Reaxys Training Part 1 November 14, 2018November 14, 2018

Agenda Scenario #1 Advanced Data Search Scenario #2 Compounds with a generalized structure with Staph aureus IC50 data Scenario #3 Trifluoromethylation reactions

Scenario #1 Advanced Data Search

Advanced Data Search -Introduction Select the Advanced Search link The Advanced Search feature enables you to drill into the database by querying on data fields. Advanced Search queries use the following syntax: <fieldcode> <operator> <field value> Detailed descriptions of the fields can be found in the Reaxys Help in the Searching Property Data section. Detailed descriptions of the operators can be found in the Reaxys Help in the Advanced Search Operators section. Select the Show fields and Operators link to view and select fields If you know the codes and operators you would like to use, you can simply type them into this box. For example: IDE.CN = 'cisplatin' AND CIT.PY='2009'

Advanced Search Operators - Use an asterisk (*) as a wild card - Use single quotes (‘ ‘) around values (see examples in upcoming slides)

Fields - There are over 800 searchable fields in Reaxys - You can search in specific fields or search the Basic Index - There is a Basic Index for Reactions, Substances, and Citations

Context Is Important Find information on “silica modification” Query from Reactions Tab Query from Substances Tab Terms found in Substance Details Terms found in Reaction Details Context Is Important Query from Text tab Terms found in Titles and Abstracts Find information on “silica modification” Examples shown from each of the 3 contexts in Reaxys.

Advanced Search Example (Multiple Fields) -Select a field Search for substances with: Density between 0.9-1.1 g/cc at 20 deg. Viscosity of 0.02-0.12 P at 20 deg. Surface tension between 55-65 dyn/cm. 1.  Click the Advanced Search link. Click Show fields and Operators. 2.  Choose a data field. Click [+] near Physical Data. Then click the desired field: Density of the Liquid. 1 2

... Advanced Search -Add density value 2 1 4 3 1.  Select the = operator from the drop-down menu. 2.  Click the   button to open the index so that you can select the density value that you need. 3.  Type the desired value in the "Search For" box. The exact range you are looking for (0.9-1.1) may not be there. Click the most similar entry (0.9-1) and click the Transfer button. 4. Then, simply type your edits into the large box. ... 2 1 4 3 Edit the new query. Click the desired value

... Advanced Search -Specify density temperature 4 1 3 2 PROXIMITY Operator: values are related To ensure that your results include the specified density value along with the corresponding specified temperature, the PROXIMITY “field-joining” operator must be used. 1.  Select the density Measurement Temperature field. 2.  Select PROXIMITY from the drop-down menu that appears. 3.  Click the button to open the index so that you can select the density temperature value that you need. AND Operator: values are not related ... 4 4. Type the desired value (20) in the "Search For" box, select 20, then click the Transfer button. 1 3 2 Select the PROXIMITY Operator DEN.DEN='0.9 - 1.1' PROXIMITY DEN.T='20'

... Advanced Search -Add viscosity constraints 1 4 2 3 5 6 7 “Field-joining” Operator   1.  Select the appropriate viscosity field. 2.  Select the AND operator for the “field-joining” operator. Select BETWEEN for the “value” operator. Click the box to open the index. 5.  Type the first number of the desired range value (0.02-0.12) in the "Search For" box, click the appropriate entry and then click the Transfer button. “Value” Operator DEN.DEN='0.9 - 1.1' PROXIMITY DEN.T='20' AND DV.DV between 0.02 and 0.1 6 DEN.DEN='0.9 - 1.1' PROXIMITY DEN.T='20' AND DV.DV between 0.02 and 0.12 ... Edit the new query   Hint: You can use either the AND or BETWEEN “value” operator when adding a range of numbers.   6.  Edit the new query. 7. Add the viscosity temperature value (20) using the PROXIMITY “field-joining” operator. 7 DEN.DEN='0.9 - 1.1' PROXIMITY DEN.T='20' AND DV.DV between 0.02 and 0.12 PROXIMITY DV.T='20'

-Add surface tension constraints Advanced Search -Add surface tension constraints 1 Surface tension = 55-65 2 Surface tension temperature = 20 Complete query DEN.DEN='0.9 - 1.1' PROXIMITY DEN.T='20' AND DV.DV between 0.02 and 0.12 PROXIMITY DV.T='20' AND ST.ST='55 - 65' PROXIMITY ST.T='20' 12

Advanced Search Results 1 Substance with 357 citations View Citations Substance availability info Click hyperlinks for reactions View Hit only (see following slide)

Advanced Search Results -”Hit Only” example

Scenario #2 Compounds with a generalized structure with Staph aureus IC50s data

Scenario #2 Find acid or ester substances with antibacterial activity against Staph aureus. Retrieve only those substances with reported IC50 values and export the data in a SAR table.

Let’s open MarvinSketch and draw a general structure for our substructure search.

Include additional options Then add the Advanced Properties parameters to look for antibacterial effects, staph aureus as the species, and ic50 as the type Include additional options Include additional options. Then add the Advanced Properties parameters to look for antibacterial effects, staph aureus as the species, and ic50 as the type

Notice the link for Hit Data View the results. Notice the link for Hit Data View the results. Notice the link for Hit Data

Export results in a variety of formats

Scenario #3 Trifluoromethylation reactions

Scenario #3 Find products of trifluoromethylation reactions that use palladium-containing catalysts. Limit the list to patents from 2006 – the present. Select a reaction and, for the product, view the Markush table and related compounds. Export data to different file types.

