RANIRESTAT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H11BrFN3O4
Molecular Weight	420.189
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=C(CN2C(=O)C3=CC=CN3[C@@]4(CC(=O)NC4=O)C2=O)C=CC(Br)=C1

InChI

InChIKey=QCVNMNYRNIMDKV-QGZVFWFLSA-N

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

HIDE SMILES / InChI

Molecular Formula	C17H11BrFN3O4
Molecular Weight	420.189
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://adisinsight.springer.com/drugs/800005030
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/9767647 | https://www.ncbi.nlm.nih.gov/pubmed/24785785

Ranirestat (AS-3201, SX-3030, SX-3202) is an oral aldose reductase inhibitor. (-)-enantiomer (AS-3201) is 10 times more potent in inhibition of the aldose reductase and 500 times more potent in the in vivo activity than the corresponding (+)-enantiomer (SX-3202). Ranirestat is being developed by Dainippon Sumitomo Pharma (formerly Dainippon Pharmaceutical) for the treatment of diabetic complications, primarily diabetic neuropathy. Ranirestat is a well-tolerated front-line inhibitor. It reproducibly exhibits some degree of measurable objective beneficial outcomes in diabetic neuropathy.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Aldose reductase 44 Target ID: CHEMBL1900 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9767647 \| https://www.ncbi.nlm.nih.gov/pubmed/11444967	Inhibitor 8297		15.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Diabetic neuropathy 23 Sources: http://adisinsight.springer.com/drugs/800005030	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
3213 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32437025	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	RANIRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3016 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32437025	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	RANIRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3644 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32437025	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	RANIRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
60.4 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32437025	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	RANIRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
67 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32437025	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	RANIRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
71.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32437025	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	RANIRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
105.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32437025	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	RANIRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
131.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32437025	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	RANIRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
133.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32437025	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	RANIRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Analyte	Population
0.665% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32437025	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	RANIRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.03% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32437025	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	RANIRESTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.77% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32437025	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	RANIRESTAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00AC27	https://www.1pchem.com/search?query=1P00AC27
BLD Pharm	BD630320	http://www.bldpharm.com/search/Search.html?keyword=BD630320
BOC Sciences	147254-64-6	http://www.bocsci.com/description.asp?cas=147254-64-6
Chem Scene	CS-4282	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-4282
ChemShuttle	172334	https://www.chemshuttle.com/catalogsearch/result/?q=172334
Hairui	RASA015	http://www.hairuichem.com/en/product/search.do?q=RASA015
MedChem Express	HY-15314	https://www.medchemexpress.com/search.html?q=HY-15314&ft=&fa=&fp=
MolPort	MolPort-006-170-073	https://www.molport.com/shop/molecule-link/MolPort-006-170-073
ShangHai Biochempartner	BCP14386	http://www.biochempartner.com/search_BCP14386
Toronto Research Chemicals	M199808	https://www.trc-canada.com/product-detail/?CatNum=M199808
Toronto Research Chemicals	R119950	https://www.trc-canada.com/product-detail/?CatNum=R119950
eMolecules	275155872	https://orderbb.emolecules.com/search/#?query=275155872
eMolecules	302082565	https://orderbb.emolecules.com/search/#?query=302082565
eMolecules	53745173	https://orderbb.emolecules.com/search/#?query=53745173
mcule	MCULE-4070029470	https://mcule.com/MCULE-4070029470/

PubMed

Title	Date	PubMed
Uridine diphosphate sugar-selective conjugation of an aldose reductase inhibitor (AS-3201) by UDP-glucuronosyltransferase 2B subfamily in human liver microsomes.	2004 Apr 1	15013842
Long-term effects of ranirestat (AS-3201) on peripheral nerve function in patients with diabetic sensorimotor polyneuropathy.	2006 Jan	16373898
Effects of long-term treatment with ranirestat, a potent aldose reductase inhibitor, on diabetic cataract and neuropathy in spontaneously diabetic torii rats.	2013	23671855
Effect of ranirestat, a new aldose reductase inhibitor, on diabetic retinopathy in SDT rats.	2014	25215304
Evaluation of ranirestat for the treatment of diabetic neuropathy.	2014 Jul	24785785
Safety and efficacy of ranirestat in patients with mild-to-moderate diabetic sensorimotor polyneuropathy.	2015 Dec	26313450
Effect of Ranirestat on Sensory and Motor Nerve Function in Japanese Patients with Diabetic Polyneuropathy: A Randomized Double-Blind Placebo-Controlled Study.	2016	26881251
Ranirestat has a stronger inhibitory activity on aldose reductase and suppresses inflammatory reactions in high glucose-exposed endothelial cells.	2016 Jul	27190083

Patents

Sample Use Guides

In Vivo Use Guide

10-80 mg/day for several weeks to months

Route of Administration: Oral

In Vitro Use Guide

High glucose significantly increased sorbitol levels, superoxide generation and vascular cell adhesion molecule-1 mRNA levels in, and THP-1 cell adhesion to, human umbilical vein endothelial cells, all of which were prevented by 500 nM ranirestat

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:52:32 GMT 2023` Edited by `admin` on `Fri Dec 15 15:52:32 GMT 2023`
Record UNII	Z26P56GFTV
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

RANIRESTAT

Official Name

English

AS-3201

Code

English

(3R)-2'-(4-BROMO-2-FLUOROBENZYL)SPIRO(PYRROLIDINE-3,4'(1'H)-PYRROLO(1,2-A)PYRAZINE)-1',2,3',5(2'H)-TETRONE

Systematic Name

English

ranirestat [INN]

Common Name

English

RANIRESTAT [JAN]

Common Name

English

Ranirestat [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C72880