5 Departure – Initial status 2005Chemical Drawing, DB toolsmolecule, reaction and query structruresCustomers needed Markush funcionality, especially patents.
6 What are Markush structures and how to get them?
7 Markush structuresGeneric notation for describing many molecules (= Markush library) in a compact form.Main usage:Combinatorial chemistryChemistry-related patents
8 Markush structures Current features handled: R-groups Atom lists, bond listsPosition variation bondLink nodesRepeating unitsHomology groups (aryl, alkyl, etc.)
9 How to get Markush structures? Drawing – Marvin Sketch
10 How to get Markush structures? Patent literature (VMN format coming in 5.3 – Derwent World Patent Index)
11 How to get Markush structures? Combinatorial chemistry – Reagent clippingReplace reacting group with attachment point (Reactor tool)Turn fragments to R-group definitions (Molconvert tool)Add a scaffold (Molconvert tool)
12 How to get Markush structures? Combinatorial chemistry – R-group decompositionFilter and identify ligands in chemical libraryCreate Markush structure from R-table(R-group decomposition tool)
14 Markush Enumeration Markush enumeration plugin Full enumeration Selected parts onlyRandom enumerationCalculate library sizeScaffold alignment and coloringMarkush codeOptional example homology group enumeration
15 Markush storage & search JChem Base and Instant JChemNo enumeration involvedCan handle complex Markush structures (1040 or more)Substructure and Full structure searchBasic query features supported
16 Markush storage & search Substructure hit visualizationQueryResult in original Markush
17 Markush storage & search Substructure hit visualization: „Markush structure reduction”QueryResult in original MarkushReduced result
18 What’s new Homology groups Import reagent files as R-groups 19 built-in groupsMarvin templates for easier sketchingCustomizable:Examples (for built-in groups),User-defined homology groupsImport reagent files as R-groupsPosition variation and Repeating units
20 Main use cases Patent search hits refining, White space analysis, Markush structure curation,In-house storage of small Markush DB,etc...
21 Under development.VMN import (Derwent World Patent Index) 5.3 – this yearHomology variation queries (narrow translation)Maximum common substructure searchBiased enumerationAll Markush features of .VMN formatOverlap analysis of Markush structuresConditions for Markush variables
22 Future work for the community Lack of open Markush file format standards.Community needs patent Markush data.Call for Markush patent content holders to make data accessible.Solution?InChI or CML(XML) extensions?Open up existing format specifications?Marvin (mrv) format???
23 SummaryMarkush structure storage, search and enumeration at ChemAxon now reaching patent coverageContinuous development, improvements in the pipeline
24 AcknowledgementsDevelopment team: Nóra Máté, Róbert Wágner, Szilárd Dóránt, Tamás Csizmazia, Ferenc Csizmadia, et al.Tim Miller and Linda Clark at Thomson Reuters for useful discussions, help and example .VMN filesMany early adopters and colleagues within the field for suggestions and feedback
25 Interested? We are looking for further early adopters Currently running individual projects with pharma companies to test and enhance functionality.If you are interested, please contact us.