Synthesis of α-fluorocinnamate derivatives as novel cathepsin S inhibitors with in vitro antiproliferative activity against pancreatic cancer cells.

Cathepsins, key members of the papain-like family of cysteine proteases, are crucial for proteolysis processes within human cells, including osteolysis, immunomodulation and apoptosis. Recent research has highlighted the significant role of cathepsins, particularly the L, S, K, and B subtypes, in pancreatic cancer. This has driven the development of novel cathepsin inhibitors as potential treatments to inhibit tumor progression, migration and invasion.

First total synthesis of caerulomycin K: a case study on selective, multiple C-H functionalizations of pyridines.

Caerulomycins, natural alkaloids with antimicrobial properties, have been previously synthesized starting with highly pre-functionalized building blocks or requiring many functional group manipulations. In this work, we report the first total synthesis of caerulomycin K, a diversely trifunctionalized pyridine readily assembled in three steps exploiting the recent advancements in the C-H activation of N-heterocycles.

Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives.

The main protease (M) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered a highly conserved viral target. Disruption of the catalytic activity of M produces a detrimental effect on the course of the infection, making this target one of the most attractive for the treatment of COVID-19. The current success of the SARS-CoV-2 M inhibitor Nirmatrelvir, the first oral drug for the treatment of severe forms of COVID-19, has further focused the attention of researchers on this important viral target, making the search for new M inhibitors a thriving and exciting field for the development of antiviral drugs active against SARS-CoV-2 and related coronaviruses.