5,6,7,8-TETRAHYDROPYRIDO[3,4-d]PYRIMIDINES: A RECENT PERSPECTIVE ON SYNTHESIS AND BIOACTIVITY

Adagrasib, a selective KRAS G12C inhibitor, stands out with its favorable pharmacokinetic profile, including a prolonged half-life (around 23 hours) compared to Sotorasib. The synthetic approach for Adagrasib involves utilizing the 5,6,7,8-tetrahydro pyrido[3,4-d]pyrimidine (1) scaffold. The selective functionalization of a 5,6,7,8- tetrahydropyrido[3,4-d]pyrimidine nucleus through three different types of reactions: Suzuki coupling at the C-2 position, nucleophilic substitution at the C-4 position, and electrophilic substitution at the C-7 position, enables the generation of diverse molecules with latent therapeutic applications. Research continues to explore its potential in combination therapies and other tumor types, highlighting the importance of the 5,6,7,8-tetrahydro pyrido[3,4- d]pyrimidine scaffold. These synthetic advancements, including the demonstration of promising biological activity, are encouraging and driving the development for synthesis of new drugs. Hence, recent progress in the preparation and pharmacological evaluation of 1 covers the literature up to September 2024. This review is arranged chronologically and according to biological activity, highlighting key advancements in the field.