developing cas products for substructure searching...

Developing CAS Products for Substructure Searching by Chemists

Linda Toler

®

Kurt Loening Symposium, August 20012

Developing CAS Products for Substructure Searching

� Evolution of the CAS Registry� Development of substructure searching

for CAS products� Future challenges


Evolution of the CAS Registry


Evolution of the CAS Registry

Names and MFs

Fragment Codes and

Linear Notations


Building the CAS Registry

Late 1950’s

Dyson linear notation

Register Number


1959 1965

Registry I Morgan

Connection Table




Sample of a CAS Connection Table

CAS Registry Number: 125417-03-0

Rank # : 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15Atom : C C C C C C C C C O C C C C CBond to: 8 8 1 4 4 4 5 5 6 6 7 7 11 13 10 12 8 14 9 15Bond is: -- -- -- -* -* -* -* =* -* -* =* -* -* -* RC -* RC -* RC -*Mol Form: C14 H20 O

ooo


1959 1965


- Covered organic molecules- CAS Registry Number- “Normalized” ring bonds

Registry I Morgan

Connection Table


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1959 1965


1968

Registry II

- Covered all compound classes- Standardized stereo descriptors- “Normalized” tautomer bonds

Registry I Morgan

Connection Table



1959 1965


1968

Registry II

1973

Registry III

Streamlined internal handling and display of connection table information

Registry I Morgan

Connection Table



CAS Registry Handles New Chemistry

� Superconducting substances of the 1980s� registered ranges of element compositions � registered non-stochiometric compositions

RN 301237-56-9 REGISTRYCN Barium calcium mercury rhenium oxide (Ba4Ca1.5Hg2Re0.5O8.5)

(9CI) (CA INDEX NAME)MF Ba . Ca . Hg . O . ReAF Ba4 Ca1.5 Hg2 O8.5 Re0.5

Component | Ratio | Component | | Registry Number

==============+====================+===================O | 8.5 | 17778-80-2Ca | 1.5 | 7440-70-2Ba | 4 | 7440-39-3Re | 0.5 | 7440-15-5Hg | 2 | 7439-97-6



� “Textual” descriptions of stereochemistry became outdated and difficult to use � Upgraded connection tables to include stereo

parityRN 350021-96-4 REGISTRYCN Benzeneethanol, .beta.-[(2-furanylmethyl)[(1R)-1-methyl-2-

propynyl]amino]-, (.beta.R)- (9CI) (CA INDEX NAME)

Absolute stereochemistry.



� Emphasis on biomolecules mushroomed in the 1990’s� Macromolecules represented via one letter

codes for their basic building blocks

RN 349518-49-6 REGISTRYCN G protein-coupled receptor 35 (mouse fragment) (9CI)

(CA INDEX NAME)FS PROTEIN SEQUENCESQL 93

SEQ 1 AHMVWANLAV FVICFLPLHV VLTVQVSLNL NTCAARDTFS RALSITGKLS

51 DTNCCLDAIC YYYMAREFQE ASKPATSSNT PHKSQDSQIL SLT


CAS Registry Today

World’s Largest, Most Diverse Substance Collection

Polymers3%

Alloys2%

Coordination compounds

5%

"Inorganics"2%

Sequences 43%"Organic"

45%

>32,400,000 records


CAS Registry Today

Know for the Quality and Integrity of Its Structural Information

<Pictures of CAS Registry staff>


� CAS Registry Numbers are used throughout the world to identify substances

– Databases– Handbooks– Government regulatory agencies– Consumer products

CAS Registry Today

An International Resource for Substance Identification


CAS Registry Today

Largest publicly available structure searchable compound collection

Connection Tables>18.3M

Biosequences>13.9M


Substructure Searching in the CAS Registry


“Substructure” Searching Can Mean Different Things

� Compounds with structures� answers contain specified structural

characteristics� Alloys and non-stochiometric inorganics

� answers are compounds of various composition ranges

� Protein and nucleic acid sequences� answers are sequences containing the same

string of building-block residues


“Substructure” Searching Can Mean Different Things

� Compounds with structures� answers contain specified structural

characteristics


� Query Input� Easy-to-use query input mechanism� Flexible query definition options

-C; -CH3; R=Me, Et, or n-Pr; Ak� Retrieval

� Quick, comprehensive retrieval of all matching compounds

� Tools for dealing with registration “idiosyncracies”

What Should a Good Substructure Search System Offer?


