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Synthesis of 5,6-Dichloroindan-1-Acids and their Tetrazolyl Derivatives as Analgesic and Anti-inflammatory Agents
Abstract
Indan derivatives, namely, 5-(5',6'-dichloroindan-1'-yl)-tetrazole (12a) and 5-(5',6'-dichloroindan-1'-yl)- methyltetrazole (12b), were synthesized conveniently from 5,6-dichloroindan-1-carboxylic acid (9a) and 5,6- dichloroindan-1-acetic acid (9b), respectively, as potential analgesic and anti-inflammatory agents. The analgesic and anti-inflammatory properties of 9a, 9b, 12a and 12b were evaluated by the acetic acid induced writhing in Swiss albino mice and the carrageenan-induced rat paw edema models, respectively. Compounds 9a and 12a exhibited significant analgesic activity with the doses of 50 and 100 mg/kg body weight, comparable to that of the positive controls, phenylbutazone, indomethacin and aminopyrine. The anti-inflammatory potencies of 9a and 12a were also comparable to that of the positive control, phenylbutazone. Compounds 9b and 12b showed analgesic and anti-inflammatory activities, but were weaker than that of compounds 9a and 12a.
... Among the compounds that he isolated and identified from this genus mainly belong to the phytochemical classes of flavonoids and sesquiterpenes, and many of those were new compounds. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] The very first joint publication, where SDS was a co-author, was published in the leading journal, Phytochemistry, 2 which described the isolation and identification of two new compounds, viscosumic acid (21) and a feruloyl derivative of quercetin galactoside (9), together with a known flavonoid, 3'5-dihydroxy-3,4',5',7-tetramethoxyflavone (1) from Polygonum viscosum Buch-Ham. (Figures 1 and 2). ...
... Collaborative bioactivity studies, mainly but not exclusively, on the analgesic and antiinflammatory activities, were with the crude extracts and isolated compounds from the genera Polygonum, 11,[17][18][19][20][21] Phyllanthus 15 and Nicotiana, 16 but also included several synthetic indan derivatives. 13,14 The most recent bioactivity study was on the isolated rare polymethoxyflavones (Figure 1) from the Nicotiana plumbaginifolia Viv. of the family Solanaceae, where it was demonstrated that these flavonoids possess significant antinociceptive property, as evident in the acetic-acid-induced writhing, hot plate, tail immersion, formalin and carrageenan-induced paw edema tests. 16 These compounds could also display neuropharmacological effects in mice. ...
... Among the sesquiterpenes only viscoazulone (19) showed anti-HIV activity with an IC 50 value of 33.13 g/ml). Polygosumic acid (14), isolated from P. viscosum was shown to possess antibacterial activity, and found to inhibit the growth of penicillinresistant Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) in the resazurin assay with MIC ranging between 0.05 and 0.10 mg/mL). 9 Viscozulenic acid methyl ether (18) and viscoazucinic acid (16) showed low levels of antibacterial activity. ...
Professor Bidyut Kanti Datta, a renowned professor of the Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, died at the age of 73 on Friday 11 September 2020 in Canada (Canadian time 7.10 am and BD time 5.10 pm), as a consequence of COVID-19 infection followed by pneumonia. This article is a brief review of his research work where the authors of this article are immensely proud to be associated with. Prof Datta published more than 60 research articles in reputed journals, and the lead author (SDS) of this article, one of his former students from the University of Dhaka, is a co-author of 20 of those publications. These 20 publications resulted from a long-standing research collaboration that spanned over two decades, especially research involving various Bangladeshi species of the genus Polygonum L. of the family, Polygonaceae, and they demonstrate the breadth and depth of research activities that Prof Datta was involved in, and his long-standing commitment to research that underpinned and enriched his teaching offerings to hundreds of students he taught in higher education sector in Bangladesh. Dhaka Univ. J. Pharm. Sci. 19(2): 97-103, 2020 (December)
... Indane nucleus subsequently being an appealing framework for therapeutic scientists (an isostere of indole ring, fig. 1) numerous indane based compounds (Bjarnason and Hayllar, 1993) are used clinically to treat various diseases including antiplatelet compounds (Palladino et al., 2003, Nigar et al., 2015. Furthermore, many other synthetic derivatives of indanone/indane ring system are medicinally important such as anti-inflammatory (Bepary et al., 2008, Kumar Pal et al., 2012, Saravanan et al., 2006, analgesic (Kumar Pal et al., 2012, Saravanan et al., 2006, antiplatelet aggregation (Amidi et al., 2013), and thromboxane A 2 antagonist (Shinozaki et al., 1999). Out of these biological activities of indanone and their derivatives, anti-inflammatory activity is of particular interest. ...
