ReaxysFileTM on STN®: Significantly more
content and further enhancements
FIZ Karlsruhe
Agenda
• ReaxysFile on STN : Database overview
– Enhancements
– Content
– Figures
•
•
•
•
What is in a substance document
Patent information in ReaxysFile on STN
Reactions in ReaxysFile
Search types that can be run in ReaxysFile
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 ReaxysFile 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 ReaxysFile - Enhancements
• Significantly more substances were added
• Addition of inorganic substances including
coordination compounds and alloys
• Information from selected patents is included
– ReaxysFile 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
ReaxysFile 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
– Indexing from approximately 400 Journals
6
All important chemistry-related disciplines
are covered in ReaxysFile
• 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 ReaxysFile (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 ReaxysFile 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 ReaxysFile 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 is indicated in the Field
Availability (FA) table (part of the IDE display)
– References are included within the property display or
all can be displayed using D ALLREF or D ALLPAT
10
Content of ReaxysFile 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):
Chemical Name (CN):
Autonom Name (AUN):
Lin. Struct. Formula (LSF):
Molec. Formula (MF):
Formula Weight (FW):
InChi Key: (INCHI):
Alternate InChi Key: (AINCHI):
Compound Type (CTYPE):
Markush Ref. Count (MARKREF):
. . . .
5920389
(+)-pyrrolidine carboxylic acid,
o o o
Pyrrolidine-1-carboxylic acid
C5H9NO2
C5 H9 N O2
115.132
NYCVCXMSZNOGDH-UHFFFAOYSA-N
NYCVCXMSZNOGDH-QDQILVOLCO
heterocyclic
0
12
Sample substance record (cont.)
Field Availability:
IDE display (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
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
Displaying Patent specific data (PSD)
=> D 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:
Title:
Patent Number:
Inventor:
Patent Assignee:
Abstract:
Main IPC:
Secondary IPC:
Patent
Glucocorticoid receptor modulators
US2002/107235
Kevin K., Liu; Bradley P., Morgan; Ralph P., Robinson
Liu, Kevin K.; Morgan, Bradley P.; Robinson, Ralph P.
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
C07D 279/12
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:
Patent Number
EP1201649
US2002/107235
EP1201649
---
Glucocorticoid receptor modulators
Kind Code Publ. Date
A1
2002/05/02
A1
2002/08/08
B1
2006/05/31
-----
Application No
EP2001-309064
US2001-6215
EP2001-309064
US2000-243993P
Filing Date
2001/10/25
2001/10/26
2001/10/25
2000/10/28
Indexed Patent
--yes
-----
16
Displaying a specific field
=> D MP
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
Displaying Information on Reactions
=> D RX
. . . .
Reaction:
RX
. . . .
Product (.PRO):
React. Struct. Keywords (.SKW):
Record type (.RTYP):
No. of React. Details (.NVAR):
Preparation reactants (.BLB):
No. of References (.NUMREF):
(+)-pyrrolidine carboxylic acid
half reaction
half reaction, has preparation
2
5920389
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 ReaxysFile 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 ReaxysFile on STN
• ReaxysFile 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 ReaxysFile 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 ReaxysFile
Although patents are available throughout ReaxysFile, 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: Indexing of reaction data (RX)
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. . .
RX
. . .
Reaction ID:
Reactant AN (.RAN):
Reactant (.RCT):
22874415
13197503, 5336292
1-(4-chlorobutyl)-4,5-dichloro-2-methyl-1H-imidazole, ...
Product AN (.PAN):
Product (.PRO):
13218853
2-<4-<4-(4,5-dichloro-2methylimidazol-1-yl)...
React.
Record
Number
No. of
mapped reaction
full reaction, has preparation
3
2
Struct. Keywords (.SKW):
type (.RTYP):
of Bond Changes (.NBC):
React. Details (.NVAR):
25
Example: Indexing of one reaction detail
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-2-methylimidazol-1-yl)butyl]-piperazin-1yl}-5-fluoropyrimidine are obtained in the form of an oil.
Reaction Details:
RX
Reaction RID (.RID):
Reaction Classification (.CL):
Yield (.YDT):
Reagent (.RGT):
Solvent (.SOL):
Time (.TIM):
Other Conditions (.COND):
Location (.LCN):
Example title (.TI):
22874415.1
Preparation
83 percent
potassium carbonate
N,N-dimethyl-formamide
12
Heating / reflux
Page column 3-4
EXAMPLE 2 ...
26
Example: Corresponding reaction indexing
...
Reaction Details:
RX
Reaction RID (.RID):
Reaction Classification (.CL):
Yield (.YDT):
Reagent (.RGT):
Solvent (.SOL):
Time (.TIM):
Other Conditions (.COND):
Location (.LCN):
Example title (.TI):
Fulltext of reaction (.TXT):
22874415.1
Preparation
83 percent
potassium carbonate
N,N-dimethyl-formamide
12
Heating / reflux
Page column 3-4
EXAMPLE 2
Preparation of
2-<4-<4-(4,5-dichloro-2...
27
Reaction indexing in ReaxysFile
• 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
ReaxysFile, identify the Accession Numbers for
the substances and search these numbers as
reactants or products
28
Reaction indexing in ReaxysFile (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 ReaxysFile
• Search techniques have not changed with the
reload of ReaxysFile
• 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
Simple search example
=> FIL REAXYSFILE
=> 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
L1
Display substance identification (IDE) and
superfield crystal information (CRY).
ANSWER 5 OF 53 REAXYSFILE COPYRIGHT 2012 Elsevier Properties SA. on STN
Accession Number (AN):
Chemical Name (CN):
Lin. Struct. Formula (LSF):
Molec. Formula (MF):
. . . .
17051734
Ba2CuO(x)Tl2, tetragonal
Tl2Ba2CuO(6-x)
Ba2 Cu O Tl2
33
Simple search example (cont.)
Field Availability:
IDE display (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
. . . .
CRY
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,
<1993>, 607 - 610
. . . .
display.
34
Additional ReaxysFile 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 ReaxysFile on STN
STN regularly offers e-seminars on:
• Physical Property Searching in ReaxysFile
– Find substances
– Find physical properties
– Tips for managing display costs
• Reaction Searching in ReaxysFile
– 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
• ReaxysFile 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
For more information …
CAS
E-mail: [email protected]
Support and Training:
www.cas.org
FIZ Karlsruhe
[email protected]
Support and Training:
www.stn-international.de