Benzo-l,4-oxazines

The Enantiomers of 2-Donor-Substituted Benzopyrans and Benzo-l,4-oxazines and Their Thermal Racemization... 

Therefore, the present chapter will describe the physical methods available for the investigation of the enantiomers of 2-donor-substituted benzopyrans and benzo-l,4-oxazines. Some examples of their stereoanalytical characterization will be given. Subsequently, it will be shown that thermal racemization is a novel and... 

Dihydro-(benzo-l,4-oxazine) werden mit Eisen/Salzsaure aus -(2-Nitro-phenoxy)-alkoholen erhalten (s. Bd. VIM, S. 555, Tab. S. 559, 560). 

Compound 71 is a potent 5-HT5-receptor antagonist that suffers from poor brain penetration and has a B/P ratio of 0.1. Efforts to decrease the molecular weight and hydrogen bond acceptors led to a new benzo[l,4]oxazine (72) that maintains in vitro potency and has similar structural features (i.e. piperazine and sulfonamide) to 71. Compound 72 has an improved PK profile with enhanced brain penetration and a B/P ratio of 1.8. 

The molecular descriptors obtained by computation of molecular mechanics and quantum chemical methods are used to describe the molecular structures of A -(3-Oxo-3,4-dihydro-2//-benzo[l,4]oxazine-6-carbonyl) guanidines. The three-dimensional structures of the molecules are optimized with the software Hyperchem. Prior to the semi-empirical quantum chemical computation, all structures of the compounds are submitted to MM+ computation of molecular mechanics for energy optimization. The structural descriptors are obtained via the computation of semi-empirical method PM3. The computations are carried out at restricted Hartree-Fock level without configuration interaction. 

Bao, X. H., Lu, W. C., Liu, L. and Chen, N. Y. (2003). Hyper-polyhedron model applied to computer-aided molecular screening of N-(3-Oxo-3,4-dihydro-2H-benzo[l,4]oxazine-6-carbonyl) guanidines as Na/H exchange inhibitors, Acta pharmacologica sinica, 24, pp. 472. 

The 0X0 structures of l,3-oxazin-4-onium and benzo-l,3-oxazin-4-onium salts, but not their 4-hydroxy forms, have been confirmed by H-NMR spectra in which the chemical shifts of methyl groups in position 2 were almost identical for both NH- and NMe-substituted salts 106 (75KGS460 77KGS328, 77KGS704, 77ZOR2459). 

CHEMISTRY OF PYRIDO[2,l-c][l,4]OXAZINES Benzo Derivatlvee of Pyrldo[2,1-c][l,4]thlazlne... 

By considering the possible locations of the three heteroatoms and fusion of the bicyclic 6-6 system of pyrido[x,y-z][l, ]oxazines and thiazines, it is possible to write 24 isomers for each of the oxygen and sulfur analogues. The same number of isomeric structures holds also for the pyrano- as well as the thiopyrano[x,y-z][l, ]oxazines and thiazines. Fusion of a benzo ring on bond [e] or bond [d] of the former system and on bond [e] of the second system will lead to 12 isomeric structures in each case for each heteroatom. Each of the 12 structures could be divided into 6, 4, and 2 structures belonging to the [1,2], [1,3] and [l,4]oxazines and thiazines, respectively. 

De Wald HA, Heffner TG, Jaen JC, Lustgarten DM, McPhail AT, Meltzer LT, Pugsley TA, Wise LD (1990) Synthesis and dopamine agonist properties of ( )-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[l]benzo-pyrano [4,3-b]-l,4-oxazin-9-ol and its enantiomers. J Med Chem 33 445 150. 

The benzo-derivatives of the salts 86, i.e. benzo-l,3-oxazin-4-onium salts 89, are formed under the same conditions by acylation of salicylonitrile 88, which is a structural analog of the enol form 85 of the / -ketonitrile71 (equation 32). 

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