Structure Searching with STN Express

Introduction The REGISTRY database contains chemical substance information. Bibliographic references and abstracts of papers discussing substances retrieved by a structure search are stored in the CAplus database. The L-number generated in the full-file structure search is the key to locating relevant references.

Why Do a Structure Search? Introduction Why Do a Structure Search? There are a number of ways to locate information about a chemical compound: Chemical name Molecular formula Etc. Structure Each access point has unique advantages. Dictionary

Introduction Dictionary Searching by dictionary is a powerful method for retrieving at least broad classes of substances in Registry, useful also in structure searching.

Introduction Dictionary - Chemical name Chemical names may be systematic or trade names. However, systematic names can be complex and difficult to derive: Benzeneacetonitrile, α-[3-[[2-(3,4-dimethoxyphenyl)ethyl] methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl)-

Introduction Dictionary - Molecular formula Many compounds have the same molecular formula: C27H38N2O4 is shared by >250 compounds in the CAS REGISTRY database

Introduction Dictionary - Chemical name, Molecular formula Name, and Molecular formula, fragments, are inside the BI.

Introduction Structure Each compound has an unique structure

Structure-Searchable STN Databases Introduction Structure-Searchable STN Databases A number of STN databases are searchable by structure. The REGISTRY database, produced by CAS, is the world's largest collection of chemical compounds.

Introduction A sample of structure-searchable databases on STN:

Basic Strategy for Structure Searching Introduction Basic Strategy for Structure Searching Locating substance information via structure searching is accomplished in four main steps: Draw the structure Search the structure Display the structure matches retrieved Locate the desired information about the structure matches of interest

Structure Drawing

Structure Drawing Accessing the Structure Drawing Screen The structure drawing screen is accessed via the STN Express main tool bar via the prepare query icon:

Structure Drawing Structure drawing screen has 7 main parts:

Structure Drawing

Structure Drawing Most chemical structures can be drawn using the following techniques: Drawing chains Drawing rings and ring systems Connecting rings and chains Specifying atoms Specifying shortcuts Specifying bonds Erasing and undoing

Structure Drawing When structures are drawn using STN Express tools, the following defaults apply: Atoms in the structure match the element in the current atom box. When the structure drawing screen is opened, the current atom is set to C (carbon). Bonds in the structure match the bond in the current bond box. When the structure drawing screen is opened, the current bond is set to single. PREFERENCES

Structure Drawing Drawing Chains

Drawing Rings and Ring Systems Structure Drawing Drawing Rings and Ring Systems (continued on next slide)

Drawing Rings and Ring Systems Structure Drawing Drawing Rings and Ring Systems

Drawing Rings and Ring Systems Structure Drawing Drawing Rings and Ring Systems

Drawing Rings and Ring Systems Structure Drawing Drawing Rings and Ring Systems

Structure Drawing

Connecting Rings and Chains Structure Drawing Connecting Rings and Chains

Connecting Rings and Chains Structure Drawing Connecting Rings and Chains

Structure Drawing Specifying Atoms When structures are drawn with the pencil tool, ring tool, or chain tool, the atoms in the structure are whatever element appears in the current atom box. Atoms may be changed.

Structure Drawing Specifying Atoms

Structure Drawing Specifying Atoms

Structure Drawing Tips Inserting an Atom When inserting an atom in a structure, look for an "A" to appear in the body of the pencil tool, indicating that the pencil tip is in correct position, directly over an atom. Illustration:

Structure Drawing Specifying Shortcuts When structures are drawn with the pencil tool, ring tool, or chain tool, the atoms in the structure are whatever element appears in the current atom box. Atoms may be changed to any of the pre-drawn shortcuts.

Structure Drawing Specifying Shortcuts

Structure Drawing Specifying Bonds When structures are drawn with the pencil tool, ring tool, or chain tool, the atoms in the structure are whatever element appears in the current atom box. Bonds may be changed.

Structure Drawing Specifying Bonds

Structure Drawing Specifying Bonds

Structure Drawing Correcting Mistakes

Structure Drawing Tips Resetting Default Settings for Atoms/Bonds When "multiple use" is selected for an atom or shortcut, the default atom is changed to that selection and will remain in effect until defaults are reset by clicking the default atom/bond icon:

Structure Drawing Tips Changing atoms Atoms can be changed by doing the following: Click the selection tool. Click to highlight the atoms to be changed (shift). Select the new atoms.

Displaying Carbon Atoms Structure Drawing Displaying Carbon Atoms Carbon atoms in a structure can be displayed as To toggle between options, click the carbon display icon:

Structure Drawing After a structure is built, it must be saved prior to using it in an STN structure search

Structure Drawing Saving the Structure

Structure Drawing Saving the Structure X

Structure Drawing Verify the Structure:

Skills Practice Draw and save each structure below, using the techniques just discussed.

