Azoles are a class of five-membered

heterocyclic A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...

compounds containing a

nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...

atom and at least one other non-carbon atom (i.e.

sulfur Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...

, or

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...

) as part of the ring. Their names originate from the

Hantzsch–Widman nomenclature In organic chemistry, Hantzsch–Widman nomenclature, also called the extended Hantzsch–Widman system (named for Arthur Rudolf Hantzsch and ), is a type of systematic chemical nomenclature used for naming heterocyclic parent hydrides having no ...

. The parent compounds are

aromatic In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...

and have two

double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betw ...

s; there are successively reduced analogs (azolines and

azolidine Pyrrolidine, also known as tetrahydropyrrole, is an organic compound with the molecular formula (CH2)4NH. It is a cyclic secondary amine, also classified as a saturated heterocycle. It is a colourless liquid that is miscible with water and most ...

s) with fewer. One, and only one, lone pair of electrons from each

heteroatom In chemistry, a heteroatom () is, strictly, any atom that is not carbon or hydrogen. Organic chemistry In practice, the term is usually used more specifically to indicate that non-carbon atoms have replaced carbon in the backbone of the molecula ...

in the ring is part of the aromatic bonding in an azole. Names of azoles maintain the prefix upon reduction (e.g.,

pyrazoline Pyrazoline is a heterocyclic A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with ...

, pyrazolidine). The numbering of ring atoms in azoles starts with the heteroatom that is not part of a double bond, and then proceeds towards the other heteroatom.

Imidazole Imidazole (ImH) is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole Diazole refers ...

and other five-membered aromatic heterocyclic systems with two nitrogens are extremely common in nature and form the core of many

biomolecules A biomolecule or biological molecule is a loosely used term for molecules present in organisms that are essential to one or more typically biological processes, such as cell division, morphogenesis, or development. Biomolecules include large ...

, such as

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...

Compound classes

;Nitrogen only Imidazol.svg,

Pyrazol.svg,

Pyrazole Pyrazole is an organic compound with the formula C3H3N2H. It is a heterocycle characterized by a 5-membered ring of three carbon Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent ...

1,2,3-Triazole structure.svg, 1,2,3-Triazole 1,2,4-Triazole structure.svg, 1,2,4-Triazole Tetrazole Structural Formulae.png,

Tetrazole Tetrazoles are a class of synthetic organic heterocyclic compound, consisting of a 5-member ring of four nitrogen atoms and one carbon atom. The name tetrazole also refers to the parent compound with formula CH2N4, of which three isomers can be f ...

Pentazol.svg,

Pentazole Pentazole is an aromatic molecule consisting of a five-membered ring with all nitrogen atoms, one of which is bonded to a hydrogen atom. It has the molecular formula . Although strictly speaking a homocyclic, inorganic compound, pentazole has ...

;N,O compounds Oxazol.svg,

Oxazole Oxazole is the parent compound for a vast class of heterocyclic aromatic organic compounds. These are azoles with an oxygen and a nitrogen separated by one carbon. Oxazoles are aromatic compounds but less so than the thiazoles. Oxazole is a weak ...

Isoxazol.svg,

Isoxazole Isoxazole is an electron-rich azole with an oxygen atom next to the nitrogen. It is also the class of compounds containing this ring. Isoxazolyl is the univalent radical derived from isoxazole. Occurrence Isoxazole rings are found in some natura ...

1,2,3-oxadiazole.svg, 1,2,3-oxadiazole
(unstable) 1,2,4-oxadiazole.png,

Oxadiazole Oxadiazoles are a class of heterocyclic aromatic chemical compound of the azole family; with the molecular formula C2H2N2O. There are four isomers of oxadiazole: File:1,2,3-oxadiazole.svg, 1,2,3-oxadiazole File:1,2,4-oxadiazole.svg, 1,2,4-oxadiazo ...

(1,2,4-Oxadiazole) Furazan_numbering.png,

Furazan Furazan, or 1,2,5-oxadiazole, is a heterocyclic aromatic organic compound consisting of a five-atom ring containing 1 oxygen and 2 nitrogen atoms. The furazan ring system is also found in the steroid furazabol. Furazan and its derivatives are ob ...

(1,2,5-oxadiazole) 1,3,4-oxadiazole.svg , 1,3,4-oxadiazole ;N,S compounds Thiazol.svg,

Thiazole Thiazole, or 1,3-thiazole, is a heterocyclic compound that contains both sulfur and nitrogen. The term 'thiazole' also refers to a large family of derivatives. Thiazole itself is a pale yellow liquid with a pyridine-like odor and the molecular for ...

Isothiazol - Isothiazole.svg,

Isothiazole An isothiazole, or 1,2-thiazole, is a type of organic compound containing a five-membered aromatic ring that consists of three carbon atoms, one nitrogen atom, and one sulfur atom.''Heterocyclic Chemistry'', 3rd Edition, J.A. Joule, K. Mills, and ...

1,2,3-thiadiazole-numbered-2D-skeletal.png ,

Thiadiazole In chemistry thiadiazoles are a sub-family of azole compounds, with the name thiadiazole originating from the Hantzsch–Widman nomenclature. Structurally, they are five-membered heterocyclic compounds containing one sulfur and two nitrogen atoms. T ...

(1,2,3-Thiadiazole) 1,2,4-thiadiazole-2D-skeletal.png , 1,2,4-thiadiazole 1,2,5-thiadiazole-2D-skeletal.png , 1,2,5-thiadiazole 1,3,4-thiadiazole-2D-skeletal.png , 1,3,4-thiadiazole

Use as anti-fungal agents

The search for

antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as crypto ...

agents with acceptable toxicity profiles led first to the discovery of

ketoconazole Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candid ...

, the first azole-based oral treatment of systemic fungal infections, in the early 1980s. Later, triazoles

fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prevent ...

and

itraconazole Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given by mouth ...

, with a broader spectrum of antifungal activity and improved safety profile were developed. In order to overcome limitations such as sub-optimal spectra of activity, drug-drug interactions, toxicity, development of resistance and unfavorable

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...

, analogues were developed. Second-generation

triazole A triazole is a heterocyclic compound featuring a five-membered ring of two carbon atoms and three nitrogen atoms with molecular formula C2H3N3. Triazoles exhibit substantial isomerism, depending on the positioning of the nitrogen atoms within t ...

s, including

voriconazole Voriconazole, sold under the brand name Vfend among others, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, and infections by '' ...

posaconazole Posaconazole, sold under the brand name Noxafil among others, is a triazole antifungal medication. It was approved for medical use in the United States in September 2006, and is available as a generic medication. Medical uses Posaconazole is u ...

and

ravuconazole Ravuconazole (codenamed BMS-207147 and ER-30346) is a potent triazole antifungal, the development of which was discontinued in 2007. The drug has shown to have a similar spectrum of activity to voriconazole, with an increased half-life. Howev ...

, are more potent and more active against resistant pathogens.

References

External links

*
Nomenclature, IUPAC
{{Authority control Functional groups