American Journal Of Biomedical Science & Pharmaceutical Innovation
19
https://theusajournals.com/index.php/ajbspi
VOLUME
Vol.05 Issue03 2025
PAGE NO.
19-24
10.37547/ajbspi/Volume05Issue03-05
Safety assessment of the 4- (6-phenyl-7h - [1,2,4] triazolo
[3,4-b] [1,3,4] thiadiazine-3-
yl
) -aniline compound and the
effects of the substance on respiration and cardiac
activity
Rahimboev Suhrob Davlatyor o‘g‘li
Institute of Chemistry of Plant Substances Academy of Sciences of Republic of Uzbekistan
Sanoev Zafar Isomiddinovich
Institute of Chemistry of Plant Substances Academy of Sciences of Republic of Uzbekistan
Khamroyev Tolmas Tolibovich
Institute of Chemistry of Plant Substances Academy of Sciences of Republic of Uzbekistan
Abdinazarov Ibrokhimjon Tuychiyevich
Institute of Chemistry of Plant Substances Academy of Sciences of Republic of Uzbekistan
Rashidov Sohib Zamon o‘g‘li
Institute of Chemistry of Plant Substances Academy of Sciences of Republic of Uzbekistan
Ismoilova Dilnoza Safaraliyevna
Institute of Chemistry of Plant Substances Academy of Sciences of Republic of Uzbekistan
Elmuradov Burkhon
Institute of Chemistry of Plant Substances Academy of Sciences of Republic of Uzbekistan
Received:
28 January 2025;
Accepted:
27 February 2025;
Published:
25 March 2025
Abstract:
4-(6-phenyl-7H-[1,2,4]-triazolo-[3,4-b] - [1,3,4] - thiadiazine-3- yl) - aniline compound belongs to the
group of triazole derivatives, belongs to class IV low-toxic compounds in acute toxicity, and sodium belongs to the
compounds of this group, taking into account the presence of Due to its ability to block ion channels, it can be
concluded that the 1.0 mg/kg dose studied during the experiment led to bradycardia in exchange for a decrease
in the activity of the sinus node, which is considered the main regulator of the first-order heart rhythm.
Keywords:
Acute toxicity, accumulation, number of breaths, blood pressure, cardiac activity, rhythm.
Introduction:
Epilepsy is a chronic disease that is
accompanied by a violation of the functioning of the
neurons of the central nervous system, characterized
by seizures and loss of ES Hus in exchange for a
dysbalance of the activity of the excitatory and
inhibitory mediators of the brain [1, 2]. Over the past
few decades, more than 20 new antiepileptic drugs
have been created, including escarbazepine acetate
[3], perampanel [4] and ezogabin [5]. However, a large
percentage of the population does not achieve a stable
anticonvulsant effect with monotherapy [6], and about
American Journal of Applied Science and Technology
20
https://theusajournals.com/index.php/ajast
American Journal of Applied Science and Technology (ISSN: 2771-2745)
30% of patients have refractory epilepsy and require a
combination of treatment [7, 8]. In addition, many
antiepileptic drug drugs have serious side effects [9, 10]
and need lifelong treatment. Therefore, the search for
more selective and safer anticonvulsant agents is of
particular interest. In the same point of view, several
antiepileptic drugs of different approaches were
studied for the development of [11-13]. The GAMK-A
receptor is a major target for a number of
therapeutically important drugs such as barbiturates,
steroids, anesthetics, and benzodiazepines [14,15].
