ReaxysFile on STN - significantly more content ... - STN International

<strong>ReaxysFile</strong> TM on STN ® : Significantly more
content and further enhancements
FIZ Karlsruhe

Agenda
• <strong>ReaxysFile</strong> on STN : Database overview
– Enhancements
– Content
– Figures
• What is in a substance document
• Patent information in <strong>ReaxysFile</strong> on STN
• Reactions in <strong>ReaxysFile</strong>
• Search types that can be run in <strong>ReaxysFile</strong>
2

What do chemists want to know about a
specific substance?
• What is it?
– Is it novel? Patented?
– What are its physical
characteristics (weight,
melting point, etc.)
• What does it do?
– Is it a reagent? Solvent?
– What is its bioactivity?
– Is it toxic?
• How can I make it?
– How can I change it?
– How can I make it with a
higher yield?
A wealth of experimentally validated
data which can be searched, filtered
and ranked to find the most relevant
answer to a specific question quickly.
3

What is <strong>ReaxysFile</strong> on STN?
• The important collection of chemical substances
and property data
• Substance based database of structures,
substance identification related reaction data
• Numerically searchable physical properties
• Bioactivity data from journals and patents
• Citations to journal and patent references
All available references and all available patents for a
particular substance can be displayed in one step!
4

Reload of <strong>ReaxysFile</strong> - Enhancements
• Significantly more substances were added
• Addition of inorganic substances including
coordination compounds and alloys
• Information from selected patents is included
– <strong>ReaxysFile</strong> is not like bibliographic patent files on
STN
– Information is based on a specific substance
• Some fields and formats were added to make
additional content search- and displayable
• A REACH display format is available
5

<strong>ReaxysFile</strong> on STN: Some figures
• File REAXYSFILE
– More than 19 million substances
• Organic, inorganic and organometallic
• About 1.5 million coordination compounds and 130,000
alloys
– Almost 16 million reaction documents with 31 million
single reactions
– Coverage from 1771 onwards
– Excerption of approximately 400 Journals
6

All important chemistry-related disciplines
are covered in <strong>ReaxysFile</strong>
• Synthetic chemistry
– Experimental reaction and substance data
• Medicinal chemistry, biochemistry and life
sciences
– Structure-activity-relationship data
• Analytical and physical chemistry
– Validated spectral data such as NMR shifts and
additional physical property data
7

All important chemistry-related disciplines
are covered in <strong>ReaxysFile</strong> (cont.)
• Environmental chemistry
– Information such as toxicant uptake in biological
systems
• Materials chemistry
– Coordination compounds and catalysts, alloys,
glasses, ceramics, and factual data
• REACH data
– All available relevant properties can be displayed by
using
=> D REACH
8

Content of <strong>ReaxysFile</strong> substance records
• Substances with a structural formula
• Substances which may be described by means
of names or information about the components
– Biomolecules, mixtures, polymers, solid solutions, etc.
• Inorganic substances described by fields derived
from MF (e.g. alloys)
• Coordination compounds and multicomponent
substances with structural formulas only for the
carbon containing part
9

Content of <strong>ReaxysFile</strong> substance records
• Substance identification (D IDE)
– Includes various information like chemical name,
molecular formula or often chemical structure
– Search for this information serves as starting point for
a search when all or selected information on a
substance is requested, e.g. for a REACH search
• Properties
– The availability of a property can be checked (D IDE)
in the field availability FA
– References are displayed with the selected property
or all can be displayed by D ALLREF and D ALLPAT
10

Content of <strong>ReaxysFile</strong> substance records
• Properties (continued)
– Patent specific data (PSD) are treated as property
data and are listed in the field availability (/FA)
• Reactions
– Information on the role of a substance in a reaction
document and the reaction conditions
– D RX provides all details of the reactions
– References are included in D ALLREF
– Search the Accession Number (AN) of a substance as
Product or Reactant in Reaction file segment
11

Sample substance record
L1 ANSWER 1 OF 1 REAXYSFILE COPYRIGHT 2012 Elsevier Properties SA. on STN
IDE display.
Accession Number (AN): 5920389
Chemical Name (CN): (+)-pyrrolidine carboxylic acid,
o o o
Autonom Name (AUN): Pyrrolidine-1-carboxylic acid
Lin. Struct. Formula (LSF): C5H9NO2
Molec. Formula (MF): C5 H9 N O2
Formula Weight (FW): 115.132
InChi Key: (INCHI): NYCVCXMSZNOGDH-UHFFFAOYSA-N
Alternate InChi Key: (AINCHI): NYCVCXMSZNOGDH-QDQILVOLCO
Compound Type (CTYPE): heterocyclic
Markush Ref. Count (MARKREF): 0
. . . .
12

