PreviewTips and Tricks

Chemistry

November 2005

2006 Edition

• CAS... we are scientists, creating and delivering the most complete and effective digital information environment for scientific research and discovery

• CAS is a self-sustaining division of the American Chemical Society

• CAS employs 1250 staff members in Columbus, Ohio

Chemical Abstracts Service, CAS

2006 Edition

• CAS Content... the world’s largest collection of chemical and related scientific information for the research community including:

• Most authoritative collection of substance information available

• Worldwide coverage of current and comprehensive journals and patents

Chemical Abstracts Service, CAS

2006 Edition

SciFinder content• CAplus from CAS with 25.6 mil references,

abstracts and detailed indexing from 1907-– Sources: 9,500 journals, patents from 50 offices,

internet journals and preprint servers, conferences, theses and report

– Citations from journals and patents 1997-

• Registry from CAS with ~83.5 mil substances– Small molecules, biosequences, polymers,

inorganics, alloys, complexes

– Single compounds have experimental data from InfoChem and CAS and have calculated data from ACDlabs

2006 Edition

SciFinder content• CASREACT from CAS with 9.2 mil single

and multi-step reactions– From journals and patents, 1907-

• ChemCats from CAS with supplier data from 914 catalogues– Screening compounds, fine chemicals and some

bulk for 8 mil compounds

• Chemlist from CAS with regulatory information

• Medline from NLM with 15.5 mil records from 1950-– Sources: 3200 journals

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Unique and comprehensive databases: Creating Content

2006 Edition

SciFinder benefits• Easy access to largest database covering

chemistry and related sciences relevant to drug discovery– Solid look at IP status for substances and biosequences– Advanced analysis tools to handle larger answer sets in

a creative way– Powerful alerting due to high currency of the

information– Content and interface designed by scientists for

scientists– Big time save not having to run experiments that are

well documented in the literature– Big money save not having to continue projects that

have already received patent protection by competition

2006 Edition

Agenda

• Structure searching features

• Substance viewer features

• Get related feature

• Reaction searching in SF2006

• Novel compound or freedom to operate?

2006 Edition

Structures in SciFinder

• The CAS Registry file contains over 26.4 million small molecules or small sequences

• At present over 6.2 mil structures have defined stereochemistry in the structure

• Stereochemistry is not available for certain classes of compounds– Coordination compounds, allenes and

cumulenes (not searchable), stereo bond between two ring systems

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Structure searching in SF

• SciFinder and Scholar use a broader structure search, which includes tautomers and related compounds– Double bond geometry may be impacted

by a tautomer– Carbohydrates and hemiacetals may

have different configurations (included as hits)

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Searching a stereo structure

2006 Edition

Automatic analyze by stereo

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Absolute stereo answers

• These answers will have the R-stereoisomers pictured either with the bond into the plane or out of the plane. The author must have provided complete configuration of the stereo node.

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Absolute stereo mirror image answers

• These answers will have the S-stereoisomers pictured either with the bond into the plane or out of the plane. It is also called the “meso” compound of our structure.

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Relative stereo answers

• These answers will have the stereochemistry defined relative to another chiral center. The stereochemistry could be shown as R,S or S,R being identical for relative stereoisomers. Relative stereo answers can be useful for structure searches with multiple chiral centers.

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Stereo answers not matching

• These answers do not have the desired stereochemistry at the node we searched, but there is stereochemistry elsewhere in the molecule. In this case it is the Z double bond geometry. If we had searched a compound with R,R bonds, we would also see the R,S and S,R answers in this set.

2006 Edition

No stereo in answer structure

• These answers will be completely flat structures (or racemic mixtures) with no other stereochemistry in the structure that was searched. Some compounds with stereochemistry in the name may still be found in this set.

