123464-89-1 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
Check Digit Verification of cas no
The CAS Registry Mumber 123464-89-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,3,4,6 and 4 respectively; the second part has 2 digits, 8 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 123464-89:
(8*1)+(7*2)+(6*3)+(5*4)+(4*6)+(3*4)+(2*8)+(1*9)=121
121 % 10 = 1
So 123464-89-1 is a valid CAS Registry Number.
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
123464-89-1Relevant articles and documents
Discovery and structure-activity relationship of quinuclidine benzamides as agonists of α7 nicotinic acetylcholine receptors
Bodnar, Alice L.,Cortes-Burgos, Luz A.,Cook, Karen K.,Dinh, Dac M.,Groppi, Vincent E.,Hajos, Mihaly,Higdon, Nicole R.,Hoffmann, William E.,Hurst, Raymond S.,Myers, Jason K.,Rogers, Bruce N.,Wall, Theron M.,Wolfe, Mark L.,Wong, Erik
, p. 905 - 908 (2007/10/03)
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
-
, (2008/06/13)
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.