N-<2(R)-<(tert-butoxycarbonyl)amino>-3-<(triphenylmethyl)thio>propyl>-N-phenylethylisoleucine amide | 157324-99-7

• 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: N-<2(R)-<(tert-butoxycarbonyl)amino>-3-<(triphenylmethyl)thio>propyl>-N-phenylethylisoleucine amide
• 英文别名: N-[2(R)-(t-butoxycarbonyl)amino-3-triphenylmethylmercaptopropyl ]-L-isoleucine-phenethylamide；N-[2(R)-(t-butoxycarbonyl)amino-3-triphenylmethylmercaptopropyl]-L-isoleucine-phenethylamide；tert-butyl N-[(2R)-1-[[(2S,3S)-3-methyl-1-oxo-1-(2-phenylethylamino)pentan-2-yl]amino]-3-tritylsulfanylpropan-2-yl]carbamate
• CAS: 157324-99-7
• 化学式: C₄₁H₅₁N₃O₃S
• 分子量: 665.94
• InChiKey: VACLZYWAEHYPAQ-USXOCHBLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  48
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-<2(R)-<(tert-butoxycarbonyl)amino>-3-<(triphenylmethyl)thio>propyl>-N-phenylethylisoleucine amide 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以44%的产率得到N-(2(R)-amino-3-mercaptopropyl)-N-phenylethylisoleucine amide
  参考文献：
  名称：

  Pseudodipeptide Inhibitors of Protein Farnesyltransferase

  摘要：

  A series of pseudodipeptide amides are described that inhibit Ras protein farnesyltransferase (PFTase). These inhibitors are truncated versions of the C-terminal tetrapeptide (CAAX motif) of Ras that serves as the signal sequence for PFTase-catalyzed protein farnesylation. In contrast to CAAX peptidomimetics previously reported, these inhibitors do not have a C-terminal carboxyl moiety, yet they inhibit farnesylation in vitro at <100 nM. Despite the absence of the X residue in the CAAX motif, which normally directs prenylation specificity, these pseudodipeptides are greater than 100-fold selective for PFTase over type 1 protein geranylgeranyltransferase.

  DOI：

  10.1021/jm00020a010
• 作为产物：
  描述：

  L-异亮氨酸 在 3 A molecular sieve 、 sodium cyanoborohydride 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 、 3-羟基-1,2,3-苯并三嗪-4(3H)-酮 作用下， 以 乙醇 为溶剂， 反应 48.5h， 生成 N-<2(R)-<(tert-butoxycarbonyl)amino>-3-<(triphenylmethyl)thio>propyl>-N-phenylethylisoleucine amide
  参考文献：
  名称：

  Pseudodipeptide Inhibitors of Protein Farnesyltransferase

  摘要：

  A series of pseudodipeptide amides are described that inhibit Ras protein farnesyltransferase (PFTase). These inhibitors are truncated versions of the C-terminal tetrapeptide (CAAX motif) of Ras that serves as the signal sequence for PFTase-catalyzed protein farnesylation. In contrast to CAAX peptidomimetics previously reported, these inhibitors do not have a C-terminal carboxyl moiety, yet they inhibit farnesylation in vitro at <100 nM. Despite the absence of the X residue in the CAAX motif, which normally directs prenylation specificity, these pseudodipeptides are greater than 100-fold selective for PFTase over type 1 protein geranylgeranyltransferase.

  DOI：

  10.1021/jm00020a010

文献信息

• Inhibitors of farnesyl protein transferase
  申请人：Merck & Co., Inc.

  公开号：US05352705A1

  公开（公告）日：1994-10-04

  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醇-蛋白转移酶（FTase）和致癌基因蛋白Ras的法尼基化的化合物。本发明还涉及包含本发明化合物的化疗组合物以及抑制法尼醇-蛋白转移酶和致癌基因蛋白Ras的方法。
• US5352705A
  申请人：——

  公开号：US5352705A

  公开（公告）日：1994-10-04