(4S,5S)-5-(tert-butoxycarbonylamino)-4-(tert-butyldimethylsilyloxy)-6-phenyl-2-(4-(pyridin-2-yl)benzyl)hexanoic acid | 854753-94-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (4S,5S)-5-(tert-butoxycarbonylamino)-4-(tert-butyldimethylsilyloxy)-6-phenyl-2-(4-(pyridin-2-yl)benzyl)hexanoic acid
• 英文别名: (4S,5S)-5-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-6-phenyl-2-[4-(2-pyridinyl)benzyl]hexanoic Acid；(4S,5S)-5-[(tert-butoxycarbonyl)amino]-4-{[tert-butyl(dimethyl)silyl]oxy}-6-phenyl-2-(4-pyridin-2-ylbenzyl)hexanoic acid；(4S,5S)-4-[tert-butyl(dimethyl)silyl]oxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-phenyl-2-[(4-pyridin-2-ylphenyl)methyl]hexanoic acid
• CAS: 854753-94-9
• 化学式: C₃₅H₄₈N₂O₅Si
• 分子量: 604.862
• InChiKey: ZGGIHBDIVXUIMY-JDWSMFLASA-N

物化性质

• 沸点：
  720.4±60.0 °C(predicted)
• 密度：
  1.088±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.91
• 重原子数：
  43
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  97.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4S,5S)-5-(tert-butoxycarbonylamino)-4-(tert-butyldimethylsilyloxy)-6-phenyl-2-(4-(pyridin-2-yl)benzyl)hexanoic acid 在 二苯基膦叠氮化物 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 [(2S,4S,5S)-4-hydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-phenyl-1-(4-pyridin-2-ylphenyl)hexan-2-yl]carbamic acid
  参考文献：
  名称：

  HIV protease inhibiting compounds

  摘要：

  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。

  公开号：

  US20050148623A1
• 作为产物：
  描述：

  {1-[5-oxo-4-(4-pyridin-2-ylbenzyl)tetrahydrofuran-2-yl]-2-phenylethyl}carbamic acid tert-butyl ester 、 叔丁基二甲基氯硅烷 在 lithium hydroxide 、 咪唑 、 4-二甲氨基吡啶 作用下， 以 N-甲基吡咯烷酮 为溶剂， 生成 (4S,5S)-5-(tert-butoxycarbonylamino)-4-(tert-butyldimethylsilyloxy)-6-phenyl-2-(4-(pyridin-2-yl)benzyl)hexanoic acid
  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 David A.

  公开号：US20100249181A1

  公开（公告）日：2010-09-30

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

  公开了一种化合物，其化学式为，用作HIV蛋白酶抑制剂。还公开了用于抑制HIV感染的方法和组合物。
• 2-Pyridyl P1′-Substituted Symmetry-Based Human Immunodeficiency Virus Protease Inhibitors (A-792611 and A-790742) with Potential for Convenient Dosing and Reduced Side Effects
  作者：David A. DeGoey、David J. Grampovnik、Charles A. Flentge、William J. Flosi、Hui-ju Chen、Clinton M. Yeung、John T. Randolph、Larry L. Klein、Tatyana Dekhtyar、Lynn Colletti、Kennan C. Marsh、Vincent Stoll、Mulugeta Mamo、David C. Morfitt、Bach Nguyen、James M. Schmidt、Sue J. Swanson、Hongmei Mo、Warren M. Kati、Akhteruzzaman Molla、Dale J. Kempf

  DOI：10.1021/jm900044w

  日期：2009.4.23

  A series of symmetry-based HIV protease inhibitors was designed and synthesized. Modification of the core regiochemistry and stereochemistry significantly affected the potency, metabolic stability, and oral bioavailability of the inhibitors, as did the variation of a pendent arylmethyl P3 group. Optimization led to the selection of two compounds, 10c (A-790742) and 9d (A-792611), for advancement to preclinical studies. Both compounds displayed low nanomolar potency against wild type HIV in the presence of human serum, low rates of metabolism in human liver microsomes, and high oral bioavailability in animal models. The compounds were examined in a preclinical model for the hyperbilirubinemia observed with some HIV PIs, and both exhibited less bilirubin elevation than comparator compounds. X-ray crystallographic analyses of the new cores were used to examine differences in their binding modes. The antiviral activity of the compounds against protease inhibitor resistant strains of HIV was also determined.