Discovery and SAR of hydrazide antagonists of the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor type 1 (PAC1-R)

Xenia Beebe; Daria Darczak; Rachel A Davis-Taber; Marie E Uchic; Victoria E Scott; Michael F Jarvis; Andrew O Stewart

doi:10.1016/j.bmcl.2008.01.052

Discovery and SAR of hydrazide antagonists of the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor type 1 (PAC1-R)

Bioorg Med Chem Lett. 2008 Mar 15;18(6):2162-6. doi: 10.1016/j.bmcl.2008.01.052. Epub 2008 Jan 18.

Authors

Xenia Beebe¹, Daria Darczak, Rachel A Davis-Taber, Marie E Uchic, Victoria E Scott, Michael F Jarvis, Andrew O Stewart

Affiliation

¹ Neuroscience Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-1066, USA. xenia.b.searle@abbott.com

PMID: 18272364
DOI: 10.1016/j.bmcl.2008.01.052

Abstract

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.

MeSH terms

Calcium / metabolism
Cells, Cultured
Humans
Hydrazines / chemistry*
Magnetic Resonance Spectroscopy
Molecular Structure
Pituitary Adenylate Cyclase-Activating Polypeptide / metabolism
Radioligand Assay
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / antagonists & inhibitors*
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / metabolism
Structure-Activity Relationship

Substances

ADCYAP1 protein, human
ADCYAP1R1 protein, human
Hydrazines
Pituitary Adenylate Cyclase-Activating Polypeptide
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
Calcium