Selective Modulation of Gq/Gs pathways by Naphtho Pyrano Pyrimidines as antagonists of the Neuropeptide S Receptor.
Antagonists of the Neuropeptide S Receptor have been postulated as promising therapeutics in the treatment of respiratory, sleep, anxiety, and addictive disorders. Here we present the SAR of a new series of orthosteric antagonists. Neuropeptide S Receptor signaling is coupled to both Gq and Gs proteins, and we observe that different analogues in this structural series can selectively antagonize these two pathways. Many G-protein coupled receptors transduce signals through multiple pathways. Selective antagonism of these pathways may lead the way to the development of more targeted pharmacological profiles and therapies.
NIH Chemical Genomic Center, National Human Genome Research Institute, National Institutes of Heath, 9800 Medical Center Drive, Rockville, 20850, MD, USA.
Joshua G
JG
McCoy
Juan J
JJ
Marugan
Ke
K
Liu
Wei
W
Zheng
Noel
N
Southall
Wenwei
W
Huang
Markus
M
Heilig
Christopher P
CP
Austin