Glipizide Chemical Properties

Melting point:

208-209°C

Density 

1.34±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

methanol: 1.9 mg/mL

pka

pKa 5.9 (Uncertain)

form 

solid

color 

white

Merck 

14,4442

BCS Class

2 (CLogP), 4 (LogP)

CAS DataBase Reference

29094-61-9(CAS DataBase Reference)

EPA Substance Registry System

2-Pyrazinecarboxamide, N-[2-[4-[[[(cyclohexylamino)carbonyl]amino]sulfonyl]phenyl]ethyl]-5-methyl- (29094-61-9)

Safety Information

Hazard Codes 

Xn,Xi

Risk Statements 

21-36/38-46-62-63

Safety Statements 

24/25-53-36/37-26-25

WGK Germany 

3

RTECS 

YS7640000

F 

10

HS Code 

29350090

Toxicity

LD50 in mice, rats (g/kg): >3, 1.2 i.p. (Ambrogi)

MSDS

• Language:English Provider:1-Cyclohexyl-3-[[p-[2-(5-methylpyrazinecarboxamido)ethyl]phenyl]sulfonyl]urea
• Language:English Provider:ACROS
• Language:English Provider:SigmaAldrich

Glipizide Usage And Synthesis

Description

Glipizide is an oral rapid- and short-acting anti-diabetic medication classified as a second-generation sulfonylurea. It is commonly used as an adjunct to diet in combination with proper exercise program for controlling high blood sugar and its associated symptomatology in people with type II diabetes (non-insulin-dependent diabetes mellitus). Besides, it is effective to lessen the risk of heart attack or stroke and help prevent kidney damage, blindness, nerve problems, loss of limbs, sexual function problems, which can be resulted from hypertension.
Glipizide is an oral hypoglycemic drug that is rapidly absorbed and completely metabolized in human body. It is occasionally be administrated with other diabetes pharmaceuticals but it is not a cure for diabetes. Glipizide lowers blood glucose by stimulating the pancreas to release more natural insulin. The FDA approved glipizide in May 1984.

References

https://en.wikipedia.org/wiki/Glipizide
http://www.medicinenet.com/glipizide/article.htm
http://www.medicinenet.com/glipizide_tablet-oral/article.htm
https://www.drugbank.ca/drugs/DB01067

Chemical Properties

Crystalline Solid

Originator

Minidiab,Carlo Erba,Italy,1973

Uses

sweetener, treatment of portoencephalopathy

Uses

Labelled Glipizide . A sulfonylurea hypoglycemic agent. Used as an antidiabetic.;Labeled Glipizide, intended for use as an internal standard for the quantification of Glipizide by GC- or LC-mass spectrometry.

Uses

A hypoglycemic agent that enhances insulin secretion.

Definition

ChEBI: An N-sulfonylurea that is glyburide in which the (5-chloro-2-methoxybenzoyl group is replaced by a (5-methylpyrazin-2-yl)carbonyl group. An oral hypoglycemic agent, it is used in the treatment of type 2 diabetes mellitus.

Manufacturing Process

5-Methyl pyrazine-2-carboxylic acid is refluxed with thionyl chloride in anhydrous benzene for approximately 12 hours. Benzene and thionyl chloride excess is removed by distillation. Then some anhydrous dioxane is added and this acid chloride solution is allowed to drop into p-(β-aminoethyl)- benzenesulfonamide suspension in dioxane and anhydrous pyridine. The resulting mixture is then refluxed for 3 hours. Dioxane is removed by distillation and then the residue is washed with water and acetic acid. The raw acylated sulfonamide is then filtered and crystallized from 95% ethanol, thus obtaining a product of MP 200° to 203°C.
This product is then reacted with cyclohexyl isocyanate to give glipizide.

brand name

Glucotrol (Pfizer).

Therapeutic Function

Oral hypoglycemic

General Description

Glipizide is N-[2-[4-[[[(cyclohexylamino)carbonyl]amino]sulfonyl]phenyl]ethyl]-5-methyl-2-pyrazinecarboxamide;this compound can also be named as the urea—seepreceding discussion (Glucotrol, generic). In the UnitedStates, combinations are available with metformin (Metaglip,generic; tablets, mg glipizide/mg metformin as hydrochloride:2.5/250, 2.5/500, 5/500). Extended-release tablets are available(Glucotrol XL, generic). The pyrazine moiety within thisstructure renders the molecule significantly more hydrophilicthan the similar molecule glyburide, albeit also moderatelyless potent on a dosage as well as target-level basis.

