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11th November 2015 @ 12:05

Planning for the next round of synthesis is taking place over on GHI358.

This post only contains the strings for all the molecules mentioned there.


Nemesis OC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4CNCCC4)N32 InChI=1S/C18H21N5O2/c24-15(13-5-2-1-3-6-13)12-25-17-11-20-10-16-21-22-18(23(16)17)14-7-4-8-19-9-14/h1-3,5-6,10-11,14-15,19,24H,4,7-9,12H2 SNDLBGDEOQPBOQ-UHFFFAOYSA-N

CRO OC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4COC4)N32 InChI=1S/C16H16N4O3/c21-13(11-4-2-1-3-5-11)10-23-15-7-17-6-14-18-19-16(20(14)15)12-8-22-9-12/h1-7,12-13,21H,8-10H2 ZLHKTQHFEDMDIZ-UHFFFAOYSA-N

NW Aliphatic FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(C)(C)OC)N32 InChI=1S/C17H18F2N4O3/c1-17(2,24-3)10-25-14-9-20-8-13-21-22-15(23(13)14)11-4-6-12(7-5-11)26-16(18)19/h4-9,16H,10H2,1-3H3 QPGDQEMNKJULOO-UHFFFAOYSA-N

Sydney Grammar Pyridine OC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CN=CC=C4)N32 InChI=1S/C18H15N5O2/c24-15(13-5-2-1-3-6-13)12-25-17-11-20-10-16-21-22-18(23(16)17)14-7-4-8-19-9-14/h1-11,15,24H,12H2 GXHFRJHPAQDHIG-UHFFFAOYSA-N

Dimethyl Amine FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(C4=CC=CC=C4)N(C)C)N32 InChI=1S/C22H21F2N5O2/c1-28(2)18(15-6-4-3-5-7-15)14-30-20-13-25-12-19-26-27-21(29(19)20)16-8-10-17(11-9-16)31-22(23)24/h3-13,18,22H,14H2,1-2H3 WSXRPWJACRAQOI-UHFFFAOYSA-N

Homologous Alcohol FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(C4=CC=CC=C4)CO)N32 InChI=1S/C21H18F2N4O3/c22-21(23)30-17-8-6-15(7-9-17)20-26-25-18-10-24-11-19(27(18)20)29-13-16(12-28)14-4-2-1-3-5-14/h1-11,16,21,28H,12-13H2 MGANJQKOPZQELF-UHFFFAOYSA-N

Homologous Amine FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(C4=CC=CC=C4)CN)N32 InChI=1S/C21H19F2N5O2/c22-21(23)30-17-8-6-15(7-9-17)20-27-26-18-11-25-12-19(28(18)20)29-13-16(10-24)14-4-2-1-3-5-14/h1-9,11-12,16,21H,10,13,24H2 ZAYFESUSYJEUPU-UHFFFAOYSA-N

Shackleford FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OC(C)C(C4=CC=CC=C4)O)N32 InChI=1S/C21H18F2N4O3/c1-13(19(28)14-5-3-2-4-6-14)29-18-12-24-11-17-25-26-20(27(17)18)15-7-9-16(10-8-15)30-21(22)23/h2-13,19,21,28H,1H3 XGFALCXCRQYLSD-UHFFFAOYSA-N

Swain FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OC(C)C4=CC=C(Cl)C(Cl)=C4)N32 InChI=1S/C20H14Cl2F2N4O2/c1-11(13-4-7-15(21)16(22)8-13)29-18-10-25-9-17-26-27-19(28(17)18)12-2-5-14(6-3-12)30-20(23)24/h2-11,20H,1H3 ILDZQTSEZGQWFR-UHFFFAOYSA-N

Reversed Amide FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(NC(C4=CC=NC(C(F)(F)F)=C4)=O)N32 InChI=1S/C19H11F5N6O2/c20-18(21)32-12-3-1-10(2-4-12)16-29-28-15-9-25-8-14(30(15)16)27-17(31)11-5-6-26-13(7-11)19(22,23)24/h1-9,18H,(H,27,31) NMZQYYGTOGZVCK-UHFFFAOYSA-N

MMV669848 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(CN4CC(C=CC=C5)=C5C4)N32 InChI=1S/C21H17F2N5O/c22-21(23)29-18-7-5-14(6-8-18)20-26-25-19-10-24-9-17(28(19)20)13-27-11-15-3-1-2-4-16(15)12-27/h1-10,21H,11-13H2

MMV668957 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(N4CCC(C5=CC=CC=C5)C4)N32 InChI=1S/C22H19F2N5O/c23-22(24)30-18-8-6-16(7-9-18)21-27-26-19-12-25-13-20(29(19)21)28-11-10-17(14-28)15-4-2-1-3-5-15/h1-9,12-13,17,22H,10-11,14H2