Structure Search Strategy

Structure Search Strategy In this section, you will learn how to Determine the type of structure search to do, based on your information needs Upload a structure to STN Run a structure search in REGISTRY and display structure matches Locate CAplus references to structures of interest

Structure Search Strategy Preview Structure searches can be run to locate Exact matches of a structure Structures containing a structural skeleton or fragment of interest Literature references discussing structures of interest The steps involved in all structure searches follow a similar order.

Structure Search Strategy Preview To locate research papers discussing a structure of interest

Structure Search Strategy Search Question: Locate references discussing the preparation of the following substance:

Structure Search Strategy Step 1: Draw and save the structure Step 2: Logon to STN and enter a structure-searchable database (The FILE command is used to enter a structure-searchable database) FILE 'HOME' ENTERED => FILE REGISTRY

Structure Search Strategy Step 3: Upload the structure

Structure Search Strategy Step 3: Upload the structure

Structure Search Strategy Step 4: Run a sample structure search The perspective of the search question is to locate exact matches on a given structure. A sample structure search searches a portion of the database. It is a no-cost option that is used to evaluate the effectiveness of a structure search by Testing the structure search to ensure it will run within system limits Verifying that the types of answers retrieved are the types of answers desired

Structure Search Strategy The SEARCH command is used to run a sample structure search. At the command line, 3 additional pieces of information are required: A) L-number assigned to the structure during uploading

Structure Search Strategy Type of structure search Three types of structure searches are possible, depending on the types of substance matches desired: Variability in bonds is allowed in all type of searches

Structure Search Strategy Scope of the structure search Two scopes of structure searches are possible

Structure Search Strategy => S L1 EXACT SAM SAMPLE SEARCH INITIATED 13:45:28 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 6 TO ITERATE 100.0% PROCESSED 6 ITERATIONS 2 ANSWERS SEARCH TIME: 00.00.01 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE** PROJECTED ITERATIONS: 6 TO 266 PROJECTED ANSWERS: 2 TO 124 L2 2 SEA EXA SAM L1 This search is projected to run to completion online within system limits. Structure matches ("answers") are placed in an answer set that is given the next available L-number.

Structure Search Strategy Step 5: Evaluate structure matches The no-cost D SCAN feature is used to evaluate structure search results. D SCAN randomly selects an answer from the answer set and displays it:

Structure Search Strategy => D SCAN L2 2 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN Benzeneacetonitrile, a-[3-[[2-(3,4- dimethoxyphenyl)ethyl]methylamino]propyl]-3,4- dimethoxy-a-(1-methylethyl)-, (aS)- (9CI) MF C27 H38 N2 O4 CI COM Absolute stereochemistry. HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):1 Structure matches are in line with the desired results. Specify here the number of additional answers you want to see.

Structure Search Strategy L2 2 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN Benzeneacetonitrile, α-[3-[[2-(3,4-dimethoxyphenyl) ethyl]methylamino]propyl]-3,4-dimethoxy-α-(1- methylethyl)-, labeled with deuterium (9CI) MF C27 H34 D4 N2 O4 ALL ANSWERS HAVE BEEN SCANNED

Structure Search Strategy Step 6: Run a full-file structure search A full-file structure search searches the entire database. The SEARCH command is also used to run a full-file structure search. At the command line, 3 additional pieces of information are required: L-number assigned to the structure during uploading Type of structure search Scope of the structure search - e.g., full

Structure Search Strategy => S L1 EXACT FULL FULL SEARCH INITIATED 13:50:30 FILE 'REGISTRY' FULL SCREEN SEARCH COMPLETED - 67 TO ITERATE 100.0% PROCESSED 67 ITERATIONS 17 ANSWERS SEARCH TIME: 00.00.01 L3 17 SEA EXA FUL L1 The results of a full-file structure search are placed in a new answer set.

Structure Search Strategy Option: Evaluate answers => D SCAN L3 17 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN Benzeneacetonitrile, a-[3-[[2-(3,4- dimethoxyphenyl)ethyl]methylamino]propyl]-3,4- dimethoxy-a-(1-methylethyl)-, labeled with deuterium (9CI) MF C27 H38 N2 O4 CI COM HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0

Structure Search Strategy

Structure Search Strategy Recall the Search Question: Locate references discussing the preparation of the following substance:

Structure Search Strategy => FILE CAPLUS => S L3/PREP 7690 L3 2726608 PREP/RL L4 49 L3/PREP (L3 (L) PREP/RL) Recall: L3 is the answer set resulting from the full-file structure search. Syntax: Type a slash and the CAS Role after the L-number The no-cost D SCAN feature is also available in CAplus. When the answer set contains more than one answer, D SCAN randomly selects an answer from the set and displays it. Evaluating results

Structure Search Strategy Evaluating results => D SCAN L4 49 ANSWERS CAPLUS COPYRIGHT 2001 ACS    TI Investigation of radiochemical purity of 99mTc- verapamil ST verapamil technetium 99m labeling radiochem purity IT 52-53-9DP, Verapamil, 99mTc-labeled 14133-76-7DP, Technetium 99, verapamil labeled with, preparation RL: PNU (Preparation, unclassified); PRP (Properties); PREP (Preparation) (preparation and radiochem. purity of 99mTc- verapamil) HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0 The CAS RN from the REGISTRY answer set that caused the answer to be retrieved is highlighted.

