Medicinal interest benzodiazepines

One of the most common synthetic approaches to the construction of heterocyclic compounds involves the reaction of /3-keto esters with bifunctional nucleophiles. Thus a variety of reactions of (1) with different bifunctional heteronucleophiles, including hydrazine, substituted aminotriazoles, 2-aminopyridines, o-phenylenediamines, and o-aminothiophenol, lead to polynuclear condensed thieno compounds (e.g. 2-8) of potential medicinal interest featuring the pyrazolone, pyrimidinone, benzodiazepine, and benzothiazepine nuclei. Cannabinoid analogs can be prepared through cyclization of the condensation products of (1) with bifunctional oxygenated nucleophiles such as substituted resorcinols. ... 

The interest in compounds with potential medicinal activity has stimulated the appearance of a number of additional reports on 1,4-benzodiazepines.219a The antibiotic anthramycin has been recently shown to be a 1,4-benzodiazepine derivative (206a).219b... 

About 6000 chemical entities can be used, in various pharmaceutical formulations, to treat human or animal diseases all attempts towards their classification represent arbitrary procedures. The first reason for that is that not a single drag has ever been encountered which exhibits only one biological activity. The antimalarial drug chloroquine is also active on some inflammatory processes, the anxiolytic benzodiazepines possess antiepileptic properties, etc. On the other hand, the scientific communities have different needs a chemical classification may sometimes be very useful to medicinal chemists but strictly of no interest to a social security employee. Conversely pharmacologists and physicians will probably prefer the physiological classification. 

Reviews of interest are listed below general interest <84CHEC-i(7)593, B-89MI906-01 > 2,3-dihydro-diazepinium salts, syntheses, and reactions <93AHC(56)I> 1,4- and 1,5-diazepines and reduced derivatives, syntheses, and reactions 1,4-benzodiazepines spectroscopic aspects, medicinal chemistry, and clinical aspects . 

This chapter deals with preparations for nasal administration, with a local or a systemic effect. Classical nasal preparations were always associated with local ailments, but nowadays the interest in the nasal route for systemi-cally acting substances and direct nose to brain delivery is increasing. Fast absorption, the possibility of high blood levels and a patient friendly dosage form are the reasons. Nasal administration of medicines with local effect is the first choice for the treatment of topical nasal disorders. It is also an attractive route for low dose active substances with a systemic effect, such as peptides or benzodiazepines (e.g. midazolam). When compared to parenteral administration nasal administration is more easily applied and causes less risk of infection. 

For example, a medicinal chemist interested in phosphodiesterases (PDE) and using diazepam as a lead structure will rapidly prepare compounds (CI-1044) that are out of scope of the original patents, precisely because they exhibit dominantly PDE inhibiting properties and almost no more affinity for the benzodiazepine receptor (Figure 9.6). 

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