A new class of indanones 4 easily obtained by aryne type condensations, followed by transposition of the benzocyclobutanols 3 thus formed, were transformed into the corresponding oximinopropanolamines 7. These compounds were studied for their potential beta-blocking properties. It was found that 7 have generally low beta 1-blocking properties. Their beta 2-blocking action varies from low to very high. Interestingly one of them (7b) has the highest beta 2 activity/beta 1 activity (343) value known to date.

1The effects of three different H2-receptor antagonists (cimetidine, ranitidine and oxmetidine) were tested on isolated preparations of guinea-pig trachea and human bronchus against contractions induced by acetylcholine, histamine and potassium chloride (KCl). In addition, their influence on calcium concentration-response curves in guinea-pig tracheal spirals was examined in a potassium-rich solution (30 mM). Finally, their effects were studied in vivo against acetylcholine and histamine-induced bronchoconstriction in anaesthetized guinea-pigs. 2 In guinea-pig isolated trachea, oxmetidine -in contrast to cimetidine and ranitidine, which were completely inactive -induced a concentration-dependent relaxation regardless of the excitatory stimulus: its -log EC, values (i.e. the negative log concentration that caused a 50% relaxation) were 3.46 + 0. 11, 4.61 ± 0.09 and 4.20 ± 0.12 against acetylcholine, histamine and KC1, respectively. In Ca2+-free, K+-enriched solution, the compound was able to inhibit Ca2"-induced contractions at concentrations close to those needed to counteract the spasmogenic effect of histamine in normal Krebs solution. Results obtained in the human bronchus preparation were similar to those observed in guinea-pig tracheal spirals. 3 When tested against acetylcholine or histamine-induced bronchoconstriction in vivo, oxmetidine (10 and 30 mg Kg-' intravenously) significantly reduced the increase in pulmonary airway resistance (Raw) induced by both agents. Once again, cimetidine and ranitidine were completely ineffective.4 In summary, oxmetidine displayed non-specific antispasmogenic activity on guinea-pig and human airways. This effect, which is independent of H2-receptor blockade, represents a side-effect of the drug which may be connected to its interference with Ca2" influx and the action or release of intracellular Ca2+.

Page 2183. Table I. Footnote b should read "The ratio of ED50 (retinoic acid) to ED50 (a test compound), both values having been obtained in concurrent experiments. This is also the case in the other tables." The same is the case in the description of "relative activity" in the Experimental Section (page 2188, left column, lines 35-37).

The known acetals (I) are treated with hydrochloric acid to give the indanones (II) which are converted into the oximes (IV) by reaction with hydroxylamine hydrate (III).