Post on 15-Jan-2016
1
Structure Searching with STN Express
2
• 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.
Introduction
3
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.
Introduction
Dictionary
4
Dictionary
• Searching by dictionary is a powerful method for retrieving at least broad classes of substances in Registry, useful also in structure searching.
Introduction
5
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
6
Dictionary - Molecular formula
• Many compounds have the same molecular formula:
C27H38N2O4 is shared by >250 compounds in the CAS REGISTRY database
Introduction
7
Dictionary - Chemical name, Molecular formula
• Name, and Molecular formula, fragments, are inside the BI.Name, and Molecular formula, fragments, are inside the BI.
Introduction
8
Structure
• Each compound has an unique structure
Introduction
(CH2)3
Pr-i Me
OMeMeO
OMeOMe
CN
C N CH2 CH2
9
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
10
A sample of structure-searchable databases on STN:
Introduction
Structure-searchable databases Type of substance
REGISTRY Organic, inorganic, biochemical, biosequence
BEILSTEIN Organic
GMELIN Inorganic
MARPAT Markush structures from patent claims
CASREACT, CHEMINFORMRX, DJSMONLINE
Organic reactions
DCR Organic
11
Basic Strategy for Structure Searching
• Locating substance information via structure searching is accomplished in four main steps:
1 Draw the structure2 Search the structure3 Display the structure matches retrieved4 Locate the desired information about the structure
matches of interest
Introduction
12
Structure Drawing
13
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
14
Structure Drawing
Structure drawing screen has 7 main parts:
15
Helpful HINT
Tool tips describe STN Express structure drawing tools. Position the cursor over the structure drawing tool of interest. The tool tip appears:
Structure Drawing
16
• 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
17
• 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
18
Drawing ChainsIf you want to Follow these steps:
Draw a chainfreehand
1. Click the pencil tool:
2. Place the cursor on the drawing screen atthe point where you want to start drawing.
3. Click, drag, and release to draw a linerepresenting an atom bonded to anotheratom.
4. Repeat step 3, as needed.
Draw a chainusing the chaintool
1. Click the chain tool:
2. The Chain Length option box appears.Scroll to select the desired length. ClickOK.
3. Click on the drawing screen to place thechain.
Structure Drawing
19
Drawing Rings and Ring SystemsIf you want to Follow these steps:
Draw a single ring 1. Click the ring tool:
2. The Ring Description option box appears.Select the desired ring from the
Common ring icons, e.g.,
Scrollable list of ring descriptions
Click OK.
3. Click on the drawing screen to place thering.
(continued on next slide)
Structure Drawing
20
If you want to Follow these steps:
Draw a single ringusing a template
1. Click the Template! pull-down menu.
2. The Open Template dialog box appears showinga list of files containing ring templates.Highlight the file of interest. Click Open.
3. The Template option box appears. Double-clickon a ring of interest.
4. Click on the drawing screen to place the ring.
Structure DrawingDrawing Rings and Ring Systems
21
If you want to Follow these steps:
Draw a side-fusedring system
Draw the left-most ring:
1. Click the ring tool:
2. The Ring Description option box appears.Select the desired ring from the
Common ring icons, e.g.,
Scrollable list of ring descriptions
Click OK.
3. Click on the drawing screen to place the ring.
Draw the next ring:4. Repeat steps 1-2, selecting a different ring
component.5. Align the cursor with the middle of the bond
where fusion is to occur.
6. Click to place the ring.
Drawing Rings and Ring Systems
Structure Drawing
22
If you want to Follow these steps:
Draw a spiro-fused ring system
Draw one ring:
1. Click the ring tool:
2. The Ring Description option box appears.Select the desired ring from the
Common ring icons, e.g.,
Scrollable list of ring descriptions
Click OK.
3. Click on the drawing screen to place the ring.
Draw the next ring:4. Repeat steps 1-2, selecting a different ring
component.5. Align the cursor with the atom where fusion is
to occur:
6. Click to place the ring.
Structure DrawingDrawing Rings and Ring Systems
23
noteSide-fused systems can also be drawn using keyboardcommands in the Ring Description option box.
Keyboard commands are a series of numbers specifyingthe ring sizes to fuse together from left to right. A letter isspecified before a ring number (u or d) to indicate that thenext ring should be fused to the preceding ring in ahorizontal direction
u - one face up
d - one face down
This keyboardcommand
Creates this ring system
665
6u5
6d65
Structure Drawing
24
Connecting Rings and ChainsIf you want to Follow these steps:
Connect a ring toan existing chain 1. Click the ring tool:
2. The Ring Description option box appears.Select the desired ring from the
Common ring icons, e.g.,
Scrollable list of ring descriptions
Click OK.
3. Align the cursor with the atom wherebonding is to occur:
4. Click to place the ring.
Structure Drawing
25
If you want to Follow these steps:
Connect a chain toan existing ring 1. Click the chain tool:
2. The Chain Length option box appears.Scroll to select the desired length. ClickOK.
3. Align the cursor with the atom wherebonding is to occur:
4. Click to place the chain.
Structure Drawing
Connecting Rings and Chains
26
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
27
If you want to Follow these steps:
Change one or more atoms to one of the elements in the common atoms palette
1. Click the pencil tool:
2. From the common atoms palette, click the element
Once, to change 1 atom in the structure
Twice, to change >1 atom in the structure
3. Place the cursor over the atom(s) to be changed. Click.
Structure Drawing
Specifying Atoms
28
If you want to Follow these steps:
Change one ormore atoms to anelement not in thecommon atomspalette
1. Click the pencil tool:
2. From the Draw pull-down menu, selectAtom.
3. The Atom Selection menu appears. Clickthe radio button associated with the atomof interest. Click Single Use or MultipleUse.
