3-S-amino-2R-hydroxy-1-[(2-aminobenzothiazol-6-sulfonyl)(2-methylpropyl)amino]-4-phenylbutane | 183554-21-4

• 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: 3-S-amino-2R-hydroxy-1-[(2-aminobenzothiazol-6-sulfonyl)(2-methylpropyl)amino]-4-phenylbutane
• 英文别名: 2R-hydroxy-3-[[(2-aminobenzothiazol-6-yl)sulfonyl](2-methyl-propyl)amino]-1S-(phenylmethyl) propylamine；2-amino-N-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N-(2-methylpropyl)-1,3-benzothiazole-6-sulfonamide
• CAS: 183554-21-4
• 化学式: C₂₁H₂₈N₄O₃S₂
• 分子量: 448.61
• InChiKey: OCRADCOZUGRQCG-PKOBYXMFSA-N

物化性质

• 沸点：
  677.6±65.0 °C(Predicted)
• 密度：
  1.334±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  159
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-S-amino-2R-hydroxy-1-[(2-aminobenzothiazol-6-sulfonyl)(2-methylpropyl)amino]-4-phenylbutane 在 三乙胺 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 18.0h， 生成 ((2S,3R)-3-hydroxy-4-(N-isobutylbenzo[d]thiazole-6-sulfonamido)-1-phenylbutan-2-yl)carbamic acid tert-butyl ester
  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
• 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 、 copper(II) sulfate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 18.0h， 生成 3-S-amino-2R-hydroxy-1-[(2-aminobenzothiazol-6-sulfonyl)(2-methylpropyl)amino]-4-phenylbutane
  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

• Sulfonylalkanoylamino hydroxyethylamino sulfonamide retroviral protease
  申请人：G.D. Searle & Co.

  公开号：US05985870A1

  公开（公告）日：1999-11-16

  Selected sulfonylalkanoylamino hydroxyethylamine sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease. The present invention relates to such retroviral protease inhibitors and, more particularly, relates to selected novel compounds, composition and method for inhibiting retroviral proteases, such as human immunodeficiency virus (HIV) protease, prophylactically preventing retroviral infection or the spread of a retrovirus, and treatment of a retroviral infection.

  选定的磺胺烷酰胺羟乙基胺磺酰胺化合物作为逆转录病毒蛋白酶抑制剂具有有效性，特别是作为HIV蛋白酶的抑制剂。本发明涉及这种逆转录病毒蛋白酶抑制剂，更特别地涉及选定的新化合物、组合物和用于抑制逆转录病毒蛋白酶的方法，例如人类免疫缺陷病毒（HIV）蛋白酶，预防逆转录病毒感染或逆转录病毒的传播，以及治疗逆转录病毒感染。
• Broad spectrum 2-(substituted-amino)-benzothiazole sulfonamide hiv protease inhibitors
  申请人：——

  公开号：US20040116485A1

  公开（公告）日：2004-06-17

  The present invention concerns the compounds having the formula 1 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 aminoC 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 alkyloxycarbonylamino 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.

  本发明涉及具有以下式子的化合物 1 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（&boxH；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 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 2-(SUBSTITUTED-AMINO)-BENZOTHIAZOLE SULFONAMIDE HIV PROTEASE INHIBITORS
  申请人：Tibotec Pharmaceuticals Ltd.

  公开号：EP1370543B1

  公开（公告）日：2006-10-25
• US7659404B2
  申请人：——

  公开号：US7659404B2

  公开（公告）日：2010-02-09
• [EN] BROADSPECTRUM 2-(SUBSTITUTED-AMINO)-BENZOTHIAZOLE SULFONAMIDE HIV PROTEASE INHIBITORS<br/>[FR] SULFAMIDES DE 2-AMINO-BENZOTHIAZOLE SUBSTITUE EN TANT QU'INHIBITEURS DE LA PROTEASE DU VIH A LARGE SPECTRE
  申请人：TIBOTEC PHARM LTD

  公开号：WO2002083657A2

  公开（公告）日：2002-10-24

  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 C1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, aryl, Het?1, Het2; R¿1 may also be a radical of formula (R11aR11b)NC(R10aR10b)CR9-; t is 0, 1 or 2; R2 is H or C1-6alkyl; L is -C(=O)-, -O-C(=O)-, -NR8-C(=O)-, -O-C1-6alkanediyl-C(=O)-, -NR8-C1-6?alkanediyl-C(=O)-, -S(=O)2-, -O-S(=O)2-, -NR8-S(=O)2; R3 is C1-6alkyl, aryl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, 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; A is C1-6alkanediyl, -C(=O)-, -C(=S)-, -S(=O)2-, C1-6alkanediyl-C(=O)-, C1-6alkanediyl-C(=S)- or C1-6alkanediyl-S(=O)2-; R5 is H, OH, C1-6alkyl, Het?1C¿1-6alkyl, Het2C1-6alkyl, optionally substituted aminoC1-6alkyl; R6 is C1-6alkylO, Het?1, Het1O, Het2, Het2¿O, aryl, arylO, C¿1-6?alkyloxycarbonylamino or amino; and in case -A- is other than C1-6alkanediyl then R?6¿ may also be C¿1-6?alkyl, Het?1C¿1-4alkyl, Het1OC1-4alkyl, Het2C1-4alkyl, Het2OC1-4alkyl, arylC1-4alkyl, arylOC1-4alkyl or aminoC1-4alkyl; whereby each of the amino groups in the definition of R6 may optionally be substituted; R5 and -A-R6 taken together with the nitrogen atom to which they are attached may also form Het?1 or Het2¿. 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.