叔-丁基((2S,3S)-3-羟基-4-(异丁基氨基)-1-苯基丁烷-2-基)氨基甲酯 | 143225-31-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 叔-丁基((2S,3S)-3-羟基-4-(异丁基氨基)-1-苯基丁烷-2-基)氨基甲酯
• 英文名称: (2S,3S)-3-[N-(tert-butyloxycarbonyl)amino]-1-(isobutylamino)-4-phenylbutan-2-ol
• 英文别名: 2(S)-hydroxy-3(S)-(t-butyloxycarbonyl)amino-1-isobutylamino-4-phenylbutane；tert-Butyl (2S,3S)-3-hydroxy-4-(isobutylamino)-1-phenylbutan-2-ylcarbamate；tert-butyl N-[(2S,3S)-3-hydroxy-4-(2-methylpropylamino)-1-phenylbutan-2-yl]carbamate
• CAS: 143225-31-4
• 化学式: C₁₉H₃₂N₂O₃
• 分子量: 336.475
• InChiKey: NVEPLQDORJSXRO-IRXDYDNUSA-N

物化性质

• 熔点：
  88.5-89.5 °C(Solv: hexane (110-54-3))
• 沸点：
  484.7±45.0 °C(Predicted)
• 密度：
  1.039±0.06 g/cm3(Predicted)
• 溶解度：
  溶于二氯甲烷

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  70.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  叔-丁基((2S,3S)-3-羟基-4-(异丁基氨基)-1-苯基丁烷-2-基)氨基甲酯 在 palladium on activated charcoal 盐酸 、 氢气 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  发现了一类新型的有效的HIV-1蛋白酶抑制剂，其中含有（R）-（羟乙基）脲等排烷。

  摘要：

  DOI：

  10.1021/jm00054a014
• 作为产物：
  描述：

  (2S,3S)-N-tert-butyloxycarbonyl-2-amino-3-hydroxy-1-phenyl-4-nitrobutane 在 palladium on activated charcoal sodium tetrahydroborate 、 氢气 、 magnesium sulfate 作用下， 以 乙醇 为溶剂， 反应 9.0h， 生成 叔-丁基((2S,3S)-3-羟基-4-(异丁基氨基)-1-苯基丁烷-2-基)氨基甲酯
  参考文献：
  名称：

  re- andsi-Face-Selective Nitroaldol Reactions Catalyzed by a Rigid Chiral Quaternary Ammonium Salt: A Highly Stereoselective Synthesis of the HIV Protease Inhibitor Amprenavir (Vertex 478)

  摘要：

  Either amprenavir (1) or its C(2) diastereomer can be synthesized in a simple way by the use of a nitroaldol reaction carried out in the presence of one or the other of the two ammonium ions 2. The 1,3-diamino-2-hydroxypropyl structural element of 1 is also found in many other peptidomimetics and HIV protease inhibitors. Described here is a new strategy for possible application to direct and stereocontrolled synthesis of such compounds.

  DOI：

  10.1002/(sici)1521-3773(19990712)38:13/14<1931::aid-anie1931>3.0.co;2-4

文献信息

• Crystalline Darunavir
  申请人：Mylan Laboratories LTD

  公开号：US20140350270A1

  公开（公告）日：2014-11-27

  The present invention relates to a non-solvated crystalline Darunavir, process for its preparation and pharmaceutical composition comprising it. The present invention also relates to a process for the preparation of amorphous Darunavir from a non-solvated crystalline Darunavir.

  本发明涉及一种非溶剂化结晶的达芦那韦，其制备方法以及包含它的药物组合物。本发明还涉及从非溶剂化结晶的达芦那韦制备无定形达芦那韦的过程。
• Synthesis, biological evaluation, and modeling studies of inhibitors aimed at the malarial proteases plasmepsins I and II
  作者：Daniel Muthas、Daniel Nöteberg、Yogesh A. Sabnis、Elizabeth Hamelink、Lotta Vrang、Bertil Samuelsson、Anders Karlén、Anders Hallberg

  DOI：10.1016/j.bmc.2005.06.048

  日期：2005.9

  The increasing resistance of the malarial parasite to antimalarial drugs is a major contributor to the reemergence of the disease and increases the need for new drug targets. The two aspartic proteases, plasmepsins I and II, from Plasmodium falciparum have recently emerged as potential targets. In an effort to inhibit these hemoglobinases, a series of inhibitors encompassing a basic hydroxyethylamine

  疟原虫对抗疟药的抗药性增加是该病重新出现的主要原因，并增加了对新药靶标的需求。最近已经出现了来自恶性疟原虫的两种天冬氨酸蛋白酶，纤溶酶I和II，作为潜在的靶标。为了抑制这些血红蛋白酶，制备了一系列以碱性羟乙基胺过渡态等排体为中心片段的抑制剂。合成的化合物在P1'位置变化，并表现出31至> 2000 nM的生物活性。为了使结果合理化，使用了分子对接和3D-QSAR分析。
• Ethylaziridine derivatives and their preparation methods
  申请人：Samchully Pharm. Co., Ltd.

