Benzodiazepines involved

One of the more important routes for the metabohsm of benzodiazepines involves the introduction of a hydroxyl group at the 3 position in the heterocychc ring. The fact... 

An alternate synthetic strategy for benzodiazepines involves the condensation of resin-bound a-amino esters 17 with 2-aminobenzophenone imines followed by TFA treatment of the intermediate to effect cleavage and cyclization [27], The parallel synthesis of 40 discrete benzodiazepine analogs 18 was performed, and expected SAR data were generated in a bioassay based on the inhibition of fluoronitrazepam (Fig. 4). 

It is therefore not surprising that an alternative approach to the synthesis of benzodiazepines involves the reaction of /3-chlorovinylcarbonyl compounds with o-phenylenediamine. In the first example methyl 3-chlorovinyl ketone was used to obtain 5-methylbenzodiazepinium chloride (62 JPR163). An extensive investigation has been made of the use of /3-chlorovinylaldehydes for the preparation of 2,3-substituted benzodiazepines (64ZC458 67CB584). The preferred conditions for reaction were in... 

The first representative of ring system Type III was obtained by Sorrentino during the synthesis of 1,2,3,5-tetrahydro-3//-l,4-benzodiazepines. Ring expansion of 2-halomethyl-1 -methyl-4-phenyl-1,2,3,4-tetrahydroquinazo-lines to 1,4-benzodiazepines involves the formation of azirino[2, l-6]quina-zolines of type 30. This step is followed by cleavage of the C—N bond of the aziridine ring by the action of sodium borohydride. 

Two alternative unsuccessful approaches to the preparation of 3-oxo-benzodiazepines involved the 3-hydroxyimino- and 3-methylenebenzo-diazepines. 

The elimination of most benzodiazepines involves their metabolism by liver enz5Tnes, including cytochrome P450 isozymes. In a patient with liver dysfunction, lorazepam, which is metabolized extrahepatically, is less hkely to cause excessive CNS depression. Benzodiazepines are not eliminated via the kidneys or lungs. Flumazenil is used to reverse excessive CNS depression caused by benzodiazepines. The answer is (C). 

The scarcity of structural studies of benzodiazepines and benzothiazepines is because of the difficulty encoimtered in the cycfization of these seven-membered heterocycles. In general, cycfization of linear precursors is in principle, an excellent route to heterocycles. However, for cycloheptane rings, this reaction is disfavored by entropic and enthalpic factors besides trans annular interactions [105,106]. Hence, these heterocycles are usually obtained in good yield only when configurational and/or conformational constraints facilitate intramolecular cycfization. These facts kindle further interest in the study of their conformational featines. Here, the structural details of a few diazepines, benzodiazepines, and benzothiazepines are discussed. Benzodiazepines involve the fusion of benzene rings with diazepine rings, whereas... 

RR/Sa02 Respiratory depression RR< 10 Sa02 < 90% Manage airway + give O2 If benzodiazepines involved, give flumazenil ... 

A decrease in the basic properties of the reagent in going from 1,2-diaminoethane to 1,2-diaminobenzene leads, in the case of ynaminoketones (X = Me), to the 1,3-orientation of binucleophile and the formation of the benzodiazepines 356, suggesting that the carbonyl group is also involved in the heterocyclization. 

The mesoionic compound 3-phenylsydnone (10) (see Houben-Weyl, Vol. E8c, p 398ff) reacts with benzocyclobutadiene (9), generated by the action of zinc on /ra x-l, 2-dibrotno-l, 2-dihy-drobenzocyclobutadiene(8), to give 3-phenyl-3//-2,3-benzodiazepine(13). The process involves sequential 1,3-dipolar cycloaddition to give 11, decarboxylation to 12 and, finally, valence... 

Benzodiazepines and other anxiolytics. Although benzodiazepines are widely used in the treatment of acute alcohol withdrawal, most nonmedical personnel involved in the treatment of alcoholism are opposed to the use of medications that can induce any variety of dependence to treat the anxiety, depression, and sleep disturbances that can persist for months following withdrawal. Researchers have debated the pros and cons of the use of benzodiazepines for the management of anxiety or insomnia in alcoholic patients and other substance abuse patients during the postwithdrawal period (Ciraulo and Nace 2000 Posternak and Mueller 2001). 

Tenn, C. C. Niles, L. P. (1995). Central-type benzodiazepine receptors mediate the antidopaminergic effect of clonazepam and melatonin in 6-hydroxydopamine lesioned rats involvement of a GABAergic mechanism. J. Pharmacol. Exp. Ther. 274, 84-9. 

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