“compound 9” is an investigational prodrug of pibrentasvir (ABT-530), a key component of AbbVie’s marketed HCV combination Mavyret. Pibrentasvir (PIB) is the largest approved oral small molecule since 1983 (MW = 1113, not including the peptide semaglutide at MW = 4113), and came with some solubility issues (aq. sol. pH 7 = <0.0001 mg/mL). The [...]

MK-5204 is a broad spectrum Candida antifungal agent derived from the natural product, enfumafungin. I was impressed that the molecule not only demonstrates oral efficacy but also has good oral PK in higher species (dog, cyno), given that the molecule is a large zwitterion with several very polar groups, including a primary amide, primary [...]

Infection with the malaria parasite, Plasmodium falciparum, is a leading cause of fatality in the tropical regions of the world, with over 240M infections and >600k deaths each year. Currently, over half of the world population is at risk of infection and with the rise of resistance against current treatments, the need for new antimalarials is clear. At the ACS Fall 2024 conference in Denver, CO, Novartis outlined the structure and discovery story of NVP-IWY357, a novel antimalarial that has no cross-resistance to current drugs and the potential to achieve a single-dose cure.

Recently, Novartis disclosed a new class of brain-penetrant, covalent agents against kinetoplastid parasites in Science. Kinetoplastid parasites cause Chagas disease (T. cruzi), sleeping sickness (T. brucei), and leishmaniasis (Leishmania), but there are few effective treatment options, especially for infections in the brain (e.g. stage II sleeping sickness).

GSK2818713 is an HCV NS5A replication complex inhibitor with an interesting biphenylene linker. The crowded, hotly competitive NS5A space has led to a lot of creative chemical scaffolds including this one.