Identification

Name
Enalkiren
Accession Number
DB03395  (EXPT03298)
Type
Small Molecule
Groups
Experimental
Description
Not Available
Structure
Thumb
Synonyms
Not Available
External IDs
A-64662 / ABBOTT-64662
International/Other Brands
ENALKIREN
Categories
UNII
0U7YZ42Z47
CAS number
113082-98-7
Weight
Average: 656.8557
Monoisotopic: 656.426133554
Chemical Formula
C35H56N6O6
InChI Key
KQXVERRYBYGQJZ-WRPDIKACSA-N
InChI
InChI=1S/C35H56N6O6/c1-22(2)15-30(42)32(44)27(16-23-9-7-6-8-10-23)40-34(46)29(18-25-20-37-21-38-25)41-33(45)28(39-31(43)19-35(3,4)36)17-24-11-13-26(47-5)14-12-24/h11-14,20-23,27-30,32,42,44H,6-10,15-19,36H2,1-5H3,(H,37,38)(H,39,43)(H,40,46)(H,41,45)/t27-,28-,29-,30-,32+/m0/s1
IUPAC Name
3-amino-N-[(1S)-1-{[(1S)-1-{[(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl]carbamoyl}-2-(1H-imidazol-5-yl)ethyl]carbamoyl}-2-(4-methoxyphenyl)ethyl]-3-methylbutanamide
SMILES
COC1=CC=C(C[C@H](NC(=O)CC(C)(C)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)N[C@@H](CC2CCCCC2)[C@@H](O)[C@@H](O)CC(C)C)C=C1

