Identification

Name
Candoxatrilat
Accession Number
DB11623
Type
Small Molecule
Groups
Experimental
Description

A dicarboxylic acid monoamide obtained by formal condensation between the amino group of cis-4-aminocyclohexanecarboxylic acid and the cyclopentanecarboxylic acid group of 1-[(2S)-2-carboxy-3-(2-methoxyethoxy)propyl]cyclopentanecarboxylic acid. A potent inhibitor of neutral endopeptidase (NEP, neprilysin, EC 3.4.24.11), it is used as its 2,3-dihydro-1H-inden-5-yl ester prodrug in the treatment of chronic heart failure.

Structure
Thumb
Synonyms
  • Candoxatrilate
External IDs
UK-73,967 / UK-73967
Categories
UNII
7WU8BZ90TH
CAS number
123122-54-3
Weight
Average: 399.484
Monoisotopic: 399.225702407
Chemical Formula
C20H33NO7
InChI Key
ACZWIDANLCXHBM-HRCADAONSA-N
InChI
InChI=1S/C20H33NO7/c1-27-10-11-28-13-15(18(24)25)12-20(8-2-3-9-20)19(26)21-16-6-4-14(5-7-16)17(22)23/h14-16H,2-13H2,1H3,(H,21,26)(H,22,23)(H,24,25)/t14-,15-,16+/m0/s1
IUPAC Name
(1s,4s)-4-{1-[(2S)-2-carboxy-2-[(2-methoxyethoxy)methyl]ethyl]cyclopentaneamido}cyclohexane-1-carboxylic acid
SMILES
COCCOC[C@H](CC1(CCCC1)C(=O)N[C@H]1CC[C@H](CC1)C(O)=O)C(O)=O

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
ANeprilysin
inhibitor
Human
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
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Candoxatrilat.Approved, Investigational
AlfuzosinThe serum concentration of Alfuzosin can be increased when it is combined with Candoxatrilat.Approved, Investigational
Ambroxol acefyllinateThe serum concentration of Ambroxol acefyllinate can be decreased when it is combined with Candoxatrilat.Experimental, Investigational
AmineptineThe serum concentration of Amineptine can be increased when it is combined with Candoxatrilat.Illicit, Withdrawn
AminophyllineThe serum concentration of Aminophylline can be decreased when it is combined with Candoxatrilat.Approved
AmitriptylineThe serum concentration of Amitriptyline can be increased when it is combined with Candoxatrilat.Approved
AmitriptylinoxideThe serum concentration of Amitriptylinoxide can be increased when it is combined with Candoxatrilat.Approved, Investigational
AmoxapineThe serum concentration of Amoxapine can be increased when it is combined with Candoxatrilat.Approved
BoceprevirThe serum concentration of Candoxatrilat can be decreased when it is combined with Boceprevir.Approved, Withdrawn
ButriptylineThe serum concentration of Butriptyline can be increased when it is combined with Candoxatrilat.Approved
ClarithromycinThe therapeutic efficacy of Clarithromycin can be decreased when used in combination with Candoxatrilat.Approved
ClomipramineThe serum concentration of Clomipramine can be increased when it is combined with Candoxatrilat.Approved, Investigational, Vet Approved
CyclophosphamideThe risk or severity of adverse effects can be increased when Candoxatrilat is combined with Cyclophosphamide.Approved, Investigational
DelavirdineThe serum concentration of Delavirdine can be decreased when it is combined with Candoxatrilat.Approved
DesipramineThe serum concentration of Desipramine can be increased when it is combined with Candoxatrilat.Approved, Investigational
DibenzepinThe serum concentration of Dibenzepin can be increased when it is combined with Candoxatrilat.Experimental
DiethylstilbestrolThe serum concentration of Diethylstilbestrol can be decreased when it is combined with Candoxatrilat.Approved, Investigational
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Candoxatrilat.Approved
DihydroergotamineThe serum concentration of Dihydroergotamine can be increased when it is combined with Candoxatrilat.Approved, Investigational
DimetacrineThe serum concentration of Dimetacrine can be increased when it is combined with Candoxatrilat.Approved, Withdrawn
DosulepinThe serum concentration of Dosulepin can be increased when it is combined with Candoxatrilat.Approved
DyphyllineThe serum concentration of Dyphylline can be decreased when it is combined with Candoxatrilat.Approved
Ergoloid mesylateThe serum concentration of Ergoloid mesylate can be increased when it is combined with Candoxatrilat.Approved
ErgonovineThe serum concentration of Ergonovine can be increased when it is combined with Candoxatrilat.Approved
ErgotamineThe serum concentration of Ergotamine can be increased when it is combined with Candoxatrilat.Approved
Estradiol cypionateThe serum concentration of Estradiol cypionate can be decreased when it is combined with Candoxatrilat.Approved, Investigational, Vet Approved
Estradiol valerateThe serum concentration of Estradiol valerate can be decreased when it is combined with Candoxatrilat.Approved, Investigational, Vet Approved
EtravirineThe serum concentration of Etravirine can be decreased when it is combined with Candoxatrilat.Approved
GarlicThe serum concentration of Candoxatrilat can be decreased when it is combined with Garlic.Approved, Nutraceutical
IprindoleThe serum concentration of Iprindole can be increased when it is combined with Candoxatrilat.Experimental
LofepramineThe serum concentration of Lofepramine can be increased when it is combined with Candoxatrilat.Experimental
MelitracenThe serum concentration of Melitracen can be increased when it is combined with Candoxatrilat.Experimental, Investigational
MestranolThe serum concentration of Mestranol can be decreased when it is combined with Candoxatrilat.Approved
MethylergometrineThe serum concentration of Methylergometrine can be increased when it is combined with Candoxatrilat.Approved
MidazolamThe serum concentration of Midazolam can be increased when it is combined with Candoxatrilat.Approved, Illicit
NefazodoneThe serum concentration of Nefazodone can be increased when it is combined with Candoxatrilat.Approved, Withdrawn
OpipramolThe serum concentration of Opipramol can be increased when it is combined with Candoxatrilat.Investigational
PethidineThe risk or severity of adverse effects can be increased when Candoxatrilat is combined with Pethidine.Approved
ProtriptylineThe serum concentration of Protriptyline can be increased when it is combined with Candoxatrilat.Approved
RiociguatThe serum concentration of Riociguat can be increased when it is combined with Candoxatrilat.Approved
St. John's WortThe metabolism of Candoxatrilat can be increased when combined with St. John's Wort.Approved, Investigational, Nutraceutical
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Candoxatrilat.Approved, Investigational
TemsirolimusThe risk or severity of adverse effects can be increased when Candoxatrilat is combined with Temsirolimus.Approved
TianeptineThe serum concentration of Tianeptine can be increased when it is combined with Candoxatrilat.Approved, Investigational
TipranavirThe serum concentration of Candoxatrilat can be decreased when it is combined with Tipranavir.Approved, Investigational
TriazolamThe serum concentration of Triazolam can be increased when it is combined with Candoxatrilat.Approved, Investigational
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Drug
D03349
KEGG Compound
C11721
PubChem Compound
443380
PubChem Substance
347828015
ChemSpider
16736848
BindingDB
50281657
ChEBI
3354
ChEMBL
CHEMBL434492
Wikipedia
Candoxatril

