Sulfonylureas (UK: sulphonylurea) are a class of
organic compounds
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The s ...
used in medicine and agriculture, for example as
antidiabetic drugs
Drugs used in diabetes treat diabetes mellitus by altering the glucose level in the blood. With the exceptions of insulin, most GLP receptor agonists ( liraglutide, exenatide, and others), and pramlintide, all are administered orally and are ...
widely used in the management of
diabetes mellitus type 2
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...
. They act by increasing
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
release from the
beta cell
Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dimini ...
s in the
pancreas
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...
. A number of sulfonylureas are also used as
herbicide
Herbicides (, ), also commonly known as weedkillers, are substances used to control undesired plants, also known as weeds.EPA. February 201Pesticides Industry. Sales and Usage 2006 and 2007: Market Estimates. Summary in press releasMain page fo ...
s, because they can interfere with
plant
Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclud ...
biosynthesis
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...
of certain
amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
.
Sulfonylureas are also used experimentally to inhibit
interleukin 1 beta
Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the ''IL1B'' gene."Catabolin" ...
release from the
NALP3
NLR family pyrin domain containing 3 (NLRP3) (previously known as NACHT, LRR and PYD domains-containing protein 3 ALP3and cryopyrin), is a protein that in humans is encoded by the ''NLRP3'' gene located on the long arm of chromosome 1.
NLRP3 is ...
(or NLRP3)
inflammasome
Inflammasomes are cytosolic multiprotein oligomers of the innate immune system responsible for the activation of inflammatory responses. Activation and assembly of the inflammasome promotes proteolytic cleavage, maturation and secretion of pro-in ...
.
Drugs
* First-generation drugs include
acetohexamide
Acetohexamide (trade name Dymelor) is a first-generation sulfonylurea medication used to treat diabetes mellitus type 2, particularly in people whose diabetes cannot be controlled by diet alone.
Mechanism of action
Acetohexamide bind to an AT ...
,
carbutamide
Carbutamide (brand name Glucidoral) is an anti-diabetic drug of the sulfonylurea class, developed by Servier.
It is classified as first-generation.
It was patented in 1953 and approved for medical use in 1956.
See also
* Hellmuth Kleinsorge
...
,
chlorpropamide
Chlorpropamide is a drug in the sulfonylurea class used to treat diabetes mellitus type 2. It is a long-acting first-generation sulfonylurea.
Mechanism of action
Like other sulfonylureas, chlorpropamide acts to increase the secretion of insulin, ...
,
glycyclamide (tolcyclamide),
metahexamide
Metahexamide ( INN) is an anti-diabetic drug from the group of sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of ...
,
tolazamide
Tolazamide is an Wiktionary:oral, oral blood glucose lowering medication, drug used for people with Type 2 diabetes. It is part of the sulfonylurea (medicine), sulfonylurea family (ATC A10BB).
Synthesis
para-toluenesulfonamide, ''para''-Toluene ...
and
tolbutamide
Tolbutamide is a first-generation potassium channel blocker, sulfonylurea oral hypoglycemic medication. This drug may be used in the management of type 2 diabetes if diet alone is not effective. Tolbutamide stimulates the secretion of insulin by ...
.
* Second-generation drugs include
glibenclamide
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 f ...
(glyburide),
glibornuride
Glibornuride ( INN) is an anti-diabetic drug from the group of sulfonylureas. It is manufactured by MEDA Pharma and sold in Switzerland under the brand name Glutril.
Synthesis
Gliburnide is an endo-endo derivative made from camphor-3-carboxam ...
,
gliclazide
Gliclazide, sold under the brand name Diamicron among others, is a sulfonylurea type of anti-diabetic medication, used to treat type 2 diabetes. It is used when dietary changes, exercise, and weight loss are not enough. It is taken by mouth.
...
,
glipizide
Glipizide, sold under the brand name Glucotrol among others, is an anti-diabetic medication of the sulfonylurea class used to treat type 2 diabetes. It is used together with a diabetic diet and exercise. It is not indicated for use by itself in ...
,
gliquidone
Gliquidone ( INN, sold under the trade name Glurenorm) is an anti-diabetic medication in the sulfonylurea class. It is classified as a second-generation sulfonylurea. It is used in the treatment of diabetes mellitus type 2. It is marketed by th ...
,
glisoxepide
Glisoxepide (INN) is an orally available anti-diabetic drug from the group of sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in th ...
and
glyclopyramide
Glyclopyramide ( INN, marketed under the tradename Deamelin-S) is a sulfonylurea drug used in the treatment of diabetes. It has been marketed in Japan
Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East ...
.