We are looking for trifluoromethylation reactions that result in aromatic compounds using palladium-containing compounds. Let’s open MarvinSketch and draw a general structure for our substructure search. Next, we’ll specify palladium by opening the Reaction Details Reagent/Catalyst fields and entering palladium a couple of different ways, including wildcards. We are looking for trifluoromethylation reactions that result in aromatic compounds using palladium-containing compounds. Let’s open MarvinSketch and draw a general structure for our substructure search. Next, we’ll specify palladium by opening the Reaction Details Reagent/Catalyst fields and entering palladium a couple of different ways, including wildcards.

This results in a list of over 19,000 reactions This results in a list of over 19,000 reactions. However, notice that the first one isn’t exactly what we are looking for because it has a similar substance as the reactant. I will try to eliminate these unwanted reactions by, first, repeating the query specifying Starting Material instead of Product. Then, after getting the results, I will subtract the second list from the first list. This results in a list of over 19,000 reactions. However, notice that the first one isn’t exactly what we are looking for because it has a similar substance as the reactant. I will try to eliminate these unwanted reactions by, first, repeating the query specifying Starting Material instead of Product. Then, after getting the results, I will subtract the second list from the first list.

This list management is done by selecting the History button and then selecting the 2 queries of interest. Here are my 2 queries that resulted in over 19,000 hits. I’ll click the Combine button and then click to eliminate the second list from the first list. This list management is done by selecting the History button and then selecting the 2 queries of interest. Here are my 2 queries that resulted in over 19,000 hits. I’ll click the Combine button and then click to eliminate the second list from the first list.

We now have a list of over7,000 reactions. For this example, I’d like to view reactions from patents, so I’ll filter the list by Document Type. We now have a list of over7,000 reactions. For this example, I’d like to view reactions from patents, so I’ll filter the list by Document Type.

I now have a list of 82 reactions. Scrolling through the reactions...notice the Reaction Details. The Hit Details (those with palladium-containing catalysts) are separated from the other Reaction Details (those without palladium). I now have a list of 82 reactions. The Experimental Procedure section of the patent is included in the details. You can also view the Abstract and the Full Text. Some catalysts are hyperlinked to the substance record for that catalyst. I now have a list of 82 reactions. Scrolling through the reactions...notice the Reaction Details. The Hit Details (those with palladium-containing catalysts) are separated from the other Reaction Details (those without palladium). Some catalysts are hyperlinked to the substance record for that catalyst. The Experimental Procedure section of the patent is included in the details. You can also view the Abstract and the Full Text.

I see some Reaction Details that include multi-steps. Click View Scheme to see all the steps at once. Clicking ahead to the last page.... Clicking ahead to the last page....I see some Reaction Details that include multi-steps. Click View Scheme to see all the steps at once. This screen is called the Synthesis Planner.

This screen is called the Synthesis Planner. In addition to displaying a reaction scheme, the Synthesis Planner also lets you change steps in the reaction and add reactions from different sources. For example, clicking on Synthesize here will display a new list of reactions from which to choose. Information on purchasing compounds is also available by clicking the blue “e” for emolecules.com or the blue diamond for Symyx Available Chemicals Directory In addition to displaying a reaction scheme, the Synthesis Planner also lets you change steps in the reaction and add reactions from different sources. For example, clicking on Synthesize here will display a new list of reactions from which to choose. Information on purchasing compounds is also available.

Click the Citations tab to view the patent records. Now, I’m going to narrow the results down by filtering for patents from 2006 – present. A list of 24 reactions from 19 patents results. This includes: Patent Assignees, Inventors, IPC codes, all application numbers, and other patent numbers. There are also a links to the substances and reactions from the patent. Let’s see what kind of information can be found by clicking the Front Page link. Now, I’m going to narrow the results down by filtering for patents from 2006 – present. A list of 24 reactions from 19 patents results. Click the Citations tab to view the patent records. Here is the information that you will find under the Front Page link. This includes: Patent Assignees, Inventors, IPC codes, all application numbers, and other patent numbers. There is also a link to the substances and reactions from the patent

If you can’t see the structure clearly, click the magnifying glass. Now, right-click, open the menu, and select Markush Details to view the markush structure with it’s substituents displayed in a table. If you can’t see the structure clearly, click the magnifying glass. The Product is part of a Markush structure, as described in the patent. Click to view the related markush structure. Back to the Reactions list..... Let’s look at the last reaction in the list. Right-click the grey box under the Product. Back to the Reactions list..... Let’s look at the last reaction in the list. Right-click the grey box under the Product. The Product is part of a Markush structure, as described in the patent. Click to view the related markush structure. If you can’t see the structure clearly, click the magnifying glass. Now, right-click, open the menu, and select Markush Details to view the markush structure with it’s substituents displayed in a table.

..........as well as this list of possible uses. This tells us that in Claim 9 of this patent the structures portrayed in this table are also claimed by the author.......... ..........as well as this list of possible uses. This tells us that in Claim 9 of this patent the following structures are also claimed by the author..........as well as this list of possible uses.

Here is the list of 23 compounds. They can also be viewed in a grid. From this display, we can also get the related compounds specifically mentioned in the patent (all of the related structures from the table may not be available). From this display, we can also get the related compounds specifically mentioned in the patent (all of the related structures may not be available). Here is the list of 23 compounds. They can also be viewed in a grid.

Here are some examples of Excel, SD File, and PDF formats. It’s easy to export results in a variety of formats by clicking the Output button. Here are some examples of Excel, SD File, and PDF formats. It’s easy to export results in a variety of formats by clicking the Output button. Here are some examples of Excel, SD File, and PDF formats.

Thank You! End of Part 1