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
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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
Guide to Malaria Pharmacology Comments
Halofantrine was developed by the Walter Reed Army Institute of Research and was a key compound identified during a antimalarial drug discovery programme that ran from 1963 until 1976 [2]. The licensed drug was used in the treatment of both P. falciparum and P. vivax malaria but this has declined significantly due to potentially lethal cardiotoxic side effects and variable pharmacokinetic properties. It is not recommended for prophylactic use.

Potential Target/Mechanism Of Action: As the precise mechanism of action of halofantrine is not yet known, we do not have a molecular target for this compound. There is some evidence that suggests that halofantrine inhibits the haem detoxification pathway in the parasite, and that this action causes lethal haem toxicity [1,3].