U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C15H20N2O2.ClH
Molecular Weight 296.792
Optical Activity ( - )
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Sazetidine A hydrochloride

SMILES

Cl.OCCCCC#CC1=CC(OC[C@@H]2CCN2)=CN=C1

InChI

InChIKey=KWQOEGGWZHGKHO-UQKRIMTDSA-N
InChI=1S/C15H20N2O2.ClH/c18-8-4-2-1-3-5-13-9-15(11-16-10-13)19-12-14-6-7-17-14;/h9-11,14,17-18H,1-2,4,6-8,12H2;1H/t14-;/m0./s1

HIDE SMILES / InChI
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
Molecular Formula C15H20N2O2
Molecular Weight 260.3315
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27444741 | https://www.ncbi.nlm.nih.gov/pubmed/22297831 | https://www.ncbi.nlm.nih.gov/pubmed/20535453 | https://www.ncbi.nlm.nih.gov/pubmed/18719450 | https://www.ncbi.nlm.nih.gov/pubmed/20435920 | https://www.ncbi.nlm.nih.gov/pubmed/24422997

Sazetidine-A (6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol or AMOP-H-OH) is a "silent desensitizer" of neuronal nicotinic acetylcholine receptors (nAChRs), meaning that it desensitizes the receptor without first activating it. Later it was shown that Sazetidine-A is an agonist of native and recombinant alpha4beta2 nAChRs but shows differential efficacy on alpha4beta2 nAChRs subtypes. In animal models it is able to regulate the gain in body weight, alcohol and nicotine dependence. Sazetidine-A exerts analgesic, antidepressant and anxiolytic properties.

CNS Activity

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Agonist
2678
 0.64 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Sazetidine-A, a novel ligand that desensitizes alpha4beta2 nicotinic acetylcholine receptors without activating them.
2006 Oct
Sazetidine-A is a potent and selective agonist at native and recombinant alpha 4 beta 2 nicotinic acetylcholine receptors.
2008 Jun
Nicotinic partial agonists varenicline and sazetidine-A have differential effects on affective behavior.
2010 Aug
Effects of sazetidine-A, a selective alpha4beta2 nicotinic acetylcholine receptor desensitizing agent on alcohol and nicotine self-administration in selectively bred alcohol-preferring (P) rats.
2010 Aug
The high-affinity nAChR partial agonists varenicline and sazetidine-A exhibit reinforcing properties in rats.
2010 Dec 1
Chemistry and pharmacological characterization of novel nitrogen analogues of AMOP-H-OH (Sazetidine-A, 6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol) as α4β2-nicotinic acetylcholine receptor-selective partial agonists.
2010 Oct 14
Sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor ligand: effects on dizocilpine and scopolamine-induced attentional impairments in female Sprague-Dawley rats.
2011 Jun
Discovery of isoxazole analogues of sazetidine-A as selective α4β2-nicotinic acetylcholine receptor partial agonists for the treatment of depression.
2011 Oct 27
Dissociation between duration of action in the forced swim test in mice and nicotinic acetylcholine receptor occupancy with sazetidine, varenicline, and 5-I-A85380.
2011 Sep
Cholinergic receptor system as a target for treating alcohol abuse and dependence.
2012 Aug
Novel medication targets for the treatment of alcoholism: preclinical studies.
2012 Aug
Assessing the effects of chronic sazetidine-A delivery on nicotine self-administration in both male and female rats.
2012 Jul
Effects of sazetidine-A, a selective α4β2* nicotinic receptor desensitizing agent, on body temperature regulation in mice and rats.
2012 May 5
A new radioligand binding assay to measure the concentration of drugs in rodent brain ex vivo.
2012 Nov
Acute activation, desensitization and smoldering activation of human acetylcholine receptors.
2013
Chemistry and pharmacological studies of 3-alkoxy-2,5-disubstituted-pyridinyl compounds as novel selective α4β2 nicotinic acetylcholine receptor ligands that reduce alcohol intake in rats.
2013 Apr 11
Effects of chronic sazetidine-A, a selective α4β2 neuronal nicotinic acetylcholine receptors desensitizing agent on pharmacologically-induced impaired attention in rats.
2013 Mar
Divergent functional effects of sazetidine-a and varenicline during nicotine withdrawal.
2013 Sep
Nicotinic receptor modulation to treat alcohol and drug dependence.
2014
The unique α4+/-α4 agonist binding site in (α4)3(β2)2 subtype nicotinic acetylcholine receptors permits differential agonist desensitization pharmacology versus the (α4)2(β2)3 subtype.
2014 Jan
Synthesis and pharmacological characterization of new neuronal nicotinic acetylcholine receptor ligands derived from Sazetidine-A.
2014 Jul 1
Decreasing nicotinic receptor activity and the spatial learning impairment caused by the NMDA glutamate antagonist dizocilpine in rats.
2014 Oct 15
Pharmacologically distinct nicotinic acetylcholine receptors drive efferent-mediated excitation in calyx-bearing vestibular afferents.
2015 Feb 25
The role of alpha5 nicotinic acetylcholine receptors in mouse models of chronic inflammatory and neuropathic pain.
2015 Oct 15
PKCε phosphorylates α4β2 nicotinic ACh receptors and promotes recovery from desensitization.
2015 Sep
Evidence for the role of β2* nAChR desensitization in regulating body weight in obese mice.
2016 Nov
The effect of sazetidine-A and other nicotinic ligands on nicotine controlled goal-tracking in female and male rats.
2017 Feb
Patents

Patents

WO2008011484A3
3
WO2009039460A2
3
WO2009039460A3
3
WO2013071097A1
3

Sample Use Guides

In Vitro Use Guide
In the absence of PNU-120596, sazetidine-A elicited mecamylamine-sensitive increases in fluorescence in SH-SY5Y cells (EC50 4.2 µM) but no responses from primary cortical neurons. In the presence on PNU-120596, an additional response to sazetidine-A was observed in SH-SY5Y cells (EC50 0.4 µM) and robust responses were recorded in 14 % of cortical neurons.
Substance Class Chemical
Created
by admin
on Sat Dec 16 19:33:01 GMT 2023
Edited
by admin
on Sat Dec 16 19:33:01 GMT 2023
Record UNII
YUU6E4XT44
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Sazetidine A hydrochloride
Common Name English
5-Hexyn-1-ol, 6-[5-[(2S)-2-azetidinylmethoxy]-3-pyridinyl]-, hydrochloride (1:1)
Systematic Name English
(S)-6-(5-(azetidin-2-ylmethoxy)pyridin-3-yl)hex-5-yn-1-ol dihydrochloride
Systematic Name English
Code System Code Type Description
PUBCHEM
77108155
Created by admin on Sat Dec 16 19:33:01 GMT 2023 , Edited by admin on Sat Dec 16 19:33:01 GMT 2023
PRIMARY
CAS
1197329-42-2
Created by admin on Sat Dec 16 19:33:01 GMT 2023 , Edited by admin on Sat Dec 16 19:33:01 GMT 2023
PRIMARY
FDA UNII
YUU6E4XT44
Created by admin on Sat Dec 16 19:33:01 GMT 2023 , Edited by admin on Sat Dec 16 19:33:01 GMT 2023
PRIMARY
EPA CompTox
DTXSID701010180
Created by admin on Sat Dec 16 19:33:01 GMT 2023 , Edited by admin on Sat Dec 16 19:33:01 GMT 2023
PRIMARY
Related Record Type Details
Structure of Sazetidine A
PARENT -> SALT/SOLVATE
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966