1,2,4-triazole derivatives have been found to exhibit
many biological activities, including anticonvulsant [16,
17], anti-fungal [18-20], neurotrophic heterocyclic
activity [21-24], anti-inflammatory [25-27], and
antibacterial [28-31], based on experiments. The
molecular structure and bioactivity of commercially
available antiepileptic drugs are spatially long
hydrophobic domains (typically phenyl rings),
hydrogen-binding domains, and electron-donor
fragments, elements required for high anticonvulsant
activity. In addition, various other compounds with a
1,2,4-triazole
moiety
were
found
to
have
anticonvulsant properties in several animal models of
epilepsy [32-35]. These findings prompted us to look
for
1,2,4-triazole-based
compounds
with
anticonvulsant activity and determine if the derived
derivatives could act on the allosteric site of GABA-A
receptors. The combination of 4-(6-phenyl-7h-
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-3-yl) - aniline
conditionally (D-286) has been studied for its overall
pharmacological activities and effects on vital organs.
METHODS
4-(6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-
3- yl) is an aniline compound, with the substance twine-
80 as a solvent, ethaminal-sodium as a narcosis agent,
aconitin substance for arrhythmia calling purposes,
mass 18-24 g white mice, 180-220 g white rats, cat with
a mass of 2.2 kg, ZOOMED IM-10 cardiomonitor, a
Schiller cardiovit at-1 electrocardiograph device was
used. Experiments were carried out in a room with 30-
60% air humidity, 400 Lux lighting at a temperature of
15-250C. The substance was observed for 14 days after
one administration. The compound was evaluated for
acute toxicity in oral white mice, venous white rats,
cumulative properties, effects on vital organ function,
and effects on heart rhythm. The results obtained were
processed using statistical methods.
RESULTS AND DISCUSSIONS
1, Experiments on acute toxicity of the 2,4-triazole
derivative D-286 were performed in white mice by oral
administration of twin-80, administered at a dose of
500 mg/kg to a dose of 4,500 mg/kg to assess the
resorbtive effect and the time of death.
In acute toxicity experimental animals, rates are
assessed from a dose of up to 100% mortality with
significant changes in the div. Each group receives at
least 6 experimental animals. Acute toxicity of the
compound
4-(6-phenyl-7H-(1,2,4)-triazolo(3,4-b)-
(1,3,4)-thiadiazine-3-yl) - aniline (D-286) was studied in
white mice by oral administration at a dose of 500
mg/kg to 4,500 mg/kg. At a dose of 500-1000 mg/kg, no
significant changes were observed in experimental
animals. From a dose of 1500 mg/kg, general
powerlessness, motion attenuation began to be
observed. With an increase in dose at doses of 2000-
4500 mg/kg, tremor, tail reaction, sustained Tonico-
clonic seizures, and death began to be observed at
intervals of 3-7 hours. The average death dose was
LD50 = 2150 mg/kg. The compound D-286 was studied
intravenously at a dose of 100-500 mg/kg in white rats
with a mass of 170-230 g. From a dose of 300 mg/kg,
death began to be observed in experimental animals
due to respiratory failure, tremor, seizures. The results
obtained were LD50=351.25 mg/kg when the average
death dose was administered intravenously after
statistical processing.
Determination of cumulative property in the
compound D-286, calculated from 1,2,4-triazole
derivatives with high anti-seizure activity, in different
proportions of the dose of LD50. It was carried out
using the method proposed by R. K. Lim. No deaths
were reported during the experiment and the 15-day
follow-up period after the compounds were sent for 28
days. The results obtained are shown in Table 1.
Table 1.
Assessment of cumulative effects of compounds with activity higher than 1,2,4-
triazole derivatives when administered orally in white mice
Experience days
1-4
5-8
9-12
13-16
17-20
21-24
25-28
cumulative
coefficient
Cc
LD
50
share
0.1
0.15
0.22
0.34
0.5
0.75
1.12
American Journal of Applied Science and Technology
21
https://theusajournals.com/index.php/ajast
American Journal of Applied Science and Technology (ISSN: 2771-2745)
Cc=27348/2150=
12.72
According to the results obtained, it turns out that the
compound D-286 of the 1,2,4-triazole derivative does
not have a cumulative property.
