Enlicitide decanoate (MK-0616) is a beautifully complex macrocyclic (not so small) peptide (or rather pseudo-peptide). This 1720 Da heavy beauty with 10 stereocentres is an inhibitor that blocks interaction between PCSK9 and LDL receptor and is under development at Merck for atherosclerotic cardiovascular disease. Most macrocyclic peptide drugs have to be injected. Enlicitide, however, is orally…
Although Hetero-Diels-Alder will play a central role, I am not going to speak about gender. Not today. Instead, I would like to highlight another major advancement in organic chemistry that enables synthesis of alkenes from alkynes. Alkynes serve as versatile building blocks in organic synthesis, drug discovery, and materials science. We chemists use them for…
Why nucleoside analogs matter and why they’re hard to make Nucleoside analogs (NAs) are among the most successful drug classes in medicine, with more than 30 currently approved for treating viral infections such as HIV/AIDS and hepatitis, as well as certain cancers. These synthetic mimics of natural nucleosides act as antimetabolites through diverse mechanisms: inhibiting…
The number of spirocyclic-N-heterocycles has increased dramatically in the recent years. From 10,000 in 2023 ➡️ 90,000 in 2025 (Substructure search on Reaxys). Functionalized spirocycles are highly valuable synthetic building blocks, especially in medicinal chemistry. 💊 However, if you want to decorate them a little bit more, you are likely tapping into the chemical space…