PF-03654746

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H24F2N2O
Molecular Weight	322.3928
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCNC(=O)[C@H]1C[C@](F)(C1)C2=CC(F)=C(CN3CCCC3)C=C2

InChI

InChIKey=SXMBKHYDZOCBMT-PPUGGXLSSA-N

InChI=1S/C18H24F2N2O/c1-2-21-17(23)14-10-18(20,11-14)15-6-5-13(16(19)9-15)12-22-7-3-4-8-22/h5-6,9,14H,2-4,7-8,10-12H2,1H3,(H,21,23)/t14-,18-

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20864505
Curator's Comment: http://www.pfizer.com/sites/default/files/product-pipeline/pipeline_2011_0228.pdf

PF-03654746 is a potent, selective antagonist of the human H3 receptor, developed by Pfizer. It was in the clinical trial phase II for the treatment of excessive daytime sleepiness (EDS) associated with narcolepsy, Tourette syndrome as well as potential anti-allergy applications and in phase I of clinical trial for the treatment of Schizophrenia and Alzheimer's disease, but these investigations were discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Histamine H3 receptor 44 Target ID: CHEMBL264 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21928839	Antagonist 2778

Conditions

Condition	Modality	Highest Phase	Product
Allergic rhinitis 100 Sources: https://clinicaltrials.gov/ct2/show/NCT00562120	Primary	Phase II 1132	Unknown Approved Use Unknown
Narcolepsy 20 Sources: https://clinicaltrials.gov/ct2/show/NCT01006122	Primary	Phase II 1132	Unknown Approved Use Unknown
Schizophrenia 298 Sources: https://clinicaltrials.gov/ct2/show/NCT01346163	Primary	Phase I 428	Unknown Approved Use Unknown
Tourette's syndrome 20 Sources: https://clinicaltrials.gov/ct2/show/NCT01475383	Primary	Phase II 1132	Unknown Approved Use Unknown
Alzheimer’s disease 272 Sources: https://clinicaltrials.gov/ct2/show/NCT01028911	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
14020 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21928839	300 mg/kg 1 times / day multiple, oral dose: 300 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered:		PF-03654746 plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
189000 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21928839	300 mg/kg 1 times / day multiple, oral dose: 300 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered:		PF-03654746 plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.7% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21928839	300 mg/kg 1 times / day multiple, oral dose: 300 mg/kg route of administration: Oral experiment type: MULTIPLE co-administered:		PF-03654746 plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY503650	https://www.001chemical.com/chem/1039399-17-1
001 Chemical	DY581100	https://www.001chemical.com/chem/935840-31-6
Achemtek	0102-011962	http://www.achemtek.com/935840-31-6
BLD Pharm	BD01188466	http://www.bldpharm.com/products/935840-31-6.html
Chem Scene	CS-0003013	http://www.chemscene.com/935840-31-6.html
DC Chemicals	DC23422	http://www.dcchemicals.com/product_show-DC23422.html
MedChem Express	HY-11045	https://www.medchemexpress.com/pf-03654746.html
Molcore	MC503650	https://www.molcore.com/product/1039399-17-1
Molcore	MC581100	https://www.molcore.com/product/935840-31-6
Smolecule	S539092	http://www.smolecule.com/products/s539092
THE BioTek	bt-278939	https://www.thebiotek.com/product/inhibitors/bt-278939
eNovation Chemicals	D676150	https://www.enovationchem.com/ProductDetails.asp?ProductID=D676150

PubMed

Title	Date	PubMed
Discovery of two clinical histamine H(3) receptor antagonists: trans-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidinylmethyl)phenyl]cyclobutanecarboxamide (PF-03654746) and trans-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-(2-methylpropyl)cyclobutanecarboxamide (PF-03654764).	2011 Nov 10	21928839

Patents

Sample Use Guides

In Vivo Use Guide

excessive daytime sleepiness (EDS) associated with narcolepsy: Each patient will receive PF-03654746 tablets in a fixed dose titration schedule beginning at 0.25 mg QD for 5 days; then up to 0.50 mg QD for another 5 days; and up to 1.0 mg QD for an additional 5 days Schizophrenia: PF-03654746 will be administered in a flexible titration regimen, beginning with 0.5 mg/d. If 0.5 mg/d is well tolerated, the dose will be increased to 1.0 mg/d after 5 days. If 1.0 mg/d is not well tolerated, the dose will be decreased to 0.5 mg/d, with the goal of achieving a stable dose of PF-03654746 within the first two weeks of dosing and avoiding further dose changes during the final week of dosing.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

PF-03654746

Common Name

English

CYCLOBUTANECARBOXAMIDE, N-ETHYL-3-FLUORO-3-(3-FLUORO-4-(1-PYRROLIDINYLMETHYL)PHENYL)-, TRANS-

Common Name

English

PF 03654746

Code

English

Code System Code Type Description

EPA CompTox

DTXSID401029522