Cyanoacrylamides

Acrylamides are the most popular covalent warheads present in approved drugs. α-Cyanoacrylamides are a novel class of electrophilic warheads currently under active investigation in the field of covalent drug discovery. They combine moderate reactivity with high selectivity, making them an attractive alternative to irreversible warheads such as acrylamides or vinyl sulfones. Due to the presence of an electron-withdrawing cyano-group, Cyanoacrylamides are capable of forming reversible covalent bonds with nucleophilic residues, particularly the thiol groups of cysteine. This enables controlled residence time and helps to reduce the risk of off-target effects.

Cyanoacrylamide warheads have already been applied in a number of promising compounds, especially for kinase targeting, such as FM409 and PRN1008 (BTK inhibitor). Cyanoacrylamides can also be used for other targets, such as Chst15. An example of a related compound, Entacapone, has been approved for the treatment of Parkinson’s disease.

Enamine has almost 5k compounds in stock (90%+ pure by LCMS and/or NMR analysis), which can be delivered as dry powders or in any customized plated formats. Access to our extensive building block inventory, combined with validated synthetic approaches, enabled the creation of a 19-million-compound REAL Cyanoacrylamide Array. Compounds from this array can be synthesized within 3–4 weeks in our parallel synthesis department, with an on-time delivery rate exceeding 80%.

Explore our pre-plated Cyanoacrylamide fragments and screening libraries—ready for immediate use.