Synthesis and biological activity of steroid conjugates of five-membered N-heterocycles with one or two nitrogen atoms: A review covering the years 2020-2025.

Steroidal scaffolds are central to drug discovery due to their unique three-dimensional frameworks and biological relevance. The fusion or conjugation of these cores with five-membered heterocycles has emerged as a promising strategy to enhance pharmacological profiles, particularly in anticancer and anti-inflammatory research. This review focuses on the design, synthesis, and biological evaluation of steroid-heterocycle hybrids incorporating pyrrole, pyrazole, imidazole, isoxazole, oxazole, oxadiazole, thiazole and thiadiazole moieties. Compounds are categorized based on their linkage type: steroids with fused heterocyclic rings, directly conjugated systems, flexible spacer-linked hybrids and shared atomic frameworks (spirosteroids). Structure-Activity Relationships (SAR) are discussed to elucidate the impact of different heterocyclic systems on bioactivity. By systematically analyzing over ninety recent studies, this review provides a comprehensive reference for medicinal chemists interested in optimizing steroid-based drug candidates through strategic heterocycle incorporation.