968-81-0 Usage
Description
Acetohexamide, a sulfonylurea derivative, is a hypoglycemic agent with moderate uricosuric activity. It is a first-generation medication primarily used in the treatment of diabetes mellitus type 2.
Uses
Used in Pharmaceutical Industry:
Acetohexamide is used as a hypoglycemic agent for the treatment of diabetes mellitus type 2. It helps in lowering blood sugar levels by stimulating the release of insulin from the pancreas, thus managing the glucose levels in the body.
Additionally, Acetohexamide is used as a uricosuric agent for its moderate uricosuric activity, which aids in increasing the excretion of uric acid in the urine, helping to prevent the formation of uric acid stones and managing hyperuricemia.
Originator
Dymelor ,Lilly ,US ,1964
Manufacturing Process
Preparation of p-Acetylbenzenesulfonamide: 100 grams of paminoacetophenone
were dissolved in a solvent mixture containing 165 ml of
12 N hydrochloric acid and 165 ml of glacial acetic acid. The mixture was
cooled with stirring to about 0°C. A solution containing 56.2 grams of sodium
nitrite and 175 ml of water was added dropwise with stirring to the acidic
solution while maintaining the temperature below 5°C.
After the addition had been completed, the acidic solution containing pacetylphenyldiazonium
chloride formed in the above reaction was added
dropwise with stirring to a mixture of 530 ml of glacial acetic acid and 530 ml
of benzene which had been previously cooled, and the cooled solution
saturated with sulfur dioxide and to which had been added 34 g of cupric
chloride dihydrate. After the addition had been completed, the reaction
mixture was stirred at about 40°C for three hours, and was then poured into
3,000 ml of an ice-water mixture.
The benzene layer containing p-acetylbenzenesulfonyl chloride formed in the
above reaction was separated, and the acidic aqueous phase was extracted
twice with 250 ml portions of benzene. The benzene layers were combined,
the combined extracts were filtered, and the benzene was evaporated from
the resulting filtrate in vacuum.The solid residue comprising p-acetylbenzenesulfonyl chloride was dissolved in
100 ml of dioxane, and the solution was added to 200 ml of 14% aqueous
ammonium hydroxide. The resulting solution was stirred overnight at ambient
room temperature. The p-acetylbenzenesulfonamide thus prepared was
collected by filtration. Recrystallization of the filter cake from aqueous ethanol
yielded purified p-acetylbenzenesulfonamide melting at about 176°C to 179°C.
Preparation of N-p-Acetylphenylsulfonyl-N'-Cyclohexylurea: A reaction mixture
consisting of 32.7 grams of p-acetylbenzenesulfonamide and 64 grams of
anhydrous potassium carbonate in 350 ml of anhydrous acetone was stirred at
refluxing temperature for about 1% hours, thus forming the potassium salt of
p-acetylbenzenesulfonamide. 30.9 grams of cyclohexylisocyanate were added
dropwise to the reaction mixture. Refluxing and stirring were continued during
the course of the addition and for an additional 16 hours.
The acetone was removed by evaporation in vacuum, and about 750 ml of
water were added to dissolve the resulting residue. The solution was filtered.
The potassium salt of N-p-acetylphenylsulfonyl-N'-cyclohexylurea formed in
the above reaction, being water-soluble, passed into the filtrate. Acidification
of the filtrate with 6 N aqueous hydrochloric acid caused the precipitation of
N-p-acetylphenylsulfonyl-N'-cyclohexylurea which was collected by filtration.
Recrystallization of the filter cake from 90% aqueous ethanol yielded purified
N-p-acetylphenylsulfonyl-N'-cyclohexylurea melting at about 188-190°C.
Fire Hazard
Flash point data for ACETOHEXAMIDE are not available; however, ACETOHEXAMIDE is probably combustible.
Clinical Use
Acetohexamide is metabolized in the liver to a reducedform, the α -hydroxyethyl derivative. This metabolite, themain one in humans, possesses hypoglycemic activity.Acetohexamide is intermediate between tolbutamide andchlorpropamide in potency and duration of effect on bloodsugar levels.
Safety Profile
Human reproductive effects by an unspecified route: stillbirth. Mildly toxic by ingestion. When heated to decomposition it emits very toxic fumes of SO, and NOx,.
Synthesis
Acetohexamide, 1-(p-acetyl phenylsulfonyl)-3-cyclohexylurea
(26.2.6), is made in an analogous scheme by reacting p-chlorobenzenesulfonylamide with
cyclohexylisocyanate. The necessary p-acetylbenzenesulfonylamide is made by diazotating
of p-aminoacetophenone in the presence of sulfur dioxide and copper(II) chloride,
forming the sulfonylchloride 26.2.4, which is reacted further with ammonia to give the
sulfonamide (26.2.5). Reacting this with cyclohexylisocyanate gives acetohexamide
(26.2.6).
Check Digit Verification of cas no
The CAS Registry Mumber 968-81-0 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 9,6 and 8 respectively; the second part has 2 digits, 8 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 968-81:
(5*9)+(4*6)+(3*8)+(2*8)+(1*1)=110
110 % 10 = 0
So 968-81-0 is a valid CAS Registry Number.
InChI:InChI=1/C15H20N2O4S/c1-11(18)12-7-9-14(10-8-12)22(20,21)17-15(19)16-13-5-3-2-4-6-13/h7-10,13H,2-6H2,1H3,(H2,16,17,19)
968-81-0Relevant articles and documents
Combinations comprising dipeptidylpeptidase-iv inhibitor
-
, (2008/06/13)
The invention relates to a combination which comprises a DPP-IV inhibitor and at least one further antidiabetic compound, preferably selected from the group consisting of insulin signalling pathway modulators, like inhibitors of protein tyrosine phosphatases (PTPases), non-small molecule mimetic compounds and inhibitors of glutamine-fructose-6-phosphate amidotransferase (GFAT), compounds influencing a dysregulated hepatic glucose production, like inhibitors of glucose-6-phosphatase (G6Pase), inhibitors of fructose-1,6-bisphosphatase (F-1,6-BPase), inhibitors of glycogen phosphorylase (GP), glucagon receptor antagonists and inhibitors of phosphoenolpyruvate carboxykinase (PEPCK), pyruvate dehydrogenase kinase (PDHK) inhibitors, insulin sensitivity enhancers, insulin secretion enhancers, α-glucosidase inhibitors, inhibitors of gastric emptying, insulin, and α2-adrenergic antagonists, for simultaneous, separate or sequential use in the prevention, delay of progression or treatment of conditions mediated by dipeptidylpeptidase-IV (DPP-IV), in particular diabetes, more especially type 2 diabetes mellitus, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose, metabolic acidosis, ketosis, arthritis, obesity and osteoporosis; and the use of such combination for the cosmetic treatment of a mammal in order to effect a cosmetically beneficial loss of body weight.
