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Al Mustansiriyah Journal of Pharmaceutical Sciences, 202, Vol. 2, No.3 (Review article)
AJPS (202) 65
Synthesis and Biological Activities of Some 1,2,4-Triazole Derivatives: A
Review
Dina Saleem M. Ameen*, Mohammed Dheyaa Hamdi*, Ayad Kareem Khan*
* Pharmaceutical Chemistry Department, College of Pharmacy, Mustansiriyah
University, Baghdad-Iraq.
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DOI:
Abstract:
This review is about 1,2,4-triazoles
include their synthesis; their physio-
chemical properties, SAR, reactions,
derivatives. Finally, their biological
activities with a demonstrated showing
different requirements to achieve different activity.
Key words: Heterocyclic, Triazole, Biological Activities.
ـــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــــ
1,2,4-triazoles *,**,* *
triazoles
Introduction
Five heterocyclic compounds define as
five-membered ring with one or more
heteroatom. Heterocyclic compounds offer
a wide range of physical, chemical, and
biological properties, allowing them being
used in a range of applications (1). The s-
triazole group is found in a number of
well-known medications, including
triazolam, alprazolam, and etizolam (2).
Triazole is a noteworthy class of
heterocyclic compounds that exhibits a
wide variety of pharmacological actions. It
is a five-membered, di unsaturated ring
structure with three nitrogen atoms in a
heterocyclic core and is also known as
pyrrodiazoles (3). 1,2,4-triazoles and some
of their derivatives have anti-inflammatory
properties, as well as analgesic, diuretic,
bronchodilator, anticancer, antioxidant,
and antibacterial properties (4). In the
industry, the use of selected 1,2,4-triazole
derivatives conferred good stability and
heat resistance in many molecular
materials, as well as highlighted the
corrosion inhibiting capabilities of certain
metals (5). Fungicides, bactericidals, and
herbicides are all considered 1,2,4-triazoles
in agriculture (6). A 1,2,3-triazole ring is a
desirable unit because it is resistant to
metabolic destruction because oxidative/
Reductive conditions, and enhances
Article Info:
Received Jul 2022
Accepted Oct 2022
Corresponding Author email:
ayad@uomustansiriyah.edu.iq
orcid: https://orcid.org/0000-0002-1941-054X
Al Mustansiriyah Journal of Pharmaceutical Sciences, 202, Vol. 2, No.3 (Review article)
AJPS (202) 66
solubility by attaching to biomolecular
targets. The pharmacophoric group refers
to this ring. It's also found in the structure
of drugs like tazobactam and cefatrizine
(7). Triazole is a crystalline solid that is
white to pale yellow in color and has a
mild, distinctive odor. It is soluble in
aqueous and alcohol, melts at 120°C, and
boils at 260°C. It exists as two isomeric
chemical compounds, 1,2,3-triazole and
1,2,4-triazole (Fig.1), both of which have
the molecular formula C2H3N3 and have a
molecular weight of 69.06 (8). The two
isomers are as follows (9)
i ii
Pellizzari Reaction
The Pellizzari reaction is the process of
synthesizing 1,2,4-triazole derivatives
from a solution of amide and acyl
hydrazide. Heating a mixture of formamide
and hydrazine hydrochloride with KOH
produces 1,2,4-triazole, the compound
2,3,5-triphenyl-1,2,4-triazole was
synthesized using benzamide and benzoyl
hydrazide, for example high temperature
and long time (10)
Figure (1): The Pellizzari Reaction.
Einhorn–Brunner reaction
The Einhorn–Brunner reaction is the
synthesis of 1,2,4-triazoles via
condensation between hydrazines or mono
substituted hydrazines and diacylamines in
the presence of mild acid at 140°C (11).
Using this scenario: 1,5-diphenyl1,2,4-
triazole was synthesized from N-formyl
benzamide and phenyl hydrazine (12).
R1, R2, R3: alkyl or aryl
Figure (2): Einhorn–Brunner reaction.
Synthesis of 1,2,4- triazoles from nitriles
and hydrazonoyl chlorides via 1,3-
dipolar cyclo-addition
1,3 dipolar cycloaddition synthesis of
1,3,5-trisubstituted 1,2,4-triazoles from
nitriles and hydrazonoyl chlorides is
carried out in a single flask (13).
