May, 2008 Presenting: Szabolcs Csepregi The ChemAxon Markush project overview and development discussion

Contents What is a Markush structure Goal of ChemAxon Markush project Summary of current functionality Planned features towards patents Development discussions roundtable

What is Markush structure A description of compound classes by generic notation: –R-groups (substituent variation) –Atom, bond lists –Repeating units (link nodes and groups) –Position variation (variable point of attachment) –Homology variation (e.g. alkyl, aryl) –Conditions for generic features: occurrence lists, dependency, etc. Used for description of: –Patent claims –Combinatorial libraries

ChemAxon Markush project Goals: –Extend structural search capabilites to combinatorial Markush structures –Markush enumeration Complications: –Practical examples may be very complex, methods using explicit enumeration may be impossible –Extension of current molecular formats (generic features) Timeline –Pilot study started in 2005 Q4, –First prototype shown at UGM, 2006 June –Released in JChem 5.0, 2008

Current functionalities – features Combinatorial Markush structure handling Markush features handled in search & enumeration: –R-groups (nesting to any depth) –Atom lists –Bond lists –Link nodes –Position variation (JChem 5.1, 2008 Summer)

Current functionalities – Enumeration Markush enumeration plugin –Full enumeration –Selected parts only –Random enumeration –Calculate library size: exact size of huge Markush libraries arbitrary precision or Magnitude

Current functionalities – Enumeration From JChem 5.1, 2008 Summer: Coloring: scaffold and each R-group parts get different colors Alignment: as original scaffold

Current functionalities – Markush database tables Available in JChem Base and Instant JChem Search in the Markush library space of combinatorial Markush structures –No enumeration involved – can handle very complex Markush structures (tested up to 10 40, but no explicit limits were built in.) –Search types: Substructure Exact structure (contained in the Markush library) Exact fragment Perfect (same Markush structure) –Stereochemistry, query atoms, bonds, query properties: Aromatic/aliphatic atom, ring atom and bond, chain bond, number of bonds handled

Current functionalities – reduction Markush structure reduction to display substructure hits: All matchings of the query to the Markush structure are reduced into less generic structures. (Generic parts overlapping the hit are expanded.) Example: Markush Reduced hit library structure + Query

Integration in Instant JChem Markush tables: create, import, insert, search Show / hide R-groups for Markush table views Markush enumeration / hit reduction dialog

Example web application Uses Marvin applets Markush search, insert, import, enumeration, coloring, Markush reduction integrated

Recent improvements in drawing Zoom to scaffold, R-group definitions or selection Repeating unit with repetition ranges

Planned features towards Patents Markush features (drawing, search & enumeration): Homology variation (using predefined generic atoms - alkyl, aryl, etc.) –Properties (# of atoms, branching points, # of heteroatoms, etc.) Multiple graphical attachment points of R-groups Repeating units with repetition range (repeating groups) Bridged definition of multiple R-atoms R1, R2= H, CH3, NO2 or together form a ring

Planned features towards Patents Search Markush structures in Markush tables (Markush on query side) –Is there an overlap between libraries? –What is the overlap?

Development discussions We plan to work closely with publishers during development to provide the right tools for patent Markush data. Are these tools or a combined offer (content + tools) useful for you or your organization? –What type of usage do you envision? – departments, types of usage –Portal vs. in-house installation? In-house or purchased data? etc. What other functionalities would you like to see? Interested in evaluation/collaboration? –or providing test data?

Development discussions Thank you!