Field Availability:
Sample substance record (cont.)
Code Name Occurrence
======================================================
o o o
IR Infrared Spectrum 1
MP Melting Point 1
MS Mass Spectrum 1
NMR Nuclear Magnetic Resonance 1
PSD Patent Specific Data 2
This substance also occurs in Reaction Documents:
Code Name Occurrence
========================================================
RX Reaction Documents 2
RX.PAN Product AN 2
IDE display (cont.).
PSD gives selected information:
• Title of the patent and the location where the substance is mentioned
• Information on prophetic substances and Related Markush structure
13

=> D PSD
Displaying Patent specific data (PSD)
L1 ANSWER 1 OF 1 REAXYSFILE COPYRIGHT 2012 Elsevier Properties SA. on STN
Patent Specific Data:
PSD
Location in Patent: Claim
Reference(s):
1. Patent: Glucocorticoid receptor modulators; for details
see display format ALLPAT
2. Patent: 4-hydroxy-benzopyran-2-ones and
4-hydroxy-cycloalkylbpyran-2-ones useful to treat
retroviralinfections; for details see display format
ALLPAT
o o o
PSD
Prophetic compound: prophetic product
Reference(s):
1. Patent: Modified tripeptides; for details see display
format ALLPAT
14

Display all patents with information on a
particular substance with ALLPAT
=> D ALLPAT
L1 ANSWER 1 OF 1 REAXYSFILE COPYRIGHT 2012 Elsevier Properties SA. on STN
All Patents:
ALLPAT
Reference: Patent
Title: Glucocorticoid receptor modulators
Patent Number: US2002/107235
Inventor: Kevin K., Liu; Bradley P., Morgan; Ralph P., Robinson
Patent Assignee: Liu, Kevin K.; Morgan, Bradley P.; Robinson, Ralph P.
Abstract: The present invention provides non-steroidal
compounds of Formula I, and prodrugs and
pharmaceutically acceptable salts thereof, which are
selective modulators (e.g., agonists, partial . . . .
inflammation and others as described below. The
present invention also provides processes for
preparing these compounds. 1
Main IPC: C07D 279/12
Secondary IPC: A61K 31/535; A61K 31/54; A61K 31/553; A61K 31/554;
A61K 31/55; C07D 265/30
Priority Number Priority Date
US2000-243993P 2000/10/28
. . . .
15

Display all patents with information on a
particular substance with ALLPAT (cont.)
. . . .
PATENT INFORMATION
Patent Title: Glucocorticoid receptor modulators
Patent Number Kind Code Publ. Date Application No Filing Date Indexed Patent
EP1201649 A1 2002/05/02 EP2001-309064 2001/10/25 ---
US2002/107235 A1 2002/08/08 US2001-6215 2001/10/26 yes
EP1201649 B1 2006/05/31 EP2001-309064 2001/10/25 ---
--- --- --- US2000-243993P 2000/10/28 ---
16

=> D MP
Displaying a specific field
L1 ANSWER 1 OF 1 REAXYSFILE COPYRIGHT 2012 Elsevier Properties
SA. on STN
Melting Point:
Value |Ref.
(MP) |
(Cel) |
===========+====
132 - 136 |1
Reference(s):
1. Patent: 4-hydroxy-benzopyran-2-ones and
4-hydroxy-cycloalkylbpyran-2-ones useful to treat retroviral
infections; see display format ALLPAT
17

=> D RX
. . . .
Displaying Information on Reactions
Reaction:
RX
. . . .
Product (.PRO): (+)-pyrrolidine carboxylic acid
React. Struct. Keywords (.SKW): half reaction
Record type (.RTYP): half reaction, has preparation
No. of React. Details (.NVAR): 2
Preparation reactants (.BLB): 5920389
No. of References (.NUMREF): 2
Reaction Details:
. . . .
Reference(s):
1. Patent: 4-hydroxy-benzopyran-2-ones and
4-hydroxy-cycloalkylbpyran-2-ones useful to treat
retroviral infections; for details see display format
ALLPAT
18

Patent Information in <strong>ReaxysFile</strong> on STN
• The information is derived from selected patents
– IPC Classes C07 (Organic Chemistry), A61K and
secondary IPC C07 (Medicinal, Dental, Cosmetic
Preparations), and C09B (Dyes)
– English-language patents from WIPO, EPO and-or
USPTO
• Only one family member is indexed
• Main areas indexed from patents are
reactions/preparations, uses, spectral data,
bioactivity and basic physical data
19

Patent Information in <strong>ReaxysFile</strong> on STN
• <strong>ReaxysFile</strong> is substance-oriented database, not
a bibliographic patent database
– Patent information is connected directly with the
substance that is described
– Best starting point for a search is the substance
identification
• All patents with information on the particular
substance can be displayed with D ALLPAT
20