... Indane nucleus subsequently being an appealing framework for therapeutic scientists (an isostere of indole ring, fig. 1) numerous indane based compounds (Bjarnason and Hayllar, 1993) are used clinically to treat various diseases including antiplatelet compounds (Palladino et al., 2003, Nigar et al., 2015. Furthermore, many other synthetic derivatives of indanone/indane ring system are medicinally important such as anti-inflammatory (Bepary et al., 2008, Kumar Pal et al., 2012, Saravanan et al., 2006, analgesic (Kumar Pal et al., 2012, Saravanan et al., 2006, antiplatelet aggregation (Amidi et al., 2013), and thromboxane A 2 antagonist (Shinozaki et al., 1999). Out of these biological activities of indanone and their derivatives, anti-inflammatory activity is of particular interest. ...
This research based on the anti-inflammatory and antiplatelet aggregation properties of some new thiazolyl hydrazone derivatives of 1-indanone. In this regard a thiosemicabazone and twelve thiazolyl derivatives of 1-indanone have been synthesized. Out of these synthetic compounds seven derivatives 1-3, 6, 11-13 exhibited varying degree of anti-inflammatory action with IC50 esteems going from 5.1±1.3 - 78.8±4.6μM/mL. Compound 1 (IC50 =5.1±1.9μM) displayed potent result than standard ibuprofen (IC50 = 11.2±1.9 μM). In antiplatelet aggregation assay, five compounds 1, 5, 6, 8 and 11 were observed to be dynamic with IC50 esteems observed in the range of 38.34-255.7±4.1μM, wher eas, aspirin (IC50 = 30.3±2.6 μM) was used as standard. However, compound 11 was found to be good active for both anti-inflammatory and antiplatelet aggregation activities (IC50 = 13.9±4.9μg/mL) (IC50 = 38.60±3.1μM), respectively.
... Various indan derivatives possessing anti-inflammatory activity have been reported [3][4][5][6][7][8][9][10]. Indan-1-carboxylic acid seems to involve essential conformation of phenyl acetic acids for exerting the anti-inflammatory activity [11] Research in this area has led to the development of Clidanac, 6-chloro-5-cyclohexylindan-1-carboxylic acid, with an ED 30 of 0.85 mg/kg [12]. ...
A series of ester derivatives of (6-chloro-3-oxo-2,3-dihydro-1H-inden-l-yl)acetic acid were synthesized and screened for their analgesic and anti-inflammatory activities. These were designed to serve as possible potential nonsteroidal anti-inflammatory agents free from gastrointestinal toxicity and sulphur sensitivity. The synthesized compounds exhibited useful analgesic activity but low anti-inflammatory activity. Few selected compounds were also screened for their antipyretic and ulcerogenic potential. The compounds showed no ulcer formation at the dose level of 100 mg/kg p.o. Aspirin was used as the standard nonsteroidal anti-inflammatory agent. Experimental results indicate that compound 5d holds promise to serve as a novel lead for designing better (less toxic) analgesic antipyretics. Please cite this article in press as Saumendra Mohan Ray et al. Synthesis and biological evaluation of (6-chloro-3-oxo-2,3-dihydro-1H-inden-1-yl)acetic acid esters as anti-inflammatory agents devoid of ulcerogenic potential at the tested dose level.
... Various indan derivatives possessing anti-inflammatory activity have been reported [3][4][5][6][7][8][9][10]. Indan-1-carboxylic acid seems to involve essential conformation of phenyl acetic acids for exerting the anti-inflammatory activity [11] Research in this area has led to the development of Clidanac, 6-chloro-5-cyclohexylindan-1-carboxylic acid, with an ED 30 of 0.85 mg/kg [12]. ...
