nivegacetor   Click here for help

GtoPdb Ligand ID: 13509

Compound class: Synthetic organic
Comment: The chemical structure for nivegacetor was obtained from WHO proposed INN list 131 (August 2024). The INN record describes the compound as a γ-secretase modulator. The catalytic subunit of the γ-secretase is PSEN1 (presenilin-1). Nivegacetor was developed for potential to slow amyloidogenesis in Alzheimer's disease [1]. The precise enantiomeric structure is difficult to idenitfy, but the SMILES provided for the CAS number (from the INN record) resolves to PubChem CID 153606610. Nivegacetor is predicted to be the INN for the Roche clinical stage γ-secretase modulator RG6289 [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 9
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 86.41
Molecular weight 469.49
XLogP 3.47
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 COC1=CC(=CN=N1)N2C[C@@]3([H])CC[C@@]([H])(C2)[C@@H]3NC4=NN5CC[C@H](C5=N4)OC6=CC(=CC(=C6)F)F
Isomeric SMILES N([C@H]1[C@@]2(CN(C[C@]1(CC2)[H])C=3C=C(OC)N=NC3)[H])C=4N=C5N(N4)CC[C@H]5OC6=CC(F)=CC(F)=C6
InChI InChI=1S/C23H25F2N7O2/c1-33-20-9-17(10-26-29-20)31-11-13-2-3-14(12-31)21(13)27-23-28-22-19(4-5-32(22)30-23)34-18-7-15(24)6-16(25)8-18/h6-10,13-14,19,21H,2-5,11-12H2,1H3,(H,27,30)/t13-,14+,19-,21-/m1/s1
InChI Key YYYGNCPNCFDABE-QWUQOBSTSA-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. Frei B, Ratni H. (2020)
7-phenoxy-n-(3-azabicyclo[3.2.1]octan-8-yl)-6,7-dihydro-5h-pyrrolo[1,2-b][1,2,4]triazol-2-amine derivatives and related compounds as gamma-secretase modulators for the treatment of alzheimer's disease.
Patent number: WO2020120521A1. Assignee: Hoffmann-La Roche. Priority date: 11/12/2019. Publication date: 18/06/2020.
2. Nordvall G, Lundkvist J, Sandin J. (2023)
Gamma-secretase modulators: a promising route for the treatment of Alzheimer's disease.
Front Mol Neurosci, 16: 1279740. [PMID:37908487]