Synthesis of novel 1,2-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one derivatives

Synthesis, QSAR modeling, and molecular docking of novel fused 7‐deazaxanthine derivatives as adenosine A2A receptor antagonists

“…A variety of the alkyl residues was introduced in the last step of the synthetic route – the diazepine ring closure with various primary aliphatic amines. First, methyl 1,3‐dimethyl‐2,4‐dioxo‐2,3,4,7‐tetrahydro‐1 H ‐pyrrolo[2,3‐ d ]pyrimidine‐6‐carboxylate 1 was converted into 8‐(bromomethyl)‐2 H ‐pyrimido[5′,4′:4,5]pyrrolo[2,1‐ c ][1,4]oxazine 3 according to the previously described methods (Muzychka et al, 2012; Yaremchuk et al, 2018). Upon a brief heating of compound 3 with sodium methoxide in methanol, it was transformed into methyl 1,3‐dimethyl‐7‐(oxiran‐2‐ylmethyl)‐2,4‐dioxo‐2,3,4,7‐tetrahydro‐1 H ‐pyrrolo[2,3‐ d ]pyrimidine‐6‐carboxylate 4 .…”

“…Derived QSAR models gave good stability and predictive ability with q 2 > 0.60. Eleven representatives of the new heterocyclic system pyrimido[5′,4′:4,5]pyrrolo [1,2a] [1,4]diazepine were synthesized, and their activity against the A 2A receptor was evaluated. Molecular docking demonstrated that the potential biological activity of novel fused 7-deazaxanthine derivatives may be associated with adenosine A 2A receptor interaction, that is confirmed by the calculated high energy of complexation and the quality of the formed stabilizing interactions between the studied ligands and the adenosine A 2A receptor model.…”

“…Upon a brief heating of compound 3 with sodium methoxide in methanol, it was transformed into methyl 1,3-dimethyl-7-(oxiran-2-ylmethyl)-2,4-di oxo-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-d]pyrimidine-6carboxylate 4. The target pyrimido[5′,4′:4,5]pyrrolo [1,2a] [1,4] and various primary aliphatic amines under reflux in methanol.…”

Zinc Chloride Mediated Synthesis of 3H‐Oxazol‐2‐one and Pyrrolo‐oxazin‐1‐one from Ynamide

“…One should also mention the work of Wei describing the synthesis of pyrido‐ and pyrrolo[1,2‐ c ][1,3]oxazinon‐1‐ones through a nucleophilic addition‐cyclization process of N , O ‐acetal with ynamides. The pyrrolo[1,2‐ a ]pyrazinone core was also obtained by Kucher during the iodolactonization of methyl 7‐allylpyrrolo[2,3‐ d ]pyrimidine‐6‐carboxylate. In general, intramolecular cycloisomerization reactions that involve an ynamide functionality are achieved either by electrophilic cyclization or by using expensive transition metal catalysts, as described previously by some of us .…”

Mechanistic Insights into the Reaction of N‐Propargylated Pyrrole‐ and Indole‐Carbaldehyde with Ammonia, Alkyl Amines, and Branched Amines: A Synthetic and Theoretical Investigation

“…The pyrrolo‐pyrazinone 2 and its derivatives were found to have significant activity in the blockade of apomorphine stereotype and apomorphine‐induced climbing . Bromopyrrole alkaloids containing the pyrrolo[1,2‐ a ]pyrazine structural fragment such as longamide B( 3 ) and peramine ( 4 ) show immunosuppressive, antibacterial, and anti‐insect defensive activities (Figure ) …”