1156-19-0 Usage
Description
Tolazamide, also known as Tolinase, is a first-generation sulfonylurea derivative used as an oral hypoglycemic agent for the treatment of type 2 diabetes mellitus. It is a white to off-white crystalline powder that is odorless or has a slight odor. Tolazamide inhibits the sulfonylurea receptor 1 (SUR1) linked to the inwardly rectifying potassium channel (KIR6.2), which in turn stimulates the β-cells in the pancreas to release insulin. It is more potent than tolbutamide and nearly equal in potency to chlorpropamide.
Uses
Used in Pharmaceutical Industry:
Tolazamide is used as an oral hypoglycemic agent for the treatment of non-insulin-dependent diabetes mellitus without expressed microvascular complications. It enhances glucose uptake in combination with insulin and has been shown to reduce glomerulosclerosis and albumin excretion in a rat model of insulin-dependent diabetes induced by streptozotocin.
Used in Research and Development:
Tolazamide is used as a research compound to study the effects of sulfonylurea receptor 1 inhibition on glucose uptake and insulin secretion. It is also used to investigate the mechanisms of action and potential improvements in the treatment of type 2 diabetes.
Used in Drug Formulation:
Tolazamide is used in the formulation of oral hypoglycemic drugs for the management of type 2 diabetes. It is available in various dosage forms, such as tablets and capsules, for easy administration to patients.
Originator
Tolinase,Upjohn,Italy,1964
Manufacturing Process
1-Nitrosohexamethyleneimine: A solution of 89.5 grams of
hexamethyleneimine, 75 ml of concentrated hydrochloric acid and 36 ml of
water was heated to 70°C on a steam bath. The solution was made acidic by
adding 5 ml of 2 N hydrochloric acid. While maintaining the reaction mixture
at 70° to 75°C, a solution of 67 grams of sodium nitrite in 95 ml of water was
added with stirring over a period of 1 hour. The mixture was then stirred at
70°C for 2 hours, and then cooled. The upper oily layer was separated and
the aqueous layer was then extracted with ether. The combined ether extract
and oil was dried over anhydrous magnesium sulfate and concentrated to
dryness. Upon distillation of the residue there was obtained 1-
nitrosohexamethyleneimine as a yellow oil, boiling at 136° to 138°C/34 mm.
1-Aminohexamethyleneimine: To a mixture of 15.18 grams of lithium
aluminum hydride and 400 ml of anhydrous ether was added about 10% of a
solution of 51.27 grams of 1-nitrosohexamethyleneimine in 100 ml of
anhydrous ether. The mixture was refluxed until the reaction started. The
remainder of the solution was added at such a rate as to maintain gentle
reflux. Refluxing was continued for 2 hours more, followed by the successive
addition of 16 ml of water, 12 ml of 20% aqueous sodium hydroxide solution
and 56 ml of water. The inorganic precipitate was removed by filtration and
washed with ether. The filtrate and ether washes were dried and the ether
was removed by evaporation. Upon distillation of the residue there was
obtained 25.46 grams (56%) of 1-aminohexamethyleneimine as a colorless
liquid boiling at 94° to 96°C/55 mm.
N-(4-Methylbenzenesulfonyl)-N'-Hexamethyleneiminourea Free Base: A
mixture of 11.42 grams of 1-aminohexamethyleneimine and 24.33 grams of
4-methylbenzenesulfonylurethane was heated at 130°C (oil-bath temperature)
for 2 hours. The resulting ethanol and unreacted amine were removed at 15
mm pressure for 2 hours while keeping the oil bath at 130°C. The residue was
cooled and recrystallized from methanol, giving 16.73 grams (54%) of N-(4-
methylbenzenesulfonyl)-N'-hexamethyleneiminourea free base melting at 163°
to 166°C. After a second recrystallization from methanol, the melting point
was 163.5° to 166.5°C.
Therapeutic Function
Oral hypoglycemic
Air & Water Reactions
TOLAZAMIDE may be sensitive to prolonged exposure to air. Insoluble in water.
Reactivity Profile
TOLAZAMIDE is an amide. Amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx). TOLAZAMIDE is incompatible with acids. .
Fire Hazard
Flash point data for TOLAZAMIDE are not available; however, TOLAZAMIDE is probably combustible.
Synthesis
Tolazamide is 1-hexahydro-1H-azepin-1-yl)-3-(p-toluenesulfonyl)urea
(26.2.8). By maintaining structural similarities with first-generation drugs, this drug differs
from the other drugs examined in that it has a semicarbazide group instead of a urea
residue, and an azepine group instead of a cyclohexyl group. It is synthesized by reacting with ethyl-(p-toluenesulfonyl)carbamate (26.2.7), which is made from p-toluenesulfonamide
and ethylchloroformate, with 1-aminoazepine.
Check Digit Verification of cas no
The CAS Registry Mumber 1156-19-0 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 1,1,5 and 6 respectively; the second part has 2 digits, 1 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 1156-19:
(6*1)+(5*1)+(4*5)+(3*6)+(2*1)+(1*9)=60
60 % 10 = 0
So 1156-19-0 is a valid CAS Registry Number.
InChI:InChI=1/C14H21N3O3S/c1-12-6-8-13(9-7-12)21(19,20)16-14(18)15-17-10-4-2-3-5-11-17/h6-9H,2-5,10-11H2,1H3,(H2,15,16,18)
1156-19-0Relevant articles and documents
Sulfonylurea compound synthesis method
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Paragraph 0027; 0032-0055, (2021/11/26)
The invention discloses a sulfonylurea compound synthesis method, which comprises: respectively dissolving p-toluenesulfonyl isocyanate and an amino compound in an organic solvent to obtain a p-toluenesulfonyl isocyanate organic solution and an amino compound organic solution; under the protection of nitrogen and/or inert gas, dropwise adding the amino compound organic solution into the p-toluenesulfonyl isocyanate organic solution for reaction; and after the reaction is finished, carrying out rotary evaporation to remove the solvent, and removing impurities to obtain the sulfonylurea compound. According to the synthesis method, the sulfonylurea compound can be prepared at the room temperature through specific raw material selection, energy consumption is reduced, meanwhile, the synthesis method is easy to operate, the synthesized product is easy to separate, and the purity of the product is high.
