Issue 10, 2013 - Research and application progress of triazole derivatives

Research and application progress of triazole derivatives

Triazole derivatives have the characteristics of high efficiency, low toxicity, broad spectrum, low resistance, double effect (sterilization, long control), and have a wide range of biological activities, such as antibacterial, antispasmodic, anti-inflammatory, anti-platelet agglomeration and regulation of plant growth, etc.
, in today's medicine, pesticide, chemical industry, more and more widely
used.

1.
Medicine

1.
The structure of triazole fungicides newly developed by antifungal drugs
in recent years has the following characteristics: multi-substituted triazoles are used as the mother nucleus, and other structures are modified, such as replacing hydrogen atoms on methyl groups with multiple halogen atoms; The molecule contains two or more chiral carbon atoms; Multiple methods such as the formation of thick heterocycles to achieve the purpose of
improving activity or specificity.
At present, research on this class of drugs mainly focuses on the structural modification
of triazolpropanol antifungal drugs and triazole-containing pentacycline antifungal drugs.

Triazole-containing pentacycline antifungal drugs have been marketed ketoconazole, itraconazole and salpaconazole, of which itraconazole is easy to take orally, has a wide antibacterial spectrum, has a very prominent effect on Aspergillus, and is very effective
in the treatment of non-acute Aspergillus infection in immunodeficient patients.

2.
Antitumor drugs
triazoles can be used as aromatase inhibitors, by inhibiting aromatase activity, preventing androgens from being converted into estrogen in women's bodies, thereby reducing estrogen levels and treating breast cancer disease
in menopausal women.
Anastrozole, letrozole and vochlorazole have been used in clinical practice, all of which are third-generation aromatase inhibitors, which have the characteristics of reversible, efficient, specific, and less toxic side effects, and are successfully used as chemotherapeutic drugs
for the prevention and treatment of breast cancer in triazole derivatives.

Triazoles can also inhibit angiogenesis by interfering with endothelial cell proliferation, as angiogenesis inhibitors for adjuvant therapy of prostate cancer, lung cancer, malignant blood and other diseases, such as non-cell-specific angiogenesis inhibitors carbamoyltriazoles, whose anti-cancer activity research has entered the phase II clinical stage, the mechanism of action is to interfere with the expansion of endothelial cells on the extracellular matrix, affecting the integrity
of blood vessels.

3.
Antiviral drugs In terms of antivirals, virazoles are the earliest triazole-containing drugs

used in antivirals.
The diphosphate derivatives and triphosphate derivatives obtained after structural modification are not easy to hydrolyze and are more active than virazole
.
The non-nucleoside triazole-containing compound Maraviroc (UK-427857) is the first novel immunodeficiency virus (HIV) complex receptor CCR5 inhibitory to enter phase III clinical trials, with strong HIV inhibitory activity
.

4.
As a new anticonvulsant drug, anticonvulsant and antipsychotic triazole
derivatives have strong anticonvulsant effect and low neurotoxicity, which is a potential research field
.
At present, such drugs have been used in clinical practice are lorazole and triazolam
.
Rufinamide, which is in phase III clinical trials, is able to limit the activation of sodium-dependent action potentials in neurons and stabilize cell membranes
.
Rufinamide has been shown to be a lead compound
in a family of triazole derivatives with anticonvulsant activity.

In addition, triazole compounds have many research and applications in the field of medicine, such as antihypertensive, contraception, sedation, hypnosis, anti-inflammatory, antibacterial, anti-allergic and other physiological activities and medicinal effects
.

Second, the field of pesticides

After decades of development, triazole pesticides have expanded the scope of application and control objects, from the past mainly used as fungicides, to now have developed a variety of efficient, low-toxicity herbicides, insecticides, plant growth regulators, showing strong vitality
.
At present, triazole compounds have become an important area for
the development of new pesticides.

1.
Fungicide
triazole fungicide has the advantages of high efficiency, broad spectrum, low toxicity, long duration, good internal conduction and bactericidal characteristics with protective and therapeutic effects, which is a milestone
in the development of agricultural fungicides.
It inhibits the biosynthesis of ergosterol by interacting with cytochrome P450, thereby achieving a bactericidal effect
.

At present, more than 40 varieties of triazole fungicides have been put on the market
.
In 1974, Bayer successfully developed triazolone is the first commercial product of triazole fungicides, and since then, the company has successively developed triazole, enazole, propiconazole and pentaconazole, which are currently commonly used triazole fungicides
for the prevention and control of wheat diseases in China 。 Recently developed new triazole compounds include Italian Isagro flutrezole, cyanamide hydroxyzole, Germany Bayer prothionazole and DuPont flusilazole, compared with commonly used triazolone and other triazole fungicides, the molecular structure of these products changes greatly, and most of them contain fluorine, not only for cereal crop rust, powdery mildew, but also for streak blight and other diseases have good activity and long
effective life.

