management and use of chemistry databases and...
TRANSCRIPT
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MANAGEMENT AND USE OFCHEMISTRY DATABASES
AND PATENT LITERATURE
Hands-on problem solving
Ulrich Jordis
Rajkot, 3.2.2011
Exercise 1:Find the structurefor a trival name
„The optimal conditions for the transformation of galantamine(I) to the official hypotensive apochlorine (II) wereestablished. I was heated in 20% HCl at 100° 3 hrs., the baseof II was pptd. in alk. medium, transformed to II with HCl, and recrystd. from EtOH (m. 163-6°) in 78% overall „
Where would you start searching?
compare the various results obtained via
Reaxys
GlobalSearch
Chemspider
SciFinder
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Exercise 2
Find a Synthesis for
NOH
O
OH
Br
Answer Ex.2: SciFinder
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Reaxys Exercise 4:
Find a synthesis via Reaxys for
N
N
O
N+
OO
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Answer 4:
General Exercise 5:
You are interested in morphothebaine.
Search for
•Structure
•Registry number
•Synthesis
•Books that contain information about it
•One possibility: start using GlobalSearch and look at resultsfrom ChemSpider!
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General exercise 6:You are interested in thiophene analogs of gefitinib - are such compounds patentable?
In Reaxys: Practice Markush search
In SciFinder: Practice the concepts of similarity search and Markush search
S
N
N
NH
F
Cl
N
NH
N
N
O
Cl
F
O
O
gefitinib (=iressa)
Exercise 7:
SciFinder: Search for similar structures & Markush structures
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Markush in Reaxys
Exercise 14
• Look for bromonitromethane
a) using the molecular formulab) using the namec) via the structure
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Exercise 15
• Locate the following compound names:– galanthamine– galantamin– galantamine– Galanthamin
• What do you learn from the result?
Reaxys Exercise 16
• Retrieve all citations that deal with thefollowing substructure:
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Is the following structure available as starting material?
S
SS
Exercise 17
What Hiyama-type couplings are known on thiophene?
Exercise 18
Hint: use this reaction with subtitution allowed on all atoms and chooseReaction Data -> reaction type = hiyama
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Is the following structure available as starting material?
N N
COOH
O
F
F
F
Cl
Exercise 19
Is the crystal structure of RN 89541-34-4 known?
Exercise 20
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Find complexes of any of Be, Mg, Ca. Sr, Ba withthe thiourea substructure:
Exercise 21
You are working on the crystallization of brushite:Are there any patents in this field?
Are there possible applications for your results?
Hint: did you find the following patent?Levinson, Douglas. Rapid identification of conditions, compounds, or compositions that inhibit, prevent, induce, modify, or reverse transitions of physical state, and therapeutic use. PCT Int. Appl. (2002),
SciFinder Exercise 22
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SciFinder Exercise 23• What ring systems are
known that contain the following substructure:
Analyze for precision and choose „ring skeletons / ring skeletons with atoms“
S
N
N
SciFinder Exercise 24• What fluorine substituted
thiophenes are known?:
•Use the variable attachment tool!•Can you exclude all benzo[b]thiophenes in the answers?
6F
5
4
S
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Exercise 24• Answers
Explore various synthesis trees for imatinib
Exercise 25
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You should get a result similar to this!
Search the following reaction:
Exercise 28
Cl
N
NH
a) As drawnb) Substructure on heteroatomsc) Substructure on all atoms
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Search the following structure usingthe options•As drawn, no salts, include related Markush
Exercise 29
and look in at the Markush structures foun!
N
NH
Cl
Find an experimental procedure for thesynthesis of the following structure:
Exercise 30
N
NH
Cl
Hint: show experimental procedure for patent answers in Reaxys
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Search the following reaction:
Exercise 31
Cl
N
NH
a) As drawnb) Substructure on heteroatomsc) Substructure on all atoms
Search for the isolation of curcumin as a natural product
Exercise 32
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Can you find the structure of all substances that have beenisolated so far
a)from curcuma (=tameric)?
b)from galanthus?
Exercise 33
Search the following reaction:
OH
O
N
O
N
H
+
Reaxys Exercise 34
Hint: search also for substructure on all atoms
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Search for the following reaction that uses water as solvent andGives > 90% yield
Exercise 35
What is known about theantimycobacterial activity of
Exercise 36
N
NHO
NH2
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a) Why do you get 6861 answerssearching for tartaric acid in Reaxys?
b) How can you limit theseresults for tartaric acid itself?
c) Why are there still 45 substances?
Exercise 37
Exercise 38• Locate the following
structure:
O
N
O
O
Limit to
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SciFinder Exercise 39• What is the difference between
the following two structures?
Hint: look using the „microscope view“ at the stereochemical descriptors!
