Ranirestat

Identification

Name
Ranirestat
Accession Number
DB05327  (DB12811)
Type
Small Molecule
Groups
Investigational
Description

Ranirestat 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. It has been used in trials studying the treatment of Mild to Moderate Diabetic Sensorimotor Polyneuropathy.

Structure
Thumb
Synonyms
Not Available
External IDs
AS-3201 / SX 3030 / SX 3201
Categories
UNII
Z26P56GFTV
CAS number
147254-64-6
Weight
Average: 420.189
Monoisotopic: 418.991696707
Chemical Formula
C17H11BrFN3O4
InChI Key
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[[email protected]@]3(CC(=O)NC3=O)C2=O)C=CC(Br)=C1

Pharmacology

Indication

Investigated for use/treatment in neuropathy (diabetic).

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Ranirestat 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. Ranirestat showed good penetration into the nerve tissue, resulting in dose-dependent inhibition of intraneural accumulation of sorbitol and fructose in a clinical study.

TargetActionsOrganism
UAldose reductaseNot AvailableHuman
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
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

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
PubChem Compound
153948
PubChem Substance
175426978
ChemSpider
135685
BindingDB
50067407
ChEMBL
CHEMBL334830
Wikipedia
Ranirestat

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2, 3CompletedTreatmentMild to Moderate Diabetic Sensorimotor Polyneuropathy1
3CompletedTreatmentDiabetic Neuropathies1

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
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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as fluorobenzenes. These are compounds containing one or more fluorine atoms attached to a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Halobenzenes
Direct Parent
Fluorobenzenes
Alternative Parents
Bromobenzenes / Pyrrolidine-2-ones / Aryl bromides / Aryl fluorides / N-substituted carboxylic acid imides / Pyrroles / Dicarboximides / N-unsubstituted carboxylic acid imides / Heteroaromatic compounds / Lactams
show 8 more
Substituents
Bromobenzene / Fluorobenzene / Aryl bromide / Aryl fluoride / Aryl halide / 2-pyrrolidone / Pyrrolidone / Carboxylic acid imide, n-substituted / Carboxylic acid imide / Heteroaromatic compound
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Details
1. Aldose reductase
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
Uniprot Name
Aldose reductase
Molecular Weight
35853.125 Da

Drug created on November 18, 2007 11:23 / Updated on December 01, 2017 15:35