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Identification
NameAS-3201
Accession NumberDB05327
TypeSmall Molecule
GroupsInvestigational
Description

AS-3201 is a structurally novel and stereospecifically potent aldose reductase (AKR1B; EC 1.1.1.21) inhibitor, which contains a succinimide ring that undergoes ring-opening at physiological pH levels.

Structure
Thumb
SynonymsNot Available
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
UNIINot Available
CAS numberNot Available
WeightAverage: 420.189
Monoisotopic: 418.991696707
Chemical FormulaC17H11BrFN3O4
InChI KeyInChIKey=QCVNMNYRNIMDKV-QGZVFWFLSA-N
InChI
InChI=1S/C17H11BrFN3O4/c18-10-4-3-9(11(19)6-10)8-21-14(24)12-2-1-5-22(12)17(16(21)26)7-13(23)20-15(17)25/h1-6H,7-8H2,(H,20,23,25)/t17-/m1/s1
IUPAC Name
(3R)-2'-[(4-bromo-2-fluorophenyl)methyl]-2',3'-dihydro-1'H-spiro[pyrrolidine-3,4'-pyrrolo[1,2-a]pyrazine]-1',2,3',5-tetrone
SMILES
FC1=C(CN2C(=O)C3=CC=CN3[C@@]3(CC(=O)NC3=O)C2=O)C=CC(Br)=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylmethylamines. These are compounds containing a phenylmethtylamine moiety, which consists of a phenyl group substituted by an methanamine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylmethylamines
Direct ParentPhenylmethylamines
Alternative Parents
Substituents
  • Phenylmethylamine
  • Benzylamine
  • Halobenzene
  • Fluorobenzene
  • Dicarboximide
  • Bromobenzene
  • 2-pyrrolidone
  • Pyrrolidone
  • Aryl halide
  • Aryl fluoride
  • Aryl bromide
  • Heteroaromatic compound
  • Pyrrolidine
  • Pyrrole
  • Carboxylic acid imide, n-unsubstituted
  • Carboxylic acid imide
  • Tertiary amine
  • Lactam
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organobromide
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationInvestigated for use/treatment in neuropathy (diabetic).
PharmacodynamicsNot Available
Mechanism of actionAS-3201 alleviates diabetic neuropathy, a complication of diabetes, by inhibiting aldose reductase and thereby inhibiting the accumulation of intracellular sorbitol that causes diabetic neuropathy. This drug has a stronger inhibitory effect and is longer acting compared to other drugs in this therapeutic area. AS-3201 showed good penetration into the nerve tissue, resulting in dose-dependent inhibition of intraneural accumulation of sorbitol and fructose in a clinical study.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9933
Blood Brain Barrier+0.8041
Caco-2 permeable-0.5688
P-glycoprotein substrateSubstrate0.5408
P-glycoprotein inhibitor IInhibitor0.5266
P-glycoprotein inhibitor IINon-inhibitor0.8159
Renal organic cation transporterNon-inhibitor0.6945
CYP450 2C9 substrateNon-substrate0.8841
CYP450 2D6 substrateNon-substrate0.7981
CYP450 3A4 substrateSubstrate0.5985
CYP450 1A2 substrateNon-inhibitor0.6987
CYP450 2C9 inhibitorNon-inhibitor0.6249
CYP450 2D6 inhibitorNon-inhibitor0.8934
CYP450 2C19 inhibitorNon-inhibitor0.5843
CYP450 3A4 inhibitorNon-inhibitor0.629
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.744
Ames testNon AMES toxic0.7064
CarcinogenicityNon-carcinogens0.8581
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4876 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9859
hERG inhibition (predictor II)Non-inhibitor0.7574
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0295 mg/mLALOGPS
logP2.3ALOGPS
logP1.79ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)8.52ChemAxon
pKa (Strongest Basic)-6.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area88.48 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity90.5 m3·mol-1ChemAxon
Polarizability35.02 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Bril V, Buchanan RA: Long-term effects of ranirestat (AS-3201) on peripheral nerve function in patients with diabetic sensorimotor polyneuropathy. Diabetes Care. 2006 Jan;29(1):68-72. [PubMed:16373898 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Glyceraldehyde oxidoreductase activity
Specific Function:
Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
Gene Name:
AKR1B1
Uniprot ID:
P15121
Molecular Weight:
35853.125 Da
Comments
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Drug created on November 18, 2007 11:23 / Updated on September 16, 2013 17:26