Isosteric Replacement of Ester Linkage of Lysophospholipids with Heteroaromatic Rings Retains Potency and Subtype Selectivity.
Chem Pharm Bull (Tokyo)
; 71(7): 584-615, 2023.
Article
in En
| MEDLINE
| ID: mdl-37394607
ABSTRACT
Our group has reported various derivatives of lysophosphatidylserine (LysoPS) as potent and subtype-selective agonists for G-protein-coupled receptors (GPCRs). However, the ester linkage between the glycerol moiety and fatty acid or fatty acid surrogate is present in all of them. In order to develop these LysoPS analogs as drug candidates, appropriate pharmacokinetic consideration is essential. Here, we found that the ester bond of LysoPS is highly susceptible to metabolic degradation in mouse blood. Accordingly, we examined isosteric replacement of the ester linkage with heteroaromatic rings. The resulting compounds showed excellent retention of potency and receptor subtype selectivity, as well as increased metabolic stability in vitro.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lysophospholipids
/
Receptors, G-Protein-Coupled
Limits:
Animals
Language:
En
Journal:
Chem Pharm Bull (Tokyo)
Year:
2023
Type:
Article