164520-14-3

Upstream product

• 137-43-9 Cyclopentyl bromide 
• 42285-76-7 6-Methyl-3-phenylpyrimido[5,4-e][1,2,4]triazine-5,7(6H,8H)-dione 
• 164520-16-5 1-Isopropyl-6-methyl-3-phenyl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione 
• 164520-07-4 1-Butyl-6-methyl-3-phenyl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione 

Downstream Products

• 42285-87-0 3-Methyl-6-phenyl-1-(2-propyl)-7-azalumazine 
• 42285-86-9 3-Methyl-6-phenyl-1-propyl-7-azalumazine 
• 76278-67-6 1-Butyl-3-methyl-6-phenyl-7-azalumazine 
• 25696-85-9 3-phenylfervenulin 
• 164520-16-5 1-Isopropyl-6-methyl-3-phenyl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione 
• 164520-06-3 6-Methyl-3-phenyl-1-propyl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione 
• 164520-07-4 1-Butyl-6-methyl-3-phenyl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione 
• 32502-63-9 3-phenyltoxoflavin 
• 42285-76-7 6-Methyl-3-phenylpyrimido[5,4-e][1,2,4]triazine-5,7(6H,8H)-dione 

Relevant academic research and scientific papers

3-PHENYL ANALOGS OF TOXOFLAVINE AS KINASE INHIBITORS

The present invention concerns the compounds of formula (I) the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n represents an integer being 0, 1 or 2; m represents an integer being 0 or 1; R1 represents C I -4alkyl; R2 represents C I -4alkyl; R3 represents CI-4alkyl; or R2 and R3 taken together with the carbon atom to which they are attached form a C3-8cycloalkyl or Het1 wherein said C3-8cycloalkyl or Het1 each independently may optionally be substituted with C1-4alkyloxycarbonyl; R4 represents halo or C I -4alkyloxy; R5 represents C 1-4alkyloxycarbonyl, -O-(mono- or di(C1-4alkyl)aminosulfonyl), CI-4alkyl substituted with one or where possible more substituent being selected from Het3 or NR6R7, C1-4alkyloxy substituted with one or where possible more substituents being selected from amino, Het4or NR8R9; R6 and R7are each independently selected from hydrogen, C I-4alkyl, C I-4alkyloxyC1-4alkyl, -Het5 or CI-4alkyl substituted with one or where possible more substituents being selected from hydroxy, or Het5; R8 and R9 are each independently selected from hydrogen, C,1-4alkyl, -Het7 or mono- or di(C 1-4alkyl)aminosulphonyl; Het3represents a heterocycle selected from piperidinyl, or piperazinyl wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible two or three substituents each independently selected from hydroxy, aminosulfonyl, amino, mono-or di(C 1-4 alkyl)aminosulfonyl, hydroxyC 1-4alkyloxyC1-4alkyl or C1-4alkyloxy; Het4represents a heterocycle selected from morpholinyl, piperidinyl or piperazinyl wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible two or three substituents each independently selected from C1-4alkyl, C1-4alkyloxycarbonyl or mono- or di(C1-4alkyl)aminosulfonyl; Het5 represents a heterocycle selected from pyridinyl or piperidinyl wherein said monocyclic heterocycles each independently may optionally be substituted with one, or where possible two or three substituents each independently selected from aminosulfonyl, or mono- or di(Cl-4alkyl)aminosulfonyl; Het7 represents piperidinyl.

General syntheses of 1-alkyltoxoflavin and 8-alkylfervenulin derivatives of biological significance by the regioselective alkylation of reumycin derivatives and the rates of transalkylation from 1-alkyltoxoflavins into nucleophiles

Regioselective alkylations of reumycin derivatives under alkaline conditions with a dialkyl sulfate or alkyl halide in 1,4-dioxane or DMF to provide 1-alkyltoxoflavin or 8-alkylfervenulin derivatives of biological significance, are described. Namely, the primary and secondary alkylations of reumycin derivatives with appropriate dialkyl sulfates or alkyl bromides under alkaline conditions in 1,4-dioxane gave predominantly 1-alkyltoxoflavin derivatives, while the same alkylations in DMF instead of 1,4-dioxane gave predominantly 8-alkylfervenulin derivatives. In the case of tertiary alkylation, the reumycin derivative with 2-bromo-2-methylpropane in both solvents under the same conditions yielded only the 1-alkyltoxoflavin derivative. Moreover, the rates of transalkylation from 1-alkyltoxoflavin derivatives into nucleophiles, e.g. DMF and n-butylamine, are also described. That is, the toxoflavin derivatives possessing a primary alkyl group at the 1-position were easily dealkylated from the 1-position by heating with DMF, whereupon reumycin (i.e., 1-dealkyltoxoflavin, 8-dealkylfervenulin) derivatives were formed. In other words, transalkylation from the toxoflavin derivatives into DMF took place, However, the transalkylation of 1-alkyltoxoflavin derivatives possessing a secondary or tertiary alkyl group at the 1-position was not observed under such conditions. On the other hand, when heating 1-alkyltoxoflavin derivatives with n-butylamine in 1,4-dioxane, the transalkylations were more easily observed even in the case of 1-alkyltoxoflavin derivatives substituted by a tertiary alkyl group.

Facile and general syntheses of 1-alkyltoxoflavin and 8-alkylfervenulin derivatives of biological significance by the regiospecific alkylation of reumycin (1-demethyltoxoflavin, 8-demethylfervenulin) derivatives

Regiospecific alkylation of reumycins (6) under alkaline conditions with a dialkyl sulfate or alkyl halide in dioxane and in DMF to provide 1-alkyltoxoflavins (5) of biological significance and 8-alkylfervenulins (7), respectively, is described.