78. Tricyclic pyridine derivatives with high affinity to the central benzodiazepine receptor

Article abstract of DOI:10.1002/hlca.19900730402

Novel tricyclic heterocycles were prepared and evaluated for their affinity to the central benzodiazepine receptor. The most potent compounds with IC⁵⁰'s in the nanomolar range were found among thienoquinolizines and benzo[a]quinolizines (cf. Tables 2-5). The central ring of the tricyclic ring system may be partially unsaturated (cf. Tables 2 and 4) or fully unsaturated (cf. Tables 3 and 5) without loss of the high affinity to the receptor. The position of the ester group in the pyridinone ring is crucial for good binding (cf. Tables 1 and 2). It may be replaced by a broad variety of functional groups, e.g., amides, alkyl carbamates, alkyl groups, and hydroxyalkyl groups (cf. Tables 2-5). In the benzo[a]quinolizines, shifting the halogen atom from C(10) to C(9) leads to complete loss of affinity to the benzodiazepine receptor (cf. Table 4).