TRICYCLIC PYRIDINE-DERIVATIVES WITH HIGH-AFFINITY TO THE CENTRAL BENZODIAZEPINE RECEPTOR

被引:29
作者
FISCHER, U [1 ]
MOHLER, H [1 ]
SCHNEIDER, F [1 ]
WIDMER, U [1 ]
机构
[1] F HOFFMANN LA ROCHE & CO LTD,GRENZACHERSTR 124,CH-4002 BASEL,SWITZERLAND
关键词
D O I
10.1002/hlca.19900730402
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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). Copyright © 1990 Verlag GmbH & Co. KGaA, Weinheim
引用
收藏
页码:763 / 781
页数:19
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