Discovery and Structure-Activity Relationships of Trisubstituted Pyrimidines/Pyridines as Novel Calcium-Sensing Receptor Antagonists.
作者
Yang, Wu;Ruan, Zheming;Wang, Yufeng;Van Kirk, Katy;Ma, Zhengping;Arey, Brian J.;Cooper, Christopher B.;Seethala, Ramakrishna;Feyen, Jean H. M.;Dickson, John K.;
[摘要]：The trisubstituted pyrimidine I was identified through high-throughput screening as a novel calcium-sensing receptor (CaSR) antagonist. Small mol. CaSR antagonists and/or neg. allosteric modulators have the potential to act as an anabolic agent for the treatment of osteoporosis. The investigation of structure-activity relationships around I resulted in the identification of II (R = 3,4,5-Me3C6H2, 2,6-Me2-3-pyridinyl), which showed efficacy at promoting PTH release in vivo and exhibited improved potency and soly. over the original lead I.
