Glybuzole

Last updated
Glybuzole
Glybuzole.svg
Skeletal structure of glybuzole
Clinical data
Other namesDesaglybuzole, Gludiase [1]
Pregnancy
category
  • AU:X (High risk)
Routes of
administration 		Oral
Identifiers
  • N-(5-tert-Butyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide [1]
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard 100.014.620 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C12H15N3O2S2
Molar mass 297.39 g·mol−1
3D model (JSmol)
Density 1.344 [2]  g/cm3
Melting point 163 [1]  °C (325 °F)
  • CC(C)(C)C1=NN=C(S1)NS(=O)(=O)C2=CC=CC=C2
  • InChI=S/C12H15N3O2S2/c1-12(2,3)10-13-14-11(18-10)15-19(16,17)9-7-5-4-6-8-9/h4-8H,1-3H3,(H,14,15) [1]

Glybuzole is a hypoglycaemic medicine, mainly used to treat diabetes mellitus type 2. It is an oral antidiabetic drug (OAD), when administered in the right dose it will help bring the blood glycose level down by stimulating the insulin production. Similar medicines are glimepiride, glipizide, glibenclamide, gliclazide, and gliquidone.

Contents

Structure

The molecular formula of glybuzole is C12H15N3O2S2. It is also known as desaglybuzole or gludiase. The systematic name is N-(5-tert-butyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide. [1] It consists of a benzene ring connected to sulfonamide. The nitrogen-atom of the sulfonamide is bound to a thiadiazole. In this thiadiazole two nitrogen-atoms and one sulfur-atom are present. The thiadiazole is bound to a tert-butyl group.

Mechanism of action

Glybuzole has an anti-hyperglycaemic activity. Glybuzole is a sulfonylurea and can therefore lower the blood glucose levels. [1] Sulfonylureas can bind to receptors at β-pancreatic cells which are specific for sulfonylurea binding. When a sulfonylurea binds to its receptor, the ATP-dependent channels for K+ ions will be blocked. Therefore, the flow of K+ ions into the β-pancreatic cell will stop and the cell membrane becomes depolarized. As a result, calcium ions will flow into the cell and that will then cause the contraction of actomyosin filaments which are responsible for the exocytosis of insulin. Finally, the increased secretion of insulin can then lead to a decrease in the blood glucose level. [3]

Function

Glybuzole is a hypoglycaemic medicine that is primarily used to treat diabetes mellitus type 2. Glybuzole and other sulfonylureas cannot be used to treat diabetes type 1, because they are ineffective if insulin production is inhibited, in such cases as diabetes type 1 and post-pancreatectomy. [4]

Side effects

The main side effects of glybuzole and other sulfonylureas are induction of hypoglycaemia, weight gain, abdominal upset, headache, and hypersensitivity reactions. Hypoglycaemia is mainly caused by excesses in insulin production due to doses that are too high, or due to the eating habits of the patient. [5]

Contraindications

It should not be taken if the patient has a hypersensitivity for sulfonylureas.

Interactions

There are some drugs that prolong the effects of drugs such as glybuzole and thereby increase the possibility of hypoglycaemia, these drugs include allopurinol, sulfonamides, acetylsalicylic acid and derivatives and fibrates. [6] [7]

Toxicity

Glybuzole is a drug with low toxicity, it causes no irritation. Sometimes it results in dyspnoea, or shortness of breath, and it could result in hypoglycaemia. [8]

In case of pregnancy, there are more severe toxic effects as tested in rats. At a dose of 2100 mg/kg, there were cases of fetal death, developmental abnormalities in the central nervous system, the eye and ear, and craniofacial abnormalities (including face and nose) 7 to 13 days after conception. At a lower dose (1050 mg/kg) it resulted in fetotoxicity (no death, but e.g. stunted fetus), and developmental abnormalities in the musculoskeletal system. [9]

For several rodent species the lethal dose has been investigated for several exposure routes, this is displayed in table 1. [9]

Table 1: LD50 doses for several organisms and exposure routes. [9]

