At least 90% of our available compound libraries, as well as all the effort towards their enrichment is based on chemical templates. Each year we design 3,000+ novel templates, select ~1,000 ones for further chemical validation, and populate those with final library samples in parallel synthesis mode. The designed templates are selected for further validation and collection enrichment based on their a) novelty (Reaxys and SciFinder zero scores), and b) dissimilarity coefficient (the higher the better) towards templates that represent existing collection. The average number of compounds in the sub-libraries produced around a given template is ~225, though it varies based on the number of incorporated diversity points.
The design of such novel templates is largely based on a) literature analysis (recently published articles & patents), b) ChemDiv’s internal chemical research (novel methods, reactions, multicomponent organic synthesis), c) rational drug design – considering and addressing upfront multiple medicinal chemistry issues, such as cLogP, MW, HBA, HBD, NRB, etc., as well as d) their chemical feasibility. ChemDiv’s in-house collection of 20,000+ building blocks enables production of maximally diverse chemical space around any given template.
This approach enables enriching our collection by ~200,000 novel compounds every year. It also provides for built-in SAR. When stock available analogs around a given template are exhausted, the template’s core can be easily re-produced and re-populated with any desirable substitution pattern (from 20,000+ available building blocks or provided by partner). This continuous validation process of novel templates provides a large pool of synthetically realizable chemistry made available to our partners. Deploying this knowledge can be translated into:
1. Synthesis of next generation focused libraries around a given template;
2. Quick production of novel libraries against a selected biological target;
3. Selection of amenable templates based on partners’ ideas (active centers, given pharmacophores, etc.) and rapid synthesis of libraries around those;
4. Delivery of bulk intermediates for further libraries assembly by partners;