compound 72 [WO2013026806]   Click here for help

GtoPdb Ligand ID: 8166

Synonyms: compound 8c [PMID 25264830] [3] | EHT 5372 [1]
Compound class: Synthetic organic
Comment: This is compound 72, an invention covered by patent WO2013026806 [5]. Compound 72 is a highly potent dual DYRK1A/1B inhibitor (DYRK = dual-specificity tyrosine-regulated kinase).
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
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 6
Hydrogen bond donors 2
Rotatable bonds 4
Topological polar surface area 112.02
Molecular weight 369.05
XLogP 3.53
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 COC(=N)c1nc2c(s1)c1c(ncnc1cc2)Nc1ccc(cc1)Cl
Isomeric SMILES COC(=N)c1nc2c(s1)c1c(ncnc1cc2)Nc1ccc(cc1)Cl
InChI InChI=1S/C17H12ClN5OS/c1-24-15(19)17-23-12-7-6-11-13(14(12)25-17)16(21-8-20-11)22-10-4-2-9(18)3-5-10/h2-8,19H,1H3,(H,20,21,22)
InChI Key BGXZIBSLBRKDTP-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/)
No information available.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Compound 72 was developed primarily for its potential to modulate the enhanced activity of DYRK1A in Down's syndrome-related Alzheimer's disease. Additional uses covered by the patent include treatment of other neurodegenerative conditions and some cancers (specifically certain solid tumours) [5].
The DYRK1A gene is located within the Down Syndrome (DS) critical region on chromosome 21. Trisomy of chromosome 21 leads to overexpression of DYRK1A and amyloid precursor protein (APP), and this may underlie the Tau and amyloid pathologies associated with early onset Alzheimer's disease in DS [2,4,6-7]. Pharmacological inhibition of DYRK1A activity would aim to modify the course of AD pathogenesis.