1,3,4-Oxadiazole: A New Profile of Biological Activities

 

Ajay A. Kharche, Shriram H. Bairagi, Nilesh K. Gorde and Sachin S. Laddha

Ideal College of Pharmacy and Research, Adarsh Vidya Nagari, Via Kalyan Rly. Station, Malang Road, At-Bhal, Post: Dwarli, Dist: Thane (MS) 421301.

*Corresponding Author E-mail: paresh2009@ymail.com

 

ABSTRACT:

The small and simple 1,3,4-oxadiazole nucleus is present in compounds involved in research aimed at evaluating new products that possess interesting biological activities, such as antimicrobial, antitumor, anticonvulsant, antiviral, analgesic and antiinflammatory. The present review focuses on the 1,3,4-oxadiazole with potential activities that are now in development.

 


 

INTRODUCTION:

1,3,4-Oxadiazoles are unicyclic ring system which found to have diverse chemical reactivity and broad spectrum of biological activity.

 

Although they have been known from long ago to be biologically active, their varied biological features are still of great scientific interest. 1,3,4-oxadiazole show antitumor activity, especially the phenyl-substituted 1,3,4-oxadiazole1-2, while phenacyl-1,3,4-oxadiazole exert ulcerogenic activity3. Recently, Zheng Li et al.4 have described the synthesis of 2-(3-methylbenzoylamino)-5-aryloxymethyl-1,3,4-oxadiazoles as potential monoamine oxidase inhibitor. Given below is a brief account of various alterations conducted on 1,3,4-oxadiazole ring and their associated biological activities.

 

ANTIMICROBIAL ACTIVITY:

1,3,4-oxadiazole show a wide spectrum of antimicrobial activity and a considerable amount of work has been done on the synthesis of new potent antibacterial and antifungal 1,3,4-oxadiazoles. Khanum, S.A. et al5, prepared some new 5-(2-aroylaryloxy)methyl-1,3,4-oxadiazole-2-(3H)thiones (1) and screened them for their antibacterial activity against E.coli, B.subtilis, P.fluorescens, P.solanacearum, and for their antifungal activity against C.albicans, C.krusei, C.parapsilosis, A.flavus, A.ochraceous, F.moniliforme. The antifungal screening results have been shown that the halo substituted compounds exhibit significant activity. In case of antibacterial activity all the compounds have shown higher activity.

 

Various 1,3,4-oxadiazole derivatives were prepared by Kadi, A.A. et al6, and found to possess good activity against S.aureus, B.subtilis, E.coli, P.aeuroginosa and C.albicans. Some 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles (2) (R=C6H5, 4-FC6H4, 4-ClC6H4, 4-BrC6H4, 4-NO2C6H4, 3,5-(NO2)2C6H3, 3,4-(OCH3)2C6H3, 2-Thienyl, 1-Adamantyl) were synthesized and studied for their antibacterial and antifungal activities. All compound shows moderate activity against B.subtilis, C.albicans.

 

Hui, X.P. et al7, synthesized 4-acetyl-2-(5-methylisoxazol-3-yl)-5-substituted-1,3,4-oxadiazoles (3) (a]R1=CH3, R2= C6H5 b] R1=H, R2= 4O2NC6H4 c] R1=H, R2= C6H5) and studied for their antibacterial activity. All compound shows moderate activity against E.coli, S.aureus, B.subtilis.

 

Mogilaiah, K. et al8, worked on a few 3-(5-aryl-1,3,4-oxadiazol-2-yl)-2-2phenyl-1,8-naphthyridine (4) and found them active against E.coli, P.aeruginosa, B.subtilis and B.mycoides.

 

Peesapati, V. et al9, synthesized a few 2,5-Disubstituted-1,3,4-oxadiazole derivatives and found to possess moderate antibacterial activity against gram positive bacteria S.aureus and gram negative bacteria Klebsiella.

 

Mogilaiah, K. et al10, has prepared a series of multi-substituted 1,3,4-oxadiazole 5-aryl-2-(2-trifluoromethyl-1,8-naphthyridin-3-yl)-1,3,4-oxadiazole (5) and tested for their antibacterial and antifungal activity against gram negative bacteria E.coli, P.aeruginosa and gram positive bacteria B.subtilis, B.mycoides. The antifungal testing was carried out against C.lunata and F.oxysporum using filter paper disc method. The synthesized compound possesses a broad spectrum of activity against the tested microorganism.

 

Dhiman, A.M. et al.11, prepared 2-(3-aryl-1H-pyrazol-3-yl)-3-substituted amino-1,3,4-oxadiazoles (6) and tested for their antibacterial activity against pathogenic bacteria S.aureus, E.coli, S.dysenteriae, S.typhi, K.pneumoniae, P.vulgaris and P.mirabilis following cup plate method. All the compound was active against both the gram negative and gram positive bacteria.

