GSK369796   Click here for help

GtoPdb Ligand ID: 10411

Synonyms: N-tert-Butyl isoquine
Antimalarial Ligand
Compound class: Synthetic organic
Comment: GSK369796 is a 4-aminoquinoline antimalarial compound that was synthesised using amodiaquine as the template molecule [3].

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 3
Hydrogen bond donors 3
Rotatable bonds 5
Topological polar surface area 57.18
Molecular weight 355.15
XLogP 4.79
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES Clc1ccc2c(c1)nccc2Nc1ccc(c(c1)O)CNC(C)(C)C
Isomeric SMILES Clc1ccc2c(c1)nccc2Nc1ccc(c(c1)O)CNC(C)(C)C
InChI InChI=1S/C20H22ClN3O/c1-20(2,3)23-12-13-4-6-15(11-19(13)25)24-17-8-9-22-18-10-14(21)5-7-16(17)18/h4-11,23,25H,12H2,1-3H3,(H,22,24)
InChI Key ZVMMVSSEAMUNGI-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Guide to Malaria Pharmacology Comments
GSK369796 was developed by academics at Liverpool as part of a public-private partnership managed by the Medicines for Malaria Venture (MMV) [3]. This research collaboration, utilised the 4-aminoquinoline scaffold of amodiaquine to design and synthesise derivatives active against both chloroquine-susceptible and chloroquine-resistant P. falciparum strains.

Potential Target/Mechanism Of Action: As the precise MOA of GSK369796 is not yet known, we do not have a molecular target for this compound. It is thought that GSK369796 has a similar MOA to chloroquine, killing the malaria parasite by causing a build up of toxic heme by inhibiting the enzyme that normally converts it to non-toxic haemozoin [1].