Displaying CAplus answers in more detail Structure Search Strategy Displaying CAplus answers in more detail The DISPLAY command is used to show additional information for the answers retrieved from CAplus. Several predefined display formats are available:

Structure Search Strategy Summary

Structure Search Strategy Summary

Skills Practice Locate studies on the following substance, as well as stereoisomers and radiolabeled forms. Display the bibliographic information for the first 3 answers in the CAplus answer set. Locate references reporting the preparation of the following specific substance or any of its salts. Display the BIB, ABS, and HITSTR information for the first 3 answers in the CAplus answer set.

Substructure Searching

Skills Practice Using the structure in the Search Question, run the following searches: Exact full Family full Substructure full

Skills Practice Use D SCAN to look at the answers retrieved in each search. Note the different kinds of substances retrieved by each type of search.

Substructure Searching In this section, you will learn how to draw structures for substructure searches to retrieve matches with the desired Ring system fusion Bonding patterns Substitution at open positions

Substructure Searching Default Assumptions STN Express assigns attribute information to the rings and chains in a substructure query. These attributes determine the types of answers retrieved by a substructure search. Default assumptions can be modified.

Substructure Searching Ring Systems The default assumption for ring systems is called "isolated/embedded". STN automatically searches for each ring system in a structure As drawn, without other rings attached to it via bonds (isolated) As part of a larger ring system, with other rings fused to it (embedded) An option exists to specify that a ring system in a structure be isolated.

Substructure Searching Search Question: Locate substances with the following characteristics: Requirements: R and R' = anything, including hydrogen No substitution at the carbon in the ring marked with an asterisk (*) The ring may be further substituted at the other open sites, but there may be no additional rings fused at these positions

Building the Structure Substructure Searching Building the Structure Don’t draw any atom Draw a Hydrogen Look at the following procedure

Substructure Searching Ring isolation To prevent the substructure search from retrieving the ring system as part of a larger ring system, isolate the ring by doing the following:

Substructure Searching Ring isolation

Substructure Searching Ring isolation

Substructure Searching => FILE REGISTRY => Uploading C:\Program Files\Stnexp\Queries\sss-ring.str L1 STRUCTURE UPLOADED => D L1 L1 HAS NO ANSWERS L1 STR

Substructure Searching => S L1 SSS SAM (or only: => S L1) SAMPLE SEARCH INITIATED 14:49:50 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 380 TO ITERATE 100.0% PROCESSED 380 ITERATIONS 1 ANSWERS SEARCH TIME: 00.00.01 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE** PROJECTED ITERATIONS: 6431 TO 8769 PROJECTED ANSWERS: 1 TO 80 L2 1 SEA SSS SAM L1

Substructure Searching => D SCAN L2 1 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN 3-Pyridinecarboxylic acid, 1-ethoxy-1,4-dihydro- 4-(phenylimino)-, ethyl ester (9CI) MF C16 H18 N2 O3 CI COM ALL ANSWERS HAVE BEEN SCANNED

Substructure Searching => S L1 SSS FULL (or only: => S L1 FULL) FULL SEARCH INITIATED 14:50:08 FILE 'REGISTRY' FULL SCREEN SEARCH COMPLETED - 8011 TO ITERATE 100.0% PROCESSED 8011 ITERATIONS 21 ANSWERS SEARCH TIME: 00.00.01 L3 21 SEA SSS FUL L1 => D SCAN L3 21 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN 3-Pyridinecarboxylic acid, 5-cyano-1,4-dihydro-4- imino-6-methyl-1-(phenylmethyl)-, ethyl ester (9CI) MF C17 H17 N3 O2 HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):1

Skills Practice If this structure was drawn and Ring Isolation set to Isolated would the following substances be retrieved in a substructure search?

Skills Practice If this structure was drawn and Ring Isolation set to Isolated would the following substances be retrieved in a substructure search?

Skills Practice Run the search for this fragment twice: One with the ring isolated One with the ring isolated embedded Look at the differences

Substructure Searching Atoms Atoms in a substructure query may be Ring Chain Ring/Chain

Substructure Searching Atoms The default assumption for atom retrieval depends on the location of an atom in the substructure query.