1,2,4-triazole, (ii) 1,2,3-triazole
Al Mustansiriyah Journal of Pharmaceutical Sciences, 202, Vol. 2, No.3 (Review article)
AJPS (202) 67
Figure (3): Synthesis of 1,2,4-triazole derivatives.
The reaction can be applied to both
aromatic and al aliphatic nitriles with N-
arylhy-drazonoyl chlorides having
different substitution
(14). A reasonable 1,3-dipolar
was suggested
for the reaction of imidate (resulted from
nitrile) with nitrilimine (resulted from
hydrazonoyl) chloride in one flask to
generate the proposed 1,2,4-triazole (15).
Synthesis of 1,2,4-triazoles via copper-
catalyzed domino nucleophilic
substitution/oxidative cyclization
The first strategy is based on a Cu-
catalyzed domino intermolecular
nucleophilic substitution/ring closure
between two molecules of amidine HCl in
a single flask (16). This is a one pot which
involves the formation of two bonds A
copper-catalyzed domino reaction
involving two molecules of an imidate
hydrochloride and an ammonium source
can also yield 3,5-diaryl triazoles in
one pot (17). Two carbon-nitrogen bonds
and one nitrogen-nitrogen bond are formed
in a single synthetic step using this
approach (18).
Figure (4): General scheme for Synthesis of 1,2,4-triazoles via copper-catalyzed
domino nucleophilic substitution/oxidative cyclization
Synthesis of 1,2,4-triazoles by
microwave-assisted N-acylation of
amide derivatives and the consecutive
reaction with hydrazine hydrochlorides
For the synthesis of 1,3,5-trisubstituted-
1,2,4-triazoles, N-acylation of amides and
cyclization with hydrazines is considered
one of the finest procedures (19).
Reactions were carried out under mild
conditions within a short time and yielding
good product yields. The synthesis can
alternatively be done in a one-pot
sequential reaction utilizing K2CO3 or
H2SO4 and microwave irradiation to
Al Mustansiriyah Journal of Pharmaceutical Sciences, 202, Vol. 2, No.3 (Review article)
AJPS (202) 68
benzamide with acetic anhydride to
produce N-acylate benzamide (20). The
process was completed in 3 minutes to the
application of microwave irradiation (as a
source of energy) (21).
Figure (5): Synthesis of N-acylate benzamide.
Pyridine use a catalyst to help producing a
purer 1,2,4-triazoles in some situations.
The synthesis could be improved by
utilizing phenylhydrazine HCl, a greater
power of microwave irradiation power
(300 W), and a higher temperature (200
C) (22).
Figure (6): Synthesis of 1,2,4-triazole derivatives.
N-arylation of 1H-1,2,4-triazole
The use of prominent facet CuO
nanoparticles as a catalyst for 1,2,4-
triazoles N-arylation at room temperature
with aryl iodides under ligand-free
conditions is reported as a simple, efficient
technique and economic method (23). The
catalyst was reusable, and a wide range of
substrates were successfully reacted.
Because of the broad breadth of this
catalyst, researchers are looking into
transformations using less reactive azoles
such as pyrazole and imidazole (24).
Several azole derivatives are found to be
successful in combining with aryl iodide to
produce the necessary N-arylated products
in high yields (25).
Figure (7): General equation of N-arylation of 1H-1,2,4-triazole.
Biological activities of 1,2,4-triazoles
The chemistry of 1,2,4-triazoles and their
fused heterocyclic derivatives attracted a
lot of attention and have been use in a wide
application in life. A number of 1,2,4-
triazoles have been included into a diverse
range of therapeutically interesting drug
competitors that have the following
qualities (26):
Antibacterial activity
Al Mustansiriyah Journal of Pharmaceutical Sciences, 202, Vol. 2, No.3 (Review article)
AJPS (202) 69
Gram- negative and Gram-positive
bacterial strains were inoculated with
1,2,4-triazole compounds newly
synthesised for their ability to suppress
growth in vitro.
Drug-resistant strains (e.g., MRSA, VRE)
should be tested for possible antibacterial
properties of newly discovered
compounds. Some derivatives have also
shown antituberculosis action, as
evidenced by numerous investigations
(27).
