PHA-543613 DIHYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H17N3O2.2ClH
Molecular Weight	344.236
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=USJDQOUQSDDWPO-GXKRWWSZSA-N

InChI=1S/C15H17N3O2.2ClH/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);2*1H/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

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16821801 | https://www.ncbi.nlm.nih.gov/pubmed/20598018 | https://www.ncbi.nlm.nih.gov/pubmed/26389120 | https://www.ncbi.nlm.nih.gov/pubmed/23079470

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
Neuronal acetylcholine receptor protein alpha-7 subunit 77 Target ID: CHEMBL4980 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16821801	Agonist 2678		8.8 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Schizophrenia 298 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16821801	Primary	Phase I 428	Unknown Approved Use Unknown
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26389120	Primary	Preclinical	Unknown Approved Use Unknown
Pain 614 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23079470	Primary	Preclinical	Unknown Approved Use Unknown
Alzheimer’s disease 272 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25881725 https://www.ncbi.nlm.nih.gov/pubmed/26647792	Primary	Preclinical	Unknown Approved Use Unknown

C_max

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
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

T_1/2

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

F_unbound

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: 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

AE	Significance	Dose	Population
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

CYP3A4	CYP2C9	CYP2D6	hERG
		inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP19A1 60	HLM 31

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP19A1 60	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743083#sid=144210766	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/16821801/	unlikely [IC50 >10 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
HLM 31	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16821801/	likely

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/16821801/

Sourcing

Vendor/Aggregator	ID	URL
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

Title	Date	PubMed

Patents

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 `Fri Dec 15 15:31:20 GMT 2023` Edited by `admin` on `Fri Dec 15 15:31:20 GMT 2023`
Record UNII	Z7950E6X01
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

PHA-543613 DIHYDROCHLORIDE

Common Name

English

FURO(2,3-C)PYRIDINE-5-CARBOXAMIDE, N-(3R)-1-AZABICYCLO(2.2.2)OCT-3-YL-, DIHYDROCHLORIDE

Systematic Name

English

FURO(2,3-C)PYRIDINE-5-CARBOXAMIDE, N-(3R)-1-AZABICYCLO(2.2.2)OCT-3-YL-, HYDROCHLORIDE (1:2)

Systematic Name

English

PHA-543613 DIHYDROCHLORIDE SALT

Common Name

English

PHA-543613E

Common Name

English

Code System Code Type Description

CAS

892497-82-4

Created by admin on Fri Dec 15 15:31:20 GMT 2023 , Edited by admin on Fri Dec 15 15:31:20 GMT 2023

SUPERSEDED

FDA UNII

Z7950E6X01

Created by admin on Fri Dec 15 15:31:20 GMT 2023 , Edited by admin on Fri Dec 15 15:31:20 GMT 2023

PRIMARY

CAS

478148-58-2

Created by admin on Fri Dec 15 15:31:20 GMT 2023 , Edited by admin on Fri Dec 15 15:31:20 GMT 2023

PRIMARY

PUBCHEM

11493927

Created by admin on Fri Dec 15 15:31:20 GMT 2023 , Edited by admin on Fri Dec 15 15:31:20 GMT 2023

PRIMARY

Related Record Type Details


					R36R9KVD6Y

PHA-543613

ACTIVE MOIETY

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/16821801 | https://www.ncbi.nlm.nih.gov/pubmed/20598018 | https://www.ncbi.nlm.nih.gov/pubmed/26389120 | https://www.ncbi.nlm.nih.gov/pubmed/23079470

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Approved Use

Approved Use

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16821801 | https://www.ncbi.nlm.nih.gov/pubmed/20598018 | https://www.ncbi.nlm.nih.gov/pubmed/26389120 | https://www.ncbi.nlm.nih.gov/pubmed/23079470

C_max

T_1/2

F_unbound

Drug as perpetrator