A thioamide (rarely, thionamide, but also known as thiourylenes) is a

functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the res ...

with the general structure R–CS–NR′R″, where R, R′, and R″ are organic groups. They are analogous to

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...

s 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 l ...

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

s with phosphorus sulfides such as

phosphorus pentasulfide Phosphorus pentasulfide is the inorganic compound with the formula ( monomer) or ( dimer). This yellow solid is the one of two phosphorus sulfides of commercial value. Samples often appear greenish-gray due to impurities. It is soluble in carb ...

, 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 sy ...

or the reaction of nitriles 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 und ...

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

thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The t ...

, reducing the synthesis of

triiodothyronine Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate. Production of T3 and its prohormone thyrox ...

(T₃) and

thyroxine 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 38 ...

(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 exten ...

. 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 Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...

dermatitis Dermatitis is inflammation of the skin, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened. The area of skin involved can ...

fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...

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

References

{{Thyroid hormone receptor modulators Functional groups