* Third-generation drugs include
glimepiride
Glimepiride, is an anti-diabetic medication used to treat type 2 diabetes. It is less preferred than metformin. Use is recommended together with diet and exercise. It is taken by mouth. Glimepiride takes up to three hours for maximum effect and l ...
, although it is sometimes considered a second-generation agent.
Medical uses
Sulfonylureas are used primarily for the treatment of
diabetes mellitus
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
type 2. Sulfonylureas are ineffective where there is absolute deficiency of insulin production such as in type 1 diabetes or post-pancreatectomy.
Sulfonylureas can be used to treat some types of neonatal diabetes. While historically, people with hyperglycemia and low blood insulin levels were diagnosed with type 1 diabetes by default, it has been found that patients who receive this diagnosis before 6 months of age are often, in fact, candidates for receiving sulfonylureas rather than insulin throughout life.
A 2011
Cochrane systematic review
A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
evaluated the effects on treatment of
Latent Autoimmune Diabetes in Adults
Slowly evolving immune-mediated diabetes, or latent autoimmune diabetes in adults (LADA), is a form of diabetes that exhibits clinical features similar to both type 1 diabetes (T1D) and type 2 diabetes (T2D), and is sometimes referred to as type 1 ...
(LADA) and found that Sulfonylureas did improve metabolic control of
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
at 3 and 12 months, even worsening
HbA1c
Glycated hemoglobin, also known as HbA1c, glycohemoglobin, hemoglobin A1c, A1C, is a form of hemoglobin (Hb) that is chemically linked to a sugar. Most monosaccharides, including glucose, galactose and fructose, spontaneously (i.e. non-enzymati ...
levels in some cases, when compared to insulin.
The same review did not find improvement of fasting C-peptide following treatment with sulfonylurea.
Still, it is important to highlight that the studies available to be included in this review presented considerable flaws in quality and design.
While prior sulfonylureas were associated with worse outcomes, newer agents do not appear to increase the risk of death, heart attacks, or strokes. This is further reinforced by a 2020
Cochrane systematic review
A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
which did not find enough evidence of reduction of all-cause mortality, serious adverse events, cardiovascular mortality, non-fatal
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
, non-fatal
stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
or end-stage renal disease when comparing
metformin
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...
monotherapy to sulfonylureas.
This same review also did not find improvement in health-related quality of life.
In individuals with
impaired-glucose tolerance, a 2019 systematic review only found one suitable trial comparing the effects of Sulphonylurea with
Metformin
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...
in reduction or delay of risk of developing type 2 diabetes, however this trial did not report patient-relevant outcomes.
Side effects
Sulfonylureas – as opposed to
metformin
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...
, the
thiazolidinedione
The thiazolidinediones , abbreviated as TZD, also known as glitazones after the prototypical drug ciglitazone, are a class of heterocyclic compounds consisting of a five-membered C3NS ring. The term usually refers to a family of drugs used i ...
s,
pramlintide
Pramlintide (trade name Symlin) is an injectable amylin analogue drug for diabetes (both type 1 and 2), developed by Amylin Pharmaceuticals (now a wholly owned subsidiary of AstraZeneca). Pramlintide is sold as an acetate salt.
Pharmacology
Pram ...
and other newer treatments – may induce
hypoglycemia
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 belo ...
as a result of excesses in insulin production and release. Hypoglycemia appears to happen more often with sulfonylureas than compared to other treatments.This typically occurs if the dose is too high, and the patient is fasting. Some people attempt to change eating habits to prevent this, however it can be counterproductive.
Like
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, sulfonylureas can induce weight gain, mainly as a result of their effect to increase insulin levels and thus utilization of glucose and other metabolic fuels. Other side-effects are: gastrointestinal upset,
headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
and
hypersensitivity
Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune s ...
reactions.
The safety of sulfonylurea therapy in pregnancy is unestablished. Prolonged hypoglycemia (4 to 10 days) has been reported in children borne to mothers taking sulfonylureas at the time of delivery.
Impairment of liver or kidney function increase the risk of hypoglycemia, and are contraindications. Since other antidiabetic drugs cannot be used either under these circumstances, insulin therapy is typically recommended during pregnancy and in liver and
kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
, although some of the newer agents offer potentially better options.
A 2011 Cochrane review found evidence that treatment of
LADA using sulfonylureas lead to earlier insulin dependence in approximately 30% of cases.
