(5S,1'S)-carbetoxy-5-<1-<<(1',1-dimethylothoxy)carbonyl>amino>-2-phenylmethyl>dihydrofuran-2(3H)-one | 193338-94-2

• 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: (5S,1'S)-carbetoxy-5-<1-<<(1',1-dimethylothoxy)carbonyl>amino>-2-phenylmethyl>dihydrofuran-2(3H)-one
• 英文别名: 3-carbethoxy-5(S)-<1'-(S)-<(tert-butyloxycarbonyl)amino>-2-phenylethyl>dihydrofuran-2(3H)-one；5-(1-tert-butoxycarbonylamino-2-phenylethyl)-2-oxo-tetrahydrofuran-3-carboxylic avid ethyl ester；(4S,5S)-5-<1-(t-Boc-amino)-2-phenylethyl>-3-carbethoxydihydrofuran-2-2(3H)-one；(5S,1-S)-3-carboethoxy-5-(1-((1-,1-dimethylethoxycarbonyl)amino)-2-phenylethyl)-dihydrofuran-2-(3H)-one；(5S,1'S)-3-carboethoxy-5-(1-(Boc-amino)-2-phenylethyl)dihydrofuran-2(3H)-one；3-carbethoxy-5(S)-{1'-(S)-[(tert-butyloxycarbonyl)amino]-2-phenylethyl}dihydrofuran-2(3H)-one；5(S)-[1(S)-(Boc-amino)-2-phenylethyl]-3(R,S)-ethoxycarbonyl-dihydrofuran-2-(3H)-one；ethyl (5S)-5-[(1S)-1-[(2-methylpropan-2-yl)oxycarbonylamino]-2-phenylethyl]-2-oxooxolane-3-carboxylate
• CAS: 193338-94-2
• 化学式: C₂₀H₂₇NO₆
• 分子量: 377.437
• InChiKey: ALIRBAQAJOSDKA-YVZMLIKISA-N

物化性质

• 熔点：
  157.3 °C(Solv: heptane (142-82-5))
• 沸点：
  543.8±45.0 °C(Predicted)
• 密度：
  1.173±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (5S,1'S)-carbetoxy-5-<1-<<(1',1-dimethylothoxy)carbonyl>amino>-2-phenylmethyl>dihydrofuran-2(3H)-one 在 咪唑 、 lithium hydroxide 、 四丁基氟化铵 、 sodium ethanolate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 126.0h， 生成 N-{(2R,4S,5S)-2-苯甲基-5-[(叔-丁氧基羰基)氨基]-4-羟基-6-苯基己酰}-L-亮氨酰-L-苯丙氨酸酰胺
  参考文献：
  名称：

  HIV-1 protease inhibitors based on hydroxyethylene dipeptide isosteres: An investigation into the role of the P1' side chain on structure-activity

  摘要：

  A systematic investigation was undertaken to determine the role of the P1' sidechain in a series of hydroxyethylene isostere based inhibitors of HIV-1 protease. Substitution and homologation of the benzyl P1' side chain of the Phe-Phe isostere based pseudo peptides 1 (L-682,679) and 2 (L-685,434) with various heteroalkyl groups leads to a series of extremely potent inhibitors of the enzyme. Several examples of the most potent inhibitors were very effective in an ex vivo cell based viral spread assay using human H9 T-lymphocytes and the IIIb isolate of HIV-1. Compound 19 is 120 times more potent than 1 and 16 times more potent than 2 in inhibiting the spread of infection in this assay.

  DOI：

  10.1021/jm00088a004
• 作为产物：
  描述：

  (1S)-1-(2R)-环氧乙基-2-苯乙基氨基甲酸叔丁酯 、 丙二酸二乙酯 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 以82%的产率得到(5S,1'S)-carbetoxy-5-<1-<<(1',1-dimethylothoxy)carbonyl>amino>-2-phenylmethyl>dihydrofuran-2(3H)-one
  参考文献：
  名称：

  有效，立体选择性地合成用于HIV蛋白酶抑制剂A-792611的羟乙烯二肽等位异构体核心

  摘要：

  描述了羟乙烯二肽等排物1的立体选择性合成。该路线采用α/γ-取代内酯的底物定向动力学质子化，以提供所需的立体化学。展示了一种在保留立体化学的情况下将非对映异构体富集的内酯转化为开环形式的方法。公开了在霍夫曼重排中利用N，N-二溴-5，5-二甲基乙内酰脲的新方法。该途径用于从氨基丙氨酸衍生的环氧化物2中以46％的产率制备氨基糖醇1（HIV蛋白酶抑制剂A-792611的核心部分）。

  DOI：

  10.1021/jo060737s

文献信息

• HIV protease inhibiting compounds
  申请人：DeGoey A. David

  公开号：US20050148623A1

  公开（公告）日：2005-07-07

  A compound of the formula is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.

