Azole
Encyclopedia
An azole is a class of five-membered nitrogen
heterocyclic ring
compounds containing at least one other non-carbon atom of either nitrogen
, sulfur
, or oxygen
. The parent compounds are aromatic and have two double bond
s; there are successively reduced
analogs (azolines and azolidines) with fewer. One, and only one, lone pair of electrons from each heteroatom
in the ring is part of the aromatic bonding in an azole. Names of azoles maintain the prefix upon reduction (e.g., pyrazoline, 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.
(Six-membered aromatic heterocyclic systems with two nitrogens include pyrimidine
and purine
, important biochemicals.)
A "dioxole" is a similar compound with two oxygen atoms in a five membered ring. Dioxolane
is a derivative of dioxole.
(an important component of the fungal plasma membrane).
Some azole drugs have adverse side-effects.
Some azole drugs may disrupt estrogen production in pregnancy, affecting pregnancy outcome.
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
heterocyclic ring
Cyclic compound
In chemistry, a cyclic compound is a compound in which a series of atoms is connected to form a loop or ring.While the vast majority of cyclic compounds are organic, a few inorganic substances form cyclic compounds as well, including sulfur, silanes, phosphanes, phosphoric acid, and triboric acid. ...
compounds containing at least one other non-carbon atom of either nitrogen
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
, sulfur
Sulfur
Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...
, or oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
. The parent compounds are aromatic and have two double bond
Double bond
A double bond in chemistry is a chemical bond between two chemical elements involving four bonding electrons instead of the usual two. The most common double bond, that between two carbon atoms, can be found in alkenes. Many types of double bonds between two different elements exist, for example in...
s; there are successively reduced
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....
analogs (azolines and azolidines) with fewer. One, and only one, lone pair of electrons from each heteroatom
Heteroatom
In organic chemistry, a heteroatom is any atom that is not carbon or hydrogen. Usually, the term is used to indicate that non-carbon atoms have replaced carbon in the backbone of the molecular structure...
in the ring is part of the aromatic bonding in an azole. Names of azoles maintain the prefix upon reduction (e.g., pyrazoline, pyrazolidine
Pyrazolidine
Pyrazolidine is a heterocyclic compound.-See also:* Pyrazole* Pyrazoline...
). 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.
(Six-membered aromatic heterocyclic systems with two nitrogens include pyrimidine
Pyrimidine
Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...
and purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
, important biochemicals.)
Compound classes
The azoles include:- 1 nitrogen (but it only includes one nitrogen and no other heteroatom)
- pyrrolePyrrolePyrrole is a heterocyclic aromatic organic compound, a five-membered ring with the formula C4H4NH. It is a colourless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., N-methylpyrrole, C4H4NCH3...
- pyrrole
- 2 or more nitrogen atoms
- pyrazolePyrazolePyrazole refers both to the class of simple aromatic ring organic compounds of the heterocyclic diazole series characterized by a 5-membered ring structure composed of three carbon atoms and two nitrogen atoms in adjacent positions, and to the unsubstituted parent compound...
- imidazoleImidazoleImidazole is an organic compound with the formula C3H4N2. This aromatic heterocyclic is a diazole and is classified as an alkaloid. Imidazole refers to the parent compound, whereas imidazoles are a class of heterocycles with similar ring structure, but varying substituents...
, included in histidineHistidineHistidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans... - triazoleTriazoleTriazole refers to either one of a pair of isomeric chemical compounds with molecular formula C2H3N3, having a five-membered ring of two carbon atoms and three nitrogen atoms.The two isomers are:*1,2,3-Triazole 100px*1,2,4-Triazole 100px...
, included in RibavirinRibavirinRibavirin is an anti-viral drug indicated for severe RSV infection , hepatitis C infection and other viral infections. Ribavirin is a prodrug, which when metabolised resembles purine RNA nucleotides... - tetrazoleTetrazoleTetrazoles are a class of synthetic organic heterocyclic compound, consisting of a 5-member ring of four nitrogen and one carbon atom . The simplest is tetrazole itself, CN4H2. They are unknown in nature...
- pentazolePentazolePentazole is an aromatic chemical molecule consisting of a five-membered ring with all nitrogen atoms, one of which is bonded to a hydrogen atom. It has a molecular formula of HN5. Its SMILES structure is...
- pyrazole
- 1 nitrogen atom and 1 oxygen atom
- oxazoleOxazoleOxazole 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...
- isoxazoleIsoxazoleIsoxazole is an azole with an oxygen atom next to the nitrogen. It is also the class of compounds containing this ring.Isoxazole rings are found in some natural products, such as ibotenic acid. Isoxazoles also form the basis for a number of drugs, including the COX-2 inhibitor valdecoxib...
- oxazole
- 1 nitrogen atom and 1 sulfur atom
- thiazoleThiazoleThiazole, 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 formula C3H3NS...
- isothiazoleIsothiazoleAn isothiazole 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. Isothiazole is a member of a class of compounds known as azoles...
- thiazole
A "dioxole" is a similar compound with two oxygen atoms in a five membered ring. Dioxolane
Dioxolane
Dioxolane is a heterocyclic acetal with the chemical formula 2O2CH2. It is related to tetrahydrofuran by interchange of one oxygen for a CH2 group. The corresponding saturated 6-membered C4O2 rings are called dioxanes. The isomeric 1,2-dioxolane is an peroxide...
is a derivative of dioxole.
Uses
Many azoles are used as antifungal drugs, inhibiting the fungal enzyme 14α-demethylase which produces ergosterolErgosterol
Ergosterol is a sterol found in fungi, and named for ergot, a common name for the members of the fungal genus Claviceps from which ergosterol was first isolated. Ergosterol does not occur in plant or animal cells...
(an important component of the fungal plasma membrane).
Antifungals
- ClotrimazoleClotrimazoleClotrimazole is an antifungal medication commonly used in the treatment of fungal infections such as vaginal yeast infections, oral thrush, and ringworm...
- PosaconazolePosaconazolePosaconazole is a triazole antifungal drug.Posaconazole is marketed in the United States, the European Union, and in other countries by Schering-Plough under the trade name Noxafil...
- RavuconazoleRavuconazoleRavuconazole is a potent triazole antifungal, being developed by Bristol-Myers Squibb, that is currently in phase I/II clinical trials. . The drug has a shown to have a similar spectrum of activity to voriconazole, with an increased half-life. However, ravuconazole has limited activity against...
- EconazoleEconazoleEconazole nitrate is an antifungal medication of the imidazole class. It is used as a cream under the brand names Spectazole , Ecostatin , Pevaryl and Pevisone to treat skin infections such as athlete's foot, tinea, pityriasis versicolor, ringworm, and jock itch...
- KetoconazoleKetoconazoleKetoconazole is a synthetic antifungal drug used to prevent and treat fungal skin infections, especially in immunocompromised patients such as those with AIDS or those on chemotherapy. Ketoconazole is sold commercially as an anti-dandruff shampoo, topical cream, and oral tablet.Ketoconazole is...
- VoriconazoleVoriconazoleVoriconazole is a triazole antifungal medication that is generally used to treat serious, invasive fungal infections. These are generally seen in patients who are immunocompromised, and include invasive candidiasis, invasive aspergillosis, and certain emerging fungal infections.-Invasive...
Precautions
Some people are allergic to azole(s).Some azole drugs have adverse side-effects.
Some azole drugs may disrupt estrogen production in pregnancy, affecting pregnancy outcome.