This document describes the synthesis and characterization of new benzotriazole derivatives (Va-Vg) for potential central nervous system (CNS) activity. The derivatives were synthesized in multiple steps starting from O-phenylenediamene. The intermediates and final compounds were characterized using techniques like IR, 1H NMR, mass spectrometry and elemental analysis. All compounds were screened for CNS activity through gross behavioral studies and locomotor activity tests. Compound Vb containing a 4-chloro substitution showed the most promising depressant activity among the test compounds, followed by Vg and Ve.
FDA’s emphasis on quality by design began with the recognition that increased testing does not improve product quality (this has long been recognized in other industries).In order for quality to increase, it must be built into the product. To do this requires understanding how formulation and manufacturing process variables influence product quality.Quality by Design (QbD) is a systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management. A presentation compiled from material freely available on the WEB to introduce the concepts of QbD for beginners.
UV Spectrophotometric Method Development and Validation for Quantitative Esti...Sagar Savale
U.V Spectrophotometric method have been widely employed in determination of individual components in a mixture or fixed dose combination. Our aim is to develop spectroscopic method for estimation of the paracetamol in ternary mixture by using U.V spectrophotometry.
Pharmaceutical aerosols have been playing a crucial role in the health and wellbeing of millions of people throughout the world for many years. These products include pressurized metered dose inhalers (MDIs), dry powder inhalers (DPIs), nebulizers, sublingual’s, skin sprays (coolants, anaesthetics, etc.) and dental sprays. The technology’s continual advancement, the ease of use, and the more desirable pulmonary-rather-than-needle delivery for systemic drugs has increased the attraction for the pharmaceutical aerosol in recent years.
Many of the tests required for the evaluation of MDIs are similar to those used for other dosage forms. These include description, identification, and assay of the active ingredient; microbial limits; moisture content; net weight, degradation products and impurities (if any); extractable; and any other tests deemed appropriate for the active ingredient.
After the manufacturing of the drug, it is essential that these should be stored properly. The stability of drug during it’s storage depend on so many factor and proper packaging is one of them. The pharmaceutical products are in direct contact with the container and closures. So improper packaging and poor quality of container may lead to deterioration of the product.
An efficient synthesis, characterization and antibacterial activity of novel ...iosrjce
IOSR Journal of Applied Chemistry (IOSR-JAC) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of applied chemistry and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Chemical Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Synthesis and antimicrobial activity of some methyl (4- (benzo[d]oxazol-2-yl)...QUESTJOURNAL
ABSTRACT: In the present study, a new series of methyl (4-(benzo[d]oxazol-2-yl)phenyl) carbamodithioate amine derived from methyl (4-(benzo[d]oxazol-2-yl)phenyl) carbamodithioate (4TO1-TO6) have been synthesized by reacting the thio methyl group with different amines in presence of ethenol. The structural assessment of the compounds (TO 1- TO 6) was made on the basis of spectral data. The synthesized compounds were screened for their in vitro growth inhibiting activity against different strains of bacteria and fungi viz., Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, S. aureus, Candida albicans and Cryptococcus neoformans were compared with standard agents such as Norfloxacin (10μg/ml) and Amphotericin B (10μg/ml) using broth dilution method. Compounds exhibit moderate to high antibacterial and antifungal activity
FDA’s emphasis on quality by design began with the recognition that increased testing does not improve product quality (this has long been recognized in other industries).In order for quality to increase, it must be built into the product. To do this requires understanding how formulation and manufacturing process variables influence product quality.Quality by Design (QbD) is a systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management. A presentation compiled from material freely available on the WEB to introduce the concepts of QbD for beginners.
UV Spectrophotometric Method Development and Validation for Quantitative Esti...Sagar Savale
U.V Spectrophotometric method have been widely employed in determination of individual components in a mixture or fixed dose combination. Our aim is to develop spectroscopic method for estimation of the paracetamol in ternary mixture by using U.V spectrophotometry.
Pharmaceutical aerosols have been playing a crucial role in the health and wellbeing of millions of people throughout the world for many years. These products include pressurized metered dose inhalers (MDIs), dry powder inhalers (DPIs), nebulizers, sublingual’s, skin sprays (coolants, anaesthetics, etc.) and dental sprays. The technology’s continual advancement, the ease of use, and the more desirable pulmonary-rather-than-needle delivery for systemic drugs has increased the attraction for the pharmaceutical aerosol in recent years.
