OpenSourceMalaria:Triazolopyrazine (TP) Series

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(PfATP4 Activity: added scheme of structures of original 5 PfATP4 activities)
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The following five compounds were evaluated. Structures, potency and metabolism/solubility are here.
The following five compounds were evaluated. Structures, potency and metabolism/solubility are here.
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[[Image:Original PfATP4 Activities.tif|thumb|center|500px|The Five Compounds Initially Evaluated for PfATP4 activity]]
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[[Image:Original PfATP4 Activities.tif|thumb|center|600px|The Five Compounds Initially Evaluated for PfATP4 activity]]
MMV669000:  (potency: inactive)
MMV669000:  (potency: inactive)

Revision as of 00:19, 28 August 2013

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Contents

Open Source Malaria Series 4: The Triazolopyrazine (TP) Series

Introduction

Preamble

This series of compounds arises from industrial work that cannot be disclosed, followed by some hit-to-lead work funded directly by MMV which can. The series is based on a triazolopyrazine core. There is evidence that these compounds may be PfATP4 inhibitors. OSM started to look at this series following a decision by MMV to release their data into the public domain.

Current Aims

Further hit-to-lead work. Validate PfATP4 activity. Improve potency and drug likeness.

Prior Knowledge of the Series

Potency of Hits and Analogs

PfATP4 Activity

The following five compounds were evaluated. Structures, potency and metabolism/solubility are here.

The Five Compounds Initially Evaluated for PfATP4 activity
The Five Compounds Initially Evaluated for PfATP4 activity

MMV669000: (potency: inactive)

MMV669304: (potency: 280 nM)

MMV669360: (potency: 356 nM)

MMV669542: (potency: 185 nM)

MMV669848: (potency: 114 nM)

(Note the correlation: compound inactive in PfATP4 assay is the inactive analog)

Strings
MMV669000: O=C(N1CC(C=CC=C2)=C2C1)C3=CN=CC4=NN=C(C5=CC=C(OC(F)F)C=C5)N43; InChI=1S/C21H15F2N5O2/c22-21(23)30-16-7-5-13(6-8-16)19-26-25-18-10-24-9-17(28(18)19)20(29)27-11-14-3-1-2-4-15(14)12-27/h1-10,21H,11-12H2
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
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
MMV669542: FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(C(NC4=CC=CC(Cl)=C4)=O)N32; InChI=1S/C19H12ClF2N5O2/c20-12-2-1-3-13(8-12)24-18(28)15-9-23-10-16-25-26-17(27(15)16)11-4-6-14(7-5-11)29-19(21)22/h1-10,19H,(H,24,28)
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

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