The effect of drug substance on breathing and heart
function
. Study of the effect of D
–
286 on arterial blood
pressure in a research setting. Studies investigating the
effects of D-286 on arterial blood pressure were
conducted on a ZOOMED IM-10 cardiomonitor, in cats
with a div weight of 2.2 kg, the substance studied was
sent to the intra-abdominal introduction at a dose of
1.0 mg/kg. Prior to the experiments, preliminary
indications demonstrated in cardiomonitor were
recorded by calling narcosis using a cat's intra-
abdominal introduction 40 mg/kg dose of ethaminal
sodium. In studies, arterial blood pressure was
monitored for 2 hours, starting from 10 minutes of the
experiment, and the indicators on the cardiomonitor
were recorded. In this experiment, in addition to
arterial blood pressure, indicators such as the number
of heart contractions, div temperature, saturation
were also recorded. As a result of the study carried out,
it was assessed by the differences that occurred in
relation to the initial indicators demonstrated on the
cardiomonitor. In studies carried out, arterial blood
pressure under the influence of a dose of 1.0 mg/kg of
the D-286 compound was observed almost no changes
in the oxygen saturation of hemoglobin i.e. saturation
indicators. A decrease in div temperature at 1-1.5
℃
,
a decrease in the number of breaths, as well as a return
to the initial state after 2 hours can be seen. In contrast,
the number of cardiac contractions can be seen to have
increased compensatorically after initial narcosis from
124 to 141 times, and later decreased experimentally
from 135 to 94 times after administration of the
studied substance, leading to bradycardia (Table 2).
Table 2.
The effect of D-286 on AQB, number of breaths and other indicators.
№
Substance D-286 at a dose of 1.0 mg / kg
Indicators studied in cardiomonitor
The time when the
observation was
carried out in
minutes
Blood pressure in
mmHg
heart rate
number
Number
of
breaths
Body
temperature
at
℃
Saturation in
%
1.
Initial condition
125/83
124
12
37.6
87
2.
D-286 1.0 mg/kg
10 minutes after
administration
113/46
141
11
37.6
87
3.
20
114/57
135
9
36.9
85
4.
30
121/80
130
8
36.3
85
5.
40
126/71
121
8
36.8
85
6.
50
119/66
114
8
36.6
84
7.
60
119/66
113
8
36.5
86
8.
70
123/76
111
8
36.1
85
9.
80
118/76
105
7
36.8
86
10.
90
125/83
104
7
36.6
85
11.
100
135/79
100
7
36.7
85
12.
120
133/78
98
9
36.8
86
American Journal of Applied Science and Technology
22
https://theusajournals.com/index.php/ajast
American Journal of Applied Science and Technology (ISSN: 2771-2745)
13.
130
129/82
94
12
37.3
86
Determination of the effect of the D-286 compound on
cardiac electrophysiological indicators. The effect of
the D-286 compound on the electrophysiological
indicators of the heart scientific studies conducted in
the study div weight 180-220 g. in laboratory white
rats up to, SCHILLER CARDIOVIT was achieved by
recording on the standard II connection of the AT-1 ECG
hardware. For this purpose, the studied compound is
evaluated for normal cardiac activity as well as
antiarrhythmic activity in peripheral Genesis disorders
of the heart rhythm through arrhythmia models called
through a chemical compound of arrhythmic nature.
Before the start of the experiment, an
electrocardiogram (ECG) analysis was carried out on
the standard connection II in animals, and after that
aconitin was sent to the tail vein in rats with a dose of
12-15 mcg/kg, which is called mixed in animals of all
experimental groups-ventricular extrasystole. The
formation of cardiac rhythm disturbances began in 1-2
minutes after the cessation of administration of
aconitin, based on the rule. Writing in EKG was
conducted in 1; 3; 5; 10; 15 and 20 minutes after
administration of aconitin. The substance under study
was administered 60 minutes before oral aconitin
administration at doses of 1.0; 10.0; 30.0 and 60.0
mg/kg, and at doses of 1.0; 2.0 and 10.0 mg/kg after
arrhythmia caused by aconitin. All the experiments
carried out were carried out in accordance with the
Control Research Scheme. The activity of the studied
compound was assessed by its prevention of heart
rhythm disturbances called aconitin.
