Tag Archives: Malaria

OSM PfATP4 competition hidden set prediction

The final hidden test set for the PfATP4 competition has been released here.

All of the 400 compounds contained in the "MASTER SHEET" section of the spreadsheet were submitted to predictions using our earlier described PfATP4 Ion Regulation Activity classification model.

  1. The “Predicted PfATP4 Ion Regulation Activity Class” is the predicted class for the actual molecule (being 1.0 = “active”, 0.0 = “inactive”, and 0.5 = “partially active”).

  2. The “PfATP4 Active Class Probability” is the probability of the actual molecule to be active.

Molecules are reported below in rank order with the most probable to be active at the top.

 

ID

Predicted PfATP4 Ion Regulation Activity Class

PfATP4 Active Class Probability

MMV006239

1.0

0.733

MMV021057

1.0

0.667

MMV676186

1.0

0.533

MMV688550

1.0

0.533

MMV461553

1.0

0.467

MMV676571

0.0

0.467

MMV019551

0.0

0.467

MMV688350

0.0

0.467

MMV001493

0.0

0.467

MMV688509

0.0

0.467

MMV688756

0.0

0.467

MMV676603

0.0

0.467

MMV689000

0.0

0.467

MMV024829

0.0

0.4

MMV688270

0.0

0.4

MMV161996

0.0

0.4

MMV020520

0.0

0.4

MMV021660

0.0

0.4

MMV011903

0.0

0.4

MMV688362

0.0

0.4

MMV687699

0.0

0.4

MMV688754

0.0

0.4

MMV688508

0.0

0.4

MMV047015

0.0

0.4

MMV676008

0.0

0.4

MMV688327

0.0

0.4

MMV688703

0.0

0.4

MMV676604

0.0

0.4

MMV688775

0.0

0.4

MMV689437

0.0

0.4

MMV637953

0.0

0.333

MMV688313

0.0

0.333

MMV407539

0.0

0.333

MMV676162

0.0

0.333

MMV688845

0.0

0.333

MMV675968

0.0

0.333

MMV687703

0.0

0.333

MMV687812

0.0

0.333

MMV687803

0.0

0.333

MMV675997

0.0

0.333

MMV663250

0.0

0.333

MMV1088520

0.0

0.333

MMV676478

0.0

0.333

MMV021375

0.0

0.333

MMV688921

0.0

0.333

MMV687813

0.0

0.333

MMV000011

0.0

0.333

MMV688994

0.0

0.333

MMV020591

0.0

0.267

MMV020710

0.0

0.267

MMV003152

0.0

0.267

MMV676269

0.0

0.267

MMV676270

0.0

0.267

MMV202553

0.0

0.267

MMV675998

0.0

0.267

MMV689709

0.0

0.267

MMV611037

0.0

0.267

MMV019189

0.0

0.267

MMV687180

0.0

0.267

MMV090930

0.0

0.267

MMV688371

0.0

0.267

MMV687749

0.0

0.267

MMV668727

0.0

0.267

MMV688271

0.0

0.267

MMV676442

0.0

0.267

MMV688279

0.0

0.267

MMV687762

0.0

0.267

MMV676480

0.0

0.267

MMV687765

0.0

0.267

MMV000062

0.0

0.267

MMV1110498

0.0

0.267

MMV687700

0.0

0.267

MMV687798

0.0

0.267

MMV024114

0.0

0.267

MMV687796

0.0

0.267

MMV676526

0.0

0.2

MMV102872

0.0

0.2

MMV676386

0.0

0.2

MMV031011

0.0

0.2

MMV020517

0.0

0.2

MMV1030799

0.0

0.2

MMV011691

0.0

0.2

MMV675993

0.0

0.2

MMV676528

0.0

0.2

MMV688889

0.0

0.2

MMV019234

0.0

0.2

MMV688360

0.0

0.2

MMV676600

0.0

0.2

MMV690028

0.0

0.2

MMV688891

0.0

0.2

MMV687696

0.0

0.2

MMV676536

0.0

0.2

MMV671636

0.0

0.2

MMV688980

0.0

0.2

MMV020670

0.0

0.2

MMV687800

0.0

0.2

MMV000023

0.0

0.2

MMV019807

0.0

0.2

MMV024937

0.0

0.2

MMV020391

0.0

0.2

MMV688943

0.0

0.2

MMV676384

0.0

0.2

MMV687776

0.0

0.2

MMV022236

0.0

0.2

MMV024311

0.0

0.2

MMV099637

0.0

0.2

MMV676477

0.0

0.2

MMV688776

0.0

0.2

MMV023949

0.0

0.2

MMV688273

0.0

0.2

MMV688755

0.0

0.2

MMV676182

0.0

0.2

MMV024101

0.0

0.2

MMV676053

0.0

0.133

MMV146306

0.0

0.133

MMV1198433

0.0

0.133

MMV688793

0.0

0.133

MMV020321

0.0

0.133

MMV007133

0.0

0.133

MMV024406

0.0

0.133

MMV202458

0.0

0.133

MMV688553

0.0

0.133

MMV676472

0.0

0.133

MMV019790

0.0

0.133

MMV688274

0.0

0.133

MMV006901

0.0

0.133

MMV688410

0.0

0.133

MMV676589

0.0

0.133

MMV688471

0.0

0.133

MMV020165

0.0

0.133

MMV023985

0.0

0.133

MMV676204

0.0

0.133

MMV1236379

0.0

0.133

MMV676191

0.0

0.133

MMV688766

0.0

0.133

MMV676350

0.0

0.133

MMV676380

0.0

0.133

MMV009054

0.0

0.133

MMV688467

0.0

0.133

MMV019087

0.0

0.133

MMV024443

0.0

0.133

MMV688934

0.0

0.133

MMV688853

0.0

0.133

MMV690027

0.0

0.133

MMV020388

0.0

0.133

MMV1028806

0.0

0.133

MMV688557

0.0

0.133

MMV687254

0.0

0.133

MMV028694

0.0

0.133

MMV026490

0.0

0.133

MMV676406

0.0

0.133

MMV688466

0.0

0.133

MMV689061

0.0

0.133

MMV023388

0.0

0.133

MMV010576

0.0

0.133

MMV688179

0.0

0.133

MMV688852

0.0

0.133

MMV687730

0.0

0.133

MMV676439

0.0

0.133

MMV688936

0.0

0.133

MMV676159

0.0

0.133

MMV689758

0.0

0.133

MMV023969

0.0

0.133

MMV000063

0.0

0.133

MMV658993

0.0

0.133

MMV084603

0.0

0.133

MMV688411

0.0

0.133

MMV153413

0.0

0.133

MMV688417

0.0

0.133

MMV676382

0.0

0.133

MMV010545

0.0

0.133

MMV032967

0.0

0.133

MMV1029203

0.0

0.133

MMV010764

0.0

0.133

MMV687248

0.0

0.133

MMV006372

0.0

0.133

MMV688798

0.0

0.133

MMV689243

0.0

0.133

MMV690102

0.0

0.133

MMV687729

0.0

0.133

MMV676398

0.0

0.133

MMV023860

0.0

0.133

MMV688122

0.0

0.133

MMV690103

0.0

0.133

MMV030734

0.0

0.133

MMV688543

0.0

0.133

MMV676605

0.0

0.133

MMV688470

0.0

0.133

MMV676599

0.0

0.133

MMV676050

0.0

0.133

MMV023370

0.0

0.133

MMV688978

0.0

0.133

MMV688469

0.0

0.133

MMV001625

0.0

0.133

MMV687251

0.0

0.133

MMV687794

0.0

0.133

MMV687273

0.0

0.133

MMV687807

0.0

0.067

MMV228911

0.0

0.067

MMV200748

0.0

0.067

MMV676509

0.0

0.067

MMV688955

0.0

0.067

MMV676474

0.0

0.067

MMV676554

0.0

0.067

MMV687243

0.0

0.067

MMV688472

0.0

0.067

MMV020081

0.0

0.067

MMV676470

0.0

0.067

MMV687188

0.0

0.067

MMV407834

0.0

0.067

MMV688942

0.0

0.067

MMV020982

0.0

0.067

MMV023953

0.0

0.067

MMV007471

0.0

0.067

MMV188296

0.0

0.067

MMV688554

0.0

0.067

MMV026468

0.0

0.067

MMV007920

0.0

0.067

MMV016136

0.0

0.067

MMV022478

0.0

0.067

MMV676597

0.0

0.067

MMV024035

0.0

0.067

MMV053220

0.0

0.067

MMV676161

0.0

0.067

MMV688407

0.0

0.067

MMV006741

0.0

0.067

MMV019838

0.0

0.067

MMV676584

0.0

0.067

MMV007803

0.0

0.067

MMV688958

0.0

0.067

MMV676260

0.0

0.067

MMV688795

0.0

0.067

MMV688762

0.0

0.067

MMV676063

0.0

0.067

MMV676064

0.0

0.067

MMV019721

0.0

0.067

MMV020320

