DSM421   Click here for help

GtoPdb Ligand ID: 10020

PDB Ligand Antimalarial Ligand
Compound class: Synthetic organic
Comment: DSM421 was being developed as a backup compound to DSM265, the clinical lead for the triazolopyrimidine structural class of antimalarial compounds, but it has not been progressed due to unpredicted off-target toxicity [1,3].

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 5
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 68
Molecular weight 358.1
XLogP 2.83
No. Lipinski's rules broken 0
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Canonical SMILES Cc1cc(Nc2ccc(nc2)C(F)(F)F)n2c(n1)nc(n2)C(F)(F)C
Isomeric SMILES Cc1cc(Nc2ccc(nc2)C(F)(F)F)n2c(n1)nc(n2)C(F)(F)C
InChI InChI=1S/C14H11F5N6/c1-7-5-10(22-8-3-4-9(20-6-8)14(17,18)19)25-12(21-7)23-11(24-25)13(2,15)16/h3-6,22H,1-2H3
Guide to Malaria Pharmacology Comments
DSM421 retains the efficacy and pharmacokinetic properties of DSM265 that predict utility as single dose treatment or once-weekly chemopreventative. As a further advantage over DSM265, DSM421's physical and chemical properties indicate that it will be easier to formulate [3]. The structure is one of those claimed in patent WO2016151521 [2].

Potential Target/Mechanism Of Action: DSM421 is a selective inhibitor of malarial DHODH in vitro.
Target Candidate Profiles
Profile Intended Use Target Stage Comment References
TCP-1 reduce parasite burden asexual blood stages
TCP-4 chemoprotection hepatic schizonts