Tolrestat

Cas No.:	82964-04-3
Chemical Name:	2-(6-Methoxy-N-methyl-5-(trifluoromethyl)naphthalene-1-carbothioamido)acetic acid
Synonyms:	2-(6-Methoxy-N-methyl-5-(trifluoromethyl)naphthalene-1-carbothioamido)acetic acid;N-[[6-Methoxy-5-(trifluoromethyl)naphthalen-1-yl]thioxomethyl]-N-methylglycine;[(6-Methoxy-5-trifluoromethyl-naphthalene-1-carbothioyl)-methyl-amino]-acetic acid;2-[[6-methoxy-5-(trifluoromethyl)naphthalene-1-carbothioyl]-methylamino]acetic acid;AY-27773;Tolrestat;Alredase;N-(6-Methoxythio-5-(trifluoromethyl)-1-naphthoyl)sarcosine;Tolrestatum;Tolrestatum [Latin];CID 53359;N-[[6-Methoxy-5-(trifluoromethyl)-1-naphthalenyl]thioxomethyl]-N-methyl-glycine;N-[[5 -(Trifluoromethyl)-6-methoxy-lnaphthalenyl]thioxomethyl]-N-methylglycine;Tolrestatin
SMILES:	OC(=O)CN(C)C(=S)C1C2=C(C=CC=1)C(C(F)(F)F)=C(OC)C=C2
Formula:	C16H14NO3F3S
M.Wt:	357.34746
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Tolrestat is a potent, orally active aldose reductase inhibitor with IC50 of 35 nM.
Target:	IC50: 35 nM (Aldose Reductase)
In Vivo:	Tolrestat (1.8 mg/kg per day) causes a reversal to normal RBC sorbitol levels diabetic rats[1]. In 21-day diabetic rats, the estimated ID in the sciatic nerve and lenses is 4.8 and about 20 for tolrestat, and 1.7 and 2.2 for (±)sorbinil,respectively[2]. Either tolrestat or sorbinil inhibits tissue AR activity but does not significantly affect plasma lipoprotein levels, or affect the body weight of the mice or their general health. Accumulation of cholesterol-rich foam cells is significantly increased in aortic roots of tolrestat-fed mice[3].
Animal Administration:	For a period of four days, rats weighing about 70 g are given unlimited access to water and Chow supplemented with 20% (wt/wt) galactose and tolrestat at various dose levels. Rats used as control receive chow containing galactose (20%, wt/wt) or glucose (20%, wt/wt). The rats are killed; the lenses and sciatic nerves are removed and homogenized in 5% trichloroacetic acid; the deproteinized extracts are then analyzed for galactitol by a modification of a method for glycerol determination. The values obtained in the group fed 20% glucose are used for background correction.
References:	[1]. Sestanj K, et al. 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. [2]. Simard-Duquesne N, et al. The effects of a new aldose reductase inhibitor (tolrestat) in galactosemic and diabetic rats. Metabolism. 1985 Oct;34(10):885-92. [3]. Srivastava S, et al. Aldose reductase protects against early atherosclerotic lesion formation in apolipoprotein E-null mice. Circ Res. 2009 Oct 9;105(8):793-802.