1

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

2

Exercise 2

Find a Synthesis for

NOH

O

OH

Br

Answer Ex.2: SciFinder

3

Reaxys Exercise 4:

Find a synthesis via Reaxys for

N

N

O

N+

OO

4

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!

5

6

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

7

Markush in Reaxys

Exercise 14

• Look for bromonitromethane

a) using the molecular formulab) using the namec) via the structure

8

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:

9

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

10

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

11

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

12

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

13

Exercise 24• Answers

Explore various synthesis trees for imatinib

Exercise 25

14

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

15

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

16

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

17

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

18

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

19

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

20

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

21

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

22

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!

23

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

24

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!)

25

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?

26

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

27

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

28

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

29

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!

30

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!

31

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?

32

Exercise 63

• Was there ever A Case of Criminal Poisoning using anthrax?

Exercise 64

• Does glycine have an effect against snoring?