Initially, the compound D-286 was used through the
above-mentioned dosages and injection methods, the
changes caused by its action on the normative
electrophysiological indicators of the heart were
recorded in the II standard connection of the ECG for
60-70 minutes after the introduction of the substance.
When the D-286 compound was administered orally at
doses of 1.0; 10.0; 30.0 and 60.0 mg/kg, it was observed
that the number of heart contractions in 50-60 minutes
of the study decreased by an average of 30-35 times
compared to the original. No changes were observed in
pqrst tooth voltage, with the intervals of PQ(R) and QRS
(T) extending by 4-6% compared to the original. These
results obtained indicate a decrease or slowdown in
cardiac AV and Inter-ventricular conduction under the
influence of the studied substance.
It was observed that the substance studied showed
anti-arrhythmia
activity
called
by
aconitin,
corresponding to each dose, when administered orally
at the doses noted above. Heart rhythm disturbances
in the form of polyphocals associated with cardiac
conduction disorders occurred in the first minute after
the introduction of aconitin at a dose of 1.0 mg/kg, and
symptoms of recovery began to occur in these rhythm
disturbances, which occurred from 11 minutes of the
study, and a complete recovery of the rhythm was
observed in 20-25 minutes. With aconitin exposure at
doses of 10.0; 30.0 and 60.0 mg/kg, heart rhythm
disturbances in the form of polyphocals occurred at
4.0; 2.0 and 1.5 minutes of the study, respectively, and
from 10; 13 and 15 minutes began to develop signs of
a begging of a disturbed rhythm. At a dose of 10 mg/kg,
after 10 minutes of the study, the broken rhythm was
completely restored according to all indicators, while at
a dose of 30 mg/kg it was restored after 18 minutes, at
a dose of 60 mg/kg, the rhythm recovery time was 5
minutes.Also, rhythm disturbances caused by aconitin
exposure when the substance studied was injected
intravenously for treatment purposes-from 3-4
minutes of the study under the action of a dose of 1.0
mg/kg-to the recovery of the disturbed rhythm-this
rhythm recovery took up to 8-10 minutes. Signs of
recovery of rhythm disturbances caused by aconitin
exposure at doses of 2.0 and 10.0 mg/kg began to occur
from 5 and 11 minutes of the study, and a complete
recovery of rhythm occurred at 10 and 16 minutes.
CONCLUSION
Thus, the compound 4-(6-phenyl-7H-[1,2,4]-triazolo-
[3,4-b]-[1,3,4]-thiadiazine-3-yl)-aniline belongs to the
group of triazole derivatives, according to Stefanov on
acute toxicity, class IV is among the less toxic
compounds, and considering the presence of the
sodium ion channel blocking property among these
group compounds, the sinus, which was considered the
first-order main controller of heart rhythm at a dose of
1.0 mg/kg studied during the experiment it can be
concluded that nodini caused bradycardia in exchange
for decreased activity. Although few signs of
bradycardia occur under the influence of the
substance, it does not negatively affect the normative
electrophysiological indicators of the heart. In addition,
in cardiac arrhythmias called by aconitin, its activity
against arrhythmias can be associated with the siege of
Na+ channels.
REFERENCES
Strine TW, Kobau R, Chapman DP, Thurman DJ, Price P,
Balluz LS. Psychological distress comorbidities and
health behaviors among U.S. adults with seizures:
results from the 2002 National Health Interview Survey.