0.0

0.067

MMV020289

0.0

0.067

MMV688474

0.0

0.067

MMV032995

0.0

0.067

MMV688704

0.0

0.067

MMV688372

0.0

0.067

MMV688547

0.0

0.067

MMV022029

0.0

0.067

MMV687170

0.0

0.067

MMV019993

0.0

0.067

MMV687138

0.0

0.067

MMV676461

0.0

0.067

MMV676555

0.0

0.067

MMV688844

0.0

0.067

MMV688796

0.0

0.067

MMV012074

0.0

0.067

MMV676412

0.0

0.067

MMV688854

0.0

0.067

MMV676377

0.0

0.067

MMV688416

0.0

0.067

MMV688797

0.0

0.067

MMV676539

0.0

0.067

MMV688178

0.0

0.067

MMV495543

0.0

0.067

MMV676057

0.0

0.067

MMV676512

0.0

0.067

MMV023183

0.0

0.067

MMV688352

0.0

0.067

MMV667494

0.0

0.067

MMV688991

0.0

0.067

MMV009135

0.0

0.067

MMV069458

0.0

0.067

MMV1037162

0.0

0.067

MMV687706

0.0

0.067

MMV595321

0.0

0.067

MMV688364

0.0

0.067

MMV024195

0.0

0.067

MMV020623

0.0

0.067

MMV085499

0.0

0.067

MMV1019989

0.0

0.067

MMV020136

0.0

0.067

MMV553002

0.0

0.067

MMV688761

0.0

0.067

MMV688941

0.0

0.067

MMV687775

0.0

0.067

MMV085071

0.0

0.067

MMV661713

0.0

0.067

MMV688180

0.0

0.067

MMV687172

0.0

0.067

MMV001059

0.0

0.067

MMV688124

0.0

0.067

MMV688514

0.0

0.067

MMV687145

0.0

0.067

MMV688361

0.0

0.067

MMV688548

0.0

0.067

MMV011765

0.0

0.067

MMV687246

0.0

0.067

MMV688415

0.0

0.067

MMV560185

0.0

0.067

MMV676358

0.0

0.067

MMV000016

0.0

0.067

MMV689255

0.0

0.067

MMV023233

0.0

0.067

MMV001499

0.0

0.067

MMV688990

0.0

0.067

MMV676379

0.0

0

MMV676449

0.0

0

MMV688938

0.0

0

MMV676445

0.0

0

MMV020152

0.0

0

MMV020512

0.0

0

MMV675996

0.0

0

MMV688771

0.0

0

MMV002529

0.0

0

MMV689029

0.0

0

MMV687189

0.0

0

MMV007638

0.0

0

MMV676431

0.0

0

MMV675994

0.0

0

MMV392832

0.0

0

MMV272144

0.0

0

MMV675995

0.0

0

MMV676395

0.0

0

MMV676388

0.0

0

MMV689028

0.0

0

MMV023227

0.0

0

MMV020120

0.0

0

MMV011511

0.0

0

MMV062221

0.0

0

MMV676411

0.0

0

MMV676444

0.0

0

MMV084864

0.0

0

MMV001561

0.0

0

MMV687747

0.0

0

MMV063404

0.0

0

MMV016838

0.0

0

MMV688552

0.0

0

MMV688330

0.0

0

MMV676468

0.0

0

MMV634140

0.0

0

MMV637229

0.0

0

MMV676383

0.0

0

MMV652003

0.0

0

MMV687239

0.0

0

MMV000907

0.0

0

MMV676877

0.0

0

MMV676520

0.0

0

MMV024397

0.0

0

MMV688774

0.0

0

MMV676048

0.0

0

MMV676389

0.0

0

MMV676409

0.0

0

MMV676492

0.0

0

MMV393144

0.0

0

MMV006833

0.0

0

MMV676524

0.0

0

MMV688768

0.0

0

MMV689244

0.0

0

MMV688773

0.0

0

MMV658988

0.0

0

MMV085210

0.0

0

MMV004168

0.0

0

MMV007625

0.0

0

MMV020537

0.0

0

MMV688763

0.0

0

MMV026550

0.0

0

MMV003270

0.0

0

MMV676476

0.0

0

MMV659010

0.0

0

MMV675969

0.0

0

MMV688939

0.0

0

MMV045105

0.0

0

MMV688125

0.0

0

MMV085230

0.0

0

MMV687146

0.0

0

MMV011229

0.0

0

MMV688555

0.0

0

MMV688888

0.0

0

MMV026020

0.0

0

MMV689060

0.0

0

MMV688846

0.0

0

MMV054312

0.0

0

MMV689480

0.0

0

MMV676881

0.0

0

MMV019742

0.0

0

MMV688283

0.0

0

MMV676501

0.0

0

MMV008439

0.0

0

MMV676558

0.0

0

MMV659004

0.0

0

MMV676602

0.0

0

MMV000858

0.0

0

MMV021013

0.0

0

MMV026356

0.0

0

MMV676401

0.0

0

MMV688345

0.0

0

MMV688262

0.0

0

MMV020291

0.0

0

MMV026313

0.0

0

MMV002816

0.0

0

MMV002817

0.0

0

MMV687801

0.0

0

MMV393995

0.0

0

MMV676588

0.0

0

Synthesis of 5-chloro-3-(2,4-dichlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine (AEW 276-2)

 

Crude AEW 272-2 (6.12 g, 20.3 mmol, 1 equiv.) was dissolved in anhdrous CH­2Cl2 (203 mL) and (diacetoxyiodo)benzene (6.60 g, 20.3 mmol, 1 equiv.) was added. The reaction mixture was stirred at rt for 3 h and then quenched by the addition of a saturated aqueous solution of sodium hydrogen carbonate. Aqueous layers were separated and then extracted with CH­2Cl2 and then organic layers were combined and washed with brine (× 1), dried (MgSO4), filtered and evaporated. The crude mixture was then purified by

NMR

 

Hazard and Risk Assesment:


Strings:


InChI=1S/C11H7Cl3N4/c12-8-2-1-7(3-9(8)13)4-16-18-11-6-15-5-10(14)17-11/h1-6H,(H,17,18)/b16-4+

to

InChI=1S/C11H5Cl3N4/c12-7-2-1-6(3-8(7)13)11-17-16-10-5-15-4-9(14)18(10)11/h1-5H

ClC1=CN=CC(N/N=C/C2=CC(Cl)=C(Cl)C=C2)=N1

to

ClC1=CN=CC2=NN=C(C3=CC(Cl)=C(Cl)C=C3)N21

Synthesis of 2-Chloro-6-hydrazinylpyrazine (AEW 85-x)

Repeat of Synthesis of 2-Chloro-6-hydrazinylpyrazine (AEW 85-1), see also Synthesis of 2-Chloro-6-hydrazinylpyrazine (AEW 85-2) and Synthesis of 2-Chloro-6-hydrazinylpyrazine (AEW 85-3)

 

2,6-dichloropyrazine (21 g, 141 mmol, 1 eq) was dissolved in EtOH (282 mL, 0.50 M), and hydrazine hydrate (13.5 mL, 270 mmol, 2 eq) added. The reaction mixture was stirred at reflux for 8 hours.

The solvent was removed under reduced pressure to give a pale yellow solid. Water (~150 mL) and EtOAc (~200 mL) were added, and the mixture was shaken in an attempt to dissolve all solid. The organic layer was removed, the aqueous layer extracted with EtOAc (3 x 100 mL), and the combined organic layers washed with brine (~30 mL) before being concentrated under reduced pressure to yield a yellow solid 

Data:

Crude 300 MHz Data:

AEW 85.pdf
AEW 85.zip

Hazard and Risk Assessment:

See Synthesis of 2-Chloro-6-hydrazinylpyrazine (AEW 85-1)

InChi Strings:

InChI=1S/C4H2Cl2N2/c5-3-1-7-2-4(6)8-3/h1-2H

to

InChI=1S/C4H5ClN4/c5-3-1-7-2-4(8-3)9-6/h1-2H,6H2,(H,8,9)

Synthesis of (E)-2-chloro-6-(2-(4-chlorobenzylidene)hydrazineyl)pyrazine (AEW x-x)

Apologies this lab experiment was performed on Thurs/Fri 4/5th May

Outcome:

Obtained the desired product in quantitative yields. NMR Spectra to be uploaded asap.

Reason for Experiment: Synthesised for SSP Class 2017

 

Scheme:

 

Procedure:


AEW 85 (5.00 g, 34.6 mmol, 1.00 equiv.) was dissolved in EtOH (346 mL) and then 4-chlorobenzaldehyde (4.86 g, 34.6 mmol, 1.00 equiv.) was added. The brown/orange soln. was stirred for ten minutes at room temperature. A pale brown solid crashed out of the reaction mixture. The reaction was stirred for a further 2 h and then progress monitored by TLC (10% EtOAc in Hexane) - reaction complete.