Many of the tests required for the evaluation of MDIs are similar to those used for other dosage forms. These include description, identification, and assay of the active ingredient; microbial limits; moisture content; net weight, degradation products and impurities (if any); extractable; and any other tests deemed appropriate for the active ingredient.
After the manufacturing of the drug, it is essential that these should be stored properly. The stability of drug during it’s storage depend on so many factor and proper packaging is one of them. The pharmaceutical products are in direct contact with the container and closures. So improper packaging and poor quality of container may lead to deterioration of the product.
An efficient synthesis, characterization and antibacterial activity of novel ...iosrjce
IOSR Journal of Applied Chemistry (IOSR-JAC) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of applied chemistry and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Chemical Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Synthesis and antimicrobial activity of some methyl (4- (benzo[d]oxazol-2-yl)...QUESTJOURNAL
ABSTRACT: In the present study, a new series of methyl (4-(benzo[d]oxazol-2-yl)phenyl) carbamodithioate amine derived from methyl (4-(benzo[d]oxazol-2-yl)phenyl) carbamodithioate (4TO1-TO6) have been synthesized by reacting the thio methyl group with different amines in presence of ethenol. The structural assessment of the compounds (TO 1- TO 6) was made on the basis of spectral data. The synthesized compounds were screened for their in vitro growth inhibiting activity against different strains of bacteria and fungi viz., Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, S. aureus, Candida albicans and Cryptococcus neoformans were compared with standard agents such as Norfloxacin (10μg/ml) and Amphotericin B (10μg/ml) using broth dilution method. Compounds exhibit moderate to high antibacterial and antifungal activity
An Efficient Synthetic Approach Towards 4-Cyano-3-(Methylthio)-5-Oxo-2H-Pyraz...inventionjournals
ABSTRACT: Synthesis of novel heterocyclic 4-cyano -3-(methylthio)-5-oxo-2H-pyrazole-1(5H)- carbothioamide (3) was prepared by condensing ethyl-2-cyano-3,3-bis (methylthio)acrylate (1) with thiosemicarbazide (2) in DMF and catalytic amount of potassium carbonate. Compound (3) has methylthio group at third position, which is replaced by different nucleophiles such as substituted anilines| phenols| hetryl amines| compounds containing active methylene group to afford 3-substituted derivatives of compound (3). All the newly synthesized compounds were screened for their antimicrobial activity.
Synthesis, characterization and biological activities of novel 2-mercaptobenz...ijperSS
ABSTRACT
A new series of Benzoxazol-2-ylthio-N-(4-substituted) acetohydrazide derivatives (IVa-IVk), were obtained by synthesising new Schiff’s bases derived from benzoxolyl-2-mercaptoaceto hydrazide derivatives by treating with various aryl/hetero aryl aldehydes. Their chemical structures have been confirmed by 1H-NMR, 13C-NMR, FT-IR and ESI-MS spectral data. The synthesised derivatives (IVa-IVk) were screened for their in vitro antimicrobial activities by agar diffusion method. Among the synthesized compounds IVb, IVe, and IVk shown strong antibacterial activity and the compounds IVb, IVe and IVf exhibited strong antifungal activity.
Key words: Benzoxazole, aryl/hetero aryl aldehydes, schiff’s bases, antibacterial activity, antifungal activity.
A series of novel 5-[2-(4-fluorobenzyl)-6-aryl-imidazo[2,1-b][1,3,4]thiadiazol-5-ylmethylene] thiazolidine-2,4-dione derivatives (4a-d) were synthesized. These final compounds (4a-d) were synthesized by Knoevenagel condensation of 2-(4-fluorobenzyl)-6-arylimidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehydes (3a-d) with thiazolidine-2,4-dione. All the newly synthesized compounds were screened for their invivo hypoglycemic and hypolipidemic activity in male Wister rats. The Structures of all the newly synthesized compounds were established by analytical and spectral data.