Substructure Searching Search Question: Locate substances with the following characteristics: R, R', and R" = anything, including H The ring system may be substituted at all of the open sites There may be additional rings fused to the ring system R' and R" may form a ring with the N, e.g.,

Building the Structure Substructure Searching Building the Structure Don’t draw any atom Rings isolated/embedded Look at the following procedure

Substructure Searching Ring/chain atoms To allow the substructure search to retrieve a chain atom as part of a ring or a chain, do the following:

Substructure Searching Ring/chain atoms

Substructure Searching => FILE REGISTRY => Uploading C:\Program Files\Stnexp\Queries\sss-atom-rc.str L1 STRUCTURE UPLOADED => D L1 L1 HAS NO ANSWERS L1 STR

Substructure Searching => S L1 SSS SAM SAMPLE SEARCH INITIATED 15:06:29 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 15 TO ITERATE 100.0% PROCESSED 15 ITERATIONS 4 ANSWERS SEARCH TIME: 00.00.01 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE** PROJECTED ITERATIONS: 68 TO 532 PROJECTED ANSWERS: 4 TO 200 L2 4 SEA SSS SAM L1

Substructure Searching => D SCAN L2 4 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN 3-Quinolinecarboxylic acid, 4-(4-hydroxy-3- methoxyphenyl)-6,7-dimethoxy-2-(1H-1,2,4-triazol -1-ylmethyl)-, ethyl ester (9CI) MF C24 H24 N4 O6 HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):1 Note: The N atom is part of a ring in this substructure match.

Substructure Searching => D SCAN L2 4 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN 3-Quinolinecarboxylic acid, 2-[(dibutylamino) methyl]-4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-, ethyl ester (9CI) MF C31 H42 N2 O6 HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0 Note: The N atom is part of a chain in this substructure match.

Substructure Searching => S L1 SSS FULL FULL SEARCH INITIATED 15:06:52 FILE 'REGISTRY' FULL SCREEN SEARCH COMPLETED - 288 TO ITERATE 100.0% PROCESSED 288 ITERATIONS 114 ANSWERS SEARCH TIME: 00.00.01 L3 114 SEA SSS FUL L1 => D SCAN L3 114 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN 3-Quinolinecarboxylic acid, 4-(3,4-dimethoxy phenyl)-6,7-dimethoxy-2-(4-thiomorpholinylmethyl)-, ethyl ester (9CI) MF C27 H32 N2 O6 S HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0

Substructure Searching

Substructure Searching Bonding Patterns Each bond in a substructure query has three characteristics associated with it: Bond type - Whether the bond is part of a ring or a chain Bond structure - Whether the bond is single, double, triple, or unspecified Bond value - Whether the bond is exact or part of an alternating single/double bond system (e.g., tautomers)

Substructure Searching Bond Type Bonds in a substructure query may be Ring Chain Ring/Chain

Substructure Searching Bond Type

Substructure Searching Bond Type An option exists to specify that a bond type be ring/chain.

Substructure Searching Search Question: Expand the previous query to retrieve substructure matches where the O atoms and the CH2—N chain are also parts of rings fused onto the quinoline ring. Requirements: There may be any type of substitution at all open sites There may be additional rings fused to the ring system

Building the Structure Substructure Searching Building the Structure Don’t draw any atom Ring isolated/embedded Look at the following procedure

Substructure Searching Bond type To allow the substructure search to retrieve a chain bond as part of a ring or a chain, do the following:

Substructure Searching => FILE REGISTRY => Uploading C:\Program Files\Stnexp\Queries\sss-bond-rc.str L1 STRUCTURE UPLOADED => D L1 L1 HAS NO ANSWERS L1 STR

Substructure Searching => S L1 SSS SAM SAMPLE SEARCH INITIATED 17:20:56 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 2128 TO ITERATE 47.0% PROCESSED 1000 ITERATIONS 3 ANSWERS INCOMPLETE SEARCH (SYSTEM LIMIT EXCEEDED) SEARCH TIME: 00.00.01 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE** PROJECTED ITERATIONS: 39795 TO 45325 PROJECTED ANSWERS: 3 TO 278 L2 3 SEA SSS SAM L1

Substructure Searching => S L1 SSS FULL FULL SEARCH INITIATED 17:23:15 FILE 'REGISTRY' FULL SCREEN SEARCH COMPLETED - 42125 TO ITERATE 100.0% PROCESSED 42125 ITERATIONS 133 ANSWERS SEARCH TIME: 00.00.01 L3 133 SEA SSS FUL L1 => D SCAN L3 133 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN 1,4-Dioxino[2,3-g]quinoline-8-carboxylic acid, 9- (3,4-dimethoxyphenyl)-2,3-dihydro-7-(1- piperidinylmethyl)-, ethyl ester (9CI) MF C28 H32 N2 O6 HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):1

Skills Practice Have you found this answer? Locate references discussing compounds containing the following substructure Requirements: Any of the atoms may be part of a ring There may be any type of substitution at any open site Have you found this answer?

