Abstract
The preparation of a series of 2-(1H-imidazol-1-ylmethyl)-substituted carboxylic acids of benzo[b]furan, benzo-[b]thiophene, indole, and naphthalene is described. All compounds showed a similar level of activity as TxA2 synthetase inhibitors in vitro, having IC50 values between 1 and 7 X 10(-8) M. In the cases examined, compounds had, at most, only negligible activity against PGI2 synthetase, cyclooxygenase, and steroid 11 beta-hydroxylase. The benzo[b]thiophenes generally showed the greatest potency in vivo, and compounds 72, 73, and 75 caused almost complete inhibition of thromboxane production for 6 h after oral administration of 0.5 mg/kg to conscious dogs. In the case of 73 and 75, thromboxane production was still inhibited by 80% after 24 h.
MeSH terms
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Animals
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Benzofurans / pharmacology*
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Carboxylic Acids / pharmacology*
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Chemical Phenomena
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Chemistry
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Cyclooxygenase Inhibitors
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Cytochrome P-450 Enzyme System*
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Dogs
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Epoprostenol / antagonists & inhibitors
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Epoprostenol / biosynthesis
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Imidazoles / pharmacology*
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Indoles / pharmacology*
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Intramolecular Oxidoreductases*
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Male
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Naphthalenes / pharmacology
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Rats
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Steroid 11-beta-Hydroxylase / antagonists & inhibitors
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Thiophenes / pharmacology*
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Thromboxane-A Synthase / antagonists & inhibitors*
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Thromboxane-A Synthase / blood
Substances
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Benzofurans
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Carboxylic Acids
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Cyclooxygenase Inhibitors
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Imidazoles
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Indoles
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Naphthalenes
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Thiophenes
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Cytochrome P-450 Enzyme System
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Epoprostenol
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Steroid 11-beta-Hydroxylase
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Intramolecular Oxidoreductases
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prostacyclin synthetase
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Thromboxane-A Synthase