Synthesis And Antibacterial Activity Of 3-[(3-Phenyl-5-Thioxo-1, 5-Dihydro-4h...inventionjournals
A series of 3-[(3-phenyl-5-thioxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)imino]-1,3-dihydro-2Hindole-2-one derivatives were synthesised through the nucleophilic substitution at carbonyl carbon of Isatin. Structure of synthesized compounds were elucidated by using IR, 1H NMR & 13C NMR spectrometry. Synthesised compounds showed significant antibacterial activity against E.coli (ATCC 35218), S.aureus (ATCC 25323), E.faecalis (Clinical isolate), K. Pneumonia, P. aeruginosa (ATCC 27893) using agar well diffusion method.
IJERA (International journal of Engineering Research and Applications) is International online, ... peer reviewed journal. For more detail or submit your article, please visit www.ijera.com
Synthesis of substituted 1, 2, 4-triazole derivatives by Microwave irradiationIOSR Journals
Various substituted Triazole-Thiol containing different functional group have been synthesized by microwave method. The title product 1-[(3H-indol-2-ylamino) methyl]-4-phenyl-4, 5-dihydro-1H-1, 2, 4-triazole-3-thiol is synthesized by using amino benzothiazole. The final structures have been established on the basis of their chemical analysis and spectral data. All micro-wave synthesized compounds results into good yield as compared to conventional method of which fluoro substituted compound shows maximum yield.
Synthesis, Molecular Docking and Antimicrobial Evaluation of New Tetrahydrobe...ijtsrd
A series of novel derivatives of Tetrahydrobenzothienopyrimidine hydrazone were synthesized and product structure was elucidated by 1NMR, C13NMR and mass spectroscopy. The synthesized compounds were evaluated against fungal and bacterial strains. The synthesized compounds showed significant antibacterial activity against Staphylococcus aureus MTCC 96, Staphylococcus pyrogenes MTCC 442, and Escherichia coli MTCC 443, Pseudomonas aeruginosa MTCC 1688 and against fungal strains Candida albicans MTCC 227, Aspergillus niger MTCC 282, Aspergillus clavatus MTCC 1323. Some derivatives showed promising result against gram positive, gram negative bacterial and fungal strains than standard drug ampicillin and grieseofulvin. In- silico molecular docking studies of the synthesized compounds was done by using GRIP batch docking method of Vlife MDS 3.0 software to study their observed activity which showed a significant correlation between the binding score and biological activity for synthesized compounds. Neetu Chopra | Kiranpreet kaur | Sanjeev Kumar "Synthesis, Molecular Docking and Antimicrobial Evaluation of New Tetrahydrobenzothienopyrimidine Derivatives" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-2 | Issue-6 , October 2018, URL: http://www.ijtsrd.com/papers/ijtsrd18756.pdf
Simple Synthesis of Some Novel Polyfunctionally Derivatives of 2H-Coumarin-2-...IOSRJAC
Compound (2) was prepared from the reaction of ethyl-2-oxo-2H-coumarin-3-carboxylate (1) with ethylcyanoacetate in ethanol containing a catalytic amount of piperidine as catalyst. Compound (2) is the key intermediate for the synthesis of several series of new compounds such as ((pyrimidine, tetrazine, piperidine, oxazepine)-2H-coumarin-2-one derivatives by reaction with selected reagents such as urea, cyanoacetamide, cyanoacetohydrazide, orthoaminophenol and 5-aminotriazole.
Synthesis, Characterization and invitro Anti- inflammatory activity of 1, 3, ...SriramNagarajan19
Oxadiazole derivatives have played a vital part in the development of heterocyclic compounds. In this present work, a series of 5-(2-aminophenyl)-1,3,4-oxadiazole-2(3H)-thione derivatives (1-10) have been synthesized by Mannich reaction. The reaction progress of the synthesized compounds was checked by TLC. The structures of the newly synthesized compounds were confirmed by IR and 1H NMR spectral data. The in-vitro anti-inflammatory activity of 1, 3, 4-oxadiazole compounds (1-10) was assessed by HRBC Membrane Stabilization Method. Among the newly synthesized 1,3,4-oxadiazole derivatives, compounds OFP, OAP, OBNP, OPBNP, ORP, OUP, OPClBP, OFD, OAD and OBND possessed highly significant anti-inflammatory activity at a dose of 1000µg/ml when compared with standard, Diclofenac potassium.