Substructure Searching Bond Structure Bonds in a substructure query may be drawn as Single Double Triple Unspecified

Substructure Searching Bond Structure

Substructure Searching Search Question: Locate substances with the following characteristics: Requirements: R is a carbon atom in a chain The bond may be single or double No additional ring fusion is desired on either ring system Any substitution may be present at all open sites

Building the Structure Substructure Searching Building the Structure Draw a C atom Look at the following procedure Rings are isolated Don’t draw any atom

Substructure Searching Bond structure To allow the substructure search to retrieve a bond that is single or double, do the following:

Substructure Searching Bond structure

Substructure Searching Bond structure

Substructure Searching => FILE REGISTRY => Uploading C:\Program Files\Stnexp\Queries\sss-unspec-.str L1 STRUCTURE UPLOADED => D L1 L1 HAS NO ANSWERS L1 STR Both ring systems were isolated.

Substructure Searching => S L1 SSS SAM SAMPLE SEARCH INITIATED 12:04:39 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 605 TO ITERATE 100.0% PROCESSED 605 ITERATIONS 9 ANSWERS SEARCH TIME: 00.00.01 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE** PROJECTED ITERATIONS: 10625 TO 13575 PROJECTED ANSWERS: 9 TO 360 L2 9 SEA SSS SAM L1

Substructure Searching => D SCAN L2 9 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN Isoquinoline, 1,2-dibenzoyl-6,7-diethoxy-1,2,3,4- tetrahydro- (7CI) MF C27 H27 N O4 HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):1 Here, the bond to the O is a double bond. Note the double bonds in the fused ring!

Substructure Searching L2 9 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN 1-Isoquinolinemethanol, 1,2,3,4-tetrahydro-6,7- dimethoxy-2-methyl-a-phenyl-, [S-(R*,S*)]- (9CI) MF C19 H23 N O3 Absolute stereochemistry. HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0 Here, the bond to the O is a single bond.

Substructure Searching => S L1 SSS FULL FULL SEARCH INITIATED 12:05:40 FILE 'REGISTRY' FULL SCREEN SEARCH COMPLETED - 12523 TO ITERATE 100.0% PROCESSED 12523 ITERATIONS 148 ANSWERS SEARCH TIME: 00.00.01 L3 148 SEA SSS FUL L1

Substructure Searching Bond Value Bonds in a substructure query may be Exact Normalized Exact/Normalized

Substructure Searching Bond Value STN Express automatically assigns bond values based on characteristics of a substructure. It often assigns a bond to be exact or normalized to maximize the answers retrieved by a query. Generally, the bond values assigned by the software do not lead to undesirable answers.

Substructure Searching Bond Value Run three exact full searches for the previous structure. With all exact bonds With all normalized bonds With all exact-normalized bonds Look at the differences

Substructure Searching Bond Value With all exact bonds => l1 exa full FULL SEARCH INITIATED 09:27:14 FULL SCREEN SEARCH COMPLETED - 4911 TO ITERATE   100.0% PROCESSED 4911 ITERATIONS 305 ANSWERS SEARCH TIME: 00.00.01 L2 305 SEA EXA FUL L1 => l2 not ids/ci 222437 IDS/CI L3 74 L2 NOT IDS/CI

Substructure Searching Bond Value With all exact bonds => d scan L3 74 ANSWERS REGISTRY COPYRIGHT 2003 ACS IN Cyclohexane-d7 (6CI, 7CI, 9CI) MF C6 H5 D7  

Substructure Searching Bond Value With all normalized bonds => l4 exa full FULL SEARCH INITIATED 09:29:16 FULL SCREEN SEARCH COMPLETED - 20679 TO ITERATE   100.0% PROCESSED 20679 ITERATIONS 1820 ANSWERS SEARCH TIME: 00.00.01 L5 1820 SEA EXA FUL L4 => l5 not ids/ci 222437 IDS/CI L6 182 L5 NOT IDS/CI

Substructure Searching Bond Value With all normalized bonds => d scan L6 182 ANSWERS REGISTRY COPYRIGHT 2003 ACS IN Benzene, tetracosamer, radical ion(1+) (9CI) MF (C6 H6)24 CI PMS, RIS CM 1  

Substructure Searching Bond Value With all exact-normalized bonds => l7 exa full FULL SEARCH INITIATED 09:30:29 FULL SCREEN SEARCH COMPLETED - 29534 TO ITERATE   100.0% PROCESSED 29534 ITERATIONS 2160 ANSWERS SEARCH TIME: 00.00.01 L8 2160 SEA EXA FUL L7 => l2 or l5 L9 2125 L2 OR L5 => l8 not l9 L10 35 L8 NOT L9

Substructure Searching Bond Value With all exact-normalized bonds => d scan L10 35 ANSWERS REGISTRY COPYRIGHT 2003 ACS IN Cyclohexenylium-1-d (9CI) MF C6 H8 D  

Substructure Searching

Substructure Searching Bond value To change the bond values assigned by STN Express, do the following:

Normalized Bonds in REGISTRY Substructure Searching Normalized Bonds in REGISTRY In rings, normalized bonds are used when Alternating single and double bonds can be drawn all the way around a ring There are an even number of atoms in the ring In chains (or part of rings), normalized bonds are used only for certain tautomers Structure drawing preview: STN Express determines normalized bonds as you draw.

