Novel potassium channel activators. III. Synthesis and pharmacological evaluation of 3,4-dihydro-2H-1,4-benzoxazine derivatives: modification at the 2 position

A new series of 3,4-dihydro-2H-1,4-benzoxazine derivatives, where various substituents were introduced into one of the geminal dimethyl groups at the 2 position, were synthesized and their potassium channel-activating activity was evaluated. Introduction of a hydroxyl group, as in compound 5, resulted in good solubility in water and a long duration of action compared with the parent compound 1. Introduction of a nitrato group, as in compound 8, produced typical nitrate activity such as exhibited by nitroglycerine in addition to potassium channel-activating activity. X-ray structural analysis of compound 5 showed that the sum of the bond angles around the N atom at the 4 position was 357.8 degrees, suggesting that the N atom had an approximately sp2-like planar bond configuration.     

Synthesis of 3-Phenyl-6-formyl-3, 4-dihydro-2H-1, 3-benzoxazine

Benzoxazine is a novel class of thermosetting resins, which possesses lots of outstanding properties such as no by-products and near-zero shrinkage during polymerization as well as good molecular design flexibility1-2. Furthermore, polybenzoxazines (PBZs)…     

Synthesis and antiherpetic activity of novel purine conjugates with 7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine

Chemistry of Heterocyclic Compounds - A method for the synthesis of novel purine conjugates with 7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine containing fragments of ω-amino acids with...     

Some derivatives of 3-aryl-2H-1,4-benzoxazine

Arylacyl esters of o-acetamidophenol, which are cyclized to 3-aryl-2H-1,4-benzoxazines by a saponification of the acetamido group, are obtained by the reaction of -bromomethyl aryl ketones with potassium o-acetamidophenoxide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 164–166, February, 1971.     

Synthesis of 2-(2-imidazolinyl) substituted 2,3-dihydro-4H-1,4-benzothiazine and 3,4-dihydro-2H-1,4-benzoxazines

An investigation into the synthesis of benzoxazine, benzoxathiane and benzothiazine derivatives of 2-(2-imidazolinyl)-1,4-benzodioxane has been carried out.     

Synthesis of 2-phenyl-3,4-dihydro-2H- and -3,4,5,6-tetrahydro-2H-1,6-benzothiazocine derivatives

The resynthesis of 2-phenyl-3,4-dihydro-2H-benzothiazocin-5(6H)-one (1) was investigated in order to prepare derivatives with potential CNS activity. Lactam 1 could be converted to amidine derivatives 6a-e via the intermediacy of the thioether 5a. Reduction of 1 with lithium aluminum hydride gave amine 8a . Reductive alkylation of 8a gave 9a and 9b while acylation of 8a gave derivatives 10a-d . No interesting biological properties were found for these compounds.     

Synthesis of 3,4-dihydro-2H-1,3,5-thiadiazines

3,4-Dihydro-2H-1,3,5-thiadiazines substituted at the 3 and 6 positions were synthesized by treatment of N-substituted N,N-bis(1H-1,2,3-benzotriazol-1-ylmethyl)-amines with thioamides and zinc bromide in dry CH(2)Cl(2) at room temperature for 48-60 h in 48-80% yields.     

Synthesis of chalcogeno lactones. II. 3, 4-dihydro-1 H-2-benzothiin-3-one, 3,4-dihydro-1H-2-benzoselenin-3-one and 3,4-dihydro-1H-2-benzotellurin-3-one

The synthesis of 3, 4-dihydro-1H-benzothiin-3-one and its selenium and tellurium analogs is reported from o-bromomethylphenylacetyl chloride and sodium hydrogen chalcogenates, via phase-transfer catalysis.     

Heterocyclic compound studies. II. Synthesis of 1,4-benzodioxin, 1,4-benzoxathiin, 1,4-benzoxazine and 1,4-benzothiazine derivatives

Benzocondensed six-membered heterocyclic rings containing two heteroatoms have been synthesized by a generally applicable method starting from disubstituted benzene compounds and methyl 4-chlorobutynoate ( 1 ) or methyl 4-bromobutenoate ( 2 ). The reactions with 1 yield a mixture of endo and exo (E or Z) isomers. The ¹³C nmr spectroscopy was used to assign the structure of the synthesized compounds.     

Synthesis and biological activities of new 2-substituted 1,4-benzoxazine derivatives.