Searching bibliographic patent information
• Focus of <strong>ReaxysFile</strong> is on physical, chemical
and bioactivity properties
• Bibliographic patent information is not fully
standardized; Records based on older patents
may sometimes yield confusing results
• Fields include: patent number (/PN), Assignee
(/PA), Inventor (/IN), Title (/TI), Language (/LA)
• Available field codes may vary between
substance and reaction documents
21

Patents in <strong>ReaxysFile</strong>
Although patents are available throughout <strong>ReaxysFile</strong>, the volume
and detail of patent coverage increased significantly from 2003.
22

Patent documents: which data are indexed?
23

Example: Reaction information in a patent
EXAMPLE 2
Preparation of 2-{4-[4-(4,5-dichloro-2-methylimidazol-1-yl)butyl]piperazin-1-yl}-5-fluoro pyrimidine
A mixture of 3.5 g (0.02 mol) of 5-fluoro-2-(piperazin-1-yl)pyrimidine, 6.04 g (0.025 mol) of
1-(4-chlorobutyl)-4,5-dichloro-2-methyl-1H-imidazole and 4.14 g (0.03 mol) of potassium carbonate in
200 ml of dimethylformamide is maintained at reflux for 12 hours. The mixture is subsequently
evaporated to dryness and the resulting crude product is redissolved in chloroform and washed
repeatedly with water. The organic phase is dried and evaporated, and then the resulting crude product
is purified by chromatography on a column of silica gel. 6.4 g (83% yield) of 2-({-[4-(4,5-dichloro-2methylimidazol-1-yl)butyl]-piperazin-1-yl}-5-fluor
opyrimidine are obtained in the form of an oil.
IR (film), cm@-1 : 2944, 1610, 1555, 1503, 1449, 1402, 1361, 1243, 786.
@1 H NMR (CDCl3, 300 MHz), .delta.1.54 (m, 2H), 1.73 (m, 2H), 2.34 (s, 3H), 2.38 (m, 2H),
2.43 (m, 4H) 3.74 (m, 4H), 3.85 (m, 2H), 8.15 (s, 2H).
24

EXAMPLE 2
Example: Indexing of reaction data (RX)
Preparation of 2-{4-[4-(4,5-dichloro-2-methylimidazol-1-yl)butyl]piperazin-1-yl}-5-fluoro pyrimidine
A mixture of 3.5 g (0.02 mol) of 5-fluoro-2-(piperazin-1-yl)pyrimidine, 6.04 g (0.025 mol) of
1-(4-chlorobutyl)-4,5-dichloro-2-methyl-1H-imidazole and 4.14 g (0.03 mol) of potassium carbonate in 200 ml
of dimethylformamide is maintained at reflux for 12 hours. The mixture is subsequently evaporated to
dryness and the resulting crude product is redissolved in chloroform and washed repeatedly with water. . .
RX
Reaction ID: 22874415
Reactant AN (.RAN): 13197503, 5336292
Reactant (.RCT): 1-(4-chlorobutyl)-4,5-di-
chloro-2-methyl-1H-imidazole, ...
Product AN (.PAN): 13218853
Product (.PRO): 2-

EXAMPLE 2
Example: Indexing of one reaction detail
Preparation of 2-{4-[4-(4,5-dichloro-2-methylimidazol-1-yl)butyl]piperazin-1-yl}-5-fluoro pyrimidine
A mixture of 3.5 g (0.02 mol) of 5-fluoro-2-(piperazin-1-yl)pyrimidine, 6.04 g (0.025 mol) of
1-(4-chlorobutyl)-4,5-dichloro-2-methyl-1H-imidazole and 4.14 g (0.03 mol) of potassium carbonate in 200 ml
of dimethylformamide is maintained at reflux for 12 hours. The mixture is subsequently evaporated to
dryness and the resulting crude product is redissolved in chloroform and washed repeatedly with water. The
organic phase is dried and evaporated, and then the resulting crude product is purified by chromatography
on a column of silica gel. 6.4 g (83% yield) of 2-({-[4-(4,5-dichloro-2-methylimidazol-1-yl)butyl]-piperazin-1yl}-5-fluoropyrimidine
are obtained in the form of an oil.
Reaction Details:
RX
Reaction RID (.RID): 22874415.1
Reaction Classification (.CL): Preparation
Yield (.YDT): 83 percent
Reagent (.RGT): potassium carbonate
Solvent (.SOL): N,N-dimethyl-formamide
Time (.TIM): 12
Other Conditions (.COND): Heating / reflux
Location (.LCN): Page column 3-4
Example title (.TI): EXAMPLE 2 ...
26

