ID: ALA537778

Max Phase: Preclinical

Molecular Formula: C20H14Br2N4

Molecular Weight: 470.17

Molecule Type: Small molecule

Representations

Synonyms (4): TCMDC-125776 | GNF-Pf-2233 | MMV007224 | TCMDC-125776
Synonyms from Alternative Forms(4):

Canonical SMILES:  Brc1ccc(Nc2nc3ccccc3nc2Nc2ccc(Br)cc2)cc1

Standard InChI:  InChI=1S/C20H14Br2N4/c21-13-5-9-15(10-6-13)23-19-20(24-16-11-7-14(22)8-12-16)26-18-4-2-1-3-17(18)25-19/h1-12H,(H,23,25)(H,24,26)

Standard InChI Key:  NVDLICVFRRZMPR-UHFFFAOYSA-N

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Properties

Molecular Weight: 470.17

Molecular Weight (Monoisotopic): 467.9585

AlogP: 6.64

#Rotatable Bonds: 4

Polar Surface Area: 49.84

Molecular Species: NEUTRAL

HBA: 4

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 4

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa:

CX Basic pKa: 2.31

CX LogP: 6.91

CX LogD: 6.91

Aromatic Rings: 4

Heavy Atoms: 26

QED Weighted: 0.35

Np Likeness Score: -0.86

References

1. Gamo FJ, Sanz LM, Vidal J, de Cozar C, Alvarez E, Lavandera JL, Vanderwall DE, Green DV, Kumar V, Hasan S, Brown JR, Peishoff CE, Cardon LR, Garcia-Bustos JF..  (2010)  Thousands of chemical starting points for antimalarial lead identification.,  465  (7296): [PMID:20485427] [10.1038/nature09107]

2. Plouffe D, Brinker A, McNamara C, Henson K, Kato N, Kuhen K, Nagle A, Adrián F, Matzen JT, Anderson P, Nam TG, Gray NS, Chatterjee A, Janes J, Yan SF, Trager R, Caldwell JS, Schultz PG, Zhou Y, Winzeler EA..  (2008)  In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen.,  105  (26): [PMID:18579783] [10.1073/pnas.0802982105]

3. Meister S, Plouffe DM, Kuhen KL, Bonamy GM, Wu T, Barnes SW, Bopp SE, Borboa R, Bright AT, Che J, Cohen S, Dharia NV, Gagaring K, Gettayacamin M, Gordon P, Groessl T, Kato N, Lee MC, McNamara CW, Fidock DA, Nagle A, Nam TG, Richmond W, Roland J, Rottmann M, Zhou B, Froissard P, Glynne RJ, Mazier D, Sattabongkot J, Schultz PG, Tuntland T, Walker JR, Zhou Y, Chatterjee A, Diagana TT, Winzeler EA..  (2011)  Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery.,  334  (6061): [PMID:22096101] [10.1126/science.1211936]

4. Simon Macdonald, Paul Willis, Paul Kowalczyk, Thomas Spangenberg, Jeremy Burrows and Tim Wells. Medicines for Malaria Venture (MMV), PO Box 1826, 20, rte de Pré-Bois, 1215 Geneva 15, Switzerland and SCYNEXIS Inc. P.O. Box 12878 Research Triangle Park, North Carolina 27709-2878 USA. Malaria Box,  [10.6019/CHEMBL2028040]

5. Ben Gold, Thulasi Warrier, Selin Somersan, Landys Lopez-Quezada, Julia Roberts, David Little and Carl Nathan.. Malaria Box Tuberculosis Screening Data,  [10.6019/CHEMBL2094260]

6. Conor Caffrey and Brian Suzuki; Center for Discovery and Innovation in Parasitic Diseases, Dept. of Pathology, University of California San Francisco (www.cdipd.org).. Malaria Box Schistosomiasis Screening Data,  [10.6019/CHEMBL2363022]

7. UCSF DeRisi Lab. UCSF DeRisi Lab MMV Box Apicoplast Screening,  [10.6019/CHEMBL2448809]

8. University of Vermont. MMV Box Cryptosporidium parvum screening set,  [10.6019/CHEMBL3137356]

9. Nao-aki Watanabe, Takaaki Horii and Koji Sagane. Next Generation Systems Core Function Unit, Eisai Production Creation Systems, Eisai Co., Ltd. 1-3 Tokodai 5 - Chome, Tsukuba-shi, Ibaraki 300-2635, JAPAN. MMV Box P. falciparum screening,  [10.6019/CHEMBL3137361]

10. Northwick Park. MMV Box Onchocerca lienalis screening set,  [10.6019/CHEMBL3137381]

11. Boyom, F.F., Fokou, P.V.T., Tchokouaha, L.R.Y., Spangenberg, T., Mfopa, A.N., Kouipou, R.M.T., Mbouna, C.J., Donkeng Donfack, V.F., Zollo, P.H.A. University of Yaoundé, IMPM Yaoundé and MMV.. MMV Malaria Box screening against Toxoplasma gondii and Entamoeba histolytica.,  [10.6019/CHEMBL3301448]