Epilepsia. 2005 Jul;46(7):1133-9. doi:10.1111/j.1528-
American Journal of Applied Science and Technology
23
https://theusajournals.com/index.php/ajast
American Journal of Applied Science and Technology (ISSN: 2771-2745)
1167.2005.01605.x, PMID 16026567.
Ashhar MU, Ahmad MZ, Jain V, Agarwal NB, Ahmad FJ,
Jain GK. Intranasal pitavastatin attenuates seizures in
different experimental models of epilepsy in mice.
Epilepsy Behav. 2017
Oct 1;75:56-9. doi: 10.1016/j.yebeh.2017.07.004, PMID
28826009.
Soares DA Silva P, Pires N, Bonifacio MJ, Loureiro AI,
Palma N, Wright LC. Eslicarbazepine acetate for the
treatment of focal epilepsy: an update on its proposed
mechanisms of action. Pharmacol Res Perspect. 2015
Mar;3(2):e00124.
Doi:10.1002/prp2.124,
PMID
26038700
Hanada T. The discovery and development of
perampanel for the treatment of epilepsy. Expert Opin
Drug
Discov.
2014
Apr
1;9(4):449-58.
doi:
10.1517/17460441.2014.891580, PMID 24559052.
Large CH, Sokal DM, Nehlig A, Gunthorpe MJ, Sankar R,
Crean CS. The spectrum of anticonvulsant efficacy of
retigabine (ezogabine) in animal models: implications
for clinical use.
Epilepsia. 2012 Mar;53(3):425-36. doi: 10.1111/j.1528-
1167.2011.03364.x, PMID 22221318.
Kamboj VK, Verma PK, Dhanda A, Ranjan S. 1,2,4-
triazole derivatives as a potential scaffold for
anticonvulsant activity. Cent Nerv Syst Agents Med
Chem. 2015 Apr 1;15(1):17-22. doi:
10.2174/1871524915666150209100533,
PMID
25675400.
Ben Menachem E. Medical management of refractory
epilepsy practical treatment with novel antiepileptic
drugs. Epilepsia. 2014 Jan;55 Suppl 1:3-8. doi:
10.1111/epi.12494, PMID 24400690.
Luszczki JJ, Plech T, Wujec M. Effect of 4-(4-
bromophenyl)-5-(3-
chlorophenyl)-2,4-dihydro-3H-
1,2,4-triazole-3-thione on the anticonvulsant action of
different classical antiepileptic drugs in the mouse
maximal electroshock induced seizure model. Eur J
Pharmacol.
2012
Sep
5;690(1-3):99-106.
doi:
10.1016/j.ejphar.2012.06.023, PMID 22732650.
Loring DW, Meador KJ. Cognitive side effects of
antiepileptic drugs in children. Neurology. 2004 Mar
23;62(6):872-7.
doi:
10.1212/01.wnl.0000115653.82763.07,
PMID
15037684.
Chen B, Choi H, Hirsch LJ, Katz A, Legge A, Buchsbaum
R. Psychiatric and behavioral side effects of
antiepileptic drugs in adults with epilepsy. Epilepsy
Behav. 2017 Nov 1;76:24-31. doi:
10.1016/j.yebeh.2017.08.039, PMID 28931473.
Deka D, Chakravarty PI, Purkayastha AY. Evaluation of
the anticonvulsant effect of aqueous extract of Centella
asiatica in albino mice. Int J Pharm Pharm Sci.
2017;9(2):312-4. doi:
10.22159/ijpps.2017v9i2.15483.
Karakucuk Iyidogan A, Basaran E, Tatar Yilmaz G, Oruc
Emre EE. Development of new chiral 1,2,4-triazole-3-
thiones and 1,3,4-thiadiazoles with promising in vivo
anticonvulsant activity targeting GABAergic system and
voltage-gated sodium channels (VGSCs). Bioorg Chem.
2024
Oct
1;151:107662.
doi:10.1016/j.bioorg.2024.107662, PMID 39079390.
