N-α-(tert-butoxycarbonyl)-S-(triphenylmethyl)-L-cysteinal | 149910-63-4

• 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-α-(tert-butoxycarbonyl)-S-(triphenylmethyl)-L-cysteinal
• 英文别名: N-Boc-S-trityl-L-cysteinal；N-Boc-S-trityl-(L)-cysteinal；tert-butyl N-[(2R)-1-oxo-3-tritylsulfanylpropan-2-yl]carbamate
• CAS: 149910-63-4
• 化学式: C₂₇H₂₉NO₃S
• 分子量: 447.598
• InChiKey: BVIZOEBRLRZHGI-XMMPIXPASA-N

物化性质

• 沸点：
  566.8±50.0 °C(Predicted)
• 密度：
  1.151±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-α-(tert-butoxycarbonyl)-S-(triphenylmethyl)-L-cysteinal 在 3 A molecular sieve 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 sodium cyanoborohydride 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 N-<2(R)-<(tert-butoxycarbonyl)amino>-3-<(triphenylmethyl)thio>propyl>-N-phenylisoleucine 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：

  Boc-Cys(Trt)-OH 在 N-甲基哌啶 、 lithium aluminium tetrahydride 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 生成 N-α-(tert-butoxycarbonyl)-S-(triphenylmethyl)-L-cysteinal
  参考文献：
  名称：

  Pseudopeptide Inhibitors of Ras Farnesyl-Protein Transferase

  摘要：

  Inhibitors of Ras farnesyl-protein transferase are described. These are reduced pseudopeptides related to the C-terminal tetrapeptide of the Ras protein that signals farnesylation. Deletion of the carbonyl groups between the first two residues of the tetrapeptides either preserves or improves activity, depending on the peptide sequence. The most potent in vitro enzyme inhibitor described (IC50 = 5 nM) is Cys[PSICH2NH]Ile[PSICH2NH]Phe-Met(3). To obtain compounds able to suppress Ras farnesylation in cell culture, further structural modification to include a homoserine lactone prodrug was required. Compound 18(Cys[PSICH2NH]Ile[PSICH2NH]Ile-homoserine lactone)reduced the extent of Ras farnesylation by 50 % in NIH3T3 fibroblasts in culture at a concentration of 50 muM. Structure-activity studies also led to 12 (Cys[PSICH2NH]Val-Ile-Leu), a potent and selective inhibitor of a related enzyme, the type-I geranylgeranyl protein transferase.

  DOI：

  10.1021/jm00032a004

文献信息

• Inhibitors of prenyl transferases
  申请人：Univeristy of Pittsburgh

  公开号：US05965539A1

  公开（公告）日：1999-10-12

  Compounds which inhibit prenyl transferases, particularly farnysyltransferase and geranylgeranyl transferase I, processes for preparing the compounds, pharmaceutical compositions containing the compounds, and methods of use.

  抑制戊二烯基转移酶，特别是戊二烯基转移酶和戊二烯基转移酶I的化合物，制备这些化合物的方法，含有这些化合物的药物组合物，以及使用方法。
• Inhibitors of farnesyltransferase
  申请人：University of Pittsburgh

  公开号：US05834434A1

  公开（公告）日：1998-11-10

  Peptidomimetics of the formula C.beta.X where C is cysteine, X is any naturally occuring amino acid, and .beta. is a hydrophobic spacer, most notably 2-phenyl-4-aminobenzoic acid. These compounds are effective inhibitors of p2lras farnesyltrasferase, block Ras-dependent oncogenic signalling and inhibit human tumor growth in vivo in animal models. Pro-drugs made by functionalizing terminal amino and carboxylic acid groups of peptides and peptidomimetics are also disclosed. Such functionalized derivatives demonstrate increased cell uptake. Other structural modifications are also disclosed.

  公式为C.beta.X的肽类模拟物，其中C代表半胱氨酸，X代表任何自然存在的氨基酸，.beta.代表疏水间隔物，尤其是2-苯基-4-氨基苯甲酸。这些化合物是p2lras法尼基转移酶的有效抑制剂，可以阻断Ras依赖的致癌信号传导，并在动物模型中有效抑制人类肿瘤生长。还披露了通过功能化肽和肽类模拟物的末端氨基和羧基团制备的前药。这些功能化衍生物表现出增加的细胞摄取。还披露了其他结构修饰。
• Method of treating cancer
  申请人：——

  公开号：US20030220241A1

  公开（公告）日：2003-11-27

  The present invention relates to methods of treating cancer using a combination of a compound which is a PSA conjugate and a compound which is a inhibitor of prenyl-protein transferase, which methods comprise administering to said mammal, either sequentially in any order or simultaneously, amounts of at least two therapeutic agents selected from a group consisting of a compound which is a PSA conjugate and a compound which is a inhibitor of prenyl-protein transferase. The invention also relates to methods of preparing such compositions.

  本发明涉及使用一种PSA共轭物和一种前脂蛋白转移酶抑制剂的组合治疗癌症的方法，该方法包括向所述哺乳动物施用来自以下组中选择的至少两种治疗剂的量，所述组包括一种PSA共轭物和一种前脂蛋白转移酶抑制剂，所述治疗剂可以顺序给药或同时给药。该发明还涉及制备这种组合物的方法。
• Stereoselective synthesis of chiral thiol-containing 1,2-aminoalcohols via SmI2-mediated coupling
  作者：Carina Doler、Michael Friess、Florian Lackner、Hansjörg Weber、Roland C. Fischer、Rolf Breinbauer

  DOI：10.1016/j.tet.2020.131249

  日期：2020.12

  The stereoselective synthesis of highly functionalized aminohydroxythiols represents a synthetic challenge as the oxidation sensitivity and coordinating property of the thiol group interferes with many established synthetic methods. The SmI2/LiBr-mediated reductive coupling between Ellman N-sulfinylimines, containing thiol groups protected either as trityl thioether or dihydrothiazolidine, and aldehydes

  高度官能化的氨基羟基硫醇的立体选择性合成代表了一项合成挑战，因为硫醇基团的氧化敏感性和配位特性会干扰许多已建立的合成方法。包含被保护为三苯甲基硫醚或二氢噻唑烷的巯基的Ellman N-亚磺酰亚胺基与醛之间的SmI 2 / LiBr介导的还原偶联使得醛类能够以高对映选择性和非对映选择性合成手性氨基羟基硫醇。已经为18个实施例确定了该反应的范围，并将其用于生物合成研究所需的复杂中间体的合成。
• Inhibitors of farnesyl-protein transferase
  申请人：Merck & Co., Inc.

  公开号：US05736539A1

  公开（公告）日：1998-04-07

  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. The compounds of formula A are representative of the compounds of the present invention: ##STR1##

  本发明涉及抑制法尼基-蛋白转移酶（FTase）和致癌基因蛋白Ras的法尼酰化的化合物。该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-蛋白转移酶和致癌基因蛋白Ras的方法。式A的化合物代表了本发明的化合物：##STR1##