 

Padmavathi, V. et al.12, prepared a series of 2-(arylsulfonylmethyl)-5-aryl-1,3,4-oxadiazoles (7) and tested for in vitro antimicrobial activity against the gram positive bacteria S.aureus, B.subtilis and gram negative bacteria K.pneumoniae, P.vulgaris and fungi F.solani, C.lunata and A.niger. followed by agar disc diffusion method using nutrient agar medium. The findings obtained showed that some of the tested compound displayed moderate to high activity towards gram positive bacteria and moderate activity towards gram negative bacteria. While some exhibit least activity against both bacteria.

 

Liu, F. et al.13, worked on a few 2-substituted sulfinyl-5-(3,4,5-Trimethoxyphenyl)-1,3,4-oxadiazole (8) and were tested against three pathogenic fungi namely G.zeae, F.oxysporum, C.mandshurica by the poison plate technique and it was found that all the compounds possess moderate antifungal activity against all these fungi.

 

Some 2-{4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl}-5-substituted-1,3,4-oxadiazoles (9) were prepared by Gaonkar, S.L. et al14 and studied for their antimicrobial activity by disc diffusion and micro dilution method against B.subtilis, E.coli, P.fluorescens, X.campestris, X.oryzae, A.niger, A.flavus, F.oxysporum. Among the series of oxadiazole synthesized some compounds shows significant inhibition while some shows moderate activity.

 

Zou, X.J. et al15, worked on a few 5-[1-aryl-1,4-dihydro-6-methypyridazin-4-one-3-yl]-2-arylamino-1,3,4-oxadiazole (10) and tested for antifungal activity in vivo on wheat leaf rust, Puccinia recondite and found biologically active.

 

Shetgiri, N.P. et al16, prepared 2-oxymethyl-[substitutedphenyl]-5-phenyl-1,3,4-oxadiazole (11) and screened for their antibacterial activity against pathogenic organisms B.subtilis, E.coli and S.flemeri and antifungal activity against S.aureus, C.albicans and A.niger followed by cup plate method. All the compounds exhibit moderate activity against these microorganisms.

 

Some 2-amino-4-[5-{(2-chlorophenyl)-1,3,4-oxadiazol}-2-yl]-6-aryl/substituted aryl-7-oxo-6,7-dihydrothiazolo[4,5-d]pyrimidine-5(H)-thiones (12) were prepared by Hazarika, J. et al17, and screened for fungitoxic and antibacterial activity C.verruciformis, A.tenuis, B.cerius, B.subtilis, E.coli, P.solanarium. From these some derivatives did not show activity against P.solanarium, remaining all possess significant to moderate activity against all the fungi and bacteria.

 

Rai, K.M. et al.18, Synthesized 2-(4-pyridyl)-5-alkyloxy-1,3,4-oxadiazoles and tested for their fungicidal activity against C.albicans, A.flavus, A.ochraceous and F.moniliforme. It was found that all derivatives exhibit moderate antifungal activity.

 

Shah, V.R. et al19, prepared 2-(p-Methoxyphenyl)amino-5-p-(nicotinamido-phenyl)-1,3,4-oxadiazole (13) and screened for their in vitro antimicrobial activity by cup plate agar diffusion method against a variety of bacterial strains such as E.coli, S.typhosa, S.citrus, B.megaterium, among all the derivatives few showed highest activity (26-30mm) against the above microbes.

 

Khan, M.H. et al20, prepared a series of 5-aryl-2-[spiro-(1,3-dithiolane)-2,4’-(3’-chloro-2’-azetidinon)-1’-yl]-1,3,4-oxadiazoles (14) and screened for antibacterial and antifungal activity against A.niger, P.oryzae, F.oxysporum, C.sacchari, E.coli, S.typhi, B.aureus by agar growth technique and filter paper disc method. It was found that some compounds exhibit antifungal activity 75-85% at 100ppm concentration against P.oryzae, F.oxysporum. whereas some compounds showed strong antibacterial activity  and some showed moderate activity against E.coli and S.typhi.

 

The series of 5-aryl-2-thiones derivatives of 1,3,4-oxadiazole (15) were synthesized by Krasovskii, A.N. et al21, and evaluated for their in vitro tuberculostatic activity by the method of serial dilutions using the Levenstein-Jensen dense egg culture medium, against M.tuberculosis, M.bovinus, and M.avium, and the activity was expressed as the minimum inhibitory concentration (MIC), some substances exhibited appreciable activity particularly against M.tuberculosis.

