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Details

Stereochemistry ABSOLUTE
Molecular Formula C15H17N3O2
Molecular Weight 271.315
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PHA-543613

SMILES

C1CN2CCC1[C@]([H])(C2)NC(=O)c3cc4ccoc4cn3

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 271.315
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

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.

Originator

Curator's Comment:: # Pfizer

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
8.8 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
151 ng/mL
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
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
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
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
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
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%
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%
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: Page: p.1191
healthy, ADULT
n = 8
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources: Page: p.1191
Other AEs: Nausea...
Other AEs:
Nausea
Sources: Page: p.1191
AEs

AEs

AESignificanceDosePopulation
Nausea
40 mg single, oral
Studied dose
Dose: 40 mg
Route: oral
Route: single
Dose: 40 mg
Sources: Page: p.1191
healthy, ADULT
n = 8
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources: Page: p.1191
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
unlikely [IC50 >10 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
likely
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
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
Genetic variation within the Chrna7 gene modulates nicotine reward-like phenotypes in mice.
2014 Feb
Patents

Patents

Sample Use Guides

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
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 Jun 26 11:00:29 UTC 2021
Edited
by admin
on Sat Jun 26 11:00:29 UTC 2021
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
ChEMBL
CHEMBL214268
Created by admin on Sat Jun 26 11:00:29 UTC 2021 , Edited by admin on Sat Jun 26 11:00:29 UTC 2021
PRIMARY
FDA UNII
R36R9KVD6Y
Created by admin on Sat Jun 26 11:00:29 UTC 2021 , Edited by admin on Sat Jun 26 11:00:29 UTC 2021
PRIMARY
EPA CompTox
478149-53-0
Created by admin on Sat Jun 26 11:00:29 UTC 2021 , Edited by admin on Sat Jun 26 11:00:29 UTC 2021
PRIMARY
PUBCHEM
9930121
Created by admin on Sat Jun 26 11:00:29 UTC 2021 , Edited by admin on Sat Jun 26 11:00:29 UTC 2021
PRIMARY
CAS
892497-69-7
Created by admin on Sat Jun 26 11:00:29 UTC 2021 , Edited by admin on Sat Jun 26 11:00:29 UTC 2021
SUPERSEDED
CAS
478149-53-0
Created by admin on Sat Jun 26 11:00:29 UTC 2021 , Edited by admin on Sat Jun 26 11:00:29 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> AGONIST
PHA-543,613: A SELECTIVE AND POTENT AGONIST WITH NOOTROPIC PROPERTIES.
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
Related Record Type Details
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