Synthesis and anti-histaminic evaluation of N-phenyl-(alkyl)-5-(dialkylamino)methyl-2-amino-2-oxazolines.
New N-phenyl(alkyl)-5-(dialkylamino)methyl-2-amino-2-oxazolines, 5a-e, have been synthesized from the corresponding 3-phenyl(alkyl)carbamoyl-2-iminooxazolidines 2. A two-stage hydrolysis reaction led finally to the corresponding ring-opened N-phenyl(alkyl)-N'-[1-(3-(dialkylamino)-propan-2-ol)]ureas 4. The oxazoline ring was regenerated through an intramolecular nucleophilic substitution involving an halogen atom introduced by the reaction of thionyl chloride on 4. Pharmacological properties of 5a-e were evaluated on histaminic and adrenergic receptors in guinea-pig trachea and rat aorta. Compounds 5b and 5e showed a selective anti-histaminic effect on guinea-pig airways, but a significant response was obtained for a concentration >10(-6) M. No pharmacological activity was obtained with oxazoline 5c whereas oxazolines 5a and 5d seemed to present a non-selective effect on the contractile mechanism of the smooth muscle cell.
Bosc
J J
JJ
EA 2962-Pharmacochimie, UFR des Sciences Pharmaceutiques, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
Pourageaud
F
F
Girodet
P O
PO
Molimard
M
M
Jarry
C
C
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects
D006634:Histamine H1 Antagonists; D010080:Oxazoles; D010656:Phenylephrine; D006632:Histamine; D000109:Acetylcholine