((2S,3R)-3-hydroxy-4-(N-isobutyl-2-methylthiobenzothiazole-6-sulfonamido)-1-phenylbutan-2-yl)carbamic acid tert-butyl ester | 473739-21-8

• 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: ((2S,3R)-3-hydroxy-4-(N-isobutyl-2-methylthiobenzothiazole-6-sulfonamido)-1-phenylbutan-2-yl)carbamic acid tert-butyl ester
• 英文别名: {(1S,2R)-1-Benzyl-2-hydroxy-3-[isobutyl-(2-methylsulfanyl-benzothiazole-6-sulfonyl)-amino]-propyl}-carbamic acid tert-butyl ester；tert-butyl N-[(2S,3R)-3-hydroxy-4-[2-methylpropyl-[(2-methylsulfanyl-1,3-benzothiazol-6-yl)sulfonyl]amino]-1-phenylbutan-2-yl]carbamate
• CAS: 473739-21-8
• 化学式: C₂₇H₃₇N₃O₅S₃
• 分子量: 579.806
• InChiKey: YFSMPHOSOUJING-XZOQPEGZSA-N

物化性质

• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  171
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ((2S,3R)-3-hydroxy-4-(N-isobutyl-2-methylthiobenzothiazole-6-sulfonamido)-1-phenylbutan-2-yl)carbamic acid tert-butyl ester 在 三乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 {(1S,2R)-1-Benzyl-2-hydroxy-3-[isobutyl-(2-methanesulfinyl-benzothiazole-6-sulfonyl)-amino]-propyl}-carbamic acid (3R,3aS,6aR)-(hexahydro-furo[2,3-b]furan-3-yl) ester
  参考文献：
  名称：

  Design of HIV-1 Protease Inhibitors Active on Multidrug-Resistant Virus

  摘要：

  On the basis of structural data gathered during our ongoing HIV-1 protease inhibitors program, from which our clinical candidate TMC114 9 was selected, we have discovered new series of fused heteroaromatic sulfonamides. The further extension into the P2' region was aimed at identifying new classes of compounds with an improved broad spectrum activity and acceptable pharmacokinetic properties. Several of these compounds display an exceptional broad spectrum activity against a panel of highly cross-resistant mutants. Certain members of these series exhibit favorable pharmacokinetic profiles in rat and dog. Crystal structures and molecular modeling were used to rationalize the broad spectrum profile resulting from the extension into the P2' pocket of the HIV-1 protease.

  DOI：

  10.1021/jm049454n
• 作为产物：
  描述：

  2-甲硫基苯并噻唑 在 氯磺酸 、 三乙胺 作用下， 反应 3.0h， 生成 ((2S,3R)-3-hydroxy-4-(N-isobutyl-2-methylthiobenzothiazole-6-sulfonamido)-1-phenylbutan-2-yl)carbamic acid tert-butyl ester
  参考文献：
  名称：

  Design of HIV-1 Protease Inhibitors Active on Multidrug-Resistant Virus

  摘要：

  On the basis of structural data gathered during our ongoing HIV-1 protease inhibitors program, from which our clinical candidate TMC114 9 was selected, we have discovered new series of fused heteroaromatic sulfonamides. The further extension into the P2' region was aimed at identifying new classes of compounds with an improved broad spectrum activity and acceptable pharmacokinetic properties. Several of these compounds display an exceptional broad spectrum activity against a panel of highly cross-resistant mutants. Certain members of these series exhibit favorable pharmacokinetic profiles in rat and dog. Crystal structures and molecular modeling were used to rationalize the broad spectrum profile resulting from the extension into the P2' pocket of the HIV-1 protease.

  DOI：

  10.1021/jm049454n

文献信息

• Design and Development of Highly Potent HIV-1 Protease Inhibitors with a Crown-Like Oxotricyclic Core as the P2-Ligand To Combat Multidrug-Resistant HIV Variants
  作者：Arun K. Ghosh、Kalapala Venkateswara Rao、Prasanth R. Nyalapatla、Heather L. Osswald、Cuthbert D. Martyr、Manabu Aoki、Hironori Hayashi、Johnson Agniswamy、Yuan-Fang Wang、Haydar Bulut、Debananda Das、Irene T. Weber、Hiroaki Mitsuya

  DOI：10.1021/acs.jmedchem.7b00172

  日期：2017.5.25

  Design, synthesis, and evaluation of a new class of exceptionally potent HIV-1 protease inhibitors are reported. Inhibitor 5 displayed superior antiviral activity and drug-resistance profiles. In fact, this inhibitor showed several orders of magnitude improved antiviral activity over the FDA approved drug darunavir. This inhibitor incorporates an unprecedented 6–5–5 ring-fused crown-like tetrahydropyranofuran

  据报道，设计，合成和评估了一类新型的特别有效的HIV-1蛋白酶抑制剂。抑制剂5显示出优异的抗病毒活性和耐药性。实际上，与FDA批准的药物darunavir相比，该抑制剂的抗病毒活性提高了几个数量级。这种抑制剂结合了前所未有6-5-5的稠环冠状tetrahydropyranofuran作为P2配体和氨基苯并噻唑作为P2'配体与（- [R）-羟乙基磺酰胺等排物。该手性抑制剂的冠状P2配体已使用手性Diels-Alder催化剂以光学活性形式高效合成，提供了高对映体纯度的关键中间体。抑制剂结合的HIV-1蛋白酶的两个高分辨率X射线结构揭示了与HIV-1蛋白酶的骨架原子的广泛相互作用，并提供了对这些新抑制剂结合特性的分子洞察力。
• 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。
• 一种氮杂烷酮衍生物或其药学上可接受的盐及其制备方法和应用、药物组合物
  申请人：中国医学科学院医药生物技术研究所

  公开号：CN117304129A

  公开（公告）日：2023-12-29

  本发明涉及生物医药技术领域，具体涉及一种氮杂烷酮衍生物或其药学上可接受的盐及其制备方法和应用、药物组合物。与现有的蛋白酶抑制剂相比，本发明提供的氮杂烷酮衍生物的分子柔性更佳，能更好的适应蛋白酶氨基酸残基突变所带来的酶结合口袋的结构变化。此外，本发明通过在化合物中通过引入氮杂烷酮结构，显著增强了氮杂烷酮衍生物分子和蛋白酶的结合能力，具有明显的HIV‑1蛋白酶抑制活性，并且对野生和耐药型HIV‑1具有显著的抑制活性以及较低的细胞毒性，体外药代动力学研究显示其具有较好的成药性，作为HIV蛋白酶抑制剂具有良好的应用前景，有望成为一种新的HIV蛋白酶抑制剂。
• US9024038B2
  申请人：——

  公开号：US9024038B2

  公开（公告）日：2015-05-05
• US9346820B2
  申请人：——

  公开号：US9346820B2

  公开（公告）日：2016-05-24