N-succinimidyl 3-(2-thienyl)acrylate | 159312-33-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: N-succinimidyl 3-(2-thienyl)acrylate
• 英文别名: 3-(2-Thienyl)acrylic acid N-hydroxysuccinimide ester；(2,5-dioxopyrrolidin-1-yl) (E)-3-thiophen-2-ylprop-2-enoate
• CAS: 159312-33-1
• 化学式: C₁₁H₉NO₄S
• 分子量: 251.263
• InChiKey: MZWGWBYJDSENEP-ZZXKWVIFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  91.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Boc-Trp-Lys-Asp-Phe-NH2 、 N-succinimidyl 3-(2-thienyl)acrylate 在 N-甲基吗啉 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-3-[(S)-2-[(S)-2-tert-Butoxycarbonylamino-3-(1H-indol-3-yl)-propionylamino]-6-((E)-3-thiophen-2-yl-acryloylamino)-hexanoylamino]-N-((S)-1-carbamoyl-2-phenyl-ethyl)-succinamic acid
  参考文献：
  名称：

  Development of potent and selective CCK-A receptor agonists from Boc-CCK-4: tetrapeptides containing Lys(N.epsilon.)-amide residues

  摘要：

  A series of Boc-CCK-4 derivatives represented by the general structure Boc-Trp-Lys(N(epsilon)-COR)-Asp-Phe-NH2, where R is an aromatic, heterocyclic, or aliphatic group, are potent and selective CCK-AT receptor agonists. These amide-bearing compounds complement the previously described urea-based tetrapeptides (Shiosaki et al. J. Med. Chem. 1991, 34, 2837-2842); structure-activity studies revealed parallel as well as divergent trends between these two series. A significant correlation was observed between pancreatic binding affinity and the resonance constant R of the phenyl substituent in one particular series of derivatives. Sulfation of phenolic amides appended onto the epsilon-amino group of the lysine did not affect affinity for the CCK-AT receptor in contrast to the 500-fold increase in binding potency observed upon sulfation of CCK-8, suggesting that the lysine appendage and the sulfated tyrosine in CCK-8, both key structural elements that impart high affinity for the CCK-A receptor, are interacting differently with the receptor. The amide-bearing tetrapeptides are full agonists relative to CCK-8 in stimulating pancreatic amylase release while being partial agonists in eliciting phosphoinositide (PI) hydrolysis. Both effects were blocked by selective CCK-A receptor antagonists.

  DOI：

  10.1021/jm00089a010
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 3-（2-噻嗯基）丙烯酸 以 二氯甲烷 为溶剂， 生成 N-succinimidyl 3-(2-thienyl)acrylate
  参考文献：
  名称：

  Derivatives of tetrapeptides as CCK agonists

  摘要：

  公式（I）的选择性和有效的Type-A CCK受体激动剂为：X--Y--Z--Q（I）或其药学上可接受的盐，其中，X选自##STR1##，Y选自##STR2##，Z为##STR3##，Q为##STR4##或其药学上可接受的盐，可用于治疗胃肠道疾病（包括胆囊疾病）、中枢神经系统疾病、胰岛素相关疾病和疼痛，以及食欲调节。

  公开号：

  US05270302A1

文献信息

• CCK-A-Selective Tetrapeptides Containing Lys(N.epsilon.)-Amide Residues: Favorable in vivo and in vitro Effects of N-Methylation at the Aspartyl Residue
  作者：Michael J. Bennett、A. L. Nikkel、Bruce R. Bianchi、Thomas R. Miller、Lisa Bednarz、David G. Witte、Michael Stashko、Song Shung Wang、Paul A. Gore

  DOI：10.1021/jm00037a006

  日期：1994.5

  Previous structure-activity studies on a series of CCK-A selective tetrapeptide agonists, typified by A-71623 (Boc-Trp-Lys(CONH-Ph-o-Me)-Asp-(N-Me)Phe-NH2), have shown that replacement of the Lys(N-epsilon-carbamoyl) substituent with N-epsilon-acyl substituents resulted in partial agonists with moderate to high affinities for the CCK-A receptor and that replacement of the C-terminal dipeptide with either (N-Me)Asp-Phe or (N-Me)Asp-(N-Me)Phe was highly favorable to in vitro and in vivo CCK activity. The present study demonstrates that although analogues in the epsilon-amide series that are N-methylated at the Phe position are weakly active or inactive in an in vivo rat appetite suppression assay, incorporation of (N-Me)Asp or (N-Me)Asp-(N-Me)Phe modifications in this series results in analogues with markedly improved in vivo activity. In in vitro assays, there is minimal effect of N-methylation pattern on binding affinity, whereas there is a trend toward improved functional activity in the phosphatidylinositol hydrolysis assay in analogues containing (N-Me)Asp.
• EP0449884A4
  申请人：——

  公开号：EP0449884A4

  公开（公告）日：1991-10-30
• DERIVATIVES OF TETRAPEPTIDES AS CCK AGONISTS
  申请人：ABBOTT LABORATORIES

  公开号：EP0449884A1

  公开（公告）日：1991-10-09
• US5270302A
  申请人：——

  公开号：US5270302A

  公开（公告）日：1993-12-14
• [EN] DERIVATIVES OF TETRAPEPTIDES AS CCK AGONISTS
  申请人：ABBOTT LABORATORIES

  公开号：WO1990006937A1

  公开（公告）日：1990-06-28

  (EN) Tetrapeptide analogs are disclosed which possess CCK agonist activity.(FR) Les analogues de tétrapeptides décrits possèdent une activité similaire à la cholécystokinine (CCK).