4. Place the cursor over the atom(s) to bechanged. Click.
Specifying Atoms
Structure Drawing
29
TipsInserting 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
30
• 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
31
If you want to Follow these steps:
Change one ormore atoms to oneof the shortcuts
1. Click the pencil tool:
2. Click the shortcut tool:
3. The Shortcuts menu appears. Click theradio button associated with the shortcutof interest. Click Single Use or MultipleUse.
4. Place the cursor over the atom(s) to bechanged. Click.
Structure Drawing
Specifying Shortcuts
32
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
33
If you want to Follow these steps:
Change one or more bonds to one of the bonds in the common bonds palette
1. Click the pencil tool:
2. From the common bonds palette, click the bond
Once, to change 1 bond in the structure
Twice, to change >1 bond in the structure
3. Place the cursor over the bond(s) to be changed. Click.
Structure Drawing
Specifying Bonds
34
If you want to Follow these steps:
Change one ormore bonds to abond not in thecommon bondspalette
1. Click the pencil tool:
2. From the Draw pull-down menu, select Bond.
3. The Bond Selection menu appears. Click theradio button associated with the bond ofinterest. Click Single Use or Multiple Use.
4. Place the cursor over the bond(s) to bechanged. Click.
Structure DrawingSpecifying Bonds
35
Correcting MistakesIf you want to Follow these steps:
Undo the lastmodification made Click the undo icon:
Erase an atom andits attached bond 1. Click the eraser tool:
2. Click the atom to be erased.
Clear the drawingwindow
From the Edit pull-down menu, selectClear All.
Structure Drawing
36
TipsResetting 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
37
TipsChanging atoms• Atoms can be changed by doing the following:
1 Click the selection tool.2 Click to highlight the atoms to be changed (shift).3 Select the new atoms.
Structure Drawing
38
Displaying Carbon Atoms
• Carbon atoms in a structure can be displayed as
• To toggle between options, click the carbon display icon:
Structure Drawing
39
Step Action
1
Click the save icon:
2 The Save Query As dialog box appears.
In the File Name: entry box, type a name forthe structure. For Windows, the nameshould have 8 or fewer characters.
Click OK.
After a structure is built, it must be saved prior to using it in an STN structure search
Structure Drawing
40
Saving the StructureStep Action
3 A Saving dialog box appears. Deselect anychecked boxes.
Click Save.
Structure Drawing
41
Saving the StructureStep Action
3 A Saving dialog box appears. Deselect anychecked boxes.
Click Save.
Structure Drawing
X
42
Structure Drawing
Verify the Structure:
43
Draw and save each structure below, using the techniques just discussed.
Skills Practice
44
Structure Search Strategy
45
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
46
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
47
To locate research papers discussing a structure of interest
Step 1 Draw and save the structure.
Step 2 Logon to STN and enter a structure-searchable database.
Step 3 Upload the structure.
Step 4 Run a sample structure search.
Step 5 Evaluate structure matches.
Step 6 Run a full-file structure search.
Step 7 Find references discussing the structure matches of interest.
Preview
Structure Search Strategy
48
Search Question:Locate references discussing the preparation of the following substance:
Structure Search Strategy
49
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
50
Step 3: Upload the structure
Step Action
1 Click the Upload Structure Query icon:
2 The Structure File: dialog box appears. Click tohighlight the name of the structure file ofinterest. Click Open.
3 The structure is uploaded into STN. An L-number is assigned to the structure:
=>Uploading C:\Program
Files\Stnexp\Queries\pract1.str
L1 STRUCTURE UPLOADED
Structure Search Strategy
51
S t e p A c t i o n
3 V e r i f y t h e s t r u c t u r e o n l i n e :
= > D L 1 L 1 H A S N O A N S W E R S L 1 S T R
C H 2C H 2
C H 2N
C H 2C H 2
M e O
M e O
i - P r C N
M e O
M e O
M e
Step 3: Upload the structure
Structure Search Strategy
52
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 ensureTesting the structure search to ensure it will run within system limitsit will run within system limits
Verifying that the types of answersVerifying that the types of answers retrieved are the types of answers retrieved are the types of answers
desireddesired
Structure Search Strategy
53
• 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
54
B) Type of structure search
Three types of structure searches are possible, depending
on the types of substance matches desired:
Use this type of structure search: To retrieve this type of substance
match Exact Family Substructure
Exact substance X X X
Stereoisomers X X X
Salts X X
Mixtures X X
Substitution at open sites
X
Variability in bonds is allowed in all type of searches
Structure Search Strategy
55
C) Scope of the structure search
Two scopes of structure searches are possible
Scope of structure search When you want to search
Sample Full
A portion of the database at no cost
X
The entire database X
Structure Search Strategy
56
=> SS L1L1 EXACTEXACT SAMSAM
SAMPLE SEARCH INITIATED 13:45:28 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 6 TO ITERATE
100.0% PROCESSED 6 ITERATIONS 2 ANSWERSSEARCH TIME: 00.00.01
FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE**PROJECTED ITERATIONS: 6 TO 266PROJECTED 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
57
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
58
=> 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.
