Synthesis and biological evaluation of novel pyrimidine derivatives as sub-micromolar affinity ligands of GalR2.
GalR1 and GalR2 represent unique pharmacological targets for treatment of seizures and epilepsy. A novel series of 2,4,6-triaminopyrimidine derivatives were synthesized and found to have sub-micromolar affinity for GalR2. Optimization of a series of 2,4,6-triaminopyrimidines led to the discovery of several analogs with IC50 values ranging from 0.3 to 1 μM.
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, United States.
Vasudeva Naidu
VN
Sagi
Tianyu
T
Liu
Xiaoying
X
Lu
Tamas
T
Bartfai
Edward
E
Roberts
D000927:Anticonvulsants / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D044092:Receptor, Galanin, Type 2 / Q000737:chemistry*; D012640:Seizures
D000927:Anticonvulsants; D008024:Ligands; D011743:Pyrimidines; D044092:Receptor, Galanin, Type 2; C012070:2,4,6-triaminopyrimidine