Simple and Eco-friendly Synthesis of Glycosides bearing triazolo[3,4-b][1,3,4...IOSRJAC
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Facial and Simple Synthesis of Some New (Pyrazole and Triazole) Coumarin Deri...IOSRJAC
2-oxo-2H-coumarin-3-carbohydrazide (2) which prepared from the reaction of ethyl-2-oxo-2Hcoumarin-3-carboxylate (1) with hydrazine hydrate in ethanol containing a catalytic amount of piperidine mixture consider a good and available starting intermediate for synthesis of series of functionalized coumarins. So, compound (2) was utilized as a key for the synthesis of some new (pyrazole, triazole)-2H- coumarin-2-one derivatives by the reaction with some selected reagents.
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
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3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
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FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
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Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
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Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
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Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
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Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Synthesis and characterization of new benzotriazole derivatives for possible CNS activity
1. Srikanth L et al / Int. J. of Farmacia, 2017; Vol-(3) 2: 65-72
65
International Journal of Farmacia
Journal Home page: www.ijfjournal.com
Synthesis and characterization of new benzotriazole derivatives for possible
CNS activity
P. Swarnalatha1
, L. Srikanth*2
, G. Sridhar Babu3
, J. Venkateshwar Rao2
, P. S. Malathy2
,
B.Srinivas2
1
Department of Pharmaceutical Chemistry, Talla Padmavathi College of Pharmacy,
Warangal,Telangana State, India
2
Department of Pharmaceutical Chemistry, SVS School of Pharmacy, Warangal,
Telangana State, India
3
Department of Pharmaceutical Chemistry, Sri Shivani College of Pharmacy,
Warangal,Telangana State, India
Corresponding Author: L. Srikanth
*
E-mail:srikanth802@gmail.com
ABSTRACT
In view of the biological prominence of benzotriazole derivatives, it is planned to synthesize new benzotriazole
derivatives. So, some new 2-(1H-benzo[d][1,2,3]triazol-1-yl)-N'-(2-substituted benzylidene) acetohydrazides (Va-
Vg) have been synthesized as depicted in scheme-I. The intermediates and final compounds were purified and their
chemical structures have been confirmed by IR, 1
H NMR, Mass and by elemental analysis. All the newly synthesized
compounds were screened for their CNS activity (Gross behavioral studies and loco motor activity). Among the
compounds tested, compound Vb with 4-Chloro substitution on the phenyl ring showed more promising depressant
activity among all the test compounds followed by Vg and Ve.
Keywords: Benzotriazole, Anti-inflammatory agents, CNS activity, Gross behavioral studies and loco motor
activity.
INTRODUCTION
A heterocyclic is an organic compound with a ring
containing one or more carbons and at least one other
element, namely O, S and N. About half of the known
organic compounds contain at least one heterocyclic
component, thus heterocyclic compounds are very
widely distributed in nature. Their functions are often
of fundamental importance to living systems as they
play a vital role in the metabolism of all living cells
[1].
Benzotriazole is a benzofusedtriazole moiety.
Benzotriazole containing compounds have been found
to possess varied applications in organic synthesis in
medicines and industry as biologically active systems,
as dye stuffs and fluorescent compounds, as corrosion
inhibitors, as photostabilizers [2]. They show
anticancer, antimicrobial, antifungal, anticonvulsants
and antinociceptive activity. The fungicides
containing triazoles are known germicides absorbed
inside by plants basing on the high efficiency and the
qualities of disinfecting the plants, the triazolone,
triazolol have become important type of fungicides
[3].
A survey of literature reveals that the
benzotriazole nucleus is found to have various
2. Srikanth L et al / Int. J. of Farmacia, 2017; Vol-(3) 2: 65-72
66
pharmacological activities like anti-inflammatory [4],
antimicrobial [5], antifungal [6] and anticancer
activities [7]. It is also known from the literature that
molecules containing benzotriazole nucleus possess
CNS activity and various other pharmacological
activities [8]. It has been considered as prime
importance to take up such synthesis of new
compounds containing benzotriazole nucleus with a
view to get more potent compounds and screen them
for CNS activity. In view of these valid observations
in our present study, we reported the synthesis and
screening of 2-(1H-benzo[d][1,2,3]triazol-1-yl)-N'-(2-
substituted benzylidene) acetohydrazides.