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 Solubility0.766 mg/mLALOGPS
logP1.47ALOGPS
logP1.87ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)4.08ChemAxon
pKa (Strongest Basic)0.48ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area122.16 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity100.73 m3·mol-1ChemAxon
Polarizability42.2 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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 dicarboxylic acids and derivatives. These are organic compounds containing exactly two carboxylic acid groups.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Dicarboxylic acids and derivatives
Direct Parent
Dicarboxylic acids and derivatives
Alternative Parents
Fatty amides / Secondary carboxylic acid amides / Dialkyl ethers / Carboxylic acids / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Dicarboxylic acid or derivatives / Fatty acyl / Fatty amide / Carboxamide group / Secondary carboxylic acid amide / Carboxylic acid / Dialkyl ether / Ether / Carbonyl group / Organonitrogen compound
Molecular Framework
Aliphatic homomonocyclic compounds
External Descriptors
dicarboxylic acid monoamide, dicarboxylic acid (CHEBI:3354)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:8168535). Biologically important in the destruction of opioid peptide...
Gene Name
MME
Uniprot ID
P08473
Uniprot Name
Neprilysin
Molecular Weight
85513.225 Da
References
  1. Alabaster CT, Machin I, Samuels GM, Sutton MR: The effects of UK-79,300, an orally-absorbed atriopeptidase inhibitor, in a conscious dog model of cardiac insufficiency. Br J Pharmacol. 1989 Dec;98 Suppl:823P. [PubMed:2611529]
  2. Sansoe G, Aragno M, Mastrocola R, Restivo F, Mengozzi G, Smedile A, Rosina F, Danni O, Parola M, Rizzetto M: Neutral endopeptidase (EC 3.4.24.11) in cirrhotic liver: a new target to treat portal hypertension? J Hepatol. 2005 Nov;43(5):791-8. Epub 2005 Jun 20. [PubMed:16085334]

Drug created on October 14, 2016 11:02 / Updated on August 02, 2018 06:27