Ro-24-4736
Names
[ CAS No. ]:
125030-71-9
[ Name ]:
Ro-24-4736
[Synonym ]:
5-{3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a] [1,4]diazepin-2-yl]-2-propynyl}phenanthridin-6(5H)-one
Ro-24-4736
6(5H)-Phenanthridinone,5-(3-(4-(2-chlorophenyl)-9-methyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepin-2-yl)-2-propynyl)
Biological Activity
[Description]:
Ro 24-4736 is a potent, selective, p.o.-active platelet-activating factor (PAF) antagonist with a long duration of action.
[Related Catalog]:
[Target]
[In Vitro]
Ro 24-4736 competes with [3H]PAF for its receptor site on dog platelets with an IC50 of 9.8±1.0 nM and selectively inhibits PAF-induced aggregation of guinea pig, dog and human platelets with concentration dependence[1].
[In Vivo]
Ro 24-4736 dose-dependently inhibits in vivo bronchoconstriction (ID50 of 0.006-mg/kg p.o.) and ex vivo platelet aggregation (ID50 of 0.004 mg/kg p.o.) induced by PAF in guinea pigs. Time course studies show complete blockade of PAF-induced platelet aggregation (ex vivo) up to 8 hr after a single p.o. dose of 0.03 mg/kg as well as a long duration of action in vivo (30 hr). The in vivo PAF antagonistic activity is specific because, even at high p.o. doses (up to 10 mg/kg), Ro 24-4736 shows no inhibitory activity toward the bronchoconstrictor effects of leukotriene D4 or histamine. In comparison with other PAF antagonists evaluated in this guinea pig model, Ro 24-4736 is markedly superior in terms of p.o. potency, bioavailability and p.o. duration of action. Studies are also performed with Ro 24-4736 in additional in vivo models. When administered p.o. to sensitized guinea pigs, the drug attenuates inhaled antigen-induced airway hyper-reactivity without effect on bronchoalveolar lavage leukocyte accumulation[1]. Ro 24-4736 is a new platelet activating factor antagonist. The tissue distribution of the 14C-label in male rats following a single intravenous dose of 1.0 mg/kg of 14C-Ro 24-4736 indicats appreciable uptake by the liver, kidney, heart and gastrointestinal tract. Peak plasma and tissue concentrations are seen at 5 minutes after dosing except for the small intestine (4 hrs) and abdominal fat, stomach and large intestine (4 hrs). At 48 hours, only 3.5% of the dose is present in the tissues, and 6.1% in the lumen of the gastrointestinal tracts[2].
[References]
[Related Small Molecules]
Chemical & Physical Properties
[ Density]:
1.41g/cm3
[ Boiling Point ]:
819.6ºC at 760mmHg
[ Molecular Formula ]:
C31H20ClN5OS
[ Molecular Weight ]:
546.04100
[ Flash Point ]:
449.5ºC
[ Exact Mass ]:
545.10800
[ PSA ]:
93.31000
[ LogP ]:
5.59700
[ Vapour Pressure ]:
5.81E-27mmHg at 25°C
[ Index of Refraction ]:
1.749
[ Storage condition ]:
2-8℃