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20th January 2014 @ 22:28

In this post, how to conduct a search for the commercial availability of a series of similar compounds is exemplified by the search for molecules relevant to series four.

Following Mat Todd’s condensation of the MMV amide spreadsheet into an easy-to-read wiki entry, I have conducted an amine availability search to assist in the selection of five affordable amines to be used in the synthesis of some series four compounds. We will probably choose five new amines and one from the existing library so we can verify the potency results.

Based upon the data already collected for this small library, it seems that high potency requires the inclusion of halogens on the amide substituent and an acyclic amine.

 

Searches were carried out in the following manner:

1. The chemical search engine, eMolecules was used.

2. I began the search with one of the amines from the library, MMV670944, which had promising potency.

MMV670944.PNG

3. This molecule was drawn into eMolecules and an ‘Exact Structure Search’ conducted.

amine_1.png

4. From the results page it was then possible to check the availability and price of the compound by clicking on the ‘Supplier’s ID’ links. Supplier availability and pricing for possibly amines is summerised below.

amine_2.PNG

5. Once the suppliers had been searched, I clicked back to the eMolecules search page. I then conducted a ‘Similiarity Search’ on the same amine. The ‘Similarity Search’ tool proved more useful than the ‘Substructure Search’ function.

amine_3.PNG

6. This yielded a results page showing the suppliers of similar molecules which appear in order of decreasing similarity.

amine_4.PNG

7. Following this, ‘Similarity Searches’ for the following high-potency amides, was conducted.

Amines used for similarity search.png

8. From the resulting searches, amines of interest were selected based on the following criteria.

The amines were:

- not prohibitively expensive

- halogenated

- acyclic (however, in the MMV library there was only one example of a cyclic amide which was also halogenated, so this combination could require further attention)

              

Prices of selected amines from the MMV library:

From MMV library ACS.png


Prices of possible new amines:

Possible amines to try ACS.png
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20th January 2014 @ 11:23

There are excellent how-to guides for using the lab notebook and Github.

There are a few extra general guidelines common to both that need to be borne in mind. These are summarized below, and were originally described here and here. Some points are also mentioned in this guide to making the perfect chemistry ELN entry.

1) Context. A lab book post or a GitHub Issue must have some context, to be clear to an outsider or someone who arrives at the project at that point. For an experiment there should be a reason given for the experiment somewhere near the start, ideally with a link to another experiment or to the literature. For a good example see here. For a Github Issue there needs to be some link out to the reason for a particular issue having arisen and why it needs to be solved. For a good example see here.

2) Completion. If an experiment has been completed, a sentence to this effect (along with the conclusion derived from the experiment) needs to be placed near the beginning of the entry. For Github issues, Issues should be closed, ideally with a comment as to why the Issue is being closed, or perhaps with a link to a more recent Issue that was opened that supersedes the existing issue and makes it redundant.

3) All data. Remember that an ELN entry needs to include all data relevant to an experiment. Raw and processed data. Everything should be present that allows us to write up the compound's synthesis for publication.

4) Citations. ELN entries are the bedrock of the project. If something is being discussed on Github, or elsewhere, about some aspect of the lab work, include links to the ELN to justify statements. e.g. rather than saying "Reaction X appears to be working" instead say "Reaction X appears to be working based on the NMR spectrum [here]" Also within Github, if there are Issues relevant to other issues, simply pasting in the URL for one issue will create a link between them automatically, which can be very useful.

5) Schemes - all ELN entries should have schemes. Github entries mentioning molecules should have pictures - very easy to drag and drop.

6) Strings - Inchis need to be added to ELN entries for molecules that have been synthesized, whether they are the product of a reaction or they have been employed as reagents. Smiles appear to be less effective.

7) Tags in Github. To allow OSM to maintain active collections of activity (e.g. all molecules being made, or all activity on a particular series) we must used Github tags. When creating or commenting on an issue, please consider whether the right tags are being used.

8) When making a molecule. Create a Github Issue for the molecule. Tag it with "Being Synthesised". Provide an approximate timeline for completion of the synthesis, either using Github itself or by writing in a deadline to the Issue. Close the Issue when the molecule has been made.