Exercise 40
• Try to find reactions for the preparation of 4,5-dichloro-phthalic anhydride
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Exercise 41
• What reagents are known to replace an aromatic bromine against hydrogen?– Define different search strategies an
analyze the results
Exercise 42
• Find labelled (= containing eitherdeuterium, tritium or 13C) analogs of
• A) tolperison• B) formoterol• C) ciprofloxacin
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Exercise 44
• Are there any improvements to the synthesis of thiacalixarenes describedby H. Kumagai et al. Tetrahedron Lett. 1997, 38, 3971
Locate this reference in SciFinder and find citing references!
Exercise 45
R
What methods exist for the creation of a C-C bond between a cycloprapane and a phenyl ring?
Hint: search for reaction substructure marking this bon as „make/break“ and filter by reaction type!
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Exercise 46• What is known about the mechanism of action of
antituberculosis drugs?
Advanced Exercise 50:
You have been asked to prepare a sample of deuterated fumaricacid monomethyl ester:
Describe your search strategy!
If you do not find a direct answer – what will you do?
OH
O
O
O
CD3
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Advanced (SciFinder) 51:
Try to explore the novelty of this structure and look forsimilar structures
Further examples to getfamiliar with SciFinder
(old but still good to practice!)
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Exercise 49
Additional On-Line Questions1. Cyclosporin A2. Stanozolol3. Anhydrous calcium carbonate4. Sildenafil und alle seine Salze5. Augmentin6. Clavulanic acid und alle seine Salze7. Polystyrene (homopolymer)8. Das Copolymer von Styrene, 1,3-butadiene und
acrylonitrile9. Die CAS Registry Number für CH5+ (die
protonisierte Form von Methan)10. Titanium aluminium nitride
SciFinder Exercise 50• The following structure is cited to have
activity against gram-positive bacteria: • Inhibition of Gram positive bacteria with furanones. Kjelleberg,
Staffan; Steinberg, Peter David; Holmstrom, Carola; Back, Arthur. (Unisearch Limited, Australia). PCT Int. Appl. (1999), 22 pp. CODEN:
PIXXD2 WO 9953915O
O
Br
BrO
O
Which similar furanones are known?
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SciFinder Exercise 51Do a substructure search using
OO
1. Lock out further rings2. Get the references3. Analyse/refine using „gram positive“4. look at the answers from Medline!
SciFinder: Searching for chemical reactions: 5 icons to define
search options
Icons for searchingreactions
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Exercise 53
Product
O
O
O
NS
Explore the following (half-)reaction and explainthe differences that result from either option as shown below:
Exercise 54
• You have been asked to write an article about the influence of tobacco smoke on pregnant women: find references that help you most efficiently to write such a paper
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Exercise 55• How many concepts will be identified in
each of the following questions:
1. antibiotic resistance in pigs or poultry2. antibiotic resistance in pigs and poultry3. resistance to antibiotics in pigs or poultry4. resistance to antibiotics in pigs (poultry)5. pig antibiotic resistance
Exercise 56: more topics to explore
1. antibiotic resistance in pigs or poultry2. forensic studies on drug overdose3. methods for prediction (warning) of earthquakes4. pharmaceuticals for the treatment of glaucoma5. defense pheromones used by insects6. studies on the DNA of cheetahs (acinonyx)7. conducting polymers in textiles8. materials for the replacement of bones (e.g. of knees or hips)9. removal of free fatty acids from edible oils10. removal of the bitter components from the juice of citrus fruits11. theoretical calculations on the entropy of DNA12. inhibitors for tyrosine kinase13. biological availability, pharmacokinetics, and absorption of itraconazole14. why fish do not freeze in cold water of the Antarctic or Arctic oceans
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Exercise 57
• Explore the fields of research of the Saurashtra University
• Hint: Use Company Name / Organization and then
• Limit the answers to papers authored byJoshi, H. S.
Exercise 58
Analyse the results
a) By CA Section Title
b) Index term
c) Author name … sort by frequency to find the authors that have the most publications!
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Exercise 59
• Locate the substance caldesmon II– Look at the registy entry: what do you see?– Get all references and remoce duplicates:
explain the reason for duplicates to appearin SciFinder
Exercise 60• Hit the Databases button in
Scifinder to display the following screen: explain!
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Exercise 61• Explore the
influence of vitamin C on the common cold. – Identify the
following referenceHemila, H. Vitamin C and common cold
incidence: A review of studies with subjects under heavy physical stress. International Journal of Sports Medicine (1996), 17(5), 379-383. CODEN: IJSMDA ISSN:0172-4622. CAN 125:246261 AN 1996:564895 CAPLUS
– Via the get related button look for
Exercise 62
• What inventions by Albert Einstein were patented?
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Exercise 63
• Was there ever A Case of Criminal Poisoning using anthrax?
Exercise 64
• Does glycine have an effect against snoring?