MATERIALS AND METHODS
The chemicals and solvents used for the
experimental work were commercially procured from
E. Merck, India, S.D. Fine Chem, India and
Qualigens, India. Silica gel G used for analytical
chromatography (TLC) was obtained from S.D. Fine
Chem, India. Melting points were determined in an
open glass capillary using a Kjeldahl flask containing
liquid paraffin and are uncorrected. The proton
magnetic resonance spectra (1H NMR) were recorded
on a Bruker 300 MHz instrument (Bruker, Germany)
in DMSO/CDCl3 using TMS as internal standard.
Chemical shifts (δ) are expressed in ppm. The infrared
spectra of compounds were recorded in KBr on a
FTIR- -8400S, Fourier Transform (Shimadzu), Japan
infrared spectrophotometer. Mass spectra were
recorded on LC-MS/MS (API-4000 TM), Applied
BioSystems, MDS SCIEX (Canada).
Scheme-1
METHODOLGY
Synthesis of benzotriazole (II)
A mixture of O-phenylenediamene (10.8g, 0.1
mol), glacial acetic acid (11.5 ml, 0.2 mol) and 30 ml
of water was taken in a 250 ml beaker. The mixture
was heated slightly. The clear solution of sodium
nitrite was added. The reaction mixture became warm
and within 2–3 minutes reached a temperature of
about 85ºC. After cooling the resulting pale brown
NH2
NH2
N
H
N
N
N
N
N
CH2COOC2H5
N
N
N
CH2CONHNH2
N
N
N
CH2CONHN C
H
R
1 2
3
4
(I) (II) (III)
(IV)(Va-Vg)
R = H ; 4-Cl ; 3-OCH3, 4-OH ; 3-OCH3 ;
2-Cl ; 2-OH ; 4-N(CH3)2
1) NaNO2, HCl & Glacial acetic acid.
2) Ethylchloroacetate, Anhydrous K2CO3 & Dry acetone.
3) NH2.NH2.H2O (99%) & Methanol.
4) Various Aromatic aldehydes, methanol & feew drops of glacial acetic acid.
3. Srikanth L et al / Int. J. of Farmacia, 2017; Vol-(3) 2: 65-72
67
compound was filtered and washed thoroughly with
ice-cold water [9]. The compound was purified by
recrystallization using boiling water, at 99 ºC - 100ºC.
Synthesis of Ethyl 2-(1H-
benzo[d][1,2,3]triazol-1-yl)acetate (III)
A mixture of benzotriazole (II, 0.01 mol),
anhydrous potassium carbonate (0.02 mol) and
ethylchloroacetate (0.01 mol) in dry acetone was
stirred on a magnetic stirrer for 20 hrs. The inorganic
solids were filtered and solvent was removed on a
rotavapour. The residue was poured onto crushed ice.
The compound thus separated was washed with cold
water and recrystallized from ethanol, m.p.; 72o
C,
yield; 50%.
Synthesis of 2-(1H-benzo[d][1,2,3]triazol-1-yl)
acetohydrazide (IV)
A mixture of Ethyl 1H-benzotriazol-1-yl acetate
(III, 0.01 mol) in ethanol (75 ml), and hydrazine
hydrate (0.02 mol, 99%) was refluxed for 1.5 hrs.
After cooling the resulting solid was filtered, washed
thoroughly with cold water, dried and recrystallized
from ethanol, m.p.; 170o
C - 172o
C, yield; 60%. IR
(KBr)(cm-1
): 3373(N-H2 str.), 3202(N-H str.), 3155
(Ar-H str.), 1687 (C=O str.), 1650-1540 (C=C str.).
H1
NMR (DMSO-d6): δ 9.6, (s, 1H, CONH), 8.1-7.3
(m, 4H, Ar-H), 5.4 (s, 2H, -CH2-), 4.4 (s, 2H, -NH2).
EI-MS: m/z= 191(M+
).
