Covalent Screening Library
Diverse and most reliable source of Covalent Modifiers
8 301 compounds
Covalent screening became an integral part of Drug Discovery process. Covalent probes play essential role in discovery of new technologies, investigation of new proteins and assessment of their drugability.
A number of successful examples, when converting lead molecule to covalent binders leads to increase of overall efficacy, acknowledged this approach as a powerful tool for medicinal chemists.
To create a reliable source of covalent modifiers Enamine focused on elaboration of parallel synthesis approaches to synthesize series of new valuable covalent compounds. The latest building blocks were used to produce a number of high quality covalent binders. All our efforts have resulted in production of the largest commercially available collection of covalent compounds. Most diverse molecules with representation of all available covalent “warheads” have been pre-plated into representative Covalent Screening Library.
Enamine Covalent Screening Library has been extracted from the "Rule of Five" compliant subset of the Screening Collection using substructure searches of specified structural features. Active functionalities able to form covalent bonds with protein residues have been analyzed, and the “warheads” listed below were selected as optimal in terms of reactivity and essential stability. Additionally, the chemical environment of each reactive group was checked to be suitable for moderate reactivity of the compound. Molecules with non-druglike cores and structural features were removed from the library using internal structure filters and in-house elaborated rules. The final set of selected compounds has been evaluated manually to avoid too reactive entities and eliminate structural shortcomings of the substructure searches.
Structural fragments used for the selection
- Acrylamides, acrylonitriles
- Activated terminal acetylenes
- Cloracetamides, Alkyl halides
- Epoxides, aziridines
- Alkyl thioles, disulfides
- β-lactams, -lactones
- Sulfonyl fluorides/esters
- Carbamates, activated Aryl ureas
- 2-cyano/-Cl nitrogen heterocycles
- Vinylsulfones, -sulfonamides
- Boronic acids