-09-03

  The present disclosure relates generally to certain diacylglycerol lactone compounds, pharmaceutical compositions comprising said compounds, and methods of making and using said compounds and pharmaceutical compositions. The compounds and compositions disclosed herein may be used for the treatment or prevention of diseases, disorders, or infections modifiable by protein kinase C (PKC) agonists, such as HIV.

  本公开涉及某些二酰基甘油内酯化合物，包括该化合物的药物组合物，以及制备和使用该化合物和药物组合物的方法。本文所披露的化合物和组合物可用于治疗或预防可通过蛋白激酶C（PKC）激动剂，如HIV，可调节的疾病、疾病或感染。