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Advancements in Novel Chemistry and CNS-Active Agents Selection

Explore methodology for compound selection, in silico modeling, and reference compounds for CNS-active agents since 2010. Discover over 600 molecules with BBB permeability determination and descriptor distributions for effective compound design. Validate CNS LibraryChemDiv’s activity with PubMed examples and statistical data on heterocycles diversity.

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Advancements in Novel Chemistry and CNS-Active Agents Selection

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  1. CNS BBB Library ChemDiv Inc.

  2. PubChem Database Thomson Integrity SciFinder Protein Data Bank Scientific publication & Patents (2010-2015) Knowledge Mining Sources

  3. Knowledge Progression & Selection 3 Reference Compounds > 20K ►2D-Topological analogues ►Kohonen-based modeling ► BBB profiling CNS Library >17K ►2D-clustering procedure ► isosteric and bioisosteric morphing ► singeltones assignment ► >600 Templates Design ►Focus on novel chemistry ►MedChem Filters FOCUS ON NOVEL CHEMISTY CNS-active agents claimed since 2010

  4. Reference Compounds (Examples) Disclosed since 2010

  5. Methodology for Compound Selection Kohonen-based in silico modeling Ref cmpds: >600 molecules with exp. determined BBB permeability BBB Permeability av. classification power: 87% Descriptors: MW, LogP, HBA, HBD, Sp3, Zagreb, PSA, Ss GREEN – BBB(+) ref cmpds BLUE – BBB(-) ref cmpds Points – compounds from CNS library. More than 90% are localized in BBB(+) areas or in proximity to the BBB(+)-associated neurons of high priority

  6. Descriptor Distributions 6

  7. Validation of CNS LibraryChemDiv’s Design & Activity (PubMed Examples)

  8. CNS Library Statistics Diversity in Heterocycles: 1085 unique heterocycles Clusters (Tanimoto metrics, min cmpds per cluster – 10, similarity threshold 0.6): 397 Singeltones: 11245 Av. structures in cluster: 15 Screens: 11938 Diversity: 0.85 Basic aliphatic nitrogen: 42.5%cmpds Diversity Plot

  9. Examples of Scaffolds 11

  10. Examples of Compounds 12

  11. Thank you

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