May, 2008

Presenting: Szabolcs Csepregi

The ChemAxon Markush projectoverview 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 structureA 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 projectGoals:

– 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 1040, 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 PatentsMarkush 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!