Synthesis and pharmacological evaluation of 5-dialkylaminomethyl-2-amino-2-oxazolines as H1-antagonists.
New 5-dialkylaminomethyl-2-amino-2-oxazolines have been synthezised in two steps from the corresponding dialkylamines. They were evaluated in-vitro as H1-antagonists. Compounds 1c, 1d and 1j significantly antagonized histamine-induced contraction of guinea-pig trachea with a rightward shift of the concentration-response curve to histamine. Compound 1f, 5-[(4-benzyl-1-piperidinyl)methyl]-2-amino-2-oxazoline, induced an increase in acetylcholine Emax (the maximal response to acetylcholine 10(-3) M) and a shift to the left of the concentration-response curve. The lack of effect of this compound on histamine-induced contraction rules out a non-selective potentiation of the contraction mechanisms. Preliminary structure-activity results were reported partly based on physicochemical results.
Bosc
J J
JJ
EA 2962 Pharmacochimie, Université Victor Segalen Bordeaux 2, France.
Jarry
C
C
Martinez
B
B
Molimard
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D010080:Oxazoles; D014665:Vasodilator Agents; D006632:Histamine; D000109:Acetylcholine