ONO-7300243
Names
[ CAS No. ]:
638132-34-0
[ Name ]:
ONO-7300243
[Synonym ]:
Benzeneacetic acid, 4-[[(3,5-dimethoxy-4-methylbenzoyl)(3-phenylpropyl)amino]methyl]-
(4-{[(3,5-Dimethoxy-4-methylbenzoyl)(3-phenylpropyl)amino]methyl}phenyl)acetic acid
Biological Activity
[Description]:
ONO-7300243 is a novel, potent lysophosphatidic acid receptor 1 (LPA1) antagonist with IC50 of 0.16 μM.
[Related Catalog]:
[Target]
IC50: 0.19-0.13 μM (LPA1)[1]
[In Vitro]
ONO-7300243 shows modest in vitro activity (IC50=0.16 μM). ONO-7300243 exhibits almost identical levels of antagonist activity in vitro[1].
[In Vivo]
ONO-7300243 shows good efficacy in vivo. The oral dosing of 17a at 30 mg/kg leads to reduced intraurethral pressure in rats. ONO-7300243 shows stronge effects in vivo (88% inhibition at 10 mg/kg i.d., 62% inhibition at 3 mg/kg i.d.) compared with compound 12g. The results reveal that ONO-7300243 shows good membrane permeability and good metabolic stability against rat liver microsomes (MS). ONO-7300243 exhibits good selectivity towards LPAl over LPA2, most likely because low molecular weight and low lipophilicity lead to reduced compound promiscuity and increased selectivity. ONO-7300243 inhibits the LPA-induced IUP increase in a dose dependent manner (ID50=11.6 mg/kg p.o.) up to 1 h after dosing. Significant effects are observed at 10 and 30 mg/kg (p<0.05 vs.vehicle). ONO-7300243 (30 mg/kg, p.o.) leads to a significant decrease in the IUP in conscious rats without LPA stimulation compared with the vehicle without affecting the mean blood pressure (MBP). The results of a rat pharmacokinetic study of ONO-7300243 show that this material had a rapid clearance (CLtot=15.9 mL/min/kg at 3 mg/kg i.v.) and a short half-life (0.3 h)[1].
[Animal admin]
Rats[1] The oral administration of ONO-7300243 (30 mg/kg, p.o.) is investigated to determine its effect on rat IUP. ONO-7300243 is studied in an LPA-induced rat intraurethral pressure (IUP) model.
[References]
[Related Small Molecules]
Chemical & Physical Properties
[ Density]:
1.2±0.1 g/cm3
[ Boiling Point ]:
688.1±55.0 °C at 760 mmHg
[ Molecular Formula ]:
C28H31NO5
[ Molecular Weight ]:
461.549
[ Flash Point ]:
369.9±31.5 °C
[ Exact Mass ]:
461.220215
[ LogP ]:
5.59
[ Vapour Pressure ]:
0.0±2.3 mmHg at 25°C
[ Index of Refraction ]:
1.591
[ Storage condition ]:
-20℃