Synthesis and biological evaluation of new 2-(4,5-dihydro-1H-imidazol-2-yl)-3,4-dihydro-2H-1,4-benzoxazine derivatives.
2-(4,5-Dihydro-1H-imidazol-2-yl)-3,4-dihydro-2H-1,4-benzoxazine derivatives and tricyclic analogues with a fused additional ring on the nitrogen atom of the benzoxazine moiety have been prepared and evaluated for their cardiovascular effects as potential antihypertensive agents. The imidazoline ring was generated by reaction of the corresponding ethyl ester with ethylenediamine. Affinities for imidazoline binding sites (IBS) I(1) and I(2) and alpha(1) and alpha(2) adrenergic receptors were evaluated as well as the effects on mean arterial blood pressure (MAP) and heart rate (HR) of spontaneously hypertensive rats. With few exceptions the most active compounds on MAP were those with high affinities for IBS and alpha(2) receptor. Among these, compound 4h was the most interesting and is now, together with its enantiomers, under complementary pharmacological evaluation.
Institut de Chimie Organique et Analytique, UMR-CNRS 6005, BP 6759, Université d'Orléans, 45067 Orléans Cedex 2, France.
Frédérique
F
Touzeau
Axelle
A
Arrault
Gérald
G
Guillaumet
Elizabeth
E
Scalbert
Bruno
B
Pfeiffer
Marie-Claire
MC
Rettori
Pierre
P
Renard
Jean-Yves
JY
Mérour
D000313:Adrenal Medulla / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D001794:Blood Pressure / Q000187:drug effects; D002417:Cattle; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054755:Imidazoline Receptors; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D010078:Oxazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C474574:6-fluoro-2-(4,5-dihydro-1H-imidazol-2-yl)-4-methyl-3,4-dihydro-2H-1,4-benzoxazine; D000959:Antihypertensive Agents; D007093:Imidazoles; D054755:Imidazoline Receptors; D010078:Oxazines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; C410887:imidazoline I1 receptors