MMV669304 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(CCCC4=CC=CC=C4)N32 InChI=1S/C21H18F2N4O/c22-21(23)28-18-11-9-16(10-12-18)20-26-25-19-14-24-13-17(27(19)20)8-4-7-15-5-2-1-3-6-15/h1-3,5-6,9-14,21H,4,7-8H2

MMV671652 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(N[C@H](C4=CC=C(F)C(F)=C4)CO)N32 InChI=1S/C20H15F4N5O2/c21-14-6-3-12(7-15(14)22)16(10-30)26-17-8-25-9-18-27-28-19(29(17)18)11-1-4-13(5-2-11)31-20(23)24/h1-9,16,20,26,30H,10H2/t16-/m0/s1

MMV669008 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(N4CC(OC5=CC(F)=C(F)C=C5)C4)N32 InChI=1S/C21H15F4N5O2/c22-16-6-5-14(7-17(16)23)31-15-10-29(11-15)19-9-26-8-18-27-28-20(30(18)19)12-1-3-13(4-2-12)32-21(24)25/h1-9,15,21H,10-11H2

MMV669353 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(N4CC(C5=CC=CC=C5)C4)N32 InChI=1S/C21H17F2N5O/c22-21(23)29-17-8-6-15(7-9-17)20-26-25-18-10-24-11-19(28(18)20)27-12-16(13-27)14-4-2-1-3-5-14/h1-11,16,21H,12-13H2

MMV671653 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(N4N=CC(C5=CC(F)=C(F)C=C5)=C4)N32 InChI=1S/C21H12F4N6O/c22-16-6-3-13(7-17(16)23)14-8-27-30(11-14)19-10-26-9-18-28-29-20(31(18)19)12-1-4-15(5-2-12)32-21(24)25/h1-11,21H

MMV671678 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(N4C=CN=C4CC5=CC(F)=C(F)C=C5)N32 InChI=1S/C22H14F4N6O/c23-16-6-1-13(9-17(16)24)10-18-28-7-8-31(18)20-12-27-11-19-29-30-21(32(19)20)14-2-4-15(5-3-14)33-22(25)26/h1-9,11-12,22H,10H2

MMV669360 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(COCC4=CC=C(F)C(F)=C4)N32 InChI=1S/C20H14F4N4O2/c21-16-6-1-12(7-17(16)22)10-29-11-14-8-25-9-18-26-27-19(28(14)18)13-2-4-15(5-3-13)30-20(23)24/h1-9,20H,10-11H2

MMV670243 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(CCCC4=CC(F)=C(F)C=C4)N32 InChI=1S/C21H16F4N4O/c22-17-9-4-13(10-18(17)23)2-1-3-15-11-26-12-19-27-28-20(29(15)19)14-5-7-16(8-6-14)30-21(24)25/h4-12,21H,1-3H2

The Crazy Hemiacetal FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OC(O)C(O)C4=CC=CC=C4)N32 InChI=1S/C20H16F2N4O4/c21-20(22)29-14-8-6-13(7-9-14)18-25-24-15-10-23-11-16(26(15)18)30-19(28)17(27)12-4-2-1-3-5-12/h1-11,17,19-20,27-28H LBNIPJYOUJPJNQ-UHFFFAOYSA-N

The Ketone FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(C(CC4=CC=NC(C(F)(F)F)=C4)=O)N32 InChI=1S/C20H12F5N5O2/c21-19(22)32-13-3-1-12(2-4-13)18-29-28-17-10-26-9-14(30(17)18)15(31)7-11-5-6-27-16(8-11)20(23,24)25/h1-6,8-10,19H,7H2 NRTCUOWGNGMJIN-UHFFFAOYSA-N

The Sulfoxide FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C([S+]([O-])CC4=CC=NC(C(F)(F)F)=C4)N32 InChI=1S/C19H12F5N5O2S/c20-18(21)31-13-3-1-12(2-4-13)17-28-27-15-8-25-9-16(29(15)17)32(30)10-11-5-6-26-14(7-11)19(22,23)24/h1-9,18H,10H2 JITAVHCKEWUUSI-UHFFFAOYSA-N

The Sulfone FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(S(CC4=CC=NC(C(F)(F)F)=C4)(=O)=O)N32 InChI=1S/C19H12F5N5O3S/c20-18(21)32-13-3-1-12(2-4-13)17-28-27-15-8-25-9-16(29(15)17)33(30,31)10-11-5-6-26-14(7-11)19(22,23)24/h1-9,18H,10H2 DHPQHOFGWSYVQF-UHFFFAOYSA-N

The Urea FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(N([H])C(N([H])C4=CC(C(F)(F)F)=NC=C4)=O)N32 InChI=1S/C19H12F5N7O2/c20-17(21)33-12-3-1-10(2-4-12)16-30-29-15-9-25-8-14(31(15)16)28-18(32)27-11-5-6-26-13(7-11)19(22,23)24/h1-9,17H,(H2,26,27,28,32) MXAOEFDAAVOYKX-UHFFFAOYSA-N

