OpenSourceMalaria:GSK Arylpyrrole Series: Difference between revisions

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{{OSDDMalaria}}
{{OSDDMalaria}}


1) The initial two leads have the general structure:<br>
== The Arylpyrrole Series ==


[[Image:Arylpyrrole Generic.png|none|left|120px|GSK Tres Cantos Arylpyrrole Generic Structure]]<br>
The initial two leads have the general structure:
<br>
 
[[Image:Arylpyrrole Generic.png|thumb|center|120px|GSK Tres Cantos Arylpyrrole Generic Structure]]


These compounds are currently under study by the Todd lab at the University of Sydney and the Medicines for Malaria Venture, Geneva. As an open source project, anyone may participate:<br>
These compounds are currently under study by the Todd lab at the University of Sydney and the Medicines for Malaria Venture, Geneva. As an open source project, anyone may participate:<br>
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Series was [http://pubs.acs.org/doi/abs/10.1021/ml200135p listed as one of the most promising leads] from TCAMS set (though lacking aryl F)<br>
Series was [http://pubs.acs.org/doi/abs/10.1021/ml200135p listed as one of the most promising leads] from TCAMS set (though lacking aryl F)<br>


2) The two known series examples:<br>
A number of these compounds and intermediates are [[OSDDMalaria:GSK_Arylpyrrole_Series:available_compounds|available]] for biological testing from Todd group by request. 


'''TCMDC 123812'''<br>
=== The two known series examples ===


[[Image:Arylpyrrole 1.png|none|left|260px|TCMDC123812]]<br>
==== TCMDC 123812 ====
<br>
 
[[Image:Arylpyrrole 1.png|thumb|center|260px|TCMDC123812]]


InChI=1/C15H15FN2O3/c1-9-7-13(15(20)21-8-14(17)19)10(2)18(9)12-5-3-11(16)4-6-12/h3-7H,8H2,1-2H3,(H2,17,19)<br>
InChI=1/C15H15FN2O3/c1-9-7-13(15(20)21-8-14(17)19)10(2)18(9)12-5-3-11(16)4-6-12/h3-7H,8H2,1-2H3,(H2,17,19)<br>
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Resynthesis:<br>
Resynthesis:<br>


'''TCMDC 123794'''<br>
==== TCMDC 123794 ====


[[Image:Arylpyrrole 2.png|none|left|260px|TCMDC123794]]<br>
[[Image:Arylpyrrole 2.png|thumb|center|260px|TCMDC123794]]
<br>


InChI=1/C26H25FN4O4/c1-16-14-22(17(2)30(16)20-12-10-19(27)11-13-20)26(34)35-15-23(32)28-24-18(3)29(4)31(25(24)33)21-8-6-5-7-9-21/h5-14H,15H2,1-4H3,(H,28,32)<br>
InChI=1/C26H25FN4O4/c1-16-14-22(17(2)30(16)20-12-10-19(27)11-13-20)26(34)35-15-23(32)28-24-18(3)29(4)31(25(24)33)21-8-6-5-7-9-21/h5-14H,15H2,1-4H3,(H,28,32)<br>
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The proposed resynthesis strategy for these two compounds:<br>
The proposed resynthesis strategy for these two compounds:<br>
[[Image:arylpyrrolesynth.png|thumb|450px|center|Proposed Synthesis Strategy]]<br>
[[Image:arylpyrrolesynth.png|thumb|450px|center|Proposed Synthesis Strategy]]<br>


3) Known "Near Neighbours" contained in the Tres Cantos set
== Other known incidences of these molecules/this series ==


[[Image:Near neighbours.png|none|600px|left|Known GSK Arylpyrrole Near Neighbours]]<br>
Related compounds are known to inhibit the proteasome, according to [http://www.nature.com/nature/journal/v467/n7312/abs/nature09299.html this Nature paper].<br>
 
=== Known "[[OSDDMalaria:GSK_Arylpyrrole_Series:Near Neighbours|Near Neighbours]]" contained in the Tres Cantos set ===
 
[[Image:Near neighbours.png|thumb|450px|center|Known GSK Arylpyrrole Near Neighbours]]<br>


Data/links for these compounds:
Data/links for these compounds:
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CCn1c(cc(c1C)C=C2C(=O)NC(=Nc3ccccc3)S2)C
CCn1c(cc(c1C)C=C2C(=O)NC(=Nc3ccccc3)S2)C