Synthesis of 2-(1H-benzo[d][1,2,3]triazol-1-
yl)-N'-(2-substituted benzylidene)
acetohydrazide (Va - Vg)
A mixture of an appropriate aromatic aldehyde
(0.01 mol) and 2-(1H-benzo[d][1,2,3]triazol-1-yl)
acetohydrazide (IV, 0.01 mol) in methanol (50 ml)
containing 3-4 drops of glacial acetic acid was
refuxed on a water bath for about 30 min. and cooled.
The crystalline solid which separated out during
raction was filtered and recrystallized from suitable
solvent(s). The products were characterized by TLC
& spectral data. Seven new compounds were prepared
by following the above detailed procedure and their
physical data is presented in Table-1.
Spectral data of 2-(1H-benzo[d][1,2,3]triazol-
1-yl)-N'-(phenylmethylidene) acetohydrazide
(Va)
m.p.; 232o
C - 234o
C, yield; 65%.IR (KBr)(cm-1
):
3228 (N-H str.), 3142 (Ar-H str.), 1673 (C=O str.),
1623-1558 (C=C str.), 1543 (C=N str.). H1
NMR
(DMSO-d6): δ 10.8, (s, 1H, NH acid hydrazide), 8.2-
6.9 (m, 10H, Ar-H including benzylidine proton), 6.1
(s, 2H, -CH2-). EI-MS: m/z = 281(M+
).
Spectral data of (E)-N'-(4-chlorobenzylidene)-
2-(1H-benzo[d][1,2,3]triazol-1-
yl)acetohydrazide (Vb)
m.p.; 236o
C - 238o
C, yield; 70%.IR (KBr)(cm-1
):
3235 (N-H str.), 3148 (Ar-H str.), 1662 (C=O str.),
1635-1560 (C=C str.), 1540 (C=N str.), 765 (C-Cl).
H1
NMR (DMSO-d6): δ 10.2, (s, 1H, NH acid
hydrazide), 8.4-7.1 (m, 9H, Ar-H including
benzylidine proton), 5.8 (s, 2H, -CH2-). EI-MS: m/z =
313(M+
).
Spectral data of (E)-N'-(4-
methoxybenzylidene)-2-(1H-
benzo[d][1,2,3]triazol-1-yl)acetohydrazide
(Vc)
m.p.; 220o
C - 222o
C, yield; 65%.IR (KBr)(cm-1
):
3230 (N-H str.), 3140 (Ar-H str.), 1660 (C=O str.),
1639-1568 (C=C str.), 1547 (C=N str.). H1
NMR
(DMSO-d6): δ 10.4, (s, 1H, NH acid hydrazide), 8.6-
7.4 (m, 9H, Ar-H including benzylidine proton), 5.8
(s, 2H, -CH2-), 4.4 (s, 3H, OCH3). EI-MS: m/z =
309(M+
).
Spectral data of (E)-N'-(4-hydroxy-3-
methoxybenzylidene)-2-(1H-
benzo[d][1,2,3]triazol-1-yl)acetohydrazide
(Vd)
m.p.; 210o
C - 212o
C, yield; 70%.IR (KBr)(cm-1
):
3415 (OH str.), 3275 (N-H str.), 3152 (Ar-H str.),
1665 (C=O str.), 1630-1560 (C=C str.), 1541 (C=N
str.). H1
NMR (DMSO-d6): δ 10.6, (s, 1H, NH acid
hydrazide), 8.5-7.2 (m, 8H, Ar-H including
benzylidine proton), 5.6 (s, 2H, -CH2-), 4.9 (s, 1H,
OH), 4.1 (s, 3H, OCH3). EI-MS: m/z = 325(M+
).
Spectral data of (E)-N'-(4-
(dimethylamino)benzylidene)-2-(1H-
benzo[d][1,2,3]triazol-1-yl)acetohydrazide
(Ve)
m.p.; 224o
C - 226o
C, yield; 70%.IR (KBr)(cm-1
):
3264 (N-H str.), 3137 (Ar-H str.), 2920 (CH3 C-H),
1658 (C=O str.), 1628-1569 (C=C str.), 1547 (C=N
str.). H1
NMR (DMSO-d6): δ 10.1, (s, 1H, NH acid
hydrazide), 8.4-7.1 (m, 9H, Ar-H including
benzylidine proton), 5.3 (s, 2H, -CH2-), 3.8 (s, 6H,
N(CH3)2). EI-MS: m/z = 322(M+
).
