compound 22 [WO2019141694A1]   Click here for help

GtoPdb Ligand ID: 12181

Compound class: Synthetic organic
Comment: Compound 22 is a phosphatidylinositol 4-kinase beta (PI4KIIIβ) inhibitor that was designed by GSK as an inhalation drug that's proposed to reduce the severity of viral lung infections that often exacerbate COPD symptoms. Its chemical structure is claimed in patent WO2019141694A1 [1]. PI4KIIIβ activity regulates pools of phosphatidylinositol-4 phosphate (PI4P) that are crucial for the integrity of cell membranes, and it is principally active within the Golgi network. Experimental evidence indicates that PI4KIIIβ is involved in the genomic replication of a range of RNA viruses (e.g. human rhinovirus, enteroviruses 68 and 71, poliovirus, coxsackie virus, hepatitis C virus, bovine kobuvirus, aichi virus and rubella). It was also reported to be required for spike protein mediated cell entry of the 2002/2003 version of SARS coronavirus [2]. These findings led to the emergence of PI4KB as a potential target for the development of broad spectrum antiviral agents.
This structure was disclosed as 'compound 30' during a 'first disclosures' session at the XXVll EFMC International Symposium on Medicinal Chemistry in September 2022.
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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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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 8
Hydrogen bond donors 3
Rotatable bonds 10
Topological polar surface area 120.81
Molecular weight 581.31
XLogP 4.51
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 OC[C@@H](N(C(=O)c1cc(ccc1C)c1c(C)nn2c1nc(cc2NCc1cccc(c1)c1nccn1C)C(O)(C)C)C)C
Isomeric SMILES Cc1c(cc(cc1)c1c2nc(cc(n2nc1C)NCc1cc(ccc1)c1nccn1C)C(C)(C)O)C(=O)N(C)[C@@H](C)CO
InChI InChI=1S/C33H39N7O3/c1-20-11-12-24(16-26(20)32(42)39(7)21(2)19-41)29-22(3)37-40-28(17-27(33(4,5)43)36-31(29)40)35-18-23-9-8-10-25(15-23)30-34-13-14-38(30)6/h8-17,21,35,41,43H,18-19H2,1-7H3/t21-/m0/s1
InChI Key LGILUCRVDGGDMI-NRFANRHFSA-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/)
Classification Click here for help
Compound class Synthetic organic
Database Links Click here for help
GtoPdb PubChem SID 472319303
PubChem CID 139330094
Search Google for chemical match using the InChIKey LGILUCRVDGGDMI-NRFANRHFSA-N
Search Google for chemicals with the same backbone LGILUCRVDGGDMI
UniChem Compound Search for chemical match using the InChIKey LGILUCRVDGGDMI-NRFANRHFSA-N
UniChem Connectivity Search for chemical match using the InChIKey LGILUCRVDGGDMI-NRFANRHFSA-N