1-[[[[hexahydrofuro[2,3-b]furan-3-yl]oxy]carbonyl]oxy]-2,5-pyrrolidinedione | 333798-23-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃类
• 英文名称: 1-[[[[hexahydrofuro[2,3-b]furan-3-yl]oxy]carbonyl]oxy]-2,5-pyrrolidinedione
• 英文别名: Carbonic acid 2,5-dioxo-pyrrolidin-1-yl ester hexahydro-furo[2,3-b]furan-3-yl ester；2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl (2,5-dioxopyrrolidin-1-yl) carbonate
• CAS: 333798-23-5
• 化学式: C₁₁H₁₃NO₇
• 分子量: 271.227
• InChiKey: VCFNCYVHQSHFRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  91.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-[[[[hexahydrofuro[2,3-b]furan-3-yl]oxy]carbonyl]oxy]-2,5-pyrrolidinedione 、 2-dimethylamino-benzothiazole-6-sulfonic acid (3-amino-2-hydroxy-4-phenyl-butyl)-isobutyl amide 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以90%的产率得到{(1S,2R)-1-benzyl-3-[(2-dimethylamino-benzothiazole-6-sulfonyl)-isobutyl-amino]-2-hydroxy-propyl}-carbamic acid hexahydro-furo[2,3-b]furan-3-yl ester
  参考文献：
  名称：

  [EN] BROADSPECTRUM 2-AMINO-BENZOTHIAZOLE SULFONAMIDE HIV PROTEASE INHIBITORS
  [FR] INHIBITEURS BROADSPECTRUM 2-AMINO-BENZOTHIAZOLE SULFONAMIDE HIV PROTEASE INHIBITORS

  摘要：

  本发明涉及使用2-氨基苯并噻唑，其具有式（I），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，-0-，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，有利于抑制患有该突变HIV蛋白酶的哺乳动物中的突变HIV蛋白酶。它还涉及式（I）的新化合物。

  公开号：

  WO2004014371A1

文献信息

• Resistance-repellent retroviral protease inhibitors
  申请人：Eissenstat Michael

  公开号：US20050267074A1

  公开（公告）日：2005-12-01

  Resistance-repellent and multidrug resistant retroviral protease inhibitors are provided. Pharmaceutical composition comprising such compounds, and methods of using such compounds to treat HIV infections in mammals, are also provided.

  提供了抗药性和多药耐药性逆转录病毒蛋白酶抑制剂。还提供了包含这些化合物的药物组合物，以及使用这些化合物来治疗哺乳动物HIV感染的方法。
• [EN] BROADSPECTRUM SUBSTITUTED OXINDOLE SULFONAMIDE HIV PROTEASE INHIBITORS<br/>[FR] OXINDOLE SULFONAMIDES SUBSTITUES INHIBITEURS A LARGE SPECTRE DE LA PROTEASE DU VIH
  申请人：TIBOTEC PHARM LTD

  公开号：WO2004016619A1

  公开（公告）日：2004-02-26

  The present invention concerns the compounds having the formula (I) N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein R1 and R8 each are H, optionally substituted C 1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, aryl, Het1, Het2; R1 may also be a radical of formula (R11aR11b)NC(R10a R10b)CR9-; t is 0, 1 or 2; R2 is H or C1-6alkyl; L is -C(=O)-, -O-C(=O)-, -NR8-C(=O)-, -O-C1-6 alkanediyl-C(=O)-, -NR8-C1-6alkanediyl-C(=O)-, -S(=O)2-, -O-S(=O)2-, -NR8-S(=0)2 ; R3 is C1-6alkyl, aryl, C3-7 cycloalkyl, C3-7cycloalkylC1-4 alkyl, or arylC1-4alkyl; R4 is H, C1-4alkylOC(=O), carboxyl, aminoC(=O), mono- or di(C1-4alkyl)aminoC(=O), C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl or optionally substituted C1-6alkyl; formula (II) is formula (III) or formula (IV) ; R5a and R5b is C2-6alkenyl, C2-6 alkynyl, C3-7cycloalkyl or C1-6alkyl, optionally substituted on one or more atoms; R5a and R5b may also be hydrogen, aryl, Het1, Het2; R6 is hydrogen or C1-6alkyl optionally substituted on one ore more carbon atoms. It further relates to their use as broadspectrum HIV protease inhibitors, processes for their preparation as well as pharmaceutical compositions and diagnostic kits comprising them. It also concerns combinations thereof with another anti-retroviral agent, and to their use in assays as reference compounds or as reagents.

