ChemicalBook CAS DataBase List 2728291-29-8

2728291-29-8

Name	P2Y14R antagonist 1
CAS	2728291-29-8
Molecular Formula	C15H12BrN3O2
Molecular Weight	346.18
MOL File	2728291-29-8.mol

Chemical Properties

Boiling point	684.8±40.0 °C(predicted)
density	1.627±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)
pka	12.30±0.30(predicted)

Hazard Information

Uses

P2Y14R antagonist 1 (compound I-17) is a selective P2Y14R antagonist with an IC50 of 0.6 nM. It exhibits potent P2Y14R antagonistic activity, both in vitro and in vivo efficacy, and favorable pharmacokinetic profiles. P2Y14R antagonist 1 reduces the release of inflammatory factors and cell pyroptosis through the NOD-like receptor family pyrin domain-containing 3 (NLRP3)/gasdermin D (GSDMD) signaling pathway. P2Y14R antagonist 1 holds promise for research in the field of acute gouty arthritis[1].

in vivo

P2Y14R antagonist 1 (compound I-17) (5-20 mg/mL, i.p., 1 h) can promote the inflammatory response caused by MSU crystal injection-induced acute gouty arthritis in the MSU-induced mouse gout model^[1].

1.19
Pharmacokinetic Analysis in MC38 Syngeneic Model^[1]

P2Y14R antagonist 1	C_max(g/mL)	T_1/2(h)	T_max (h)	AUC_0-∞(h ng/mL)	CL (L/h/kg)	F (%)
i.v. (10 mg/kg)	1533	7.6	18	1765	3.5
p.o. (30 mg/kg)	2895	12.60	32	2845	14.80	75

Animal Model:	Acute gouty arthritis model^[1]
Dosage:	5-20 mg/mL
Administration:	Intraperitoneal injection (i.p.) , Injection time: 60 min
Result:	Effectively reduced paw swelling in the MSU-induced mouse gout model, significantly decreased the production of pro-inflammatory cytokines IL-1β, IL-6, and IL-18 induced by MSU, markedly inhibited inflammatory cell infiltration in foot tissues induced by MSU, and significantly suppressed the increase of NLRP3 induced by MSU.

IC 50

P2Y14 Receptor: 0.6 nM (IC₅₀); P2Y2 Receptor: > 100 nM (IC₅₀); P2Y6 Receptor: 89.7 nM (IC₅₀); P2Y12 Receptor: > 100 nM (IC₅₀); P2Y1 Receptor: > 100 nM (IC₅₀); NLRP3

References

[1] Liu W, et al. Discovery of N-Substituted Acetamide Derivatives as Promising P2Y14R Antagonists Using Molecular Hybridization Based on Crystallographic Overlay. J Med Chem. 2024 Jun 27;67(12):10233-10247. DOI:10.1021/acs.jmedchem.4c00555

Spectrum Detail

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