opensourcemalaria / osm_to_do_list Goto Github PK

We currenty have synthetic teams in Sydney, Edinburgh, Lucknow and the US with varying resources available. We need more synthetic input or commercial teams who can donate/sell final compounds to the team.

The team wants to expand! It would be great if more people attended the next online meeting. The teams discussed the possibility of contacting some medicinal chemists directly to invite them to participate in the next meeting.

with Alice, still requires some input/conversation from other sources which is largely dealt with in other issues.

We'd like to set up a survey featuring the question: "Which of these molecules should we make next?" along with:

1. Pictures of each molecule, up to perhaps 10
2. a free text box (either 1 total or 1 next to each choice) that allows the voter to input some justification for the choices, or suggestions for other molecules.
3. a link to the current consultation document: http://malaria.ourexperiment.org/uri/39f

Surveymonkey says that multiple images is not possible unless it's done manually:

http://help.surveymonkey.com/articles/en_US/kb/Can-I-add-images-or-pictures-into-the-survey

Maybe these guys: http://www.surveylegend.com/why-legend

An enhance profile of OSM-S-111 is required for the paper and the team would also like to explore the properties of OSM-S-106 further.

Experimental needs to be completed prior to circulation for proof reading by willing members of the team/community

The team need to consider alternative series to explore or to share with other branches of the OSDDMalaria team.
A wiki page has been constructed http://openwetware.org/wiki/OSDDMalaria:Other_GSK_Series_Under_Consideration
where series from the TCAMS set are being proposed and the results of preliminary searches are also posted.

Synthesis of the chloro material is below, with links.

Starting material for this synthesis costs us $226 per 25g. The 4-chlorothienopyrimidine product is available from Acros for $293 per 25 g. Given this, do we just buy it? Or should we request some from an interested company as a contribution?

Links:
http://malaria.ourexperiment.org/uri/2a4
and
http://malaria.ourexperiment.org/uri/2a6

InChI=1S/C6H3ClN2S/c7-6-5-4(1-2-10-5)8-3-9-6/h1-3H

InChI=1S/C13H11N3O2S2/c14-13-12-9(4-5-16-13)7-11(19-12)8-2-1-3-10(6-8)20(15,17)18/h1-7H,(H2,14,16)(H2,15,17,18)

Full data needed for the paper, @murrayfold made this compound which was clean by proton NMR but with residual DMF. Following purification, and removal of DMF the compound was very insoluble and so spectra were very weak.

Once new site is launched, contact Sydney Uni volunteer research site, to ask if people would like to help out, either with lab work, or with non-chemistry things to do with searches, wiki updates, help with things such as the molecule polls. This would mean we have a clear Label for non-lab based things to help people ID what they can do outside a wet lab environment.
http://sydney.edu.au/research/involved/volunteer.shtml

The Sydney branch of the OSDDMalaria team agreed to trial GitHub and decide if use of the program should be rolled out across the OSDDMalaria team.

In order to learn more about our hit compound the team need to determine the activity of OSM-S-106 at different stages in the malaria life cycle.

Can't remember the codes (?), but do we need to chase Sanjay for characterisation data for the Lucknow compounds that were biologically evaluated?

Google account is currently osddmalaria, and needs to be changed to:

opensourcemalaria

This will have knock-on effects on:
gmail
G+
Youtube

It appears that changing a name is OK, but the desired name might need to not exist first:
https://support.google.com/accounts/answer/19870?hl=en&ref_topic=2382809

We might also want to ask about OSM-S-111

InChI=1S/C12H11N5O2S/c13-12-11-10(15-6-16-12)5-9(17-11)7-2-1-3-8(4-7)20(14,18)19/h1-6,17H,(H2,13,15,16)(H2,14,18,19)

Knime is a very useful tool that @murrayfold has worked with and showed Alice how to use. Prior to George's visit, this should be installed on the Sydney machine(s) and users should be playing with this program. It would be great if other members of the team (Patrick in Edinburgh, Lucknow etc.) all familiarised themselves with this program.

1S/C12H10N4O2S2/c13-12-11-9(15-6-16-12)5-10(19-11)7-2-1-3-8(4-7)20(14,17)18/h1-6H,(H2,13,15,16)(H2,14,17,18)
Structure:

Link: http://openwetware.org/wiki/OSDDMalaria:GSK_Amino-thienopyrimidine_Series

InChI=1S/C13H11N3O2S2/c14-10-4-5-16-11-7-12(19-13(10)11)8-2-1-3-9(6-8)20(15,17)18/h1-7H,(H2,14,16)(H2,15,17,18)

A group of 49 undergraduate students have been working on the synthesis of near-neighbour analogs. There is currently no data online but we hope to receive this soon.

Original project Google doc gave OSM-S-70: 63% inhibition at 40 microM, whereas this:
http://malaria.ourexperiment.org/biological_data/5010/Preliminary_Results_for_Phase_1_or_Round_3_of_Screening.html
says 9.4 microM.

