(3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(2-{[2-(1-pyrrolidinyl)ethyl]amino}-1,3-benzothiazol-6-yl)sulfonyl]amino}propylcarbamate

• 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: (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(2-{[2-(1-pyrrolidinyl)ethyl]amino}-1,3-benzothiazol-6-yl)sulfonyl]amino}propylcarbamate
• 英文别名: [(3aS,4R,6aR)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl] N-[(2S,3R)-3-hydroxy-4-[2-methylpropyl-[[2-(2-pyrrolidin-1-ylethylamino)-1,3-benzothiazol-6-yl]sulfonyl]amino]-1-phenylbutan-2-yl]carbamate
• 化学式: C₃₄H₄₇N₅O₇S₂
• 分子量: 701.908
• InChiKey: ZCNACGKIKDEZFC-OFGMPYHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  48
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  179
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2-甲硫基苯并噻唑 在 氯磺酸 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 7.5h， 生成 (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-1-benzyl-2-hydroxy-3-{isobutyl[(2-{[2-(1-pyrrolidinyl)ethyl]amino}-1,3-benzothiazol-6-yl)sulfonyl]amino}propylcarbamate
  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

• Use of a Sulfonamide Compound For Improving the Pharmacokinetics of a Drug
  申请人：Van 'T Klooster Gerben Albert Eleutherius

  公开号：US20080287488A1

  公开（公告）日：2008-11-20

  A method for improving the pharmacokinetics of drugs, which are metabolized by cytochrome P450 monooxygenase is disclosed. More specifically it relates to a method for improving the pharmacokinetics of retroviral protease inhibitors and in particular for improving the pharmacokinetics of human immunodeficiency virus (HIV) protease inhibitors. A pharmaceutical composition and its use in the manufacture of a medicament for the inhibition or treatment of an HIV infection or AIDS in a human being are also part of the invention.

  本发明揭示了一种改善通过细胞色素P450单加氧酶代谢的药物的药代动力学的方法。更具体地，它涉及一种改善逆转录病毒蛋白酶抑制剂药物代谢动力学的方法，特别是针对改善人类免疫缺陷病毒（HIV）蛋白酶抑制剂药物代谢动力学的方法。本发明还涉及一种制药组合物及其在制造用于抑制或治疗人类免疫缺陷病毒感染或艾滋病的药物中的使用。
• 2-(SUBSTITUTED-AMINO)-BENZOTHIAZOLE SULFONAMIDE HIV PROTEASE INHIBITORS
  申请人：De Kock Herman

  公开号：US20090209583A1

  公开（公告）日：2009-08-20

  The present invention relates to 2-(substituted-amino)-benzothiazole sulfonamide compounds and derivatives, their use as protease inhibitors, in particular as broad-spectrum HIV protease inhibitors, processes for their preparation as well as pharmaceutical compositions and diagnostic kits comprising them. The present invention also concerns combinations of the present 2-(substituted-amino)-benzothiazole sulfonamide compounds and derivatives with another anti-retroviral agent. It further relates to their use in assays as reference compounds or as reagents.

  本发明涉及2-(取代氨基)-苯并噻唑磺酰胺化合物及其衍生物，它们的用途是蛋白酶抑制剂，特别是广谱HIV蛋白酶抑制剂，以及它们的制备方法、制药组合物和诊断试剂盒。本发明还涉及将本发明的2-(取代氨基)-苯并噻唑磺酰胺化合物和衍生物与另一种抗逆转录病毒药物组合使用。此外，本发明还涉及将其用作参考化合物或试剂的检测方法。
• 2-(Substituted-amino)-benzothiazole sulfonamide HIV protease inhibitors
  申请人：Tibotec Pharmaceuticals

  公开号：EP2035432B1

  公开（公告）日：2012-02-08
• MUTATIONAL PROFILES IN HIV-1 PROTEASE CORRELATED WITH PHENOTYPIC DRUG RESISTANCE
  申请人：Meyer De Sandra

  公开号：US20070269816A1

  公开（公告）日：2007-11-22

  The present invention is directed to the field of nucleic acid diagnostics and the identification of base variation in target nucleic acid sequences. More particularly, the present invention relates to the use of such genotypic characterization of a target population of HIV and the subsequent association, i.e., correlation, of this information to phenotypic interpretation in order to correlate virus mutational profiles with drug resistance. The invention also relates to methods of utilizing the mutational profiles of the invention in drug development, i.e., drug discovery, drug design, drug modification, and therapy, treatment design, clinical management and diagnostic analysis.
• US7217506B2
  申请人：——

  公开号：US7217506B2

  公开（公告）日：2007-05-15