Substructure Searching Bond Value

Normalized bonds are used for certain tautomeric chains: Substructure Searching Normalized bonds are used for certain tautomeric chains: 1 3 2 H Central atom 2 = C, N, P, As, Sb, S, Se, Te, Cl, Br, I Hetero atoms 1 and 3 = N, O, S, Se, Te One hetero atom must have a hydrogen (or D, T, or a charge)

Substructure Searching Bond Value

Substructure Searching Bond Value

Substructure Searching Bond Value

Substructure Searching Normalized bonds Not normalized bonds Examples Examples acids amines amides Keto-enol tautomers do not fit the REGISTRY tautomer normalized bond rule, so you have to build a query to find both variations.

Substructure Searching Normalized bonds Not normalized bonds benzenes thiophenes thiazoles anthracenes cyclooctaquinolizinium Normalized is not synonymous with aromatic.

Substructure Searching Please run a Full Exact search for the following structures and look at the differences. Exact bonds Normalized bonds Exact/Normalized bonds Exact bonds 10 6 16 5

Substructure Searching If you draw with STN Express the following structure how the software considers the value bonds? Why?

Substructure Searching If you run an Exact full search of this structure with all bonds Normalized you get 1 answer If you run an Exact full search of this structure with all bonds Exact/Normalized do you get the previous answer?

Do these rings have normalized bonds? Substructure Searching Do these rings have normalized bonds?

Do these rings have normalized bonds? Substructure Searching Do these rings have normalized bonds? YES YES 1 – 14 C’s in ring, alternating single and double 2 – 26 atoms in ring system, all alternating single and double bonds 3- 13 atoms in ring, single bonds in center ring NO single exact bonds are denoted

Substructure Searching Search Question: STN Express assigned "exact/normalized" bonds to the highlighted bonds in the following structure: Eliminate the answers where the C6 rings contain alternating single and double bonds.

Substructure Searching => FILE REGISTRY => Uploading C:\Program Files\Stnexp\Queries\sss-bond-value.str L1 STRUCTURE UPLOADED => D L1 L1 HAS NO ANSWERS L1 STR

Substructure Searching => S L1 SSS SAM SAMPLE SEARCH INITIATED 14:02:02 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 28 TO ITERATE 100.0% PROCESSED 28 ITERATIONS 3 ANSWERS SEARCH TIME: 00.00.01 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE** PROJECTED ITERATIONS: 243 TO 877 PROJECTED ANSWERS: 3 TO 163 L2 3 SEA SSS SAM L1

Substructure Searching => D SCAN L2 3 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN 1-Naphthalenemethanol, decahydro-a-[6-methoxy-2,3- bis(phenylmethoxy)phenyl]-2,5,5,8a-tetramethyl-, (1S,2S,4aS,8aS)- (9CI) MF C36 H46 O4 Absolute stereochemistry. HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):1

Skills Practice Run two searches for the following structures. No ring fusions, other double bonds, or substitutions, are allowed. No salts or mixture desired. Which kind of search?

=> l1 exa full L2 6

=> l3 exa full L4 74 => l4 not l2 L5 74

Skills Practice => l6 exa full L7 157 Can you run only one search for retrieving both the structures? Which searching structure? Which kind of search? => l6 exa full L7 157

=> l7 not l2 L8 151 L7 NOT L2   => l8 not l4 L9 77 L8 NOT L4

Skills Practice Run two different searches for the reported structures (Full SSS, STN Express default). - Are the results different? If yes,why?

=> l1 full   L2 2531

=> l3 full   L4 2184

=> l2 and l4 L5 1486

=> l2 not l4 and nc=1 L6 832

=> l4 not (l2 or m/els) and nc=1

Skills Practice Which structure search should be run in order to collect all the previous results?

  => l7 full L8 12146

=> l8 not (l2 or l4) L11 1058

Substructure Searching BONDS Be carefull with cycles with odd number of atoms. Expecially if they contain hetero atoms. The bonds are not normalized usually (unless…). The position of double bonds depends on nomenclature. Which the best way for searching them?

