eleclazine   Click here for help

GtoPdb Ligand ID: 8413

Synonyms: GS-6615 | GS6615
Compound class: Synthetic organic
Comment: Eleclazine is a sodium channel inhibitor, modulating cardiac late Na+ currents via the Nav1.5 (gene symbol SCN5A) channel. The compound is a dihydrobenzodiazepine type structure. Dihydrobenzodiazepine scaffolds are being developed as α-helix mimetics, with the potential to inhibit protein-protein interactions [1,3-5]. This chemical structure and its use is covered by patent US20150038489 [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 CDK toolkit. 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 4
Hydrogen bond donors 0
Rotatable bonds 5
Topological polar surface area 64.55
Molecular weight 415.11
XLogP 3.89
No. Lipinski's rules broken 0
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.

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Canonical SMILES O=C1N(CCOc2c1cc(cc2)c1ccc(cc1)OC(F)(F)F)Cc1ncccn1
Isomeric SMILES O=C1N(CCOc2c1cc(cc2)c1ccc(cc1)OC(F)(F)F)Cc1ncccn1
InChI InChI=1S/C21H16F3N3O3/c22-21(23,24)30-16-5-2-14(3-6-16)15-4-7-18-17(12-15)20(28)27(10-11-29-18)13-19-25-8-1-9-26-19/h1-9,12H,10-11,13H2
InChI Key YNUAEEJQYHYLMS-UHFFFAOYSA-N
References
1. Antuch W, Menon S, Chen QZ, Lu Y, Sakamuri S, Beck B, Schauer-Vukasinović V, Agarwal S, Hess S, Dömling A. (2006)
Design and modular parallel synthesis of a MCR derived alpha-helix mimetic protein-protein interaction inhibitor scaffold.
Bioorg Med Chem Lett, 16 (6): 1740-3. [PMID:16427279]
2. Belardinelli L, Rajamani S, Zeng D. (2015)
Compound and methods for treating long qt syndrome.
Patent number: US20150038489 A1. Assignee: Gilead Sciences, Inc.. Priority date: 01/08/2013. Publication date: 05/02/2015.
3. Cummings MD, Schubert C, Parks DJ, Calvo RR, LaFrance LV, Lattanze J, Milkiewicz KL, Lu T. (2006)
Substituted 1,4-benzodiazepine-2,5-diones as alpha-helix mimetic antagonists of the HDM2-p53 protein-protein interaction.
Chem Biol Drug Des, 67 (3): 201-5. [PMID:16611213]
4. Grasberger BL, Lu T, Schubert C, Parks DJ, Carver TE, Koblish HK, Cummings MD, LaFrance LV, Milkiewicz KL, Calvo RR et al.. (2005)
Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that activate p53 in cells.
J Med Chem, 48 (4): 909-12. [PMID:15715460]
5. Raboisson P, Marugán JJ, Schubert C, Koblish HK, Lu T, Zhao S, Player MR, Maroney AC, Reed RL, Huebert ND et al.. (2005)
Structure-based design, synthesis, and biological evaluation of novel 1,4-diazepines as HDM2 antagonists.
Bioorg Med Chem Lett, 15 (7): 1857-61. [PMID:15780621]