2006 Edition

Three types of structure searches

• Exact search

• Substructure search

• Similarity search

• Additional filters

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Example: Warfarin (81-81-2)

2006 Edition

Exact structure search• Retrieves 135 answers

– 47 single compound substances• 14 unlabelled compounds

• 33 radio-labelled compounds

– 88 salts and mixtures

• Of these there are 26 tautomers

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Substructure search

• Retrieves 613 answers– 424 single compound substances

• 375 unlabelled compounds

• 49 radio-labelled compounds

– 189 salts and mixtures

• There are 57 tautomers

• There are 38 compounds with a mol weight of >500

• All 135 answers of the exact search are included in this answer

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Similarity search

• Ranks the compounds according to their Tanimoto similarity score based on structural attributes

The 109 compounds with a score of ≥ 99 are the same as the 135 exact compounds minus the 26 tautomers

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Substructure is very different from similarity search

Unique answer for similarity search

Unique answer for substructure search

2006 Edition

Additional analyze features

• Analyze by real-atom attachment– Useful to see a breakdown of the types of

substitution at different nodes of your query

• Analyze by ring skeleton– Beware this only analyzes the rings that

are part of the query structure, not any ring

• Analyze by precision– Separates out the exact structure, close

and loose tautomer answers

2006 Edition

Example query structure

X = any HalogenR1=O/N

You may define an R-group as the VAP node; you may define multiple VAP nodes to the same ring system

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Classes of substances

Substance class or the type of study can be selected using the additional options before the search

2006 Edition

Analyze your answers

2006 Edition

Real atom attachment

Makes a distinction between C and Ak and CbSelect option to refine your search

2006 Edition

Real atom attachment (2)

Cannot analyze a node that is part of a repeating group.

Halogen attachments are in addition to the X drawn at a variable position

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Variable node analyze

Compounds may have additional halogen substitution on the phenyl ring, so numbers may be higher

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Precision analyze

Conventional structure match exactlyClosely assoc. tautomers have 1 bond shifted or createdLoosely assoc. tautomers have bigger variationMake a selection to remove unwanted answers

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Precision analyze: close tautomer

This compound is considered a close tautomer, because the second double bond in the ring, could also be drawn as a keto substituent, which would have matched the query.

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Ring skeleton analyze

Option to analyze only the shape, the shape and atoms, the shape, atoms and bonds or rings that have at least one atom in common with the query structure

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Refine substances

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Refine: want a maximum of 2 halogens anywhere on the phenyl

Replaced the specific phenyl with a generic Cb node. One X is drawn; second optional halogen is defined as R2=H,X. The tool “lock substitution” prevents additional substituents

2006 Edition

Agenda

• Structure searching features

• Substance viewer features

• Get related feature

• Reaction searching in SF2004

• Novel compound or freedom to operate?

2006 Edition

Search options from substance viewer

= Same as Get References

= View 3D (Accelrys software)

= Commercial suppliers

= Search exact compound in a reaction explore

= Regulatory information

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Exact reaction link: specify the role in the reaction

Could work very well for reactions in water or reactions with a specific catalyst

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Exact reaction link results

Leads to 871 reactions from 258 documents

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Get Reference Link

Records from 1907-1966 are not associated to any roles

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Get Reference link

Not all publications in Chemical Abstracts are selected for CASREACT !! (only 258 out of 480 with reaction indexing)

2006 Edition

Agenda

• Structure searching features

• Substance viewer features

• Get related feature

• Reaction searching in SF2004

• Novel compound or freedom to operate?

2006 Edition

Get related feature

• Starting your search from a text explore• Obtain all the substances indexed in the

reference list – Answer set must be <1000 references

– Refine with structure fragments or calculated properties

• Obtain all reactions indexed from the listed references

• Obtain the older cited references or forward citing references– Answer set must be <500 references

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RC metathesis (2000-2005)

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Limit the related substances that are indexed as products

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All indexed products

We are interested in compounds with a ring 10-30 atoms

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All indexed products

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411 large rings as products

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Get References again

SciFinder didn’t remember the original search at this point

2006 Edition

Hard to do this search starting with all large ring compounds

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Agenda

• Structure searching features

Substance viewer features

• Get related feature

• Reaction searching in SF2004

• Novel compound or freedom to operate?

