TOLRESTAT

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H14F3NO3S
Molecular Weight	357.347
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

COC1=CC=C2C(=CC=CC2=C1C(F)(F)F)C(=S)N(C)CC(O)=O

InChI

InChIKey=LUBHDINQXIHVLS-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description

Tolrestat is an orally active aldose reductase inhibitor. It was used for the pharmacological control of certain diabetic complications. It was discontinued by Wyeth in 1997 because of the risk of severe liver toxicity and death.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Aldose reductase 45	Inhibitor 8,504		35.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Diabetic neuropathy 23	Primary		Approved 8,583	Alredase

C_max

Value	Dose	Analyte	Population
11.3 μg/mL	200 mg single, oral	TOLRESTAT plasma	Homo sapiens
11.1 μg/mL	200 mg single, oral	TOLRESTAT plasma	Homo sapiens
14.8 μg/mL	200 mg 2 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
27 μg/mL	200 mg 2 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
21 μg/mL	200 mg 2 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
30 μg/mL	200 mg 2 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
23 μg/mL	200 mg 2 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
15.9 μg/mL	200 mg 1 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
18.1 μg/mL	200 mg 1 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
18.2 μg/mL	200 mg single, oral	TOLRESTAT plasma	Homo sapiens
18.5 μg/mL	200 mg single, oral	TOLRESTAT plasma	Homo sapiens
19 μg/mL	200 mg single, oral	TOLRESTAT plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
55.1 μg × h/mL	200 mg single, oral	TOLRESTAT plasma	Homo sapiens
57.1 μg × h/mL	200 mg 2 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
86 μg × h/mL	200 mg single, oral	TOLRESTAT plasma	Homo sapiens
104 μg × h/mL	200 mg single, oral	TOLRESTAT plasma	Homo sapiens
193 μg × h/mL	200 mg single, oral	TOLRESTAT plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
13 h	200 mg single, oral	TOLRESTAT plasma	Homo sapiens
13.9 h	200 mg single, oral	TOLRESTAT plasma	Homo sapiens
13.9 h	200 mg 2 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
11.4 h	200 mg 2 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
17.2 h	200 mg 2 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
15.2 h	200 mg 2 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
15.2 h	200 mg 2 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
10.9 h	200 mg 1 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
10.8 h	200 mg 1 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
10.6 h	200 mg single, oral	TOLRESTAT plasma	Homo sapiens
11.7 h	200 mg single, oral	TOLRESTAT plasma	Homo sapiens
16.4 h	200 mg single, oral	TOLRESTAT plasma	Homo sapiens

F_unbound

Value	Dose	Analyte	Population
0.64%	200 mg single, oral	TOLRESTAT plasma	Homo sapiens
0.64%	200 mg single, oral	TOLRESTAT plasma	Homo sapiens
0.76%	200 mg 2 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
0.73%	200 mg 2 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
0.77%	200 mg 2 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens
0.8%	200 mg 2 times / day steady-state, oral	TOLRESTAT plasma	Homo sapiens

PubMed

Show entries

Title	Date	PubMed
N-[5-(trifluoromethyl)-6-methoxy-1-naphthalenyl]thioxomethyl]- N-methylglycine (Tolrestat), a potent, orally active aldose reductase inhibitor.	1984 Mar	6422042
Aldose reductase inhibitors: a potential new class of agents for the pharmacological control of certain diabetic complications.	1985 Jul	3925146
Synthesis and aldose reductase inhibitory activity of 5-arylidene-2,4-thiazolidinediones.	2002 Apr	11836118
Nitric oxide prevents aldose reductase activation and sorbitol accumulation during diabetes.	2002 Oct	12351453
Aldose reductase mediates cytotoxic signals of hyperglycemia and TNF-alpha in human lens epithelial cells.	2003 Feb	12490536

Showing 1 to 5 of 20 entries

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Patents

Sample Use Guides

In Vivo Use Guide

200 mg 1 time a day, in the morning before breakfast

Route of Administration: Oral

In Vitro Use Guide

In the lens, a 18% inhibition (p < 0.01) was observed in the presence of 8 micromol/L Tolrestat. In the optic nerve, a 12% (p < 0.05) and a 21% (p < 0.01) reduction was recorded at 4 and 8 micromol/L Tolrestat, respectively.

Show entries

Name

Type

Language

TOLRESTAT

Official Name

English

ALREDASE

Preferred Name

English

Tolrestat [WHO-DD]

Common Name

English

tolrestat [INN]

Common Name

English

TOLRESTAT [MART.]

Common Name

English

Showing 1 to 5 of 11 entries

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Show entries

Classification Tree

Code System

Code

Aldose reductase inhibitors

WHO-VATC

QA10XA01

Enzyme Inhibitor

NCI_THESAURUS

C72880

Aldose reductase inhibitors

WHO-ATC

A10XA01

Showing 1 to 3 of 3 entries

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Code System

Code

Type

Description

INN

5529

PRIMARY

CAS

82964-04-3

PRIMARY

MESH

C040550

PRIMARY

NCI_THESAURUS

C96310

PRIMARY

SMS_ID

100000077766

PRIMARY

Showing 1 to 5 of 18 entries

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ACTIVE MOIETY


					0T93LG5NMK

TOLRESTAT

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound