N-α-(tert-butoxycarbonyl)-N-tert-butyl-(D)-tyrosinamide | 1363377-67-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-α-(tert-butoxycarbonyl)-N-tert-butyl-(D)-tyrosinamide
• 英文别名: Boc-(D)-Tyr-NH-t-Bu；tert-butyl N-[(2R)-1-(tert-butylamino)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamate
• CAS: 1363377-67-6
• 化学式: C₁₈H₂₈N₂O₄
• 分子量: 336.431
• InChiKey: SBWARAJUOMBGLT-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-α-(tert-butoxycarbonyl)-N-tert-butyl-(D)-tyrosinamide 、 西多福韦 在 N,N-二异丙基乙胺 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 O-[(5S)-5-[(4-amino-2-oxopyrimidin-1(2H)-yl)methyl]-2-oxido-1,4,2-dioxaphosphinan-2-yl]-N-α-(tert-butoxycarbonyl)-N-tert-butyl-(D)-tyrosinamide 、 O-[(5S)-5-[(4-amino-2-oxopyrimidin-1(2H)-yl)methyl]-2-oxido-1,4,2-dioxaphosphinan-2-yl]-N-α-(tert-butoxycarbonyl)-N-tert-butyl-(D)-tyrosinamide
  参考文献：
  名称：

  Tyrosine-Based 1-(S)-[3-Hydroxy-2-(phosphonomethoxy)propyl]cytosine and -adenine ((S)-HPMPC and (S)-HPMPA) Prodrugs: Synthesis, Stability, Antiviral Activity, and in Vivo Transport Studies

  摘要：

  Eight novel single amino acid (6-11) and dipeptide (12, 13) tyrosine P-O esters of cyclic cidofovir ((S)-cHPMPC, 4) and its cyclic adenine analogue ((S)-cHPMPA, 3) were synthesized and evaluated as prodrugs. In vitro IC50 values for the prodrugs (<0.1-50 mu M) vs vaccinia, cowpox, human cytomegalovirus, and herpes simplex type 1 virus were compared to those for the parent drugs ((S)-HPMPC, 2; (S)HPMPA, 1; IC50 0.3-35 mu M); there was no cytoxicity with KB or HFF cells at <= 100 mu M. The prodrugs exhibited a wide range of half-lives in rat intestinal homogenate at pH 6.5 (<30-1732 min) with differences of 3-10x between phostonate diastereomers. The tyrosine allcylamide derivatives of 3 and 4 were the most stable. (L)-Tyr-NH-i-Bu cHPMPA (11) was converted in rat or mouse plasma solely to two active metabolites and had significantly enhanced oral bioavailability vs parent drug 1 in a mouse model (39% vs <5%).

  DOI：

  10.1021/jm2001426
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 1-羟基苯并三唑 、 三乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 2.25h， 生成 N-α-(tert-butoxycarbonyl)-N-tert-butyl-(D)-tyrosinamide
  参考文献：
  名称：

  Tyrosine-Based 1-(S)-[3-Hydroxy-2-(phosphonomethoxy)propyl]cytosine and -adenine ((S)-HPMPC and (S)-HPMPA) Prodrugs: Synthesis, Stability, Antiviral Activity, and in Vivo Transport Studies

  摘要：

  Eight novel single amino acid (6-11) and dipeptide (12, 13) tyrosine P-O esters of cyclic cidofovir ((S)-cHPMPC, 4) and its cyclic adenine analogue ((S)-cHPMPA, 3) were synthesized and evaluated as prodrugs. In vitro IC50 values for the prodrugs (<0.1-50 mu M) vs vaccinia, cowpox, human cytomegalovirus, and herpes simplex type 1 virus were compared to those for the parent drugs ((S)-HPMPC, 2; (S)HPMPA, 1; IC50 0.3-35 mu M); there was no cytoxicity with KB or HFF cells at <= 100 mu M. The prodrugs exhibited a wide range of half-lives in rat intestinal homogenate at pH 6.5 (<30-1732 min) with differences of 3-10x between phostonate diastereomers. The tyrosine allcylamide derivatives of 3 and 4 were the most stable. (L)-Tyr-NH-i-Bu cHPMPA (11) was converted in rat or mouse plasma solely to two active metabolites and had significantly enhanced oral bioavailability vs parent drug 1 in a mouse model (39% vs <5%).

  DOI：

  10.1021/jm2001426