Tricyclic Pyridine Derivatives with High Affinity to the Central Benzodiazepine Receptor

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Abstract
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).