A series of new 1,4-benzoxazine derivatives (XI, XII) possessing (4-phenyl-1-piperazinyl)alkyl moieties at the 2-position and related compounds (XIII) were synthesized and tested for calcium antagonistic, calmodulin antagonistic and antihypertensive activities. Various compounds had in vitro calmodulin antagonistic activity superior or comparable to that of trifluoperazine. Among these compounds, tetrahydronaphtho[2,3-b] [1,4]oxazine derivatives such as 51, 53, 54, 58, 59, 60, 73 and 75 showed potent antihypertensive effects in spontaneously hypertensive rats. Optical isomers of 51 were also synthesized and evaluated biologically. No differences in biological activities were seen between the enantiomers.     

Synthesis of phenyl-substituted 2H-3,4-dihydro-3-aminomethyl-1,4-benzoxazines. Intermediates for 1H-2,3,3a,4-tetrahydroimidazo[5,1-c][1,4]benzoxazin-1-one derivatives. Part II

The synthesis of 2H-3, 4-dihydro-3-aminomethyl-1, 4-benzoxazines substituted by one phenyl group in the 2, 3 or α-position is reported. The two diastereoisomers of the 2-phenyl-derivative were independently synthesized from ethyl trans-3-phenylglycidate by a stereospecific route. A previous attempt at the synthesis of these same compounds gave rise to an unexpected aliphatic-aromatic ketone rearrangement.     

An efficient synthesis of the optically active isomers of 2H-1,4-benzoxazine derivatives,novel KATP channel modulators

2H-1,4-Benzoxazine amidine derivatives are drugs acting as modulators of the skeletal muscle and pancreatic beta cell ATP-sensitive-K⁺ (KATP) channels. With the aim of evaluating the influence of absolute configuration on the biological activity of these drugs, we herein report the optimization of a synthetic route to obtain both enantiomers of some of these compounds with improved chemical yield and high enantiomeric excess.     

Novel synthesis of spirocyclic-3,4-dihydro-2H-benzo[b][1,4]oxazine derivatives

A two-step procedure involving acid catalyzed ring opening of spirocyclic epoxides with 2-haloanilines and subsequent palladium-catalyzed intramolecular C–O bond formation to provide spirocyclic-3,4-dihydro-2H-benzo[b][1,4]oxazine derivatives is described.     

Photophysical and Electrochemical Investigations on Photoconducting Poly(6-tert-butyl-3,4-dihydro-2H-1,3-benzoxazine)

Poly(6-tert-butyl-3,4-dihydro-2H-1,3-benzoxazine) was synthesized by thermally activated cationic ring opening polymerization. The structure of the polymer was confirmed by spectral and thermal studies. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were estimated using cyclic voltammetry and optical absorption. Modulated photocurrent measurement technique was employed to study the spectral and field dependence of photocurrent. Photocurrent of the order of 1.5 µA/m² was obtained for polymer at a biasing electric field of 40 V/µm.     

Synthesis of 3-benzoyl-3,4-dihydro-2H- and 3,4-dihydro-2,2-disubstituted-benzopyrans via alkynyl grignard reagents

The versatility of the new route to a substituted chromane via a lithiated allene recently described by us [1] is reported. The relatively more stable alkynols 2–4 were readily identified and thus provide evidence for the formation of vinyl acetylene carbinol as an intermediate in the new route. Accordingly, phenylacetylene magnesium bromide [2] reacted with suitable aldehyde or ketone to give the alkynols 2–4 which condensed further with the same or different aldehyde or ketone to give 3-benzoyl heteroring-substituted chromanes 5–17.     

Studies on the chemistry of 1,4-oxazines,XV: Synthesis of ethyl 3,4-dihydro-4-tosyl-2H-1,4-benzoxazine-3-carboxylate

A four step synthesis of ethyl 3,4-dihydro-4-tosyl-2H-1,4-benzoxazine-3-carboxylate (4) from the acetal5 is described.

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Studien zur Chemie der 1,4-Oxazine, 15. Mitt.: Synthese des 3,4-Dihydro-4-tosyl-2H-1,4-benzoxazin-3-carbonsäureethylesters (Kurze Mitteilung)

Zusammenfassung Eine Synthese des 3,4-Dihydro-4-tosyl-2H-1,4-benzoxazin-3-carbon-säureethylesters (4) über vier Stufen wird, ausgehend vom Acetal5, beschrieben.