 

Various 4-(5-substituted-1,3,4-oxadiazol-2-yl)pyridines derivatives (16) containing different functional groups have been synthesized and all the compounds have been screened for their in vitro antimycobacterial  activity against five clinical isolates of M.tuberculosis and compared with standards (Isoniazid, Streptomycin). Some pentadecyl and heptadecyl substituted compounds showed an interesting activity against M.tuberculosis H37RV.22

 

Various 5-aryl-2-thio-1,3,4-oxadiazoles (17) derivatives were prepared by Macaev, F. et al23, and screened for their in vitro antimycobacterial activity against M.tuberculosis H37RV using the Microplate Alamar Blue Assay (MABA) method, and taking Rifampicin as an standard. All the derivatives possess significant to moderate activity against M.tuberculosis. Some derivatives of 2,5-disubstituted-1,3,4-oxadiazoles were synthesized by Kagthara et al24 and screened for their antitubercular activity against M.tuberculosis H37RV.

 

ANTITUMOR ACTIVITY:

Some 3-acetyl-2-substituted phenyl-5-(3,4,5-trimehtoxyphenyl)-2,3-dihydro-1,3,4-oxadiazole (18) derivatives were synthesized by Jin L. et al25, the in vitro antitumor activity of all new compounds was evaluated against PC3, BGC823, and Bcap37 cells by MTT method. They found that highest inhibitory activity was achieved when R=2,4-dimethoxy and R=3,5-dichloro at 1 and 5 µM, respectively.

 

Novel indolyl-1,3,4-oxadiazoles (19) was prepared by Kumar, D. et al26, and all these derivatives were screened for their in vitro anticancer activity against human cancer cell lines from prostate (PC3, DU145 and LnCaP), breast (MCF7 and MDMDA231), and pancreas (PaCa2). Most of the compounds decreased cell viability significantly as established by colorimetric MTT mitochondrial assay with IC50 values ranging from 1 µM to 1 mM concentration. They found that when R=C6H5 and R = CH2C6H5 the compound exhibit moderate activity against MCF7. A significant increase in activity and selectivity was observed against PC3, MCF7 and PaCa2 when R=4-pyridyl.

 

Aboraia, A.S. et al27, synthesized a series of 5-(2-hydroxyphenyl)-3-substituted-2,3-dihydro-1,3,4-oxadiazole-2-thione derivatives and evaluated in the 3-cell line panel consisting of NCIH460 (lung), MCF7 (breast), and SF-268 (CNS). The compounds exerted a different inhibitory effect, depended on the concentration and type of cells. The best inhibitory effect was achieved with compounds (20a) and (20b). All of them inhibited the growth of examined tumor cell lines and also normal fibroblasts. Other examined compounds exhibited a moderate inhibitory effect, depending on type of the cells.

 

Formagio, A.S.N. et al28, synthesized a series of β-carboline derivatives, 3-(2-substituted-1,3,4-oxadiazol-5-yl) (21). The anticancer activity of all synthesized 1,3-disubstituted β-carboline derivatives was evaluated in vitro against eight human tumor cell lines: melanoma (UACC-62), breast (MCF7), lung (NCI-460), leukemia (K-562), ovarian (OVCAR), prostate (PCO-3), colon (HT-29), and renal (786-0). And it was found that, 2 compounds exhibit moderate anticancer activity against these tumor cell lines when R=H and R=Cl.

 

Liszkiewicz, H. et al29, prepared a series of 5-(2-amino-3-pyridyl)-2-hydrazin-1,3,4-oxadiazole (22), 5-(2-amino-3-pyridyl)-2-(2-pyridylmethylamino-1,3,4-oxadiazole (23), 5-(2-amino-3-pyridyl)-2-piperidin-1,3,4-oxadiazole (24). All these compounds are tested for their antiproliferative activity in vitro against the cells of human cancer cell lines: A549, HCV29T, SW707, T47D. And it was found that these compounds revealed significant cytotoxic activity against the cells of all 4 lines applied.

 

Some 2,5-disubstituted-1,3,4-oxadiazole derivatives (R=Ph, 3-ClC6H4, 2-NO2-4-ClC6H3 etc.) was prepared by Shah, H.P. et al30, and screened for their anticancer activity against the cells of human cancer cell line.

 

ANTICONVULSANT ACTIVITY:

Zarghi, A. et al31, synthesized a series of 2-substituted-5-(2-benzyloxyphenyl)-1,3,4-oxadiazoles (25), Benzodiazepine activity of the synthesized compounds was determined through the evaluation of the ability of the compounds to protect mice against convulsion induced by a lethal dose of PTZ and electroshock. And he found that the compound with amino group on position 2 of oxadiazole ring and fluoro substituent at the para position of benzyloxy group has the best anticonvulsant activity in both PTZ and MES models.

 

Some 5-methyl-3-[p-(6’-aryl-2’-thioxo-1’,2’,5’,6’-tetrahydopyrimidin-4’-yl)-phenyl]-3H-2-oxo-Δ4-1,3,4-oxadiazoles (26) was prepared by Kamble, R.R. et al32, and screened for anticonvulsant activity, he found that compound with R=p-CH3C6H4- and R=p-ClC6H4- possess promising activity, compared to that of standard phenytoin.