Triazole hybrides of quinolone
antibacterial agents
A considerable number of 1,2,4-triazole
combinations with fluoroquinolone
medicines have been combined into
therapeutically promising drug candidates
(1). It has been shown that novel nalidixic
acid derivatives with antimicrobial
activity, such as 1,2,4 triazole-3-thione
derivatives 1-2 (Figure 9), have
antibacterial effects on both Gram-positive
(B. subtilis, S. aureus) and Gram-negative
bacteria (P. aeruginosa, E. coli and K.
pneumonia) (1). The MIC of 16 g/mL for
the azomethine derivatives against P.
aeruginosa was shown to be highly active.
If the 2-phenyl ring has a chloro-
substituent (compound 2) than compounds
1 and 3, showed the greatest antibacterial
effectiveness against all tested microbes,
compared to streptomycin, which had an
MMIC of 2–15 mg/ml.
Figure (8): 1,2,4-triazole-3-thione derivatives.
1.1.1. 1,2,4-Triazoles as anti-tubercular
agents
Most people who get TB get it from
Mycobacterium tuberculosis, which is
responsible for the disease in around a
third of the world's population. This
bacteria's proliferation is inhibited by a
number of medications that have been
developed specifically for this purpose. A
Al Mustansiriyah Journal of Pharmaceutical Sciences, 202, Vol. 2, No.3 (Review article)
AJPS (202) 70
multidrug regimen is the only treatment
option for TB infections right now (28).
UNICEF and WHO have initiated directly
observed treatment short courses (DOTS)
to combat long-term non-adherence and
multidrug resistance (MDR) or XDR. Anti-
tuberculosis properties have been
discovered in a collection of pyridine-
1,2,4-triazole derivatives that were
produced by researchers (29). Using
rifampicin as a reference medication, Rode
et al. reported the synthesis and biological
activity of novel 3-aryl-5-(alkylthio)-1H-
1,2,4-triazoles derivatives in 2016 (30).
Twenty-five produced compounds of
triazole derivatives showed promising anti-
TB activity in the dormant stage and 20
compounds in the active stage, according
to the anti-mycobacterial activity data. The
anti-TB activity of compounds 69 (IC50 =
0.03 g/mL) and 70 (IC50 = 0.89 g/mL) was
exceptional (31).
It has been reported that Dixit and his
colleagues have developed hybrid triazole
compounds for the treatment of multiple-
resistant M. tuberculosis. They created a
verapamil/thioridazine hybrid (TZ). When
tested against M. tuberculosis, compounds
71-74 had MIC values as low as 8, 4, 32,
and 64 g/ml. They hypothesised that the
synergistic action of these chemicals
would lead to increased potency and
decreased toxicity (32).
Antifungal Activity
Antifungal drugs such as voriconazole and
fluconazole, which have been approved by
the FDA, are the major antifungal agents
used to treat invasive fungal diseases.
Antifungal triazoles directly inhibit the
14a-lanosterol demethylase (CYP51) in
CYP450, which results in the inhibition of
sterol biosynthesis in cell membranes (33).
When Wang et al. made and tested phenyl-
pyrazole and piperazine thiones in 2016,
they discovered that they were effective
antifungal agents. To compare the percent
concentration inhibition of mycelium rate
of growth with the positive controls
carbendazim, triadimefon and
chlorothalonil, the synthesised compounds
were tested against six fungi (34).
Maximum age inhibition percentages of
75% and 91.8 percent were found for
1,2,4-triazole thione 65. Compound 65 was
the most effective of the bis-1,2,4 triazole
thiones against Rhizoctonia cerealis, with a
maximum inhibition of 83.9 percent (35).
Figure 10: General structure
of antifungal 1,2,4-triazoles.
Figure 9: General structure of anti TB
1,2,4-triazole.
Figure 10: General structure of
compounds .
Al Mustansiriyah Journal of Pharmaceutical Sciences, 202, Vol. 2, No.3 (Review article)
AJPS (202) 71
Antiviral Activity
For viral infections, a wide variety of
antiviral drugs are available, but these
agents have limitations like a limited
spectrum of action, drug resistant strains
and inability to combat latent viruses.
Since this is the case, newer antiviral drugs
must be developed that have a broader
antiviral spectrum and are not susceptible
to drug resistance (36). For the first time,
Chudinov et al. synthesized and tested
ribavirin analogues for treatment of herpes
simplex, hepatitis C, syphilis and influenza
A viruses. No toxic effects were observed
at the highest concentration of the
synthesized analogues (1250 M).