'''Potential synthesis strategy toward near-neighbours:'''
==== Potential synthesis strategy toward near-neighbours ====


[[Image:Nearneighbour.png|thumb|center|450px|Current synthesis toward near neighbours]]
[[Image:Nearneighbour.png|thumb|center|450px|Current synthesis toward near neighbours]]


Experimental information available from [http://malaria.ourexperiment.org/uri/32 PMY 13-1], [http://malaria.ourexperiment.org/uri/33 PMY 14-1] and [http://malaria.ourexperiment.org/uri/39 PMY 16-1].
Experimental information available from [http://malaria.ourexperiment.org/uri/32 PMY 13-1], [http://malaria.ourexperiment.org/uri/33 PMY 14-1] and [http://malaria.ourexperiment.org/uri/39 PMY 16-1].
4) Other known incidences of these molecules/this series<br>
Related compounds are known to inhibit the proteasome, according to [http://www.nature.com/nature/journal/v467/n7312/abs/nature09299.html this Nature paper].<br>

Revision as of 20:21, 1 November 2011

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The Arylpyrrole Series

The initial two leads have the general structure:

GSK Tres Cantos Arylpyrrole Generic Structure

These compounds are currently under study by the Todd lab at the University of Sydney and the Medicines for Malaria Venture, Geneva. As an open source project, anyone may participate:
Coordination/Discussion site
Electronic Lab Notebooks
Compounds are commercially-available
Series was listed as one of the most promising leads from TCAMS set (though lacking aryl F)

A number of these compounds and intermediates are available for biological testing from Todd group by request.

The two known series examples

TCMDC 123812

TCMDC123812

InChI=1/C15H15FN2O3/c1-9-7-13(15(20)21-8-14(17)19)10(2)18(9)12-5-3-11(16)4-6-12/h3-7H,8H2,1-2H3,(H2,17,19)
SMILES: O=C(N)COC(=O)c2c(n(c1ccc(F)cc1)c(c2)C)C
CAS Registry Number: 733026-12-5
Chemspider page
ChEMBL Page
Resynthesis:

TCMDC 123794

TCMDC123794

InChI=1/C26H25FN4O4/c1-16-14-22(17(2)30(16)20-12-10-19(27)11-13-20)26(34)35-15-23(32)28-24-18(3)29(4)31(25(24)33)21-8-6-5-7-9-21/h5-14H,15H2,1-4H3,(H,28,32)
SMILES: Fc1ccc(cc1)n2c(cc(c2C)C(=O)OCC(=O)NC=4C(=O)N(c3ccccc3)N(C=4C)C)C
Chemspider page
ChEMBL Page
Resynthesis:

The proposed resynthesis strategy for these two compounds:

Proposed Synthesis Strategy


Other known incidences of these molecules/this series

Related compounds are known to inhibit the proteasome, according to this Nature paper.

Known "Near Neighbours" contained in the Tres Cantos set

Known GSK Arylpyrrole Near Neighbours


Data/links for these compounds:

TCMDC-123563, CHEMBL546966, CHEMBL page: 637010 Cc1ccc(cc1)n2c(cc(c2C)C(=O)CN3C(=O)C(NC3=O)Cc4ccccc4)C

TCMDC-125698, CHEMBL587989, CHEMBL: 627784 Cc1cc(c(n1c2ccc(cc2)Cl)C)C=C3C(=O)N(C(=Nc4ccccc4)S3)C5CCCC5

TCMDC-125697, CHEMBL581336, CHEMBL: 640978 CCOC(=O)c1ccc(cc1)n2c(cc(c2C)C=C3C(=O)N(C(=Nc4ccccc4)S3)C5CCCC5)C

TCMDC-125659, CHEMBL528140, CHEMBL: 626220 Cc1ccnc(c1)n2c(cc(c2C)C=C3C(=O)N(C(=Nc4ccccc4)S3)Cc5ccco5)C

TCMDC-124103, CHEMBL588465, CHEMBL: 643107 Cc1cc(cc(c1)n2c(cc(c2C)C=C3C(=O)NC(=Nc4ccc(cc4)Cl)S3)C)C

TCMDC-124456, CHEMBL548395, CHEMBL: 640006 CCn1c(cc(c1C)C=C2C(=O)NC(=Nc3ccccc3)S2)C

Potential synthesis strategy toward near-neighbours

Current synthesis toward near neighbours

Experimental information available from PMY 13-1, PMY 14-1 and PMY 16-1.

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