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Details

Stereochemistry ACHIRAL
Molecular Formula C25H22F3N5O4S
Molecular Weight 545.533
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ALVELESTAT

SMILES

CN1N=CC=C1C2=C(C)N(C(=O)C(=C2)C(=O)NCC3=NC=C(C=C3)S(C)(=O)=O)C4=CC(=CC=C4)C(F)(F)F

InChI

InChIKey=QNQZWEGMKJBHEM-UHFFFAOYSA-N
InChI=1S/C25H22F3N5O4S/c1-15-20(22-9-10-31-32(22)2)12-21(23(34)30-13-17-7-8-19(14-29-17)38(3,36)37)24(35)33(15)18-6-4-5-16(11-18)25(26,27)28/h4-12,14H,13H2,1-3H3,(H,30,34)

HIDE SMILES / InChI

Molecular Formula C25H22F3N5O4S
Molecular Weight 545.533
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22267768 | https://www.ncbi.nlm.nih.gov/pubmed/23391369 | https://clinicaltrials.gov/ct2/show/NCT02597101?term=AZD-9668&phase=1&rank=8

Avelestat, also known as AZD9668, is a novel, oral inhibitor of neutrophil elastase (NE), an enzyme implicated in the signs, symptoms, and disease progression in NE-driven respiratory diseases such as bronchiectasis, Cystic Fibrosis and chronic obstructive pulmonary disease via its role in the inflammatory process, mucus overproduction, and lung tissue damage. Its development was discontinued due to unknown reasons. Nevertheless, this drug in the phase II of clinical trial as adjunctive therapy in improving insulin sensitivity of insulin-resistant type 2 diabetic subjects. The drug's clinical profile suggests that it will be well tolerated with few, if any, side effects, and the existence of simple methods that can indirectly measure its activity in vivo.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
12.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Palliative
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
621.7 nM
60 mg 2 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ALVELESTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
60 mg 2 times / day steady-state, oral
Studied dose
Dose: 60 mg, 2 times / day
Route: oral
Route: steady-state
Dose: 60 mg, 2 times / day
Sources: Page: p.117
unhealthy, ADULT
n = 202
Health Status: unhealthy
Condition: COPD
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 202
Sources: Page: p.117
Sourcing

Sourcing

PubMed

PubMed

TitleDatePubMed
AZD9668: pharmacological characterization of a novel oral inhibitor of neutrophil elastase.
2011 Oct
Discontinued drugs 2011: pulmonary, allergy, gastrointestinal and arthritis.
2012 Nov
Patents

Sample Use Guides

2 x 30 mg oral tablets twice daily (bid) for 12 weeks
Route of Administration: Oral
In cell-based assays, AZD9668 inhibited plasma Neutrophil elastase (NE) activity in zymosan-stimulated whole blood. In isolated human polymorphonuclear cells, AZD9668 inhibited NE activity on the surface of stimulated cells and in the supernatant of primed, stimulated cells. AZD9668 showed good crossover potency to NE from other species.
Substance Class Chemical
Created
by admin
on Thu Jul 06 02:23:47 UTC 2023
Edited
by admin
on Thu Jul 06 02:23:47 UTC 2023
Record UNII
6Y5629322X
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ALVELESTAT
INN  
INN  
Official Name English
N-((5-(METHANESULFONYL)PYRIDIN-2-YL)METHYL)-6-METHYL-5-(1-METHYL-1H-PYRAZOL-5-YL)-2-OXO-1-(3-(TRIFLUOROMETHYL)PHENYL)-1,2-DIHYDROPYRIDINE-3-CARBOXAMIDE
Systematic Name English
AZD-9668
Code English
Alvelestat [WHO-DD]
Common Name English
3-PYRIDINECARBOXAMIDE, 1,2-DIHYDRO-6-METHYL-5-(1-METHYL-1H-PYRAZOL-5-YL)-N-((5-(METHYLSULFONYL)-2-PYRIDINYL)METHYL)-2-OXO-1-(3-(TRIFLUOROMETHYL)PHENYL)-
Systematic Name English
AZD9668
Code English
alvelestat [INN]
Common Name English
MPH-966
Code English
MPH966
Code English
6-METHYL-5-(1-METHYL-1H-PYRAZOL-5-YL)-N-((5-(METHYLSULFONYL)PYRIDIN-2-YL)METHYL)-2-OXO-1-(3-(TRIFLUOROMETHYL)PHENYL)-1,2-DIHYDROPYRIDINE-3-CARBOXAMIDE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C783
Created by admin on Thu Jul 06 02:23:47 UTC 2023 , Edited by admin on Thu Jul 06 02:23:47 UTC 2023
FDA ORPHAN DRUG 804020
Created by admin on Thu Jul 06 02:23:47 UTC 2023 , Edited by admin on Thu Jul 06 02:23:47 UTC 2023
Code System Code Type Description
CAS
848141-11-7
Created by admin on Thu Jul 06 02:23:47 UTC 2023 , Edited by admin on Thu Jul 06 02:23:47 UTC 2023
PRIMARY
NCI_THESAURUS
C125714
Created by admin on Thu Jul 06 02:23:47 UTC 2023 , Edited by admin on Thu Jul 06 02:23:47 UTC 2023
PRIMARY
FDA UNII
6Y5629322X
Created by admin on Thu Jul 06 02:23:47 UTC 2023 , Edited by admin on Thu Jul 06 02:23:47 UTC 2023
PRIMARY
SMS_ID
100000156677
Created by admin on Thu Jul 06 02:23:47 UTC 2023 , Edited by admin on Thu Jul 06 02:23:47 UTC 2023
PRIMARY
DRUG BANK
DB11863
Created by admin on Thu Jul 06 02:23:47 UTC 2023 , Edited by admin on Thu Jul 06 02:23:47 UTC 2023
PRIMARY
EPA CompTox
DTXSID40233875
Created by admin on Thu Jul 06 02:23:47 UTC 2023 , Edited by admin on Thu Jul 06 02:23:47 UTC 2023
PRIMARY
MESH
C568080
Created by admin on Thu Jul 06 02:23:47 UTC 2023 , Edited by admin on Thu Jul 06 02:23:47 UTC 2023
PRIMARY
PUBCHEM
46861623
Created by admin on Thu Jul 06 02:23:47 UTC 2023 , Edited by admin on Thu Jul 06 02:23:47 UTC 2023
PRIMARY
INN
9391
Created by admin on Thu Jul 06 02:23:47 UTC 2023 , Edited by admin on Thu Jul 06 02:23:47 UTC 2023
PRIMARY
EVMPD
SUB130609
Created by admin on Thu Jul 06 02:23:47 UTC 2023 , Edited by admin on Thu Jul 06 02:23:47 UTC 2023
PRIMARY
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