The Triazole FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(C4=CN(C5=CC(C(F)(F)F)=NC=C5)[N][N]4)N32 InChI=1S/C20H11F5N8O/c21-19(22)34-13-3-1-11(2-4-13)18-30-29-17-9-26-8-15(33(17)18)14-10-32(31-28-14)12-5-6-27-16(7-12)20(23,24)25/h1-10,19H XXNFDIRYVMBYOF-UHFFFAOYSA-N

The Burns FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(C(C(F)(F)F)N([H])C4=CC=NC(C(F)(F)F)=C4)N32 InChI=1S/C20H12F8N6O/c21-18(22)35-12-3-1-10(2-4-12)17-33-32-15-9-29-8-13(34(15)17)16(20(26,27)28)31-11-5-6-30-14(7-11)19(23,24)25/h1-9,16,18H,(H,30,31) ORWCWEGIHLHCSF-UHFFFAOYSA-N

The Tianyi OC(C1=CC=CC=C1)COC2=CN=CC3=NC(C)=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C22H19F2N3O3/c1-14-21(16-7-9-17(10-8-16)30-22(23)24)27-19(26-14)11-25-12-20(27)29-13-18(28)15-5-3-2-4-6-15/h2-12,18,22,28H,13H2,1H3 VGNPLLBRBOUQAA-UHFFFAOYSA-N

Chase Hop1 FC(C=C1)=C(F)C=C1CCOC2=CN=CC(N3N=NN=C3C4=CC=C(Cl)C=C4)=N2 InChI=1S/C19H13ClF2N6O/c20-14-4-2-13(3-5-14)19-25-26-27-28(19)17-10-23-11-18(24-17)29-8-7-12-1-6-15(21)16(22)9-12/h1-6,9-11H,7-8H2 HHZUPBCYYAXEQO-UHFFFAOYSA-N

Chase Hop2 FC(C=C1)=C(F)C=C1CCOC2=NC=NC(NC3=NN=C(C4=CC=C(Cl)C=C4)S3)=N2 InChI=1S/C19H13ClF2N6OS/c20-13-4-2-12(3-5-13)16-27-28-19(30-16)26-17-23-10-24-18(25-17)29-8-7-11-1-6-14(21)15(22)9-11/h1-6,9-10H,7-8H2,(H,23,24,25,26,28) BDGBDNWYLOQTMB-UHFFFAOYSA-N

MMV639565 OSM-S-272 FC1=C(F)C=CC(CCOC2=CN=CC3=NN=C(C4=CC=C(Cl)C=C4)N32)=C1 InChI=1S/C19H13ClF2N4O/c20-14-4-2-13(3-5-14)19-25-24-17-10-23-11-18(26(17)19)27-8-7-12-1-6-15(21)16(22)9-12/h1-6,9-11H,7-8H2 PMHUSEXABGDNGS-UHFFFAOYSA-N

MMV669846 OSM-S-273 FC1=C(F)C=CC(CCOC2=CN=CC3=NC=C(C4=CC=C(Cl)C=C4)N32)=C1 InChI=1S/C20H14ClF2N3O/c21-15-4-2-14(3-5-15)18-10-25-19-11-24-12-20(26(18)19)27-8-7-13-1-6-16(22)17(23)9-13/h1-6,9-12H,7-8H2 MQHQNFQVEXYAMO-UHFFFAOYSA-N

MMV670250 OSM-S-274 FC1=C(F)C=CC(CCOC2=CN=CC3=CN=C(C4=CC=C(Cl)C=C4)N32)=C1 InChI=1S/C20H14ClF2N3O/c21-15-4-2-14(3-5-15)20-25-11-16-10-24-12-19(26(16)20)27-8-7-13-1-6-17(22)18(23)9-13/h1-6,9-12H,7-8H2 JHORUMGXLQTHAD-UHFFFAOYSA-N

 

This post authored by Mat Todd.

16th April 2015 @ 00:36

One of the key issues to solve in open source drug discovery and development programs is how to obtain physical samples of molecules for evaluation. A number of different methods can be envisaged, ranging from direct funding of synthesis (e.g. from grant money, hiring local researchers) through student classes to individual pro bono contributions from academia or industry. A possibility we’d like to build with community help this year is the Molecular Craigslist. We were speaking with Assay Depot about this idea - CEO Kevin Lustig has for a long time been pioneering new ways to source inputs for research projects.

