Characterisation of furoxancarbonitriles as a new class of vasodilators.
The synthesis, structural characterization, NO-donor properties, and in vitro vasodilating activities of a series of furoxancarbonitriles 2, 17-22a, b are reported. Some derivatives (2b, 2a, 18b, 21b, 22b) are more potent vasodilating agents than sodium nitroprusside (SNP), the reference compound, some others display similar potency (17b, 19b, 20b). Log EC50 values fit well on the linear correlation log EC50 versus log C0.1(1 min) (namely the logarithm of the concentration able to release 2.6 mumol l-1 min-1 of NO) found in a previous work. The haemodynamic profile in anaesthetised pigs for some selected derivatives (2a, b, 19a, b) is also presented. These profiles are consistent with that known for another furoxan NO-donor (4-hydroxymethyl-3-furoxancarboxamide, CAS 1609) and suggest similar characteristic of in vivo NO-release.
Gasco
A M
AM
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Italy.
Boschi
D
D
Di Stilo
A
A
Medana
C
C
Gasco
A
A
Martorana
P A
PA
Schönafinger
K
K
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007441:Intubation, Gastrointestinal; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000737:chemistry; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
D009570:Nitriles; D010069:Oxadiazoles; D014665:Vasodilator Agents; D009569:Nitric Oxide