Rani S, Teotia S, Nain S. Recent advancements and
biological activities of triazole derivatives: a short
review. Pharm Chem J. 2024 Apr 15;57(12):1909-17.
doi: 10.1007/s11094-024-03096- z.
Mula M. GABAergic drugs in the treatment of epilepsy:
modern or outmoded? Future Med Chem. 2011
Feb;3(2):177-82. doi: 10.4155/fmc.10.296, PMID
21428812.
Froestl W. An historical perspective on GABAergic
drugs. Future Med Chem. 2011 Feb;3(2):163-75. doi:
10.4155/fmc.10.285, PMID 21428811.
Rahimboyev, S., Sanoev, Z., Hamroyev, T., Abdinazarov,
I., Rashidov, S., Ismoilova, D.., & Elmuradov, B. (2025).
5-(p-aminofenil)-4-amino-1,2,4-triazol-3(2H)-tionning
o‘tkir zaharliligi va tutqanoqqa qarshi faolligi.
Евразийский журнал медицинских и естественных
наук, 5(2 Part 2), 110–118. извлечено от https://in
-
academy.uz/index.php/EJMNS/article/view/46508
Sanoev Z.I., Ismailova D.S., Rakhimboev S.D., Tolibovich
T.T., Elmuradov B.J., Abdinazarov I.T., Rashidov S.Z.
(2023). Synthesis And Research Anticonvulsant Activity
Of Annulated Triazolo-thiadiazine Derivative In
Laboratory Animals. Biomedical & Pharmacology
Journal. Vol. 16(4), p. 2457-2467.
Matin MM, Matin P, Rahman MR, Ben Hadda T, Almalki
FA, Mahmud S. Triazoles and their derivatives:
chemistry synthesis and therapeutic applications. Front
Mol Biosci. 2022 Apr
25;9:864286. doi: 10.3389/fmolb.2022.864286, PMID
35547394, PMCID PMC9081720.
1Zhang Y, Wang M, Ahmed M, HE L, JI M, QI Z. Synthesis
fungicidal activity and SAR of 3,4-dichloroisothiazole
based cycloalkyl sulfonamides. Bioorg Med Chem Lett.
2019
Jun
1;29(11):1345-9.
doi:
10.1016/j.bmcl.2019.03.047, PMID 30956010.
Zhang Y, Wang M, Ahmed M, He L, JI M, QI Z. Synthesis
fungicidal
activity
and
SAR
of
3,4-
dichloroisothiazolebased
cycloalkylsulfonamides.
Bioorg Med Chem Lett. 2019;29(11):1345-49. doi:
American Journal of Applied Science and Technology
24
https://theusajournals.com/index.php/ajast
American Journal of Applied Science and Technology (ISSN: 2771-2745)
10.1016/j.bmcl.2019.03.047, PMID 30956010.
Sanoyev, Z. (2025). 1-(4´-metoksifenil)-6,7dimetoksi-
1,2,3,4-tetragidroizoxinolinning tutqanoqqa qarshi
faolligi.
Евразийский журнал медицинских и
естественных наук, 5(1), 285–293. извлечено от
https://in-
academy.uz/index.php/EJMNS/article/view/44142.
Sanoev, Z. I., & Mirzaev, Y. R. (2020). Pharmacological
activity of the possessing new atypical neuroleptics 1-
phenyltetrahydroisoquinoline structure. The American
Journal of Medical Sciences and Pharmaceutical
Research, 18-26.
Sanoev, Z. I., & Mirzaev, Y. R. (2021). Research of a New
Atypical Neuroleptic 1-(3 , 4 -Methylenedioxyphenyl)-
6, 7-Methylenedioxy-1, 2, 3, 4-Tetrahydroisoquinoline
on the Central Nervous System. Annals of the
Romanian Society for Cell Biology, 25(2), 2363-2369.
