Introduction.
-The opium alkaloid noscapine (1) is widely used as cough depressant. Its antitussive effect is similar to that of codeine, while it does not show respiratory depression, constipation, and dependence liability. Recently, high-affinity binding sites were found for 1 in guinea-pig brain. These binding sites are supposedly different from those previously described for antitussives such as codeine, other opioids, or dextromethorphan [l]. Since it was also demonstrated that 1 shows efficacy against liver failure in rats, it could be effective in the treatment of hepatopathy [2].
In view of the pharmacological properties of the isoquinoline alkaloid noscapine (l), it was of interest to prepare its 3-benzazepine analogues, e.g. 2 and 3, and to evaluate these derivatives pharmacologically.
Chemistry. -Since treatment of nornarceine ethyl ester hydrochloride (4. HC1; readily available from noscapine (1) [3]) with formalin in EtOH did not afford the ~f f n n j c ~ product 5 but the Pictet-Spengler product 6 (Scheme I), position 7 of the benzodioxole ring had to be blocked reversibly.