Daglutril

Identification

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Name
Daglutril
Accession Number
DB05796  (DB12995)
Type
Small Molecule
Groups
Investigational
Description

Daglutril is an orally active, mixed neutral endopeptidase/endothelin converting enzyme inhibitor under development for the treatment of essential hypertension and congestive heart failure.

Structure
Thumb
Synonyms
  • ((3S)-3-{1-((2R)-2-Ethoxycarbonyl-4-phenylbutyl)cyclopentanecarboxamido}-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)acetic acid
External IDs
SLV 306 / SLV-306 / SLV306
Categories
UNII
KKV299446X
CAS number
182821-27-8
Weight
Average: 534.6432
Monoisotopic: 534.272986958
Chemical Formula
C31H38N2O6
InChI Key
XMQODGUTLZXUGZ-RPBOFIJWSA-N
InChI
InChI=1S/C31H38N2O6/c1-2-39-29(37)24(15-14-22-10-4-3-5-11-22)20-31(18-8-9-19-31)30(38)32-25-17-16-23-12-6-7-13-26(23)33(28(25)36)21-27(34)35/h3-7,10-13,24-25H,2,8-9,14-21H2,1H3,(H,32,38)(H,34,35)/t24-,25+/m1/s1
IUPAC Name
2-[(3S)-3-{1-[(2R)-3-ethoxy-3-oxo-2-(2-phenylethyl)propyl]cyclopentaneamido}-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl]acetic acid
SMILES
CCOC(=O)[C@H](CCC1=CC=CC=C1)CC1(CCCC1)C(=O)N[C@H]1CCC2=CC=CC=C2N(CC(O)=O)C1=O

Pharmacology

Indication

Investigated for use/treatment in congestive heart failure and hypertension.

Pharmacodynamics
Not Available
Mechanism of action

SLV306 increased plasma natriuretic peptides and big endothelin-1 levels in a dose-dependent manner, confirming neutral endopeptidase and endothelin-converting enzyme inhibition. The combined inhibition of neutral endopeptidase and endothelin-converting enzyme may be useful in heart failure by reducing right and left cardiac filling pressures

TargetActionsOrganism
UNeprilysinNot AvailableHumans
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
Not Available
Food Interactions
Not Available

References

General References
  1. Tabrizchi R: SLV-306. Solvay. Curr Opin Investig Drugs. 2003 Mar;4(3):329-32. [PubMed:12735234]
  2. Dickstein K, De Voogd HJ, Miric MP, Willenbrock R, Mitrovic V, Pacher R, Koopman PA: Effect of single doses of SLV306, an inhibitor of both neutral endopeptidase and endothelin-converting enzyme, on pulmonary pressures in congestive heart failure. Am J Cardiol. 2004 Jul 15;94(2):237-9. [PubMed:15246912]
External Links
PubChem Compound
3038505
PubChem Substance
175427034
ChemSpider
2302069

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentHigh Blood Pressure (Hypertension)2

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 Solubility0.0015 mg/mLALOGPS
logP4.02ALOGPS
logP5.01ChemAxon
logS-5.6ALOGPS
pKa (Strongest Acidic)3.88ChemAxon
pKa (Strongest Basic)0.36ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area113.01 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity145.94 m3·mol-1ChemAxon
Polarizability57.79 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6453
Blood Brain Barrier-0.5088
Caco-2 permeable-0.717
P-glycoprotein substrateSubstrate0.8924
P-glycoprotein inhibitor IInhibitor0.7708
P-glycoprotein inhibitor IINon-inhibitor0.8609
Renal organic cation transporterNon-inhibitor0.8335
CYP450 2C9 substrateNon-substrate0.7613
CYP450 2D6 substrateNon-substrate0.8342
CYP450 3A4 substrateSubstrate0.6213
CYP450 1A2 substrateNon-inhibitor0.8909
CYP450 2C9 inhibitorNon-inhibitor0.5797
CYP450 2D6 inhibitorNon-inhibitor0.835
CYP450 2C19 inhibitorInhibitor0.5315
CYP450 3A4 inhibitorInhibitor0.525
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5778
Ames testNon AMES toxic0.8331
CarcinogenicityNon-carcinogens0.9322
BiodegradationNot ready biodegradable0.9963
Rat acute toxicity2.4160 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9892
hERG inhibition (predictor II)Inhibitor0.7382
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 dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Dipeptides
Alternative Parents
N-acyl-alpha amino acids and derivatives / Benzazepines / Azepines / Fatty acid esters / Benzene and substituted derivatives / Fatty amides / Dicarboxylic acids and derivatives / Tertiary carboxylic acid amides / Secondary carboxylic acid amides / Lactams
show 8 more
Substituents
Alpha-dipeptide / N-acyl-alpha amino acid or derivatives / Benzazepine / Alpha-amino acid or derivatives / Azepine / Fatty acid ester / Monocyclic benzene moiety / Fatty acyl / Dicarboxylic acid or derivatives / Benzenoid
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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

Drug created on November 18, 2007 11:27 / Updated on June 04, 2019 06:19