1 Structure Searching with STN Express. 2 The REGISTRY database contains chemical substance information. Bibliographic references and abstracts of papers

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


Draw a side-fusedring system

Draw the left-most ring:

1. Click the ring tool:




Click OK.


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


Draw a spiro-fused ring system

Draw one ring:

1. Click the ring tool:




Click OK.


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:


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:




Click OK.

3. Align the cursor with the atom wherebonding is to occur:


Structure Drawing

25


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


Change one or more atoms to one of the elements in the common atoms palette


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


Change one ormore atoms to anelement not in thecommon atomspalette


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


• Atoms may be changed to any of the pre-drawn shortcuts.

Structure Drawing

Specifying Shortcuts

31


Change one ormore atoms to oneof the shortcuts


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


• Bonds may be changed.

Structure Drawing

33


Change one or more bonds to one of the bonds in the common bonds palette


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


Change one ormore bonds to abond not in thecommon bondspalette


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


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.


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


48

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


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


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


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


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


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


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


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


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.


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:


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


59


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


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


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.


62

Option: Evaluate answers

=> D SCAN


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


(CH2)3

i-Pr Me

OMeMeO

OMeOMeCN

C N CH2 CH2


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


64

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


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


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)


The CAS RN from the REGISTRY answer set that caused the answer to be retrieved is highlighted.


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)


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


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


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


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


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.


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


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


Don’t draw any atom

Draw a Hydrogen


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:


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:


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.


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


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


FULL FILE PROJECTIONS: ONLINE **COMPLETE** BATCH **COMPLETE**PROJECTED ITERATIONS: 6431 TO 8769PROJECTED ANSWERS: 1 TO 80L2 1 SEA SSS SAM L1


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


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


OEt

Me

Ph

NC

CH2

N

C

ONH


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


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


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.,


92

Building the Structure

Worksheet


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.,




Rings isolated/embedded


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:


94

Step Action

3 The Node Characteristics dialog box appears. Select Ring/Chain. Click OK.



Ring/chain atoms


95

=> FILE REGISTRY

=> Uploading C:\Program Files\Stnexp\Queries\sss-atom-rc.strL1 STRUCTURE UPLOADED


NO

O

CH2N


96

=> S L1 SSS SAMSAMPLE SEARCH INITIATED 15:06:29 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 15 TO ITERATE



L2 4 SEA SSS SAM L1


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


OEtMeO

OMe

MeO

C

O

CH2N

NN

N

OH

Note: The N atom is part of a ring in this substructure match.


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


Note: The N atom is part of a chain in this substructure match.

N(Bu-n)2

OEtMeO

OMe

MeO

OMe

C

O

CH2N


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


OEtMeO

OMe

MeO

OMe

C

O

CH2N

NS


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.


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)


102

Bond Type• Bonds in a substructure query may be

Ring Chain Ring/Chain


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.


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:


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


106

Building the StructureWorksheet


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



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.



Bond type


108

=> FILE REGISTRY

=> Uploading C:\Program Files\Stnexp\Queries\sss-bond-rc.strL1 STRUCTURE UPLOADED


NO

O

CH2N


109


47.0% PROCESSED 1000 ITERATIONS 3 ANSWERSINCOMPLETE SEARCH (SYSTEM LIMIT EXCEEDED)SEARCH TIME: 00.00.01


L2 3 SEA SSS SAM L1


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


OEt

MeOOMe

C

O

CH2NN

O

O


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


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


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


115


Worksheet


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


Draw a C atom


Rings are isolated


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


117

Step Action

3 The Bond Selection dialog box appears. Select Unspecified. Click Single Use.


Bond structure

118

Step Action

4 Position the cursor over the bond to be changed. Click to place the bond.

Bond structure


119

=> FILE REGISTRY

=> Uploading C:\Program Files\Stnexp\Queries\sss-unspec-.strL1 STRUCTURE UPLOADED


N

H

H

H

H H

O

Both ring systems were isolated.


120




L2 9 SEA SSS SAM L1


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


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


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.


Here, the bond to the O is a single bond.

