Pyridazino[3,4-b][1,5]Benzodiazepin-5-Ones: Synthesis and Biological Evaluation

Abstract

Starting from 3,6-dichloropyridazine-4-carboxylic acid chloride, a series of pyridazino[3,4- b][1,5]benzodiazepin-5-ones bearing various substituents in positions 3, 6, 8 and 11 was prepared via N-alkyl-3-alkylamino-6-chloro- N-(2-chloro-5-nitrophenyl)-pyridazine-4-carboxamides. The latter were smoothly accessible by treatment of N-alkyl-3,6-dichloro-N-(2-fluorophenyl)-pyridazine-4-carboxamides with primary aliphatic amines. The new tricyclic compounds, which are structurally related to nevirapine and congeners were screened as human immunodeficiency virus type 1 reverse transcriptase inhibitors; the influence of the substitution pattern on inhibitory potency is discussed.

Regiospecific Synthesis and Structural Studies of 3,5-Dihydro-4H-pyrido[2,3-b][1,4]diazepin-4-ones and Comparison with 1,3-Dihydro-2H-benzo[b][1,4]diazepin-2-ones

“… 2 Note that there are compounds like nevirapine that are both [ b ] and [ e ] [1,4]diazepines. 3 , 4 We have previously published some results in the field of benzo[ b ][1,4]diazepines ( Figure 1 ). 5 − 7 …”

“…However, there are some important drugs that contain the benzo­[ b ]­[1,4] structure, for instance, the anxiolytic clobazam (7-chloro-1-methyl-5-phenyl-1,5-benzodiazepine-2,4-dione) and the atypical antipsychotic olanzapine ({2-methyl-4-(4-methyl-1-piperazinyl)-10 H -thieno­[2,3- b ]­[1,5]­benzodiazepine}) . Note that there are compounds like nevirapine that are both [ b ] and [ e ] [1,4]­diazepines. , We have previously published some results in the field of benzo­[ b ]­[1,4]­diazepines (Figure ). − …”