Dibenzodiazepine derivative

Mechanism of Action A dibenzodiazepine derivative that interferes with the binding of dopamine at dopamine receptor sites binds primarily at nondopamine receptor sites. Therapeutic Effect Diminishes schizophrenic behavior. 

Mechanism of Action A dibenzodiazepine derivative that interferes with the binding of dopamine at postysnaptic receptor sites in brain. Strong anticholinergic effects. Therapeutic Effect Suppresses locomotor activity, produces tranquilization. Pharmacokinetics Onset of action occurs within 1 hr. Metabolized to active metabolites 8-hydroxyloxapine, 7-hydroxyloxapine, and 8-hydroxyamoxapine. Excreted in urine. Half-life 4 hr... 

Clozapine, a tricyclic dibenzodiazepine derivative, was the first atypical AP to be approved by the FDA in 1989. It was originally thought that increased affinity to the 5HT2A receptor, in combination with a lower or no affinity to the D2 receptors, might define a compound as an atypical AP [12, 13], However, studies have shown that... 

Phenothiazines and related drugs, e.g., chlorpromazine (Largactil/ Thorazine). Some tricyclic antidepressants, e.g., amitriptyline Dibenzodiazepine derivatives and thienobenzodiazepines, e.g., clozapine, olanzapine Benzodiazepines, e.g., diazepam (Valium), nitrezepam (Librium) and lorazepam Barbiturates Opiates... 

Dibenzodiazepine-derived heterodimer ligands, such as HX600, may therefore represent useful tools for revealing previously unknown physiological roles of the NR4A1-RXR and NR4A2-RXR heterodimers. 

It is a dibenzodiazepine derivative. It is an unusual antipsychotic agent which hardly produces any extrapyramidal symptoms. It possesses the ability to suppress symptoms of tardive dyskinesia. 

Metabolic Hypertriglyceridemia Beta-blockers, clomiphene, corticosteroids, dibenzodiazepine-derived atypical antipsychotics (clozapine, olanzapine, and quetiapine), estrogens, furosemide, isotretinoin, propofol, protease inhibitors, retinoid derivatives, tamoxifen, thiazides... 

A second example is provided with the dibenzodiazepine derivatives and antipsychotic agents clozapine and quetiapine (Seroquel). While clozapine use... 

The in situ formation of a ketimine provided the cyclization precursor, which furnished on imine arylation the densely functionalized dibenzodiazepine derivative (Scheme 13.96). When the keto functionality was replaced by an ester moiety, which is reactive toward ammonia under the reaction conditions, an amide cyclization precursor is generated in situ (Scheme 13.97). The arylation of the spawned amide by the aryl chloride fragment furnished the dibenzoxazepinone derivatives in good to excellent yields. 

He L, Peng Y, Fu X, Chen X, Liu H. Dibenzodiazepine derivative quetiapine- and olanzapine-induced chronic interstitial nephritis. Ren Fail 2013 35(5) 657-9. 

Scheme 60 Dibenzodiazepine derivatives from orfho-chloranil 4.

This mode is conveniently illustrated by the reaction of A4,AP-dinitroaryI-amidines 180 with 4 to give the dibenzodiazepine derivatives 181 in good yield (Scheme 60, 03T5887). 

A three-component approach to dibenzodiazepine derivatives in aqueous medium has also been reported because of several important pharmaceutical properties of such scaffolds. Sangshetti and coworkers have developed an oxalic acid-catalyzed condensation of diamine, dicarbonyl compound, and an aromatic aldehyde in water [101] (Scheme 31). The reaction proceeded rapidly and almost in near-quantitative yield. Newly prepared dibenz[l,4]-diazepine-l-one derivatives 148 were evaluated for biological activity and some of the prepared compounds were found to have promising anxiolytic activity. 

---