Discovery and SAR of hydrazide antagonists of the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor type 1 (PAC1-R).
Potent small molecule antagonists for the PAC(1)-R have been discovered. Previously known antagonists for the PAC(1)-R were slightly truncated peptide ligands. The hydrazides reported here are the first small molecule antagonists ever reported for this class B GPCR.
Beebe
Xenia
X
Neuroscience Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-1066, USA. xenia.b.searle@abbott.com
Darczak
Daria
D
Davis-Taber
Rachel A
RA
Uchic
Marie E
ME
Scott
Victoria E
VE
Jarvis
Michael F
MF
Stewart
Andrew O
AO
D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D006834:Hydrazines / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism; D011869:Radioligand Assay; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
C495401:ADCYAP1 protein, human; C495503:ADCYAP1R1 protein, human; D006834:Hydrazines; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D002118:Calcium