4. Srikanth L et al / Int. J. of Farmacia, 2017; Vol-(3) 2: 65-72
68
Spectral data of (E)-N'-(4-
(dimethylamino)benzylidene)-2-(1H-
benzo[d][1,2,3]triazol-1-yl)acetohydrazide
(Vf)
m.p.; 218o
C - 220o
C, yield; 60%.IR (KBr)(cm-1
):
3428 (OH str.), 3258 (N-H str.), 3124 (Ar-H str.),
1652 (C=O str.), 1621-1563 (C=C str.), 1549 (C=N
str.). H1
NMR (DMSO-d6): δ 10.6, (s, 1H, NH acid
hydrazide), 8.2-6.8 (m, 9H, Ar-H including
benzylidine proton), 5.2 (s, 2H, -CH2-), 4.6 (s, 1H,
OH). EI-MS: m/z = 295(M+
).
Spectral data of (E)-N'-(4-
(dimethylamino)benzylidene)-2-(1H-
benzo[d][1,2,3]triazol-1-yl)acetohydrazide
(Vg)
m.p.; 230o
C - 232o
C, yield; 75%.IR (KBr)(cm-1
):
3351 (N-H str.), 3135 (Ar-H str.), 1650 (C=O str.),
1625-1569 (C=C str.), 1545 (C=N str.), 762 (C-Cl).
H1
NMR (DMSO-d6): δ 10.2, (s, 1H, NH acid
hydrazide), 8.2-7.1 (m, 9H, Ar-H including
benzylidine proton), 5.1 (s, 2H, -CH2-). EI-MS: m/z =
313(M+
).
Table 1: Physical data of 2-(1H-benzo[d][1,2,3]triazol-1-yl)-N'-(2-substituted benzylidene) acetohydrazide (Va
-Vg)
S.
No.
Compound Substituents
(R)
Molecular
Formula
Molecular
Weight
Melting Point
o
C
Yield
%
1 Va -H C15H13N5O 281 232-234 65
2 Vb 4-Cl C15H12N5OCl 313 236-238 70
3 Vc 4-OCH3 C16H15N5O2 311 220-222 65
4 Vd 3-OCH3
4-OH
C16H15N5O3 325 210-212 70
5 Ve 4-N(CH3)2 C17H18N6O 322 224-226 70
6 Vf 2-OH C15H13N5O2 295 218-220 60
7 Vg 2-Cl C15H12N5OCl 313 230-232 75
BIOLOGICAL EVALUATION
Action on central nervous system – gross
behavioral studies
Materials
0.1% Sodium CMC, Test compounds
Instruments: Sonicator
Animals: Mice
All the seven newly synthesized compounds were
screened for gross behavioral changes, continuously
for 5 hrs at 1 hr interval after administration of the
compounds. There after the observations were
recorded intermittently for 24 hrs and compared with
that of control group [10].
In the behavioral profile, the animals have been
observed for changes in their
Awareness
Alertness
Visual Placing
Stereotype
Passivity
Writhing
N
N
N
CH2CONHN C
H
R
(Va-Vg)
6. Srikanth L et al / Int. J. of Farmacia, 2017; Vol-(3) 2: 65-72
70
2 + - - - - - - - -
3 + - - - - - - - -
4 + - - - - - - - -
5 + - - - - - - - -
24 + - - - - - - - -
Ve ½ - + - + - - - - -
1 - - - + - - - - -
2 - - - + - - - - -
3 - - - - - - - - -
4 + - - - - - - - -
5 + - - - - - - - -
24 + - - - - - - - -
Vf ½ - + - + - - - - -
1 - - - + - - - - -
2 + - - - - - - - -
3 + - - - - - - - -
4 + - - - - - - - -
5 + - - - - - - - -
24 + - - - - - - - -
Vg ½ - - - + - - - - -
1 - - - + - + - - -
2 - - - + - - - - -
3 - - - + - - - - -
4 - - - - - - - - -
5 + - - - - - - - -
24 + - - - - - - - -
LOCOMOTOR ACTIVITY
Materials: 0.1% Sodium CMC, Test compounds
Instruments: Sonicator and Actophotometer
Animals: Mice
The locomotor activity was studied by using
actophotometer, which operates on photoelectric cells,
which are connected in circuit with a counter. When
animals cut off beam of light falling on the photocells,
a count was recorded. Healthy male mice weighing
between 20-25 gm were used. Animals were fasted
for overnight and divided into groups of six animals
in each group. The test compounds suspended in 0.1%
Sodium CMC are administered at a dose of 100
mg/kg body weight i.p. The response (counts) was
recorded after 30 min. of administration of drug or
test compound [11].
