98416-69-4

Upstream product

• 600-22-6 pyruvic acid methyl ester 
• 1575-37-7 4-Bromo-benzene-1,2-diamine 
• 321-23-3 4-bromo-2-fluoronitrobenzene 
• 617-35-6 2-oxo-propionic acid ethyl ester 

Downstream Products

• 1392413-56-7 6-bromo-3-chloro-2-methylquinoxaline 
• 98416-72-9 6-bromo-2-chloro-3-methylquinoxaline 
• 1417408-91-3 7-bromo-1-(2-chlorophenyl)-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline 
• 1427029-40-0 1-(2-chlorophenyl)-7-ethynyl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline 
• 1427029-41-1 1-(2-chlorophenyl)-4-methyl-7-trimethylsilanylethynyl-[1,2,4]triazolo[4,3-a]quinoxaline 

Relevant academic research and scientific papers

Synthesis of isomeric (E)-[4-(dimethylamino)phenyl]-vinylquinoxalines – precursors for a new class of nonlinear optical chromophores

[Figure not available: see fulltext.] Methods are presented for the preparation of isomeric (Е)-3-, (Е)-6-, (Е)-7-[4-(dimethylamino)phenylethenyl]quinoxalin-2-ones and 2-phenylquinoxalines – compounds of “donor–π-bridge” type, which serve as precursors for new nonlinear optical chromophores with potentially high first hyperpolarizability values. The introduction of dimethylanilinoethenyl moiety at position 3 of the quinoxaline system was achieved in good yields by fusion of 3-methyl derivatives with 4-(dimethylamino)benzaldehyde at 220°С in the presence of catalytic amounts of acetic anhydride and pyridine during the synthesis of 3-(dimethylaminophenylethenyl)quinoxalin-2-ones or as a result of condensation of these reactants by the action of 20 М sodium hydroxide solution in the presence of Aliquat 336 during the synthesis of 3-(dimethylaminophenylethenyl)-2-phenylquinoxalines. The introduction of dimethylanilinoethenyl moiety at positions 6 and 7 was achieved by Heck reaction of p-dimethylaminovinylbenzene with 6- or 7-bromoquinoxalines in the presence of palladium acetate. The structures of isomeric 6-bromo- and 7-bromo-3-methyl derivatives of quinoxalines were confirmed by X-ray diffraction analysis.

COMBINATIONS COMPRISING PDE 2 INHIBITORS SUCH AS 1-ARYL-4-METHYL- [1,2,4] TRIAZOLO [4,3-A] QUINOXALINE COMPOUNDS AND PDE 10 INHIBITORS FOR USE IN THE TREATMENT OF NEUROLOGICAL OR METABOLIC DISORDERS

The present invention relates to combinations of phosphodiesterase 2 (PDE2) inhibitors with inhibitors of phosphodiesterase 10 (PDE 10). In particular, the invention relates to combinations of 1-aryl-4- methyl-[1,2,4]triazolo[4,3-a]-quinoxaline derivatives which have been found to inhibit phosphodiesterase 2 (PDE2), with inhibitors of phosphodiesterase 10 (PDE10). Particular PDE10 inhibitors are selected from the group of MP-10, PQ-10, TP-10, papaverine, and the compounds disclosed in WO 2011/051342 and in WO 2011/110545. The invention is also directed to pharmaceutical compositions comprising such combinations, to processes for preparing such compositions, to the use of PDE2 inhibitors, in particular of 1- aryl-4-methyl- [1,2,4]triazolo[4,3-a]-quinoxaline derivatives for the potentiation of said PDE10 inhibitors, and to the use of said PDE10 inhibitors for the potentiation of the effect of said PDE2 inhibitors, in particular, 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]-quinoxaline derivatives, and to the use of such combinations and compositions for the prevention and treatment of disorders in which PDE2 and PDE10 are involved, such as neurological and psychiatric disorders, and endocrinological or metabolic diseases.

TRIAZOLOPYRAZINE DERIVATIVES AND THEIR USE FOR TREATING NEUROLOGICAL AND PSYCHIATRIC DISORDERS

The present invention is directed to triazolopyrazine compounds of Formula (I). Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds as therapeutic agents treating neurological and psychiatric disorders.

1-ARYL-4-METHYL-[1,2,4]TRIAZOLO[4,3-a]QUINOXALINE DERIVATIVES

The present invention relates to novel l-aryl-4-methyl-[l,2,4]triazolo[4,3-a]- quinoxaline derivatives as inhibitors of phosphodiesterase 2 (PDE2) and to a lesser extent of phosphodiesterase 10 (PDE10) or as inhibitors of both, phosphodiesterases 2 and 10. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which PDE2 is involved, or disorders in which both PDE2 and PDE10 are involved, such as neurological and psychiatric disorders, and endocrinological or metabolic diseases. The present invention also relates to radiolabeled compounds which may be useful for imaging and quantifying the PDE2 enzyme in tissues, using positron- emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a host, in vitro or in vivo and to precursors of said compounds.

Discovery of a new series of [1,2,4]triazolo[4,3-a]quinoxalines as dual phosphodiesterase 2/phosphodiesterase 10 (PDE2/PDE10) inhibitors

The synthesis, preliminary evaluation and structure-activity relationship (SAR) of a series of 1-aryl-4-methyl[1,2,4]triazolo[4,3-a]quinoxalines as dual phosphodiesterase 2/phosphodiesterase 10 (PDE2/PDE10) inhibitors are described. From this investigation compound 31 was identified, showing good combined potency, acceptable brain uptake and high selectivity for both PDE2 and PDE10 enzymes. Compound 31 was subjected to a microdosing experiment in rats, showing preferential distribution in brain areas where both PDE2 and PDE10 are highly expressed. These promising results may drive the further development of highly potent combined PDE2/PDE10 inhibitors, or even of selective inhibitors of PDE2 and/or PDE10.