Solid filtered under vacuum to give a pale yellow solid 9.8 g, that was dried at the high vac to yield a pale beige/brown powder in quantitative yield. Used as crude in following SSP reactions without NMR evaluation

Hazard and Risk Assessment:

HIRAC SSP OSDD Prac 1 2016.doc

Data:

TLC at 40 min (10% EtoAc in Hexane)

AEW 273-1 (10% EtoAc in Hex).JPG

NMR

Strings:

ClC1=CN=CC(N/N=C/C2=CC=C(Cl)C=C2)=N1

to

ClC1=CN=CC2=NN=C(C3=CC=C(Cl)C=C3)N21

 

InChI=1S/C11H8Cl2N4/c12-9-3-1-8(2-4-9)5-15-17-11-7-14-6-10(13)16-11/h1-7H,(H,16,17)/b15-5+

to

InChI=1S/C11H6Cl2N4/c12-8-3-1-7(2-4-8)11-16-15-10-6-14-5-9(13)17(10)11/h1-6H

Synthesis of (E)-2-chloro-6-(2-(2,4-dichlorobenzylidene)hydrazineyl)pyrazine (AEW 273-2)

Apologies this lab experiment was performed on Thurs/Fri 4/5th May

Outcome:

Obtained the desired product in quantitative yields. NMR Spectra to be uploaded asap.

Reason for Experiment: Synthesised for SSP Class 2017

 

Scheme:

 

Procedure:


AEW 85 (5.00 g, 34.6 mmol, 1.00 equiv.) was dissolved in EtOH (346 mL) and then 2,4-dichlorobenzaldehyde (6.05 g, 34.6 mmol, 1.00 equiv.) was added. The brown/orange soln. was stirred for ten minutes at room temperature. A pale brown solid crashed out of the reaction mixture. The reaction was stirred for a further 2 h and then progress monitored by TLC (10% EtOAc in Hexane) - reaction complete.

Solid filtered under vacuum to give a pale brown solid 11.2 g, that was dried at the high vac to yield a pale beige/brown powder in quantitative yield. Used as crude in following SSP reactions without NMR evaluation

Hazard and Risk Assessment:

HIRAC SSP OSDD Prac 1 2016.doc

Data:

TLC at 40 min (10% EtoAc in Hexane)

AEW 273-1 (10% EtoAc in Hex).JPG

NMR

Strings:

InChI=1S/C4H5ClN4/c5-3-1-7-2-4(8-3)9-6/h1-2H,6H2,(H,8,9)

and

InChI=1S/C7H4Cl2O/c8-6-2-1-5(4-10)7(9)3-6/h1-4H

to

InChI=1S/C11H7Cl3N4/c12-8-2-1-7(9(13)3-8)4-16-18-11-6-15-5-10(14)17-11/h1-6H,(H,17,18)/b16-4+

ClC1=CN=CC(NN)=N1

and

[H]C(C1=CC=C(Cl)C=C1Cl)=O

to

ClC1=CN=CC(N/N=C/C2=CC=C(Cl)C=C2Cl)=N1

Predictions for PfATP4 competition

The final test set of 400 compounds for the PfATP4 competition have been released here. As such, I appeneded all of the compounds in the "MASTER SHEET" portion of the spreadsheet to 'modelB.csv' (described in my earlier notebook entry) and labled them as test compounds (e.g. set "C") and ran the prediction regression. 

 

Results 

The potency predictions are reported below in rank order, with most potent at the top. 