OrganismExposure routeReported dose
(=normalized dose)
Mouse intraperitoneal 235 mg/kg
Mouse intravenous 193 mg/kg
Mouse oral 550 mg/kg [8]
Mouse subcutaneous 248 mg/kg
Rabbitintraperitoneal300 mg/kg
Rabbitintravenous118 mg/kg
Rabbitoral967 mg/kg
Ratintraperitoneal249 mg/kg
Ratoral500 mg/kg
Ratsubcutaneous310 mg/kg

Synthesis

A general way to synthesize sulfonamides is to perform a substitution reaction with an amine, a pyridine and a sulfonyl chloride (Figure 1). [10]

General structures of the reactants required to synthesize a sulfonamide Synthesis Glybuzole general.jpg
General structures of the reactants required to synthesize a sulfonamide

Figure 1: General structures of the reactants required to synthesize a sulfonamide

This method of synthesizing a sulfonamide is often used for the synthesis of glybuzole. Glybuzole can be synthesized using benzenesulfonyl chloride, 2-amino-5-tert-butyl-1,3,4-thiadiazole and pyridine. [11] The reaction that will proceed is a bimolecular nucleophilic substitution reaction (SN2) (Figure 2). The nitrogen atom from the amino-group of 2-amino-5-tert-butyl-1,3,4-thiadiazole will attack the sulfur atom of benzene-sulfonyl chloride, leading to a chloride ion being removed from the benzenesulfonyl chloride. The intermediate which is now formed still has a positive charge. This positive charge is removed due to the uptake of a hydrogen atom by pyridine and the final product of interest, glybuzole, is produced.

Reaction mechanism of the bimolecular nucleophilic substitution reaction in the synthesis of glybuzole from benzenesulfonyl chloride and 2-amino-5-tert-butyl-1,3,4-thiadiazole, using pyridine. Synthesis Glybuzole.jpg
Reaction mechanism of the bimolecular nucleophilic substitution reaction in the synthesis of glybuzole from benzenesulfonyl chloride and 2-amino-5-tert-butyl-1,3,4-thiadiazole, using pyridine.

Figure 2: Reaction mechanism of the bimolecular nucleophilic substitution reaction in the synthesis of glybuzole from benzenesulfonyl chloride and 2-amino-5-tert-butyl-1,3,4-thiadiazole, using pyridine.

Related Research Articles

<span class="mw-page-title-main">Hypoglycemia</span> Health condition

Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose below 70 mg/dL (3.9 mmol/L), symptoms associated with hypoglycemia, and resolution of symptoms when blood sugar returns to normal. Hypoglycemia may result in headache, tiredness, clumsiness, trouble talking, confusion, fast heart rate, sweating, shakiness, nervousness, hunger, loss of consciousness, seizures, or death. Symptoms typically come on quickly.

<span class="mw-page-title-main">Glimepiride</span> Group of stereoisomers

Glimepiride is an antidiabetic medication within the sulfonylurea class, primarily prescribed for the management of type 2 diabetes. It is regarded as a second-line option compared to metformin, due to metformin's well-established safety and efficacy. Use of glimepiride is recommended in conjunction with lifestyle modifications such as diet and exercise. It is taken by mouth, reaching a peak effect within three hours and lasting for about a day.

<span class="mw-page-title-main">Sulfonamide (medicine)</span> Molecular moiety or the drug class that uses it

Sulfonamide is a functional group that is the basis of several groups of drugs, which are called sulphonamides, sulfa drugs or sulpha drugs. The original antibacterial sulfonamides are synthetic (nonantibiotic) antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame. The sulfonylureas and thiazide diuretics are newer drug groups based upon the antibacterial sulfonamides.

<span class="mw-page-title-main">Sulfonylurea</span> Class of organic compounds used in medicine and agriculture

Sulfonylureas or sulphonylureas are a class of organic compounds used in medicine and agriculture. The functional group consists of a sulfonyl group (-S(=O)2) with its sulphur atom bonded to nitrogen atom of a ureylene group (N,N-dehydrourea, a urea derivative). The side chains R1 and R2 distinguish various sulfonylureas.