A series of ester derivatives of (6-chloro-3-oxo-2,3-dihydro-1H-inden-l-yl)acetic acid were synthesized and screened for their analgesic and anti-inflammatory activities. These were designed to serve as possible potential nonsteroidal anti-inflammatory agents free from gastrointestinal toxicity and sulphur sensitivity. The synthesized compounds exhibited useful analgesic activity but low anti-inflammatory activity. Few selected compounds were also screened for their antipyretic and ulcerogenic potential. The compounds showed no ulcer formation at the dose level of 100 mg/kg p.o. Aspirin was used as the standard nonsteroidal anti-inflammatory agent. Experimental results indicate that compound 5d holds promise to serve as a novel lead for designing better (less toxic) analgesic antipyretics. Please cite this article in press as Saumendra Mohan Ray et al. Synthesis and biological evaluation of (6-chloro-3-oxo-2,3-dihydro-1H-inden-1-yl)acetic acid esters as anti-inflammatory agents devoid of ulcerogenic potential at the tested dose level.
... Various indan derivatives possessing anti-inflammatory activity have been reported [3][4][5][6][7][8][9][10]. Among the various indan-1alkanoic acids prepared as potential anti-inflammatory agents [1,3,4,11], some of the compounds not only showed anti-inflammatory activity comparable to phenylbutazone but were also much less ulcerogenic. ...
... Generally, they play an active and critical role in the biochemistry of human or animal physiology. They have been involved in studies as antibacterial [3], anti-inflammatory [4], antiplatelet [5], antimicrobial [6], anticancer [7], antifungal [8], and analgesic and antiseptic [9]. ...
Our search for new antibiotics led to the syntheses and biological evaluation of new classes of dicarboxylic acid analogues. The syntheses involve nucleophilic addition of different substituted benzylamine, aniline, alkylamine, and 4-hydroxyl-L-proline with carbamoylbenzoic acid. The results of the antimicrobial activity as indicated by the zone of inhibition (ZOI) showed that
Z
10
is the most active against
Pseudomonas aeruginosa
(32 mm) and least active against
Candida stellatoidea
(27 mm) and Vancomycin Resistant
Enterococci (VRE)
(27 mm), while
Z
7
shows the least zone of inhibition (22 mm) against Methicillin Resistant
Staphylococcus aureus (MRSA)
. The minimum inhibition concentration (MIC) determination reveals that
Z
10
inhibits the growth of tested microbes at a low concentration of 6.25
μ
g/mL, while
Z
9
and
Z
12
inhibits the growth of most microbes at a concentration of 12.5
μ
g/mL, recording the least MIC. The Minimum Bactericidal/Fungicidal Concentration (MBC/MFC) results revealed that
Z
10
has the highest bactericidal/fungicidal effect on the test microbes, at a concentration of 12.5
μ
g/mL, with the exception of
Candida stellatoidea
and Vancomycin Resistant
Enterococci (VRE)
with MBC/MFC of 25
μ
g/mL. The result of this investigation reveals the potential of the target compounds (
Z
1
–
3
,
5
,
7
–
12
) in the search for new antimicrobial agents.
Following induction of inflammation, the nuclear factor kappa B (NF-κB) in activated macrophages induces the transcription of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and cyclooxygenase (COX), an inflammatory enzyme implicated in the synthesis of prostaglandins (PGs). The latter are involved in the transition and the maintenance of chronic inflammation underling various chronic disorders that require treatment. Concerning this, many anti-inflammatory drugs are available to treat the inflammatory disorders, but their therapeutic use is associated with a variety of side effects. Therefore, the discovery of new safer and potential anti-inflammatory drugs is necessary. In this regard, thiosemicarbazones (TSC) compounds and their metals complexes attracted high interest due to their wide range of biological activities, interestingly, the anti-inflammatory activity. They are formed by the action of thiosemicarbazide on an aldehyde or ketone, and contain a sulfur atom in place of the oxygen atom. Their ability to form a stable complex with transition metal is known to enhances the biological activity and reduces the side effects of the parent compound. Thus, this review article describes the inflammatory response mediated by NF-κB-COX-PGs and summarizes the anti-inflammatory activity of different thiosemicarbazones derivatives synthesized in research area.
