FRM-024   Click here for help

GtoPdb Ligand ID: 11752

Synonyms: compound 41 [PMID: 34550687] | FRM024
Compound class: Synthetic organic
Comment: FRM-024 is a CNS-penetrating γ secretase modulator that was developed for its capacity to improve amyloid processing and potential as an Alzheimer's disease therapeutic [1]. Gamma secretase modulators reduce the levels of the toxic longer amyloid β (Aβ) chains (Aβ42, Aβ43) that accummulate in Alzheimer's brains. They do not alter total Aβ levels. In particular, such modulators may afford potential for clinical intervention in patients with inherited loss-of-function mutations in presenilin genes which increase production of the toxic forms of Aβ.
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 3
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 73.04
Molecular weight 423.15
XLogP 5.37
No. Lipinski's rules broken 1
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 COc1nc(ccc1n1cnc(c1)C)C1=NO[C@@H]([C@@H](N1)c1ccc(cc1)Cl)C1CC1
Isomeric SMILES Clc1ccc([C@@H]2NC(=NO[C@@H]2C2CC2)c2ccc(n3cc(C)nc3)c(OC)n2)cc1
InChI InChI=1S/C22H22ClN5O2/c1-13-11-28(12-24-13)18-10-9-17(25-22(18)29-2)21-26-19(14-5-7-16(23)8-6-14)20(30-27-21)15-3-4-15/h5-12,15,19-20H,3-4H2,1-2H3,(H,26,27)/t19-,20+/m0/s1
InChI Key IOQORVDNYPOZPL-VQTJNVASSA-N
References
1. Bursavich MG, Harrison BA, Acharya R, Costa DE, Freeman EA, Hrdlicka LA, Jin H, Kapadnis S, Moffit JS, Murphy D et al.. (2021)
Discovery of the Oxadiazine FRM-024: A Potent CNS-Penetrant Gamma Secretase Modulator.
J Med Chem, 64 (19): 14426-14447. [PMID:34550687]