Details of the Drug

General Information of Drug (ID: DM69OR8)

Drug Name

FR167653

Synonyms

HMPQTEPEMQZWQH-ROUUACIJSA-N; 2-(5-AMINO-6-OXO-2-PHENYL-6H-PYRIMIDIN-1-YL)-N-[2-(5-TERT-BUTYL-1,3,4-OXADIAZOL-2-YL)-1-(METHYLETHYL)-2-HYDROXYETHYL]ACETAMIDE; AC1NR9VL; SCHEMBL15034365; 2-(5-amino-6-oxo-2-phenylpyrimidin-1-yl)-N-[(1S,2S)-1-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1-hydroxy-3-methylbutan-2-yl]acetamide; ONO-6818

Indication

Disease Entry	ICD 11	Status	REF
Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 1	[1]

Drug Type

Small molecular drug

Structure

3D MOL is unavailable

2D MOL

#Ro5 Violations (Lipinski):
1

Molecular Weight

525.5

Topological Polar Surface Area

Not Available

Rotatable Bond Count

4

Hydrogen Bond Donor Count

3

Hydrogen Bond Acceptor Count

10

Chemical Identifiers

Formula: C24H20FN5O6S
IUPAC Name: 1-[7-(4-fluorophenyl)-8-pyridin-4-yl-3,4-dihydro-1H-pyrazolo[5,1-c][1,2,4]triazin-2-yl]-2-phenylethane-1,2-dione;sulfuric acid
Canonical SMILES: C1CN(NC2=C(C(=NN21)C3=CC=C(C=C3)F)C4=CC=NC=C4)C(=O)C(=O)C5=CC=CC=C5.OS(=O)(=O)O
InChI: InChI=1S/C24H18FN5O2.H2O4S/c25-19-8-6-17(7-9-19)21-20(16-10-12-26-13-11-16)23-28-30(15-14-29(23)27-21)24(32)22(31)18-4-2-1-3-5-18;1-5(2,3)4/h1-13,28H,14-15H2;(H2,1,2,3,4)
InChIKey: KCPHXRBKBLJJJJ-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 135484078
CAS Number: 158876-66-5
TTD ID: D05QMG

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Neutrophil elastase (NE)	TTPLTSQ	ELNE_HUMAN	Inhibitor	[2]
Stress-activated protein kinase 2a (p38 alpha)	TTQBR95	MK14_HUMAN	Inhibitor	[3], [4]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Chronic obstructive pulmonary disease

ICD Disease Classification

CA22

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Neutrophil elastase (NE)	DTT	ELANE	2.35E-01	-0.55	-0.82

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012873)
2	Neutrophil elastase inhibitors as treatment for COPD. Expert Opin Investig Drugs. 2002 Jul;11(7):965-80.
3	Prevention of the onset and progression of collagen-induced arthritis in rats by the potent p38 mitogen-activated protein kinase inhibitor FR167653. Arthritis Rheum. 2003 Sep;48(9):2670-81.
4	Involvement of p38 mitogen-activated protein kinase followed by chemokine expression in crescentic glomerulonephritis. Am J Kidney Dis. 2001 Dec;38(6):1169-77.
5	Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome. Expert Opin Emerg Drugs. 2007 Sep;12(3):461-77.
6	Evaluation of human neutrophil elastase inhibitory effect of iridoid glycosides from Hedyotis diffusa. Bioorg Med Chem Lett. 2010 Jan 15;20(2):513-5.
7	Neutrophil elastase inhibitor (sivelestat) reduces the levels of inflammatory mediators by inhibiting NF-kB. Inflamm Res. 2009 Apr;58(4):198-203.
8	Company report (Proteo Biotech AG)
9	Clinical pipeline report, company report or official report of AstraZeneca (2009).
10	Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY 5-8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases. ChemMedChem. 2015 Jul;10(7):1163-73.
11	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2358).
12	Lipid Peroxide-Mediated Oxidative Rearrangement of the Pyrazinone Carboxamide Core of Neutrophil Elastase Inhibitor AZD9819 in Blood Plasma Samples. Drug Metab Dispos. 2015 Oct;43(10):1441-9.
13	Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
14	Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum. 2009 May;60(5):1232-41.
15	Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
16	c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.