Compound 68 was the most active of the
synthesized analogues, with an EC50 value
of 19 M (37).
Anticancer Activity
They were inspired to develop many drugs,
one of which is the cancer-fighting agent
thiazoles. There are numerous heterocyclic
rings containing nitrogen atoms in both
natural and synthetic products, which have
powerful anticancer properties against a
wide range of human cancer cell lines (38).
Letrozole is an aromatase inhibitor-
containing triazole structural unit used to
treat cancer. It has been found that the
most important subclass of bioactive 5-
membered heterocyclic organic
compounds for medicinal chemistry is
1,2,4-thiadiazoles, which show
significant biological actions such as
cyclooxygenase inhibitors, human
leukemia (39). 3,5-bis(pyridin-3-yl)-1,2,4 -
thiadiazole (2) is an aromatase inhibitor
and is used to treat a variety of cancer
types (40).
Structure activity relationships of
triazole derivatives
SAR such as triazoles, it can highlight the
concept and benefit of using triazoles in
compounds (41). Triazoles can be
employed for stabilization because have
multi electron pair in nitrogen atoms, chain
lengthening, drug receptor interactions,
activity, structural lengthening, and even
degradation prevention. As a result, each
chemical should be investigated separately
(42). Azoles are antifungal medicines that
work by inhibiting the enzyme lanosterol
14-demethylase (CYP51), which is
involved in fungi's sterol production.
Itraconazole, fluconazole, posaconazole
and voriconazole are all orally active
azoles that have a broad spectrum of
activity against yeasts and filamentous
fungus (43). Azole medicines have been
utilized as first-line antifungal treatments
because of their broad antifungal spectrum,
higher efficacy, and lower toxicity (44). A
robust a structure-activity model
connections time and money could be
factors helpful in designing and surveying
novel azoles, which are a major family of
significant antifungal medicines (45).
Important structural properties for future
investigations in the field can be obtained,
Figure (11): Structure of compound 68.
Figure 12: Structure of letrozole.
Al Mustansiriyah Journal of Pharmaceutical Sciences, 202, Vol. 2, No.3 (Review article)
AJPS (202) 72
modelled, and summarized from other
triazoles that have already been produced
(46). All azole medicines, in general, share
the same basic model, which includes A
heme binding group, side chain A, side
chain B, and a three-atom connector (47).
A. Heme binding groups
CYP51 enzyme lanosterol 14-demethylase
(CYP51) is a member of the CYP51 family
of cytochrome P450 enzymes, which is
responsible for the antifungal activity of
azoles (48). Iron in the triazole ring of the
azole medicines can be substituted for the
sixth coordination position of the iron in
lanosterol's 14-demethylase cofactor.
Ergosterol production in fungus is
regulated by the 14 a-demethylation of
lanosterol (49). Ergosterol levels in cell
membranes drop when CYP51 is inhibited.
As a result, the lipid bilayer becomes less
fluid and fungal growth is slowed. The 14
a-methyl-3,6-diol produced from 14-
methyl-fecosterol is one of the hazardous
metabolites that accumulates when CYP51
is inhibited (50). The heme ring is essential
for the azole group's antifungal activity
without any modification that attach to the
linker with N-1 atom. The porphyrin active
site is bounded by triazole or tetrazole
rings, with the iron of the active site
aligned with the length of its coordinated
bond. (43). Adding a simple or bulky
group to the N-4 of the triazole may have
an effect on its activity because it prevents
the triazole from attaching to the heme
(51). Triazole compounds also contain:
B. The three atoms linker:
A three-atom linker is
only one of several
possible configurations for this linker.
There is a particular gap between the arms
of the structure, resulting in higher
potency, because of this three-atom
configuration (52).
There are few exceptions to this rule,
including clotrimazole analogues and vinyl
imidazole derivations, for which carbon is
the linker group's number one atom (53).
In the linker, the majority of the atoms are
carbon-2 and carbon-3. The
carbons chirality has a significant impact
on the antifungal action (54).
For example:
• Adding a hydroxyl group to C-2, for
example, has various advantages,
including increased potency via water
and an indirect H-bond molecules in
Enhanced pharmacokinetics, the active
site, and water solubility, as well as
more stable and better tolerated
metabolism (55). Several prodrugs,
such fluconazole phosphate ester,
voriconazole, and ravuconazole
phosphate ester, should also complete
the C-2 substitution. (56).
