Synthesis and Acetylcholinesterase Inhibitory Activity of Novel Trilaciclib Analogs

Trilaciclib is a CDK4/6 inhibitor, used to treat the bone marrow damage in chemotherapy patients. A series of thirteen novel structural trilaciclib analogs was obtained to evaluate their activity against acetylcholinesterase. An effective method for the synthesis of 4,7-substituted 8,9-dihydropyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidine derivatives from a new methyl 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate was developed. Most of the synthesized pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidine derivatives inhibited acetylcholinesterase in the micromolar range. The obtained data can be used for designing more potent acetylcholinesterase inhibitors with the pyrazino[1',2':1,5]pyrrolo[2,3-d]pyrimidine scaffold.