  本发明涉及具有以下式（I）的化合物：N-氧化物、盐、立体异构体形式、消旋混合物、前药、酯及其代谢物，其中R1和R8各自为H，可选择地取代的C1-6烷基，C2-6烯基，C3-7环烷基，芳基，Het1，Het2；R1也可以是式（R11aR11b）NC（R10a R10b）CR9-的基团；t为0、1或2；R2为H或C1-6烷基；L为-C（=O）-，-O-C（=O）-，-NR8-C（=O）-，-O-C1-6烷二基-C（=O）-，-NR8-C1-6烷二基-C（=O）-，-S（=O）2-，-O-S（=O）2-，-NR8-S（=0）2；R3为C1-6烷基，芳基，C3-7环烷基，C3-7环烷烷基，或芳基C1-4烷基；R4为H，C1-4烷基氧基（=O），羧基，氨基（=O），单烷基或二烷基氨基（=O），C3-7环烷基，C2-6烯基，C2-6炔基或可选择地取代的C1-6烷基；式（II）为式（III）或式（IV）；R5a和R5b为C2-6烯基，C2-6炔基，C3-7环烷基或C1-6烷基，可选择地取代一个或多个原子；R5a和R5b也可以是氢，芳基，Het1，Het2；R6为氢或C1-6烷基，可选择地取代一个或多个碳原子。它还涉及它们作为广谱HIV蛋白酶抑制剂的用途，以及它们的制备方法、包括它们的药物组合物和诊断试剂盒。它还涉及与另一种抗逆转录病毒药物的组合物，并将它们用作参考化合物或试剂在测定中的用途。
• [EN] METHODS FOR THE PREPARATION OF (3R,3aS,6aR) HEXAHYDRO-FURO[2,3-b]FURAN-3-OL<br/>[FR] PROCEDES DE PREPARATION DE (3R,3AS,6AR)HEXAHYDRO-FURO[2,3-B]FURAN-3-OL
  申请人：TIBOTEC PHARM LTD

  公开号：WO2005095410A1

  公开（公告）日：2005-10-13

  The present invention relates to methods for the preparation of diastereomerically pure (3R,3aS,6aR) hexahydro-furo[2,3-b]furan-3-ol (6) as well as a novel intermediate, (3aR,4S,6aS) 4-methoxy-tetrahydro-furo[3,4-b]furan-2-one (4) for use in said methods. More in particular the invention relates to a stereoselective method for the preparation of diastereomerically pure (3R,3aS,6aR) hexahydro-furo[2,3-b]furan-3-ol, as well as methods for the crystallization of (3aR,4S,6aS) 4-methoxy-tetrahydro-furo[3,4-b]furan- 2-one and for the epimerization of (3aR,4R,6aS) 4-methoxy-tetrahydro-furo[3,4-b]-furan-2-one to (3aR,4S,6aS) 4-methoxy-tetrahydro-furo[3,4-b]furan-2-one.

  本发明涉及制备对映异构体纯度高的(3R,3aS,6aR)六氢呋喃[2,3-b]呋喃-3-醇（6）的方法，以及用于该方法的新型中间体(3aR,4S,6aS) 4-甲氧基四氢呋喃[3,4-b]呋喃-2-酮（4）。更具体地说，本发明涉及一种立体选择性的制备对映异构体纯度高的(3R,3aS,6aR)六氢呋喃[2,3-b]呋喃-3-醇的方法，以及用于(3aR,4S,6aS) 4-甲氧基四氢呋喃[3,4-b]呋喃-2-酮的结晶方法和(3aR,4R,6aS) 4-甲氧基四氢呋喃[3,4-b]-呋喃-2-酮的外消旋化为(3aR,4S,6aS) 4-甲氧基四氢呋喃[3,4-b]呋喃-2-酮的方法。
• [EN] METHODS FOR THE PREPARATION OF BENZOXAZOLE SULFONAMIDE COMPOUNDS AND INTERMEDIATES THEREOF<br/>[FR] PROCEDE POUR LA PREPARATION DE COMPOSES SULFONAMIDE DE BENZOXAZOLE ET LEURS INTERMEDIAIRES
  申请人：TIBOTEC PHARM LTD

  公开号：WO2005030739A1

  公开（公告）日：2005-04-07

  The present invention relates to methods for the preparation of benzoxazole sulfonamide compounds of formula (9) as well as novel intermediates of formula (6) for use in said method. More in particular the invention relates to methods for the Preparation of 2-amino-benzoxazole sulfonamide compounds which make use of 2-mercapto-benzoxazole sulfonamide intermediates, more in particular methods employing the intermediate 1-Benzy1-2-hydroxy-3-[isobutyl­(2-methylsulfanyl-benzoxazole-6-sulfonyl)-amino)-propyl)-carbamic ester, and to methods amenable to industrial scaling up. Said benzoxazole sulfonamide compounds are particularly useful as HIV protease inhibitors. The substituents are defined in the claims.

  本发明涉及制备苯并噁唑磺酰胺化合物的方法，其化学式为（9），以及用于该方法的新型中间体，其化学式为（6）。更具体地，本发明涉及制备2-氨基苯并噁唑磺酰胺化合物的方法，该方法利用2-巯基苯并噁唑磺酰胺中间体，更具体地，利用中间体1-苄基-2-羟基-3-[异丁基(2-甲硫基苯并噁唑-6-磺酰基)-氨基]-丙基-碳酰基酯，以及适用于工业放大的方法。所述苯并噁唑磺酰胺化合物特别适用于HIV蛋白酶抑制剂。取代基在权利要求中定义。
• 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。