  披露了一种公式的化合物作为HIV蛋白酶抑制剂。还披露了用于抑制HIV感染的方法和组合物。
• Synthesis and antiviral activity of a series of HIV-1 protease inhibitors with functionality tethered to the P1 or P1' phenyl design
  作者：Wayne J. Thompson、Paula M. D. Fitzgerald、M. Katharine Holloway、Emilio A. Emini、Paul L. Darke、Brian M. McKeever、William A. Schleif、Julio C. Quintero、Joan A. Zugay

  DOI：10.1021/jm00088a003

  日期：1992.5

  group to the P1 or P1' substituent of a Phe-based hydroxyethylene isostere, the antiviral potency of a series of HIV protease inhibitors was improved. The optimum enhancement of anti-HIV activity was observed with the 4-morpholinylethoxy substituent. The substituent effect is consistent with a model derived from inhibitor docked in the crystal structure of the native enzyme. An X-ray crystal structure

  通过将极性亲水基团束缚到基于Phe的羟乙烯等排物的P1或P1'取代基上，一系列HIV蛋白酶抑制剂的抗病毒效力得到了提高。用4-吗啉基乙氧基取代基观察到抗HIV活性的最佳增强。取代基效应与衍生自停泊在天然酶的晶体结构中的抑制剂的模型一致。确定为2.25 A的抑制酶的X射线晶体结构验证了模型预测。
• Inhibitors of HIV protease
  申请人：MERCK & CO. INC.

  公开号：EP0480711A1

  公开（公告）日：1992-04-15

  A dipeptide isostere is the biotransformed product after incubation with a culture of Streptomyces. It inhibits HIV protease, and is useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as a compound, pharmaceutically acceptable salt, pharmaceutical composition ingredient, whether or not as a prodrug or as a combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

  二肽同分异构体是在与链霉菌培养物孵育后的生物转化产物。它抑制HIV蛋白酶，在预防或治疗HIV感染以及治疗艾滋病方面具有用途，无论是作为化合物、药学上可接受的盐、药用组合成分，无论是否作为前药或与其他抗病毒药物、抗感染剂、免疫调节剂、抗生素或疫苗的组合。还描述了治疗艾滋病的方法以及预防或治疗HIV感染的方法。
• Retroviral protease inhibiting compounds
  申请人：——

  公开号：US20030195362A1

  公开（公告）日：2003-10-16

  A retroviral protease inhibiting compound of the formula: 1 is disclosed.

  公开了一种化学式为1的逆转录病毒蛋白酶抑制化合物。
• 5-amino-4-hydroxyhexanoic acid derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US05643878A1

  公开（公告）日：1997-07-01

  Compounds of formula I ##STR1## or their hydroxy-protected derivatives, and compounds of formula I' ##STR2## wherein T is an acyl radical of formula Z ##STR3## wherein R.sup.z is unsubstituted or substituted hydrocarbyl wherein at least one carbon atom has been replaced by a hetero atom with the proviso that a hetero atom is not bonded directly to the carbonyl to which the radical R.sup.z is bonded, alkyl having two or more carbon atoms, lower alkenyl, lower alkynyl, aryl or unsubstituted or substituted amino, and wherein the radicals R.sub.1, B.sub.1, R.sub.2, R.sub.3, A.sub.1, A.sub.2 and NR.sub.4 R.sub.5 are as defined in the description, and precursors thereof, are described. The compounds have pharmaceutical activity, for example in the treatment of retroviral diseases, such as AIDS.

  式I的化合物##STR1##或其羟基保护衍生物，以及式I'的化合物##STR2##其中T是式Z的酰基基团##STR3##其中R.sup.z是未取代或取代的烃基，其中至少有一个碳原子被杂原子取代，但杂原子不直接连接到基团R.sup.z所连接的羰基上，烷基具有两个或更多碳原子，低烯烃基，低炔基，芳基或未取代或取代的氨基，其中基团R.sub.1，B.sub.1，R.sub.2，R.sub.3，A.sub.1，A.sub.2和NR.sub.4R.sub.5的定义如描述中所述，并描述了其前体。这些化合物具有药物活性，例如在治疗逆转录病毒性疾病（如艾滋病）方面。