2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl N-[3-hydroxy-4-[2-methylpropyl-[(3-pyrrolidin-1-yl-1,2-benzoxazol-5-yl)sulfonyl]amino]-1-phenylbutan-2-yl]carbamate

• 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: 2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl N-[3-hydroxy-4-[2-methylpropyl-[(3-pyrrolidin-1-yl-1,2-benzoxazol-5-yl)sulfonyl]amino]-1-phenylbutan-2-yl]carbamate
• 化学式: C₃₂H₄₂N₄O₈S
• 分子量: 642.8
• InChiKey: YPXXNUSXDOMVSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  45
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  152
• 氢给体数：
  2
• 氢受体数：
  11

文献信息

• [EN] BROADSPECTRUM SUBSTITUTED BENZISOXAZOLE SULFONAMIDE HIV PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE LA PROTEASE DU VIH DE SULFONAMIDE DE BENZISOXAZOLE SUBSTITUE A LARGE BANDE
  申请人：TIBOTEC PHARM LTD

  公开号：WO2003097616A1

  公开（公告）日：2003-11-27

  The present invention concerns the compounds having the formula N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs esters and metabolites thereof. 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.

  本发明涉及具有化学式N-氧化物、盐、立体异构体形式、消旋混合物、前药酯和代谢物的化合物。它进一步涉及它们作为广谱HIV蛋白酶抑制剂的用途，它们的制备方法，以及包含它们的制药组合物和诊断试剂盒。它还涉及它们与另一种抗逆转录病毒药物的组合，以及它们在测定中作为参考化合物或试剂的用途。
• Broadspectrum substituted benzisoxazole sulfonamide hiv protease inhibitors
  申请人：Surleraux Nestor Ghislain Dominique Louis

  公开号：US20050171173A1

  公开（公告）日：2005-08-04

  The present invention concerns the compounds having the formula N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein R 1 and R 8 each are H, optionally substituted C 1-6 alkyl, C 2-6 alkenyl, C 3-7 cycloalkyl, aryl, Het 1 , Het 2 ; R 1 may also be a radical of formula (R 11a R 11b )NC(R 10a R 10b )CR 9 —; t is 0, 1 or 2; R 2 is H or C 1-6 alkyl; L is —C(═O)—, —O—C(═O)—, —NR 8 —C(═O)—, —O—C 1-6 alkanediyl-C(═O)—, —NR 8 —C 1-6 alkanediyl-C(═O)—, —S(═O) 2 —, —O—S(═O) 2 —, —NR 8 —S(═O) 2 ; R 3 is C 1-6 alkyl, aryl, C 3-7 cycloalkyl, C 3-7 cycloalkylC 1-4 alkyl, or arylC 1-4 alkyl; R 4 is H, C 1-4 alkylOC(═O), carboxyl, aminoC(═O), mono- or di(C 1-4 alkyl)aminoC(═O), C 3-7 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl or optionally substituted C 1-6 alkyl; A is C 1-6 alkanediyl, —C(═O)—, —C(═S)—, —S(═O) 2 —, C 1-6 alkanediyl-C(═O)—, C 1-6 alkanediyl-C(═S)— or C 1-6 alkanediyl-S(═O) 2 —; R 5 is H, OH, C 1-6 alkyl, Het 1 C 1-6 alkyl, Het 2 C 1-6 alkyl, optionally substituted amino-C 1-6 alkyl; R 6 is C 1-6 alkylO, Het 1 , Het 1 O, Het 2 , Het 2 O, aryl, arylO, C 1-6 alkyloxy-carbonylamino or amino; and in case -A- is other than C 1-6 alkanediyl then R 6 may also be C 1-6 alkyl, Het 1 C 1-4 alkyl, Het 1 OC 1-4 alkyl, Het 2 C 1-4 alkyl, Het 2 OC 1-4 alkyl, arylC 1-4 alkyl, arylOC 1-4 alkyl or aminoC 1-4 alkyl; whereby each of the amino groups in the definition of R 6 may optionally be substituted; R 5 and -A-R 6 taken together with the nitrogen atom to which they are attached may also form Het 1 or Het 2 . 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.

  本发明涉及式如下的化合物 其 N-氧化物、盐类、立体异构体、外消旋混合物、原药、酯类和代谢物，其中 R 1 和 R 8 均为 H、任选取代的 C 1-6 烷基、C 2-6 烯基 3-7 环烷基、芳基、Het 1 、Het 2 ; R 1 也可以是式 (R 11a R 11b )NC(R 10a R 10b )CR 9 -；t 为 0、1 或 2；R 2 是 H 或 C 1-6 烷基；L 是-C(═O)-、-O-C(═O)-、-NR 8 -C(═O)-、-O-C 1-6 烷二基-C(═O)-，-NR 8 -C 1-6 烷二基-C(═O)-，-S(═O) 2 -、-O-S(═O) 2 -、-NR 8 -S（═O） 2 ; R 3 是 C 1-6 烷基、芳基、C 3-7 环烷基、C 3-7 环烷基C 1-4 烷基，或芳基C 1-4 烷基；R 4 是 H、C 1-4 烷基OC(═O)、羧基、氨基C(═O)、单-或二(C 1-4 烷基）氨基C(═O)、C 3-7 环烷基、C 2-6 烯基、C 2-6 炔基或任选取代的 C 1-6 烷基；A 是 C 1-6 烷二基、-C(═O)-、-C(═S)-、-S(═O) 2 -, C 1-6 烷二基-C(═O)-，C 1-6 烷二基-C(═S)-或 C 1-6 烷二基-S(═O) 2 -; R 5 是 H、OH、C 1-6 烷基、Het 1 C 1-6 烷基，Het 2 C 1-6 烷基、任选取代的氨基-C 1-6 烷基；R 6 是 C 1-6 烷基 1 ，Het 1 O、Het 2 , Het 2 O、芳基、芳基O、C 1-6 烷氧基羰基氨基或氨基；如果 -A- 不是 C 1-6 烷二基，则 R 6 也可以是 C 1-6 烷基、Het 1 C 1-4 烷基，Het 1 OC 1-4 烷基，Het 2 C 1-4 烷基，Het 2 OC 1-4 烷基，芳基C 1-4 烷基、芳基OC 1-4 烷基或氨基C 1-4 烷基；其中 R 6 可任选被取代；R 5 和-A-R 6 与它们所连接的氮原子一起也可形成 Het 1 或 Het 2 .本研究还涉及它们作为广谱 HIV 蛋白酶抑制剂的用途、制备工艺以及包含它们的药物组合物和诊断试剂盒。本研究还涉及它们与另一种抗逆转录病毒药物的组合，以及它们在检测中作为参考化合物或试剂的用途。
• BROADSPECTRUM SUBSTITUTED BENZISOXAZOLE SULFONAMIDE HIV PROTEASE INHIBITORS
  申请人：Tibotec Pharmaceuticals Ltd.

  公开号：EP1517899A1

  公开（公告）日：2005-03-30
• 広域スペクトルの置換ベンズイソキサゾールスルホンアミドＨＩＶプロテアーゼ阻害剤
  申请人：テイボテク・フアーマシユーチカルズ・リミテツド

  公开号：JP4674084B2

  公开（公告）日：2005-09-15
• US7462636B2
  申请人：——

  公开号：US7462636B2

  公开（公告）日：2008-12-09