U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C18H24F2N2O.C7H8O3S
Molecular Weight 494.594
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PF-03654746 TOSYLATE

SMILES

CC1=CC=C(C=C1)S(O)(=O)=O.CCNC(=O)[C@H]2C[C@](F)(C2)C3=CC(F)=C(CN4CCCC4)C=C3

InChI

InChIKey=IKAYTZLLIWAEDV-WXWMPIANSA-N
InChI=1S/C18H24F2N2O.C7H8O3S/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;1-6-2-4-7(5-3-6)11(8,9)10/h5-6,9,14H,2-4,7-8,10-12H2,1H3,(H,21,23);2-5H,1H3,(H,8,9,10)/t14-,18-;

HIDE SMILES / InChI

Description

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 TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
14020 ng/mL
300 mg/kg 1 times / day multiple, oral
PF-03654746 plasma
Rattus norvegicus

AUC

ValueDoseCo-administeredAnalytePopulation
189000 ng × h/mL
300 mg/kg 1 times / day multiple, oral
PF-03654746 plasma
Rattus norvegicus

Funbound

ValueDoseCo-administeredAnalytePopulation
0.7%
300 mg/kg 1 times / day multiple, oral
PF-03654746 plasma
Rattus norvegicus

PubMed

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