Pyrazoles as promising scaffold for the synthesis of anti-inflammatory and/or antimicrobial agent: A review

Mini-Reviews in Medicinal Chemistry

Volumn 10, Issue 11, 2010, Pages 1014-1033

  Bekhit, Adnan A ^a,b   Hymete, Ariaya ^b   Bekhit, Alaa El Din A ^c   Damtew, Ashenafi ^b,d   Aboul Enein, Hassan Y ^e  

^a Alexandria University Faculty of Pharmacy   (Egypt)

^b ADDIS ABABA UNIVERSITY   (Ethiopia)

^c UNIVERSITY OF OTAGO   (New Zealand)

^d Central University College   (Ethiopia)

^e NATIONAL RESEARCH CENTRE   (Egypt)

Author keywords

Anti inflammatory agents; Antimicrobial agents; Pyrazole derivatives

Indexed keywords

1 (THIAZOL 2 YL)PYRAZOLINE; 1 PHENYL 1H PYRAZOLINE DERIVATIVE; 1H PYRAZOL 3 CARBOXYLIC ACID; 1H PYRAZOLO[3,4 B]PYRIDINE DERIVATIVE; 2 (4 BROMOPHENYL) 6 (PHENYLSULFONYL) 7 (4 METHYLPHENYL) PYRAZOLO[1,5 A]PYRIMIDINE; 4 (2 BROMOACETYL) 5 METHYL 1 PHENYL 3 PHENYLCARBAMOYL 1H PYRAZOLE; 4 [5 (1 METHYL 1,2,3,6 TETRAHYDROPYRIDIN 4 YL) 3 TRIFLUOROMETHYLPYRAZOL 1 YL]BENZENESULFONAMIDE; 5 (4 HYDROXYMETHYLPHENYL) 1 (4 AMINOSULFONYLPHENYL) 3 TRIFLUOROMETHYL 1H PYRAZOLE; 5 (BENZOFURAN 2 YL)PYRAZOLE DERIVATIVE; 5 TRIFLUOROMETHYL 4,5 DIHYDRO 1H PYRAZOLE; ACETYL DIPHENYL DIHYDRO PYRAZOLE DERIVATIVE; AMPICILLIN; ANTIINFECTIVE AGENT; ANTIINFLAMMATORY AGENT; CELECOXIB; HETEROCYCLIC COMPOUND; HYDROXYPYRAZOLE DERIVATIVE; INDOMETACIN; N HYDROXYPYRID 2(1H) ONE; PYRAZOLE DERIVATIVE; PYRAZOLINE DERIVATIVE; PYRAZOLO BENZENESULFONAMIDE DERIVATIVE; PYRAZOLO[3,4 D]PYRIMIDINE; PYRAZOLO[4,3 E][1,2,4] TRIAZOLO[1,5 C]PYRIMIDINE DERIVATIVE; PYRAZOLYL BENZENESULFONAMIDE DERIVATIVE; PYRROLO[3,4 C]PYRAZOLE 4,6 DIONE DERIVATIVE; THIENO[2,3 B]PYRIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; ANTIFUNGAL ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTIMICROBIAL ACTIVITY; ARTICLE; CYTOTOXICITY; DOSE RESPONSE; DRUG DESIGN; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; IC 50; INFLAMMATION; LD 50; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; ONE POT SYNTHESIS; PAW EDEMA; STRUCTURE ACTIVITY RELATION;

EID: 77956633190     PISSN: 13895575     EISSN: None     Source Type: Journal    
DOI: 10.2174/1389557511009011014     Document Type: Article

References (85)

