Antihypertensive Effect of some Oxazolo[3,2-a]pyridines, Thiazolo[3,2-a]pyridines and Pyrido[2,1-b]oxazines in Conscious Spontaneously Hypertensive Rats

• Published in: Journal of pharmacy and pharmacology 1997-04, Vol.49 (4), p.421-425
• Main Authors: MORAN, ASUNCIÓN, MARTÍN, ELENA, VELASCO, CRISTINA, MARTÍN, M. LUISA, ROMAN, LUIS SAN, CABALLERO, ESTHER, PUEBLA, PILAR, MEDARDE, MANUEL, FELICIANO, ARTURO SAN
• Format: Article
• Language: English
• Subjects: Animals; Antihypertensive agents; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Blood Pressure - drug effects; Calcium Channel Blockers - administration & dosage; Calcium Channel Blockers - pharmacology; Calcium Channel Blockers - therapeutic use; Cardiovascular system; Disease Models, Animal; Dose-Response Relationship, Drug; Heart Rate - drug effects; Hypertension - drug therapy; Injections, Intraperitoneal; Male; Medical sciences; Nifedipine - administration & dosage; Nifedipine - pharmacology; Nifedipine - therapeutic use; Oxazines - chemistry; Oxazines - pharmacology; Oxazines - therapeutic use; Pharmacology. Drug treatments; Pyridines - chemistry; Pyridines - pharmacology; Pyridines - therapeutic use; Rats; Rats, Inbred SHR; Reference Standards; Structure-Activity Relationship
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/j.2042-7158.1997.tb06817.x

The antihypertensive activity of eighteen oxazolo[3,2‐a]pyridine, fhiazolo[3,2‐a]pyridine and pyrido[2,1‐b]oxazine derivatives has been evaluated in conscious spontaneously hypertensive rats (SHRs), and compared with that of nifedipine, used as reference. At a dose of 50 mg kg−1 (i.p.) eleven compounds resulted in a significant reduction in mean arterial blood pressure; four of the eleven were particularly effective, resulting in significant hypotension more than 6 h after administration and an effect that was still apparent after 24 h. The hypotension induced by nifedipine gradually decreased, disappearing 6–8 h after administration. The long‐lasting activity shown by these compounds is, in general, not accompanied by reflex tachycardia. Intraperitoneal administration of two oxazolo[3,2‐a]pyridine derivatives and two pyrido[2,1‐b]oxazine derivatives resulted in potent and long‐lasting antihypertensive action in SHRs. Further studies on the mechanism of action of these derivatives might help the determination of better structure–activity correlations and the design, synthesis and evaluation of better antihypertensive agents.