(CH2)3
i-PrMe
OMe
OMe
OMe
MeO
CNN S
Structure Search Strategy
59
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
(CH2)3
Pr-i Me
OMeMeO
OMeOMe
CN
C N CH2 CH2
Structure Search Strategy
60
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:1 L-number assigned to the structure during uploading2 Type of structure search3 Scope of the structure search - e.g., full
Structure Search Strategy
61
=> SS L1L1 EXACTEXACT FULLFULL
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
62
Option: Evaluate answers
=> D SCAN
L3 17 ANSWERS REGISTRY COPYRIGHT 2001 ACS
IN Benzeneacetonitrile, -[3-[[2-(3,4- dimethoxyphenyl)ethyl]methylamino]propyl]-3,4- dimethoxy--(1-methylethyl)-, labeled with deuterium (9CI)
MF C27 H38 N2 O4
CI COM
HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0
(CH2)3
i-Pr Me
OMeMeO
OMeOMeCN
C N CH2 CH2
Structure Search Strategy
63
Helpful HINT
There are fees associated with full-file searches of most structure-searchable databases. To see associated costs, type the following within the file of interest:
=> HELP COST
Structure Search Strategy
64
Recall the Search Question:Locate references discussing the preparation of the following substance:
Structure Search Strategy
65
=> FILE CAPLUS => S L3/PREP 7690 L3 2726608 PREP/RLL4 49 L3/PREP (L3 (L) PREP/RLL3 (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
66
Evaluating results
=> D SCAN L4 49 ANSWERS CAPLUS COPYRIGHT 2001 ACS
TI Investigation of radiochemical purity of 99mTc- verapamilST 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.
Structure Search Strategy
67
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:
This predefined display format
Contains these parts of the CAplus record:
BIB Bibliographic information
IBIB Bibliographic information with field names spelled out
ABS Abstract
HITSTR Index term, CA index name, and structure for the hit CAS RN
ALL Full record, all citations (BIB + ABS + indexing)
Structure Search Strategy
68
Step 1 Draw and save the structure.
Step 2 Logon to STN, and enter theREGISTRY file.
=> FILE REGISTRY
Step 3 Upload and verify the structurequery.
=> D L1
Step 4 Run a sample structure search => S L1 EXACT SAM
Structure Search Strategy
Summary
69
Step 5 Evaluate results.
Option: Modify the originalstructure, as needed.
=> D SCAN
Repeat steps 1-5.
Step 6 Run a full-file structure search,and then evaluate results.
=> S L1 EXACT FULL=> D SCAN
Step 7 Enter the CAplus file, and findreferences citing the substances.
=> FILE CAPLUS=> S L2/PREP
=> D BIB ABS HITSTR
Structure Search Strategy
Summary
70
1 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.
2 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.
Skills Practice
71
Substructure Searching
72
Using the structure in the Search Question, run the following searches:
Exact full
Family full
Substructure full
Skills Practice
73
Use D SCAN to look at the answers retrieved in each search. Note the different kinds of
substances retrieved by each type of search.
Exact Family SSS
No. of answers
Unsubstituted structure
Radiolabeled forms,stereoisomers
Salts, mixtures,polymers
Substances withadditional substitution
Skills Practice
74
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
75
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.
For this structural feature in the search
query:
STN Express makes assumptions to retrieve structure matches with the
Ring systems Ring system as drawn
Ring system as part of a larger ring system
Atom in a chain Atom in a chain only
Bond in a chain
Bond in a chain only
Substructure Searching
76
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
77
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
Substructure Searching
78
Building the StructureWorksheet
Structure search requirement
Action
R and R' = anything, including H
No substitution at the carbon in the ring marked with an asterisk (*)
The ring may be further substituted at the open sites
There may be no additional rings fused
Substructure Searching
Don’t draw any atom
Draw a Hydrogen
Don’t draw any atom
Look at the following procedure
79
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:
Step Action
1 Position the cursor over an atom in the ring system that is to be isolated.
2 Right-click. A side-menu of structural items that you can change will display. Select Ring Isolation:
Substructure Searching
80
Ring isolation
Step Action
3 The Ring Isolation dialog box appears. Select Isolated. Click OK.
4 (Option) Verify that a change was made to the structure.
Click the display attributes icon:
Substructure Searching
81
Ring isolationStep Action
5 The Query Attributes pop-up menu appears. Move the cursor to any atom in the isolated ring system. The currently assigned value is shown.
Substructure Searching
82
=> FILE REGISTRY
=> Uploading C:\Program Files\Stnexp\Queries\sss-ring.strL1 STRUCTURE UPLOADED
=> D L1L1 HAS NO ANSWERSL1 STR
N
N
O
O
H
Substructure Searching
83
=> S L1 SSS SAM (or only: => S L1or only: => S L1)SAMPLE SEARCH INITIATED 14:49:50 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 380 TO ITERATE
100.0% PROCESSED 380 ITERATIONS 1 ANSWERSSEARCH TIME: 00.00.01
FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE**PROJECTED ITERATIONS: 6431 TO 8769PROJECTED ANSWERS: 1 TO 80L2 1 SEA SSS SAM L1
Substructure Searching
84
=> D SCAN L2 1 ANSWERS REGISTRY COPYRIGHT 2001 ACSIN 3-Pyridinecarboxylic acid, 1-ethoxy-1,4-dihydro- 4-(phenylimino)-, ethyl ester (9CI)MF C16 H18 N2 O3CI COM
ALL ANSWERS HAVE BEEN SCANNED
EtO OEt
Ph
C
O
N
N
Substructure Searching
85
=> S L1 SSS FULL (or only: => S L1 FULLor 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 ANSWERSSEARCH TIME: 00.00.01L3 21 SEA SSS FUL L1
=> D SCAN L3 21 ANSWERS REGISTRY COPYRIGHT 2001 ACSIN 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
OEt
Me
Ph
NC
CH2
N
C
ONH
Substructure Searching
86
If this structure was drawn and Ring Isolation set to Isolated
would the following substances be retrieved in a substructure search?
