Dibenzo-1, 3-oxazepines

The dibenzo-oxazepine loxapine is another antipsychotic in this structural class that has a more typical neuroleptic biochemical profile with mainly antidopaminergic activity at D2-type receptors. Loxapine undergoes Phase I aromatic hydroxylation to yield several phenolic metabolites that have higher affinity for D2 receptors than the parent. Loxapine also undergoes N-demethylation to form amoxapine, which is used clinically as an antidepressant. Amoxapine binds to D2 receptors and inhibits the norepinephrine neurotransporter to block neuronal norepinephrine reuptake, a correlate of antidepressant activity. 

Phenyldibenz[r/,/][l,3]oxazepine (3) is obtained in 25% yield by treatment of the dibenzo-pyrylium perchlorate 1 with sodium azide, followed by heating the resulting azide 2 (vide supra).2 5... 

The unstable dibenz[c,/][l,2]oxazepines (312 R = CN, Cl) have been isolated as the major products of the UV irradiation of 9-cyano- and 9-chloro-acridine 10-oxides (310) in benzene (c/. the analogous Af-imide to 1,2-diazepine conversion on p. 598). Although none of the oxaziridine tautomer (311) was detectable by UV spectroscopy, the subsequent deoxygenation of (312) to acridine suggests the existence of a thermal equilibrium between (311) and (312) (79T1273). These dibenzo compounds (312) are the only fully unsaturated oxazepines yet isolated but the 2,3-benzoxazepin-l-one system (314) has recently been prepared by the reaction of benzonitrile oxide with the benzopyranone (313) (80JCS(Pl)846). 

A number of monocyclic and benzo-annelated examples of 1,2- and 1,3-thiazepines have been prepared but there has been little systematic study of these systems. The interesting photochemical interconversions of pyridine N-imides into 1,2- and 1,3-diazepines and of pyridine Af-oxides into 1,2- and 1,3-oxazepines regrettably lack parallels in thiazepine chemistry. There has been more interest in 1,4-thiazepines, as both rearrangement products and possible biogenetic precursors for penicillins and because of the pharmacological value of the benzo- and dibenzo-[l,4]thiazepines as antidepressants and coronary vasodilators. The only review (70ZC361) is excellent but not very recent. 

SYNS 2-CHLORO-l l-(4-xMETHYL-l -PIPERAZINYL)-DIBENZO(b,f)(l,4)OXAZEPINE 2-CHLORO-ll-(4-METHYL-l-PIPERAZINYL)-DIBENZO(b,f)(l,4)0X0-AZEPINE CL-62362 CL-71563 CLOXAZEPINE DIBENZOAZEPINE HF3170 LOXAPINE LW3170 OXILAPINE S-805 SUM 3170... 

CHLORO-ll-(4-METHYL-l-PIPERAZINYL)-DIBENZO(b,f)(l,4)OXAZEPINE see DCS200... 

The mechanism of the related photorearrangement of heterocyclic N-oxides is still a matter for debate. Evidence that rearrangement of the phenanthridine N-oxides (48) to the N-substituted phenanthridones (49) and the dibenzo[d,f]-1,3-oxazepines (50) proceeds by way of biradical intermediates rather... 

A more complex structure class with activity at PR is represented by the tetrahydro-1 [H]-dibenzo[fo, /]pyrido[l,2-d][l,4]oxazepine scaffold (62) [77]. This scaffold was modified mainly at the two aromatic systems and the 1-amino functionality. In addition, the central oxazepine ring has been modified to a thiazepine (63), a diazepine and an azepane ring in some examples. Comparable decorations of the whole system delivered active compounds with all these modified central ring systems. The acylation of the 1-amino function, especially with the trifluoroacetyl group (64), resulted in enhanced activity compared to free amino or alkyl substitution. Trifluorothioacetate was essential for agonism of the compounds, while thioureas... 

Makles Z, Sliwakowski M and Nousiainen P (1999). Detection of dibenzo[b,f][l,4]oxazepine in the presence of other lacrimators with thin layer chromatography. Chem Anal, 44, 257-262. 

There have been no papers dealing with the reactivity of the fully unsaturated 1,2-oxazepine or 1,2-thiazepine rings or their benzo or dibenzo derivatives, apart from rearrangements of the dibenzo[c/][l,2]oxazepines (81) as outlined in Section 9.07.7.1. The Src-electron, 1,2-oxazepinium perchlorate salts (61) (see Section 9.07.7.1) are stable, consistent with the charge delocalized seven-membered ring structure proposed, and do not undergo a Diels-Alder reaction with maleic anhydride <81ZOR881>. 

There is one possible dibenz-fused system for each of the 0, N and S, N rings. These are the dibenz[c /][l,3]oxazepine (9) and the dibenzo[fi /][l,3]thiazepine (10). Bridged systems incorporating 1,3-oxazepine or 1,3-thiazepine moieties have not been included in this chapter. 

The hypervalent-iodine-mediated tandem reaction process, reported for preparation of benzodiazepinones, when applied to 2-hydroxy-AT-arylben-zamides 92 afforded dibenzo[d,/][l,3]oxazepin-6(7fi)-ones 93 (14AGE6216). 

An almost complete resolution was attained between unlabeled and di-, tri-, or tetradeuterated drugs active on the central nervous system -l,2,3,4,10,14b-hexahydro-2-methyl- dibenzo [c,/]py-razino[l,2-fl]azepine (mianserin [VII]) and 1,3,4, 10,14b-hexahydro-2,7-dimethy l-2H-dibenzo [c,f -py-razino[l,2fl]oxazepine (Org GC 94 [VIII]). [3,3,-4,4- H4]Org GC 94 was chromatographed on p-Porasil column and n-hexane-2-propanol (90 10, v/v) to which a solution of 4% ethanol and 0.1%... 

Sulfur mustard, soman (GD) and dibenzo/b,f/-l,4-oxazepin (CR) were provided by the Department of Chemistry, Military University (VySkov, Czech Republic). Dimethyl methylphosphonate (DMMP),... 

Fig. 10 illustrates a typical reaction ion monitoring chromatograms for 100 pg of the studying compounds. Signal-to-noice ratio was excellent and in the majority of dau ters more than 400 1. An interpretable daughter spectrum was obtained also for 100 pg of DEMP and dibenzo/b,f/-l,4-oxazepin (S/N>10). 

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