1-Imidazolylcarbonyloxy-substituted tetrahydroquinolines and pyridines: synthesis and evaluation of P450 TxA2 inhibition.
The title compounds are derived from our model describing structural requirements for strong P450 TxA2 inhibition. In the present paper the syntheses of the 1-imidazolylcarbonyloxy-substituted tetrahydroquinolines 1, 3, and 4, tetrahydro-naphthalene 2 and 3-ethylpyridines 5 and 6 are described. Using our P450 TxA2 inhibition assay, 1-6 were tested for enzyme inhibitory activity. Compound 1 (5-(1-imidazolylcarbonyloxy)-5,6,7,8-tetrahydroquinoline) turned out to be the most active derivative showing a potency similar to the reference compound dazoxiben (IC50 values 1.6 and 1.1 microM).
Hartmann
R W
RW
Pharmaceutical and Medicinal Chemistry, Universität des Saarlandes, Saarbrücken, Germany.
Frotscher
M
M
D006801:Humans; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors / Q000097:blood
D011725:Pyridines; D011804:Quinolines; D013930:Thromboxane-A Synthase