Recent Advances on Pyrazole-Pyrimidine/Fused Pyrimidine Hybrids with Anticancer Potential (A Review).

Cancer, caused by the failure of the mechanism that controls cell growth and proliferation, is usually associated with severe health issues. Nowadays, chemotherapy still occupies an important place in clinical cancer treatment, but the multidrug resistance and low specificity of chemotherapeutics are the major obstacles that undermine effective cancer treatment. Pyrazole and pyrimidine/fused pyrimidine can be rewarded with significant anticancer activity and tampered with in a range of places whereby some of their derivatives have received approval to treat cancer. Notably, pyrazole-pyrimidine/fused pyrimidine hybrids, blending of pyrazole and pyrimidine/fused pyrimidine pharmacophores into in a new chemical entity, can act on different targets simultaneously in cancer cells and possess potent in vitro and in vivo activity against both drug-sensitive and drug-resistant cancers. Moreover, several pyrazole-pyrimidine/fused pyrimidine hybrids which are exemplified by ruxolitinib (pyrazole-pyrrolo[2,3-d]pyrimidine hybrid) have already applied in clinics for cancer therapy, demonstrating pyrazole-pyrimidine/fused pyrimidine hybrids are pharmacologically significant scaffolds for the exploration of novel anticancer agents. This review aims to shed light on the recent developments of pyrazole-pyrimidine/fused pyrimidine hybrids with anticancer potential, and their structure-activity relationships as well as mechanisms of action are also discussed, covering papers published from 2019 to present, to facilitate further rational design of more effective candidates. [ABSTRACT FROM AUTHOR]