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
URenin
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 Enalkiren.Approved, Investigational
AlfuzosinThe serum concentration of Alfuzosin can be increased when it is combined with Enalkiren.Approved, Investigational
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Enalkiren.Approved, Illicit, Investigational
Ambroxol acefyllinateThe serum concentration of Ambroxol acefyllinate can be decreased when it is combined with Enalkiren.Experimental, Investigational
AmineptineThe serum concentration of Amineptine can be increased when it is combined with Enalkiren.Illicit, Withdrawn
AminophyllineThe serum concentration of Aminophylline can be decreased when it is combined with Enalkiren.Approved
AmitriptylineThe serum concentration of Amitriptyline can be increased when it is combined with Enalkiren.Approved
AmitriptylinoxideThe serum concentration of Amitriptylinoxide can be increased when it is combined with Enalkiren.Approved, Investigational
AmoxapineThe serum concentration of Amoxapine can be increased when it is combined with Enalkiren.Approved
BoceprevirThe serum concentration of Enalkiren can be decreased when it is combined with Boceprevir.Approved, Withdrawn
BromocriptineThe serum concentration of Bromocriptine can be increased when it is combined with Enalkiren.Approved, Investigational
ButriptylineThe serum concentration of Butriptyline can be increased when it is combined with Enalkiren.Approved
CabergolineThe serum concentration of Cabergoline can be increased when it is combined with Enalkiren.Approved
CarbamazepineThe metabolism of Enalkiren can be increased when combined with Carbamazepine.Approved, Investigational
ClarithromycinThe therapeutic efficacy of Clarithromycin can be decreased when used in combination with Enalkiren.Approved
ClomipramineThe serum concentration of Clomipramine can be increased when it is combined with Enalkiren.Approved, Investigational, Vet Approved
CyclophosphamideThe risk or severity of adverse effects can be increased when Enalkiren is combined with Cyclophosphamide.Approved, Investigational
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Enalkiren.Approved, Investigational, Vet Approved
DelavirdineThe serum concentration of Delavirdine can be decreased when it is combined with Enalkiren.Approved
DesipramineThe serum concentration of Desipramine can be increased when it is combined with Enalkiren.Approved, Investigational
DibenzepinThe serum concentration of Dibenzepin can be increased when it is combined with Enalkiren.Experimental
DiethylstilbestrolThe serum concentration of Diethylstilbestrol can be decreased when it is combined with Enalkiren.Approved, Investigational
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Enalkiren.Approved
DihydroergotamineThe serum concentration of Dihydroergotamine can be increased when it is combined with Enalkiren.Approved, Investigational
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Enalkiren.Approved, Investigational
DimetacrineThe serum concentration of Dimetacrine can be increased when it is combined with Enalkiren.Approved, Withdrawn
DosulepinThe serum concentration of Dosulepin can be increased when it is combined with Enalkiren.Approved
DoxepinThe serum concentration of Doxepin can be increased when it is combined with Enalkiren.Approved, Investigational
DyphyllineThe serum concentration of Dyphylline can be decreased when it is combined with Enalkiren.Approved
EnfuvirtideThe serum concentration of Enfuvirtide can be increased when it is combined with Enalkiren.Approved, Investigational
Ergoloid mesylateThe serum concentration of Ergoloid mesylate can be increased when it is combined with Enalkiren.Approved
ErgonovineThe serum concentration of Ergonovine can be increased when it is combined with Enalkiren.Approved
ErgotamineThe serum concentration of Ergotamine can be increased when it is combined with Enalkiren.Approved
EstradiolThe serum concentration of Estradiol can be decreased when it is combined with Enalkiren.Approved, Investigational, Vet Approved
Estradiol cypionateThe serum concentration of Estradiol cypionate can be decreased when it is combined with Enalkiren.Approved, Investigational, Vet Approved
Estradiol valerateThe serum concentration of Estradiol valerate can be decreased when it is combined with Enalkiren.Approved, Investigational, Vet Approved
Ethinyl EstradiolThe serum concentration of Ethinyl Estradiol can be decreased when it is combined with Enalkiren.Approved
EtravirineThe serum concentration of Etravirine can be decreased when it is combined with Enalkiren.Approved
GarlicThe serum concentration of Enalkiren can be decreased when it is combined with Garlic.Approved, Nutraceutical
ImipramineThe serum concentration of Imipramine can be increased when it is combined with Enalkiren.Approved
IprindoleThe serum concentration of Iprindole can be increased when it is combined with Enalkiren.Experimental
LofepramineThe serum concentration of Lofepramine can be increased when it is combined with Enalkiren.Experimental
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Enalkiren.Approved, Investigational
MelitracenThe serum concentration of Melitracen can be increased when it is combined with Enalkiren.Experimental, Investigational
MestranolThe serum concentration of Mestranol can be decreased when it is combined with Enalkiren.Approved
MethylergometrineThe serum concentration of Methylergometrine can be increased when it is combined with Enalkiren.Approved
MidazolamThe serum concentration of Midazolam can be increased when it is combined with Enalkiren.Approved, Illicit
NefazodoneThe serum concentration of Nefazodone can be increased when it is combined with Enalkiren.Approved, Withdrawn
NortriptylineThe serum concentration of Nortriptyline can be increased when it is combined with Enalkiren.Approved
OpipramolThe serum concentration of Opipramol can be increased when it is combined with Enalkiren.Investigational
PethidineThe risk or severity of adverse effects can be increased when Enalkiren is combined with Pethidine.Approved
ProtriptylineThe serum concentration of Protriptyline can be increased when it is combined with Enalkiren.Approved
RiociguatThe serum concentration of Riociguat can be increased when it is combined with Enalkiren.Approved
SildenafilThe serum concentration of Sildenafil can be increased when it is combined with Enalkiren.Approved, Investigational
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Enalkiren.Approved
St. John's WortThe metabolism of Enalkiren can be increased when combined with St. John's Wort.Approved, Investigational, Nutraceutical
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Enalkiren.Approved, Investigational
TemsirolimusThe risk or severity of adverse effects can be increased when Enalkiren is combined with Temsirolimus.Approved
TheophyllineThe serum concentration of Theophylline can be decreased when it is combined with Enalkiren.Approved
TianeptineThe serum concentration of Tianeptine can be increased when it is combined with Enalkiren.Approved, Investigational
TipranavirThe serum concentration of Enalkiren can be decreased when it is combined with Tipranavir.Approved, Investigational
TriazolamThe serum concentration of Triazolam can be increased when it is combined with Enalkiren.Approved, Investigational
TrimipramineThe serum concentration of Trimipramine can be increased when it is combined with Enalkiren.Approved
Valproic AcidThe serum concentration of Valproic Acid can be decreased when it is combined with Enalkiren.Approved, Investigational
VerapamilThe metabolism of Verapamil can be decreased when combined with Enalkiren.Approved
ZidovudineThe serum concentration of Zidovudine can be decreased when it is combined with Enalkiren.Approved
Food Interactions
Not Available