Query Input Methods Evolved Over Time

� Screens � “Commands”� Drawing


Query Input via Screens

=> SCREEN 1867 AND 42 1199 AND 745 AND 1033 AND 1139 AND 1142 AND 1707 AND 1831

1867 TR DDDDDD42 AS C-C*C*C-C-O

1199 AA C -1C -1O -2O745 BS A *2A *1A *1A *1A *1A *1A


Query Input via Commands

=> STR:GRAPH R6, 1 C1, 3 C1, 4 C3, 5 C1, 6 C1, 9 C1:NODE 8 OH, 7 14 10 O, 11 12 13 AK :BOND ALL S, 1-7 2-3 9-14 D:RSP I, CON 11 12 13 E1, DIS

=> STR:GRAPH R6, 1 C1, 3 C1, 4 C3, 5 C1, 6 C1, 9 C1:NODE 8 OH, 7 14 10 O, 11 12 13 AK :BOND ALL S, 1-7 2-3 9-14 D:RSP I, CON 11 12 13 E1, DIS

CC

C

CC

C

2O 1

10

OH3 8

C O Ak4

14

11Ak

5

12

Ak6

13

O

9

7


Query Input Offline via Drawing



-C; -CH3; R=-CH3, Et, or n-Pr; Ak� Retrieval




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The CAS Substructure Search System Evolved Over Time

1980

Substructure searching via

screens

1960’s

Development of Prototype SSS system

1981


structure diagrams

≈


Substructure Searching Is a Two-step Process

“Iterative” Search

Structure Compilation

Screen Generation

Screen Search

Candidate Answers


The CAS Substructure Search System Evolved Over Time

1960’s 1980


screens

Development of Prototype SSS system

1981


structure diagrams

1990

Substructure searching

extended to Markush

≈

Markush specification:

R= unsaturated alkyl of 1-4 carbon atoms

R = methyl, ethyl, or n-propyl

Query structure:

C??

Ak ??







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Structural Representations Present Search Challenges

� Salts



� Enol-keto tautomers



� Pyrazoles


CAS Designed Search Tools/Systems to Address Structuring Conventions

� Query input tools to allow for all relevant structural characteristics

� Algorithms that handle structural representation conventions


STN Searchers Have a Variety of Tools To Allow for Different Structural Representations

Answers:

Unspecified bonds

Connectivity

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SciFinder Search Algorithms Handle Many Structure Conventions

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What Does the Future Hold?


� Chemical substance retrieval� Similar structures � “Shape” matching

� Converting information into knowledge� Tools for discovering “structural

relationships”� Tools for mining the diversity in the CAS

Registry for relevant substances

Customers Want More!


"To remain relevant to the work of scientists in the twenty-first century…., CAS information technology must keep pace with the evolution of the chemical sciences, including related biological sciences, and remain adaptive enough to accommodate the unexpected and exciting developments that undoubtedly lie ahead."

From: “Chemical Abstracts Service Information System", Encyclopedia of Computational Chemistry, John Wiley & Sons, November 1998.

What Does the Future Hold?


Acknowledgements

Weisgerber, D. W. (1977) Chemical Abstracts Chemical Registry System: History, Scope, and Impacts. Journal of the American Society for Information Science 48(4) p. 349-360

Fisanick, W., Amaral, N.J., Metanomski, W.V., Shively, E.R., Soukup, K.M., Stobaugh, R.E. (1998) Chemical Abstracts Information System. Encyclopedia of Computational Chemistry p. 277-315

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