(S)-2-methyl-4-(tert butoxycarbonylamino)-5-nonene | 131064-83-0

• 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: (S)-2-methyl-4-(tert butoxycarbonylamino)-5-nonene
• 英文别名: (S)-2-Methyl-4-(tert. butoxycarbonylamino)-5-nonene；tert-butyl N-[(4S)-2-methylnon-5-en-4-yl]carbamate
• CAS: 131064-83-0
• 化学式: C₁₅H₂₉NO₂
• 分子量: 255.401
• InChiKey: SGCMPWLJTOHWHF-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-2-methyl-4-(tert butoxycarbonylamino)-5-nonene 在 palladium catalyst N-甲基吗啉 、 盐酸 、 氢气 、 1-羟基苯并三唑一水物 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 氯甲酸异丁酯 作用下， 以 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 116.25h， 生成 2-{2-[2-[2-(2,2-Dimethyl-propionylamino)-3-(3H-imidazol-4-yl)-propionylamino]-3-(1H-indol-3-yl)-propionylamino]-propionylamino}-N-{[2-(3H-imidazol-4-yl)-1-(1-isobutyl-hexylcarbamoyl)-ethylcarbamoyl]-methyl}-3-methyl-butyramide
  参考文献：
  名称：

  Gastrin releasing peptide antagonists with improved potency and stability

  摘要：

  Gastrin releasing peptide (GRP) is a 27 amino acid peptide hormone which is homologous to the amphibian peptide bombesin. Two series of novel GRP antagonists were developed by C-terminal modification of N-acetyl-GRP-20-27 amide. Peptide derivatives within each series resist enzymatic degradation in serum and exhibit strong affinity for the GRP receptor. The first series of compounds replaces the Leu26-Met27 region of GRP with an alkyl ether moiety. One member of this series, N-acetyl-GRP-20-25-NH-[(S)-1-ethoxy-4-methyl-2-pentane], specifically blocked radiolabeled GRP binding with an IC50 of 6 nM. In the second series of antagonists the oxygen of the ether moiety is replaced with a methylene group, resulting in GRP antagonists which are equipotent to native GRP in receptor binding assays (IC50 = 2 nM) and are also resistant to proteolytic degradation in vitro. All of the C-terminally modified peptides tested blocked GRP-stimulated mitogenesis in Swiss 3T3 mouse fibroblasts. Representative compounds also blocked GRP-induced elevation of [Ca2+]i in human SCLC cells, and inhibited GRP-independent release of gastrin in vivo.

  DOI：

  10.1021/jm00111a027
• 作为产物：
  描述：

  丁基三苯基溴化膦 、 2-甲基-2-丙基[(2S)-4-甲基-1-氧代-2-戊烷基]氨基甲酸酯 在 potassium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 生成 (S)-2-methyl-4-(tert butoxycarbonylamino)-5-nonene
  参考文献：
  名称：

  Gastrin releasing peptide antagonists with improved potency and stability

  摘要：

  Gastrin releasing peptide (GRP) is a 27 amino acid peptide hormone which is homologous to the amphibian peptide bombesin. Two series of novel GRP antagonists were developed by C-terminal modification of N-acetyl-GRP-20-27 amide. Peptide derivatives within each series resist enzymatic degradation in serum and exhibit strong affinity for the GRP receptor. The first series of compounds replaces the Leu26-Met27 region of GRP with an alkyl ether moiety. One member of this series, N-acetyl-GRP-20-25-NH-[(S)-1-ethoxy-4-methyl-2-pentane], specifically blocked radiolabeled GRP binding with an IC50 of 6 nM. In the second series of antagonists the oxygen of the ether moiety is replaced with a methylene group, resulting in GRP antagonists which are equipotent to native GRP in receptor binding assays (IC50 = 2 nM) and are also resistant to proteolytic degradation in vitro. All of the C-terminally modified peptides tested blocked GRP-stimulated mitogenesis in Swiss 3T3 mouse fibroblasts. Representative compounds also blocked GRP-induced elevation of [Ca2+]i in human SCLC cells, and inhibited GRP-independent release of gastrin in vivo.

  DOI：

  10.1021/jm00111a027

文献信息

• Gastrin releasing peptide antagonist
  申请人：Merck & Co., Inc.

  公开号：US04943561A1

  公开（公告）日：1990-07-24

  Small cell lung carcinoma (SCLC) cells contain gastrin releasing peptide (GRP) receptors. The response of the cells to GRP is rapid growth. We have found a group of peptide derivatives that act as GRP antagonists by blocking the binding of GRP to its receptor thereby inhibiting the growth of cells that are sensitive to the growth promoting activity of GRP.

  小细胞肺癌（SCLC）细胞含有胃泌素释放肽（GRP）受体。细胞对GRP的反应是快速生长。我们发现了一组肽衍生物，通过阻断GRP与其受体的结合，从而抑制对GRP的生长促进活性敏感的细胞的生长，这些肽衍生物起到了GRP拮抗剂的作用。