<span class="mw-page-title-main">Bumetanide</span> A loop diuretic

Bumetanide, sold under the brand name Bumex among others, is a medication used to treat swelling and high blood pressure. This includes swelling as a result of heart failure, liver failure, or kidney problems. It may work for swelling when other medications have not. For high blood pressure it is not a preferred treatment. It is taken by mouth, or by injection into a vein or muscle. Effects generally begin within an hour and lasts for about six hours.

<span class="mw-page-title-main">Glibenclamide</span> Chemical compound

Glibenclamide, also known as glyburide, is an antidiabetic medication used to treat type 2 diabetes. It is recommended that it be taken together with diet and exercise. It may be used with other antidiabetic medication. It is not recommended for use by itself in type 1 diabetes. It is taken by mouth.

<span class="mw-page-title-main">Diisopropyl fluorophosphate</span> Chemical compound

Diisopropyl fluorophosphate (DFP) or Isoflurophate is an oily, colorless liquid with the chemical formula C6H14FO3P. It is used in medicine and as an organophosphorus insecticide. It is stable, but undergoes hydrolysis when subjected to moisture.

Pyrylium is a cation with formula C5H5O+, consisting of a six-membered ring of five carbon atoms, each with one hydrogen atom, and one positively charged oxygen atom. The bonds in the ring are conjugated as in benzene, giving it an aromatic character. In particular, because of the positive charge, the oxygen atom is trivalent. Pyrilium is a mono-cyclic and heterocyclic compound, one of the oxonium ions.

<span class="mw-page-title-main">Alkyl nitrite</span> Organic compounds of the form R–O–N=O

In organic chemistry, alkyl nitrites are a group of organic compounds based upon the molecular structure R−O−N=O, where R represents an alkyl group. Formally they are alkyl esters of nitrous acid. They are distinct from nitro compounds.

<span class="mw-page-title-main">Sitagliptin</span> Diabetes medication

Sitagliptin, sold under the brand name Januvia among others, is an anti-diabetic medication used to treat type 2 diabetes. In the United Kingdom it is listed as less preferred than metformin or a sulfonylurea. It is taken by mouth. It is also available in the fixed-dose combination medication sitagliptin/metformin.

In inorganic chemistry, sulfonyl halide groups occur when a sulfonyl functional group is singly bonded to a halogen atom. They have the general formula RSO2X, where X is a halogen. The stability of sulfonyl halides decreases in the order fluorides > chlorides > bromides > iodides, all four types being well known. The sulfonyl chlorides and fluorides are of dominant importance in this series.

The Chichibabin reaction is a method for producing 2-aminopyridine derivatives by the reaction of pyridine with sodium amide. It was reported by Aleksei Chichibabin in 1914. The following is the overall form of the general reaction:

<span class="mw-page-title-main">4-Toluenesulfonyl chloride</span> Chemical compound

4-Toluenesulfonyl chloride (p-toluenesulfonyl chloride, toluene-p-sulfonyl chloride) is an organic compound with the formula CH3C6H4SO2Cl. This white, malodorous solid is a reagent widely used in organic synthesis. Abbreviated TsCl or TosCl, it is a derivative of toluene and contains a sulfonyl chloride (−SO2Cl) functional group.

Electrophilic aromatic substitution is an organic reaction in which an atom that is attached to an aromatic system is replaced by an electrophile. Some of the most important electrophilic aromatic substitutions are aromatic nitration, aromatic halogenation, aromatic sulfonation, alkylation and acylation Friedel–Crafts reaction.

<span class="mw-page-title-main">Sulfenamide</span>

Sulfenamides (also spelled sulphenamides) are a class of organosulfur compounds characterized by the general formula RSNR'2, where R and R' are H, alkyl, or aryl. Sulfenamides have been used extensively in the vulcanization of rubber using sulfur. They are related to the oxidized compounds sulfinamides (RS(O)NR'2) and sulfonamides (RS(O)2NR'2).