General Description

Glipizide, 1-cyclohexyl-3-[[p-(2-(5-methylpyrazinecarboxamido)ethyl]phenyl]sulfonyl]urea(Glucotrol), is an off-white, odorless powder with a pKa of5.9. It is insoluble in water and alcohols, but soluble in 0.1 NNaOH. Even though on a weight basis, it is approximately100 times more potent than tolbutamide, the maximal hypoglycemiceffects of these two agents are similar. It is rapidlyabsorbed on oral administration, with a serum half-life of 2 to4 hours, whereas the hypoglycemic effects range from 12 to24 hours. Metabolism of glipizide is generally through oxidationof the cyclohexane ring to the p-hydroxy and m-hydroxymetabolites. A minor metabolite that occurs involves theN-acetyl derivative, which results from the acetylation of theprimary amine following hydrolysis of the amide system byamidase enzymes.

General Description

Structurally, glipizide, 1-cyclohexyl-3-[[p-[2(methylpyrazinecarboxamido)ethyl]phenyl]sulfonyl]urea(Glucotrol), is a cyclohexylsulfonylurea analog similar toacetohexamide and glyburide. The drug is absorbed rapidlyon oral administration. Its serum half-life is 2 to 4 hours, andit has a hypoglycemic effect that ranges from 12 to 24 hours.

Biochem/physiol Actions

Potassium inwardly-rectifying channel, subfamily J, member 1 (KCNJ1) plays a vital role in potassium balance. It is an ATP-dependent K+?channel blocker. The encoded protein is liable for the elimination of potassium in exchange for the absorption of sodium by the epithelial sodium channel (ENaC). Mutation in KCNJ1 is linked with several diseases, such as, antenatal Bartter syndrome and diabetes. Glipizide helps to repress the development of tumors and metastasis by preventing angiogenesis.

Clinical Use

Non-insulin dependent diabetes mellitus

Synthesis

Glipizide, 1-cyclohexyl-3-[[p-[2-(5-methylpyrazincarboxamido)ethyl]phenyl] sulfonyl]urea (26.2.13), differs from glyburide in the structure of the amide region of the molecule, in which the 2-methoxy-5-chlorobenzoic acid part is replaced with 6- methylpyrazincarboxylic acid. It is also synthesized by a synthesis alternative to those described above. In the given scheme, 6-methylpyrazincarboxylic acid is initially reacted with thionyl chloride, resulting in the corresponding chloride, which undergoes further action with 4-(2-aminoethyl)benzenesulfonamide, forming the corresponding amide 26.2.12. The resulting sulfonamide is reacted in a traditional scheme with cyclohexylisocyanate, forming the desired glipizide (26.2.13).

Veterinary Drugs and Treatments

Glipizide may be of benefit in treating cats with type II diabetes if they have a population of functioning beta cells. It has been suggested that there are two situations when glipizide can be recommended, 1) If an owner refuses to consider using insulin usually due to a fear of needles, and 2) the cat appears to be relatively well controlled on quite small doses of insulin and the owner would strongly prefer to no longer give insulin (Feldman 2005b).
While glipizide potentially could be useful in treating canine patients with type II or III diabetes, however, by the time dogs present with hyperglycemia, they are absolutely or relatively insulinopenic and glipizide would unlikely be effective.

Drug interactions

Potentially hazardous interactions with other drugs
Analgesics: effects enhanced by NSAIDs.
Antibacterials: effects enhanced by chloramphenicol, sulphonamides, tetracyclines and trimethoprim; effect reduced by rifamycins.
Anticoagulants: effect possibly enhanced by coumarins; also possibly changes to INR.
Antifungals: concentration increased by fluconazole, posaconazole and miconazole and possibly voriconazole - avoid with miconazole.
Ciclosporin: may increase ciclosporin levels.
Lipid-regulating drugs: possibly additive hypoglycaemic effect with fibrates.
Sulfinpyrazone: enhanced effect of sulphonylureas.

Metabolism

The metabolism of glipizide is extensive and occurs mainly in the liver. The primary metabolites are inactive hydroxylation products and polar conjugates and are excreted mainly in the urine.

Glipizide(29094-61-9)Related Product Information

• PHENYL VALERATE
• Ethyl cellulose
• Ethylparaben
• Phenylhydrazine
• Ethylbenzene
• Ethylurea
• Benzenesulfonamide
• Ethyl acrylate
• Ethyl acetate
• p-Toluenesulfonamide
• CYCLOHEXYLDIETHANOLAMINE
• Ethanol
• Methanesulfonamide
• Sulfanilamide
• Ethanesulfonyl chloride
• Pyrazine
• Glimepiride
• Diethyl ether