Synthesis and pharmacological evaluation of 5-dialkylaminomethyl-2-amino-2-oxazolines as H1-antagonists

New 5-dialkylaminomethyl-2-amino-2-oxazolines have been synthesized in two steps from the corresponding dialkylamines. They were evaluated in-vitro as H-1-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 E-max (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.