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Details

Stereochemistry ABSOLUTE
Molecular Formula C15H17N3O2
Molecular Weight 271.3144
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PHA-543613

SMILES

O=C(N[C@H]1CN2CCC1CC2)C3=CC4=C(OC=C4)C=N3

InChI

InChIKey=IPKZCLGGYKRDES-ZDUSSCGKSA-N
InChI=1S/C15H17N3O2/c19-15(12-7-11-3-6-20-14(11)8-16-12)17-13-9-18-4-1-10(13)2-5-18/h3,6-8,10,13H,1-2,4-5,9H2,(H,17,19)/t13-/m0/s1

HIDE SMILES / InChI
Molecular Formula C15H17N3O2
Molecular Weight 271.3144
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

PHA-543613 was discovered by Pfizer and has been under development primarily as a potential treatment of schizophrenia. PHA-543613 acts as an agonist to the Neuronal acetylcholine receptor protein alpha-7 subunit. A single human trial was conducted in healthy human volunteers, but the compound has been studied extensively in rat models for schizophrenia as well as Parkinson's disease and Alzheimer's disease.

CNS Activity

Originator

Pfizer
420
Curator's Comment: # Pfizer

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Agonist
2678
 8.8 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase I
428
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
151 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/17446264
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHA-543613 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
212 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/17446264
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHA-543613 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1140 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/17446264
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHA-543613 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1630 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/17446264
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHA-543613 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.78 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/17446264
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHA-543613 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
11.8 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/17446264
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHA-543613 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
81%
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/17446264
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHA-543613 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
81%
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/17446264
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHA-543613 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
40 mg single, oral
Studied dose
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
https://www.ncbi.nlm.nih.gov/pubmed/17446264
Page: p.1191
healthy, ADULT
n = 8
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources:
https://www.ncbi.nlm.nih.gov/pubmed/17446264
Page: p.1191
Other AEs: Nausea...
Other AEs:
Nausea
Sources:
https://www.ncbi.nlm.nih.gov/pubmed/17446264
Page: p.1191
AEs

AEs

AESignificanceDosePopulation
Nausea
40 mg single, oral
Studied dose
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources:
https://www.ncbi.nlm.nih.gov/pubmed/17446264
Page: p.1191
healthy, ADULT
n = 8
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources:
https://www.ncbi.nlm.nih.gov/pubmed/17446264
Page: p.1191
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP19A1
60
HLM
31
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP19A1
60
 no
CYP2D6
1891
 unlikely [IC50 >10 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
HLM
31
 likely
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
Alfa Chemistry
161655
http://www.alfa-chemistry.com/search.aspx?q=161655
Alfa Chemistry
16260
http://www.alfa-chemistry.com/search.aspx?q=16260
Alfa Chemistry
ACM478148582
http://www.alfa-chemistry.com/search.aspx?q=ACM478148582
Alfa Chemistry
AFI478149530
http://www.alfa-chemistry.com/search.aspx?q=AFI478149530
Axon MedChem
2109
https://www.axonmedchem.com/product/2109
BOC Sciences
478148-58-2
http://www.bocsci.com/description.asp?cas=478148-58-2
MolPort
MolPort-009-682-092
https://www.molport.com/shop/molecule-link/MolPort-009-682-092
MolPort
MolPort-023-276-658
https://www.molport.com/shop/molecule-link/MolPort-023-276-658
MolPort
MolPort-042-665-814
https://www.molport.com/shop/molecule-link/MolPort-042-665-814
MuseChem
I008724
https://www.musechem.com/product/I008724.html
MuseChem
R051806
https://www.musechem.com/product/R051806.html
Ryan Scientific
101-94086
https://ryansci.com/products?q=101-94086&list_q=&search_type=exact
Tocris
3092
https://www.tocris.com/search.php?Type=QuickSearch&Value=3092
Toronto Research Chemicals
E925918
https://www.trc-canada.com/product-detail/?CatNum=E925918
Wonderchem
WD0679E
http://www.wonder-chem.com/search.html?text=WD0679E
eMolecules
275100573
https://orderbb.emolecules.com/search/#?query=275100573
eMolecules
29703113
https://orderbb.emolecules.com/search/#?query=29703113
eMolecules
300431702
https://orderbb.emolecules.com/search/#?query=300431702
eMolecules
31430528
https://orderbb.emolecules.com/search/#?query=31430528
eMolecules
49435275
https://orderbb.emolecules.com/search/#?query=49435275
PubMed

PubMed

TitleDatePubMed
Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an agonist of the alpha7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: synthesis and structure--activity relationship.
2006 Jul 13
Metabolism and disposition of a selective alpha(7) nicotinic acetylcholine receptor agonist in humans.
2007 Jul
The frequency-dependence of the nicotine-induced inhibition of dopamine is controlled by the α7 nicotinic receptor.
2010 Sep
Patents

