Modulation of gastrointestinal nutrient sensing pathways provides a promising a new approach for the treatment of metabolic diseases including diabetes and obesity. The calcium-sensing receptor has been identified as a key receptor involved in mineral and amino acid nutrient sensing and thus is an attractive target for modulation in the intestine. Herein we describe the optimization of gastrointestinally restricted calcium-sensing receptor agonists starting from a 3-aminopyrrolidine-containing template leading to the identification of GI-restricted agonist 19 (GSK3004774).

中文翻译：

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鉴定针对GI特异性给药的钙敏感受体的强效，不可吸收激动剂

胃肠道营养物传感途径的调节为治疗包括糖尿病和肥胖症在内的代谢性疾病提供了一种有希望的新方法。钙敏感受体已被确定为涉及矿物质和氨基酸营养素敏感的关键受体，因此是肠内调节的诱人靶标。在本文中，我们描述了从包含3-氨基吡咯烷的模板开始的胃肠道限制钙敏感受体激动剂的优化，从而确定了GI限制激动剂19（GSK3004774）。