DDD85646   Click here for help

GtoPdb Ligand ID: 11455

Synonyms: compound 1a [PMID: 24451586] | IMP-366
PDB Ligand Antimalarial Ligand
Compound class: Synthetic organic
Comment: The pyrazole sulfonamide, DDD85646, was first identified as a potent N-Myristoyltransferase (NMT) inhibitor in T. brucei, the parasite that causes African sleeping sickness (trypanosomiasis) [1]. The compound also has antimalarial activity [3].

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 100.53
Molecular weight 494.11
XLogP 4.42
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES Cc1nn(c(c1NS(=O)(=O)c1c(Cl)cc(cc1Cl)c1ccnc(c1)N1CCNCC1)C)C
Isomeric SMILES Cc1nn(c(c1NS(=O)(=O)c1c(Cl)cc(cc1Cl)c1ccnc(c1)N1CCNCC1)C)C
InChI InChI=1S/C21H24Cl2N6O2S/c1-13-20(14(2)28(3)26-13)27-32(30,31)21-17(22)10-16(11-18(21)23)15-4-5-25-19(12-15)29-8-6-24-7-9-29/h4-5,10-12,24,27H,6-9H2,1-3H3
InChI Key XMBSZPZJLPTFMV-UHFFFAOYSA-N
References
1. Frearson JA, Brand S, McElroy SP, Cleghorn LA, Smid O, Stojanovski L, Price HP, Guther ML, Torrie LS, Robinson DA et al.. (2010)
N-myristoyltransferase inhibitors as new leads to treat sleeping sickness.
Nature, 464 (7289): 728-32. [PMID:20360736]
2. Schlott AC, Mayclin S, Reers AR, Coburn-Flynn O, Bell AS, Green J, Knuepfer E, Charter D, Bonnert R, Campo B et al.. (2019)
Structure-Guided Identification of Resistance Breaking Antimalarial N‑Myristoyltransferase Inhibitors.
Cell Chem Biol, 26 (7): 991-1000.e7. [PMID:31080074]
3. Wright MH, Clough B, Rackham MD, Rangachari K, Brannigan JA, Grainger M, Moss DK, Bottrill AR, Heal WP, Broncel M et al.. (2014)
Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach.
Nat Chem, 6 (2): 112-21. [PMID:24451586]