Patents

20030045540
3

Sample Use Guides

In Vivo Use Guide
Absorption, metabolism, and excretion of PHA-543613 were studied in an open-label human trial. Each participant was given PHA-543613 orally dissolved in 10 mL of Pedialyte followed by 100 mL of water. Subjects were required to fast 10 h before and 4 h after dosing.
Route of Administration: Oral
In Vitro Use Guide
Coronal Slices (250 micrometer thickness) were obtained from Sprag-Dawley Rats and equilibrated in buffer containing 50 nM PHA-543613 hydrochloride for 1 hour. Voltammetric recordings were taken in striatal tissue in the dorsal lateral striatum from slices cut posterior 1.5–2 mm from bregma. The combination of PHA-543613 with 500 nM nicotine reduced evoked dopamine to 47 ± 10% (n = 4, p < 0.05) of pre-drug evoked dopamine.
Substance Class Chemical
Created
by admin
on Sat Dec 16 10:56:28 GMT 2023
Edited
by admin
on Sat Dec 16 10:56:28 GMT 2023
Record UNII
R36R9KVD6Y
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PHA-543613
Common Name English
N-((3R)-1-AZABICYCLO(2.2.2)OCT-3-YL)FURO(2,3-C)PYRIDINE-5-CARBOXAMIDE
Systematic Name English
(R)-N-(QUINUCLIDIN-3-YL)FURO(2,3-C)PYRIDINE-5-CARBOXAMIDE
Systematic Name English
PHA-543,613
Code English
PHA-00543613
Common Name English
J3.179.420J
Code English
FURO(2,3-C)PYRIDINE-5-CARBOXAMIDE, N-(3R)-1-AZABICYCLO(2.2.2)OCT-3-YL-
Systematic Name English
Code System Code Type Description
WIKIPEDIA
PHA-543,613
Created by admin on Sat Dec 16 10:56:29 GMT 2023 , Edited by admin on Sat Dec 16 10:56:29 GMT 2023
PRIMARY
ChEMBL
CHEMBL214268
Created by admin on Sat Dec 16 10:56:29 GMT 2023 , Edited by admin on Sat Dec 16 10:56:29 GMT 2023
PRIMARY
FDA UNII
R36R9KVD6Y
Created by admin on Sat Dec 16 10:56:29 GMT 2023 , Edited by admin on Sat Dec 16 10:56:29 GMT 2023
PRIMARY
EPA CompTox
DTXSID6047284
Created by admin on Sat Dec 16 10:56:29 GMT 2023 , Edited by admin on Sat Dec 16 10:56:29 GMT 2023
PRIMARY
PUBCHEM
9930121
Created by admin on Sat Dec 16 10:56:29 GMT 2023 , Edited by admin on Sat Dec 16 10:56:29 GMT 2023
PRIMARY
CAS
892497-69-7
Created by admin on Sat Dec 16 10:56:29 GMT 2023 , Edited by admin on Sat Dec 16 10:56:29 GMT 2023
SUPERSEDED
CAS
478149-53-0
Created by admin on Sat Dec 16 10:56:29 GMT 2023 , Edited by admin on Sat Dec 16 10:56:29 GMT 2023
PRIMARY
Related Record Type Details
NEURONAL ACETYLCHOLINE RECEPTOR SUBUNIT ALPHA-7
TARGET -> AGONIST
PHA-543,613: A SELECTIVE AND POTENT AGONIST WITH NOOTROPIC PROPERTIES.
CYTOCHROME P450 2D6
METABOLIC ENZYME -> SUBSTRATE
FETAL HEPATIC FLAVIN-CONTAINING MONOOXYGENASE 1 (HUMAN)
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
Structure of PHA-543613-GLUCURONIDE
METABOLITE -> PARENT
URINE
Structure of FURANOPYRIDINE OXIDATED PHA-543613 CARBOXYLIC ACID
METABOLITE -> PARENT
URINE
Structure of PHA-543613 OXIDE (QUINUCLIDINE NITROGEN OXIDE)
METABOLITE -> PARENT
URINE
Related Record Type Details
Structure of PHA-543613
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC IN MALE

SINGLE ORAL DOSE ADMINISTRATION

Biological Half-life PHARMACOKINETIC SINGLE ORAL DOSE ADMINISTRATION

IN MALE

Biological Half-life PHARMACOKINETIC SINGLE ORAL DOSE ADMINISTRATION

IN FEMALE

Tmax PHARMACOKINETIC SINGLE ORAL DOSE ADMINISTRATION

IN FEMALE

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