Retrieved Not Retrieved
Skills Practice
87
Retrieved Not Retrieved
If this structure was drawn and Ring Isolation set to Isolated
would the following substances be retrieved in a substructure search?
Skills Practice
88
Run the search for this fragment twice:o One with the ring isolated o One with the ring isolated embedded
Look at the differences
Skills Practice
89
Atoms• Atoms in a substructure query may be
Ring Chain Ring/Chain
Substructure Searching
90
Atoms• The default assumption for atom retrieval depends on the
location of an atom in the substructure query.
If, in the substructure query, an atom is part of a
Then, in the retrieved structure matches
Chain The atom will always be part of a chain
Ring The atom will always be part of a ring
Substructure Searching
91
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.,
Substructure Searching
92
Building the Structure
Worksheet
Structure search requirement
Action
R, R', and R" = anything, including H 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 nitrogen, e.g.,
Substructure Searching
Don’t draw any atom
Don’t draw any atom
Rings isolated/embedded
Look at the following procedure
93
Ring/chain atoms• To allow the substructure search to retrieve a chain atom as
part of a ring or a chain, do the following:
Step Action
1 Position the cursor over the atom of interest.
2 Right-click. A side-menu of structural items that you can change will display. Select Node Characteristics:
Substructure Searching
94
Step Action
3 The Node Characteristics dialog box appears. Select Ring/Chain. Click OK.
4 (Option) Verify that a change was made to the structure.
Click the display attributes icon:
Ring/chain atoms
Substructure Searching
95
=> FILE REGISTRY
=> Uploading C:\Program Files\Stnexp\Queries\sss-atom-rc.strL1 STRUCTURE UPLOADED
=> D L1L1 HAS NO ANSWERSL1 STR
NO
O
CH2N
Substructure Searching
96
=> S L1 SSS SAMSAMPLE SEARCH INITIATED 15:06:29 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 15 TO ITERATE
100.0% PROCESSED 15 ITERATIONS 4 ANSWERSSEARCH TIME: 00.00.01
FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE**PROJECTED ITERATIONS: 68 TO 532PROJECTED ANSWERS: 4 TO 200
L2 4 SEA SSS SAM L1
Substructure Searching
97
=> D SCAN L2 4 ANSWERS REGISTRY COPYRIGHT 2001 ACSIN 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
OEtMeO
OMe
MeO
C
O
CH2N
NN
N
OH
Note: The N atom is part of a ring in this substructure match.
Substructure Searching
98
=> D SCAN L2 4 ANSWERS REGISTRY COPYRIGHT 2001 ACSIN 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.
N(Bu-n)2
OEtMeO
OMe
MeO
OMe
C
O
CH2N
Substructure Searching
99
=> S L1 SSS FULLFULL SEARCH INITIATED 15:06:52 FILE 'REGISTRY' FULL SCREEN SEARCH COMPLETED - 288 TO ITERATE100.0% PROCESSED 288 ITERATIONS 114 ANSWERSSEARCH TIME: 00.00.01L3 114 SEA SSS FUL L1
=> D SCANL3 114 ANSWERS REGISTRY COPYRIGHT 2001 ACSIN 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
OEtMeO
OMe
MeO
OMe
C
O
CH2N
NS
Substructure Searching
100
Helpful HINT
To change the characteristics of multiple atoms at one time, do the following:
1. Click the selection tool icon:
2. Hold down the SHIFT key while clicking on atoms whose characteristics are to be changed.
3. From the QueryDef pull-down menu, select Node Characteristics.
4. The Node Characteristics dialog box appears. Select Ring/Chain. Click OK.
Substructure Searching
101
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
102
Bond Type• Bonds in a substructure query may be
Ring Chain Ring/Chain
Substructure Searching
103
Bond TypeIf, in the substructure
query, a bond is part of a Then, in the retrieved structure
matches
Chain The bond will always be part of a chain
Ring
The bond will always be part of a ring
note
Changing chain atoms to Ring/Chain, as in the previous example, does not automatically change the bonds to that atom to Ring/Chain.
Substructure Searching
104
Bond Type
An option exists to specify that a bond type be ring/chain.
By default, the chain bonds in this substructure
Retrieve answers where the bonds are in a chain:
But not answers where the bonds are in a ring:
Substructure Searching
105
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
Substructure Searching
106
Building the StructureWorksheet
Structure search requirement
Action
Any type of substitution at all open sites
Additional rings may be fused to the ring system, including those formed by the O atoms and the CH2—N chain
Substructure Searching
Don’t draw any atom
Ring isolated/embeddedLook at the following procedure
107
• To allow the substructure search to retrieve a chain bond as part of a ring or a chain, do the following:
Step Action
1 Position the cursor over the bond of interest.
2 Right-click. The Bond Characteristics dialog box appears. Select Ring/Chain. Click OK.
3 (Option) Verify that a change was made to the structure.
