The C-H — O hydrogen bond is so well established in structural biology today, that it’s been overlooked that the C-H — O hydrogen bond was first proposed by a woman, June Sutor, in a 1960’s Nature article.[note]Sutor, D. J. “The C-H … O Hydrogen Bond in Crystals.” Nature, 1962, 195, 68-69. https://www.nature.com/articles/195068a0.pdf[/note] Her commentary …
The global cancer immunotherapy pipeline continues to explode with nearly double the number of active targets in 2019 vs. only two years ago, comprising 3,876(!!) active drugs, with a subset undergoing >5000 active clinical trials. In 2016, I listened to Dan Chen, former Global Head of Cancer Immunotherapy Development at Genentech, comment on the challenge …
Scientists from GlaxoSmithKline’s Stevenage site have an excellent article in J. Med. Chem. showing that cyclopropyl pyran (CPP) groups can serve as viable isosteres to N-pyrimidyl morpholines thanks in part to favorable cyclopropane σ -> aryl π interactions. N-aryl morpholines are privileged motifs in drug discovery, and suitable hydrogen-bond accepting isosteres are scarce. This is …
Of the record 59 FDA drug approvals from 2018, the majority were small molecules (64%). Keep at it, chemists! 🙂 Oncology and infectious diseases were the areas with most small molecule approvals, followed by genetic/rare diseases. Some more statistics below. Last year the FDA approved a record 59 novel drugs, which included 38 small molecule …
BMS-986142 is a reversible BTK inhibitor with two axial stereocenters. BMS synthetic chemists were able to make >200 kilos of this compound as a single isomer using this route. Wow. Atropisomers are a nightmare in drug discovery. Axial stereocenters are not easy to set predictably, separation of isomers is a pain, and the products are …
Adventures in Atropisomerism: A Case Study from BMS Read More »
Knochel’s group has shown that you can fluorinate Grignard reagents without decomposition via single-electron transfer reactivity (SET) by a simple solvent switch from THF to DCM. A common way to prepare aryl fluorides is through lithium-halogen exchange, followed by trapping with N-fluorosulfonimide (NFSI). This isn’t always viable, as the alkyllithium reagents used in the exchange …