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Tips and Tricks Chemistry

Tips and Tricks Chemistry. November 2005. Chemical Abstracts Service, CAS. 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

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Tips and Tricks Chemistry

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  1. Tips and TricksChemistry November 2005

  2. Chemical Abstracts Service, CAS • 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

  3. Chemical Abstracts Service, CAS • 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

  4. 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

  5. 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

  6. Unique and comprehensive databases: Creating Content

  7. 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

  8. Agenda • Structure searching features • Substance viewer features • Get related feature • Reaction searching in SF2006 • Novel compound or freedom to operate?

  9. 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

  10. 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)

  11. Searching a stereo structure

  12. Automatic analyze by stereo

  13. 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. Absolute stereo answers

  14. 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. Absolute stereo mirror image answers

  15. 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. Relative stereo answers

  16. 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. Stereo answers not matching

  17. 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. No stereo in answer structure

  18. Three types of structure searches • Exact search • Substructure search • Similarity search • Additional filters

  19. Example: Warfarin (81-81-2)

  20. 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

  21. 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

  22. 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

  23. Substructure is very different from similarity search Unique answer for substructure search Unique answer for similarity search

  24. 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

  25. Example query structure X = any Halogen R1=O/N You may define an R-group as the VAP node; you may define multiple VAP nodes to the same ring system

  26. Classes of substances Substance class or the type of study can be selected using the additional options before the search

  27. Analyze your answers

  28. Real atom attachment Makes a distinction between C and Ak and Cb Select option to refine your search

  29. Real atom attachment (2) Halogen attachments are in addition to the X drawn at a variable position Cannot analyze a node that is part of a repeating group.

  30. Variable node analyze Compounds may have additional halogen substitution on the phenyl ring, so numbers may be higher

  31. Precision analyze Conventional structure match exactly Closely assoc. tautomers have 1 bond shifted or created Loosely assoc. tautomers have bigger variation Make a selection to remove unwanted answers

  32. 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.

  33. 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

  34. Refine substances

  35. 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

  36. Agenda • Structure searching features • Substance viewer features • Get related feature • Reaction searching in SF2004 • Novel compound or freedom to operate?

  37. Search options from substance viewer = Same as Get References = View 3D (Accelrys software) = Commercial suppliers = Search exact compound in a reaction explore = Regulatory information

  38. Exact reaction link: specify the role in the reaction Could work very well for reactions in water or reactions with a specific catalyst

  39. Exact reaction link results Leads to 871 reactions from 258 documents

  40. Get Reference Link Records from 1907-1966 are not associated to any roles

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

  42. Agenda • Structure searching features • Substance viewer features • Get related feature • Reaction searching in SF2004 • Novel compound or freedom to operate?

  43. 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

  44. RC metathesis (2000-2005)

  45. Limit the related substances that are indexed as products

  46. All indexed products We are interested in compounds with a ring 10-30 atoms

  47. All indexed products

  48. 411 large rings as products

  49. Get References again SciFinder didn’t remember the original search at this point

  50. Hard to do this search starting with all large ring compounds

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