N-[2(S)-(1,1-Dimethylethoxycarbonylamino)-3(S)-methylpentyl]-N-benzylglycyl-methionine methyl ester | 178270-38-7

• 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)-(1,1-Dimethylethoxycarbonylamino)-3(S)-methylpentyl]-N-benzylglycyl-methionine methyl ester
• 英文别名: methyl (2S)-2-[[2-[benzyl-[(2S,3S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentyl]amino]acetyl]amino]-4-methylsulfanylbutanoate
• CAS: 178270-38-7
• 化学式: C₂₆H₄₃N₃O₅S
• 分子量: 509.711
• InChiKey: IZOVBPMSDSQEBY-ILWGZMRPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  35
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  122
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-[2(S)-(1,1-Dimethylethoxycarbonylamino)-3(S)-methylpentyl]-N-benzylglycyl-methionine methyl ester 在 盐酸 、 sodium hydroxide 、 3 A molecular sieve 、 potassium acetate 、 sodium cyanoborohydride 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 N-[2(S)-(2(R)-amino-3-mercaptopropylamino)-3(S)-methylpentyl]-N-benzyl-glycyl 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：

  [Benzyl-((2S,3S)-2-tert-butoxycarbonylamino-3-methyl-pentyl)-amino]-acetic acid methyl ester 在 sodium hydroxide 、 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 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-[2(S)-(1,1-Dimethylethoxycarbonylamino)-3(S)-methylpentyl]-N-benzylglycyl-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

• US5585359A
  申请人：——

  公开号：US5585359A

  公开（公告）日：1996-12-17
• <i>N</i>-Arylalkyl Pseudopeptide Inhibitors of Farnesyltransferase
  作者：S. Jane deSolms、Elizabeth A. Giuliani、Samuel L. Graham、Kenneth S. Koblan、Nancy E. Kohl、Scott D. Mosser、Allen I. Oliff、David L. Pompliano、Elaine Rands、Thomas H. Scholz、Catherine M. Wiscount、Jackson B. Gibbs、Robert L. Smith

  DOI：10.1021/jm9800907

  日期：1998.7.1

  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.