N1-(2-phenylethyl)-(2R)-2-{[N'-(4-(2-thienyl)phenylmethylene)hydrazino]carboxamido}-3-[1-(tert-butoxycarbonyl)-3-indolyl]propanamide

• 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: N1-(2-phenylethyl)-(2R)-2-{[N'-(4-(2-thienyl)phenylmethylene)hydrazino]carboxamido}-3-[1-(tert-butoxycarbonyl)-3-indolyl]propanamide
• 英文别名: tert-butyl 3-[(2R)-3-oxo-3-(2-phenylethylamino)-2-[[(E)-(4-thiophen-2-ylphenyl)methylideneamino]carbamoylamino]propyl]indole-1-carboxylate
• 化学式: C₃₆H₃₇N₅O₄S
• 分子量: 635.787
• InChiKey: BAXPASRMGDQCNH-FAWQHPFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  46
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  142
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N1-(2-phenylethyl)-(2R)-2-{[N'-(4-(2-thienyl)phenylmethylene)hydrazino]carboxamido}-3-[1-(tert-butoxycarbonyl)-3-indolyl]propanamide 在 三异丙基硅烷 、 三氟乙酸 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 以74%的产率得到N1-(2-phenylethyl)-(2R)-2-{[N'-(4-(2-thienyl)phenylmethylene)hydrazino]carboxamido}-3-(1H-3-indolyl)propanamide
  参考文献：
  名称：

  Design of Selective Peptidomimetic Agonists for the Human Orphan Receptor BRS-3

  摘要：

  New tool substances may help to unravel the physiological role of the human orphan receptor BRS-3 and its possible use as a drug target for the treatment of obesity and cancer. In continuation of our work on BRS-3, the solid- and solution-phase synthesis of a library of low molecular weight peptidomimetic agonists based on the recently developed short peptide agonist 4 is described. Functional potencies of the compounds were determined measuring calcium mobilization in a fluorometric imaging plate reader (FLIPR) assay. Focusing on the N-terminus, the D-Phe-Gln moiety of 4 was modified in a combinatorial. SAR-oriented medicinal chemistry approach. With the incorporation of N-arylated glycine and alanine building blocks azaglycine, piperazine, or piperidine and the synthesis of semicarbazides and semicarbazones, a number of highly potent and selective compounds with a reduced number of peptide bonds were obtained, which also should have enhanced metabolic stability.

  DOI：

  10.1021/jm0210921
• 作为产物：
  描述：

  tert-butyl-3-{(2R)-2-amino-2-[1-(2-phenylethyl)carbamoyl]ethyl}-1H-1-indolecarboxylate 在 哌啶 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 97.75h， 生成 N1-(2-phenylethyl)-(2R)-2-{[N'-(4-(2-thienyl)phenylmethylene)hydrazino]carboxamido}-3-[1-(tert-butoxycarbonyl)-3-indolyl]propanamide
  参考文献：
  名称：

  Design of Selective Peptidomimetic Agonists for the Human Orphan Receptor BRS-3

  摘要：

  New tool substances may help to unravel the physiological role of the human orphan receptor BRS-3 and its possible use as a drug target for the treatment of obesity and cancer. In continuation of our work on BRS-3, the solid- and solution-phase synthesis of a library of low molecular weight peptidomimetic agonists based on the recently developed short peptide agonist 4 is described. Functional potencies of the compounds were determined measuring calcium mobilization in a fluorometric imaging plate reader (FLIPR) assay. Focusing on the N-terminus, the D-Phe-Gln moiety of 4 was modified in a combinatorial. SAR-oriented medicinal chemistry approach. With the incorporation of N-arylated glycine and alanine building blocks azaglycine, piperazine, or piperidine and the synthesis of semicarbazides and semicarbazones, a number of highly potent and selective compounds with a reduced number of peptide bonds were obtained, which also should have enhanced metabolic stability.

  DOI：

  10.1021/jm0210921

文献信息

• Design of Selective Peptidomimetic Agonists for the Human Orphan Receptor BRS-3
  作者：Dirk Weber、Claudia Berger、Peter Eickelmann、Jochen Antel、Horst Kessler

  DOI：10.1021/jm0210921

  日期：2003.5.1

  New tool substances may help to unravel the physiological role of the human orphan receptor BRS-3 and its possible use as a drug target for the treatment of obesity and cancer. In continuation of our work on BRS-3, the solid- and solution-phase synthesis of a library of low molecular weight peptidomimetic agonists based on the recently developed short peptide agonist 4 is described. Functional potencies of the compounds were determined measuring calcium mobilization in a fluorometric imaging plate reader (FLIPR) assay. Focusing on the N-terminus, the D-Phe-Gln moiety of 4 was modified in a combinatorial. SAR-oriented medicinal chemistry approach. With the incorporation of N-arylated glycine and alanine building blocks azaglycine, piperazine, or piperidine and the synthesis of semicarbazides and semicarbazones, a number of highly potent and selective compounds with a reduced number of peptide bonds were obtained, which also should have enhanced metabolic stability.