1286280-72-5Relevant articles and documents
Evaluation of Amide Bioisosteres Leading to 1,2,3-Triazole Containing Compounds as GPR88 Agonists: Design, Synthesis, and Structure-Activity Relationship Studies
Rahman, Md Toufiqur,Decker, Ann M.,Laudermilk, Lucas,Maitra, Rangan,Ma, Weiya,Ben Hamida, Sami,Darcq, Emmanuel,Kieffer, Brigitte L.,Jin, Chunyang
, p. 12397 - 12413 (2021/09/02)
The orphan receptor GPR88 has been implicated in a number of striatal-associated disorders, yet its endogenous ligand has not been discovered. We have previously reported that the amine functionality in the 2-AMPP-derived GPR88 agonists can be replaced with an amide (e.g., 4) without losing activity. Later, we have found that the amide can be replaced with a bioisosteric 1,3,4-oxadiazole with improved potency. Here, we report a further study of amide bioisosteric replacement with a variety of azoles containing three heteroatoms, followed by a focused structure-activity relationship study, leading to the discovery of a series of novel 1,4-disubstituted 1H-1,2,3-triazoles as GPR88 agonists. Collectively, our medicinal chemistry efforts have resulted in a potent, efficacious, and brain-penetrant GPR88 agonist 53 (cAMP EC50 = 14 nM), which is a suitable probe to study GPR88 functions in the brain.
MODULATORS OF G PROTEIN-COUPLED RECEPTOR 88
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, (2011/04/26)
The present disclosure is generally directed to compounds which can modulate G-protein coupled receptor 88, compositions comprising such compounds, and methods for modulating G-protein coupled receptor 88.