Almasirad, A. et al33, synthesized some 2-substituted-5-[2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazole (27). The compounds were screened for their anticonvulsant activity against pentylenetetrazole (PTZ) induced lethal convulsion and maximal electroshock (MES) tests and found that all the compounds possess moderate anticonvulsant activity.

 

A series of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles (28) was designed and synthesized by Zarghi, A. et al34, and also performed in vivo anticonvulsant activity for evaluating BZD effects, he found that the compounds with amino group on position 2 of oxadiazole ring and fluoro substituent at para position of benzylthio group has the best anticonvulsant activity in both PTZ and MES models. The remaining compounds show moderate activity on both models.

 

Nassar, O.M. et al35, synthesized certain 1,3,4-oxadiazole derivatives and screened them for their anticonvulsant activity to evaluate benzodiazepine effect by using PTZ and MES models.

 

ANTIVIRAL ACTIVITY:

Tan, T.M.C. et al36, synthesized a series of 2-benzenesulfonylalkyl-5-substituted-sulfanyl-[1,3,4]-oxadiazoles (29) derivatives. The compounds were then evaluated for their anti-HBV activity. And it was found that none of the compounds tested had an effect on the production of HBsAg except (29a) which was effective in reducing HBsAg production.

 

A series of 2-arylamino-5-(D-glucopentyl or D-xylobutyl)-5H-thiazolo[4,3-b]-1,3,4-oxadiazoles (30), was synthesized and screened for their in vitro antiviral activity activity against the viral species chenopodium amaranticolor by Yadav, L.D.S. et al37, he found that compound (30a) and (30b) exhibit significant antiviral activity when compared with standard virazole at 1000 ppm. concentration.

 

Kucukguzel, S.G. et al38, prepared 2-substituted-1,3,4-oxadiazole (31) and tested for antiviral activity against: Vesiculur stomatitis virus, reovirus, sindbis virus, puntotorovirus, herpex simplex virus type 1 and 2. compound (31a) exhibit antiviral inhibition against herpex simplex virus-2 at 16µg/ml.

 

Ei-Essawy, F.A., et al39, synthesized 1-[(5-phenylamino-1,3,4-oxadiazol-2-yl)methyl]-4,6-dimethyl-1H-[1,2,3]-triazolo[4,5-d]pyrimidine-5,7(4H,6H)-dione (32) and the preliminary viral screening was carried out against HBV, he found that this compound showed moderate viral replication inhibition.

 

ANALGESIC ACTIVITY:

Jayashankar, B. et al40, synthesized some 2-(((4,5-dihydro-3-aryl-isoxazol-5-yl)methoxy)methyl)-5-aryl-1,3,4-oxadiazole (33) derivatives, all the derivatives were screened for their analgesic activity, at 100 mg/kg in acetic acid-induced assay in mice, and it was found that 5 compounds i.e. a) 2-(((4,5-Dihydro-3-p-tolylisoxazol-5-yl)methoxy)methyl)-5-(2,4-dichlorophenyl)-1,3,4-oxadiazole, b) 2-(((4,5-Dihydro-3-(3,4,5-trimethoxyphenyl)isoxazol-5-yl)methoxy)methyl)-5-(2,4-dichlorophenyl)-1,3,4-oxadiazole, c) 2-(((4,5-Dihydro-3-(3-nitrophenyl)isoxazol-5-yl)methoxy)methyl)-5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazole, d) 2-(((4,5-Dihydro-3-(4-nitrophenyl)isoxazol-5-yl)methoxy)methyl)-5-(2,4-dichlorophenyl)-1,3,4-oxadiazole, e) 2-(((4,5-Dihydro-3-(4-nitrophenyl)isoxazol-5-yl)methoxy)methyl)-5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazole are statistically significant as compared to standard drug Aspirin.

 

Some 3-[5-(Substituted aryl)-1,3,4-oxadiazol-2-yl]-1-(biphenyl-4-yl)propan-1-ones (34) was prepared by Husain, A. et al41, The analgesic activity of the synthesized compounds was evaluated by acetic acid induced writhing test, the compounds showed activity ranging from 45.12% to 72.52%. Compound (34a) showed maximum activity 72.52%, and its activity was better than that of the standard drug diclofenac (70.32%). and the remaining compound shows significant activity as compared to standard.

 

Amir, M. et al42, prepared some 2-arylamino-5-substituted-1,3,4-oxadiazoles (35) derivatives as an analgesic agents. The result showed analgesic activity ranging from 78.57% to 81.86%, better than the standard drug diclofenac (70.32%). p-Fluoro phenyl amino group, present at the second position on oxadiazole ring 38a, showed the maximum activity (81.86%). When this group was replaced by n-butyl 38b and o-methoxy phenyl 38c, the activity was found to be slightly decreased (81.31%). When these groups were replaced by p-methyl phenyl amino group 38d, the activity was further decreased (78.57%). The result shows that an electron-withdrawing group increases the analgesic activity of the compound.

