- Pyridobenzoxazepine and pyridobenzothiazepine derivatives as potential central nervous system agents: Synthesis and neurochemical study
-
In order to characterize the pharmacological profile of the different chemical classes of pyridobenzazepine derivatives, a series of N- methylpiperazinopyrido[1,4]- and -[1,5]- benzoxa- and benzothiazepine derivatives were prepared. The affinities for D2, D1, 5-HT2, and cholinergic (M) receptors were measured. In comparison to dibenzazepine reference compounds, a strong decrease of the affinities was observed, less pronounced, however, for the substituted analogues. Oxazepine and thiazepine analogues like clozapine (except 8-chloro-6-(4-methylpiperazin-1-yl)- pyrido[2,3-b][1,4]benzoxazepine (9) and 8-chloro-6-(4-methylpiperazin-1- yl)pyrido[2,3-b][1,4]-benzothiazepine (11)) were found to be inactive against apomorphine stereotypies. In the open-field test in rats, different molecules showed a high disinhibitory activity as observed with anxiolytic drugs. Moreover, 8-chloro-5-(4-methylpiperazin-1-yl)pyrido[2,3-b][1,5]benzoxazepine (14) presented a clozapine-like profile that was confirmed in the behavioral model in dogs and showed most of the behavioral characteristics described for antipsychotic drugs. Its neurochemical profile, in particular the 5-HT2/D2 ratio, was also compatible with atypical antipsychotic activity.
- Liegeois,Rogister,Bruhwyler,Damas,Thuy Phuong Nguyen,Inarejos,Chleide,Mercier,Delarge
-
p. 519 - 525
(2007/10/02)
-
- Synthesis and diuretic activity of pyrido[2,3-d]pyrimidones and related compounds
-
The synthesis of a series of pyrido[2,3-d]pyrimidine-4-one derivatives (7) and the results of a study of their potassium-sparing diuretic activity are described. Compounds 7 were prepared from 2-chloro-3-pyridinecarbonyl chloride, 1,2-dihydro-2-thioxo-3-pyridinecarbonyl chloride, 2-methylthio-3-pyridinecarbonyl chloride or 2-(p-chlorophenyl)thio-3-pyridinecarbonylchloride and different amines through the respective amides (4). Compounds 4 and 7 were assayed for diuretic and potassium-sparing activities. Although some of the compounds showed significant diuretic activity, a significant increase of the Na+/K+ index was only observed with 5-oxo-5H(1,3)thiazolo[3,2-a]pyrido[3,2-e]pyrimidine.
- Monge,Martinez-Merino,Cenarruzabeitia,et al.
-
-