ID log(ec50) EC50
MMV006239 -0.663722 0.2169093434
MMV407834 -0.49227 0.3219067377
MMV085230 -0.435151 0.3671546635
MMV047015 -0.396195 0.4016103405
MMV687807 -0.380073 0.4167995081
MMV006372 -0.301316 0.499671116
MMV687246 -0.288966 0.5140839317
MMV019189 -0.27593 0.529748656
MMV000063 -0.272942 0.5334058628
MMV001561 -0.271227 0.5355171519
MMV671636 -0.264702 0.5436227464
MMV676449 -0.25232 0.5593447438
MMV687273 -0.24481 0.5691022634
MMV688955 -0.223547 0.5976590019
MMV019087 -0.222331 0.5993346888
MMV688270 -0.221657 0.6002654537
MMV006833 -0.219929 0.6026576757
MMV689480 -0.217988 0.605357519
MMV000016 -0.217851 0.6055482434
MMV020165 -0.210743 0.6155404568
MMV688943 -0.208393 0.6188800963
MMV1028806 -0.207916 0.6195610793
MMV675968 -0.20761 0.619997785
MMV676536 -0.202214 0.6277493197
MMV676461 -0.199174 0.632157808
MMV688283 -0.197475 0.6346367574
MMV000023 -0.193034 0.6411587736
MMV020388 -0.192813 0.6414856069
MMV688703 -0.191242 0.6438099622
MMV020321 -0.190099 0.6455067979
MMV676468 -0.188977 0.6471765513
MMV676445 -0.188355 0.6481037796
MMV676411 -0.182692 0.6566104648
MMV676053 -0.181413 0.6585470994
MMV688362 -0.174245 0.6695075011
MMV024443 -0.170308 0.6756033085
MMV688761 -0.167301 0.680298304
MMV689437 -0.163373 0.6864779221
MMV675996 -0.162806 0.687375888
MMV008439 -0.162436 0.6879617217
MMV688762 -0.156979 0.6966609016
MMV676603 -0.154259 0.7010378002
MMV676159 -0.152876 0.7032725277
MMV688550 -0.146764 0.7132399518
MMV000907 -0.146491 0.7136896462
MMV676409 -0.136271 0.730682719
MMV024114 -0.132993 0.7362195234
MMV032995 -0.132344 0.7373206459
MMV676191 -0.129365 0.7423955253
MMV026550 -0.128507 0.7438631953
MMV676602 -0.128404 0.7440393237
MMV676472 -0.126018 0.7481385646
MMV024829 -0.124164 0.7513383045
MMV001493 -0.122058 0.7549905428
MMV676584 -0.118846 0.7605952056
MMV676492 -0.11828 0.7615883065
MMV003152 -0.117239 0.7634152352
MMV688754 -0.112376 0.772011279
MMV676588 -0.111996 0.7726875648
MMV688768 -0.110856 0.7747182245
MMV676558 -0.110553 0.775258815
MMV688273 -0.107241 0.7811934629
MMV020081 -0.105644 0.7840715431
MMV676401 -0.104831 0.7855404718
MMV002529 -0.103341 0.7882405192
MMV090930 -0.101495 0.7915985859
MMV010764 -0.100271 0.7938322624
MMV687801 -0.100033 0.7942683837
MMV687248 -0.0997557 0.79477522
MMV676526 -0.0967732 0.8002519904
MMV030734 -0.0960928 0.8015067145
MMV652003 -0.0945526 0.8043543797
MMV007133 -0.0935901 0.8061389205
MMV688994 -0.0930928 0.8070625741
MMV020591 -0.0906478 0.8116189729
MMV007638 -0.0896169 0.8135477869
MMV687254 -0.0882549 0.8161031824
MMV676260 -0.0874965 0.8175297027
MMV690027 -0.085387 0.821510348
MMV007803 -0.0840281 0.8240847457
MMV099637 -0.0836896 0.8247272702
MMV676555 -0.0829908 0.826055443
MMV202458 -0.0826616 0.8266817618
MMV020623 -0.0793795 0.8329530512
MMV020537 -0.0780813 0.8354466893
MMV676512 -0.0766954 0.8381169375
MMV687796 -0.0752439 0.8409228085
MMV023949 -0.0749996 0.8413959009
MMV676470 -0.0746362 0.8421003322
MMV676379 -0.0746194 0.8421328958
MMV676063 -0.0741979 0.8429505758
MMV689758 -0.0721812 0.8468740829
MMV687812 -0.0719042 0.8474144151
MMV020517 -0.0697416 0.8516446365
MMV689243 -0.0697075 0.8517114089
MMV687188 -0.069515 0.8520890276
MMV016136 -0.0687134 0.8536632261
MMV023183 -0.067957 0.8551514243
MMV690028 -0.066878 0.8572786079
MMV689709 -0.0628856 0.8651957112
MMV688469 -0.0619042 0.8671530945
MMV461553 -0.0615702 0.8678202508
MMV1030799 -0.0606314 0.8696983435
MMV687703 -0.0605446 0.8698720617
MMV676358 -0.0605285 0.8699044008
MMV553002 -0.0586204 0.8737347909
MMV688509 -0.0581968 0.8745873713
MMV675969 -0.0579905 0.8750029177
MMV687747 -0.055981 0.8790610591
MMV688330 -0.055632 0.8797676076
MMV676383 -0.0554833 0.880069035
MMV595321 -0.054179 0.8827159541
MMV688467 -0.0529625 0.8851920237
MMV687189 -0.0529473 0.8852230721
MMV659004 -0.0516271 0.8879180063
MMV687813 -0.0508994 0.8894070984
MMV690102 -0.0507498 0.8897135075
MMV676589 -0.0474766 0.8964443992
MMV689061 -0.0470264 0.8973742902
MMV676386 -0.0466438 0.8981651482
MMV676050 -0.0464202 0.898627786
MMV687170 -0.0458459 0.8998168137
MMV011229 -0.0453809 0.9007806689
MMV023985 -0.0452078 0.9011397854
MMV688766 -0.0450147 0.9015406258
MMV688756 -0.0434292 0.9048380058
MMV019551 -0.0423489 0.9070914066
MMV054312 -0.0416885 0.9084719457
MMV661713 -0.0415967 0.9086639779
MMV688773 -0.0403678 0.9112388928
MMV021375 -0.0383425 0.9154981127
MMV676380 -0.0363614 0.9196839106
