BRD1158   Click here for help

GtoPdb Ligand ID: 13360

Synonyms: BRD 1158 | BRD-1158 | exmple 47 [WO2021050700] [2]
Compound class: Synthetic organic
Comment: BRD1158 is a selective, fully reversible and brain-penetrant COX2 inhibitor [1-2]. It has a rapid target kon and koff rates which makes it a good candidate as a PET radiotracer to monitor enzyme dynamics in vivo. The radiotracer [11C]BRD1158 is particuarly suited for imaging in tissues (such as microglia) where basal COX2 expression is very low, and has demonstrated its in vivo imaging potential in rodent models that express human COX2 (including a mouse Huntington's disease model in which COX2 expression is elevated in disease-affected brain regions).
2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

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.

✖
Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 76.14
Molecular weight 328.39
XLogP 0.49
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
Click here for help

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/)

✖
Canonical SMILES CS(=O)(=O)C1=CC=C(C=C1)C2=NC(=CC=C2)NCC3=COC=C3
Isomeric SMILES CS(=O)(=O)C1=CC=C(C=C1)C2=NC(NCC3=COC=C3)=CC=C2
InChI InChI=1S/C17H16N2O3S/c1-23(20,21)15-7-5-14(6-8-15)16-3-2-4-17(19-16)18-11-13-9-10-22-12-13/h2-10,12H,11H2,1H3,(H,18,19)
InChI Key SEQJAWHEDNIYEW-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/)
Bioactivity Comments
IC50 for human COX2 is 24.6 nM determined in a rapid inhibition LCMS-based enzymatic assay with a short (2 min) incubation time [1]. In this same assay the IC50s for celecoxib and rofecoxib are 54 nM and 535 nM respectively.