A 2014 Cochrane review found tentative evidence that people treated with sulfonylureas have fewer non-fatal cardiovascular events than those treated with metformin (RR 0.7) but a higher risk of severe hypoglycemia (RR 5.6). There was not enough data available to determine the risk of mortality or of cardiovascular mortality. An earlier review by the same group found a statistically significant increase in the risk of cardiovascular death for first generation sulfonylureas relative to placebo (RR 2.6) but there was not enough data to determine the relative risk of first generation sulfonylureas relative to insulin (RR 1.4). Likewise it was not possible to determine the relative mortality risk of second generation sulfonylureas relative to metformin (RR 1.0), insulin (RR 1.0), or placebo. The FDA requires sulfonylureas to carry a label warning regarding increased risk of cardiovascular death.
A 2020
Cochrane systematic review
A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
comparing
metformin
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...
monotherapy to sulfonylureas did not find enough evidence of reduction of all-cause mortality, serious adverse events, cardiovascular mortality, non-fatal
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
, non-fatal
stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
or
end-stage renal disease
Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vom ...
.
Second-generation sulfonylureas have increased potency by weight, compared to first-generation sulfonylureas. Similarly, ACCORD (Action to Control Cardiovascular Risk in Diabetes)
and the VADT (Veterans Affairs Diabetes Trial)
studies showed no reduction in heart attack or death in patients assigned to tight glucose control with various drugs.
Interactions
Drugs that potentiate or prolong the effects of sulfonylureas and therefore increase the risk of hypoglycemia include
acetylsalicylic acid
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
and derivatives,
allopurinol
Allopurinol is a medication used to decrease high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It is taken by mouth ...
,
sulfonamide
In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...
s, and
fibrate
In pharmacology, the fibrates are a class of amphipathic carboxylic acids and esters. They are derivatives of fibric acid (phenoxyisobutyric acid). They are used for a range of metabolic disorders, mainly hypercholesterolemia (high cholesterol), ...
s. Drugs that worsen
glucose tolerance
Prediabetes is a component of the metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms but people with prediabetes often have obesit ...
, contravening the effects of antidiabetics, include
corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
s,
isoniazid
Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. For l ...
,
oral contraceptive Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control.
Female
Two types of female oral contraceptive pill, taken once per day, are widely available:
* The combin ...
s and other
estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
s,
sympathomimetic
Sympathomimetic drugs (also known as adrenergic drugs and adrenergic amines) are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in hea ...
s, and
thyroid hormone
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
rect 66 216 386 25 ...
s. Sulfonylureas tend to interact with a wide variety of other drugs, but these interactions, as well as their clinical significance, vary from substance to substance.
Structure
All pharmacological sulfonylureas contain a central ''S''-arylsulfonylurea structure with a ''p''-substituent on the phenyl ring (R
1) and various groups terminating the urea ''N'' end group (R
2). Chemically, this functionality can be easily installed by reacting
aryl
In organic chemistry, an aryl is any functional group or substituent derived from an aromatic ring, usually an aromatic hydrocarbon, such as phenyl and naphthyl. "Aryl" is used for the sake of abbreviation or generalization, and "Ar" is used as ...
sulfonamides
In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...
(R
1—C
6H
4—SO
2NH
2) with
isocyanates
In organic chemistry, isocyanate is the functional group with the formula . Organic compounds that contain an isocyanate group are referred to as isocyanates. An organic compound with two isocyanate groups is known as a diisocyanate. Diisocyan ...
(R
2—NCO).
image:Chlorpropamide.svg, Chlorpropamide
Chlorpropamide is a drug in the sulfonylurea class used to treat diabetes mellitus type 2. It is a long-acting first-generation sulfonylurea.
Mechanism of action
Like other sulfonylureas, chlorpropamide acts to increase the secretion of insulin, ...
(1st generation)
image:Tolazamide.svg, Tolazamide
Tolazamide is an Wiktionary:oral, oral blood glucose lowering medication, drug used for people with Type 2 diabetes. It is part of the sulfonylurea (medicine), sulfonylurea family (ATC A10BB).
Synthesis
para-toluenesulfonamide, ''para''-Toluene ...
(1st generation)
image:Gliclazide.svg, Gliclazide
Gliclazide, sold under the brand name Diamicron among others, is a sulfonylurea type of anti-diabetic medication, used to treat type 2 diabetes. It is used when dietary changes, exercise, and weight loss are not enough. It is taken by mouth.
...
(2nd generation)
image:Glimepiride.svg, Glimepiride
Glimepiride, is an anti-diabetic medication used to treat type 2 diabetes. It is less preferred than metformin. Use is recommended together with diet and exercise. It is taken by mouth. Glimepiride takes up to three hours for maximum effect and l ...
(2nd generation)
Mechanism of action
Sulfonylureas bind to and close
ATP-sensitive K+ (K
ATP) channels on the cell membrane of pancreatic
beta cell
Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dimini ...
s, which depolarizes the cell by preventing potassium from exiting. This
depolarization
In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is esse ...
opens voltage-gated
Ca2+ channels. The rise in intracellular calcium leads to increased fusion of
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
granules with the cell membrane, and therefore increased
secretion 440px
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...
of mature insulin.
