ELQ-300   Click here for help

GtoPdb Ligand ID: 10021

Synonyms: ELQ300
Antimalarial Ligand
Compound class: Synthetic organic
Comment: ELQ-300 is a late lead candidate from a novel class of 4(1H)-quinolone-based compounds with potent antimalarial activity [4]. The ELQs (endochin-like quinolones) are structural derivatives of endochin (PubChem CID 100474), which has potent antiplasmodial activity, but is highly metabolically unstable in mammals [1,6].

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 1
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 60.55
Molecular weight 475.08
XLogP 8.16
No. Lipinski's rules broken 1
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Canonical SMILES COc1cc2[nH]c(C)c(c(=O)c2cc1Cl)c1ccc(cc1)Oc1ccc(cc1)OC(F)(F)F
Isomeric SMILES COc1cc2[nH]c(C)c(c(=O)c2cc1Cl)c1ccc(cc1)Oc1ccc(cc1)OC(F)(F)F
InChI InChI=1S/C24H17ClF3NO4/c1-13-22(23(30)18-11-19(25)21(31-2)12-20(18)29-13)14-3-5-15(6-4-14)32-16-7-9-17(10-8-16)33-24(26,27)28/h3-12H,1-2H3,(H,29,30)
1. Cross RM, Monastyrskyi A, Mutka TS, Burrows JN, Kyle DE, Manetsch R. (2010)
Endochin optimization: structure-activity and structure-property relationship studies of 3-substituted 2-methyl-4(1H)-quinolones with antimalarial activity.
J Med Chem, 53 (19): 7076-94. [PMID:20828199]
2. Frueh L, Li Y, Mather MW, Li Q, Pou S, Nilsen A, Winter RW, Forquer IP, Pershing AM, Xie LH et al.. (2017)
Alkoxycarbonate Ester Prodrugs of Preclinical Drug Candidate ELQ-300 for Prophylaxis and Treatment of Malaria.
ACS Infect Dis, 3 (10): 728-735. [PMID:28927276]
3. Miley GP, Pou S, Winter R, Nilsen A, Li Y, Kelly JX, Stickles AM, Mather MW, Forquer IP, Pershing AM et al.. (2015)
ELQ-300 prodrugs for enhanced delivery and single-dose cure of malaria.
Antimicrob Agents Chemother, 59 (9): 5555-60. [PMID:26124159]
4. Nilsen A, LaCrue AN, White KL, Forquer IP, Cross RM, Marfurt J, Mather MW, Delves MJ, Shackleford DM, Saenz FE et al.. (2013)
Quinolone-3-diarylethers: a new class of antimalarial drug.
Sci Transl Med, 5 (177): 177ra37. [PMID:23515079]
5. Stickles AM, de Almeida MJ, Morrisey JM, Sheridan KA, Forquer IP, Nilsen A, Winter RW, Burrows JN, Fidock DA, Vaidya AB et al.. (2015)
Subtle changes in endochin-like quinolone structure alter the site of inhibition within the cytochrome bc1 complex of Plasmodium falciparum.
Antimicrob Agents Chemother, 59 (4): 1977-82. [PMID:25605352]
6. Winter R, Kelly JX, Smilkstein MJ, Hinrichs D, Koop DR, Riscoe MK. (2011)
Optimization of endochin-like quinolones for antimalarial activity.
Exp Parasitol, 127 (2): 545-51. [PMID:21040724]