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Details

Stereochemistry UNKNOWN
Molecular Formula C17H13ClN4
Molecular Weight 308.765
Optical Activity ( - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LIAROZOLE, (-)-

SMILES

ClC1=CC=CC(=C1)C(N2C=CN=C2)C3=CC=C4N=CNC4=C3

InChI

InChIKey=UGFHIPBXIWJXNA-UHFFFAOYSA-N
InChI=1S/C17H13ClN4/c18-14-3-1-2-12(8-14)17(22-7-6-19-11-22)13-4-5-15-16(9-13)21-10-20-15/h1-11,17H,(H,20,21)

HIDE SMILES / InChI

Molecular Formula C17H13ClN4
Molecular Weight 308.765
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Liarozole is an imidazole-containing compound that inhibits the cytochrome P-450-dependent metabolism of all-trans-retinoic acid (RA). Liarozole, a retinoic acid (RA) metabolism-blocking agent (RAMBA) in clinical development, has been granted orphan drug designation for congenital ichthyosis by the European Commission and the U.S. Food and Drug Administration. Later, based on the mixed results from a phase II/III trial of liarozole for the treatment of ichthyosis, Barrier decided to discontinue the development of liarozole. Liarozole displays antitumor activity against androgen-dependent and independent rat prostate carcinomas.A large phase III international study was completed comparing liarozole 300 mg twice daily with cyproterone acetate (CPA) 100 mg twice daily in a total of 321 patients with metastatic prostate cancer in relapse after first-line endocrine therapy. The results indicate that liarozole might be a possible treatment option for prostate cancer (PCA) following failure of first-line endocrine therapy.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.67 mg/L
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIAROZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
23.9 mg × h/L
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LIAROZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
PubMed

PubMed

TitleDatePubMed
Discovery of inhibitors of MCF-7 tumor cell adhesion to endothelial cells and investigation on their mode of action.
2004 Dec
Novel tetralone-derived retinoic acid metabolism blocking agents: synthesis and in vitro evaluation with liver microsomal and MCF-7 CYP26A1 cell assays.
2005 Nov 17
Small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26): synthesis and biological evaluation of imidazole methyl 3-(4-(aryl-2-ylamino)phenyl)propanoates.
2011 Apr 28
Synthesis and biological evaluation of 3-(1H-imidazol- and triazol-1-yl)-2,2-dimethyl-3-[4-(naphthalen-2-ylamino)phenyl]propyl derivatives as small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26).
2011 Oct 13
Patents

Sample Use Guides

Patients aged ≥ 14 years with moderate/severe lamellar ichthyosis [Investigator's Global Assessment (IGA) score ≥ 3] were randomized 3 : 3 : 1 to receive oral liarozole (75 or 150 mg) or placebo once daily for 12 weeks. Compared with placebo, oral liarozole, 75 or 150 mg, once daily for 12 weeks, reduced the overall severity of ichthyosis and scaling, but not erythema or pruritus, and improved DLQI in patients with moderate or severe lamellar ichthyosis.
Route of Administration: Oral
In Vitro Use Guide
In vitro, liarozole (IC50, 2.2 uM) suppressed the P-450-mediated conversion of RA to more polar metabolites by hamster liver microsomes.
Substance Class Chemical
Created
by admin
on Sat Dec 16 11:01:26 GMT 2023
Edited
by admin
on Sat Dec 16 11:01:26 GMT 2023
Record UNII
17NYD2210B
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LIAROZOLE, (-)-
Common Name English
1H-BENZIMIDAZOLE, 5-((3-CHLOROPHENYL)-1H-IMIDAZOL-1-YLMETHYL)-, (-)-
Systematic Name English
Code System Code Type Description
FDA UNII
17NYD2210B
Created by admin on Sat Dec 16 11:01:26 GMT 2023 , Edited by admin on Sat Dec 16 11:01:26 GMT 2023
PRIMARY
CAS
171849-18-6
Created by admin on Sat Dec 16 11:01:26 GMT 2023 , Edited by admin on Sat Dec 16 11:01:26 GMT 2023
PRIMARY
Related Record Type Details
ENANTIOMER -> ENANTIOMER
RACEMATE -> ENANTIOMER