Click the display attributes icon:
Bond type
Substructure Searching
108
=> FILE REGISTRY
=> Uploading C:\Program Files\Stnexp\Queries\sss-bond-rc.strL1 STRUCTURE UPLOADED
=> D L1L1 HAS NO ANSWERSL1 STR
NO
O
CH2N
Substructure Searching
109
=> S L1 SSS SAMSAMPLE SEARCH INITIATED 17:20:56 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 2128 TO ITERATE
47.0% PROCESSED 1000 ITERATIONS 3 ANSWERSINCOMPLETE SEARCH (SYSTEM LIMIT EXCEEDED)SEARCH TIME: 00.00.01
FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE**PROJECTED ITERATIONS: 39795 TO 45325PROJECTED ANSWERS: 3 TO 278
L2 3 SEA SSS SAM L1
Substructure Searching
110
=> S L1 SSS FULLFULL SEARCH INITIATED 17:23:15 FILE 'REGISTRY' FULL SCREEN SEARCH COMPLETED - 42125 TO ITERATE100.0% PROCESSED 42125 ITERATIONS 133 ANSWERSSEARCH TIME: 00.00.01L3 133 SEA SSS FUL L1
=> D SCAN L3 133 ANSWERS REGISTRY COPYRIGHT 2001 ACSIN 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
OEt
MeOOMe
C
O
CH2NN
O
O
Substructure Searching
111
Locate references discussing compounds containingthe following substructure
Requirements:
Any of the atoms may be part of a ring There may be any type of substitution at any
open site
Skills Practice
N
N NS
+
Have you found this answer?Have you found this answer?
S
N
N
N
112
Bond Structure• Bonds in a substructure query may be drawn as
Single Double Triple Unspecified
Substructure Searching
113
Bond StructureIf, in the substructure
query, the bond is Then, in the retrieved structure matches,
the bond will be
Single Single - In aromatic/tautomeric structures, these may display as double
Double Double - In aromatic/tautomeric structures, these may display as single
Triple Triple
Unspecified Single, double, or triple
Substructure Searching
114
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
Substructure Searching
115
Building the Structure
Worksheet
Structure search requirement
Action
R is a carbon atom in a chain
The bond is single or double
No additional ring fusion is desired on either ring system
Additional substitution may be present at all open sites
Substructure Searching
Draw a C atom
Look at the following procedure
Rings are isolated
Don’t draw any atom
116
• To allow the substructure search to retrieve a bond that is single or double, do the following:
Step Action
1 Draw the structure with the bond drawn as a single bond.
2 From the Draw pull-down menu, select Bond.
Bond structure
Substructure Searching
117
Step Action
3 The Bond Selection dialog box appears. Select Unspecified. Click Single Use.
Substructure Searching
Bond structure
118
Step Action
4 Position the cursor over the bond to be changed. Click to place the bond.
Bond structure
Substructure Searching
119
=> FILE REGISTRY
=> Uploading C:\Program Files\Stnexp\Queries\sss-unspec-.strL1 STRUCTURE UPLOADED
=> D L1L1 HAS NO ANSWERSL1 STR
N
H
H
H
H H
O
Both ring systems were isolated.
Substructure Searching
120
=> S L1 SSS SAMSAMPLE SEARCH INITIATED 12:04:39 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 605 TO ITERATE
100.0% PROCESSED 605 ITERATIONS 9 ANSWERSSEARCH TIME: 00.00.01
FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE**PROJECTED ITERATIONS: 10625 TO 13575PROJECTED ANSWERS: 9 TO 360
L2 9 SEA SSS SAM L1
Substructure Searching
121
=> D SCAN L2 9 ANSWERS REGISTRY COPYRIGHT 2001 ACSIN 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!
EtO
EtO
PhPh
C
O
NC
O
Substructure Searching
122
L2 9 ANSWERS REGISTRY COPYRIGHT 2001 ACSIN 1-Isoquinolinemethanol, 1,2,3,4-tetrahydro-6,7- dimethoxy-2-methyl--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.
MeMeO
MeO
Ph OH
N
HS
R
Substructure Searching
123
=> S L1 SSS FULLFULL SEARCH INITIATED 12:05:40 FILE 'REGISTRY' FULL SCREEN SEARCH COMPLETED - 12523 TO ITERATE
100.0% PROCESSED 12523 ITERATIONS 148 ANSWERSSEARCH TIME: 00.00.01
L3 148 SEA SSS FUL L1
Substructure Searching
124
Bond Value• Bonds in a substructure query may be
Exact Normalized Exact/Normalized
Substructure Searching
125
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
126
Bond Value
Substructure Searching
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
127
Bond Value
Substructure Searching
With all exact bonds
=> l1 exa fullFULL SEARCH INITIATED 09:27:14FULL SCREEN SEARCH COMPLETED - 4911 TO ITERATE 100.0% PROCESSED 4911 ITERATIONS 305 ANSWERSSEARCH TIME: 00.00.01 L2 305 SEA EXA FUL L1 => l2 not ids/ci 222437 IDS/CIL3 74 L2 NOT IDS/CI
128
Bond Value
Substructure Searching
=> d scan L3 74 ANSWERS REGISTRY COPYRIGHT 2003 ACSIN Cyclohexane-d7 (6CI, 7CI, 9CI)MF C6 H5 D7
With all exact bonds
129
Bond Value
Substructure Searching
With all normalized bonds
=> l4 exa fullFULL SEARCH INITIATED 09:29:16FULL SCREEN SEARCH COMPLETED - 20679 TO ITERATE 100.0% PROCESSED 20679 ITERATIONS 1820 ANSWERSSEARCH TIME: 00.00.01 L5 1820 SEA EXA FUL L4 => l5 not ids/ci 222437 IDS/CIL6 182 L5 NOT IDS/CI
130
Bond Value
Substructure Searching
With all normalized bonds=> d scan L6 182 ANSWERS REGISTRY COPYRIGHT 2003 ACSIN Benzene, tetracosamer, radical ion(1+) (9CI)MF (C6 H6)24CI PMS, RIS CM 1
131
Bond Value
Substructure Searching
With all exact-normalized bonds
=> l7 exa fullFULL SEARCH INITIATED 09:30:29FULL SCREEN SEARCH COMPLETED - 29534 TO ITERATE 100.0% PROCESSED 29534 ITERATIONS 2160 ANSWERSSEARCH TIME: 00.00.01 L8 2160 SEA EXA FUL L7 => l2 or l5L9 2125 L2 OR L5 => l8 not l9L10 35 L8 NOT L9
132
Bond Value
Substructure Searching
With all exact-normalized bonds
=> d scan L10 35 ANSWERS REGISTRY COPYRIGHT 2003 ACSIN Cyclohexenylium-1-d (9CI)MF C6 H8 D
D
1+
133
REGISTRY has only these bond values
(Single, double, or triple) Exact (Single, double) Normalized
With STNExpress, you can search
Exact Exact or Normalized Normalized Unspecified
Substructure Searching
134
To change the bond values assigned by STN Express, do the following:
