PNU-282987

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C14H17ClN2O.ClH
Molecular Weight	301.212
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.ClC1=CC=C(C=C1)C(=O)N[C@H]2CN3CCC2CC3

InChI

InChIKey=HSEQUIRZHDYOIX-ZOWNYOTGSA-N

InChI=1S/C14H17ClN2O.ClH/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);1H/t13-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C14H17ClN2O
Molecular Weight	264.751
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20630711 | https://www.ncbi.nlm.nih.gov/pubmed/15523001
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27729414

PNU-282987 is a potent and selective a7 nAChR agonist. This compound showed high affinity for the rat a7 nAChR (Ki = 26 nM) and activity at the a7–5-HT3 chimera (EC50 = 128 nM). In addition, PNU-282987 was found to be inactive at all tested monoamine, muscarine, glutamate, and GABA receptors at 1 uM concentration, except 5-HT3 receptors (Ki = 930 nM). The highly selective and potent a7 nAChR agonist PNU-282987 enhances GABAergic synaptic activity in the hippocampus in vitro, and reverses amphetamine induced auditory gating deficit in anesthetized rats. In addition, PNU-282987 improves the inherent gating deficit observed in a subset of rats and enhances amphetamine induced hippocampal activity. These results support the concept that a7 nAChR agonists represent a novel, potential pharmacotherapy in treatment of schizophrenia. It also has being shown that acute lung injury is reduced by PNU-282987 through changes in the macrophage profile.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Neuronal acetylcholine receptor protein alpha-7 subunit 77 Target ID: CHEMBL2492 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20828128 \| https://www.ncbi.nlm.nih.gov/pubmed/24901260	Agonist 2678		24.55 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Acute respiratory distress syndrome 5 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27729414	Primary	Preclinical	Unknown Approved Use Unknown
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23938346	Primary	Preclinical	Unknown Approved Use Unknown
Schizophrenia 298 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20630711 http://adisinsight.springer.com/drugs/800018656	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
The selective alpha7 nicotinic acetylcholine receptor agonist PNU-282987 [N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride] enhances GABAergic synaptic activity in brain slices and restores auditory gating deficits in anesthetized rats.	2005 Mar	15523001
Alpha7 nicotinic acetylcholine receptor activation ameliorates scopolamine-induced behavioural changes in a modified continuous Y-maze task in mice.	2009 Jan 5	18848931
Human platelets express functional alpha7-nicotinic acetylcholine receptors.	2011 Apr	21051662
Neurotoxicity induced by okadaic acid in the human neuroblastoma SH-SY5Y line can be differentially prevented by α7 and β2* nicotinic stimulation.	2011 Sep	21715663
Interaction of bispyridinium compounds with the orthosteric binding site of human α7 and Torpedo californica nicotinic acetylcholine receptors (nAChRs).	2011 Sep 25	21703337

Patents

Sample Use Guides

In Vivo Use Guide

Rats: eye drops of PNU-282987 resulted in neuroprotection against etinal ganglion cells (RGCs) loss in a dose-dependent manner using concentrations between 100 uM and 2 mM PNU-282987

Route of Administration: Topical

In Vitro Use Guide

PNU-282987 (1, 3, and 10 uM) incubated for 16 h after the 8-h rot/oligo period in SH-SY5Y cells produced a concentration-dependent protective effect; the maximum protective effect was achieved with 10 uM PNU282987 (50% neuroprotection)

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:53:32 UTC 2023` Edited by `admin` on `Sat Dec 16 09:53:32 UTC 2023`
Record UNII	810P1694K2
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PNU-282987

Common Name

English

BENZAMIDE, N-(3R)-1-AZABICYCLO(2.2.2)OCT-3-YL-4-CHLORO-, HYDROCHLORIDE (1:1)

Systematic Name

English

BENZAMIDE, N-1-AZABICYCLO(2.2.2)OCT-3-YL-4-CHLORO-, MONOHYDROCHLORIDE, (R)-

Systematic Name

English

BENZAMIDE, N-(3R)-1-AZABICYCLO(2.2.2)OCT-3-YL-4-CHLORO-, MONOHYDROCHLORIDE

Systematic Name

English

Code System Code Type Description

FDA UNII

810P1694K2