(4S,5S)-4-Benzyl-5-hydroxymethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester | 165727-51-5

• 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: (4S,5S)-4-Benzyl-5-hydroxymethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (4S,5S)-4-benzyl-5-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 165727-51-5
• 化学式: C₁₈H₂₇NO₄
• 分子量: 321.417
• InChiKey: MKXPZVPUICBDGD-LSDHHAIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4S,5S)-4-Benzyl-5-hydroxymethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 在 吡啶 、 盐酸 、 hexamethyldisilazide 作用下， 以 二氯甲烷 为溶剂， 反应 9.0h， 生成 (S-(R*,R*))->bis, bis(1,1-dimethylethyl ester)
  参考文献：
  名称：

  Amino Diol HIV Protease Inhibitors. 1. Design, Synthesis, and Preliminary SAR

  摘要：

  A series of HIV protease inhibitors containing a novel C-2 symmetrical ''aminodiol'' core structure were prepared from amino acid starting materials. The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds. Optimization of the structure-activity in this series led to aminodiol 9a (K-i = 100 nM; ED(50) (HIV-1) = 80 nM) containing P-1/P-1', benzyl and P-2/P-2' Boc substituents. Compound 9a is a selective inhibitor of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin. In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs. After iv and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40%) and a promising plasma elimination half-life (4 h).

  DOI：

  10.1021/jm00038a005
• 作为产物：
  描述：

  (4S,5R)-4-Benzyl-2,2-dimethyl-5-vinyl-oxazolidine-3-carboxylic acid tert-butyl ester 在 sodium tetrahydroborate 、 臭氧 作用下， 生成 (4S,5S)-4-Benzyl-5-hydroxymethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Amino Diol HIV Protease Inhibitors. 1. Design, Synthesis, and Preliminary SAR

  摘要：

  A series of HIV protease inhibitors containing a novel C-2 symmetrical ''aminodiol'' core structure were prepared from amino acid starting materials. The ability of the aminodiols to inhibit HIV replication in cell culture is comparable to their ability to inhibit the isolated enzyme, a result compatible with good cell membrane penetration by this class of compounds. Optimization of the structure-activity in this series led to aminodiol 9a (K-i = 100 nM; ED(50) (HIV-1) = 80 nM) containing P-1/P-1', benzyl and P-2/P-2' Boc substituents. Compound 9a is a selective inhibitor of HIV protease versus other aspartyl proteases such as human renin, human cathepsin D, and porcine pepsin. In addition, 9a is equipotent against HIV-1 and HIV-2 in cell culture and demonstrates similar activity in infected T-lymphocytes and PBMCs. After iv and oral administration in rats, 9a displayed significant oral bioavailability (ca. 40%) and a promising plasma elimination half-life (4 h).

  DOI：

  10.1021/jm00038a005

文献信息

• Synthesis and biological evaluation of novel allophenylnorstatine-based HIV-1 protease inhibitors incorporating high affinity P2-ligands
  作者：Arun K. Ghosh、Sandra Gemma、Elena Simoni、Abigail Baldridge、D. Eric Walters、Kazuhiko Ide、Yasushi Tojo、Yasuhiro Koh、Masayuki Amano、Hiroaki Mitsuya

  DOI：10.1016/j.bmcl.2009.11.123

  日期：2010.2

  A series of stereochemically defined cyclic ethers as P2-ligands were incorporated in an allophenylnorstatine-based isostere to provide a new series of HIV-1 protease inhibitors. Inhibitors 3b and 3c, containing conformationally constrained cyclic ethers, displayed impressive enzymatic and antiviral properties and represent promising lead compounds for further optimization.

  将一系列立体化学定义的环醚作为 P2 配体并入基于别苯去甲司他汀的等排体中，以提供一系列新的 HIV-1 蛋白酶抑制剂。抑制剂3b和3c含有构象受限的环醚，显示出令人印象深刻的酶促和抗病毒特性，并代表了有前途的先导化合物进行进一步优化。