Magnetic nano catalysts are widely used in various organic reactions due to their characteristics of magnetic separation and recycling. Magnetic Fe3O4@SiO2 nano catalyst modified by 1, 8-diazabicyclo [5.4.0]-7-undecene (DBU) was prepared and applied in the Knoevenagel reaction. The results showed that the catalyst has an excellent effect on the Knoevenagel reaction, which not only improves the reaction rate and yield, but also it can be easily separated from the reaction mixture driven by external magnetic force. Furthermore, the catalyst can be recycled 10 cycles with no loose of the catalytic activity.
A simple, efficient, and green procedure for the synthesis of 5-substituted-1H-tetrazoles via [3 + 2] cycloaddition reaction of nitriles with sodium azide is described. The reaction was catalyzed by natural and mesoporous alum nanoparticles (NPs) in DMSO at 140 °C. Alum NPs have been prepared as the new catalytic system by heating and calcination of mineral alum in a furnace. Alum NPs were characterized using FT-IR, BET, SEM-EDS, XRD, and TGA analysis. The results showed that alum, as an amorphous mineral and natural low-cost heterogeneous catalyst, provides 5-substituted-1H-tetrazoles easily with high efficiency. Some of the advantages of this method are high yields of the desired product, short reaction times, the safe catalyst, prevention of using the toxic metal catalysts, readily accessible of the catalyst, and low-cost heterogeneous catalyst.
The conjugate hydrocyanation of alpha-cyanoacrylates through chemoselective 1,4-addition to synthesise alpha, beta-dicyanopropanoates by one-pot two-step procedure using potassium hexacyanoferrate(II) as an eco-friendly cyanide source, benzoyl chloride as a promoter and potassium carbonate as a catalyst is described. The advantages of this protocol are use of a non-toxic, non-volatile and inexpensive cyanating reagent, high product yields and simple working procedure. (c) 2014 Institute of Chemistry, Slovak Academy of Sciences
Synthesis of a series of nine compounds of the class indanone-3-acetic acid derivatives was undertaken with compounds containing indane ring moiety which itself is well known as a potential carrier for inducing biological activity in organic molecules. In fact, indane derivatives are known to have a wide spectrum of biological activity such as analgesic, antiinflammatory, monoamino oxidase inhibitory, antidepressant, antibacterial activity etc. In the present work, nine indanone-3-acetic acid derivatives were prepared in the laboratory by the steps: conversion of 3-hydroxy-4-methoxy benzaldehyde to a bis(acetoacetate), hydrolysis of the bis(acetoacetate) to yield the corresponding β-phenylglutaric acid and cyclization to indanone-3-acetic acid. Condensation of different amines was effected via acid chloride formation by refluxation with thionyl chloride followed by treatment with appropriate amines for different optimum periods in benzene. Elemental analysis and IR, NMR data characterized the synthesized compounds. All the synthesized compounds were allowed to undergo antiinflammatory activity by carrageenan induced hind paw method. Some of the compounds showed appreciable activity.
Chloro and bromo substututed indanyl tetrazoles (compounds 5a, b) and indanyl methyltetrazoles (compounds 5c, 5d) have been synthesized from their respective acids through amide and nitrile routes, and characterized. The title compounds (5a, 5b, 5c and 5d) were subjected for their analgesic activity in the acetic acid induced writhing test on albino mice. The significant (p < 0.001) analgesic activity, exhibited by the compound 5b at a dose of 50 mg/kg body weight, was comparable to that of phenylbutazone and indometacin at a dose of 100 and 50 mg/kg body weight respectively. The effect of
substitution at the benzenoid part of the indan nucleus and chain length on analgesic activity was in the following order: bromine > chlorine and tetrazole > methyltetrazole
Aus der Carbonsäure (I) erhält man über (II) und (IV) das Methylcyclopentylderivat (V), das gute antiinflammatonische und anaggetische Wirkung besitzt.
The indancarbonitriles (IV), prepared from the carboxylic acids (I) via dehydration of the amides (III), are treated with sodium azide (V) to form the indanyltetrazoles (VI).
An improved synthesis of 5-substituted tetrazoles has been devised. Alkyl- or arylnitriles and inorganic azides react readily in solvents such as dimethylformamide and diethyl sulfoxide. Relatively low reaction temperatures and short reaction times are effective, and the need for pressure equipment is eliminated. The effects caused by varying the solvent, the electronegativity of the substituent on the nitrile and the nature of the azide salt have been studied and a tentative mechanism for the reaction is advanced.