2006 Edition

Reaction Searching in SF/SFS

• CASREACT database offers full reaction searching– Reactions from CAS cover 1985-present– Reactions from InfoChem 1974-1991– Common enzymatic reactions– Reactions from INPI 1840-1984

• Contains new/novel reactions not all reactions

• Details of solvents, catalysts, reagents not routinely indexed in CAplus

2006 Edition

Searching in CASREACT

• By structure fragments for products, reactant/reagents– Indicate reacting bond (reaction site)– Indicate reaction map (identical atom in

reactant and product)– Compounds indexed as solvents or catalysts

cannot be searched by structure

• By functional groups– Indicate role: product, reactant, reagent, or

non-reacting

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Searching by Functional Groups

Non-reacting role allows for searching reactions “in the presence of” a group

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Reaction Searching in SF/SFS

• Registry and CAplus– All preparative literature with most reaction

participants indexed with CASRN– Solvents, catalysts only indexed if novel or

emphasized by the author– Pre-1967 literature partially indexed by CAS

RNs• Use older names or formulas for the substance

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Coupling reaction of dialkylphenols

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Reaction example• Run a closed or open structure search

• New up front limitation options

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Reaction example• As soon as you move over any substance in the

reaction display the formula or the structure becomes a button to request more information

Click substance

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Reaction example

Information from patents and journals

Single step andmulti-step reactions; click the microscope for intermediate reaction steps

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Reaction example

Scroll down for all steps; the mouse wheel is now enabled for power-scrolling

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View options

Get only one sample reaction per documentHypertext link to other query hit reactions from that document

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Analyze Reactions

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Click on a substance for more info

Commercial availability or retrosynthetic steps

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Reaction example

• Reactions will search the compound itself as a reaction participant

• References will show the list of references limited by the usual roles

• Substance details for the Registry record• Commercial sources from Chemcats• Regulatory info from Chemlist

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No commercial availability

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Reaction example

Retrieves new reactions with this substance as the reaction product

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Reaction Information

• Creates an infinite path of reaction browsing

• Can use the [BACK] button to go to the previous reaction answers

• Is only available to SF subscription users and SciFinder Scholar users

2006 Edition

Getting references and abstracts

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References from the reactions

2006 Edition

Reaction searching

• Remember, CASREACT has a focus on novel reactions

• For a more comprehensive preparative answer, search the substance in Registry and refine by the preparation role

• If necessary search by names or by CAS number without roles for information from 1907-1966

2006 Edition

Reactions in Registry/CAplus

2006 Edition

2006 Edition

Compare to 8 documents fromour reaction search !!

More comprehensive answers

2006 Edition

Searching for specific catalysts

• Catalysts and solvents are not structure searchable in the reaction explore

• Possibility to search them via the exact, substructure or similarity search and select “Get Reactions” with the appropriate reaction role

• Example: finding reactions catalyzed by similar compounds to Proline, a well known organocatalyst

2006 Edition

Running a similarity search on Proline

2006 Edition

Selecting similar compounds, but not Proline itself

2006 Edition

Selecting similar compounds, but not Proline itself

2006 Edition

Catalysts may be given as a CAS RN

2006 Edition

Agenda

• Structure searching features

• Substance viewer features

• Get related feature

• Reaction searching in SF2004

• Novel compound or freedom to operate?

2006 Edition

Chemical patent protection can be very complex

• SciFinder provides access to 85 mil chemical compounds

• Specific substances from patent claims and examples have been registered

• Broad “Markush” claims in patents can describe thousands of compounds

• For freedom-to-operate searching you need to have a search done for prophetic compounds hidden in large Markush claims

2006 Edition

Markush answers

• A search in CAS’ Marpat database revealed compound theoretically matches the Markush definition in 7 patents– e.g., WO2005058292 by AstraZeneca

2006 Edition

Markush answers• If these are answers you need to know,

contact your information professional, a patent office, or CAS’ Science IP

PreviewTips and Tricks

Chemistry