blogs

10 Apr

Exciting times: First in vivo submissions

Published by pylioja

Subject 

Request for Help

It's exciting as usual on the project. We've submitted the three compounds for in-vivo oral evaluation in a mouse model. The original hits TCMDC-123812 and -123794 were submitted along with one of Zoe's near neighbours, ZYH 3-1. It's not the most active of our compounds with an IC50 of 26 nM, but its logP comes in at just under 5 or there abouts (see: http://www.thesynapticleap.org/node/384#comment-798). It's still pretty high so we'll see how it goes.

28 Mar

Update on the LA catalysed PS reaction

Published by KatB

It's now been about 3 weeks since I started working on the Lewis Acid (LAs) catalysed Pictet-Spengler project (see first post here). So far, I've been working on preparing the imine starting materials (1a-d) and getting them to cyclise (2a-d), just so I have a final product reference and a starting point for developing an assay to monitor the reaction.

20 Mar

Is Toxo connected to schizophrenia?

Published by bartrum

Subject 

External News

 Hi,
I thought I would point out this interesting article  http://www.theatlantic.com/magazine/archive/2012/03/how-your-cat-is-making-you-crazy/8873/ 
 
This article discusses the work of Jaroslav Flegr, a Czeck scientist who believes that Toxo is connected to schizophrenia and possibly other brain disorders.
 

12 Mar

Lewis Acid Catalysed Pictet-Spengler Reaction Model

Published by KatB

Over the next 12 weeks I will be working on a model system for the Lewis Acid catalysed Pictet-Spengler formation of substitued tetrahydroisoquinolines (e.g. 4).

After making the starting materials (3, R1 = H, OMe and R2 = H, NO2, OMe) I'll work on screening various Lewis Acids with a focus on silver(I) triflate, given recent results - see AgOTf post here.

12 Mar

Near-Neighbour Round 2 SAR

Published by pylioja

 The first results of bio-data for the 2nd round of compounds is back from the Avery group and Mat has summarised the results in his post here on synaptic leap and on Google+. We are seeing some very active compounds but as many people have pointed out, all of the highly active compounds have high logP value (ChemDraw calculated). This is something we've definitely noticed when synthesising the compounds themselves. 
 

09 Mar

Deuterated PZQ

Published by MatTodd

Subject 

Miscellaneous

Was alerted to this NCTT project/proposal for deuterated analogs of enantiopure PZQ, with the deuteration being used to slow metabolism. Would be interesting to see how many D's are incorporated, and where (presumably at least the 4' position). I hope they're using our resolution approach to make their enantiopure material. And I wonder what the deuteration does to the cost, on scale?
(original page http://nctt.nih.gov/27545311)

29 Feb

Silver(I) Triflate Catalysed PS Reactions

Published by KatB

Before I started on the triflic acid catalysed Pictet-Spengler reactions (see here), I was working on the silver(I) triflate catalysed reactions.

28 Feb

Triflic Acid Catalysed PS Reactions

Published by KatB

The use of catalytic triflic acid TfOH in the Pictet-Spengler reaction was initially performed as a control for the silver(I) triflate (AgOTf) catalysed reaction (here). All early experiments using TfOH were performed with the dimethoxy N-benzoyl PZQ analogue and catalyst loading was reduced down to 5% (KAB8-7 & KAB8-8, KAB8-9).

06 Feb

Proposed Synthesis of 'compound 3' and 'compound 4'

Published by JimCronshaw

The following compounds have been identified as potential antimalarial drugs by GSK-Tres Cantos.
Target Molecules
The top compound, known hereafter as 'compound 3', can be found on ChEMBL and ChemSpider:
https://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL535225 - ChEMBL

06 Feb

Proposed Synthesis of 'compound 3' and 'compound 4'

Published by JimCronshaw

The following compounds have been identified as potential antimalarial drugs by GSK-Tres Cantos.
Target Molecules
The top compound, known hereafter as 'compound 3', can be found on ChEMBL and ChemSpider:
https://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL535225 - ChEMBL

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