Example: Corresponding reaction indexing
...
Reaction Details:
RX
Reaction RID (.RID): 22874415.1
Reaction Classification (.CL): Preparation
Yield (.YDT): 83 percent
Reagent (.RGT): potassium carbonate
Solvent (.SOL): N,N-dimethyl-formamide
Time (.TIM): 12
Other Conditions (.COND): Heating / reflux
Location (.LCN): Page column 3-4
Example title (.TI): EXAMPLE 2
Fulltext of reaction (.TXT): Preparation of
2-

Reaction indexing in <strong>ReaxysFile</strong>
• Each reaction is a separate database record
– Display of reaction as part of a substance records are
possible , but
– Searches with a direct combination of substance and
reaction terms are not possible. These searches
always result in zero hits.
• To search for substances in the reaction part of
<strong>ReaxysFile</strong>, identify the Accession Numbers for
the substances and search these numbers as
reactants or products
28

Reaction indexing in <strong>ReaxysFile</strong> (cont.)
• A special basic index (BIRX) contains single
terms from several fields (CN, ANs, text
containing fields).
• All reaction steps and stages are indexed
29

Searching <strong>ReaxysFile</strong>
• Search techniques have not changed with the
reload of <strong>ReaxysFile</strong>
• Inorganic substance searches can be run as
they were in the former GMELIN97 database
• Substances continue to be available via
structure search, molecular formula, chemical
name, etc.
• Properties and Reaction details can be searched
as in the past
30

Often information can be obtained via a
simple search and a single display
Search Question
Obtain information on the crystal space groups of
inorganic compounds containing only barium,
copper, thallium and oxygen.
31

Search strategy
1) Search for the element symbols and restrict the
molecular formula to a total of 4 elements
2) Search for the availability of crystal space
group (CGS) data in the field availability,
CGS/FA
3) Use the most cost effective display format,
superfield CRY, to display all available crystal
system information at one time
32

=> FIL REAXYSFILE
Simple search example
=> S BA/ELS AND CU/ELS AND TL/ELS AND O/ELS AND 4/ELC AND
CSYS/FA
ELS – ELement Symbols
L1 53 BA/ELS AND CU/ELS AND TL/ELS AND O/ELS AND 4/ELC
ELC – ELement Count
AND CSYS/FA
CSYS /FA – Crystal SYStem
information availability
=> D 5 IDE CRY
Display substance identification (IDE) and
superfield crystal information (CRY).
L1 ANSWER 5 OF 53 REAXYSFILE COPYRIGHT 2012 Elsevier Properties SA. on STN
Accession Number (AN): 17051734
Chemical Name (CN): Ba2CuO(x)Tl2, tetragonal
Lin. Struct. Formula (LSF): Tl2Ba2CuO(6-x)
Molec. Formula (MF): Ba2 Cu O Tl2
. . . .
33

Field Availability:
Simple search example (cont.)
Code Name Occurrence
======================================================
o o o
CRYPH Crystal Phase 2
CSG Crystal Space Group 23
CSYS Crystal System 1
ELE Electrical Data (MCS) 2
LUM Luminescence 1
MAG Magnetic Data 2
. . . .
Crystal Space Group:
CSG
Note(s) (.COM): a = 3.8686 Angstroem, c = 23.223 Angstroem
Reference(s):
1. Triscone, G.; Junod, A.; Muller, J.; Opagiste, C.;
Couach, M.; et al.,
Journal of Alloys and Compounds, CODEN: JALCEU, 195,
, 607 - 610
. . . .
IDE display (cont.)
CRY display.
34

Additional <strong>ReaxysFile</strong> search examples
• Determine if the chemical behavior of a
substance has been described in the past
chemical literature
• Find syntheses for a given substance
• Search for members of a substance family which
are used as catalysts
• Find comprehensive physical data of
intermediates of a specific reaction
35

Resources for using <strong>ReaxysFile</strong> on STN
STN regularly offers e-seminars on:
• Physical Property Searching in <strong>ReaxysFile</strong>
– Find substances
– Find physical properties
– Tips for managing display costs
• Reaction Searching in <strong>ReaxysFile</strong>
– Find substances
– Find reactions
– Basic tips for managing display costs
For additional information, see:
http://www.stn-international.de/stn_chemistry_reaxysfile.html.
36

Summary
• <strong>ReaxysFile</strong> on STN is a substance-based
database
• Patent information is connected with the
substance mentioned
• All types of substances are included
• All references and patents which are available
for a substance can be displayed with 2 display
formats: ALLREF and ALLPAT
37

CAS
E-mail: help@cas.org
Support and Training:
www.cas.org
For more information …
FIZ Karlsruhe
helpdesk@fiz-karlsruhe.de
Support and Training:
www.stn-international.de