MeMeO

MeO

Ph OH

N

HS

R


123

=> S L1 SSS FULLFULL SEARCH INITIATED 12:05:40 FILE 'REGISTRY' FULL SCREEN SEARCH COMPLETED - 12523 TO ITERATE


L3 148 SEA SSS FUL L1


124

Bond Value• Bonds in a substructure query may be

Exact Normalized Exact/Normalized


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.


126

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

127

Bond Value


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


=> 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


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


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


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


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


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


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.


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


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


138

Bond Value

This bond value is

assigned


Normalized bonds in rings containing an even number of atoms and alternating single and double bonds


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.


140

Bond ValueThis bond value is

assigned


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.)


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


142

Normalized bonds

benzenes

N+

cyclooctaquinolizinium

thiophenes

S

N

S

thiazoles

Normalized is not synonymous with aromatic.

Substructure SearchingNot normalized bonds

anthracenes

143


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


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

145


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


147

Me

CH2 Na

N

N

YES YES

NOsingle exact bonds are denoted

Do these rings have normalized bonds?


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.


149

=> FILE REGISTRY

=> Uploading C:\Program Files\Stnexp\Queries\sss-bond-value.strL1 STRUCTURE UPLOADED


H

H

H

H H

O


150




L2 3 SEA SSS SAM L1


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.


MeMe

OMe

Me Me

Ph

PhOH

O

O

H

HS

SSS


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?


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!


179


Extend

180

Substructure Searching=> fil reg L1 STRUCTURE UPLOADED => dL1 HAS NO ANSWERSL1 STR

N

F S

F O

181


=> 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


=> 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


=> 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


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



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


187


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


188


Worksheet


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



Draw a A variable (R/C)

Rings are isolated


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


190

Step Action

3 Click to place the variable in the structure.

Variable group


191

=> FILE REGISTRY

=> Uploading C:\Program Files\Stnexp\Queries\sss-variable.strL1 STRUCTURE UPLOADED


N

N

CH2CH2

CH2Hy

A

The rings were isolated, and the node characteristic of A was set to ring/chain.


192




L2 15 SEA SSS SAM L1


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


(CH2)3

OMe

N

N

N

OO Hy

A


194

=> S L1 SSS FULL

FULL SEARCH INITIATED 16:30:53 FILE 'REGISTRY' FULL SCREEN SEARCH COMPLETED - 51401 TO ITERATE


L3 1028 SEA SSS FUL L1


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


196


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


197


Worksheet


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




Rings are isolated


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


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


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


201

Step Action

5 The Define New G-Group dialog box reappears. Continue to define the G-group as needed. Click Save.

G-group


202

Step Action

6 The G-Group Definitions dialog box reappears. Click Single Use.

G-group


203

Step Action

7 Click to place the G-group in the structure.

G-group


204

=> FILE REGISTRY

=> Uploading C:\Program Files\Stnexp\Queries\sss-ggroup.strL1 STRUCTURE UPLOADED


N

G2

CH2CH2

CH2G2

NO

G1G1 Me,Et,n-Pr,i-Pr,OH,SH,XG2 C,N


205




L2 2 SEA SSS SAM L1


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


(CH2)3

F

F

N

N

O OH G1 = FG2 = C, C


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


208


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


209


Worksheet


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


Draw a Hy variable

Rings are isolated



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:



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.



212

Step Action

5 STN Express draws a "connection" from the substituent toeach possible attachment site.



213

=> FILE REGISTRY

=> Uploading C:\Program Files\Stnexp\Queries\sss-vpa.strL1 STRUCTURE UPLOADED


N

N

CH2CH2

CH2Hy X


214

=> S L1 SSS SAM

SAMPLE SEARCH INITIATED 14:20:48 FILE 'REGISTRY' SAMPLE SCREEN SEARCH COMPLETED - 2577 TO ITERATE



L2 26 SEA SSS SAM L1


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


F at the para position

(CH2)3

Me

F

N

OH

O

N

N

N


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


=> 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


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



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



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

Documents

1 Structure Searching with STN Express. 2 The REGISTRY database contains chemical substance information. Bibliographic references and abstracts of papers