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Identification
Name Tolrestat
Accession Number DB02383 (EXPT03082)
Type small molecule
Groups withdrawn
Description

Tolrestat (INN) (AY-27773) is an aldose reductase inhibitor which was approved for the control of certain diabetic complications. While it was approved for marketed in several countries, it failed a Phase III trial in the U.S. due to toxicity and never received FDA approval. It was discontinued by Wyeth in 1997 because of the risk of severe liver toxicity and death. It was sold under the tradename Alredase. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Alredase Wyeth
Brand mixtures Not Available
Categories
  • Enzyme Inhibitors
CAS number 82964-04-3
Weight Average: 357.347
Monoisotopic: 357.064648624
Chemical Formula C16H14F3NO3S
InChI Key InChIKey=LUBHDINQXIHVLS-UHFFFAOYSA-N
InChI
InChI=1S/C16H14F3NO3S/c1-20(8-13(21)22)15(24)11-5-3-4-10-9(11)6-7-12(23-2)14(10)16(17,18)19/h3-7H,8H2,1-2H3,(H,21,22)
Plain Text
IUPAC Name
2-{1-[6-methoxy-5-(trifluoromethyl)naphthalen-1-yl]-N-methylmethanethioamido}acetic acid
SMILES
COC1=C(C2=CC=CC(C(=S)N(C)CC(O)=O)=C2C=C1)C(F)(F)F
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For the pharmacological control of certain diabetic complications.
Pharmacodynamics Not Available
Mechanism of action Not Available
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 Oral, mouse: LD50 = 300 mg/kg; Oral, rabbit: LD50 = 3200 mg/kg; Oral, rat: LD50 = 980 mg/kg.
Affected organisms
  • Humans and other mammals
Pathways 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
Property Value Source
water solubility 7.60e-03 g/l ALOGPS
logP 3.25 ALOGPS
logP 3.35 ChemAxon
logS -4.7 ALOGPS
pKa (strongest acidic) 3.95 ChemAxon
pKa (strongest basic) -3 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 49.77 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 87.89 ChemAxon
polarizability 32.08 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Sestanj K, Bellini F, Fung S, Abraham N, Treasurywala A, Humber L, Simard-Duquesne N, Dvornik D: N-[5-(trifluoromethyl)-6-methoxy-1-naphthalenyl]thioxomethyl]- N-methylglycine (Tolrestat), a potent, orally active aldose reductase inhibitor. J Med Chem. 1984 Mar;27(3):255-6. Pubmed
  2. Kador PF, Kinoshita JH, Sharpless NE: Aldose reductase inhibitors: a potential new class of agents for the pharmacological control of certain diabetic complications. J Med Chem. 1985 Jul;28(7):841-9. Pubmed
External Links
Resource Link
KEGG Drug D02323 Link_out
KEGG Compound C01621 Link_out
PubChem Compound 53359 Link_out
PubChem Substance 46508274 Link_out
ChemSpider 48194 Link_out
BindingDB 16314 Link_out
ChEBI 48549 Link_out
ChEMBL 48549 Link_out
Therapeutic Targets Database DNC001455 Link_out
HET TOL Link_out
Wikipedia http://en.wikipedia.org/wiki/Tolrestat Link_out
ATC Codes
  • A10XA01
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS show (567 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Aldose reductase

Pharmacological action: unknown
Actions: inhibitor

Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies

Organism class: human
UniProt ID: P15121 Link_out
Gene: AKR1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. 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

2. Alcohol dehydrogenase [NADP+]

Pharmacological action: unknown

Catalyzes the NADPH-dependent reduction of a variety of aromatic and aliphatic aldehydes to their corresponding alcohols. Catalyzes the reduction of mevaldate to mevalonic acid and of glyceraldehyde to glycerol. Has broad substrate specificity. In vitro substrates include succinic semialdehyde, 4- nitrobenzaldehyde, 1,2-naphthoquinone, methylglyoxal, and D- glucuronic acid. Plays a role in the activation of procarcinogens, such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the metabolism of various xenobiotics and drugs, including the anthracyclines doxorubicin (DOX) and daunorubicin (DAUN)

Organism class: human
UniProt ID: P14550 Link_out
Gene: AKR1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

3. Aldo-keto reductase family 1 member B10

Pharmacological action: unknown

Acts as all-trans-retinaldehyde reductase. Can efficiently reduce aliphatic and aromatic aldehydes, and is less active on hexoses (in vitro). May be responsible for detoxification of reactive aldehydes in the digested food before the nutrients are passed on to other organs

Organism class: human
UniProt ID: O60218 Link_out
Gene: AKR1B10 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on March 19, 2013 13:59