453560-91-3

Upstream product

• 20769-85-1 2-bromoisobutyric acid bromide 
• 99-57-0 2-hydroxy-5-nitroaniline 

Downstream Products

• 85160-84-5 3,4-dihydro-2,2-dimethyl-6-nitro-3-oxo-2H-1,4-benzoxazine 
• 136545-11-4 2,2-dimethyl-6-nitro-3,4-dihydro-2H-benzo[1,4]oxazine 
• 136544-11-1 2-(3,4-dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazin-4-yl)pyridine N-oxide 
• 136544-43-9 3,4-dihydro-4-(2-hydroxy-2-phenylethyl)-2,2-dimethyl-6-nitro-2H-1,4-benzoxazine 
• 136544-99-5 3,4-dihydro-2,2-dimethyl-6-nitro-3-oxo-4-phenacyl-2H-1,4-benzoxazine 

Relevant academic research and scientific papers

Synthesis by microwave irradiation of a substituted benzoxazine parallel library with preferential relaxant activity for guinea pig trachealis

An efficient, facile, and practical parallel combinatorial synthesis of substituted-benzoxazines under microwave irradiation was described. The procedure involved the use of a microwave oven especially designed for organic synthesis suitable for parallel synthesis of solution libraries. A demonstration 19-membered library of substituted N,N-dimethyl- and N-methyl-benzoxazine amide derivatives, structurally related to the potassium channel opener cromakalim, was generated by both conventional and microwave procedures, achieving a reduction from 7 h to 30-36 min in library generation time for the microwave approach. All the synthesized compounds were tested using the in vitro models of rat aorta and guinea pig trachea rings pre-contracted with phenylephrine and carbachol, respectively. All N,N-dimethyl amide derivatives showed a relaxant activity higher on guinea pig trachea rings than on rat aorta rings.

SUBSTITUTED ARYL-AMINE DERIVATIVES AND METHODS OF USE

The present invention provides classes of compounds, including-their pharmaceutically acceptable derivatives, useful for treating angiogenesis and related diseases such as cancer. Formula I and II wherein R is a 9- or 10-membered heterocyclyl ring selected from 7-isoquinolinyl,..2-methyl-3-oxo-2,3-dihydroindazol-6-yl, [1,6]-naphthydrin-3-yl, [1,7]-naphthydrin-2-yl, 1-oxo-2,3-dihydrobenzofuran-4-yl, 3-oxo-2,3-dihydrobenzofuran-5-yl, dihydro-benzodioxinyl, 6-quinazolinyl, 2-amino-6-quinazolinyl, 4-methylamino-6-quinazolinyl, 2,4-diamino-6 quinazolinyl, 3-oxo-3,4-dihydro-1,4-benzoxazin-6-yl, 2,2-difluoro-l;3-benzodioxol-5-yl and 2,2,3,3 tetrafluoro-2,3-dihydro-l,4-benzodioxin-6-yl, each of which is optionally substituted with one or more substituents selected from halo, haloakyl, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, N-dimethylamino-C1-6-alkyl, N-dimethylamino-C1-6-alkoxy, amino, alkyl-carbonylamino, morpholino-sulfonyl, amino-sulfonyl, oxazolyl, pyrrolyl,4 morpholinyl, carboxyl, cyano, and acetyl; wherein R1 in formula I is selected from unsubstituted or substituted phenyl, 5-6 membered heteroaryl, 9-10 membered bicyclic heterocyclyl and 11-14 membered tricyclic heterocyclyl, and R1 in formula II is selected from specific bicyclic heterocycles.

SUBSTITUTED ANTHRANILIC AMIDE DERIVATIVES AND METHODS OF USE

Selected compounds are effective for prophylaxis and treatment of diseases, such as angiogenesis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Substituted alkylamine derivatives and methods of use

Selected amines are effective for prophylaxis and treatment of diseases, such as angiogenesis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Synthesis and vasorelaxant activity of new 1,4-benzoxazine derivatives potassium channel openers

As part of a search for new potassium channel openers, the synthesis and vasorelaxant activity of new 1,4-benzoxazine derivatives derived from transformation of the benzopyran skeleton of cromakalim were described. Several new 1,4-benzoxazine derivatives were provided with significant vasorelaxant activity with an overall pharmacological behavior similar to CRK (1f, 1i, 2d, 2e, 2f and 2i).

Synthesis, biological activity and conformational study of 1,4- benzoxazine derivatives as potassium channel modulators

With the aim of discovering new molecules with K+-channel activating properties, we have synthesized derivatives of cromakalim (CRK), an important molecule which shows specific affinity towards K+ channels, by replacing the benzopyrane ring of this reference compound with a 1,4-benzoxazine moiety. A different number of substituents showing a good discrimination between hydrophobic and electronic properties have been inserted at the 6-position of the 1,4-benzoxazine ring. We describe here the synthesis and discuss the solid state conformation of these new molecules. When tested on rat aorta ring precontracted with phenylephrine, two compounds (2c and 2d) showed a concentration-dependent relaxation similar to that measured for cromakalim but less potent than this reference drug.

Novel potassium channel activators: Synthesis and structure-activity relationship studies of 3,4-dihydro-2H-1,4-benzoxazine derivatives

Strong potassium channel-activating effects were found among a series of novel 4-substituted 3,4-dihydro-2H-1,4-benzoxazine derivatives. The key step in preparation was the nucleophilic substitution of 3,4-dihydro-2H-1,4- benzoxazine (3) with activated halogenopyridines, such as halogenopyridine N- oxides (15a-c) and the borane adduct (15d) of 4-bromopyridine. Structure- activity relationship studies identified 2-(3,4-dihydro-2,2-dimethyl-6- nitro-2H-1,4-benzoxazin-4-yl)pyridine-1-oxide (16a: YM934) as the optimal compound. This compound (16a) showed a more potent oral antihypertensive effect than cromakalim in conscious spontaneously hypertensive rats.