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Details

Stereochemistry RACEMIC
Molecular Formula 2C17H13ClN4.3C4H4O4
Molecular Weight 965.746
Optical Activity ( + / - )
Defined Stereocenters 0 / 2
E/Z Centers 3
Charge 0

SHOW SMILES / InChI
Structure of LIAROZOLE FUMARATE

SMILES

OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.ClC1=CC=CC(=C1)C(N2C=CN=C2)C3=CC=C4N=CNC4=C3.ClC5=CC=CC(=C5)C(N6C=CN=C6)C7=CC=C8N=CNC8=C7

InChI

InChIKey=IDTXURCCJVODEQ-VQYXCCSOSA-N
InChI=1S/2C17H13ClN4.3C4H4O4/c2*18-14-3-1-2-12(8-14)17(22-7-6-19-11-22)13-4-5-15-16(9-13)21-10-20-15;3*5-3(6)1-2-4(7)8/h2*1-11,17H,(H,20,21);3*1-2H,(H,5,6)(H,7,8)/b;;3*2-1+

HIDE SMILES / InChI

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

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 Fri Dec 15 15:45:09 GMT 2023
Edited
by admin
on Fri Dec 15 15:45:09 GMT 2023
Record UNII
91W7VLK7J3
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LIAROZOLE FUMARATE
MART.   MI   USAN   WHO-DD  
USAN  
Official Name English
LIAROZOLE FUMARATE [MI]
Common Name English
LIAROZOLE FUMARATE [MART.]
Common Name English
R-85246
Code English
1H-BENZIMIDAZOLE, 5-((3-CHLOROPHENYL)-1H-IMIDAZOL-1-YLMETHYL)-, (±)-, (E)-2-BUTENEDIOATE (2:3)
Common Name English
Liarozole fumarate [WHO-DD]
Common Name English
LIAZAL
Brand Name English
R 85246
Code English
(±)-5-(M-CHLORO-.ALPHA.-IMIDAZOL-1-YLBENZYL)BENZIMIDAZOLE FUMARATE (2:3)
Common Name English
LIAROZOLE FUMARATE [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2018
Created by admin on Fri Dec 15 15:45:09 GMT 2023 , Edited by admin on Fri Dec 15 15:45:09 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C1524
Created by admin on Fri Dec 15 15:45:09 GMT 2023 , Edited by admin on Fri Dec 15 15:45:09 GMT 2023
PRIMARY
EVMPD
SUB130508
Created by admin on Fri Dec 15 15:45:09 GMT 2023 , Edited by admin on Fri Dec 15 15:45:09 GMT 2023
PRIMARY
PUBCHEM
11983193
Created by admin on Fri Dec 15 15:45:09 GMT 2023 , Edited by admin on Fri Dec 15 15:45:09 GMT 2023
PRIMARY
MERCK INDEX
m6798
Created by admin on Fri Dec 15 15:45:09 GMT 2023 , Edited by admin on Fri Dec 15 15:45:09 GMT 2023
PRIMARY Merck Index
SMS_ID
100000156524
Created by admin on Fri Dec 15 15:45:09 GMT 2023 , Edited by admin on Fri Dec 15 15:45:09 GMT 2023
PRIMARY
ChEMBL
CHEMBL389433
Created by admin on Fri Dec 15 15:45:09 GMT 2023 , Edited by admin on Fri Dec 15 15:45:09 GMT 2023
PRIMARY
CAS
145858-52-2
Created by admin on Fri Dec 15 15:45:09 GMT 2023 , Edited by admin on Fri Dec 15 15:45:09 GMT 2023
PRIMARY
USAN
FF-47
Created by admin on Fri Dec 15 15:45:09 GMT 2023 , Edited by admin on Fri Dec 15 15:45:09 GMT 2023
PRIMARY
FDA UNII
91W7VLK7J3
Created by admin on Fri Dec 15 15:45:09 GMT 2023 , Edited by admin on Fri Dec 15 15:45:09 GMT 2023
PRIMARY
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