  公开号：US06573388B1

  公开（公告）日：2003-06-03

  This invention is related to new ethylaziridine derivatives of formula (I) and their preparation. The compounds are useful synthetic intermediates for the synthesis of HIV protease inhibitors and oligopeptide mimetics.

  本发明涉及公式(I)的新乙基环氮烷衍生物及其制备。这些化合物是合成HIV蛋白酶抑制剂和寡肽类似物的有用合成中间体。
• METHODS FOR THE PREPARATION OF N-ISOBUTYL-N-(2-HYDROXY-3-AMINO-4-PHENYLBUTYL)-P-NITROBENZENESULFONYLAMIDE DERIVATIVES
  申请人：Zinser Hartmut Burghard

  公开号：US20100121094A1

  公开（公告）日：2010-05-13

  A process for the preparation of N-isobutyl-N-(2-hydroxy-3-amino-4-phenylbutyl)-p-nitrobenzenesulfonylamide derivatives in which a (1-benzyl-2-hydroxy-3-isobutyl-amino-propyl)-carbamic acid derivative is reacted with a p-nitrophenylsulfonyl halide to provide the desired product in a high yield and degree of purity.

  一种制备N-异丁基-N-(2-羟基-3-氨基-4-苯基丁基)-对硝基苯磺酰胺衍生物的方法，其中将(1-苄基-2-羟基-3-异丁基氨基丙基)-氨基甲酸衍生物与对硝基苯磺酰卤素反应，以高收率和纯度提供所需的产物。
• Broadspectrum 2-(substituted-amino)-benzoxazole sulfonamide hiv protease inhibitors
  申请人：——

  公开号：US20040132791A1

  公开（公告）日：2004-07-08

  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 br C 1-6 alkyl; L is —C(═O)—, —O—C(═O)—, —NR 8 —C(═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; -A-R 6 is hydroxyC 1-6 alkyl; 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.

  本发明涉及具有公式1N-氧化物、盐、立体异构体、外消旋混合物、前药、酯和其代谢物的化合物，其中R1和R8各自为H、可选取代的C1-6烷基、C2-6烯基、C3-7环烷基、芳基、Het1、Het2；R1还可以是公式（R11aR11b）NC（R10aR10b）CR9—的基团；t为0、1或2；R2为H、Br或C1-6烷基；L为—C(═O)—、—O—C(═O)—、—NR8—C(═O)—、—C1-6烷二基-C(═O)—、—NR8—C1-6烷二基-C(═O)—、—S(═O)2—、—O—S(═O)2—或—NR8—S(═O)2；R3为C1-6烷基、芳基、C3-7环烷基、C3-7环烷基C1-4烷基或芳基C1-4烷基；R4为H、C1-4烷基OC(═O)、羧基、氨基C(═O)、单烷基或二烷基氨基C(═O)、C3-7环烷基、C2-6烯基、C2-6炔基或可选取代的C1-6烷基；A为C1-6烷二基、—C(═O)—、—C(═S)—、—S(═O)2—、C1-6烷二基-C(═O)—、C1-6烷二基-C(═S)—或C1-6烷二基-S(═O)2—；R5为H、OH、C1-6烷基、Het1C1-6烷基、Het2C1-6烷基、可选取代的氨基C1-6烷基；R6为C1-6烷基O、Het1、Het1O、Het2、Het2O、芳基、芳基O、C1-6烷氧羰基氨基或氨基；如果-A-不是C1-6烷二基，则R6还可以是C1-6烷基、Het1C1-4烷基、Het1OC1-4烷基、Het2C1-4烷基、Het2OC1-4烷基、芳基C1-4烷基、芳基OC1-4烷基或氨基C1-4烷基；其中在R6的定义中的每个氨基可以选择性地被取代；-A-R6为羟基C1-6烷基；R5和-A-R6连同它们附着的氮原子也可以形成Het1或Het2。本发明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、包含它们的制药组合物和诊断试剂盒。还涉及它们与其他抗逆转录病毒药物的组合使用，以及它们作为参考化合物或试剂在测定中的用途。