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CNS BBB Library

CNS BBB Library. ChemDiv Inc. PubChem Database. Thomson Integrity. SciFinder. Protein Data Bank. Scientific publication & Patents (2010-2015). Knowledge Mining Sources. Knowledge Progression & Selection. 3. Reference Compounds > 20K. ► 2D-Topological analogues

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CNS BBB Library

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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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