Three privileged scaffolds, one pipeline: chalcones, pyrazolines and pyrazoles in drug discovery and fluorescent sensing.

Chalcones, pyrazolines, and pyrazoles constitute a uniquely powerful discovery pipeline in which each is a privileged scaffold with distinct applications, while also serving as the synthetic precursor to the next. Despite a theoretical chalcone library exceeding 680 000 unique structures accessible from commercial starting materials alone, fewer than 5140 examples have been reported in the literature-representing just 0.8% of this chemical space. Combining this precursor library with the downstream pyrazoline and pyrazole chemical spaces yields a combined landscape conservatively estimated to exceed 7.5 million unique structures, which remains largely unexplored. This review examines leading examples from 1990 to 2025 across all three scaffold classes, with particular emphasis on the most promising applications of this pipeline: anti-cancer, anti-inflammatory, anti-viral, and fluorescent sensing applications. We explore how pharmacophore hybridisation is further expanding this pipeline. Whereas previous reviews have focused on individual scaffold classes in isolation, this review takes an integrated, systematic approach that unifies all three into a single coherent discovery pipeline. We conclude with a roadmap on how the convergence of design of experiments, automated synthesis, high-throughput screening, and machine learning will unlock the potential of this vastly unexplored chemical space.