 

Khan, M.S.Y. et al43, prepared a series of 2-(Coumarin-3-yl)-5-aryl-1,3,4-oxadiazole derivatives (36), and also prepared 4-methyl-7-(5-substituted-1,3,4-oxadiazol-2-yl methoxy) Coumarin (37). The analgesic activity was carried out on wistar mice using tail flick method, he found that these all compound shows good analgesic activity in comparison to the reference drug pentazocine.

 

ANTIINFLAMMATORY ACTIVITY:

Mekuskiene, G. et al44, prepared some 5-(4,6-diphenyl-2-pyrimidinyl)-1,3,4-oxadiazole-2-thione derivatives as an antiinflammatory agents, Anti-inflammatory activity was studied by carrageenan- and bentonite-induced paw edema tests in rats. Most of the compounds were less toxic and showed higher anti-inflammatory activity than that of reference drugs – acetylsalicylic acid and ibuprofen. The most active compounds, i. e., 2-benzylthio-5-(4,6-diphenyl-2-pyrimidinyl)-1,3,4-oxadiazole (38) decreased the rats' paw edema, induced by carrageenan and bentonite, by 51.2 and 48.6% respectively. And also he prepared 3-morpholinomethyl-5-(4,6-diphenyl-2-pyrimidinyl)-1,3,4-oxadiazole-2-thione (39) which decreased the rats' paw edema, induced by carrageenan and bentonite by 43.5 and 42.2%, respectively.

 

Some 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles derivatives (40) was prepared by Kadi, A.A. et al45, The acute anti-inflammatory activity of the synthesized compounds was determined following the carrageenin-induced paw oedema method in rats. Some oxadiazole derivatives shows strong dose-dependent inhibition of carrageenin-induced oedema producing >50% inhibition at 60 mg/kg dose.

 

Akhter, M. et al46, synthesized Aroylpropionic acid based 2,5-disubstituted-1,3,4-oxadiazoles (41). The anti-inflammatory activity of compounds was carried out at an equimolar oral dose relative to 20 mg kg-1 of ibuprofen. All compounds showed inhibition of edema ranging from 24 to 90%.

 

Some indolylmethyl-1,3,4-oxadiazoles was prepared by Misra, U. et al47, They prepared 5-(Indol-3-ylmethyl)-1,3,4-oxadiazole-2-thiol (42) and screened for anti-inflammatory activity, they found the compound possess moderate anti-inflammatory activity as compared to the standard drug Indomethacin.

 

Various 5-[(biphenyl-4-yloxy)-methyl]-2-substituted-1,3,4-oxadiazoles (43) was prepared by Kumar, H. et al48, The anti-inflammatory activity of the synthesized compounds was evaluated by the carrageenan induced paw edema method of Winter et al. The compounds were tested at an equimolar oral dose relative to 10 mg/kg flurbiprofen. The tested compounds showed anti-inflammatory activity ranging from 15.90% to 81.81%, whereas standard drug flurbiprofen showed 79.54%.

 

MISCELLANEOUS:

Ke et al49, synthesized a new series of 1,3,4-oxadiazole-3(2H)-carboxamide derivatives (44) by direct heterocyclization reaction of substituted benzoylisocyanate with various aroylhydrazones as novel monoamine oxidase inhibitors (MAOIs) by kynuramine fluorimetric assay method.

 

CONCLUSIONS:

The reviewed new class of 2,5-disubstituted-1,3,4-oxadiazole has shown a wide spectrum of biological activities. 4-acetyl-2-(5-methylisoxazol-3-yl)-5-substituted-1,3,4-oxadiazoles are having significant antibacterial activity. Significant antiinflammatory activity is displayed by some new 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles and 5-(Indol-3-ylmethyl)-1,3,4-oxadiazole-2-thiol.

 

Some some 2-(((4,5-dihydro-3-aryl-isoxazol-5-yl)methoxy)methyl)-5-aryl-1,3,4-oxadiazole shows significant analgesic activity. Some β-carboline derivatives was found effective as a anticancer agents. Some 2-benzenesulfonylalkyl-5-substituted-sulfanyl-[1,3,4]-oxadiazoles was found effective as a anti-HBV agents.

The biological profile of these new generation of 1,3,4-oxadiazoles represents much more progress with regard to the older compounds.

 

REFERENCES:

1.       Ouyang X, Piatnitski EL, Pattaropong V, Chen X, He HY, Kiselyov AS, Velankar A, Kawakami J, Labelle M, Smith L, Lohman J, Lee SP, Malikzay A, Fleming J, Gerlak J, Wang Y, Rosler RL, Zhou K, Mitelman S, Camara M, Surguladze D, Doody JF and Tum CM. Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines. Bioorg Med Chem Lett. 2006; 16: 1191-1196.