References

General References
  1. Glassman HN, Kleinert HD, Boger RS, Moyse DM, Griffiths AN, Luther RR: Clinical pharmacology of enalkiren, a novel, dipeptide renin inhibitor. J Cardiovasc Pharmacol. 1990;16 Suppl 4:S76-81. [PubMed:1705633]
External Links
KEGG Drug
D03738
KEGG Compound
C07466
PubChem Compound
60594
PubChem Substance
46505948
ChemSpider
54622
BindingDB
50006202
ChEBI
4787
ChEMBL
CHEMBL300337
Therapeutic Targets Database
DNC000604

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 Solubility0.0122 mg/mLALOGPS
logP2.47ALOGPS
logP1.75ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)12.03ChemAxon
pKa (Strongest Basic)9.58ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area191.69 Å2ChemAxon
Rotatable Bond Count18ChemAxon
Refractivity180.16 m3·mol-1ChemAxon
Polarizability72.65 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6463
Blood Brain Barrier-0.9672
Caco-2 permeable-0.7867
P-glycoprotein substrateSubstrate0.8135
P-glycoprotein inhibitor INon-inhibitor0.7852
P-glycoprotein inhibitor IINon-inhibitor0.7862
Renal organic cation transporterNon-inhibitor0.8892
CYP450 2C9 substrateNon-substrate0.7924
CYP450 2D6 substrateNon-substrate0.7498
CYP450 3A4 substrateSubstrate0.6589
CYP450 1A2 substrateNon-inhibitor0.866
CYP450 2C9 inhibitorNon-inhibitor0.7568
CYP450 2D6 inhibitorNon-inhibitor0.8521
CYP450 2C19 inhibitorNon-inhibitor0.6809
CYP450 3A4 inhibitorNon-inhibitor0.5122
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6567
Ames testNon AMES toxic0.7827
CarcinogenicityNon-carcinogens0.9252
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6931 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9939
hERG inhibition (predictor II)Non-inhibitor0.6604
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 hybrid peptides. These are compounds containing at least two different types of amino acids (alpha, beta, gamma, delta) linked to each other through a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Peptidomimetics
Sub Class
Hybrid peptides
Direct Parent
Hybrid peptides
Alternative Parents
Dipeptides / Phenylalanine and derivatives / Histidine and derivatives / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Beta amino acids and derivatives / Amphetamines and derivatives / Phenoxy compounds / Methoxybenzenes / Anisoles
show 13 more
Substituents
Hybrid peptide / Alpha-dipeptide / Phenylalanine or derivatives / Histidine or derivatives / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / Beta amino acid or derivatives / N-substituted-alpha-amino acid / Alpha-amino acid or derivatives / Amphetamine or derivatives
show 35 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
peptide (CHEBI:4787)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor binding
Specific Function
Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of b...
Gene Name
REN
Uniprot ID
P00797
Uniprot Name
Renin
Molecular Weight
45057.125 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Glassman HN, Kleinert HD, Boger RS, Moyse DM, Griffiths AN, Luther RR: Clinical pharmacology of enalkiren, a novel, dipeptide renin inhibitor. J Cardiovasc Pharmacol. 1990;16 Suppl 4:S76-81. [PubMed:1705633]

Drug created on June 13, 2005 07:24 / Updated on June 02, 2018 07:16