N-{(1S,2R)-3-[(2-amino-benzothiazole-6-sulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxypropyl}-3-hydroxy-2-methyl-benzamide

• 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: N-{(1S,2R)-3-[(2-amino-benzothiazole-6-sulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxypropyl}-3-hydroxy-2-methyl-benzamide
• 英文别名: N-{(1S,2R)-3-[[(2-Amino-1,3-benzothiazol-6-yl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropyl}-3-hydroxy-2-methylbenzamide；N-[(2S,3R)-4-[(2-amino-1,3-benzothiazol-6-yl)sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]-3-hydroxy-2-methylbenzamide
• 化学式: C₂₉H₃₄N₄O₅S₂
• 分子量: 582.745
• InChiKey: QURGINYSJGZQLA-AZGAKELHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  183
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  [(1S,2R)-1-苄基-1-苄氧羰基氨基-2-羟基-4-N-异丁基氨基丙烷 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 copper(II) sulfate 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 N-{(1S,2R)-3-[(2-amino-benzothiazole-6-sulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxypropyl}-3-hydroxy-2-methyl-benzamide
  参考文献：
  名称：

  Discovery of novel benzothiazolesulfonamides as potent inhibitors of HIV-1 protease

  摘要：

  The human immunodeficiency virus (HIV) has been shown to be the causative agent for AIDS. The HIV virus encodes for a unique aspartyl protease that is essential for the production of enzymes and proteins in the final stages of maturation. Protease inhibitors have been useful in combating the disease. The inhibitors incorporate a variety of isosteres including the hydroxy-ethylurea at the protease cleavage site. We have shown that the replacement of t-butylurea moiety by benzothiazolesulfonamide provided inhibitors with improved potency and antiviral activities. Some of the compounds have shown good oral bioavailability and half-life in rats. The synthesis of benzothiazole derivatives led us to explore other heterocycles. During the course of our Studies. we also developed an efficient synthesis of benzothiazole-6-sulfonic acid via a two-step procedure starting from sulfanilamide. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.07.001

文献信息

• Broadspectrum 2-amino-benzothiazole sulfonamide hiv protease inhibitors
  申请人：Surleraux Nestor Ghislain Dominique Louis

  公开号：US20050267156A1

  公开（公告）日：2005-12-01

  The present invention relates to the use of 2-amino-benzothiazoles, having the formula wherein R 1 is hexahydrofuro[2,3-b]furanyl, tetrahydrofuranyl, oxazolyl, thiazolyl, pyridinyl, or phenyl optionally substituted with one or more substituents independently selected from C 1-6 alkyl, hydroxy, amino, halogen, aminoC 1-4 alkyl and mono- or di(C 1-4 alkyl)amino; R 2 is hydrogen or C 1-6 alkyl; L is a direct bond, —O—, C 1-6 alkanediyl-O— or —O—C 1-6 alkanediyl; R 3 is phenylC 1-4 alkyl; R 4 is C 1-6 alkyl; R 5 is hydrogen or C 1-6 alkyl; R 6 is hydrogen or C 1-6 alkyl; in the manufacture of a medicament useful for inhibiting mutant HIV protease in a mammal infected with said mutant HIV protease. It also relates to novel compounds of formula (I).

  本发明涉及使用2-氨基苯并噻唑，其具有式： 其中，R1为六氢呋喃[2,3-b]呋喃基，四氢呋喃基，噁唑基，噻唑基，吡啶基或苯基，可选地取代一个或多个取代基，独立地选择自C1-6烷基，羟基，氨基，卤素，氨基C1-4烷基和单烷基或双(C1-4烷基)氨基；R2为氢或C1-6烷基；L为直接键，-O-，C1-6烷二基-O-或-O-C1-6烷二基；R3为苯基C1-4烷基；R4为C1-6烷基；R5为氢或C1-6烷基；R6为氢或C1-6烷基；用于制造一种药物，有助于抑制携带该突变HIV蛋白酶的哺乳动物感染中的突变HIV蛋白酶。本发明还涉及式(I)的新化合物。
• BROADSPECTRUM 2-AMINO-BENZOTHIAZOLE SULFONAMIDE HIV PROTEASE INHIBITORS
  申请人：Surleraux Dominique Lois Nestor Ghislain

  公开号：US20090203742A1

  公开（公告）日：2009-08-13

  The present invention relates to the use of 2-amino-benzothiazoles, having the formula wherein R 1 is hexahydrofuro[2,3-b]furanyl, tetrahydrofuranyl, oxazolyl, thiazolyl, pyridinyl, or phenyl optionally substituted with one or more substituents independently selected from C 1-6 alkyl, hydroxy, amino, halogen, aminoC 1-4 alkyl and mono- or di(C 1-4 alkyl)amino; R 2 is hydrogen or C 1-6 alkyl; L is a direct bond, —O—, C 1-6 alkanediyl-O— or —O—C 1-6 alkanediyl; R 3 is phenylC 1-4 alkyl; R 4 is C 1-6 alkyl; R 5 is hydrogen or C 1-6 alkyl; R 6 is hydrogen or C 1-6 allyl; in the manufacture of a medicament useful for inhibiting mutant HIV protease in a mammal infected with said mutant HIV protease. It also relates to novel compounds of formula (I).

  本发明涉及使用2-氨基苯并噻唑，其具有式：其中R1为六氢呋喃[2,3-b]呋喃基，四氢呋喃基，噁唑基，噻唑基，吡啶基或苯基，可选地取代一个或多个取代基，独立选择自C1-6烷基，羟基，氨基，卤素，氨基C1-4烷基和单或双(C1-4烷基)氨基；R2为氢或C1-6烷基；L为直接键，-O-，C1-6脂肪二基-O-或-O-C1-6脂肪二基；R3为苯基C1-4烷基；R4为C1-6烷基；R5为氢或C1-6烷基；R6为氢或C1-6烯丙基；用于制造一种药物，该药物对于在感染有突变HIV蛋白酶的哺乳动物中抑制突变HIV蛋白酶是有用的。本发明还涉及式(I)的新化合物。
• Discovery of novel benzothiazolesulfonamides as potent inhibitors of HIV-1 protease
  作者：Srinivasan R Nagarajan、Gary A De Crescenzo、Daniel P Getman、Hwang-Fun Lu、James A Sikorski、Jeffrey L Walker、Joseph J McDonald、Kathryn A Houseman、Geralyn P Kocan、Nandini Kishore、Pramod P Mehta、Christie L Funkes-Shippy、Lisa Blystone

  DOI：10.1016/j.bmc.2003.07.001

  日期：2003.11

  The human immunodeficiency virus (HIV) has been shown to be the causative agent for AIDS. The HIV virus encodes for a unique aspartyl protease that is essential for the production of enzymes and proteins in the final stages of maturation. Protease inhibitors have been useful in combating the disease. The inhibitors incorporate a variety of isosteres including the hydroxy-ethylurea at the protease cleavage site. We have shown that the replacement of t-butylurea moiety by benzothiazolesulfonamide provided inhibitors with improved potency and antiviral activities. Some of the compounds have shown good oral bioavailability and half-life in rats. The synthesis of benzothiazole derivatives led us to explore other heterocycles. During the course of our Studies. we also developed an efficient synthesis of benzothiazole-6-sulfonic acid via a two-step procedure starting from sulfanilamide. (C) 2003 Elsevier Ltd. All rights reserved.