Structure-activity relationships in an imidazole-based series of thromboxane synthase inhibitors.

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Manley PW, Allanson NM, Booth RF, Buckle PE, Kuzniar EJ, Lad N, Lai SM, Lunt DO, Tuffin DP

Structure-activity relationships in an imidazole-based series of thromboxane synthase inhibitors.

J Med Chem. 1987 Sep;30(9):1588-95.

PubMed ID

3305945 [ View in PubMed

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Abstract

Analogues of 4-[[2-(1H-imidazol-1-yl)-1-[[(4-methoxyphenyl)methoxy]methyl] ethoxy]methyl]benzoic acid (5m) were prepared and evaluated as thromboxane synthase inhibitors. A series of esters of 5m showed a parabolic relationship between lipophilicity and inhibition of TxB2 generation in intact platelets, with activities up to 50 times greater than that of dazoxiben. However, on administration to rabbits the ethyl ester 5d had a short duration of action, due to rapid metabolism and excretion via deesterification and beta-glucuronidation. Attempts at replacing the carboxylate group with other potential pharmacophores were unsuccessful.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Dazoxiben	Thromboxane-A synthase	IC 50 (nM)	1290	N/A	N/A	Details