Did we resolve this?

InChI=1S/C12H10N4O3S/c13-12-11-9(15-6-16-12)5-10(19-11)7-2-1-3-8(4-7)20(14,17)18/h1-6H,(H2,13,15,16)(H2,14,17,18)

Discovery Studio (DS) is an excellent program for collating SD files and has been used to create the OSDDMalaria file. Unfortunately it doesn't run on iOS and so we could do with one OSDDMalaria computer in the lab/office that could be used to run DS and Knime (Knime works on Mac but often Knime and DS are used in parallel).

Prior to synthesis of more piperazine derivatives it is important to confirm the potency of this compounds:

Alice and Patrick will commence synthesis of the next targets and try to recruit any other chemists who are willing and able to join the synthesis team.

InChI=1S/C12H10N4O2S2/c13-11-9-5-10(19-12(9)16-6-15-11)7-2-1-3-8(4-7)20(14,17)18/h1-6H,(H2,13,15,16)(H2,14,17,18)

I attended a conference where I saw a compound labelled as SCYX-4456, a Scynexis compound, that looked relevant to our arylpyrrole series, but Google is coming up a blank and I forget which talk it was. Anyone know how to identify this compound? Other searches I've not done, or contacts at the company?

The Github account name (for the organisation) needs to be changed from OSDDmalaria to opensourcemalaria.

We need to have a discussion with Nislow's lab over their interpretation of the data provided from the Yeast MoA prediction, to provide a form of words for the paper.

http://malaria.ourexperiment.org/biological_data/5911/HIPHOP_mechanism_of_action_studies_from_Corey_Nislows_Lab.html

Identify and order compounds needed and if required request donations from commercial sources with @mattodd.

I have a note we need to "transfer ownership" of osddmalaria github from @incoherentboy - is that still the case? Who owns the OSDDMalaria group? Do me and Alice have access/ownership rights. If it's simple - a password - we can do by email. But if ownership needs to be transferred, can we do that?

This recording of Session 2 Part 2 (https://www.youtube.com/watch?v=3eP8OTFYjKA) needs to be added as a daughter page to this blog post (http://www.thesynapticleap.org/node/390), and a clear summary written of what was discussed along the lines of this example of a previous session. (To work out how to format correctly, please view the page source. Please insert time stamps for each section so that the recording can be easily navigated)

InChI=1S/C14H13N3O2S/c15-12-6-2-4-10-8-13(17-14(10)12)9-3-1-5-11(7-9)20(16,18)19/h1-8,17H,15H2,(H2,16,18,19)

Recent OSDD online meetings have been very productive although the team have noticed that the meeting audience is generally quite similar and lacks medicinal chemists from outside of the project. Prior to the next online consultation, the meeting should perhaps be more widely advertised or specific med chemists should maybe be targetted by email.

Mat and Alice should discuss this and also ask Paul for his advice on possible contributors.

This recording of Session 2 Part 3 (https://www.youtube.com/watch?v=URoDLUvEUL0) needs to be added as a child page to this blog post (http://www.thesynapticleap.org/node/390), and a clear summary written of what was discussed along the lines of this example (http://www.thesynapticleap.org/node/406) of a previous session. (To work out how to format correctly, please view the page source and copy/paste into a new child page. Please insert time stamps for each section so that the recording can be easily navigated)

edited - 10/5/13

Alice did a very nice search a while back on an alternative series from the GSK work (below). The data ought to be on the wiki, presumably? Given the latest data from the aminothienopyrimidine series, we might have to start thinking about alternative series. Paul W will be in touch with GSK about that if needed, but these kinds of searches are very useful to inform that. So first step - get the data out there on a page on the wiki (may need to create) and add disclaimer that the data may change over time and needs periodic updating (by anyone who wishes to do so).

Paper: http://www.sciencedirect.com/science/article/pii/S0040402012013488

Need to write to them to ask if any samples available.

Which compounds?

InChI=1S/C13H11N3O3S/c14-10-5-2-6-11-12(10)16-13(19-11)8-3-1-4-9(7-8)20(15,17)18/h1-7H,14H2,(H2,15,17,18)

1. Post suggested aminothienopyrimidine targets for the next round of synthesis and evaluation along with appeal for assistance.

InChI=1S/C13H12N4O2S/c14-10-5-2-6-11-12(10)17-13(16-11)8-3-1-4-9(7-8)20(15,18)19/h1-7H,14H2,(H,16,17)(H2,15,18,19)

The OSDDMalaria team need a website to advertise and organise the project. If you can assist, please contact @mattodd .

Following the consultation @mattodd and @alintheopen will discuss with Paul Willis and decide on the next 10 compounds for synthesis.

Mat received some very positive feedback from the RSC regarding tapping into the resource of their retired chemist's network. The RSC have offered to circulate OSDDMalaria's latest consultation document to ask for input from medicinal chemists regarding which compounds to target next for synthesis and evaluation.