halofantrine   Click here for help

GtoPdb Ligand ID: 10019

Synonyms: Halfan® | WR-171669
Approved drug Antimalarial Ligand
halofantrine is an approved drug (FDA (1992))
Compound class: Synthetic organic
Comment: Halofantrine is a phenanthrene containing compound and belongs to the aryl amino alcohols, a chemical class of antimalarial drugs that includes quinine, mefloquine and lumefantrine.
The INN record specifies that halofantrine is a racemic mixture of stereoisomers. We show the structure without specified stereochemistry to represent the mixture.
The marketed formulation contains halofantrine hydrochloride (PubChem CID 37392).

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 2
Hydrogen bond donors 1
Rotatable bonds 11
Topological polar surface area 23.47
Molecular weight 499.17
XLogP 8.93
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
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Canonical SMILES CCCCN(CCC(c1cc2c(Cl)cc(cc2c2c1ccc(c2)C(F)(F)F)Cl)O)CCCC
Isomeric SMILES CCCCN(CCC(c1cc2c(Cl)cc(cc2c2c1ccc(c2)C(F)(F)F)Cl)O)CCCC
InChI InChI=1S/C26H30Cl2F3NO/c1-3-5-10-32(11-6-4-2)12-9-25(33)23-16-22-21(14-18(27)15-24(22)28)20-13-17(26(29,30)31)7-8-19(20)23/h7-8,13-16,25,33H,3-6,9-12H2,1-2H3
InChI Key FOHHNHSLJDZUGQ-UHFFFAOYSA-N
References
1. Acharya BN, Kaushik MP. (2007)
Pharmacophore-based predictive model generation for potent antimalarials targeting haem detoxification pathway.
Med Chem Res, 16: 213-229. DOI: 10.1007/s00044-007-9025-8
2. Croft AM. (2007)
A lesson learnt: the rise and fall of Lariam and Halfan.
J R Soc Med, 100 (4): 170-4. [PMID:17404338]
3. de Villiers KA, Marques HM, Egan TJ. (2008)
The crystal structure of halofantrine-ferriprotoporphyrin IX and the mechanism of action of arylmethanol antimalarials.
J. Inorg. Biochem., 102 (8): 1660-7. [PMID:18508124]
4. Delves M, Plouffe D, Scheurer C, Meister S, Wittlin S, Winzeler EA, Sinden RE, Leroy D. (2012)
The activities of current antimalarial drugs on the life cycle stages of Plasmodium: a comparative study with human and rodent parasites.
PLoS Med., 9 (2): e1001169. [PMID:22363211]
5. O'Neill PM, Park BK, Shone AE, Maggs JL, Roberts P, Stocks PA, Biagini GA, Bray PG, Gibbons P, Berry N et al.. (2009)
Candidate selection and preclinical evaluation of N-tert-butyl isoquine (GSK369796), an affordable and effective 4-aminoquinoline antimalarial for the 21st century.
J. Med. Chem., 52 (5): 1408-15. [PMID:19222165]
6. Sánchez-Chapula JA, Navarro-Polanco RA, Sanguinetti MC. (2004)
Block of wild-type and inactivation-deficient human ether-a-go-go-related gene K+ channels by halofantrine.
Naunyn Schmiedebergs Arch. Pharmacol., 370 (6): 484-91. [PMID:15558243]
7. Wesche DL, Schuster BG, Wang WX, Woosley RL. (2000)
Mechanism of cardiotoxicity of halofantrine.
Clin. Pharmacol. Ther., 67 (5): 521-9. [PMID:10824631]