Step Action
1 Click the selection tool icon:
2 Hold down the Shift key while clicking on the bonds whose values are to be changed.
3 From the QueryDef pull-down menu, select Bond Characteristics.
4 The Bond Characteristics dialog box appears. Click Exact. Click OK.
Bond value
Substructure Searching
135
Normalized Bonds in REGISTRY
• In ringsIn 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)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
136
Bond Value
This bond value is
assigned
To substructures with
Normalized Certain tautomeric bonds,
Q------C====Q
Q = Heteroatoms with at least one hydrogen atom
Substructure Searching
137
Normalized bonds are used for certain tautomeric chains:
• 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)
1 32 3H 21 H
Substructure Searching
138
Bond Value
This bond value is
assigned
To substructures with
Normalized bonds in rings containing an even number of atoms and alternating single and double bonds
Substructure Searching
139
Bond ValueThis bond value
is assigned To substructures with
Exact Atoms that are not part of a "tautomeric" or "aromatic" sequence. E.g., the C-C bonds in this cyclohexane are exact single bonds.
Substructure Searching
140
Bond ValueThis bond value is
assigned
To substructures with
Normalized bonds in rings containing an even number of atoms and alternating single and double bonds (e.g., all of the bonds in the "benzo" part of the following structure, are normalized, including the "single bond" it shares with the cyclohexane ring.)
Substructure Searching
141
Normalized bondsExamples Examples
Keto-enol tautomers do not fit the REGISTRY tautomer normalized bond rule, so you have to build a query to find both variations.
acidsamines
amides
CMe2
MeCHO
Pr-iMe C
O
Not normalized bonds
Substructure Searching
142
Normalized bonds
benzenes
N+
cyclooctaquinolizinium
thiophenes
S
N
S
thiazoles
Normalized is not synonymous with aromatic.
Substructure SearchingNot normalized bonds
anthracenes
143
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
144
Substructure Searching
If you draw with STN Express the following structure how the software considers the value bonds? Why?
145
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?
146
Do these rings have normalized bonds?
Me
CH2 Na
N
N
Substructure Searching
147
Me
CH2 Na
N
N
YES YES
NOsingle exact bonds are denoted
Do these rings have normalized bonds?
Substructure Searching
148
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
149
=> FILE REGISTRY
=> Uploading C:\Program Files\Stnexp\Queries\sss-bond-value.strL1 STRUCTURE UPLOADED
=> D L1L1 HAS NO ANSWERSL1 STR
H
H
H
H H
O
Substructure Searching
150
=> S L1 SSS SAMSAMPLE SEARCH INITIATED 14:02:02 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 28 TO ITERATE
100.0% PROCESSED 28 ITERATIONS 3 ANSWERSSEARCH TIME: 00.00.01
FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE**PROJECTED ITERATIONS: 243 TO 877PROJECTED ANSWERS: 3 TO 163
L2 3 SEA SSS SAM L1
Substructure Searching
151
=> D SCANL2 3 ANSWERS REGISTRY COPYRIGHT 2001 ACSIN 1-Naphthalenemethanol, decahydro--[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
MeMe
OMe
Me Me
Ph
PhOH
O
O
H
HS
SSS
Substructure Searching
152
OH O
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?
Skills Practice
153
=> l1 exa fullL2 6
O
154
O=> l3 exa fullL4 74=> l4 not l2L5 74
155
Can you run only one search for retrieving both the structures?Which searching structure? Which kind of search?
O=> l6 exa fullL7 157
Skills Practice
156
=> l7 not l2L8 151 L7 NOT L2 => l8 not l4L9 77 L8 NOT L4
OH
157
S
N
S
N
Run two different searches for the reported structures (Full SSS, STN Express default).- Are the results different?- If yes,why?
Skills Practice
158
=> l1 full L2 2531
H
H
H
H
H
NS
159
=> l3 full L4 2184
H
H
H
H
H
NS
160
=> l2 and l4L5 1486
EtO OEt
Ph
CH
NH
CHC
C
C
OH
O
S
O
161
=> l2 not l4 and nc=1L6 832
EtS
Ph
C N CH2 CH CH2
162
=> l4 not (l2 or m/els) and nc=1 L8 698
t-BuO
Me
PhCN
S
NHCCH2
O
C
O
163
S
N
Which structure search should be run in order to collect all the previous results?
Skills Practice
164
N
S
=> l7 full
L8 12146
165
=> l8 not (l2 or l4)L11 1058
MeMe
CHS
NO
O
C+ -
166
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?