 

Though these are more things to remember, they will make the ELN and Github much better resources for the project.

This post authored by Mat Todd

10th January 2014 @ 05:36

Welcome to the OSM Team, we're delighted that you've joined the project. This aim of this blog is to provide links to all the relevant information you need to get you started. This post can be used at any institution although there will of course be different guidelines for practical work and analysis at different universities/research institutes and your supervisor will tell you everything that you need to know.

So, first up here is the OSM landing page: www.opensourcemalaria.org. This is the project's porthole and where you will find links to all of the online tools for the project:

The Wiki

First of all, head over the project wiki to find out about the story so far for the OSM project and also the current progress on different compound series. You can sign up for a wiki account here (pending Mat Todd's approval) and then you will be able to edit and contribute to these important pages.

The ELN

The most important tool for the project and most especially for us experimentalists is the electronic labnotebook (ELN - http://malaria.ourexperiment.org). This is the place where the team writes up ALL experiments and posts ALL data as soon as is physically possible. The ELN is one of the features of the OSM project that sets us apart from other drug discovery teams. All of our data and experiments can be viewed by ANYONE who has access to the internet. It is therefore really important that the ELN is maintained to the highest of standards so that anyone could follow the procedures or use the data. One important feature of the ELN is something called revision history. This means that although posts can be edited, a record is kept each time changes are made to a post. This is an essential feature for a scientific project as a lab notebook is a legal document and its is important that noone can change data or modify results. 

But what if I make an error or mistake? Don't panic, that's fine we all make mistakes! Of course its good to check over work for calculation or typographical errors before publishing but its fine to edit any errors. Each time you make an edit, a short comment is required to detail the reason that changes have been made. If something goes wrong with your experiment (even the best chemists occasionally drop a flask!), again don't worry just make a note of what happened on your lab notebook. Remember, some of the most important scientific discoveries have been the result of serendipity so it's important to record what you did accurately and what happened so that you (or any other chemist) can repeat the experiment again.

OK, so how do I complete a 'perfect' entry in the ELN?

Glad you asked:

1) First of all you need to sign up following this guide.

2) Follow this template for excellent results.

A word about Hazard and Risk Assessment (HIRAC)

The HIRAC is an essential part of each experiment and should be completed BEFORE you even remove any chemicals from the cupboard. The template is found here and a new HIRAC should be completed for every new reaction that you perform or if you scale up a reaction that has already been performed. Each HIRAC MUST be signed by either Alice or Mat prior to starting your reaction. More details can be found in the school safety handbook (also found here) and you should read this before conducting any experimental work.

GitHub

The main feed found on the project landing page is directly updated from OSM's GitHub repostitory. GitHub is the organisational tool for the project and is where the 'to do list' is hosted and edited. GitHub allows anyone (in- or outside of the project) to see what's going on and what needs to be done and hopefully prevents dupliation. To sign up to Github follow this guide and then you can join in discussions or update issues once completed. 

Twitter, G+ and Facebook 

The above social media sites are used to promote and publicise the project but also as important platforms for discussion. Many great contributions are received as comments on these sites so it would be great if you signed up for accounts (particularly for Twitter and G+).

Mugshots

All members of the team have a picture on the 'meet the team' part of the landing page. To be added to this hall of fame please sign up for a gravatar account and email opensourcemalaria@gmail.com from the address you used to sign up to gravatar. Alternatively, you can send us a picture but gravatar is preferable.

Specific Links

Many useful links for USyd chemists can be found here. Other institutions that would like to link from this page please comment below and the team will add the links.

Hopefully this page will help you to get started as part of the OSM team, it can seem daunting to sign up for so many accounts but each of these tools are helping us to run the project as efficiently and 'open-ly' as possible. As always, if you have any comments or ideas such as how to improve this blog or about the project please let the team know. Comment below or on G+, Twitter or facebook

Welcome onboard and good luck with your reactions.


Cheers,

Team OSM