<span class="mw-page-title-main">Sulfonamide</span> Organosulfur compounds containing –S(=O)2–N< functional group

In organic chemistry, the sulfonamide functional group is an organosulfur group with the structure R−S(=O)2−NR2. It consists of a sulfonyl group connected to an amine group. Relatively speaking this group is unreactive. Because of the rigidity of the functional group, sulfonamides are typically crystalline; for this reason, the formation of a sulfonamide is a classic method to convert an amine into a crystalline derivative which can be identified by its melting point. Many important drugs contain the sulfonamide group.

<i>tert</i>-Butyl peroxybenzoate Chemical compound

tert-Butyl peroxybenzoate (TBPB) an organic compound with the formula C6H5CO3CMe3 (Me = CH3). It is the most widely produced perester; it is an ester of peroxybenzoic acid (C6H5CO3H). It is often used as a radical initiator in polymerization reactions, such as the production of LDPE from ethylene, and for crosslinking, such as for unsaturated polyester resins.

<span class="mw-page-title-main">1,3,4-Oxadiazole</span> Chemical compound

1,3,4-Oxadiazole is a nitrogen and oxygen containing heterocycle, and one of the four isomers of oxadiazole.

<span class="mw-page-title-main">Glysobuzole</span> Chemical compound

Glysobuzole is an oral antidiabetic drug, it is taken once daily by oral administration and it is water soluble to become pharmaceutically active within the gastrointestinal tract. It is a sulfonamide derivative that is similar to sulfonylureas. Glysobuzole has antihyperglycemic activity, so it is able to lower blood glucose levels by increasing the release of insulin from the pancreatic beta cells. Glysobuzole functions as a modulator in metabolic processes involving insulin and therefore it is used to treat diabetes.

Pioglitazone/glimepiride, sold under the brand name Duetact among others, is a fixed-dose combination anti-diabetic medication for the treatment of type 2 diabetes. It contains the thiazolidinedione pioglitazone and the sulfonylurea glimepiride. It is taken by mouth.

References

  1. 1 2 3 4 5 6 "Glybuzole". PubChem. U.S. National Library of Medicine. February 25, 2017. Retrieved February 25, 2017.
  2. ↑ "Compound:N-(5-tert-butyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide". www.chemsrc.com. 1996. Retrieved March 2, 2017.
  3. ↑ Sola D, Rossi L, Schianca GP, Maffioli P, Bigliocca M, Mella R, et al. (August 2015). "Sulfonylureas and their use in clinical practice". Archives of Medical Science. 11 (4): 840–848. doi:10.5114/aoms.2015.53304. PMC   4548036 . PMID   26322096.
  4. ↑ Seino S (August 2012). "Cell signalling in insulin secretion: the molecular targets of ATP, cAMP and sulfonylurea". Diabetologia. 55 (8): 2096–2108. doi:10.1007/s00125-012-2562-9. PMID   22555472. S2CID   7146975.
  5. ↑ Diaßeta® (glyburide) Tablets USP - 1.25, 2.5 and 5 mg (PDF) (Technical report). Sanofi-Aventis. 2009.
  6. ↑ Haberfeld H. Austria-Codex. Österreichischer Apothekerverlag. ISBN   3-85200-196-X.
  7. ↑ Dinnendahl VM, Fricke U. Arzneistoff-Profile. Govi Pharmazeutischer Verlag. ISBN   978-3-7741-9846-3.
  8. 1 2 Oyo, Yakuri Kenkyukai (1969). "unknown". Pharmocometrics. 3: 131.
  9. 1 2 3 Yamaguchi DI, Kogushi U (1969). "unknown". Yamaguchi Medicine. 18: 21.
  10. ↑ De Boer J, Backer HJ (1954). "p-TOLYLSULFONYLMETHYLNITROSAMIDE". Organic Syntheses. 34: 96. doi:10.15227/orgsyn.034.0096.
  11. ↑ "Glybuzole". www.thieme.com. Thieme. Retrieved February 23, 2017.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.