12. Imperial-Medicines for Malaria Venture Centre of Excellence, Imperial College, London.. MMV Malaria Box gametocyte functional viability assay screening.,  [10.6019/CHEMBL3301451]

13. Medicines for Malaria Venture.. MMV Malaria Box hERG screening.,  [10.6019/CHEMBL3301458]

14. Hui Lab, SGC, University of Toronto, Canada.. MMV Malaria Box thermal shift screening.,  [10.6019/CHEMBL3301461]

15. Igarashi Lab, National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan. MMV Malaria Box anti-babesial screening.,  [10.6019/CHEMBL3301464]

16. Kaiser Lab, University Hospital Essen, Germany.. MMV Malaria Box screening against Plasmodium falciparum Deoxyhypusine hydroxylase,  [10.6019/CHEMBL3301470]

17. Ketas, T., Moore, J.P., Weill Cornell Medical College, USA.. MMV Malaria Box HIV and cytotoxicity screening.,  [10.6019/CHEMBL3301472]

18. National Cancer Institute, NIH.. MMV Malaria Box screening against the the NCI60 panel of human tumor cell lines.,  [10.6019/CHEMBL3301486]

19. St Onge, R.P. Yeast Chemical Genomics Laboratory, Stanford Genome Technology Center, Stanford University.. MMV Malaria Box yeast growth screening.,  [10.6019/CHEMBL3301546]

20. Poulsen, S-A., Andrews, K.T., Tonissen, K.F., Nawaratna, S., Eskitis Institute for Drug Discovery, Griffith University, Australia.. MMV Mararia Box screening against P. falciparum asexual stage parasites under hypoxia and bicarbonate modified culture conditions.,  [10.6019/CHEMBL3301550]

21. Taramelli Lab, University of Milan, Italy.. MMV Malaria Box screening in pLDH viability assay against Plasmodium falciparum gametocytes.,  [10.6019/CHEMBL3301555]

22. Van Voorhis Lab, University of Washington, USA.. MMV Box screening against Plasmodium falciparum protein kinases and aminoacyl tRNA synthetases.,  [10.6019/CHEMBL3301562]

23. Hain AU, Bartee D, Sanders NG, Miller AS, Sullivan DJ, Levitskaya J, Meyers CF, Bosch J..  (2014)  Identification of an Atg8-Atg3 protein-protein interaction inhibitor from the medicines for Malaria Venture Malaria Box active in blood and liver stage Plasmodium falciparum parasites.,  57  (11): [PMID:24786226] [10.1021/jm401675a]

24. Horrocks lab, Keele University, UK.. MMV box screening in the Dd2 P. falciparum strain,  [10.6019/CHEMBL3392922]

25. LT Jensen lab, Mahidol University, Thailand (submitted by: Laran T. Jensen, Worathad Chindaudomsate, Amornrat Naranuntarat Jensen). MMV box selection for compounds with potential use in combination with artemisinin using S. cerevisiae,  [10.6019/CHEMBL3392924]

26. TropIQ Health Sciences. MMV Malaria Box gametocyte standard membrane feeding assay screening.,  [10.6019/CHEMBL3430850]

27. St. Jude Leishmania screening dataset.,  [10.6019/CHEMBL3433997]

28. St. Jude Leishmania screening dataset.,  [10.6019/CHEMBL3433997]

29. Dziwornu GA, Attram HD, Gachuhi S, Chibale K..  (2020)  Chemotherapy for human schistosomiasis: how far have we come? What's new? Where do we go from here?,  11  (4.0): [PMID:33479649] [10.1039/D0MD00062K]

30. Lidumniece E, Withers-Martinez C, Hackett F, Blackman MJ, Jirgensons A..  (2022)  Subtilisin-like Serine Protease 1 (SUB1) as an Emerging Antimalarial Drug Target: Current Achievements in Inhibitor Discovery.,  65  (19.0): [PMID:36137276] [10.1021/acs.jmedchem.2c01093]

31. Padalino G, El-Sakkary N, Liu LJ, Liu C, Harte DSG, Barnes RE, Sayers E, Forde-Thomas J, Whiteland H, Bassetto M, Ferla S, Johnson G, Jones AT, Caffrey CR, Chalmers I, Brancale A, Hoffmann KF..  (2021)  Anti-schistosomal activities of quinoxaline-containing compounds: From hit identification to lead optimisation.,  226  [PMID:34536671] [10.1016/j.ejmech.2021.113823]

Source

Source(5):

• Scientific Literature
• GSK Malaria Screening
• Novartis Malaria Screening
• MMV Malaria Box
• St Jude Leishmania Screening