• C-3 could benefit from the addition of
a methyl group.
Figure (13): General structure of antifungal 1,2,4-triazoles.
Al Mustansiriyah Journal of Pharmaceutical Sciences, 202, Vol. 2, No.3 (Review article)
AJPS (202) 73
Lanosterol's C-13 binding pocket is filled
by the methyl group attached to side-chain
B, which goes in the antiperiplanar
direction of side-chain A. There is also the
necessary activity in other
substituents such as CH (double bond with
C-3) and two F or two methyl (non-chiral
C-3) (57).
Figure (14): Structure of Lanosterol.
An oxygen, sulphur, or NR2 (such as
miconazole) may be C-3, which retains
antifungal action and also conformational
limitation of the structure, such as di-
oxalene (C-2 and C-3) (ketoconazole or
itraconazole). The other pharmacokinetic
features are not enhanced by them (58).
Side chain A
Aside from the lanosterol 17-alkyl chain
and the hydrophobic tunnel that it occupies
of halogenated phenyl is important for the
inhibitory impact of side chain A (59).
Y132, for example, has a stacking
interaction with it (a conserved amino acid
found in fungi).
Only groups bigger than chlorine in C-2
and C-6, which have weak steric adherence
and diminish the inhibitors binding affinity
in the active site, are acceptable
substitutions of the phenyl ring (60).
Atoms of fluorine in C-2 and C-4 have a
stronger potency than those in C-1 and C-
2. Instead of substituting 4-fluorophenyl,
additional big bulky groups could be used
to retain the molecule's capacity to inhibit
CYP51 in the para position. (42).
Side chain B.
When optimising side chain B, one could
develop potent and favourable
pharmacokinetic features solely with this
side chain's optimization in mind. In third-
generation and hybrid structures, this side
chain has been subjected to a wide range of
alterations (61). Commonly, a linker
attaches to the tree atom linker C-3, and
antifungal activity ranges from other types
of linkers here. Studying the antifungal
properties of these compounds has shown
that they are well-tolerated and can be used
as linkages, but the antifungal activity is
reduced by ester, esteramide, and NHR
(62).
The aforementioned linkers could be used
to link modifications to the target protein's
deep binding cleft, which can form a
variety of significant hydrophobic, steric,
and H-bond interactions (63). Fluconazole,
ravuconazole, and voriconazole are
examples of short-tail structures with
potential small changes to the linkage (64).
When small hydrophobic, electron-rich,
and electron-withdrawing groups in ortho-
or para-positions join a phenyl or
heteroaromatic ring to the linker (such as –
CNs and chlorinated heteroaromatic rings),
potency is increased through possible
steric and hydrophobic interactions (65).
Al Mustansiriyah Journal of Pharmaceutical Sciences, 202, Vol. 2, No.3 (Review article)
AJPS (202) 74
Figure (15): (a) voriconazole, (b) ravuconazole, (c) fluconazole.
As an example, a fluorine on the
pyrimidine ring of the voriconazole and the
fungus Tyr122 establish an H-bond
contact. While M-position substitutions are
detrimental to activity. Oxygen (ether,
carbonyl) or Nitrogen (NR2) may be used
as an H-bond acceptor substitution in long-
tail structures like itraconazole and
posaconazole, at the para-position of the
para-phenyl ring. (66). This substitution in
figure 16 appears in some active sites, to
form an H-bond with a residue. Another
aromatic group This H-bond acceptor
group binds to steric and Van der Waals
contacts in the active site. (67).
Figure (16): (a) Itraconazole and (b) Posaconazole.
Triazole derivatives bind quickly to a
number of enzymes and receptors due to
their unusual structure, which includes
three nitrogen atoms and an electron-rich
system (68). Compound AA was shown to
be the most powerful of the 1,2,4-triazole
compounds examined, capable of reducing
viral plaques by 50% at an 80 mM dose to
neutralize herpes simplex virus-1 (HSV-1)
(69). Furthermore, compound AA had
greater selectivity than acyclovir (>200
mM vs. 80 mM) (37). The primary notion
behind AA is that it can make numerous
hydrogen bonds in the HSV-1 thymidine
kinase active site (70). Furthermore, the
triazole plays two important roles in this
compound: despite its participation in H-
bonding, it also adds stability to the
complex and acts to grow the compound in
order to fit the key groups to the active
sites (71).