MMV659010 -0.0352781 0.9219809108
MMV689000 -0.0346916 0.9232268687
MMV676539 -0.0346761 0.9232596866
MMV676186 -0.0338281 0.9250643223
MMV637229 -0.0336294 0.9254875855
MMV688122 -0.0335506 0.9256554951
MMV688941 -0.0332023 0.9263981194
MMV024035 -0.0325354 0.9278219061
MMV007920 -0.0324473 0.9280101398
MMV102872 -0.030723 0.9317019606
MMV690103 -0.0304792 0.9322250607
MMV637953 -0.0292842 0.9347938468
MMV676600 -0.0292179 0.9349365303
MMV688889 -0.0272594 0.9391621175
MMV019721 -0.026997 0.9397298343
MMV688364 -0.0263608 0.9411074646
MMV688774 -0.0262946 0.9412508939
MMV020120 -0.0258985 0.9421097871
MMV676877 -0.0258348 0.9422480307
MMV687146 -0.0258299 0.9422585621
MMV000858 -0.0237598 0.9467605442
MMV020291 -0.0218939 0.9508370428
MMV688179 -0.0217178 0.9512227367
MMV687243 -0.021089 0.9526008975
MMV676008 -0.0202795 0.9543780894
MMV688555 -0.0182815 0.9587788952
MMV021057 -0.0176341 0.9602093456
MMV023388 -0.0165055 0.9627078162
MMV688958 -0.0155807 0.9647599404
MMV002817 -0.0149127 0.9662450312
MMV495543 -0.014285 0.9676426908
MMV011903 -0.0142118 0.9678057918
MMV676509 -0.0135656 0.9692468125
MMV022029 -0.0131284 0.9702230061
MMV026468 -0.0121352 0.9724443908
MMV676431 -0.0121099 0.9725010725
MMV032967 -0.0116126 0.973615252
MMV026490 -0.0110064 0.9749752385
MMV688921 -0.0104071 0.9763215351
MMV188296 -0.0099718 0.9773006689
MMV676382 -0.00994214 0.9773674299
MMV676182 -0.00988629 0.9774931237
MMV002816 -0.00954815 0.9782544902
MMV611037 -0.00923053 0.9789701852
MMV009054 -0.00867309 0.9802275613
MMV006741 -0.00855426 0.9804958152
MMV062221 -0.00788165 0.9820155065
MMV021013 -0.0063922 0.9853892055
MMV676474 -0.00582961 0.9866665119
MMV024397 -0.00558698 0.9872179058
MMV688991 -0.00545839 0.9875102486
MMV146306 -0.00221443 0.9949140556
MMV020512 -0.00165371 0.9961994402
MMV688125 -0.000316227 0.9992721258
MMV688942 -0.000250081 0.9994243339
MMV676604 0.000105577 1.0002431286
MMV688410 0.000415908 1.0009581227
MMV011511 0.000596916 1.0013753956
MMV006901 0.000977656 1.0022536716
MMV001625 0.0015283 1.0035252407
MMV688844 0.00188613 1.0043524264
MMV688978 0.00223464 1.0051587084
MMV658988 0.00489315 1.0113306095
MMV161996 0.0053967 1.0125038923
MMV228911 0.00540872 1.0125319236
MMV688755 0.00701175 1.0162761768
MMV676597 0.00757768 1.0176013587
MMV688793 0.00851536 1.0198008183
MMV1088520 0.00970522 1.0225986647
MMV687762 0.0101459 1.0236367803
MMV019807 0.0109656 1.0255706945
MMV688891 0.0109853 1.0256171621
MMV023953 0.0112511 1.0262451024
MMV687776 0.0117397 1.0274002202
MMV676480 0.0119228 1.0278335856
MMV688553 0.0120318 1.0280915461
MMV687138 0.0125716 1.0293701526
MMV688352 0.0138485 1.0324012258
MMV689244 0.0148509 1.0347868863
MMV688853 0.0165983 1.038958687
MMV687696 0.0176987 1.0415944893
MMV688466 0.0182415 1.0428972513
MMV688470 0.0189316 1.0445557173
MMV687803 0.0189788 1.0446691659
MMV676599 0.0192072 1.0452187876
MMV023370 0.0193342 1.0455244901
MMV392832 0.0195071 1.0459408096
MMV687706 0.0198025 1.0466525747
MMV688990 0.0199586 1.0470286129
MMV676439 0.020446 1.0482044986
MMV676477 0.0216716 1.0511667377
MMV1110498 0.0219526 1.051847042
MMV688543 0.0224976 1.0531679212
MMV676881 0.0233318 1.055192836
MMV688411 0.0233322 1.0551936687
MMV001499 0.0240083 1.0568377479
MMV020152 0.0242473 1.057419377
MMV688372 0.0245463 1.0581476304
MMV688415 0.0248699 1.05893657
MMV019234 0.0254288 1.060299994
MMV688274 0.0278572 1.0662454203
MMV688776 0.0295673 1.0704521583
MMV200748 0.0308534 1.0736269296
MMV024195 0.0315951 1.0754620834
MMV023860 0.031614 1.0755087818
MMV688888 0.0323296 1.0772825716
MMV688854 0.0329199 1.0787477024
MMV393995 0.0341972 1.0819250631
MMV676389 0.0352057 1.084440446
MMV676520 0.0354993 1.0851738677
MMV688371 0.0362157 1.0869653319
MMV004168 0.0370056 1.0889441803
MMV010545 0.0377588 1.0908344425
MMV687729 0.0381533 1.0918256447
MMV676048 0.0385234 1.0927564809
MMV687700 0.0390438 1.0940667735
MMV688313 0.0393761 1.0949041701
MMV023227 0.0428561 1.103712789
MMV011765 0.0433114 1.1048706182
MMV688938 0.0436767 1.1058001691
MMV007471 0.0443609 1.1075437318
MMV688552 0.0445292 1.1079729619
MMV687730 0.0486716 1.1185917851
MMV009135 0.0497424 1.1213532481
MMV687775 0.050991 1.1245816076
MMV020320 0.051655 1.1263023996
MMV676269 0.0520492 1.1273250373
MMV676270 0.0520492 1.1273250373
MMV676478 0.0525201 1.1285482549
MMV016838 0.0555302 1.1363972149
MMV687794 0.0560505 1.137759465
