Pyrimidine nucleoside analogues and antitumour drugs based on them: fifty years in therapy

Most of the modern chemotherapeutic arsenal for the treatment of various types of cancer is based on pyrimidine nucleoside analogues. These include drugs that have been proven for decades (cytarabine, floxuridine, gemcitabine, capecitabine, azacitidine, and decitabine) as well as combinations of new antitumour agents (trifluorothymidine and tipiracil hydrochloride, decitabine and cedazuridine). New pyrimidine nucleoside analogues (doxyfluridine, tezacitabine, tiarabin, troxacitabine, etc.) and their depot forms (sapacitabine, MB-07133, etc.) are currently undergoing clinical trials for monotherapy or combination therapy for a wide range of oncological diseases. Over the past 15 years, publications have appeared describing various approaches to optimize the synthesis methods and structures of existing cancer drugs, as well as the design and synthesis of new pyrimidine nucleoside analogues with antitumour activity. This review summarizes new information and classical methods for synthesizing pyrimidine nucleoside analogues, as well as data on their antitumour activity, targets, and mechanisms of action. This review will be useful to a wide range of readers, including undergraduate and graduate students in chemistry and biology, and also specialists in chemistry, biology and medicine. The bibliography includes 216 references.