29094-61-9 Usage
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
Different sources of media describe the Uses of 29094-61-9 differently. You can refer to the following data:
1. sweetener, treatment of portoencephalopathy
2. 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.
3. 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
Different sources of media describe the General Description of 29094-61-9 differently. You can refer to the following data:
1. 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.
2. 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.
3. 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.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 29094-61-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 2,9,0,9 and 4 respectively; the second part has 2 digits, 6 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 29094-61:
(7*2)+(6*9)+(5*0)+(4*9)+(3*4)+(2*6)+(1*1)=129
129 % 10 = 9
So 29094-61-9 is a valid CAS Registry Number.
InChI:InChI=1/C21H33N5O4S/c1-15-13-24-19(14-23-15)20(27)22-12-11-16-7-9-18(10-8-16)31(29,30)26-21(28)25-17-5-3-2-4-6-17/h7-10,15,17,19,23-24H,2-6,11-14H2,1H3,(H,22,27)(H2,25,26,28)
29094-61-9Relevant articles and documents
Total Synthesis of Glipizide and Glibenclamide in Continuous Flow
Sagandira, Cloudius R.,Khasipo, Agnes Z.,Watts, Paul
, p. 16028 - 16035 (2021/10/14)
Glipizide and glibenclamide remain some of the widely prescribed antidiabetic sulfonylurea drugs for the treatment of type 2 diabetes mellitus. Herein the authors report on an isocyanate-free synthetic procedure towards the preparation of these on demand drugs at multigram scale using continuous flow technology. The safety concern over the use of isocyanates in most of the existing synthetic routes was dealt with in this present work by using N-carbamates synthesised in situ from activation of amines with chloroformates as safer alternatives. An overall yield of 80–85 % was obtained for the semi-telescoped steps within 10 min total residence time.
Preparation method of glipizide
-
Paragraph 0003, (2017/12/28)
The invention relates to a preparation method of glipizide. The method takes 4-[2-(5-methylpyrazine-2-formylamino)ethyl]benzenesulfonamide as a raw material, the material is subjected to a chlorination reaction, and then under existence of an iron catalyst, the material, carbon monoxide and cyclohexylamine are subjected to a reaction to obtain the product. The method is simple and practicable, and provides a novel process route for synthesis of glipizide.
OSMOTIC PUMP CONTROLLED RELEASE TABLET AND PREPARATION METHOD THEREOF
-
, (2012/07/14)
An osmotic pump controlled release tablet and the preparation method thereof are disclosed. The osmotic pump controlled release tablet is composed of tablet core, semipermeable membrane and optional film coating. The material of said semipermeable membrane is composed of ethyl cellulose and povidone in the ratio of 1:1?1:4 by weight. Said tablet core comprises drug containing layer and push layer. The osmotic pump controlled release tablet also characterizes in that; (1) the angle θ1 formed by the outer curved surface of the drug containing layer and the lateral surface is 120°-180°; and/or (2) the ratio of L1 to r is 0.27-1.0, wherein L1 is the vertical distance from the central vertex of the outer curved surface of the drug containing layer to the plane formed by the intersection line between the outer curved surface of the drug containing layer and the lateral surface, and r is the radius of the tablet core.
