On the basis of 8-(halogenomethyl)-1,3-dimethyl-2H-pyrimido[5',4':4,5]-pyrrolo[2,1-c][1,4]oxazines, effective approaches to obtaining phosphorylated derivatives have been proposed pyrrolo[2,3-d]pyrimidine and new α- and β-hydroxyphosphonic acids were synthesized from the pyrrolo[2,3-d]pyrimidine moiety.
The reaction of hydrolytic cleavage of the pyrimidine ring of pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidines yields a number of new pyrrolo[1,2-a]-pyrazine-1(2H)-one derivatives containing carboxamide and a methylamino group in the heterocyclic ring.
Effective methods for the synthesis of 4-amino(dimethylamino, morpholin-4-yl)-pyrrolo[2,3-d]pyrimidine-6-carboxylic acids have been developed. The interaction of 4-functionally substituted 7-deazapurine derivatives with iodine was studied and the dependence of the reaction direction on the nature of the reagent and the conditions of iodination were determined.
Approaches to the production of functionally substituted fused pyrrolo[2,3-d]-pyrimidines were found and an effective one-reactor method for the synthesis of a number of new 4,7-substituted pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidines was developed by heating 8-(iodomethyl)pyrimido[5',4':4,5]pyrrolo[2,1-c][1,4]oxazines with aliphatic amines in acetic acid.
The iodination reaction products of 4-methoxypyrrolo[2,3-d]pyrimidine-6-carboxylic acid and its methyl ester have proven to be convenient reagents for the preparation of a new tricyclic system with the pyrrolo[2,3-d]pyrimidine moiety – 2a,5a,7-triazaacenaphthylene.
On the basis of 4-amino-substituted 8-(iodomethyl)pyrimido[5',4':4,5]pyrrolo[2,1-c][1,4]oxazines, an effective method for the synthesis of previously unknown tricyclic derivatives of 1-deazapyrimido[1,2,3-cd]purine – 4,5-dihydro-3H-2a,7-diaza-5a-azoniaacenaphthylenes, which may be promising for further modifications.
Primary studies of 4,5-dihydro-3H-2a,7-diaza-5a-azoniaacenaphthylenes as acetylcholinesterase (AChE) inhibitors were performed, and compounds inhibiting AChE in the micromolar range were found.
The inhibitory activity of 4,7-substituted derivatives pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidine was investigated, and 7-[2-(dimethylamino)ethyl]-4-{[2-(dimethylamino)ethyl]amino}-8-methylpyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidin-6(7H)-one inhibits telomerase activity in vitro with IC50 = 18,6 μM and is promising for the development of specific telomerase inhibitors.
The obtained experimental data on the inhibitory effect together with the results of molecular modeling have become the basis for further chemical optimization of the structure of fused derivatives of 7-deazapurine.