But what about direct purchase of compounds from contract research organizations (CROs)? I believe that such an approach is gaining in popularity with NGOs requiring rapid synthesis of small molecules as part of in-house or sponsored projects. To get a feel for the commercial cost of single inputs to open source research projects (where the data are needed along with the compound) I decided to run one molecule, required by OSM, through Assay Depot’s suite of synthetic chemistry contract research organizations. The requirements we listed were for a few mg of the sample suitable for biological evaluation, plus all the preparative and characterization data obtained during the molecule’s preparation. There is ample synthetic precedence for the compounds in this series, but the specific analog requested (below) contains an oxetane, representing a not-completely-trivial extension of that methodology.

 

OSM Compounds Requested via Assay Depot



While we agreed not to share details of the companies providing quotations for this request, we can provide the figures quoted. I will be gradually assembling those over on Github so we can decide whether to go ahead with one of the quotes and to what extent this represents a general solution for analog synthesis for cases where we have already established precedence for the methodology.

 

 

OC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4COC4)N32

InChI=1S/C16H16N4O3/c21-13(11-4-2-1-3-5-11)10-23-15-7-17-6-14-18-19-16(20(14)15)12-8-22-9-12/h1-7,12-13,21H,8-10H2

ZLHKTQHFEDMDIZ-UHFFFAOYSA-N

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22nd March 2015 @ 21:18

The 'top ten' Series Four compounds have been defined as:

 

I (Alice) will firstly take care of compounds 14 at Sydney University meaning that we'd like to open up compounds 510 for synthesis by the community.

Two proposed synthetic routes for  5 - 10 could be accessed are:

1 Condensation of corresponding aldehyde

This route has been well established in the project and works well. Its limitation is that late stage of the right hand aryl/aromatic group is not possible.

 

2 Synthesis of triazalopyrazine core, functionalisation and cross coupling

Synthesis of chlorotriazolopyrazine, bromination and subsequent dervitisation. Tom MacDonald worked on this route as part of his honours proect and showed that the first two steps work. Development of this route would enable more expedent access of the desired compounds.

 

If you have time to synthesise some of these molecules in your laboratory or if you have access to any related compounds or building blocks then please get in touch, either below, on GitHub, Twitter or email (opensourcemalaria@gmail.com). Thanks on behalf of the @O_S_M Consortium.

 

(Originally Authored by Alice)

Attached Files
24th April 2014 @ 11:20

World Malaria Day is April 25th - it'd be great if you could help spread the word about malaria and the Open Source Malaria consortium. There's a Twibbon campaign at: http://twb.ly/1hr0pkc. This will overlay the OSM logo on your Twitter avatar (please save your old picture). You're meant to be able to customize the tweet you send out in support. If so:

If you're new to OSM, you could say this:

Join the network: #netacollaborator for @O_S_M on World Malaria Day to #defeatmalaria http://twb.ly/1hr0pkc

It'd be useful to gain support from these malaria ambassadors: http://malarianomore.org.uk/about/well-known-supporters so if anyone knows a way to encourage them to tweet the above, that'd be great.

If you've already contributed to OSM, you could say this:

I'm a contributor to @O_S_M. I work on chemistry @SydneyUni and use #openscience to #defeatmalaria #netacollaborator http://twb.ly/1hr0pkc

(If you find you can't customise the tweet, then maybe send out the Twibbon one, then paste a new tweet with one of the above)

Thank you all in advance for spreading the word about malaria and about OSM!

(post authored by Mat Todd)

9th April 2014 @ 02:40

GitHub Issue #174

The team are currently in the middle of synthesising the triazolopyrazines, both ether and amide linked compounds in the series. I (Jo Ubels) have been looking at the data from MMV on the ether linked series (example below).

I have synthesised the core triazolopyrazine rings (shown in black) with the benzonitrile group attached (pink) and am synthesising more with a chloro group in place of the nitrile. I have made one complete compound with phenethyl alcohol as the ether to test the reaction conditions. My question is, what alcohols (blue), amines or thiols should we buy to link to my compounds? Looking through the MMV data I have found that most of the alcohols already used are fluorinated so I searched for alcohols/amines/thiols with other ring substituents. A selection of alcohols that I have found can be seen in this table along with prices and shipping information.

Table of possible alcohols to buy.pdf

The alcohols that have already been tested can be found in this table, along with their potency data.

Alcohols-Amines that have been tested.pdf

Which compounds should we synthesise next based on the available alcohols? Are any of the possible alcohols particularly attractive/unattractive when paired with the nitrile or chloro group containing triazolopryazine ring cores? We need to be able to reatin potency and increase the solubility and metabolic stability of the compounds. If you can help us decide what to buy and synthesise next then we'd love to hear from you. The list of alcohols/amines/thiols is not exhaustive and I will try to add more suggestions in the next day or so.

To make suggestions you can post a comment below this blog, on GitHub, our G+ site, Twitter or last (and also least) by email to opensourcemalaria@gmail.com.

Thanks,

Jo & the OSM Team

Linked Posts
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