2.       Sengupta, Dash P, Yeligar DK and Veerendra C. Evaluation of anticancer activity of some 1,3,4-oxadiazole derivatives. Ind J Chem. 2008; 47: 460-462.

3.       Bhandari SV, Bothara KG, Raut MK, Patil AA, Sarkate AP and Mokale VJ. Design, Synthesis and Evaluation of Antiinflammatory, Analgesic and Ulcerogenicity studies of Novel S-Substituted phenacyl-1,3,4-oxadiazole-2-thiol and Schiff bases of Diclofenac acid as Nonulcerogenic Derivatives. Bioorg Med Chem. 2008; 16: 1822-1831.

4.       Li Z, Wang X, Wang X. Syntheses and Biological Activities of 2-(3-Methylbenzoylamino)-5-aryloxymethyl-1,3,4-oxadiazoles. ChemInform. 2003; 34: 1158-1162.

5.       Khanum SA, Shashikanth S, Umesha S and Kavitha R. Synthesis and antimicrobial study of novel heterocyclic compounds from hydroxybenzophenones. Eur J Med Chem. 2005; 40: 1156-1162.

6.       Kadi AA, El-Brollosy NR, Al-Deeb OA, Habib EE, Ibrahim TM, El-Emam AA. Synthesis, antimicrobial, and anti-inflammatory activities of novel 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles and 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazoles. Eur J Med Chem. 2007; 42: 235-242.

7.       Hui XP, Chu CS and Zhang ZY. Synthesis and antibacterial activities of 1,3,4-oxadiazole derivatives containing 5-methylisoxazole moiety. Ind J Chem. 2002; 41B: 2176-2179.

8.       Mogilaiah K, Chowdary DS and Rao RB. Synthesis and antibacterial activity of pyrazole and 1,3,4-oxadiazole derivatives of 2-phenyl-1,8-naphthyridine. Ind J Chem. 2001; 40B: 43-48.

9.       Peesapati V and Chitty SV. Chemistry of benzocycloheptenones: Part I- Synthesis of 2,5-disubstituted 1,3,4-thiadiazoles/oxadiazoles as biologically active heterocycles. Ind J Chem. 2003; 42B: 616-620.

10.     Mogiliah K and Reddy PR. Hypervalent iodine mediated solid state synthesis of 1,8-naphthyridinyl-1,3,4-oxadiazoles. Ind J Chem. 2001; 40B: 619-621.

11.     Dhiman AM, Wadodkar KN and Partil SD. Synthesis and antimicrobial studyof heterocyclyl substituted s-triazoles, 1,3,4-thiadiazoles, oxadiazoles and related heterocycles. Ind. J. Chem. 2001; 40B: 636-639.

12.     Padmavathi V, Reddy GS, Padmaja A, Kondaiah P and Shazia A. Synthesis, antimicrobial and cytotoxic activities of 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles. Eur J Med Chem. 2009; 44: 2106-2112.

13.     Liu F, Luo XQ, Song BA, Bhaduri PS, Yang S, Jin LH, Xue W and Hu DY. Synthesis and antifungal activity of novel sulfoxide derivatives containing trimethoxyphenyl substituted 1,3,4-thiadiazole and 1,3,4-oxadiazole moiety. Bioorg Med Chem. 2008; 16: 3632-3640.

14.     Gaonkar SL, Rai KML and Prabhuswamy B. Synthesis and antimicrobial studies of a new series of 2-{4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl}-5-substituted-1,3,4-oxadiazoles. Eur J Med Chem. 2006; 41: 841-846.

15.     Zou XJ, Lai LH, Jin GY and Zhang ZX. Synthesis, Fungicidal activity and 3D-QSAR of Pyridazinone-Substituted 1,3,4-oxadiazoles and 1,3,4-thiadiazoles. J Agric Food Chem. 2002; 50: 3757-3760.

16.     Shetgiri NP and Nayak BK. Synthesis and antimicrobial activities of Oxadiazoles, phthalazines and indolinones. Ind J Chem. 2005; 44B: 1267-1272.

17.     Hazarika J and Kataky JCS. Studies on biologically actice heterocycles: Synthesis of 2-amino-4-[5-(2-chlorophenyl)-1,3,4-oxa/thiadiazol}-2-yl]-6-aryl/substituted aryl-7-oxo-6,7-dihydrothiazolo[4,5-d]pyrimidine-5(H)-thiones as probable bioactive compounds. Ind J Chem. 2001; 40B: 255-257.

18.     Rai KM, Manoj KC, Shetty H, Rajasekhara PK and Niranjana N. Synthesis of 2-(4-pyridyl)-5-alkyloxy-1,3,4-oxadiazoles of potential biological importance. Ind J Heterocycl Chem. 1999; 8(4): 335-336.

