CNS BBB Library ChemDiv Inc..

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Presentation transcript:

CNS BBB Library ChemDiv Inc.

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

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

Reference Compounds (Examples) Disclosed since 2010

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

Descriptor Distributions 6

Validation of CNS Library ChemDiv’s Design & Activity (PubMed Examples)

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

Examples of Scaffolds 11

Examples of Compounds 12

Thank you