Tolrestat is a potent, orally bioavailable aldose reductase inhibitor (antagonist) with IC50 of 35 nM.

Physicochemical Properties

Molecular Formula	C16H14F3NO3S
Molecular Weight	357.34746
Exact Mass	357.064
CAS #	82964-04-3
PubChem CID	53359
Appearance	White to light yellow solid powder
Density	1.4±0.1 g/cm3
Boiling Point	498.1±55.0 °C at 760 mmHg
Melting Point	164-165°
Flash Point	255.0±31.5 °C
Vapour Pressure	0.0±1.3 mmHg at 25°C
Index of Refraction	1.602
LogP	3.41
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	4
Heavy Atom Count	24
Complexity	486
Defined Atom Stereocenter Count	0
InChi Key	LUBHDINQXIHVLS-UHFFFAOYSA-N
InChi Code	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)
Chemical Name	N-(6-methoxy-5-(trifluoromethyl)naphthalene-1-carbonothioyl)-N-methylglycine
Synonyms	AY27,773 AY 27773 Alredase TolrestatumAY-27773 LorestatAY27773 Tolrestat AY-27,773 AY 27,773
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vivo	In diabetic rats, tolrestat (1.8 mg/kg daily) can restore normal levels of erythrocyte sorbitol [1]. The estimated IDs for sciatic nerve and lens in 21-day diabetic rats were 1.7 and 2.2 for (±)sobinib, and 4.8 and roughly 20 for torestal [2]. Both sobinib and torestat reduced tissue AR activity, but they had no discernible effects on plasma lipoprotein levels, body weight, or overall health in the mice. Mice administered torisstat exhibit a substantial increase in the production of cholesterol-rich foam cells in the aortic root [3].
References	[1]. 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]. The effects of a new aldose reductase inhibitor (tolrestat) in galactosemic and diabetic rats. Metabolism. 1985 Oct;34(10):885-92. [3]. Aldose reductase protects against early atherosclerotic lesion formation in apolipoprotein E-null mice. Circ Res. 2009 Oct 9;105(8):793-802.
Additional Infomation	Tolrestat is a member of naphthalenes. It has a role as an EC 1.1.1.21 (aldehyde reductase) inhibitor. Tolrestat (INN) (AY-27773) is an aldose reductase inhibitor which was approved for the control of certain diabetic complications. While it was approved for marketed in several countries, it failed a Phase III trial in the U.S. due to toxicity and never received FDA approval. It was sold under the tradename Alredase but was discontinued by Wyeth in 1997 because of the risk of severe liver toxicity and death. Drug Indication For the pharmacological control of certain diabetic complications.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~139.92 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.00 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.00 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (7.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7984 mL	13.9919 mL	27.9838 mL
	5 mM	0.5597 mL	2.7984 mL	5.5968 mL
	10 mM	0.2798 mL	1.3992 mL	2.7984 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.