Leuψ(CHOH)(CH₂)₃CH₃ | 207728-44-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: Leuψ(CHOH)(CH₂)₃CH₃
• 英文别名: (4S)-4-amino-2-methylnonan-5-ol
• CAS: 207728-44-7
• 化学式: C₁₀H₂₃NO
• 分子量: 173.299
• InChiKey: ABAFATZXWZOIKK-RGURZIINSA-N

物化性质

• 沸点：
  273.9±13.0 °C(Predicted)
• 密度：
  0.884±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  12
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  46.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (叔丁氧基羰基)-L-缬氨酰-L-缬氨酸 、 Leuψ(CHOH)(CH₂)₃CH₃ 在 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 24.0h， 以65%的产率得到4-{N-[(tert-butoxycarbonyl)-L-valyl-L-valyl]amino}-2-methylnonan-5-ol
  参考文献：
  名称：

  Auxiliary Agents for the Peroral Administration of Peptide and Protein Drugs:  Synthesis and Evaluation of Novel Pepstatin Analogues

  摘要：

  The peroral administration of(poly)peptide drugs requires the development of delivery systems, which provide a protective effect toward a gastrointestinal enzymatic attack. A promising strategy for such systems represents polymer-enzyme inhibitor conjugates in which the embedded therapeutic agent is protected. However, the practical use of polymer-inhibitor conjugates has so far been limited by high production costs of these auxiliary agents. To solve this problem for delivery systems shielding from pepsinic degradation, structurally simplified analogues of the pepsin inhibitor pepstatin A have been synthesized. The synthesis of tripeptide analogues, described by McConnell et al., led us to pursue further modifications varying the C-terminus. Our target to attach a spacer moisty-enabling the free access of pepsin to the inhibitor-should be combined with an attractive synthetic approach providing low production costs in large-scale preparation. Structure modifications comprised either the side chain of the third amino acid which served as starting compound designing the C-terminus (L-leucine, L-isoleucine, L-norvaline) as the length of the spacer link, simulated by a linear alkyl group (n-butyl, n-hexyl, and n-octyl). The inhibitory activities which have been evaluated by an enzyme assay were significantly dependent on the nature of the side chain, whereas the length of the spacer had no influence on the inhibitory effect. Analogues bearing the isobutyl or n-propyl moiety as side chain displayed a strong inhibitory effect which was comparable to that pepstatin A. These congeners represent promising auxiliary agents for the peroral administration of(poly)peptide drugs.

  DOI：

  10.1021/jm980015w
• 作为产物：
  描述：

  benzyl N-[(4S)-2-methyl-5-oxononan-4-yl]carbamate 在 palladium on activated charcoal sodium tetrahydroborate 、 氢气 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 0.5h， 生成 Leuψ(CHOH)(CH₂)₃CH₃
  参考文献：
  名称：

  Auxiliary Agents for the Peroral Administration of Peptide and Protein Drugs:  Synthesis and Evaluation of Novel Pepstatin Analogues

  摘要：

  The peroral administration of(poly)peptide drugs requires the development of delivery systems, which provide a protective effect toward a gastrointestinal enzymatic attack. A promising strategy for such systems represents polymer-enzyme inhibitor conjugates in which the embedded therapeutic agent is protected. However, the practical use of polymer-inhibitor conjugates has so far been limited by high production costs of these auxiliary agents. To solve this problem for delivery systems shielding from pepsinic degradation, structurally simplified analogues of the pepsin inhibitor pepstatin A have been synthesized. The synthesis of tripeptide analogues, described by McConnell et al., led us to pursue further modifications varying the C-terminus. Our target to attach a spacer moisty-enabling the free access of pepsin to the inhibitor-should be combined with an attractive synthetic approach providing low production costs in large-scale preparation. Structure modifications comprised either the side chain of the third amino acid which served as starting compound designing the C-terminus (L-leucine, L-isoleucine, L-norvaline) as the length of the spacer link, simulated by a linear alkyl group (n-butyl, n-hexyl, and n-octyl). The inhibitory activities which have been evaluated by an enzyme assay were significantly dependent on the nature of the side chain, whereas the length of the spacer had no influence on the inhibitory effect. Analogues bearing the isobutyl or n-propyl moiety as side chain displayed a strong inhibitory effect which was comparable to that pepstatin A. These congeners represent promising auxiliary agents for the peroral administration of(poly)peptide drugs.

  DOI：

  10.1021/jm980015w

文献信息

• Evaluation of Three Different Families of Bombesin Receptor Radioantagonists for Targeted Imaging and Therapy of Gastrin Releasing Peptide Receptor (GRP-R) Positive Tumors
  作者：Rosalba Mansi、Keelara Abiraj、Xuejuan Wang、Maria Luisa Tamma、Eleni Gourni、Renzo Cescato、Sandra Berndt、Jean Claude Reubi、Helmut R. Maecke

  DOI：10.1021/jm5012066

  日期：2015.1.22

  Two new classes of radiolabeled GRP receptor antagonists are studied and compared with the well-established statine-based receptor antagonist DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (RM2, 1; DOTA:1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; Sta:(3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid). The bombesin-based pseudopeptide DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Leu?(CHOH-CH2)-(CH2)(2)-CH3 (RM7, 2), and the methyl ester DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-OCH3 (ARBA05, 3) analogues are labeled with In-111 and evaluated in vitro in PC-3 cell line and in vivo in PC-3 tumor-bearing nude mice. Antagonist potency was assessed by immunofluorescence-based receptor internalization and Ca2+ mobilization assays. The conjugates showed good binding affinity, the IC50 value of 2 (3.2 +/- 1.8 nM) being 2 and 10 times lower than 1 and 3. Compared to In-111-1, In-111-2 showed higher uptake in target tissues such as pancreas (1.5 +/- 0.5%IA/g and 39.8 +/- 9.3%IA/g at 4 h, respectively), whereas the compounds had similar tumor uptake (11.5 +/- 2.4%IA/g and 11.8 +/- 3.9%IA/g at 4h, respectively). The displacement of the radioligand in vivo was different in different receptor positive organs and depended on the displacing peptide.