Skills Practice Run two different searches for the reported structures (Full SSS, STN Express default). - Are the results different? If yes,why?

=> l1 full L2 24

=> l3 full L4 63

=> l2 not l4 L5 22 L2 NOT L4

=> l4 not l2 L6 61 L4 NOT L2

Skills Practice Which structure search should be run in order to collect all the previous results?

=> l7 full L8 225

=> l8 not l2 L9 201 L8 NOT L2   => l9 not l4 L10 140 L9 NOT L4

Skills Practice Which is the less expensive search for retrieving both of the previous compounds?

Substructure Searching BONDS BE CAREFUL WITH BONDS!

Substructure Searching Extend

Substructure Searching => fil reg   L1 STRUCTURE UPLOADED => d L1 HAS NO ANSWERS L1 STR 

Substructure Searching => l1   FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE** PROJECTED ITERATIONS: 1 TO 80 PROJECTED ANSWERS: 0 TO 0 L2 0 SEA SSS SAM L1 => l1 full FULL SEARCH INITIATED 06:07:43 FULL SCREEN SEARCH COMPLETED - 61 TO ITERATE 100.0% PROCESSED 61 ITERATIONS 0 ANSWERS SEARCH TIME: 00.00.01 L3 0 SEA SSS FUL L1

Substructure Searching => set extend on perm SET COMMAND COMPLETED   => l1 full FULL SEARCH INITIATED 06:08:38 L4 61 SEA SSS FUL L1 EXTEND CANDIDATE STRUCTURE SEARCH COMPLETED - 61 TO ITERATE 100.0% PROCESSED 61 ITERATIONS 0 ANSWERS SEARCH TIME: 00.00.01 L5 0 SEA SSS FUL L1

Substructure Searching => d scan l4

Substructure Searching Atom Substitution There are a number of ways to control atom substitution in substructure search matches:

Substructure Searching Variable Atoms A number of system-defined options are available to allow variability in atom substitution:

Substructure Searching Variable Atoms

Substructure Searching Search Question: Locate substances with the following characteristics: Requirements: R is any type of heterocyclic ring, with any type of substitution R' is any non-hydrogen ring or chain substituent No additional ring fusion is desired on either ring system Any substitution may be present at all open sites

Building the Structure Substructure Searching Building the Structure Look at the following procedure Draw a A variable (R/C) Rings are isolated Don’t draw any atom

Substructure Searching Variable group To add a variable group to an existing structure, do the following:

Substructure Searching Variable group

Substructure Searching => FILE REGISTRY => Uploading C:\Program Files\Stnexp\Queries\sss-variable.str L1 STRUCTURE UPLOADED => D L1 L1 HAS NO ANSWERS L1 STR The rings were isolated, and the node characteristic of A was set to ring/chain.

Substructure Searching => S L1 SSS SAM SAMPLE SEARCH INITIATED 16:29:55 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 2576 TO ITERATE 38.8% PROCESSED 1000 ITERATIONS 15 ANSWERS INCOMPLETE SEARCH (SYSTEM LIMIT EXCEEDED) SEARCH TIME: 00.00.01 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE** PROJECTED ITERATIONS: 48478 TO 54562 PROJECTED ANSWERS: 400 TO 1144 L2 15 SEA SSS SAM L1

Substructure Searching => D SCAN L2 15 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN 2,5-Pyrrolidinedione, 1-[3-[4-(4-methoxyphenyl)-1- piperazinyl]propyl]-(9CI) MF C18 H25 N3 O3 CI COM HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0 A Hy

Substructure Searching => S L1 SSS FULL FULL SEARCH INITIATED 16:30:53 FILE 'REGISTRY' FULL SCREEN SEARCH COMPLETED - 51401 TO ITERATE 100.0% PROCESSED 51401 ITERATIONS 1028 ANSWERS SEARCH TIME: 00.00.03 L3 1028 SEA SSS FUL L1

Substructure Searching G-Groups In addition to the STN system-defined variable groups (e.g., X), variable groups containing substituents of your own definition may be created. User-defined variable groups are called G-groups on STN. A G-group can have up to 20 substituents comprising it. Those substituents may be: Specific elements Shortcuts System-defined variable groups Structural fragments Other G-groups

Substructure Searching Search Question: Locate substances with the following characteristics: Requirements: R = C, N R' = Me, Et, n-Pr, i-Pr, OH, SH, X No additional ring fusion is allowed on either of the 6-membered rings Additional substitution may be present at all open sites

Building the Structure Substructure Searching Building the Structure Look at the following procedure Rings are isolated Don’t draw any atom

Substructure Searching G-group To define and add a G-group to an existing structure, do the following:

Substructure Searching G-group

Substructure Searching G-group

Substructure Searching G-group

Substructure Searching G-group

Substructure Searching G-group

Substructure Searching => FILE REGISTRY => Uploading C:\Program Files\Stnexp\Queries\sss-ggroup.str L1 STRUCTURE UPLOADED => D L1 L1 HAS NO ANSWERS L1 STR

