Dibenzothiazepine

Dibenzothiazepin-1 l(10//)-ones are reduced to 10,1 l-dihydrodibenzo[/>,/][l,4]lhiazepines by lithium aluminum hydride.66... 

Dibenzothiazepines lose sulfur on brief heating in diethyl phthalate in the presence of copper bronze to give phenanthridines 5.59 [Pg.335]

Receptor-Binding Studies. Quetiapine (Seroquel) is also a dibenzothiazepine derivative produced by altering the structure of clozapine. This agent has an affinity for multiple brain receptors, a low propensity to evoke EPS in preclinical tests considered predictive of antipsychotic activity, and does not produce sustained plasma prolactin levels. 

Dibenzothiazepine Quetiapine Similar to olanzapine perhaps less weight gain May require high doses if there is associated hypotension short ti/2 and twice-daily dosing... 

Stannous chloride-mediated reductive cyclisation-rearrangement of the nitro-ketone 269 (obtained from the nitro-acid, 268) gave the dibenzothiazepine derivative 270 in good overall yield mechanistically it was proposed that a hydroxylamine intermediate leads to the rearrangement after intramolecular nucleophilic addition to the ketone [02JOC8662]. 

The azathiaphenanthrene 1045 undergoes a thermal rearrangement in refluxing xylene involving ring expansion to yield the dibenzothiazepine 1047 via a Stevens-type rearrangement of the methylide intermediate 1046. 

Magnesium perchlorate has been used as a catalyst for the synthesis of benzothiazepines 153 from chalcones and 2-aminothiophenol <07JHC541> while derivatives 154 using 3-cinnamoyl coumarin as the a,p-unsaturated ketone have also been synthesised <07JHC145>. The reaction of 2-aminothiophenol with itaconic anhydride also gives the benzothiazepine system 155 <07JHC457> while dibenzothiazepines 157 were formed by denitrocyclisation of the sulfide 156 <07JHC1247>. 

The compounds dibenzothiazepine 82, dibenzooxazepine 83 and dibenzodiazepine 84 are elegantly prepared via the organolithium compound as depicted below... 

Dibenzodiazepines Clozapine Thienobenzodiazepine Olanzapine Dibenzothiazepine Quetiapine Benzixasoles Risperidone... 

Thiols are often oxidized to disulfides via a photoinitiated radical path, as with thiorfan (111, Scheme 4.67) (Gimenez et al., 1988), or up to sulfinate and sulfonate as with the antineoplastic 6-mercaptopurine (Hemmens and Moore, 1984). Both alkyl and aryl sulfides are photooxidized to sulfoxides, as in the formation of S-oxides (110) from dibenzothiazepin (109, Scheme 4.66), as well as (21) from chlorpromazine (20, Scheme 4.16) and similarly from thioridazine (Elisei et al., 2002) and diltiazem (Andrisano et al., 2001b). 

Oxazepines have previously been suggested as unstable intermediates in the photolysis of acridine N-oxide and related N-oxides now two examples, (175 R = CN) and (175 R = Cl), have been isolated for the first time. " As predicted, they are unstable and undergo a variety of isomerization reactions in the dark and under mild conditions. The novel cyclic sulphilimine (176) ring-expands when boiled in xylene to give the dibenzothiazepine (177) in moderate (26%) yield." ... 

Conformational aspects of the antidepressant drug, tianeptine (23), which is a dibenzothiazepine derivative, have been studied by H and C NMR spectroscopy. Two separate conformations for the seven-membered ring are indicated at low to room temperature. The conformational preference for the side chain involves bending over the non-substituted aromatic ring moiety <92MRC1212>. 

---