Many triazole pesticides have both bactericidal and plant growth regulation effects
.
The growth regulators of triazole plants that have now been commercialized are mainly paclobutazole, tributazole, budazole and consulazole
.

2.
Herbicide Current herbicide
development emphasizes high activity while paying more attention to safety to ensure the safety of
non-target organisms, humans and the environment.
A series of heterocyclic compounds represented by triazole have become the main direction
of herbicide development due to their high efficiency, good selectivity and high biodegradation rate.

1,2,4-Triazole herbicide is a new class of herbicides researched and developed in recent decades, which has the characteristics of high efficiency, strong selectivity and high biodegradation rate, and is a promising herbicide
.
Triazolopyrimidine sulfonamide compound is a new herbicide developed by Dow Agro Company on the basis of sulfonylureas, which is a herbicide in upland land and safe for other crops, and has now become a hot spot
in the research of ALS inhibitors.

3.
Insecticides and acaricides Most triazole compounds mainly show bactericidal
activity, but some triazole compounds have insecticidal activity
.
Triazophos, developed by Farbuwerke Hoechst in Germany, is a broad-spectrum insecticide, acaricidal and nematicide that remains a highly effective insecticide
for agricultural pest control.
Chlorazophos is a variety developed by Ciba Jiaji and used in corn, cotton, rice, sugar beet and vegetables to control a variety of pests
.
Zophid, developed by Rohm and Haas, is a selective systemic insecticide that has a rapid inhibitory effect on insect cholinesterase and can be used to control peach aphids, cotton aphids, etc
.
Because it has good systemic properties, soil application can control leaf-eating aphids, and the agent migrates up and down in the plant, which has a protective effect
on the whole crop.

Third, the chemical industry

1.
Anti-corrosion triazole compounds, as a kind of heterocyclic compounds, have the advantages of being corrosion
inhibitors in structure, such as some electronegative atoms, conjugated systems, etc.
can provide active electrons and metal surface adsorption, so triazole corrosion inhibitors have attracted increasing attention
.
Corrosion experiments have confirmed that its corrosion inhibition effect on Fe in high temperature and high concentration HCl solution is close to or exceeds the same concentration of propynol
.
Compared with high toxicity and expensive propynol, triazole derivatives have the characteristics of low toxicity, moderate price and no toxic vapor in acidification operations, and are expected to replace propynol as the main agent
for corrosion inhibitors for high-temperature acidification operations in oil wells.

Triazole compounds belong to adsorption film-forming corrosion inhibitors, the molecular structure contains both adsorption groups and hydrophobic groups, after the adsorption group is directed adsorption on the metal surface, the hydrophobic group forms a shielding or barrier layer on the periphery, which isolates the metal surface from metal ions and dissolved oxygen and inhibits metal corrosion
.

2.
Light stabilizer benzotriazole light stabilizer
is a variety developed by Swiss Ciba-Geigy company, which is characterized by low toxicity, strong ability to absorb ultraviolet rays, and is widely used in polyolefins, polyester resins, coatings, food packaging, sunscreens, etc
.
Its mechanism of action is that when benzotriazoles are exposed to ultraviolet radiation, their molecular structure changes, converting harmful light energy into heat energy, thereby protecting the material
.
BASF's recently developed benzotriazole substance Uvinul 3034 plastic light stabilizer, which has the advantages of low volatility and good heat resistance, can be widely used in
PET, PA, PC and other products.

4.
Others

Yang Guangming et al.
of Nankai University studied the synthesis and adsorption properties of chelating resins containing 4-amino-1,2,4-triazole functional groups, and found that such resins have good adsorption selectivity for transition metals, and their adsorption mechanism is mainly due to the coordination of
triazole.
Zhang Shiping of China Lucky Film Research Institute reported that 1,2,4-triazole compound can be used as a light stabilizer and anti-fog agent, which has a good stabilizing effect
in addition to improving curve contrast.
The derivative of triazole is guanide, namely 3,5-diamino-1,2,4-triazole, which can be used to make chemical molds, clothing, paper, etc.
, and the intermediate of this compound can also be used as fungicides and pesticides
.
Triazole's sodium sulfonate salt derivative is a good cleaning agent and has good uses
in textiles.