Identification

Name
Freselestat
Accession Number
DB03925  (EXPT00279)
Type
Small Molecule
Groups
Experimental, Investigational
Description
Not Available
Structure
Thumb
Synonyms
  • CP-955
Categories
Not Available
UNII
1CW4RL23VP
CAS number
208848-19-5
Weight
Average: 454.5221
Monoisotopic: 454.232853478
Chemical Formula
C23H30N6O4
InChI Key
HMPQTEPEMQZWQH-QZTJIDSGSA-N
InChI
InChI=1S/C23H30N6O4/c1-13(2)17(18(31)20-27-28-22(33-20)23(3,4)5)26-16(30)12-29-19(14-9-7-6-8-10-14)25-11-15(24)21(29)32/h6-11,13,17-18,31H,12,24H2,1-5H3,(H,26,30)/t17-,18-/m1/s1
IUPAC Name
2-(5-amino-6-oxo-2-phenyl-1,6-dihydropyrimidin-1-yl)-N-[(1R,2R)-1-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1-hydroxy-3-methylbutan-2-yl]acetamide
SMILES
CC(C)[[email protected]@H](NC(=O)CN1C(=O)C(N)=CN=C1C1=CC=CC=C1)[[email protected]@H](O)C1=NN=C(O1)C(C)(C)C

Pharmacology

Indication

Investigated for use/treatment in chronic obstructive pulmonary disease (COPD).

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

ONO-6818 inhibits neutrophil elastase activity, reducing interleukin 8 production and the formation of the complement membrane attack complex. Consequently, neutrophil elastase levels are reduced during stimulated extracorporeal circulation.

TargetActionsOrganism
UChymotrypsin-like elastase family member 1Not AvailableHuman
UNeutrophil elastase
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
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
46936829
PubChem Substance
46504912
Therapeutic Targets Database
DNC001061
HET
681

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 Solubility0.113 mg/mLALOGPS
logP1.85ALOGPS
logP1.11ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)12.1ChemAxon
pKa (Strongest Basic)0.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area146.94 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity123.81 m3·mol-1ChemAxon
Polarizability46.75 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9667
Blood Brain Barrier-0.87
Caco-2 permeable-0.6803
P-glycoprotein substrateSubstrate0.7141
P-glycoprotein inhibitor INon-inhibitor0.7395
P-glycoprotein inhibitor IINon-inhibitor0.788
Renal organic cation transporterNon-inhibitor0.9327
CYP450 2C9 substrateNon-substrate0.8244
CYP450 2D6 substrateNon-substrate0.8013
CYP450 3A4 substrateSubstrate0.6945
CYP450 1A2 substrateNon-inhibitor0.9565
CYP450 2C9 inhibitorNon-inhibitor0.7322
CYP450 2D6 inhibitorNon-inhibitor0.8971
CYP450 2C19 inhibitorNon-inhibitor0.8291
CYP450 3A4 inhibitorNon-inhibitor0.7307
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7939
Ames testNon AMES toxic0.6958
CarcinogenicityNon-carcinogens0.6939
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.3581 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9946
hERG inhibition (predictor II)Non-inhibitor0.7677
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 pyrimidones. These are compounds that contain a pyrimidine ring, which bears a ketone. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrimidines and pyrimidine derivatives
Direct Parent
Pyrimidones
Alternative Parents
Aminopyrimidines and derivatives / Hydropyrimidines / Benzene and substituted derivatives / 1,3,4-oxadiazoles / Heteroaromatic compounds / Secondary carboxylic acid amides / Secondary alcohols / Amino acids and derivatives / Lactams / Oxacyclic compounds
show 7 more
Substituents
Aminopyrimidine / Pyrimidone / Monocyclic benzene moiety / Hydropyrimidine / Benzenoid / 1,3,4-oxadiazole / Azole / Oxadiazole / Heteroaromatic compound / Amino acid or derivatives
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serine-type endopeptidase activity
Specific Function
Acts upon elastin.
Gene Name
CELA1
Uniprot ID
Q9UNI1
Uniprot Name
Chymotrypsin-like elastase family member 1
Molecular Weight
27797.995 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine-type endopeptidase activity
Specific Function
Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.
Gene Name
ELANE
Uniprot ID
P08246
Uniprot Name
Neutrophil elastase
Molecular Weight
28517.81 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. Yoshimura Y, Hiramatsu Y, Sato Y, Homma S, Enomoto Y, Jikuya T, Sakakibara Y: ONO-6818, a novel, potent neutrophil elastase inhibitor, reduces inflammatory mediators during simulated extracorporeal circulation. Ann Thorac Surg. 2003 Oct;76(4):1234-9. [PubMed:14530017]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 15:20