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Identification
NameZanapezil
Accession NumberDB04859
TypeSmall Molecule
GroupsInvestigational
DescriptionZanapezil (TAK-147) is a selective acetylcholine (ACh) esterase inhibitor under investigation as a drug for Alzheimer's disease (AD) treatment.
Structure
Thumb
Synonyms
Zanepezil
External Identifiers
  • TAK-147
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII0A0800O89N
CAS number142852-50-4
WeightAverage: 376.5344
Monoisotopic: 376.251463656
Chemical FormulaC25H32N2O
InChI KeyPMBLXLOXUGVTGB-UHFFFAOYSA-N
InChI
InChI=1S/C25H32N2O/c28-25(23-11-10-22-8-4-5-15-26-24(22)18-23)12-9-20-13-16-27(17-14-20)19-21-6-2-1-3-7-21/h1-3,6-7,10-11,18,20,26H,4-5,8-9,12-17,19H2
IUPAC Name
3-(1-benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)propan-1-one
SMILES
O=C(CCC1CCN(CC2=CC=CC=C2)CC1)C1=CC2=C(CCCCN2)C=C1
Pharmacology
IndicationFor the treatment of dementia in subjects with Alzheimer’s disease.
Structured Indications Not Available
PharmacodynamicsZanapezil is an acetylcholinesterase inhibitor being developed by Takeda for the treatment of dementia in subjects with Alzheimer’s disease. In May 2003, the company discontinued development of the compound due to a lack of a dose-dependent effect in the trials.
Mechanism of actionZanapezil inhibits the degradation of acetylcholine, a neurotransmitter, to prevent the reduction of cerebral acetylcholine levels and to enhance the mental function of patients with dementia. It is expected to act selectively on the central nervous system, resulting in fewer peripheral adverse reactions.
TargetKindPharmacological actionActionsOrganismUniProt ID
AcetylcholinesteraseProteinunknownNot AvailableHumanP22303 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Hatip-Al-Khatib I, Takashi A, Egashira N, Iwasaki K, Fujiwara M: Comparison of the effect of TAK-147 (zanapezil) and E-2020 (donepezil) on extracellular acetylcholine level and blood flow in the ventral hippocampus of freely moving rats. Brain Res. 2004 Jun 25;1012(1-2):169-76. [PubMed:15158174 ]
  2. Hatip-Al-Khatib I, Iwasaki K, Yoshimitsu Y, Arai T, Egashira N, Mishima K, Ikeda T, Fujiwara M: Effect of oral administration of zanapezil (TAK-147) for 21 days on acetylcholine and monoamines levels in the ventral hippocampus of freely moving rats. Br J Pharmacol. 2005 Aug;145(8):1035-44. [PubMed:15951830 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.982
Blood Brain Barrier+0.9946
Caco-2 permeable+0.5583
P-glycoprotein substrateSubstrate0.7921
P-glycoprotein inhibitor IInhibitor0.9285
P-glycoprotein inhibitor IINon-inhibitor0.5815
Renal organic cation transporterInhibitor0.7487
CYP450 2C9 substrateNon-substrate0.8537
CYP450 2D6 substrateSubstrate0.781
CYP450 3A4 substrateNon-substrate0.5592
CYP450 1A2 substrateInhibitor0.642
CYP450 2C9 inhibitorNon-inhibitor0.9477
CYP450 2D6 inhibitorInhibitor0.8139
CYP450 2C19 inhibitorNon-inhibitor0.9217
CYP450 3A4 inhibitorNon-inhibitor0.5365
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6221
Ames testNon AMES toxic0.7535
CarcinogenicityNon-carcinogens0.9435
BiodegradationNot ready biodegradable0.9824
Rat acute toxicity2.8114 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5952
hERG inhibition (predictor II)Inhibitor0.8697
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.000615 mg/mLALOGPS
logP5.15ALOGPS
logP4.78ChemAxon
logS-5.8ALOGPS
pKa (Strongest Acidic)17.1ChemAxon
pKa (Strongest Basic)8.74ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area32.34 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity118.68 m3·mol-1ChemAxon
Polarizability44.81 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-benzylpiperidines. These are heterocyclic Compounds containing a piperidine ring conjugated to a benzyl group through one nitrogen ring atom.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPiperidines
Sub ClassBenzylpiperidines
Direct ParentN-benzylpiperidines
Alternative Parents
Substituents
  • N-benzylpiperidine
  • Butyrophenone
  • Benzazepine
  • Acetophenone
  • Aryl alkyl ketone
  • Aryl ketone
  • Phenylmethylamine
  • Benzylamine
  • Benzoyl
  • Aralkylamine
  • Secondary aliphatic/aromatic amine
  • Azepine
  • Benzenoid
  • Monocyclic benzene moiety
  • Tertiary aliphatic amine
  • Tertiary amine
  • Ketone
  • Azacycle
  • Secondary amine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Serine hydrolase activity
Specific Function:
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name:
ACHE
Uniprot ID:
P22303
Molecular Weight:
67795.525 Da
References
  1. Hatip-Al-Khatib I, Iwasaki K, Yoshimitsu Y, Arai T, Egashira N, Mishima K, Ikeda T, Fujiwara M: Effect of oral administration of zanapezil (TAK-147) for 21 days on acetylcholine and monoamines levels in the ventral hippocampus of freely moving rats. Br J Pharmacol. 2005 Aug;145(8):1035-44. [PubMed:15951830 ]
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Drug created on October 18, 2007 18:46 / Updated on August 17, 2016 12:24