MMV688980 0.0565772 1.1391403695
MMV676605 0.0591517 1.1459132637
MMV676554 0.0591881 1.1460092028
MMV675993 0.0601665 1.1485938474
MMV020670 0.0602955 1.1489351066
MMV676395 0.0603884 1.1491808461
MMV085071 0.0613554 1.1517426298
MMV676204 0.0614497 1.1519927445
MMV688472 0.0619778 1.1533941691
MMV676406 0.0643935 1.1598276772
MMV676571 0.0645061 1.1601283879
MMV676057 0.0648739 1.1611115395
MMV688939 0.0669817 1.16676044
MMV021660 0.0680149 1.1695394283
MMV688557 0.0690728 1.1723918693
MMV688471 0.0697636 1.1742582986
MMV688797 0.0703808 1.1759281438
MMV667494 0.0705631 1.1764218789
MMV023969 0.0710687 1.1777921811
MMV676377 0.072505 1.1816938287
MMV031011 0.0746406 1.1875190955
MMV1019989 0.0748595 1.1881177933
MMV688554 0.0757791 1.1906363367
MMV026356 0.0797433 1.2015540684
MMV688775 0.081523 1.2064879641
MMV688178 0.0830692 1.2107910798
MMV687749 0.0832295 1.2112379438
MMV688417 0.0834606 1.2118827996
MMV676384 0.0871109 1.2221117559
MMV028694 0.0879489 1.2244719795
MMV045105 0.0906374 1.2320757455
MMV019742 0.0942934 1.242491469
MMV688845 0.0961384 1.2477809493
MMV688360 0.0967192 1.2494507821
MMV560185 0.0982449 1.2538480402
MMV688934 0.0983802 1.2542385813
MMV688180 0.0990334 1.2561265868
MMV676442 0.101919 1.2645006661
MMV407539 0.102138 1.2651389561
MMV687765 0.102332 1.2657043035
MMV1198433 0.103118 1.2679958468
MMV688936 0.107439 1.2806751687
MMV012074 0.108203 1.2829299437
MMV676161 0.10882 1.2847545009
MMV688474 0.108861 1.2848757306
MMV020289 0.11331 1.2981051344
MMV687800 0.113602 1.2989792051
MMV676350 0.115747 1.305410724
MMV022236 0.11576 1.3054499608
MMV011691 0.1169 1.3088798023
MMV676476 0.117598 1.3109853116
MMV024937 0.117606 1.3110105014
MMV668727 0.119508 1.3167636884
MMV688796 0.120316 1.3192166998
MMV001059 0.12376 1.3297202285
MMV688846 0.128128 1.3431606573
MMV1236379 0.132416 1.3564887263
MMV687172 0.132714 1.3574184103
MMV676528 0.134326 1.3624677135
MMV676162 0.135047 1.3647296158
MMV687180 0.137385 1.3720963009
MMV676444 0.137788 1.3733726208
MMV658993 0.139632 1.3792141953
MMV085210 0.141658 1.3856654726
MMV020982 0.145807 1.3989658633
MMV663250 0.146525 1.4012810498
MMV676412 0.147783 1.4053449477
MMV634140 0.149923 1.4122867271
MMV688407 0.151387 1.4170572406
MMV084864 0.153324 1.4233907106
MMV689029 0.159039 1.4422432957
MMV688416 0.161281 1.4497111077
MMV676064 0.16211 1.4524795638
MMV688771 0.164229 1.4595843039
MMV007625 0.165056 1.462365192
MMV022478 0.165915 1.4652625321
MMV003270 0.167121 1.4693347665
MMV675995 0.169207 1.4764098946
MMV676524 0.173317 1.4904497653
MMV688262 0.175494 1.497938405
MMV000062 0.17945 1.5116442209
MMV019790 0.179731 1.5126230475
MMV688361 0.180063 1.5137815853
MMV676501 0.181709 1.5195304549
MMV010576 0.183937 1.5273445275
MMV153413 0.186822 1.537525017
MMV084603 0.187522 1.5400028242
MMV020710 0.187704 1.5406499249
MMV689255 0.193864 1.5626597822
MMV689028 0.194443 1.5647424626
MMV053220 0.195067 1.5669916258
MMV393144 0.195694 1.5692554904
MMV687699 0.197089 1.5743043252
MMV688124 0.205609 1.6054945837
MMV024101 0.214607 1.6391056252
MMV688795 0.217925 1.6516765852
MMV689060 0.220148 1.6601527221
MMV688763 0.23176 1.7051412189
MMV688852 0.234564 1.7161835629
MMV688508 0.235226 1.7188022594
MMV024311 0.238548 1.7320000147
MMV202553 0.239915 1.7374592434
MMV688271 0.241341 1.7431746654
MMV063404 0.244633 1.7564398718
MMV688327 0.245387 1.7594919571
MMV676388 0.246194 1.7627640457
MMV688279 0.247378 1.7675752111
MMV687239 0.254092 1.7951129067
MMV688798 0.254456 1.7966182413
MMV1029203 0.258445 1.8131970119
MMV687251 0.260949 1.8236802205
MMV024406 0.262146 1.8287142416
MMV688345 0.268814 1.8570074236
MMV675997 0.280822 1.9090717332
MMV069458 0.28164 1.9126719984
MMV688548 0.283081 1.9190272605
MMV688704 0.284786 1.926576084
MMV676398 0.287079 1.9367746667
MMV000011 0.292684 1.961931364
MMV272144 0.304905 2.0179253063
MMV020136 0.31137 2.0481890734
MMV675994 0.380393 2.401006777
MMV019993 0.384626 2.4245201201
MMV020391 0.414966 2.599953971
MMV687798 0.432491 2.7070188048
MMV085499 0.486487 3.0654018729
MMV026020 0.492975 3.1115391146
MMV1037162 0.499992 3.1622175509
MMV020520 0.525354 3.352386993
MMV688514 0.545498 3.5115412552
MMV688350 0.559441 3.6261119565
MMV675998 0.572442 3.7362996319
MMV688547 0.574383 3.7530390222
MMV026313 0.593654 3.9233216724
MMV023233 0.621736 4.1853922795
MMV019838 0.62528 4.2196883833
MMV687145 0.713423 5.16919333

