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
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
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 |
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
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4980 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16821801 |
8.8 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Sources: https://www.ncbi.nlm.nih.gov/pubmed/23079470 |
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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 |
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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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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... |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
unlikely [IC50 >10 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
likely |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
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
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17446264
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20598018
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
Edited
Sat Dec 16 10:56:28 GMT 2023
by
admin
on
Sat Dec 16 10:56:28 GMT 2023
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Record UNII |
R36R9KVD6Y
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Record Status |
Validated (UNII)
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Record Version |
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Code | English | ||
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Systematic Name | English |
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PHA-543,613
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CHEMBL214268
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R36R9KVD6Y
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DTXSID6047284
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9930121
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892497-69-7
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478149-53-0
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admin on Sat Dec 16 10:56:29 GMT 2023 , Edited by admin on Sat Dec 16 10:56:29 GMT 2023
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Related Record | Type | Details | ||
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TARGET -> AGONIST |
PHA-543,613: A SELECTIVE AND POTENT AGONIST WITH NOOTROPIC PROPERTIES.
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METABOLIC ENZYME -> SUBSTRATE |
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METABOLIC ENZYME -> SUBSTRATE |
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METABOLITE -> PARENT |
URINE
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METABOLITE -> PARENT |
URINE
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METABOLITE -> PARENT |
URINE
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Tmax | PHARMACOKINETIC |
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IN MALE |
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Biological Half-life | PHARMACOKINETIC |
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SINGLE ORAL DOSE ADMINISTRATION |
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Biological Half-life | PHARMACOKINETIC |
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SINGLE ORAL DOSE ADMINISTRATION |
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Tmax | PHARMACOKINETIC |
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SINGLE ORAL DOSE ADMINISTRATION |
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