ANAVEX 3-71   Click here for help

GtoPdb Ligand ID: 13166

Synonyms: AF710B
Compound class: Synthetic organic
Comment: ANAVEX 3-71 is an oral, small molecule dual agonist of the σ1 (SIGMAR1) and M1 muscarinic acetylcholine receptors. Based on structure we matched ANAVEX 3-71 to AF710B, which appears to be the active S enantiomer of racemic AF710, in US20110281903A1 [3]. AF710B is described as both a M1 partial agonist and positive allosteric modulator in this patent and in peer reviewed articles [2,4]. AF710B was originally investigated for disease-modifying potential in Alzhermer's disease [1-2,4-6].
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 1
Rotatable bonds 4
Topological polar surface area 60.88
Molecular weight 357.51
XLogP 1.97
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 C[C@H]1N(CC2(CCN(C)CC2)S1)C(=O)CCC3=CNC4=C3C=CC=C4
Isomeric SMILES C[C@@H]1SC2(CN1C(=O)CCC3=CNC4=C3C=CC=C4)CCN(C)CC2
InChI InChI=1S/C20H27N3OS/c1-15-23(14-20(25-15)9-11-22(2)12-10-20)19(24)8-7-16-13-21-18-6-4-3-5-17(16)18/h3-6,13,15,21H,7-12,14H2,1-2H3/t15-/m0/s1
InChI Key XWMHYQATSBWUNT-HNNXBMFYSA-N
References
1. Fadiran EO, Hammond E, Tran J, Missling CU, Ette E. (2024)
Population-Based Characterization of the Pharmacokinetics and Food Effect of ANAVEX3-71, a Novel Sigma-1 Receptor and Allosteric M1 Muscarinic Receptor Agonist in Development for Treatment of Frontotemporal Dementia, Schizophrenia, and Alzheimer Disease.
Clin Pharmacol Drug Dev, 13 (1): 21-31. [PMID:38073274]
2. Fadiran EO, Hammond E, Tran J, Xue H, Chen J, Kaufmann WE, Missling CU, Darpo B. (2023)
Concentration-QTc Relationship from a Single Ascending Dose Study of ANAVEX3-71, a Novel Sigma-1 Receptor and Allosteric M1 Muscarinic Receptor Agonist in Development for the Treatment of Frontotemporal Dementia, Schizophrenia, and Alzheimer's Disease.
Clin Pharmacol Drug Dev, 12 (9): 888-901. [PMID:37515316]
3. Fisher A, Bar-Ner N, Nachum V. (2011)
Bicyclic heterocyclic spiro compounds.
Patent number: US20110281903A1. Assignee: Israel Institute for Biological Research. Priority date: 26/01/2010. Publication date: 17/11/2011.
4. Fisher A, Bezprozvanny I, Wu L, Ryskamp DA, Bar-Ner N, Natan N, Brandeis R, Elkon H, Nahum V, Gershonov E et al.. (2016)
AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s Disease.
Neurodegener Dis, 16 (1-2): 95-110. [PMID:26606130]
5. Hall H, Iulita MF, Gubert P, Flores Aguilar L, Ducatenzeiler A, Fisher A, Cuello AC. (2018)
AF710B, an M1/sigma-1 receptor agonist with long-lasting disease-modifying properties in a transgenic rat model of Alzheimer's disease.
Alzheimers Dement, 14 (6): 811-823. [PMID:29291374]
6. Orciani C, Do Carmo S, Foret MK, Hall H, Bonomo Q, Lavagna A, Huang C, Cuello AC. (2023)
Early treatment with an M1 and sigma-1 receptor agonist prevents cognitive decline in a transgenic rat model displaying Alzheimer-like amyloid pathology.
Neurobiol Aging, 132: 220-232. [PMID:37864952]