Fmoc-AzaGly-Leu-OBu^t | 872720-98-4

• 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: Fmoc-AzaGly-Leu-OBu^t
• 英文别名: Fmoc-AzaGly-Leu-OBut；tert-butyl (2S)-2-[(9H-fluoren-9-ylmethoxycarbonylamino)carbamoylamino]-4-methylpentanoate
• CAS: 872720-98-4
• 化学式: C₂₆H₃₃N₃O₅
• 分子量: 467.565
• InChiKey: KCEVCLROLKSYTF-QFIPXVFZSA-N

物化性质

• 密度：
  1.172±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Fmoc-AzaGly-Leu-OBu^t 在 水 、 三氟乙酸 作用下， 反应 1.0h， 以87%的产率得到Fmoc-azaGly-Leu-OH
  参考文献：
  名称：

  Metastin derivatives and use thereof

  摘要：

  公开号：

  EP2113513B1
• 作为产物：
  描述：

  L-亮氨酸叔丁酯盐酸盐 、 N,N'-羰基二咪唑 、 Fmoc-hydrazine hydrochloride 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 以99%的产率得到Fmoc-AzaGly-Leu-OBu^t
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Investigational Nonapeptide KISS1R Agonists with Testosterone-Suppressive Activity

  摘要：

  Metastin/kisspeptin is a 54 amino acid peptide ligand of the KISS1R receptor and is a critical regulator of GnRH secretion. The N-terminally truncated peptide, metastin(45-54), possesses a 10-fold higher receptor-binding affinity than full-length metastin and agonistic KISS1R activity but is rapidly inactivated in rodent plasma. We have developed a decapeptide analog [D-Tye(45),D-Trp(47),azaGly(51),frArg(Me)(53)]metastin(45-54) with improved serum stability compared with metastin(45-54) but with decreased KISSIR agonistic activity. Amino acid replacements at positions 45-47 led to an enhancement of KISS1R agonistic activity and metabolic stability. N-terminal truncation resulted in a stable nonapeptide, [D-Tyr(46),D-Pya(4)(47),azaGlysl,Arg(Me)(53)ssimetastin(46-54), compound 26, which displayed KISS1R binding affinities comparable to metastin(45-54) and had improved serum stability. Compound 26 reduced plasma testosterone in male rats and is the first short-length metastin analog to possess testosterone suppressive activities. Compound 26 has led to the elucidation of investigational analogs TAK-683 and TAK-448, both of which have undergone clinical evaluation for hormone-dependent diseases such as prostate cancer.

  DOI：

  10.1021/jm401056w

文献信息

• METASTIN DERIVATIVES AND USE THEREOF
  申请人：Kitada Chieko

  公开号：US20090318365A1

  公开（公告）日：2009-12-24

  The present invention provides a metastin derivative in which the amino acids comprising metastin were modified by alternative chemical substituents resulting in metastin derivatives, having excellent blood stability and exhibiting cancer metastasis inhibiting action or cancer growth inhibiting action.

  本发明提供了一种metastin衍生物，其中包含metastin的氨基酸被替代化学基团修饰，从而产生了metastin衍生物，具有出色的血液稳定性，并表现出抑制癌症转移或抑制癌症生长的作用。
• Metastin Derivatives and Use Thereof
  申请人：Kitada Chieko

  公开号：US20080312155A1

  公开（公告）日：2008-12-18

  The invention provides stable metastin derivatives having excellent biological activities (a cancer metastasis suppressing activity, a cancer growth suppressing activity, etc.). By modifying the constituent amino acids of metastin with specific modifying groups, metastin derivatives having more improved blood stability, etc. than native metastin and showing excellent cancer metastasis suppressing activity or cancer growth suppressing activity have been found. Furthermore, it has been found that these metastin derivatives exhibit effects of suppressing gonadotropic hormone secretion, suppressing sex hormone secretion, etc., which are wholly different from the effects heretofore known.

  该发明提供了稳定的metastin衍生物，具有优异的生物活性（抑制癌细胞转移的活性，抑制癌细胞生长的活性等）。通过用特定的修饰基团修饰metastin的组成氨基酸，发现比天然的metastin具有更好的血液稳定性等，同时表现出优异的抑制癌细胞转移或抑制癌细胞生长的活性。此外，发现这些metastin衍生物表现出抑制性腺激素分泌、抑制性激素分泌等完全不同于以往所知的效应。
• Metastin derivatives and use thereof
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2113513B1

  公开（公告）日：2016-05-18
• Design, Synthesis, and Biological Evaluation of Novel Investigational Nonapeptide KISS1R Agonists with Testosterone-Suppressive Activity
  作者：Taiji Asami、Naoki Nishizawa、Hisanori Matsui、Kimiko Nishibori、Yoshihiro Ishibashi、Yasuko Horikoshi、Masaharu Nakayama、Shin-ichi Matsumoto、Naoki Tarui、Masashi Yamaguchi、Hirokazu Matsumoto、Tetsuya Ohtaki、Chieko Kitada

  DOI：10.1021/jm401056w

  日期：2013.11.14

  Metastin/kisspeptin is a 54 amino acid peptide ligand of the KISS1R receptor and is a critical regulator of GnRH secretion. The N-terminally truncated peptide, metastin(45-54), possesses a 10-fold higher receptor-binding affinity than full-length metastin and agonistic KISS1R activity but is rapidly inactivated in rodent plasma. We have developed a decapeptide analog [D-Tye(45),D-Trp(47),azaGly(51),frArg(Me)(53)]metastin(45-54) with improved serum stability compared with metastin(45-54) but with decreased KISSIR agonistic activity. Amino acid replacements at positions 45-47 led to an enhancement of KISS1R agonistic activity and metabolic stability. N-terminal truncation resulted in a stable nonapeptide, [D-Tyr(46),D-Pya(4)(47),azaGlysl,Arg(Me)(53)ssimetastin(46-54), compound 26, which displayed KISS1R binding affinities comparable to metastin(45-54) and had improved serum stability. Compound 26 reduced plasma testosterone in male rats and is the first short-length metastin analog to possess testosterone suppressive activities. Compound 26 has led to the elucidation of investigational analogs TAK-683 and TAK-448, both of which have undergone clinical evaluation for hormone-dependent diseases such as prostate cancer.