(S)-6-Benzyloxycarbonylamino-2-[(R)-2-tert-butoxycarbonylamino-3-(1H-indol-3-yl)-2-methyl-propionylamino]-hexanoic acid methyl ester | 187395-77-3

• 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)-6-Benzyloxycarbonylamino-2-[(R)-2-tert-butoxycarbonylamino-3-(1H-indol-3-yl)-2-methyl-propionylamino]-hexanoic acid methyl ester
• 英文别名: Boc-D-aMeTrp-Lys(Cbz)-OMe；methyl (2S)-2-[[(2R)-3-(1H-indol-3-yl)-2-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-6-(phenylmethoxycarbonylamino)hexanoate
• CAS: 187395-77-3
• 化学式: C₃₂H₄₂N₄O₇
• 分子量: 594.708
• InChiKey: MDOFOYZXJAQYBY-XYFQYJLHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  43
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  148
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-6-Benzyloxycarbonylamino-2-[(R)-2-tert-butoxycarbonylamino-3-(1H-indol-3-yl)-2-methyl-propionylamino]-hexanoic acid methyl ester 在 palladium on activated charcoal sodium hydroxide 、 氢气 、 碳酸氢钠 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 苯甲醚 、 三乙胺 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 (S)-N-((S)-1-Carbamoyl-2-phenyl-ethyl)-3-{[(3R,13S)-3-(1H-indol-3-ylmethyl)-3-methyl-2,5,7-trioxo-1,4,8-triaza-cyclotridecane-13-carbonyl]-amino}-succinamic acid benzyl ester
  参考文献：
  名称：

  Structure-Based Design of New Constrained Cyclic Agonists of the Cholecystokinin CCK-B Receptor

  摘要：

  New constrained cyclic pseudopeptide cholecystokinin-B (CCK-B) agonists have been designed on the basis of conformational characteristics of the potent and selective CCK-B agonist Boc-Trp-(NMe)Nle-Asp-Phe-NH2 (K-i = 0.8 nm, selectivity ratio CCK-A/CCK-B > 6000) (Goudreau et al. Biopolymers, 1994, 34, 155-169). These compounds are among the first successful examples of macrocyclic constrained CCK4 analogs endowed with agonist properties and as such may be of value for the development of nonpeptide CCK-B agonists. The affinities and selectivities of these compounds for CCK-B and CCK-A receptors have been determined in vitro by measuring the displacement of [H-3]pCCK(8) binding to guinea pig cortex and pancreas membranes, respectively. The most potent compound, 8b, N-(cycloamido)-alpha-Me(R)Trp-[(2S)-2-amino-9-((cycloamido)carbonyl)nonanoyl]-Asp-Phe-NH2, has a K-i value of 15 +/- 1 nM for guinea pig cortex membranes with a good CCK-B selectivity ratio (CCK-A/CCK-B = 147). Furthermore, 8b behaved as a potent and full agonist in a functional assay which measures the stimulation of inositol phosphate accumulation in CHO cells transfected with the rat CCK-B receptor (EC(50) = 7 nM). The in vivo affinity of 8b for mouse brain CCK-B receptors was determined following intracerebroventricular injection (ID50 similar to 29 nmol/kg). 8b was also shown to cross the blood-brain barrier (0.16%), after intravenous administration in mice. 8b also increased gastric acid secretion measured in anesthetized rats after intravenous injection. Therefore, 8b appears to be an interesting pharmacological tool and is currently under investigation as a lead for further development of nonpeptide CCK-B agonists.