 

 


A link to the fulll csv can be found here. Most interesting for me is the prevalence of  spiroindolones near the top of the potency chart, which have been previously characterized in literature as potent anti-malarial compounds against PfATP4 [1,2].

 

References 

[1] https://www.ncbi.nlm.nih.gov/pubmed/20813948

[2] https://www.nature.com/articles/srep27806

Synthesis of OSM-S-106

Attempts at synthesizing OSM-S-106:

http://malaria.ourexperiment.org/aminotpseries/5827/Suzuki_coupling_using_the_same_conditions_that_are_used_to_generate_boronate_esters_JRC_502.html >28% yield

http://malaria.ourexperiment.org/aminotpseries/10415/Synthesis_of_34aminothieno32dpyrimidin6ylbenzenesulfonamide_PT23_AKA_OSMS106.html 90.5% yield

http://malaria.ourexperiment.org/aminotpseries/10468/Synthesis_of_34aminothieno32dpyrimidin6ylbenzenesulfonamide_AEW_1721_OSMS106.html 



Synthesis of OSM-S-154

Attempts at synthesizing OSM-S-154:

http://malaria.ourexperiment.org/aminotpseries/5713/Synthesis_of_3sulfamoylphenylboronic_acid_JRC_294.html 31% yield

http://malaria.ourexperiment.org/aminotpseries/4677/Synthesis_of_3sulfamoylphenylboronic_acid_JRC_491_META_ISOMER.html 61% yield

http://malaria.ourexperiment.org/aminotpseries/4666/Synthesis_of_4sulfamoylphenylboronic_acid_JRC_491_PARA_ISOMER.html 56% yield

http://malaria.ourexperiment.org/aminotpseries/4665/Synthesis_of__2sulfamoylphenylboronic_acid_JRC_481_ORTHO_ISOMER.html 22% yield

http://malaria.ourexperiment.org/aminotpseries/4038/Upscaled_synthesis_of_34455tetramethyl132dioxaborolan_2ylbenzenesulfonamide_JRC_292.html 52% yield

http://malaria.ourexperiment.org/aminotpseries/4219/Upscaled_synthesis_of_3sulfamoylphenylboronic_acid_JRC_293.html 56% yield

http://malaria.ourexperiment.org/aminotpseries/7619/Synthesis_of_34455tetramethyl132dioxaborolan2ylbenzenesulfonamide_MJT_111.html did not work