The animals were placed in actophotometer for 10
min. and scores were recorded and the results were
compared with the control. The results are presented
in Table-3.
N
N
N
CH2CONHN C
H
R
(Va-Vg)
7. Srikanth L et al / Int. J. of Farmacia, 2017; Vol-(3) 2: 65-72
71
Table 3: Locomotor activity of 2-(1H-benzo[d][1,2,3]triazol-1-yl)-N'-(2-substituted benzylidene)
acetohydrazide (Va -Vg)
S.
No.
Compound Substituents
(R)
Locomotor activity (scores)
in 10 min, n = 6
% Change in
Activity(↓)
Before
Administration
After
Administration
1 Va -H 408 177 56.6
2 Vb 4-Cl 397 86 78.34
3 Vc 4-OCH3 429 184 57.16
4 Vd 3-OCH3
4-OH
373 171 54.27
5 Ve 4-N(CH3)2 306 95 68.95
6 Vf 2-OH 387 180 53.48
7 Vg 2-Cl 420 115 72.61
n = number of animals
*The compounds were tested at a dose of 100 mg/kg (I.P)
RESULTS AND DISCUSSION
All the compounds 2-(1H-benzo[d][1,2,3]triazol-
1-yl)-N'-(2-substituted benzylidene) acetohydrazide
(Va - Vg) were schematically synthesized as planned
and were authentically identified by their physical and
spectral data.
Gross behavioral studies
All the newly synthesized compounds were
screened for gross behavioral studies. The gross
behavioral studies of the test compounds revealed that
all the test compounds exhibited central nervous
system depression in the mice.
Table 2 pertaining to the gross behavioral studies of
2-(1H-benzo[d][1,2,3]triazol-1-yl)-N'-(2-substituted
benzylidene) acetohydrazide (Va - Vg) shows that all
the compounds did not show alertness. Among the
test compounds, Vb, Vg and Ve showed more
depressant activity than the rest of the compounds.
Locomotor activity
Table 3 pertaining to the results of the locomotor
activity of the 2-(1H-benzo[d][1,2,3]triazol-1-yl)-N'-
(2-substituted benzylidene) acetohydrazide (Va - Vg)
in mice showed that all the test compounds reduced
the locomotor activity. The locomotor activity was
studied by actophotometer. The compound Vb (R = 4-
Cl) exhibited more effect among all the compounds
with 78.34% reduction activity. The compound Vg (R
= 2-Cl) reduced the locomotor activity by 72.61% and
the compounds Ve, Vc, Va, Vd and Vf were next in
the order of reduction of locomotor activity.
CONCLUSION
The proposed 2-(1H-benzo[d][1,2,3]triazol-1-yl)-
N'-(2-substituted benzylidene) acetohydrazide (Va -
Vg) derivatives were synthesized successfully as per
the planning and as such in all the reactions carried,
the expected compounds were obtained with good
yield. From the gross behavioral studies and
locomotor activity, all the newly synthesized
compounds showed CNS depressant activity in mice.
The compound Vb with 4-Chloro substitution on the
phenyl ring showed more promising depressant
activity among all the test compounds.
Acknowledgements
The authors are thankful to the Directors and
Principals of Talla Padmavathi College of Pharmacy,
Warangal, Sri Shivani Pharmacy College and SVS
School of Pharmacy, Warangal, for providing
laboratory facilities and financial support.
8. Srikanth L et al / Int. J. of Farmacia, 2017; Vol-(3) 2: 65-72
72
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