benzyl (2S,4S,5S)-5-(tert-butoxycarbonyl)amino-4-hydroxy-6-phenyl-1-(4-(pyridin-2-yl)phenyl)hexan-2-ylcarbamate | 854753-96-1

• 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: benzyl (2S,4S,5S)-5-(tert-butoxycarbonyl)amino-4-hydroxy-6-phenyl-1-(4-(pyridin-2-yl)phenyl)hexan-2-ylcarbamate
• 英文别名: Benzyl (1S,3S,4S)-4-[(tert-butoxycarbonyl)amino]-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentylcarbamate；benzyl N-[(2S,4S,5S)-4-hydroxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-phenyl-1-(4-pyridin-2-ylphenyl)hexan-2-yl]carbamate
• CAS: 854753-96-1
• 化学式: C₃₆H₄₁N₃O₅
• 分子量: 595.739
• InChiKey: TXPZELPYOPHDQL-RGRQWMLTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  44
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyl (2S,4S,5S)-5-(tert-butoxycarbonyl)amino-4-hydroxy-6-phenyl-1-(4-(pyridin-2-yl)phenyl)hexan-2-ylcarbamate 在 盐酸 、 palladium hydroxide on carbon 、 氢气 作用下， 以 1,4-二氧六环 、 甲醇 、 乙酸乙酯 为溶剂， 反应 16.0h， 生成 [(1S,2S,4S)-4-amino-1-benzyl-2-hydroxy-5-(4-pyridin-2-ylphenyl)pentyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm900044w
• 作为产物：
  描述：

  [(3S,4S)-4-tert-Butoxycarbonylamino-3-(tert-butyl-dimethyl-silanyloxy)-5-phenyl-1-(4-pyridin-2-yl-benzyl)-pentyl]-carbamic acid benzyl ester 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 40.0h， 以38%的产率得到benzyl (2S,4S,5S)-5-(tert-butoxycarbonyl)amino-4-hydroxy-6-phenyl-1-(4-(pyridin-2-yl)phenyl)hexan-2-ylcarbamate
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm900044w

文献信息

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

  公开号：US20050131017A1

  公开（公告）日：2005-06-16

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

  公开了一种公式的化合物作为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。
• 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.