Structure-activity relationship of drug-derived molecules containing spirocyclic azetidine or 2,4-methanopyrrolidine moiety, Зв’язок між структурою і активністю подібних до ліків молекул, що містять фрагменти спіроциклічних азетидинів або 2,4-метанопіролідину

<jats:p>Local structural modification of approved drugs is a productive route in medicinal chemistry. If the parent molecule has already undergone pharmacological validation, the replacement of a single moiety can alter its solubility, metabolic stability, or some other properties, without altering the remaining essential characteristics. Therefore, sp3-rich compounds have drawn attention over the last decade. Among them, spirocyclic azetidines can replace flat saturated heterocycles such as morpholine, piperazine, or piperidine. 2,4-Methanopyrrolidines are regarded as conformationally constrained analogues of proline and pyrrolidine. This review covers structure–activity relationships of drug-derived molecules containing one of these two fragment types. The approved or clinically advanced parent compound serves as a fixed point of comparison in each case. For spirocyclic azetidines, drug-derived case studies are reasonably abundant and span CNS, oncology, and antimicrobial programs. Here, the GPCR ligand AZD1979, the linezolid series, several olaparib-related compounds, bupivacaine analogues, as well as sonidegib and danofloxacin works are considered. For 2,4-methanopyrrolidines, drug-derived cases remain few. The 2025 Merck LRRK2 program stands as the principal example, supplemented by older work and by scaffold characterisation studies on which future drug-derived applications can build.</jats:p>