Design and Synthesis of 2-Alkylpyrimidine-4,6-diol and 6-Alkylpyridine-2,4-diol as Potent GPR84 Agonists.
A series of alkylpyrimidine-4,6-diol derivatives were designed and synthesized as novel GRP84 agonists based on a high-throughput screening (HTS) hit 1. 6-Nonylpyridine-2,4-diol was identified as the most potent agonist of GPR84 reported so far, with an EC50 of 0.189 nM. These novel GPR84 agonists will provide valuable tools for the study of the physiological functions of GPR84.
Department of Chemistry and Institute of Medicinal Chemistry, East China Normal University , 3663 North Zhong Shan Road, Shanghai 200062, China.
Yang
Y
Liu
Laboratory of Receptor-Based BioMedicine, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University , 1239 Siping Road, Shanghai 200092, China.
Qing
Q
Zhang
State Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 189 Guoshoujing Road, Shanghai 201203, China.
Lin-Hai
LH
Chen
CAS Key Laboratory of Receptor Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 189 Guoshoujing Road, Shanghai 201203, China.
Hui
H
Yang
Department of Chemistry and Institute of Medicinal Chemistry, East China Normal University , 3663 North Zhong Shan Road, Shanghai 200062, China.
Wei
W
Lu
Laboratory of Receptor-Based BioMedicine, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China; CAS Key Laboratory of Receptor Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guoshoujing Road, Shanghai 201203, China.
Xin
X
Xie
State Key Laboratory of Drug Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 189 Guoshoujing Road, Shanghai 201203, China.
Fa-Jun
FJ
Nan
2-alkylpyrimidine-4,6-diol; 6-alkylpyridine-2,4-diol; GPR84; agonists; structural modification