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Details

Stereochemistry ACHIRAL
Molecular Formula C17H20N4
Molecular Weight 280.3675
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of A-582941 FREE BASE

SMILES

[H][C@@]12CN(C)C[C@]1([H])CN(C2)C3=NN=C(C=C3)C4=CC=CC=C4

InChI

InChIKey=GTMRUYCIJSNXGB-GASCZTMLSA-N
InChI=1S/C17H20N4/c1-20-9-14-11-21(12-15(14)10-20)17-8-7-16(18-19-17)13-5-3-2-4-6-13/h2-8,14-15H,9-12H2,1H3/t14-,15+

HIDE SMILES / InChI
Molecular Formula C17H20N4
Molecular Weight 280.3675
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
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/17898229 | http://adisinsight.springer.com/drugs/800020139

A-582941 was found to exhibit high-affinity binding and agonism at alpha-7 nicotinic acetylcholine receptor (α7-nAChR), with acceptable pharmacokinetic properties and excellent distribution to the central nervous system. In vitro and in vivo studies indicated that A-582941 activates signaling pathways known to be involved in cognitive function such as ERK1/2 and CREB phosphorylation. A-582941 enhanced cognitive performance in behavioral assays including the monkey delayed matching-to-sample, rat social recognition, and mouse inhibitory avoidance models that capture domains of working memory, short-term recognition memory, and long-term memory consolidation, respectively. AbbVie is developing α7-nAChR agonists including A-582941 as neuroprotective agents for the treatment of cognitive disorders such as Alzheimer's disease and schizophrenia. Development is at the preclinical stage.

CNS Activity

CNS Active
3913
Curator's Comment: A-582941 is CNS penetrant and active in animals. No human data available.

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Agonist
2678
 6.17 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Broad-spectrum efficacy across cognitive domains by alpha7 nicotinic acetylcholine receptor agonism correlates with activation of ERK1/2 and CREB phosphorylation pathways.
2007 Sep 26
The selective alpha7 nicotinic acetylcholine receptor agonist A-582941 activates immediate early genes in limbic regions of the forebrain: Differential effects in the juvenile and adult rat.
2008 Jun 23
Preclinical characterization of A-582941: a novel alpha7 neuronal nicotinic receptor agonist with broad spectrum cognition-enhancing properties.
2008 Spring
In vivo evaluation of alpha7 nicotinic acetylcholine receptor agonists [11C]A-582941 and [11C]A-844606 in mice and conscious monkeys.
2010 Feb 1
α7 Nicotinic receptor agonist enhances cognition in aged 3xTg-AD mice with robust plaques and tangles.
2014 Feb
Patents

Patents

20050065178
2
20050101602
3
20080064695
3
20080070929
3
20080275048
2
20090163470
2
JP2007521323A
2

Sample Use Guides

In Vivo Use Guide
Administration of A-582941 (1 μmol/kg, i.p.) in mouse produced maximal levels in brain (286 ng/g at 0.33 h) that were 11-fold higher than the plasma C max (26 ng/ml at 0.25 h). This distribution ratio was maintained over an 8 h period, as drug cleared from brain and plasma with t 1/2 = 2.5–3.2 h. Similarly, in rat, A-582941 partitions with approximate sixfold higher levels in brain versus plasma after intraperitoneal dosing at 2–20 μmol/kg. Over this dose range, linear pharmacokinetics was observed, with brain C max (normalized to a 1 μmol/kg dose) averaging 363 ng/g and maximum plasma levels of 62 ng/ml.
Route of Administration: Intraperitoneal
In Vitro Use Guide
A-582941 increases ERK1/2 phosphorylation via α7 nAChRs in a concentration dependent manner EC50 = 95 nM
Substance Class Chemical
Created
by admin
on Sat Dec 16 09:19:27 UTC 2023
Edited
by admin
on Sat Dec 16 09:19:27 UTC 2023
Record UNII
2MUW0L49BN
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
A-582941 FREE BASE
Common Name English
2-METHYL-5-(6-PHENYLPYRIDAZIN-3-YL)OCTAHYDROPYRROLO(3,4-C)PYRROLE
Systematic Name English
PYRROLO(3,4-C)PYRROLE, OCTAHYDRO-2-METHYL-5-(6-PHENYL-3-PYRIDAZINYL)-
Systematic Name English
PYRROLO(3,4-C)PYRROLE, OCTAHYDRO-2-METHYL-5-(6-PHENYL-3-PYRIDAZINYL)-, (3AR,6AS)-REL-
Systematic Name English
Code System Code Type Description
FDA UNII
2MUW0L49BN
Created by admin on Sat Dec 16 09:19:27 UTC 2023 , Edited by admin on Sat Dec 16 09:19:27 UTC 2023
PRIMARY
CAS
848591-89-9
Created by admin on Sat Dec 16 09:19:27 UTC 2023 , Edited by admin on Sat Dec 16 09:19:27 UTC 2023
PRIMARY
CAS
1173179-34-4
Created by admin on Sat Dec 16 09:19:27 UTC 2023 , Edited by admin on Sat Dec 16 09:19:27 UTC 2023
ALTERNATIVE
PUBCHEM
44190553
Created by admin on Sat Dec 16 09:19:27 UTC 2023 , Edited by admin on Sat Dec 16 09:19:27 UTC 2023
PRIMARY
Related Record Type Details
NEURONAL ACETYLCHOLINE RECEPTOR SUBUNIT ALPHA-7
TARGET->PARTIAL AGONIST
ACTS AS PARTIAL AGONIST; ACTIVATES ERK1/2 AND CREB PHOSPHORYLATION; ENHANCES COGNITIVE PERFORMANCE. ; ALPHA 7 IN VITRO DATA: Ki = 10.8 nM
Related Record Type Details
Structure of A-582941 FREE BASE
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