Substructure Searching
167
Run two different searches for the reported structures (Full SSS, STN Express default).- Are the results different?- If yes,why?
N
N
N
Me
Ph
N
N
N
Me
Ph
Skills Practice
168
N
N
N
Me
Ph
=> l1 fullL2 24
169
N
N
N
Me
Ph
=> l3 fullL4 63
170
=> l2 not l4L5 22 L2 NOT L4
Me Ph
Ph
CH2NN
N
171
=> l4 not l2L6 61 L4 NOT L2
Me
Me
Ph CH CHN CH2N
N
172
Which structure search should be run in order to collect all the previous results?
N
N
N
Me
Ph
Skills Practice
173
N
N
N
Me
Ph
=> l7 fullL8 225
174
=> l8 not l2L9 201 L8 NOT L2 => l9 not l4L10 140 L9 NOT L4
175
MeMe
Ph
N
NN
E
176
Pr-i
i-Pr
Me
Me
Me
Me
Ph
Cl
CN
NN+
177
Skills Practice
CHCH
CHCH
CH
CH2NH2
CHCH
CHCH
CH
N
Which is the less expensive search for retrieving both of the previous compounds?
178
BONDS
BE CAREFUL WITH BONDS!
Substructure Searching
179
Substructure Searching
Extend
180
Substructure Searching=> fil reg L1 STRUCTURE UPLOADED => dL1 HAS NO ANSWERSL1 STR
N
F S
F O
181
Substructure Searching
=> l1 FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE**PROJECTED ITERATIONS: 1 TO 80PROJECTED ANSWERS: 0 TO 0 L2 0 SEA SSS SAM L1 => l1 fullFULL SEARCH INITIATED 06:07:43FULL SCREEN SEARCH COMPLETED - 61 TO ITERATE 100.0% PROCESSED 61 ITERATIONS 0 ANSWERS61 ITERATIONS 0 ANSWERSSEARCH TIME: 00.00.01L3 0 SEA SSS FUL L1
182
Substructure Searching
=> set extend on permSET COMMAND COMPLETED => l1 fullFULL SEARCH INITIATED 06:08:38 L4 61 SEA SSS FUL L1 EXTENDL4 61 SEA SSS FUL L1 EXTEND CANDIDATE STRUCTURE SEARCH COMPLETED - 61 TO ITERATE 100.0% PROCESSED 61 ITERATIONS 0 ANSWERSSEARCH TIME: 00.00.01 L5 0 SEA SSS FUL L1
183
Substructure Searching
=> d scan l4
i-BuMeS SMe
F3C CHF2
C N
O
N
CH
i-Bu Me
MeS
CF3F2CH
NO
N
C
O
184
Atom Substitution• There are a number of ways to control atom
substitution in substructure search matches:
If you want this kind of atom substitution
Build this into the substructure query:
A "class" of atoms, e.g., halogens
STN-defined variable atoms
A broadly defined list of substituents
G-group
Variable attachment positions for a ring substituent
Variable point of attachment
Substructure Searching
185
Variable Atoms• A number of system-defined options are available
to allow variability in atom substitution:When this symbol is
part of a substructure These types of matches are
retrieved
X Any halogen
A Anything, except H
Q Anything, except C or H
M Any metal
(continued on next slide)
Substructure Searching
186
Variable Atoms
When this symbol is part of a substructure
These types of matches are retrieved
(continued from previous slide)
Cb Any carbocyclic ring system
Cy Any ring system
Hy Any heterocyclic ring system
Id "Dummy node" - used in specialized polymer searches
Ak Any carbon chain
Substructure Searching
187
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
Substructure Searching
188
Building the Structure
Worksheet
Structure search requirement
Action
R is any type of heterocyclic ring with any kind 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
Substructure Searching
Look at the following procedure
Draw a A variable (R/C)
Rings are isolated
Don’t draw any atom
189
• To add a variable group to an existing structure, do the following:
Step Action
1
Click the variables icon:
2 The Variable Selection dialog box appears. Select the radio button labeled "Hy". Click Single Use.
Variable group
Substructure Searching
190
Step Action
3 Click to place the variable in the structure.
Variable group
Substructure Searching
191
=> FILE REGISTRY
=> Uploading C:\Program Files\Stnexp\Queries\sss-variable.strL1 STRUCTURE UPLOADED
=> D L1L1 HAS NO ANSWERSL1 STR
N
N
CH2CH2
CH2Hy
A
The rings were isolated, and the node characteristic of A was set to ring/chain.
Substructure Searching
192
=> S L1 SSS SAMSAMPLE SEARCH INITIATED 16:29:55 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 2576 TO ITERATE
38.8% PROCESSED 1000 ITERATIONS 15 ANSWERSINCOMPLETE SEARCH (SYSTEM LIMIT EXCEEDED)SEARCH TIME: 00.00.01
FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE**PROJECTED ITERATIONS: 48478 TO 54562PROJECTED ANSWERS: 400 TO 1144
L2 15 SEA SSS SAM L1
Substructure Searching
193
=> D SCANL2 15 ANSWERS REGISTRY COPYRIGHT 2001 ACSIN 2,5-Pyrrolidinedione, 1-[3-[4-(4-methoxyphenyl)-1- piperazinyl]propyl]-(9CI)MF C18 H25 N3 O3CI COM
HOW MANY MORE ANSWERS DO YOU WISH TO SCAN? (1):0
(CH2)3
OMe
N
N
N
OO Hy
A
Substructure Searching
194
=> 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 ANSWERSSEARCH TIME: 00.00.03
L3 1028 SEA SSS FUL L1
Substructure Searching
195
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
196
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
Substructure Searching
197
Building the Structure
Worksheet
Structure search requirement
Action
R = C, N
R' = Me, Et, n-Pr, i-Pr, OH, SH, X
No additional ring fusion on the 6-membered rings
Additional substitution at all open sites
Substructure Searching
Look at the following procedure
Look at the following procedure
Rings are isolated
Don’t draw any atom
198
• To define and add a G-group to an existing structure, do the following:
