Few selective cyclooxygenase-1 (COX-1) inhibitors have been described up to
now, although recent studies underlined the involvement of COX-1 in the carcinogenesis,
pathogenesis of neuroinflammation, cardiovascular diseases and pain. Among the known
COX-1 inhibitors none proved to be a good drug candidate, with the exception of mofezolac,
that is clinically used as an analgesic drug. New selective inhibitors were very often discovered
as a minor achievement during SAR investigations to discover selective COX-2 inhibitors (COXIBs).
After a recognition of the new COX-1 inhibitors synthesized in the last five years, it was attempted to
draw, for each chemical class, a structure which might highlight the determinant molecular features able to
switch the selectivity towards the COX-1 isoform. Overall, this review could constitute a tool to a better design
of novel selective COX-1 inhibitors, to be used in a disease theranostic approach targeting COX-1.