SAR and QSAR studies on the N-terminally acylated pentapeptide agonists for GPR54.
Publication/Presentation Date
7-12-2007
Abstract
Kisspeptins (KPs) play important roles in the regulation of physiological and pathological states through activation of the cognate receptor GPR54. Our previous studies to downsize KP agonists to the essential GPR54 pharmacophore identified peptides 1-3 as low molecular weight GPR54 agonists. In this study, the effect of N-terminal acyl groups on the activity of a series of analogues (R-Phe-Gly-Leu-Arg-Trp-NH2) was investigated in order to develop novel potent GPR54 agonists. Among the compounds developed, the most potent agonistic activity for GPR54 was observed for N-terminal 4-fluorobenzoyl analogue 29. Using quantitative structure-activity relationship studies, it was demonstrated that the inductively negative and small substituents were preferred at the 4-position of N-terminal benzoyl groups.
Volume
50
Issue
14
First Page
3222
Last Page
3228
ISSN
0022-2623
Published In/Presented At
Tomita, K., Oishi, S., Cluzeau, J., Ohno, H., Navenot, J. M., Wang, Z. X., Peiper, S. C., Akamatsu, M., & Fujii, N. (2007). SAR and QSAR studies on the N-terminally acylated pentapeptide agonists for GPR54. Journal of medicinal chemistry, 50(14), 3222–3228. https://doi.org/10.1021/jm070064l
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
17579384
Department(s)
Administration and Leadership
Document Type
Article