(S)-tert-butyl 2-(1-(2-methoxyphenyl)imidazo[1,5-a]pyridine-3-yl)pyrrolidine-1-carboxylate | 863455-75-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-tert-butyl 2-(1-(2-methoxyphenyl)imidazo[1,5-a]pyridine-3-yl)pyrrolidine-1-carboxylate
• CAS: 863455-75-8
• 化学式: C₂₃H₂₇N₃O₃
• 分子量: 393.486
• InChiKey: SJYPGQSXTNBRLM-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.08
• 重原子数：
  29.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  56.07
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 2-(1-(2-methoxyphenyl)imidazo[1,5-a]pyridine-3-yl)pyrrolidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 以99%的产率得到(S)-1-(2-methoxyphenyl)-3-(pyrrolidine-2-yl)imidazo[1,5-a]pyridine hydrochloride
  参考文献：
  名称：

  Identification of Drug-Like Inhibitors of Insulin-Regulated Aminopeptidase Through Small-Molecule Screening

  摘要：

  Intracerebroventricular injection of angiotensin IV, a ligand of insulin-regulated aminopeptidase (IRAP), has been shown to improve cognitive functions in several animal models. Consequently, IRAP is considered a potential target for treatment of cognitive disorders. To identify nonpeptidic IRAP inhibitors, we adapted an established enzymatic assay based on membrane preparations from Chinese hamster ovary cells and a synthetic peptide-like substrate for high-throughput screening purposes. The 384-well microplate-based absorbance assay was used to screen a diverse set of 10,500 compounds for their inhibitory capacity of IRAP. The assay performance was robust with Z-values ranging from 0.81 to 0.91, and the screen resulted in 23 compounds that displayed greater than 60% inhibition at a compound concentration of 10M. After hit confirmation experiments, purity analysis, and promiscuity investigations, three structurally different compounds were considered particularly interesting as starting points for the development of small-molecule-based IRAP inhibitors. After resynthesis, all three compounds confirmed low M activity and were shown to be rapidly reversible. Additional characterization included activity in a fluorescence-based orthogonal assay and in the presence of a nonionic detergent and a reducing agent, respectively. Importantly, the characterized compounds also showed inhibition of the human ortholog, prompting our further interest in these novel IRAP inhibitors.

  DOI：

  10.1089/adt.2016.708
• 作为产物：
  描述：

  2-Methoxyphenylmagnesium bromide 在 吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 31.67h， 生成 (S)-tert-butyl 2-(1-(2-methoxyphenyl)imidazo[1,5-a]pyridine-3-yl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Identification of Drug-Like Inhibitors of Insulin-Regulated Aminopeptidase Through Small-Molecule Screening

  摘要：

  Intracerebroventricular injection of angiotensin IV, a ligand of insulin-regulated aminopeptidase (IRAP), has been shown to improve cognitive functions in several animal models. Consequently, IRAP is considered a potential target for treatment of cognitive disorders. To identify nonpeptidic IRAP inhibitors, we adapted an established enzymatic assay based on membrane preparations from Chinese hamster ovary cells and a synthetic peptide-like substrate for high-throughput screening purposes. The 384-well microplate-based absorbance assay was used to screen a diverse set of 10,500 compounds for their inhibitory capacity of IRAP. The assay performance was robust with Z-values ranging from 0.81 to 0.91, and the screen resulted in 23 compounds that displayed greater than 60% inhibition at a compound concentration of 10M. After hit confirmation experiments, purity analysis, and promiscuity investigations, three structurally different compounds were considered particularly interesting as starting points for the development of small-molecule-based IRAP inhibitors. After resynthesis, all three compounds confirmed low M activity and were shown to be rapidly reversible. Additional characterization included activity in a fluorescence-based orthogonal assay and in the presence of a nonionic detergent and a reducing agent, respectively. Importantly, the characterized compounds also showed inhibition of the human ortholog, prompting our further interest in these novel IRAP inhibitors.

  DOI：

  10.1089/adt.2016.708

文献信息

• [EN] IMIDAZOPYRIDINE DERIVATIVES AS BSR-3 ANTAGONISTS<br/>[FR] DERIVES D'IMIDAZOPYRIDINE ANTAGONISTES DE BSR-3
  申请人：BIOFOCUS DISCOVERY LTD

  公开号：WO2005080390A1

  公开（公告）日：2005-09-01

  Compounds of the general formula (I): wherein X, Y, R and R’ are as described in the specification. Further included are pharmaceutical compositions comprising the compounds, processes for their preparation, as well as the use of the compounds for the preparation of a medicament against BRS-3 receptor-related disorders.

  通式（I）的化合物：其中X、Y、R和R'如规范中描述。还包括包含这些化合物的药物组合物、其制备方法，以及利用这些化合物制备用于治疗BRS-3受体相关疾病的药物的用途。