N-Imidazolyl derivatives of the naphthalene and chroman rings as thromboxane A2 synthase inhibitors

Article abstract of DOI:10.1016/0223-5234(91)90103-T

A series of N-imidazol-1-yl derivatives of 1,2-dihydronaphthalene, 1,2,3,4-tetrahydronaphthalene, 2H-1-benzopyran and some related compounds were synthesized and tested as inhibitors of thromboxane A₂ synthase in ex vivo experiments with orally treated rats.Some compounds showed good activity which was confirmed in experiments in vitro in rabbit whole blood.Some structural requirements for significant TxA₂ synthase inhibitory activity are discussed.The selected 5,6-dihydro-7-(1H-imidazol-1-yl)-2-naphthalene-carboxylic acid (compound 7) was conformationally analysed using the Sybyl molecular model system in comparison with dazoxiben.Compound 7 was further pharmacologically investigated and on the basis of its interesting activities in vitro, ex vivo and in vivo and its low toxicity was selected for clinical investigation.