  DOI：

  10.1021/jm9603072
• 作为产物：
  描述：

  (S)-methyl 2-amino-6-(benzyloxycarbonylamino)hexanoate 、 Boc-α-Me-D-Trp-OH 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 生成 (S)-6-Benzyloxycarbonylamino-2-[(R)-2-tert-butoxycarbonylamino-3-(1H-indol-3-yl)-2-methyl-propionylamino]-hexanoic acid methyl ester
  参考文献：
  名称：

  Structure-Based Design of New Constrained Cyclic Agonists of the Cholecystokinin CCK-B Receptor

  摘要：

  New constrained cyclic pseudopeptide cholecystokinin-B (CCK-B) agonists have been designed on the basis of conformational characteristics of the potent and selective CCK-B agonist Boc-Trp-(NMe)Nle-Asp-Phe-NH2 (K-i = 0.8 nm, selectivity ratio CCK-A/CCK-B > 6000) (Goudreau et al. Biopolymers, 1994, 34, 155-169). These compounds are among the first successful examples of macrocyclic constrained CCK4 analogs endowed with agonist properties and as such may be of value for the development of nonpeptide CCK-B agonists. The affinities and selectivities of these compounds for CCK-B and CCK-A receptors have been determined in vitro by measuring the displacement of [H-3]pCCK(8) binding to guinea pig cortex and pancreas membranes, respectively. The most potent compound, 8b, N-(cycloamido)-alpha-Me(R)Trp-[(2S)-2-amino-9-((cycloamido)carbonyl)nonanoyl]-Asp-Phe-NH2, has a K-i value of 15 +/- 1 nM for guinea pig cortex membranes with a good CCK-B selectivity ratio (CCK-A/CCK-B = 147). Furthermore, 8b behaved as a potent and full agonist in a functional assay which measures the stimulation of inositol phosphate accumulation in CHO cells transfected with the rat CCK-B receptor (EC(50) = 7 nM). The in vivo affinity of 8b for mouse brain CCK-B receptors was determined following intracerebroventricular injection (ID50 similar to 29 nmol/kg). 8b was also shown to cross the blood-brain barrier (0.16%), after intravenous administration in mice. 8b also increased gastric acid secretion measured in anesthetized rats after intravenous injection. Therefore, 8b appears to be an interesting pharmacological tool and is currently under investigation as a lead for further development of nonpeptide CCK-B agonists.

  DOI：

  10.1021/jm9603072

文献信息

• Structure-Based Design of New Constrained Cyclic Agonists of the Cholecystokinin CCK-B Receptor
  作者：Armand G. S. Blommaert、Hélène Dhôtel、Bertrand Ducos、Christiane Durieux、Nathalie Goudreau、André Bado、Christiane Garbay、Bernard P. Roques

  DOI：10.1021/jm9603072

  日期：1997.2.1

  New constrained cyclic pseudopeptide cholecystokinin-B (CCK-B) agonists have been designed on the basis of conformational characteristics of the potent and selective CCK-B agonist Boc-Trp-(NMe)Nle-Asp-Phe-NH2 (K-i = 0.8 nm, selectivity ratio CCK-A/CCK-B > 6000) (Goudreau et al. Biopolymers, 1994, 34, 155-169). These compounds are among the first successful examples of macrocyclic constrained CCK4 analogs endowed with agonist properties and as such may be of value for the development of nonpeptide CCK-B agonists. The affinities and selectivities of these compounds for CCK-B and CCK-A receptors have been determined in vitro by measuring the displacement of [H-3]pCCK(8) binding to guinea pig cortex and pancreas membranes, respectively. The most potent compound, 8b, N-(cycloamido)-alpha-Me(R)Trp-[(2S)-2-amino-9-((cycloamido)carbonyl)nonanoyl]-Asp-Phe-NH2, has a K-i value of 15 +/- 1 nM for guinea pig cortex membranes with a good CCK-B selectivity ratio (CCK-A/CCK-B = 147). Furthermore, 8b behaved as a potent and full agonist in a functional assay which measures the stimulation of inositol phosphate accumulation in CHO cells transfected with the rat CCK-B receptor (EC(50) = 7 nM). The in vivo affinity of 8b for mouse brain CCK-B receptors was determined following intracerebroventricular injection (ID50 similar to 29 nmol/kg). 8b was also shown to cross the blood-brain barrier (0.16%), after intravenous administration in mice. 8b also increased gastric acid secretion measured in anesthetized rats after intravenous injection. Therefore, 8b appears to be an interesting pharmacological tool and is currently under investigation as a lead for further development of nonpeptide CCK-B agonists.