N-[2(S)-(2(R)-t-butoxycarbonylamino-3-triphenylmethylmercaptopropylamino)-3(S)-methylpentyl]phenylalanyl-methionine methyl ester | 150350-34-8

• 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-[2(S)-(2(R)-t-butoxycarbonylamino-3-triphenylmethylmercaptopropylamino)-3(S)-methylpentyl]phenylalanyl-methionine methyl ester
• 英文别名: methyl (2S)-2-[[(2S)-2-[[(2S,3S)-3-methyl-2-[[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-tritylsulfanylpropyl]amino]pentyl]amino]-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoate
• CAS: 150350-34-8
• 化学式: C₄₈H₆₄N₄O₅S₂
• 分子量: 841.192
• InChiKey: LXNLDNZOXDGRGF-UUWDYQMPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.5
• 重原子数：
  59
• 可旋转键数：
  26
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  168
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-[2(S)-(2(R)-t-butoxycarbonylamino-3-triphenylmethylmercaptopropylamino)-3(S)-methylpentyl]phenylalanyl-methionine methyl ester 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]phenylalanyl-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-[(2-methylpropan-2-yl)oxycarbonylamino]pentyl]amino]-3-phenylpropanoate 在 盐酸 、 sodium hydroxide 、 3 A molecular sieve 、 potassium acetate 、 sodium cyanoborohydride 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-[2(S)-(2(R)-t-butoxycarbonylamino-3-triphenylmethylmercaptopropylamino)-3(S)-methylpentyl]phenylalanyl-methionine methyl ester
  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

文献信息

• Inhibitors of farnesyl protein transferase
  申请人：MERCK & CO. INC.

  公开号：EP0535731A2

  公开（公告）日：1993-04-07

  The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

  本发明涉及抑制法尼基蛋白转移酶（FTase）和癌基因蛋白Ras的法尼基化的化合物。 本发明进一步涉及含有本发明化合物的化疗组合物以及抑制法尼基蛋白转移酶和癌基因蛋白 Ras 的法尼基化的方法。
• US5238922A
  申请人：——

  公开号：US5238922A

  公开（公告）日：1993-08-24