A thioamide (rarely, thionamide, but also known as thiourylenes) is a functional group with the general structure R–CS–NR′R″, where R, R′, and R″ are organic groups. They are analogous to amides but they exhibit greater multiple bond character along the C-N bond, resulting in a larger rotational barrier. One of the best-known thioamides is thioacetamide, which is used as a source of the

sulfide Sulfide (British English also sulphide) is an inorganic anion of sulfur with the chemical formula S2− or a compound containing one or more S2− ions. Solutions of sulfide salts are corrosive. ''Sulfide'' also refers to chemical compounds lar ...

ion and is a building block in heterocyclic chemistry. Thioamides or anti-thyroid drugs are also a class of

drugs A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhalat ...

that are used to control thyrotoxicosis.

Preparation and structure

Thioamides are typically prepared by treating amides with phosphorus sulfides such as phosphorus pentasulfide, a reaction first described in the 1870s. Alternative routes include the use of

Lawesson's reagent Lawesson's reagent (LR) is a chemical compound used in organic synthesis as a thiation agent. Lawesson's reagent was first made popular by Sven-Olov Lawesson, who did not, however, invent it. Lawesson's reagent was first made in 1956 during a sys ...

or the reaction of

nitrile In organic chemistry, a nitrile is any organic compound that has a functional group. The prefix ''cyano-'' is used interchangeably with the term ''nitrile'' in industrial literature. Nitriles are found in many useful compounds, including met ...

s with

hydrogen sulfide Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is poisonous, corrosive, and flammable, with trace amounts in ambient atmosphere having a characteristic foul odor of rotten eggs. The unde ...

The

Willgerodt-Kindler reaction The Willgerodt rearrangement or Willgerodt reaction is an organic reaction converting an aryl alkyl ketone, alkyne, or alkene to the corresponding amide by reaction with polysulfide, ammonium polysulfide, named after Conrad Willgerodt. The formatio ...

also affords benzylthioamides. The C₂NH₂S core of thioamides is planar. Using thioacetamide as representative: the C-S, C-N, and C-C distances are 1.68, 1.31, and 1.50 Å, respectively. The short C-S and C-N distances indicate multiple bonding.

Thioamides in biochemistry and medicine

Thioamides are also a class of

that are used to control thyrotoxicosis. Thioamides have been incorporated into peptides as isosteres for the amide bond. Peptide modifications are analogues of the native peptide, which can reveal the structure-activity relationship (

SAR SAR or Sar may refer to: Places * Sar (river), Galicia, Spain * Sar, Bahrain, a residential district * Sar, Iran (disambiguation), several places in Iran * Sar, Tibet, Tibet Autonomous Region of China * Šar Mountains, in southeastern Europe ...

). Analogues of peptides can also be used as drugs with an improved oral bioavailability. Thioamides inhibit the enzyme

thyroid peroxidase Thyroid peroxidase, also called thyroperoxidase (TPO) or iodide peroxidase, is an enzyme expressed mainly in the thyroid where it is secreted into colloid. Thyroid peroxidase oxidizes iodide ions to form iodine atoms for addition onto tyrosine re ...

in the thyroid, reducing the synthesis of triiodothyronine (T₃) and thyroxine (T₄), thereby blocking uptake of iodotyrosines from the

colloid A colloid is a mixture in which one substance consisting of microscopically dispersed insoluble particles is suspended throughout another substance. Some definitions specify that the particles must be dispersed in a liquid, while others extend ...

. They also block iodine release from peripheral hormone. Maximum effects occur only after a month, since hormone depletion is caused by reduced synthesis, which is a slow process. Because thioamides can penetrate the placental barrier, caution is advised when used during pregnancy. Ten percent of patients report skin eruptions (such as macules and papules), urticaria, dermatitis, fever, and arthralgia; 0.03% of all patients develop

agranulocytosis Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing a neutropenia in the circulating blood. ...

aplastic anemia Aplastic anemia is a cancer in which the body fails to make blood cells in sufficient numbers. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood ...

also a rare adverse effect. Members of the thioamide group include

methimazole Thiamazole, also known as methimazole, is a medication used to treat hyperthyroidism. This includes Graves disease, toxic multinodular goiter, and thyrotoxic crisis. It is taken by mouth. Full effects may take a few weeks to occur. Common s ...

, carbimazole (converted ''in vivo'' to methimazole), and

propylthiouracil Propylthiouracil (PTU) is a medication used to treat hyperthyroidism. This includes hyperthyroidism due to Graves' disease and toxic multinodular goiter. In a thyrotoxic crisis it is generally more effective than methimazole. Otherwise it is t ...

References

{{Thyroid hormone receptor modulators Functional groups