19.     Shah VR, Vadodaria M and Parikh AR. Synthesis of 1,3,4-oxadiazoles having nicotinamide moiety as potential antimicrobial agents. Ind J Chem. 1997; 36B: 101-103.

20.     Khan MH and Nizamuddin. Synthesis of 5-aryl-2-[spiro-(1,3-dithiolane)-2,4’-(3’-chloro-2’-azetidinon)-1’-yl]-1,3,4-oxa(thia)diazoles and 5-aryl-2-[spiro-(1,3-dithiolane)-2,2’-(4’-thiazolidinon-3’-yl]-1,3,4-oxa(thia)diazoles as antimicrobial agents. Ind J Chem. 1997; 36B: 625-629.

21.     Krasovskii AN, Bulgakov AK, Andrushko AP, Krasovskii IA, Dyachenko AM, Bokun AA, Kravchenko NA and Demchenko AM. J Pharm Chem. 2000; 34(3): 115-117.

22.     Navarrete-Vázquez G, Molina-Salinas GM, Duarte-Fajardo ZV, Vargas-Villarreal J, Estrada-Soto S, González-Salazar F, Hernández-Núńez E and Said-Fernández S. Synthesis and antimycobacterial activity of 4-(5-substituted-1,3,4-oxadiazol-2-yl)pyridines. Bioorg Med Chem. 2007; 15(16): 5502-5508.

23.     Macaev F, Rusu G, Pogrebnoi S, Gudima A, Stingaci E, Vlad L, Shvets N, Kandemirli F, Dimoglo A, and Reynolds R. Synthesis of novel 5-aryl-2-thio-1,3,4-oxadiazoles and the study of their structure–anti-mycobacterial activities. Bioorg Med Chem. 2005; 13: 4842-4850.

24.     Kagthara PR, Shah NS, Doshi RK and Parekh HH. Synthesis of 2,5-disubstituted-1,3,4-oxadiazoles as biologically active heterocycles. Indian J Chem. 1999; 38B: 572–576.

25.     Jin L, Chen J, Song B, Chen Z, Yang S, Li Q, Hu D and Xu R. Synthesis, structure, and bioactivity of N’-substituted benzylidene-3,4,5-trimethoxybenzohydrazide and 3-acetyl-2-substituted phenyl-5-(3,4,5-trimethoxyphenyl)-2,3-dihydro-1,3,4-oxadiazole derivatives. Bioorg Med Chem Lett. 2006; 16: 5036-5040.

26.     Kumar D, Sundaree S, Johnson EO and Shah K. An efficient synthesis and biological study of novel indolyl-1,3,4-oxadiazoles as potent anticancer agents. Bioorg Med Chem Lett. 2009; 19: 4492-4494.

27.     Aboraia AS, Rahman HMA, Mahfouz NM and EL-Gendy MA. Novel 5-(2-hydroxyphenyl)-3-substituted-2,3-dihydro-1,3,4-oxadiazole-2-thione derivatives: Promising anticancer agents. Bioorg Med Chem. 2006; 14: 1236-1246.

28.     Formagio ASN, Tonin LTD, Foglio MA, Madjarof C, Carvalho JE, Ferreira WC, Cardoso FP and Sarragiotto MH. Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) β-carboline derivatives. Bioorg Med Chem. 2008; 16: 9660-9667.

29.     Liszkiewicz H, Kowalska MW, Wietrzyk J and Opolski A. Synthesis and anti-proliferative activity in vitro of new 5-(2-amino-3-pyridyl)-2-thioxo-3H-1,3,4-oxadiazole derivatives. Ind J Chem. 2003; 42B: 2846-2852.

30.     Shah HP, Shah BR, Bhatt JJ, Desai NC, Trivedi PB and Undavia NK. Synthesis of 2,5-disubstituted-1,3,4-oxadiazoles as potential antimicrobial, anticancer and anti-HIV agents. Ind J Chem. 1998; 37B: 180-182.

31.     Zarghi A, Tabatabai SA, Faizi M, Ahadian A, Navabi P, Zanganeh V and Shafiee A. Synthesis and anticonvulsant activity of new 2-substituted-5-(2-benzyloxyphenyl)-1,3,4-oxadiazoles. Bioorg Med Chem Lett. 2005; 15: 1863-1865.

32.     Kamble RR and Sudha BS. 5-methyl-3-[p-(6’-aryl-2’-thioxo-1’,2’,5’,6’-tetrahydropyrimidin-4’-yl)-phenyl]-3H-2-oxo-Δ4-1,3,4-oxadiazoles. Indian J Pharm Sci. 2006; 68(2): 249-253.

33.     Almasirad A, Tabatabai SA, Faizi M, Kebriaeezadeh A, Mehrabi N, Dalvandi A and Shafiee 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; 14: 6057-6059.

