P. Sagar, Y. Ozarde, V. Vichare, Preeti Mehta, R. Gadhave
tlooto Summary
Pyrazolopyrimidines represent a versatile and promising class with strong in vivo efficacy, selectivity, and a favorable toxicity profile, and further systematic in vivo and clinical studies are essential to translate their potential into therapeutic success.
Abstract
BACKGROUND Pyrazolopyrimidines are a fascinating class of heterocyclic compounds that have attracted considerable interest for their potential in cancer therapy. Their unique scaffold allows flexible chemical modifications, enabling them to interact with various cancer-related proteins- especially kinases that regulate tumor growth and survival.
OBJECTIVE This review highlights recent advancements in the design, synthesis, and biological evaluation of pyrazolopyrimidine derivatives, emphasizing their role as targeted anticancer agents.
METHODS We analyzed recent literature (2000-2025) covering synthetic strategies, anticancer targets, in silico studies on anticancer targets and their mechanisms, off-target mechanisms, and patent information. The review also focuses on how these methods guide the optimization of Structure- Activity Relationships (SAR) and improve compound efficacy.
RESULTS Numerous pyrazolopyrimidine derivatives demonstrated significant anticancer activity across various cell lines, including breast, liver, colorectal, and haematological malignancies. Mechanistic investigations revealed that these derivatives target key oncogenic pathways, such as CDKs, EGFR (including resistant mutants), mTOR, TOPO II, and HDACs. They exert anticancer effects by inducing apoptosis, arresting cells at S or M phases, and downregulating proliferation markers. Several studies also report favourable selectivity for cancer cells, improved bioavailability, and metabolic stability, supporting their drug-like properties.
CONCLUSION Pyrazolopyrimidines represent a versatile and promising class with strong in vivo efficacy, selectivity, and a favorable toxicity profile. Their ability to engage multiple targets and overcome resistance highlights their potential for integration in oncology. However, further systematic in vivo and clinical studies are essential to translate their potential into therapeutic success.
Citation format
SAGAR, P., et al. A comprehensive review of designing and synthetic aspects of pyrazolopyrimidine derivatives as anticancer agents. MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2026, 26.