Step Action
1 From the Draw pull-down menu, select G-groups.
G-group
Substructure Searching
199
Step Action
2 The G-Group Definitions dialog box appears. Click New.
3 The Define New G-Group dialog box appears. Select Atoms, Shortcuts, or Variables, as needed.
G-group
Substructure Searching
200
Step Action
4 The Shortcuts selection menu appears. Click to place a checkmark in the checkboxes associated with items of interest. Click OK.
G-group
Substructure Searching
201
Step Action
5 The Define New G-Group dialog box reappears. Continue to define the G-group as needed. Click Save.
G-group
Substructure Searching
202
Step Action
6 The G-Group Definitions dialog box reappears. Click Single Use.
G-group
Substructure Searching
203
Step Action
7 Click to place the G-group in the structure.
G-group
Substructure Searching
204
=> FILE REGISTRY
=> Uploading C:\Program Files\Stnexp\Queries\sss-ggroup.strL1 STRUCTURE UPLOADED
=> D L1L1 HAS NO ANSWERSL1 STR
N
G2
CH2CH2
CH2G2
NO
G1G1 Me,Et,n-Pr,i-Pr,OH,SH,XG2 C,N
Substructure Searching
205
=> S L1 SSS SAMSAMPLE SEARCH INITIATED 11:59:54 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 11 TO ITERATE
100.0% PROCESSED 11 ITERATIONS 2 ANSWERSSEARCH TIME: 00.00.01
FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE**PROJECTED ITERATIONS: 22 TO 418PROJECTED ANSWERS: 2 TO 124
L2 2 SEA SSS SAM L1
Substructure Searching
206
=> D SCANL2 2 ANSWERS REGISTRY COPYRIGHT 2001 ACSIN 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
(CH2)3
F
F
N
N
O OH G1 = FG2 = C, C
Substructure Searching
207
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
208
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
Substructure Searching
209
Building the Structure
Worksheet
Structure search requirement
Action
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
Substructure Searching
Draw a Hy variable
Rings are isolated
Don’t draw any atom
Look at the following procedure
210
• To add a substituent with a variable point of attachment to an existing structure, do the following:
Step Action
1 Draw the ring-containing component and the substituent as separate, unattached fragments.
2 Click the selection tool icon:
Variable point of attachment
Substructure Searching
211
Step Action
3 Hold down the SHIFT key. Click to highlight the substituent and then each position on the ring where the substituent may be attached.
4 From the Draw pull-down menu, select Variable Points of Attachment.
Variable point of attachment
Substructure Searching
212
Step Action
5 STN Express draws a "connection" from the substituent toeach possible attachment site.
Variable point of attachment
Substructure Searching
213
=> FILE REGISTRY
=> Uploading C:\Program Files\Stnexp\Queries\sss-vpa.strL1 STRUCTURE UPLOADED
=> D L1L1 HAS NO ANSWERSL1 STR
N
N
CH2CH2
CH2Hy X
Substructure Searching
214
=> 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 ANSWERSINCOMPLETE SEARCH (SYSTEM LIMIT EXCEEDED)SEARCH TIME: 00.00.01
FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE**PROJECTED ITERATIONS: 48497 TO 54583PROJECTED ANSWERS: 849 TO 1831
L2 26 SEA SSS SAM L1
Substructure Searching
215
=> D SCANL2 26 ANSWERS REGISTRY COPYRIGHT 2001 ACSIN 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
(CH2)3
Me
F
N
OH
O
N
N
N
Substructure Searching
216
L2 26 ANSWERS REGISTRY COPYRIGHT 2001 ACSIN 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 FULLFULL SEARCH INITIATED 14:21:19 FILE 'REGISTRY' FULL SCREEN SEARCH COMPLETED - 51428 TO ITERATE100.0% PROCESSED 51428 ITERATIONS 1310 ANSWERS SEARCH TIME: 00.00.03 L3 1310 SEA SSS FUL L1
Cl at the meta position(CH2)3
Cl
N N
OO
N
HCl2
Substructure Searching
217
SummaryIf the
substructure contains
Consider the following:
Substructure search default setting
Atoms with open sites
Can sites be freely substituted?
Should substitution be blocked?
Any substitution at open sites
Ring systems Should rings stand alone?
Can rings be embedded in larger ring systems?
Isolated/embedded ring systems
Chain atoms Should the atoms appear only in chains?
Can the atoms appear in rings?
Chain node characteristics
(continued on next slide)
Substructure Searching
218
SummaryIf the
substructure contains
Consider the following:
Substructure search default setting
Chain bonds Should the bonds appear only in chains?
Can the bonds appear in rings?
Chain bond characteristics
Sites where you want to force substitution
Are the substituents of interest defined by system-defined variables?
Are the substituents of interest user-defined?
Variables
G-groups
A ring with one or more positions where substitution may occur
Variable point of attachment
Substructure Searching
219
1 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
220
2 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
221
3 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
222
4 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
223
5 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
Skills Practice