methyl (2S)-2-[[(2S,3S)-3-methyl-2-[methyl-[(2S,3S)-3-methyl-2-[[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-tritylsulfanylpropyl]amino]pentyl]amino]pentanoyl]amino]-4-methylsulfanylbutanoate | 180311-56-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: methyl (2S)-2-[[(2S,3S)-3-methyl-2-[methyl-[(2S,3S)-3-methyl-2-[[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-tritylsulfanylpropyl]amino]pentyl]amino]pentanoyl]amino]-4-methylsulfanylbutanoate
• CAS: 180311-56-2
• 化学式: C₄₆H₆₈N₄O₅S₂
• 分子量: 821.202
• InChiKey: SQTROMGCQHNMFS-WKYGKIQMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.7
• 重原子数：
  57
• 可旋转键数：
  26
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  160
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-[[(2S,3S)-3-methyl-2-[methyl-[(2S,3S)-3-methyl-2-[[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-tritylsulfanylpropyl]amino]pentyl]amino]pentanoyl]amino]-4-methylsulfanylbutanoate 在 三乙基硅烷 、 sodium hydroxide 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 N-[2(S)-(2(R)-amino-3-mercaptopropylamino)-3(S)-methylpentyl]-N-methyl-isoleucyl-methionine
  参考文献：
  名称：

  N-Arylalkyl Pseudopeptide Inhibitors of Farnesyltransferase

  摘要：

  Inhibitors of Ras protein farnesyltransferase are described which are reduced pseudopeptides related to the C-terminal tetrapeptide of the Ras protein that signals farnesylation. Reduction of the carbonyl groups linking the first three residues of the tetrapeptide leads to active inhibitors which are chemically unstable. Stability can he restored by alkylating the central amine of the tetrapeptide. Studies of the SAR of these alkylated pseudopeptides with concomitant modification of the side chain of the third residue led to 2(S)-(2(S)-{[2(S)-(2(R)-amino-3-mercaptopropylamino)-3-(S)-methylpentyl]naphthalen-1-ylmethylamino}acetylamino)-4-methylsulfanylbutyric acid (11), a subnanomolar inhibitor. The methyl ester (10) of this compound exhibited submicromolar activity in the processing assay and selectively inhibited anchorage-independent growth of Rat1 cells transformed by v-ras at 2.5-5 mu M.

  DOI：

  10.1021/jm9800907
• 作为产物：
  描述：

  methyl (2S)-2-[[(2S,3S)-3-methyl-2-[methyl-[(2S,3S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentyl]amino]pentanoyl]amino]-4-methylsulfanylbutanoate 在 盐酸 、 3 A molecular sieve 、 potassium acetate 、 sodium cyanoborohydride 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 生成 methyl (2S)-2-[[(2S,3S)-3-methyl-2-[methyl-[(2S,3S)-3-methyl-2-[[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-tritylsulfanylpropyl]amino]pentyl]amino]pentanoyl]amino]-4-methylsulfanylbutanoate
  参考文献：
  名称：

  N-Arylalkyl Pseudopeptide Inhibitors of Farnesyltransferase

  摘要：

  Inhibitors of Ras protein farnesyltransferase are described which are reduced pseudopeptides related to the C-terminal tetrapeptide of the Ras protein that signals farnesylation. Reduction of the carbonyl groups linking the first three residues of the tetrapeptide leads to active inhibitors which are chemically unstable. Stability can he restored by alkylating the central amine of the tetrapeptide. Studies of the SAR of these alkylated pseudopeptides with concomitant modification of the side chain of the third residue led to 2(S)-(2(S)-{[2(S)-(2(R)-amino-3-mercaptopropylamino)-3-(S)-methylpentyl]naphthalen-1-ylmethylamino}acetylamino)-4-methylsulfanylbutyric acid (11), a subnanomolar inhibitor. The methyl ester (10) of this compound exhibited submicromolar activity in the processing assay and selectively inhibited anchorage-independent growth of Rat1 cells transformed by v-ras at 2.5-5 mu M.

  DOI：

  10.1021/jm9800907