The presence of two R arms prevents the
ester and pyrimidine groups from being
degraded by pH (72).
Al Mustansiriyah Journal of Pharmaceutical Sciences, 202, Vol. 2, No.3 (Review article)
AJPS (202) 75
Figure (7): Structure of triazole derivative.
It has been reported that a number of 1,2,4-
triazolo [4,3]-quinoxaline derivatives can
be prescribed as antimicrobial and antiviral
agents after being synthesised (73).
The 1,2,4-triazolo [3,4] [1,3,4] thiadiazines
were synthesised and tested for antiviral
activity against JEV and HSV-1.
Compound AB (ED50 7.8 mg/mL)
demonstrated reasonable activity
against JEV with 50% inhibition and
therapeutic index value of 32 (74).
There are two R arms in the core of this
compound, just like the AA compound.
However, it is different from the former in
that it has thiopyridazine rings instead of
pyrimidine, which is more effective. It was
discovered that the AC compounds showed
potent antiviral properties against
coxsackievirus B3 (CVB3) and enterovirus
71 (EV71) after a screening of 44 chiral
triazole derivatives (75). In comparison to
ribavirin (SI: 15), they demonstrated a
higher level of action.
Figure (19): Compound AC.
SAR studies showed that Benzyl units
(Ar) or 4-methoxyphenyl short alkyl
chains (R) were found to be favourable for
antiviral activity in SARs (76). The
introduction of 1,2,4-triazole contributes to
the H-bonding as well as to the overall
compound's stability. [1,2,4]pyrimidin-5
(4H)-ones like AD compound have been
evaluated for antiviral ability against
human enteroviruses such as (Cox
Figure (18): Structure of triazole
derivative.
Al Mustansiriyah Journal of Pharmaceutical Sciences, 202, Vol. 2, No.3 (Review article)
AJPS (202) 76
B3), (Cox B1), Poliovirus 3, and Human
Rhinovirus 14, 21, and 71 (77). Compound
AD is a promising lead compound for
developing broad spectrum anti-
enterovirus drugs (78).
Figure (20): Structure of triazole derivative.
A decrease in the Triazole's activity and
potency may be attributed to the
introduction of some bulky groups to the
triazole, which may hinder the Triazole's
capacity to share hydrogen bonds. Also,
triazole is used to stabilise the compound
by electro-resonance forces and to increase
the molecule's size (79). Studying the
1,2,4-triazole SARs as anti-TB shows the
main characteristics of these compounds.
Compounds have a number of key
characteristics, such as:
• 1,2,4-triazole ring, which is crucial for
the action and binding of TB to
intracellular targets. Attaching or
adding -NO2 to the Triazole group's
third carbon improves binding, which
in turn improves this role's high-limit
performance. However, Triazole and
NO2 both have poor TB activity,
resulting in the formation of new
groups (80).
• Links atoms range from 2-methyl to 5-
methyl groups, which are the other
component. The nitro-triazole ring is
sandwiched between this group and the
sulfamido group. Several investigations
have demonstrated that the aerobic
anti-TB activity is diminished when the
length of the linker group is decreased
(from a 4-methylene to a 2-methylene
and 3-methylene) (79). While several
antitubercular agents are available, two
compounds, BC and BB, have the most
potent antitubercular action against
both hypoxic and aerobic strains of TB.
• Bulky-withdrawing groups, such as
phenyloxyphenylacetamides,
propanamide analogues, benzyloxy
group are crucial for the binding and
activity of the medication against Mtb
(81).
Figure (21): Compound BB.
Figure (22):Compound BC.
Al Mustansiriyah Journal of Pharmaceutical Sciences, 202, Vol. 2, No.3 (Review article)
AJPS (202) 77
Figure (23): Synthesis of triazole derivatives.
Conclusions
1,2,4-triazoles derivatives have a wide
range of biological activities, which are
thought to be pharmacologically essential
to the nucleus. The chemistry of triazoles
and their heterocyclic derivatives has
gotten a lot of attention in recent years
because of their synthetic and biological
relevance. Many 1,2,4-triazole-containing
ring systems, for example, have been
incorporated into a wide range of
therapeutically promising drug candidates.
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