Synthesis of OSM-S-139

Attempts at synthesizing OSM-S-139:

http://malaria.ourexperiment.org/aminotpseries/4284/Synthesis_of_6bromothieno32dpyrimidin4amine_JRC_401.html 43% yield

http://malaria.ourexperiment.org/aminotpseries/8963/Synthesis_of_6Bromothieno32dpyrimidin4amine_CT_34.html 43% yield

http://malaria.ourexperiment.org/aminotpseries/8887/Synthesis_of_6Bromothieno32dpyrimidin4amine_CT_33.html 42% yield

http://malaria.ourexperiment.org/aminotpseries/8663/Synthesis_of_6Bromothieno32dpyrimidin4amine_CT_32.html 45% yield

http://malaria.ourexperiment.org/aminotpseries/11450/Amination_of_Bromochlorothienopyrimidine_TF151.html 60.4% yield

http://malaria.ourexperiment.org/aminotpseries/6938/Amination_of_bromochlorothienopyrimidine_AT64.html 76% yield

http://malaria.ourexperiment.org/aminotpseries/6861/Amination_of_bromochlorothienopyrimidine_AT62.html 55% yield

http://malaria.ourexperiment.org/aminotpseries/6861/Amination_of_bromochlorothienopyrimidine_AT62.html 55% yield

http://malaria.ourexperiment.org/aminotpseries/6857/Amination_of_bromochlorothienopyrimidine_AT61.html 47% yield

http://malaria.ourexperiment.org/aminotpseries/6341/Synthesis_of_6bromothieno32dpyrimid4amine_JRC_402.html 78% yield

http://malaria.ourexperiment.org/aminotpseries/3113/Synthesis_of_thieno32dpyrimidin4amine_JRC_141.html 63% yield

http://malaria.ourexperiment.org/aminotpseries/3169/Synthesis_of_thieno32dpyrimidin4amine_JRC_142.html 94% yield

http://malaria.ourexperiment.org/aminotpseries/3187/Synthesis_of_thieno32dpyrimidin4amine_JRC_143.html 

http://malaria.ourexperiment.org/aminotpseries/3197/Synthesis_of_thieno32dpyrimidin4amine_JRC_144.html 

http://malaria.ourexperiment.org/aminotpseries/8111/Synthesis_of_6Bromothieno32dpyrimidin4amine_AEW_1001.html did not work

http://malaria.ourexperiment.org/aminotpseries/8159/Synthesis_of_6Bromothieno32dpyrimidin4amine_AEW_1002.html did not work

http://malaria.ourexperiment.org/aminotpseries/8169/Synthesis_of_6Bromothieno32dpyrimidin4amine_AEW_1003.html did not work

http://malaria.ourexperiment.org/aminotpseries/8220/Synthesis_of_6Bromothieno32dpyrimidin4amine_AEW_1005.html 

http://malaria.ourexperiment.org/aminotpseries/8185/Synthesis_of_6Bromothieno32dpyrimidin4amine_AEW_1004.html 

http://malaria.ourexperiment.org/aminotpseries/10457/ynthesis_of_6Bromothieno32dpyrimidin4amine_AEW_1006.html 

http://malaria.ourexperiment.org/aminotpseries/10165/Amination_of_bromochlorothienopyrimidine_PT21.html 

http://malaria.ourexperiment.org/aminotpseries/9145/Synthesis_of_6Bromothieno32dpyrimidin4amine_CT_37.html 


Synthesis of OSM-S-121

Attempts at synthesizing OSM-S-121:

http://malaria.ourexperiment.org/aminotpseries/4372/JRC_273.html 53% yield

http://malaria.ourexperiment.org/aminotpseries/4254/Synthesis_of_4chloro6bromothieno32dpyrimidine_via_BuLi_272.html 50% yield

http://malaria.ourexperiment.org/aminotpseries/7040/Bromination_of_chlorothienopyrimidine_AT56.html 64% yield

http://malaria.ourexperiment.org/aminotpseries/10148/Synthesis_of_6Bromo4chlorothieno32dpyrimidine_PT19.html 64.8% yield

http://malaria.ourexperiment.org/aminotpseries/6863/Bromination_of_chlorothienopyrimidine_AT53.html 39% yield

http://malaria.ourexperiment.org/aminotpseries/6852/Bromination_of_chlorothienopyrimidine_AT52.html 32% yield

http://malaria.ourexperiment.org/aminotpseries/6820/Bromination_of_chlorothienopyrimidine_AT51.html 55% yield

http://malaria.ourexperiment.org/aminotpseries/6314/Synthesis_of_4chloro6bromothieno32dpyrimidine_via_BuLi_AB31.html 70% yield

http://malaria.ourexperiment.org/aminotpseries/3670/Synthesis_of_6bromothieno32dpyrimidin4amine_212.html 15% yield

http://malaria.ourexperiment.org/aminotpseries/5859/Synthesis_of_6bromo4chlorothieno32dpyrimidine_JRC_275.html did not work

http://malaria.ourexperiment.org/aminotpseries/6536/Synthesis_of_4chloro6bromothieno32dpyrimidine_via_BuLi_AB32.html 12.3% yield

http://malaria.ourexperiment.org/aminotpseries/7039/Bromination_of_chlorothienopyrimidine_AT55.html 56% yield

http://malaria.ourexperiment.org/aminotpseries/8103/Synthesis_of_6Bromo4chlorothieno32dpyrimidine_AEW_991.html 56% yield