There is some evidence that sulfonylureas also sensitize β-cells to glucose, that they limit glucose production in the
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
, that they decrease lipolysis (breakdown and release of
fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...
s by
adipose tissue
Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular e ...
) and decrease clearance of insulin by the liver.
The K
ATP channel is an octameric complex of the
inward-rectifier potassium ion channel K
ir6.x and
sulfonylurea receptor
In molecular biology, the sulfonylurea receptors (SUR) are membrane proteins which are the molecular targets of the sulfonylurea class of antidiabetic drugs whose mechanism of action is to promote insulin release from pancreatic beta cells. More ...
SUR which associate with a
stoichiometry
Stoichiometry refers to the relationship between the quantities of reactants and products before, during, and following chemical reactions.
Stoichiometry is founded on the law of conservation of mass where the total mass of the reactants equal ...
of 4:4.
Furthermore, it has been shown that sulfonylureas interact with the nucleotide exchange factor
Epac2. Mice lacking this factor exhibited a decreased glucose-lowering effect upon sulfonylurea treatment.
History
Sulfonylureas were discovered, in 1942, by the chemist Marcel Janbon and co-workers,
who were studying
sulfonamide
In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...
antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
s and discovered that the compound sulfonylurea induced
hypoglycemia
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 belo ...
in animals.
Research and development
Research and development (R&D or R+D), known in Europe as research and technological development (RTD), is the set of innovative activities undertaken by corporations or governments in developing new services or products, and improving existi ...
(
translational research
Translational research (also called translation research, translational science, or, when the context is clear, simply translation) is research aimed at translating (converting) results in basic research into results that directly benefit humans. ...
and commercial application development) for sulfonylureas as pharmaceuticals (as diagnostic and therapeutic agents in prediabetes and diabetes) happened in the 1950s and 1960s, as explored at ''
Tolbutamide § History''.
Research and development (translational research and commercial application development) for sulfonylureas as herbicides happened in the 1970s and 1980s, as explored for example in a volume of the Sloan Technology Series focusing on the sociotechnological aspects of agriculture (Canine 1995);
the
DuPont Experimental Station
The DuPont Experimental Station is the largest research and development facility of DuPont. Located on the banks of the Brandywine Creek in Wilmington, Delaware, it is home to some of the most important discoveries of the modern chemical indus ...
led this development.
Herbicides
A large number of sulfonylureas are used as
herbicide
Herbicides (, ), also commonly known as weedkillers, are substances used to control undesired plants, also known as weeds.EPA. February 201Pesticides Industry. Sales and Usage 2006 and 2007: Market Estimates. Summary in press releasMain page fo ...
s. They function by interfering with biosynthesis of the amino acids valine, isoleucine, and leucine, specifically via
acetolactate synthase
The acetolactate synthase (ALS) enzyme (also known as acetohydroxy acid or acetohydroxyacid synthase, abbr. AHAS) is a protein found in plants and micro-organisms. ALS catalyzes the first step in the synthesis of the branched-chain amino acids ( ...
inhibition. Compounds in this class include
amidosulfuron,
azimsulfuron,
bensulfuron-methyl,
chlorimuron-ethyl,
chlorsulfuron
Chlorsulfuron is an ALS (acetolactate synthase) inhibitor herbicide, and is a sulfonylurea compound. It was discovered by George Levitt in February 1976 while working at DuPont, which was the patent assignee.
Brand names
Originally introduce ...
,
ethametsulfuron-methyl,
cinosulfuron,
ethoxysulfuron,
flazasulfuron,
flupyrsulfuron-methyl-sodium,
imazosulfuron,
metsulfuron-methyl,
nicosulfuron,
oxasulfuron,
primisulfuron-methyl,
prosulfuron,
pyrazosulfuron-ethyl,
rimsulfuron,
sulfometuron-methyl
Sulfometuron methyl is an organic compound used as a herbicide. It is classed as a sulfonylurea. It functions via the inhibitition of acetolactate synthase enzyme, which catalyses the first step in biosynthesis of the branched-chain amino acids ...
,
sulfosulfuron,
thifensulfuron-methyl,
triasulfuron,
tribenuron-methyl, and
triflusulfuron-methyl.
[Arnold P. Appleby, Franz Müller, Serge Carpy "Weed Control" in Ullmann's Encyclopedia of Industrial Chemistry 2002, Wiley-VCH, Weinheim. ]
References
{{Oral hypoglycemics
Disulfiram-like drugs