Reprint f rom Molecular Connect ion Vol 25 No 1 2007

he amount and complexity ofinformation acquired and investi-gated during lead discovery and

optimization often creates daunting information bottlenecks for researchers.The new MDL® Isentris® client helpsmedicinal chemists, synthetic chemistsand information specialists dynamicallyaccess and share information from multiple sources in single, integrated

views, greatly enhancing their ability tohandle large amounts of data and to maketimely decisions based on its analysis.

As shown in Workflow scenario 1, theretrosynthetic scheme display availablewith the new Reaction Planner in MDLIsentris makes it easy to investigatedifferent synthesis pathways and quicklydecide on the best synthesis plan afterconsidering all appropriate data.

Workflow scenario 2 shows howcombining Microsoft® Excel® andIsentris® functionality enables researchersto extract data from a corporate knowledge database into Excel andmanipulate the data to discernStructure-Activity Relationships (SAR),comfortably working in the familiar Excel environment that can accelerateresearch.

T

Removing theinformation bottleneck in R&D with

MDL® Isentris®

Reprint f rom Molecular Connect ion Vol 25 No 1 2007

Step 1: Query and review results

Run a substructure reaction search inMDL Isentris with 1,4 benzodiazepineas the product against all commercialsynthesis databases (Figure 1). Propri-etary reaction data can also be includedin a single reaction search with assis-tance from Elsevier MDL (see ‘MoreInformation’ section at end of article).

Review the summary of results andselect reactions of interest for furtherinvestigation (Figure 2).

Step 2: Review reaction details

The reaction details page (Figure 3) forany given reaction provides a wealth of information including access to primary literature references (Figure 4),retrosynthetic scheme details, reaction conditions, Safety Data Sheet(SDS) information and more.

Figure 1: Run a singlesearch over multiple synthesis databases.

Figure 3: Reaction details for aselected reaction of interest

Figure 4: Link to, review and print primary reaction literature.

Figure 2: Enter a target structure in Isentris and immediately viewpreparations of the structure gathered from reaction and syntheticmethodology databases.

Workflow scenario one

More information

Contact Elsevier MDL Consulting for assistance in configuring access to proprietary reaction data from MDL Isentris client. www.mdl.com/contact

See interactive videos on MDL Isentris client. www.mdl.com/videos

To receive monthly updates on upcoming events, sign up for the Elsevier MDL Insight eNewsletter. www.mdl.com/enewsletter

Figure 7: Explore alternative reaction schemes from many sources.

Step 3: Determine commercial availability and/or precursor reactions

Reaction data displayed in MDL Isentris showswhether components of a reaction are commerciallyavailable, so that chemists can quickly determinewhether a chosen synthesis is necessary, cost-justified or prohibitive. Direct links to the MDL® AvailableChemicals Directory (MDL ACD) database provide comprehensive sourcing information (Figures 5and 6).

Step 4: Review and explore routes of synthesis

The Reaction Planner, a visual synthesis planning toolincluded in MDL Isentris, automatically generates synthesis pathways for products or reactants of interest.The system investigates multiple reaction databasesand suggests appropriate reaction steps for creating the product or reaction. A synthetic chemist can thendecide which path to take using data such as citation,yield, reagents, condition and reactant availability (Figure 7). This unique functionality can savechemists hours in planning syntheses and eliminatethe need to search several databases one at a time.

Step 5: Report reaction plan

Chemists can use the Reaction Planner to build reportsfor chosen reaction pathways (Figure 8). Researcherscan create reports on reference material, health andsafety data, compound availability and synthesis details.The result is less leg work for researchers, fasteranswers to questions and better support for decisions.

“The retrosynthetic scheme display enables chemists to quickly and efficiently determine the suitability of asynthetic route to target molecules,” says Dr. TerryWright, Senior Product Manager of MDL SyntheticMethodology Products. “Retrosynthetic schemes also provide a behind-the-scenes search for potentialstarting materials from reaction records.”

Figure 6: Creating a compound acquisition report in a shareable andeditable format is easy with MDL Isentris.

Figure 5: From MDL ACD, you can cherry-pickpackages from chemical suppliers.

Reprint f rom Molecular Connect ion Vol 25 No 1 2007

Figure 8: Build a reaction plan from precursor steps.

Reprint f rom Molecular Connect ion Vol 25 No 1 2007

“Isentris for Excel advances discovery by combining the power and usability of Isentris and Excel into one environmentwhere researchers can freely explore,

analyze, manage, present and share researchdata,” says Isentris Product Manager, Dr. Dominic John. “Researchers can extractdata from multiple sources into Excel. They

can then use the rich functionality of Excelto compute, filter, pivot and graph datawith the familiar freedom Excel provides.”

Expanded power to use Microsoft® Excel® software

In Figure 9, a researcher wants to create a listof compounds to be submitted for analysis in Excel. The left hand pane provides all theassociated data the researcher can query.Dragging and dropping the fields to the righthand pane builds the desired query.

Isentris for Excel enables researchers to preview and refine searches before placingthe data in a spreadsheet, so when theybegin collating and sorting they have precisely the data they want.

Researchers can share complex search andfiltering strategies captured by the history tree with colleagues (Figure 10). They canalso re-run the searches to provide their project team with information updates. In this scenario, researchers have imported lists of known false negatives and removedthese from the current hits of interest. Theyhave then cherry-picked the list to create the SAR results to take to Excel.

The right-hand pane in Figure 10 provides apreview of the data. Researchers are free todrag-and-drop available information from theirdata sources into this view before extractingthe data to Excel. Researchers can quicklycollect the information they need for theirSAR analysis or reports in Excel.

Next the researchers use Isentris for Excel’sRgroup decomposition and Excel Pivot functionalities to examine how various substituents at specific locations on the molecule affect inhibition in the biologicalassay (Figure 11). The goal is to find the combination of substituents with thegreatest inhibitory effect.

Innovative, out-of-the-box functionality inMDL Isentris is helping scientists accomplishtasks that were previously time-consuming orimpossible. For more information on findingthe information you need with MDL Isentris,contact your Elsevier MDL Account Manageror submit a request for information atwww.mdl.com.

Figure 9: Search and browse environment where researchers can run searches, browse results,perform Rgroup decomposition and make decisions about the data they wish to extract to Excel.

Figure 10: The history tree in the left-hand pane enables researchers to track their search and decision points.

Figure 11: Data enriched with Rgroup decomposition

Workflow scenario two

MDL, Isentris and Available Chemicals Directory are registered trademarks or trademarks of MDL Information Systems, Inc.(’Elsevier MDL’) in the United States and/or other countries. Microsoft and Excel are registered trademarks of the MicrosoftCorporation in the United States and other countries. The name ‘Isentris for Excel’ is referential only, and implies no company orproduct endorsement from, or affiliation with, the Microsoft Corporation. All other product and company names mentioned hereinmay be trademarks or registered trademarks of their respective holders. © Copyright 2007 Elsevier MDL. All rights reserved.

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