Discovery of substituted biphenyl imidazoles as potent, bioavailable bombesin receptor subtype-3 agonists

Extensive SAR studies of a series derived from RY-337, a novel non-peptidic bombesin receptor subtype-3 (BRS-3) agonist lead, led to the discovery of compound 22e with significantly improved potency at both rodent and human BRS-3. Analogs in this series demonstrated good rat pharmacokinetics. We rep...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2010-03, Vol.20 (6), p.1913-1917
Main Authors: He, Shuwen, Dobbelaar, Peter H., Liu, Jian, Jian, Tianying, Sebhat, Iyassu K., Lin, Linus S., Goodman, Allan, Guo, Cheng, Guzzo, Peter R., Hadden, Mark, Henderson, Alan J., Ruenz, Megan, Sargent, Bruce J., Yet, Larry, Kelly, Theresa M., Palyha, Oksana, Kan, Yanqing, Pan, Jie, Chen, Howard, Marsh, Donald J., Shearman, Lauren P., Strack, Alison M., Metzger, Joseph M., Feighner, Scott D., Tan, Carina, Howard, Andrew D., Tamvakopoulos, Constantin, Peng, Qianping, Guan, Xiao-Ming, Reitman, Marc L., Patchett, Arthur A., Wyvratt, Matthew J., Nargund, Ravi P.
Format: Article
Language:English
Subjects:
Agonist
Animals
Biological and medical sciences
Biological Availability
Biphenyl imidazole
Bombesin receptor subtype-3
BRS3
Drug Discovery
General and cellular metabolism. Vitamins
Humans
Imidazoles - chemistry
Imidazoles - pharmacokinetics
Imidazoles - pharmacology
Medical sciences
Pharmacology. Drug treatments
Rats
Receptors, Bombesin - agonists
Structure-Activity Relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Extensive SAR studies of a series derived from RY-337, a novel non-peptidic bombesin receptor subtype-3 (BRS-3) agonist lead, led to the discovery of compound 22e with significantly improved potency at both rodent and human BRS-3. Analogs in this series demonstrated good rat pharmacokinetics. We report SAR studies on a novel non-peptidic bombesin receptor subtype-3 (BRS-3) agonist lead series derived from high-throughput screening hit RY-337. This effort led to the discovery of compound 22e with significantly improved potency at both rodent and human BRS-3.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2010.01.154