Zanapezil

Identification

Name
Zanapezil
Accession Number
DB04859
Type
Small Molecule
Groups
Investigational
Description

Zanapezil (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 IDs
TAK-147
Categories
Not Available
UNII
0A0800O89N
CAS number
142852-50-4
Weight
Average: 376.5344
Monoisotopic: 376.251463656
Chemical Formula
C25H32N2O
InChI Key
PMBLXLOXUGVTGB-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

Indication

For the treatment of dementia in subjects with Alzheimer’s disease.

Structured Indications
Not Available
Pharmacodynamics

Zanapezil 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 action

Zanapezil 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.

TargetActionsOrganism
UAcetylcholinesteraseNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

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
PubChem Compound
198752
PubChem Substance
175426869
ChemSpider
172025
BindingDB
50037157
ChEMBL
CHEMBL75013

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not 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
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Piperidines
Sub Class
Benzylpiperidines
Direct Parent
N-benzylpiperidines
Alternative Parents
Butyrophenones / Benzazepines / Phenylmethylamines / Benzylamines / Aryl alkyl ketones / Secondary alkylarylamines / Azepines / Aralkylamines / Trialkylamines / Azacyclic compounds
show 3 more
Substituents
N-benzylpiperidine / Benzazepine / Butyrophenone / Benzylamine / Phenylmethylamine / Aryl ketone / Aryl alkyl ketone / Azepine / Secondary aliphatic/aromatic amine / Aralkylamine
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Details
1. Acetylcholinesterase
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
Uniprot Name
Acetylcholinesterase
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]

Drug created on October 18, 2007 18:46 / Updated on December 01, 2017 15:33