Substructure Searching => S L1 SSS SAM SAMPLE SEARCH INITIATED 11:59:54 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 11 TO ITERATE 100.0% PROCESSED 11 ITERATIONS 2 ANSWERS SEARCH TIME: 00.00.01 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE** PROJECTED ITERATIONS: 22 TO 418 PROJECTED ANSWERS: 2 TO 124 L2 2 SEA SSS SAM L1

Substructure Searching => D SCAN L2 2 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN 4-Piperidinol, 1-[3-(6-fluoro-1,2-benzisoxazol-3- yl)propyl]-4-(4-fluorophenyl)- (9CI) MF C21 H22 F2 N2 O2 HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0 G1 = F G2 = C, C

Variable Points of Attachment on Rings Substructure Searching Variable Points of Attachment on Rings A substituent can be tagged to appear at variable positions on a ring. The substituent may be a Specific element Shortcut System-defined variable group Structural fragment G-group

Substructure Searching Search Question: Locate substances with the following characteristics: Requirements: R is any type of heterocyclic ring with any type of substitution No additional ring fusion is desired on the phenyl or N-containing rings Any substitution may be present at all open sites There must be at least one halogen atom attached to the phenyl ring, at the positions marked with asterisks

Building the Structure Substructure Searching Building the Structure Draw a Hy variable Rings are isolated Don’t draw any atom Look at the following procedure

Variable point of attachment Substructure Searching Variable point of attachment To add a substituent with a variable point of attachment to an existing structure, do the following:

Variable point of attachment Substructure Searching Variable point of attachment

Variable point of attachment Substructure Searching Variable point of attachment

Substructure Searching => FILE REGISTRY => Uploading C:\Program Files\Stnexp\Queries\sss-vpa.str L1 STRUCTURE UPLOADED => D L1 L1 HAS NO ANSWERS L1 STR

Substructure Searching => S L1 SSS SAM SAMPLE SEARCH INITIATED 14:20:48 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 2577 TO ITERATE 38.8% PROCESSED 1000 ITERATIONS 26 ANSWERS INCOMPLETE SEARCH (SYSTEM LIMIT EXCEEDED) SEARCH TIME: 00.00.01 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE** PROJECTED ITERATIONS: 48497 TO 54583 PROJECTED ANSWERS: 849 TO 1831 L2 26 SEA SSS SAM L1

Substructure Searching => D SCAN L2 26 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN Pyrrolo[3,2-c]azepin-4(1H)-one, 5-[3-[4-(4- fluorophenyl)-1-piperazinyl]propyl]-5,6,7,8- tetrahydro-8-hydroxy-1-methyl- (9CI) MF C22 H29 F N4 O2 HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):1 F at the para position

Substructure Searching L2 26 ANSWERS REGISTRY COPYRIGHT 2001 ACS IN 1H-Indole-2,3-dione, 1-[3-[4-(3-chlorophenyl)-1- piperazinyl]propyl]-, dihydrochloride (9CI) MF C21 H22 Cl N3 O2 . 2 Cl H HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0 => S L1 SSS FULL FULL SEARCH INITIATED 14:21:19 FILE 'REGISTRY' FULL SCREEN SEARCH COMPLETED - 51428 TO ITERATE 100.0% PROCESSED 51428 ITERATIONS 1310 ANSWERS SEARCH TIME: 00.00.03 L3 1310 SEA SSS FUL L1 Cl at the meta position

Substructure Searching Summary

Substructure Searching Summary

Skills Practice Are there any patents dealing with the preparation of compounds with the following structures? If so, who holds those patents? Requirements: R = Any carbocyclic ring system. All the carbocyclic rings may be identical or they may be different and they may be substituted or unsubstituted.

Skills Practice Locate papers discussing substances with the following structure. What have these substances been used for? Requirements: R = Ring or chain carbon with any type of substitution

Skills Practice What companies recently have been working on compounds with the following structure? HINT: Look at the CS (corporate source) index in the CAplus file record. Requirements: R = Hydrogen or any non-hydrogen substituent R' = Any non-hydrogen, non-carbon substituent, e.g., a keto functionality All other open sites may have any type of substitution Rings may have other rings fused to them

Skills Practice Locate papers discussing the synthesis of the following substances: Requirements: R = X, H, -NO2, -CF3 R' = Anything but hydrogen R" = C or N Any substitution may be present at all other open sites Phenyl ring shown in the structure may not have additional rings fused to it

Skills Practice Locate references discussing compounds containing the following structure fragment: Requirements: At least 2 -OH groups must be attached to the rings labeled "A" and "B” Any substitution at the remaining open sites Ring system may have other rings fused to it