Turan Zitouni G, Sivaci M, Kilic FS, Erol K. Synthesis of
some triazolyl-antipyrine derivatives and investigation
of analgesic activity. Eur J Med Chem. 2001 Aug 1;36(7-
8):685-9. doi:10.1016/s0223-5234(01)01252-1, PMID
11600237.
Bekircan O, Kuxuk M, Kahveci B, Kolayli S. Convenient
synthesis of fused heterocyclic 1,3,5-triazines from
some N-acyl imidates and heterocyclic amines as
anticancer and antioxidant agents. Arch Pharm Int.
2005
Aug;338(8):365-72.
doi:
10.1002/ardp.200400964, PMID 16041836.
Wade PC, Vogt BR, Kissick TP, Simpkins LM, Palmer DM,
Millonig RC. 1-Acyltriazoles as antiinflammatory
agents. J Med Chem. 1982 Mar;25(3):331-3. doi:
10.1021/jm00345a021, PMID 6461764.
Mahdavi M, Akbarzadeh T, Sheibani V, Abbasi M,
Firoozpour L, Tabatabai SA. Synthesis of two novel 3-
amino-5-[4-chloro-2-
phenoxyphenyl]-4H-1,2,4-
triazoles with anticonvulsant activity. Iran J Pharm Res.
2010;9(3):265-9. PMID 24363736.
Modzelewska Banachiewicz B, Kalabun J. Synthesis and
biological action of 5-oxo-1,2,4-triazine derivatives.
Pharmazie. 1999 Jul 1;54(7):503-5. PMID 10445245.
Gupta D, Jain DK. Synthesis antifungal and antibacterial
activity of novel 1,2,4-triazole derivatives. J Adv Pharm
Technol Res. 2015 Jul 1;6(3):141-6. doi: 10.4103/2231-
4040.161515, PMID 26317080.
Gao F, Wang T, Xiao J, Huang G. Antibacterial activity
study of 1,2,4-triazole derivatives. Eur J Med Chem.
2019
Jul
1;173:274-
81.
doi:
10.1016/j.ejmech.2019.04.043, PMID 31009913.
Gulerman N, Rollas S, Kiraz M, Ekinci AC, Vidin A.
Evaluation of antimycobacterial and anticonvulsant
activities of new 1-(4-fluorobenzoyl)-4-substituted
thiosemicarbazide and 5-(4-
fluorophenyl)-4-substituted-2,4-dihydro-3H-1,2,4-
triazole-3-thione derivatives. Farmaco. 1997 Nov
1;52(11):691-5. PMID9550096.
Ikizler AA, Johansson CB, Bekircan O, Celik C. Drug
synthesis. Acta Poloniae Pharnaceutica
–
Drug Research.
1999;56(4):283-8.
Shalini M, Yogeeswari P, Sriram D, Stables JP.
Cyclization of the semicarbazone template of aryl
semicarbazones: synthesis and anticonvulsant activity
of 4,5-diphenyl-2H-1,2,4-triazol-3(4H) one. Biomed
Pharmacother.
2009
Mar
1;63(3):187-93.
doi:10.1016/j.biopha.2006.04.002, PMID 19422088.
Siddiqui N, Ahsan W. Triazole incorporated thiazoles as
a new class of anticonvulsants: design, synthesis and in
vivo screening. Eur J Med Chem. 2010 Apr
1;45(4):1536-43. doi: 10.1016/j.ejmech.2009.12.062,
PMID 20116140.
Almasirad A, Tabatabai SA, Faizi M, Kebriaeezadeh A,
Mehrabi N, Dalvandi A. Synthesis and anticonvulsant
activity
of
new
2-substituted-5-
[2-(2-
fluorophenoxy)phenyl]-1,3,4-oxadiazoles and 1,2,4-
triazoles. Bioorg Med Chem Lett. 2004 Dec
20;14(24):6057-9. doi: 10.1016/j.bmcl.2004.09.072,
PMID15546729.
