Meeting Discussion Point 5: Sourcing Compounds

[mattodd]

Background to Meeting on May 24th 2016 (#386).

Question: What are the best general strategies for sourcing new chemical compounds for OSM? Question: Are there any specific groups who might be interested in contributing compounds?

Resources:

OSM Series 4 summary wiki Lab books: Labtrove, Labarchives (Ed Tse, Chase Smith). See the Biological Evaluation ELN in particular for this Issue. Compound Database: All OSM Compounds in Google Sheet, interactive view on Cheminfo, direct download of Series 4 SDF.

Comments/suggestions below are welcome, as well as (briefly please) during the main webinar meeting on the 24th and its follow-up on June 8th (#394).

Relevant background:

Preparative synthetic chemistry is the major project roadblock. Most compounds are sourced from a research grant operating at The University of Sydney. OSM’s structure allows for and encourages total federation of all activities: any chemist can make and contribute any molecule, in return for project credit. Compounds have been made (then evaluated) at institutions in the UK, USA and India. Here is one example. We know, for example, that triazolopyridines are ineffective in Series 4 because of a contribution from students in Edinburgh. A number of crowdsourcing projects have been successfully completed, where groups of students have made molecules with OSM, e.g. in the USA and in Sydney (University and School). A group of students in Pennsylvania are currently crowdsourcing synthetic design and will report soon. We are exploring a new link with Eli Lilly’s OIDD group (#341). Question: What other sources of chemistry/compounds should be explored? Could CROs ever be convinced to contribute compounds? Should we seek formal pro bono arrangements with pharma? Would anyone like to run an undergraduate/graduate lab class to make OSM compounds, using an existing project as a template?

[drc007]

@MedChemProf I wondered if compounds of this type might be of interest.

Easy synthesis or could ask for samples? http://dx.doi.org/10.1039/C2MD20174G http://dx.doi.org/10.1016/j.bmcl.2010.01.003

Obviously potential off target activity but let's take one step at a time.

[MFernflower]

@drc007 @mattodd

I would predict off targets for your structure hop but tarpred (http://202.127.19.75:5555) seems to be down yet again :-1: :-1:

I do not do anything other than computational work but a quick search for "easy 1,2,3 triazole synthesis" produced a page containing many different ways to go about it (even some easy looking click chemistry!)

http://www.organic-chemistry.org/synthesis/heterocycles/1,2,3-triazoles.shtm

[MFernflower]

@drc007 I managed to get a lower LogP for your structure hop by omitting the left hand chlorine atom and just having hydrogen as the r-group on the side of the triazole ring.

The webservice I use to predict off targets still appears down but I plonked the SMILES of what I was screening down below:

O=C(NC1=CC=CC=C1)C3=CN=NN3(C2=CC=C(C=C2)Cl)

[drc007]

@MFernflower @mattodd I flagged the compounds because it may be possible to access compounds that have already been made by contacting the authors.

[MFernflower]

@drc007 TaRPred is back up again and I managed to get a prediction ran on the SMILES I posted above:

http://202.127.19.75:5555/view/574f7918d4973408157faec0

It is interesting to note that it predicts the target of the molecule to be Dihydroorotate dehydrogenase and also says the human CB1 receptor might be a possible off-target

[mattodd]

NB Lilly OIDD program is closing #341