123464-89-1

Basic information

• Product Name: N-(3R)-1-AZABICYCLO[2.2.2]OCT-3-YL-4-CHLOROBENZAMIDE
• Synonyms: N-(3R)-1-AZABICYCLO[2.2.2]OCT-3-YL-4-CHLOROBENZAMIDE;PNU 282987;N-(3R)-1-Azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide hydrochloride;N-(3R)-1-Azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide hydrochloride PNU 282987;PNU282987 HCl;PNU 282987(PNU 282987 hydrochloride)
• CAS NO: 123464-89-1
• Molecular Formula: C14H17ClN2O
• Molecular Weight: 264.75058
• Product Categories: Acetylcholine receptor;Inhibitors
• Mol File: 123464-89-1.mol
• Article Data: 3

Chemical Properties

• Melting Point: 240-242℃
• Boiling Point: 431.5°Cat760mmHg
• Flash Point: 214.8°C
• Appearance: /
• Density: 1.27g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.612
• Storage Temp.: Store at RT
• Solubility: Soluble in DMSO (up to 25 mg/ml)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months.
• CAS DataBase Reference: N-(3R)-1-AZABICYCLO[2.2.2]OCT-3-YL-4-CHLOROBENZAMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: N-(3R)-1-AZABICYCLO[2.2.2]OCT-3-YL-4-CHLOROBENZAMIDE(123464-89-1)
• EPA Substance Registry System: N-(3R)-1-AZABICYCLO[2.2.2]OCT-3-YL-4-CHLOROBENZAMIDE(123464-89-1)

Safety Data

• Hazardous Substances Data: 123464-89-1(Hazardous Substances Data)

Usage

Description

PNU 282987 (CAS 123464-89-1) is a selective α7 nicotinic acetylcholine receptor (nAChR) agonist (Ki?= 26 nM).1? The?a7 nAChR is a potential therapeutic target of cognitive deficits in diseases such as Alzheimer’s, Parkinson’s, schizophrenia, and attention deficit disorders – agonism of this receptor with PNU 282987 has shown potential to ameliorate these deficits.2-5

Uses

PNU 282987 is used as an activator of α-7 nicotinic acetylcholine receptor.

General Description

A potent agonist highly selective for α7 nAChRs (Ki = 26 nM). Used in investigating the roles of α7 nAChRs in sensory gating, learning and memory, cognitive functions, and treatment of Schizophrenia.

Biological Activity

Highly selective α 7 nAChR agonist (K i = 26 nM) displaying negligible blockade of α 1 β 1 γ δ and α 3 β 4 nAChRs (IC 50 ≥ 60 μ M). Found to be inactive against a panel of 32 receptors at 1 μ M, except 5-HT 3 receptors (K i = 930 nM).

Biochem/physiol Actions

Primary Targetα7 nAChRs

References

1) Bodnar?et al.?(2005),?Discovery and structure-activity relationship of quinuclidine benzamides as agonists of α7 nicotinic acetylcholine receptors; J. Med. Chem.?48?905 2) Stuckenholz?et al.?(2013),?The α7 nAChR agonist PNU-282987 reduces inflammation and MPTP-induced nigral dopaminergic cell loss in mice; J. Parkinsons Dis.?3?161 3) Vicens?et al. (2013),?Motor and anxiety effects of PNU-282987, an alpha7 nicotinic receptor agonist, and stress in an animal model of Alzheimer’s disease; Curr. Alzheimer Res.?10?516 4) Navarro?et al.?(2015),?Alpha7 nicotinic receptor activation protects against oxidative stress via heme-oxygenase I induction; Biochem. Pharmacol.?97?473 5) McLean?et al.?(2016),?Nicotinic α7 and α4β2 agonists enhance the formation and retrieval of recognition memory: Potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders; Behav. Brain Res.?302?73

InChI:InChI=1/C14H17ClN2O/c15-12-3-1-11(2-4-12)14(18)16-13-9-17-7-5-10(13)6-8-17/h1-4,10,13H,5-9H2,(H,16,18)/t13-/m0/s1

Upstream product

• 74-11-3 para-chlorobenzoic acid 
• 122-01-0 4-chloro-benzoyl chloride 
• 6530-09-2 (3R)-quinuclidin-3-amine dihydrochloride 

Relevant articles and documents

Discovery and structure-activity relationship of quinuclidine benzamides as agonists of α7 nicotinic acetylcholine receptors

A library of benzamides was tested for α7 nicotinic acetylcholine receptor (nAChR) agonist activity using a chimeric receptor in a functional, cell-based, high-throughput assay. From this library, quinuclidine benzamides were found to have α7 nAChR agonist activity. The SAR diverged from the activity of this compound class verses the 5-HT3 receptor, a structural homologue of the α7 nAChR. PNU-282987, the most potent compound from this series, was also shown to open native α7 nAChRs in cultured rat neurons and to reverse an amphetamine-induced gating deficit in rats.

Method of treating or preventing schizophrenia and/or psychosis using S-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamides and thiobenzamides

Compounds of general formula I STR1 wherein: X represents oxygen or sulphur; each of R1 and R3 independently represents hydrogen or a C1 -C4 alkyl group; Ar represents: a phenyl ring optionally substituted by one, two or three C1 -C4 alkoxy groups and/or by one or two halogen atoms; a phenyl ring of the general formula STR2 wherein R2 represents halogen, 4,5-benzo, C1 -C8 alkoxy, C1 -C4 alkylcarbonyl or Am, wherein Am represents amino, methylamino or dimethylamino, R4 represents C1 -C8 alkyl, n is 1 or 2; or a pyrimidinyl moiety of the general formula STR3 wherein R5 is C1 -C4 alkyl; and their N-oxides and pharmaceutically acceptable salts are useful as antischizophrenic and/or antipsychotic agents. A preferred compound is S(-)-4-amino-N-(1-azabicyclo[2.2.2]oct-3-yl)-5-chloro-2-methoxybenzamide.