(3aS,4S,7aR)-hexahydro-2H-furo[2,3-b]pyran-4-yl-(2S,3R)-4-(4-amino-N-isobutylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-yl carbamate | 1262482-52-9

• 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: (3aS,4S,7aR)-hexahydro-2H-furo[2,3-b]pyran-4-yl-(2S,3R)-4-(4-amino-N-isobutylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-yl carbamate
• 英文别名: [(3aS,4S,7aR)-3,3a,4,5,6,7a-Hexahydro-2H-furo[2,3-b]pyran-4-yl] N-[(1S,2R)-3-[(4-aminophenyl)sulfonyl-isobutyl-amino]-1-benzyl-2-hydroxy-propyl]carbamate；[(3aS,4S,7aR)-3,3a,4,5,6,7a-hexahydro-2H-furo[2,3-b]pyran-4-yl] N-[(2S,3R)-4-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate
• CAS: 1262482-52-9
• 化学式: C₂₈H₃₉N₃O₇S
• 分子量: 561.7
• InChiKey: NUWMLVHSFCJAQZ-UIPNDDLNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  149
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  前列腺素中间体 在 吡啶 、 2,6-二甲基吡啶 、 2,4,6-三甲基吡啶 、 三乙基硅烷 、 lithium aluminium tetrahydride 、 三氟化硼乙醚 、 四丁基氟化铵 、 potassium carbonate 、 臭氧 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 16.92h， 生成 (3aS,4S,7aR)-hexahydro-2H-furo[2,3-b]pyran-4-yl-(2S,3R)-4-(4-amino-N-isobutylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-yl carbamate
  参考文献：
  名称：

  Design and Synthesis of Potent HIV-1 Protease Inhibitors Incorporating Hexahydrofuropyranol-Derived High Affinity P₂ Ligands: Structure−Activity Studies and Biological Evaluation

  摘要：

  The design, synthesis, and evaluation of a new series of hexahydrofuropyranol-derived HIV-1 protease inhibitors are described. We have designed a stereochemically defined hexahydrofuropyranol-derived urethane as the P2-ligand. The current ligand is designed based upon the X-ray structure of la-bound HIV-1 protease. The synthesis of (3aS,4S,7aR)-hexahydro-2H-furo[2,3-b]pyran-4-ol, (-)-7, was carried out in optically active form. Incorporation of this ligand provided inhibitor 35a, which has shown excellent enzyme inhibitory activity and antiviral potency. Our structure activity studies have indicated that the stereochemistry and the position of oxygens in the ligand are important to the observed potency of the inhibitor. Inhibitor 35a has maintained excellent potency against multidrug-resistant HIV-1 variants. An active site model of 35a was created based upon the X-ray structure of 1b-bound HIV-1 protease. The model offers molecular insights regarding ligand-binding site interactions of the hexahydrofuropyranol-derived novel P2-ligand.

  DOI：

  10.1021/jm1012787

文献信息

• [EN] FUSED 6,5 BICYCLIC RING SYSTEM P2 LIGANDS, AND METHODS FOR TREATING HIV<br/>[FR] LIGANDS P2 À SYSTÈME CYCLIQUE 6,5 BICYCLIQUE FUSIONNÉ, ET PROCÉDÉS DE TRAITEMENT D'UNE INFECTION PAR LE VIH
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2012092168A1

  公开（公告）日：2012-07-05

  Inhibitors of HIV-1 protease and compositions containing them are described. Use of the inhibitors and compositions containing them to treat HIV, AIDS, and AIDS-related diseases is described.

  描述了HIV-1蛋白酶的抑制剂和含有它们的组合物。描述了使用这些抑制剂和含有它们的组合物来治疗HIV、艾滋病和艾滋病相关疾病。
• An enantioselective enzymatic desymmetrization route to hexahydro-4H-furopyranol, a high-affinity ligand for HIV-1 protease inhibitors
  作者：Arun K. Ghosh、Anindya Sarkar

  DOI：10.1016/j.tetlet.2017.07.010

  日期：2017.8

  An enantioselective synthesis of (3aS,4S,7aR)-hexahydro-4H-furo[2,3-b]pyran-4-ol, a high-affinity nonpeptide ligand for a variety of potent HIV-1 protease inhibitors is described. The key steps involved a highly enantioselective enzymatic desymmetrization of meso-diacetate, an efficient transacetalization, and a highly diastereoselective reduction of a ketone. This route is amenable to large-scale

  对映选择性合成（3a S，4 S，7a R）-六氢-4 H-呋喃[2,3 - b ]吡喃-4-醇，一种对多种有效HIV-1蛋白酶抑制剂具有高亲和力的非肽配体描述。的关键步骤涉及的高度对映体选择性酶desymmetrization内消旋-二乙酸根，一个高效transacetalization，和一个高度非对映还原酮。该途径适合于使用容易获得的起始原料进行大规模合成。
• COMPOUNDS AND METHODS FOR TREATING HIV
  申请人：GHOSH Arun K.

  公开号：US20130289067A1

  公开（公告）日：2013-10-31

  Inhibitors of HIV-1 protease and compositions containing them are described. Use of the inhibitors and compositions containing them to treat HIV, AIDS, and AIDS-related diseases is described.

  本文描述了HIV-1蛋白酶抑制剂及其组合物。描述了使用这些抑制剂和组合物来治疗HIV、艾滋病和艾滋病相关疾病的方法。
• US9024038B2
  申请人：——

  公开号：US9024038B2

  公开（公告）日：2015-05-05
• US9499558B2
  申请人：——

  公开号：US9499558B2

  公开（公告）日：2016-11-22