34.     Zarghi A, Faizi M, Shafaghi B, Ahadian A, Khojastehpoor HR, Zanganeh V, Tabatabai SA and Shafiee A. Design and synthesis of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles as benzodiazepine receptor agonists. Bioorg Med Chem Lett. 2005; 15: 3126-3129.

35.     Nassar OM, Synthesis of certain 1,3,4-oxadiazole derivatives as potential anticonvulsant. Ind J Heterocycl Chem. 1997; 7: 105-108.

36.     Tan TMC, Chen Y, Kong KH, Bai J, Li Y, Lim SG, Ang TH and Lam Y. Synthesis and the biological evaluation of 2-benzenesulfonylalkyl-5-substituted-sulfanyl-[1,3,4]-oxadiazoles as potential anti-hepatitis B virus agents. Antiviral Res. 2006; 71: 7-14.

37.     Yadav LDS and Singh S. Synthesis of antiviral acyclic C-nucleosides incorporating thiazolo-1,3,4-oxa(thia)diazole or thiazolo-1,2,4-triazole structure as a nucleobase. Ind J Chem. 2001; 40B: 440-442.

38.     Kucukguzel SG, Kucukguzel I, Tatar E, Rollas S, Sahin F, Gulluce M, Clercq ED and Kabasakal L. Synthesis of some novel heterocyclic compounds derived from diflunisal hydrazide as potential anti-infective and anti-inflammatory agents. Eur J Med Chem. 2007; 42: 893-901.

39.     El-Essawy FA, Khattab AF and Abdel-Rahman AAH. Synthesis of 1,2,4-Triazol-3-ylmethyl-, 1,3,4-Oxa-, and -Thiadiazol-2-ylmethyl-1H-[1,2,3]-triazolo[4,5-d]pyrimidinediones. Monatshefte für Chemie. 2007; 138: 777-785.

40.     Jayashankar B, Rai KML, Baskaran N and Sathish HS. Synthesis and pharmacological evaluation of 1,3,4-oxadiazole bearing bis(heterocycle) derivatives as anti-inflammatory and analgesic agents. Eur J Med Chem. 2009; 44: 3898-3902.

41.     Husain A, Ahmad A, Alam MM, Ajmal M and Ahuja P. Fenbufen based 3-[5-(substituted aryl)-1,3,4-oxadiazol-2-yl]-1-(biphenyl-4-yl)propan-1-ones as safer antiinflammatory and analgesic agents. Eur J Med Chem. 2009; 44: 3798-3804.

42.     Amir M and Shikha K. Synthesis and anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities of some new 2-[(2,6-dichloroanilino) phenyl]acetic acid derivatives. Eur J Med Chem. 2004; 39: 535-545.

43.     Khan MSY and Akhtar M. Synthesis of some new 2,5-disubstituted 1,3,4-oxadiazole derivatives and their biological activity. Ind J Chem. 2003; 42B: 900-904.

44.     Mekuskiene G, Burbuliene MM, Jakubkiene V, Udrenaite E, Gaidelis P and Vainilavicius P. 5-(4,6-Diphenyl-2-Pyrimidinyl)-1,3,4-oxadiazole-2-thione with some C-Electrophiles and N-Nucleophiles. Chem Heterocycl comp. 2003; 39 (10): 1364-1368.

45.     Kadi AA, El-Brollosy NR, Al-Deeb OA, Habib EE, Ibrahim TM and El-Emam AA. Synthesis, antimicrobial, and anti-inflammatory activities of novel 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles and 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazoles. Eur J Med Chem. 2007; 42: 235-242.

46.     Akhter M, Husain A, Azad B, Ajmal M. Aroylpropionic acid based 2,5-disubstituted-1,3,4-oxadiazoles: Synthesis and their anti-inflammatory and analgesic activities. Eur J Med Chem. 2009; 44: 2372-2378.

47.     Misra U, Hitkari A, Saxena AK, Gurtu S and Shanker K. Biologically active indolylmethyl-1,3,4-oxadiazoles, 1,3,4-thiadiazoles, 4H-1,3,4-triazoles and 1,2,4-triazines. Eur J Med Chem. 1996; 31: 629-634.

48.     Kumar H, Javed SA, Khan SA and Amir M. 1,3,4-Oxadiazole/thiadiazole and 1,2,4-triazole derivatives of biphenyl-4-yloxy acetic acid: synthesis and preliminary evaluation of biological properties. Eur J Med Chem. 2008; 43: 2688-2698.

49.     Ke S, Li Z and Qian X. 1,3,4-Oxadiazole-3(2H)-carboxamide derivatives as potential novel class of monoamine oxidase (MAO) inhibitors: Synthesis, evaluation, and role of urea moiety. Bioorg Med Chem. 2008; 16: 7565-7572.

 

 

 

 

Received on 06.09.2010        Modified on 15.09.2010

Accepted on 22.09.2010        © AJRC All right reserved

Asian J. Research Chem. 4(1):  January 2011; Page 1-12