GRL-0476 | 1075209-49-2

• 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: GRL-0476
• 英文别名: (3aS,4S,7aR)-hexahydro-2H-furo[2,3-b]pyran-4-yl-(2S,3R)-4-(N-isobutyl-4-methoxyphenyl sulfonamido)-3-hydroxy-1-phenylbutan-2-yl carbamate；(3as,4s,7ar)-Hexahydro-4h-Furo[2,3-B]pyran-4-Yl [(2s,3r)-3-Hydroxy-4-{[(4-Methoxyphenyl)sulfonyl](2-Methylpropyl)amino}-1-Phenylbutan-2-Yl]carbamate；[(3aS,4S,7aR)-3,3a,4,5,6,7a-hexahydro-2H-furo[2,3-b]pyran-4-yl] N-[(2S,3R)-3-hydroxy-4-[(4-methoxyphenyl)sulfonyl-(2-methylpropyl)amino]-1-phenylbutan-2-yl]carbamate
• CAS: 1075209-49-2
• 化学式: C₂₉H₄₀N₂O₈S
• 分子量: 576.711
• InChiKey: JOCIWRMOTYJUAO-AJIIGFCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  40
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  132
• 氢给体数：
  2
• 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 、 lithium aluminium tetrahydride 、 四丁基氟化铵 、 potassium carbonate 、 臭氧 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 13.84h， 生成 GRL-0476
  参考文献：
  名称：

  [EN] FUSED 6,5 BICYCLIC RING SYSTEM P2 LIGANDS, AND METHODS FOR TREATING HIV
  [FR] LIGANDS P2 À SYSTÈME CYCLIQUE 6,5 BICYCLIQUE FUSIONNÉ, ET PROCÉDÉS DE TRAITEMENT D'UNE INFECTION PAR LE VIH

  摘要：

  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。

  公开号：

  WO2012092168A1

文献信息

• A Photochemical Route to Optically Active Hexahydro-4<i>H</i>-furopyranol, a High-Affinity P2 Ligand for HIV-1 Protease Inhibitors
  作者：Arun K. Ghosh、William L. Robinson

  DOI：10.1021/acs.joc.9b01361

  日期：2019.8.2

  We describe here the syntheses of optically pure (3aS,4S,7aR)-hexahydro-4H-furo[2,3-b]pyran-4-ol and (3aR,4R,7aS)-hexahydro-4H-furo[2,3-b]pyran-4-ol. These stereochemically defined heterocycles are important high-affinity P2 ligands for a variety of highly potent HIV-1 protease inhibitors. The key steps involve an efficient Paternò-Büchi [2 + 2] photocycloaddition, catalytic hydrogenation, acid-catalyzed

  我们在这里描述了光学纯的（3aS，4S，7aR）-六氢-4H-呋喃[2,3-b]吡喃-4-醇和（3aR，4R，7aS）-六氢-4H-呋喃[2， 3-b]吡喃-4-醇。这些立体化学定义的杂环对于各种高效的HIV-1蛋白酶抑制剂而言都是重要的高亲和力P2配体。关键步骤涉及有效的Paternò-Büchi[2 + 2]光环加成，催化氢化，酸催化的环化反应以形成外消旋配体醇，以及固定化的Amano脂肪酶PS-30的酶促拆分。获得具有高对映体纯度的旋光配体（-）-6和（+）-6。对映体（-）-6已转化为有效的HIV-1蛋白酶抑制剂3。
• C-3 SUBSTITUTED BICYCLOOCTANE BASED HIV PROTEASE INHIBITORS
  申请人：Ghosh Arun K.

  公开号：US20140148508A1

  公开（公告）日：2014-05-29

  C3-functionalized-cyclopentanyltetrahydrofuranyl carbamates that inhibit HIV proteolytic enzymes and processes for preparing the compounds are described. Compositions comprising the disclosed compound and methods of using the compounds and/or compositions for treating patients infected with HIV are also described.

  本文描述了抑制HIV蛋白酶酶和过程的C3-官能化环戊基四氢呋喃基氨基甲酸酯。还描述了包含所述化合物的组合物以及使用该化合物和/或组合物治疗HIV感染患者的方法。
• 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。
• Method and compositions for treating HIV infections
  申请人：Purdue Research Foundation

  公开号：EP2491785A1

  公开（公告）日：2012-08-29

  Described herein are compounds and compositions that are useful in the treatment of AIDS, and AIDS-related diseases. In addition, compounds are described herein that are both a protease dimerization and a protease inhibitor.

  本文描述了可用于治疗艾滋病和艾滋病相关疾病的化合物和组合物。此外，本文还描述了既是蛋白酶二聚体又是蛋白酶抑制剂的化合物。
• Design and Synthesis of Potent HIV-1 Protease Inhibitors Incorporating Hexahydrofuropyranol-Derived High Affinity P₂ Ligands: Structure−Activity Studies and Biological Evaluation
  作者：Arun K. Ghosh、Bruno D. Chapsal、Abigail Baldridge、Melinda P. Steffey、D. Eric Walters、Yasuhiro Koh、Masayuki Amano、Hiroaki Mitsuya

  DOI：10.1021/jm1012787

  日期：2011.1.27

  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.