Demonstration of

ChemAxon's Markush Technology

Wei Deng (David)

ChemAxon UGM

Sep 26th, 2012

Boston

Start from a Patent (US4806538)

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Extract All Structures from a Patent

• Document to Structure

– When the patent document is available

– Works on Image PDF

• Chemicalize.org

– Full text available online

– Faster than D2S sometimes

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Demo: Extract Exemplified Structures from a Patent

• Find patent full text online

• Copy and paste the URL into Chemicalize

• Download all structures

• Import all structures into Instant JChem

• Do a simple filtering to remove non-

exemplified structures

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• Query atom

• any, metal, hetero ...

• Atom topology (ring, chain)

• Stereochemistry (E/Z, tetrahedral)

• Aromatic, aliphatic atoms

• Substitution count

• Block substitution (s*)

• H count

• Explicit H full support

• Ring bond count

• Isolate ring on atoms (rb*)

Additional Markush Query Features I

On Atoms

Additional Markush Query Features II

• Bond topology (chain/ring)

• Equal homology translation

• Broad translation switchable

• Simple R-group queries

On Bonds

and other ...

Demo: Generate a Markush Structure

• R-group decomposition

on exemplified structures

based on the Markush core

• Generate a Markush structures

• Add additional R-group definitions

• Enumerate the library and save as a local

file

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• R-groups

• Multiple attachment points

• Up to thousands of R-group definitions

• Nested R-groups (any depth)

• Atom lists, bond lists

• Position variation bond

• Link nodes and repeating units

Markush Structure Features I

• Homology groups (MMS: superatoms, CAS: generic definition)

(property, growing list)

• Clean graphical representation

• All features supported in MRV format

Markush Structure Features II

Demo: Analyze Enumerated Library

• Import enumerated structures back into IJC

• Similarity search 1 - dissimilarity("PF","CCOC(=O)C1=CN=C2C=CC3=C(C(C)=C(C)N3C)C2=C1O")

• Overlap Analysis

– Between the exemplified structures and the

Markush enumerated chemical space

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ChemAxon - Thomson Reuters

Markush project history

1987 Thomson Scientific (Derwent) starts indexing Markush structures

(in collaboration with Questel & INPI)

1998 INPI & Derwent Markush databases merge to form MMS

(Merged Markush Service)

2000 ChemAxon launches first version of JChem Base

2005 Chemaxon starts working on Markush technology

2008 Markush search & enumeration first release in JChem 5.0

2010 Markush DARC file format support in JChem 5.3

2012 Full MMS searchable with JChem 5.5-5.11

Search the Full Patent Database

• Complete patent database from Thomson Reuters dated back

to 1987

– VMN (Markush structures)

– DCR (Exemplified structures)

– DWPI text (non-structural information)

• Data stored in Amazon Cloud with Powerful virtual machine,

secure connection and confidential search

• Useful new features:

– Export exemplified structures

– Retrieve patent document

– Enumerate Markush structures and output result

– Notation

• Batch search of multiple queries

• Constantly improving search performance

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Demo: Patent Database Search

• New search interface overview

• Customized buttons:

– Export exemplified structures

– Retrieve patent document

– Notation view

• Markush enumeration interface

• Structure search

– Improved R-group hit visualization

– Markush viewer

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Acknowledgements

JChem base, Markush and IJC

Helpers - Cartridge, Markush Viewer,

Support, Marketing

• Steve Hajkowski

• Brian Larner

• Don Walter

• Gez Cross

• Tony Ferns

• Tim Miller

BACKUP SLIDES

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Full Text Online

• Google Patent number (US4806538)

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Paste Full Text URL to Chemicalize

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Download All Structures

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Import All Structures in Instant JChem

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Add “Lipinski Rule of 5” Chemical Term

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Filter Structures

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Save as Permanent List

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Query Builder

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Generate a Markush Structure

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Add new R3 Fragment

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Enumerate Markush Structure

• Save all structures to a local file

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Import Enumerated Structures to IJC

• Add a new data tree and structure table

• Import enumerated structures from the

Markush to this data tree

– Duplicate filter on

• Similarity calculation with “Key Compound”

SMILES: CSC[C@H]1NC(=O)[C@@H](CC2=CN(C)C3=CC=CC=C23)NC1=O

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Similarity Search with “Key Compound”

Similarity_Command.txt

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Overlap Analysis

• Between the exemplified structures and the

Markush enumerated chemical space

• Stereochemistry OFF

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Current technology in use

Thomson Reuters content: Merged Markush Service, DCR, DWPI

ChemAxon software UI: Instant JChem

Current technology in use

Thomson Reuters content: MMS, Derwent’s Chemical Resource, DWPI

ChemAxon software UI: Instant JChem

Current technology in use

Thomson Reuters content: MMS, DCR, Derwent World Patent Index

ChemAxon software UI: Instant JChem

Export Exemplified Structures

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Retrieve Patent Document

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Add Notes

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Notes Overview

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Batch Search of Multiple Queries

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