compound 4k [PMID: 39232360]   Click here for help

GtoPdb Ligand ID: 13555

Compound class: Synthetic organic
Comment: Compound 4k is reported to completely block currents through the Orai component of the calcium release activated calcium (CRAC) channel, evaluated as inhibition of NFAT activation and nuclear translocation [1]. Blockade of Orai pore was confirmed in HEK293 cells overexpressing G98S mutant or wild-type Orai1. Compound 4k does not alter the electrophysiological function of TRPM4 and TRPM7 channels. The chemical structure is claimed in patent WO2020180876A1 [2].
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 5
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 57.06
Molecular weight 310.33
XLogP 1.21
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 C1=CC2=C(C=C1)N(CC3CC3)N=C2C(=O)NC4=CC=NC=C4F
Isomeric SMILES C1(CC1)CN2N=C(C3=CC=CC=C23)C(=O)NC4=C(C=NC=C4)F
InChI InChI=1S/C17H15FN4O/c18-13-9-19-8-7-14(13)20-17(23)16-12-3-1-2-4-15(12)22(21-16)10-11-5-6-11/h1-4,7-9,11H,5-6,10H2,(H,19,20,23)
InChI Key GWAAPHZRSAMWJU-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/)
References
1. Liardo E, Pham AT, Ghilardi AF, Zhelay T, Szteyn K, Gandi NL, Ekkati A, Koerner S, Kozak JA, Sun L. (2024)
Discovery of selective Orai channel blockers bearing an indazole or a pyrazole scaffold.
Eur J Med Chem, 278: 116805. [PMID:39232360]
2. Sun L. (2020)
Orai channel inhibitors.
Patent number: WO2020180876A1. Assignee: Beth Israel Deaconess Medical Center, Inc.. Priority date: 03/03/2020. Publication date: 10/09/2020.