1. El-Emary, T.I. Synthesis and biological activity of some new pyrazolo.[3, 4-b] pyrazines. J. Chin. Chem. Soc., 2006, 53, 391-401.
2. Bekhit, A.A.; El-Sayed, O.A.; Aboul-Enein,H.Y.; Siddiqui, Y.M., Al-Ahdal, M.N. Evaluation of some pyrazoloquinolines as inhibitors of Herpes simplex virus type 1 replication. Arch. Pharm. Chem. Life Sci., 2005, 338, 74-77.
3. Erden, B.; Murat, S.; Burcu, C.E.; Sultan, N. B.; Eda, A.; Mustaf, A. Synthesis of the amide derivatives of 3-[1-(3-Pyridazinyl)-5- phenyl-1H-pyrazole-3-yl]propanoic acids as potential analgesic compounds. Turk J. Chem., 2007, 31, 677-687.
4. Wang, X.; Gu, L.; Wu, J. Apoptosis-inducing activity of new pyrazole emodi derivatives in human hepatocellular carcinoma HepG2 Cells. Biol. Pharm. Bull., 2007, 30(6), 1113-1116.
5. Pargellis, C.; Tong, L.; Churchill, L.; Cirillo, P.F.; Gilmore, T.; Graham, A.G.; Grob, P.M.; Hickey, E.R.; Moss, N.; Pav, S.; Regan, J. Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site. Nat. Struct. Biol., 2002, 9, 268-272.
6. Chimenti, F.; Maccioni, E.; Secci, D.; Bolasco, A.; Chimenti, P.; Granese, A.; Befani, O.; Turini, P.; Alcaro, S.; Ortuso, F; Cirilli, R.; La Torre, F.; Cardia, M.C.; Distinto, S. Synthesis, molecular modeling studies, and selective inhibitory activity against monoamine oxidase of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-(1H)- pyrazole derivatives. J. Med. Chem., 2005, 48, 7113-7122.
7. LeBlanc, R.; Dickson, J.; Brown, T.; Stewart, M.; Pati, H.N.; VanDerveer, D.; Arman, H.; Harris, J.; Pennington, W.; Holt, H.L. Jr; Lee, M. Synthesis and cytotoxicity of epoxide and pyrazole analogs of the combretastatins. J. Bioorg. Med. Chem., 2005, 13, 6025-6034
8. Liu, X-Y.; Yan, R-Z.; Wang, Y.; Zhan, P.; De Clercq, E.; Pannecouque, C.; Witvrouw, M.; Molina, M.T.; Vega, S.Synthesis and anti-HIV activity evaluation of novel 2,4-disubstituted 7- Methyl-1,1,3-trioxo-2,4-dihydro-pyrazolo-[4,5-e][1,2]thiadiazines. Arch. Pharm., 2008, 341(4), 216-222.
9. Ba, K.P.; Wietrzyk, J.; Opolski, A. Synthesis and antiproliferative activity in vitro of new 2-, 3,- or 4-substitued pyrido[2i,3i:3,4]pyrazolo[1, 5-A]pyramidines. Acta Poloniae Pharm. Ñ Drug Res., 2006, 63(3), 189-194.
10. Wang, S.Q.; Fang, L.; Liu, J.X.; Zhao, K. Design, synthesis, and hypnotic activity of pyrazolo[1,5-a]pyrimidine derivatives. Chin. Chem. Lett., 2004, 15(8), 885-888.
11. Narlawar, R.; Pickhardt, M.; Leuchtenberger, S.; Baumann, K.; Krause, S.; Dyrks, T.; Weggen, S.; Mandelkow, E.; Schmidt, B. Curcumin-derived pyrazoles and isoxazoles: Swiss army knives or blunt tools for Alzheimer's disease? Chem. Med. Chem., 2008, 3, 165 - 172.
12. Capparelli, M.V.; Avila, R.; Charris, J.E.; Domínguez, J.N. Crystal structure of 3-hydroxy-4-cyano-5-methylthiopyrazole, C5H5N3OS. Z. Kristallogr. NCS, 2003, 218, 35-36.
13. Al-Qahtani, A.; Siddiqui, Y.M.; Bekhit, A.A.; El-Sayed, O.A.; Aboul-Enein, H.Y.; Al-Ahdalb, M.N. Effect of pyrazoloquinoline derivatives on the growth of Leishmania donovani promastigotes. Arch. Pharm. Chem. Life Sci., 2005, 338, 484-487.
14. Palaska, E.; Erol, D.; Demirdamar, R. Synthesis and antidepressant activities of some 1,3,5-triphenyl-2-pyrazolines. Eur. J. Med. Chem., 1996, 31(1), 43-47.
15. Kaymakcioglu, B.K.; Rollas, S.; Korcegez, E.; Aricioglu, F. Synthesis and biological evaluation of new N-substituted-N'-(3,5- di/1,3,5-trimethylpyrazole-4-yl)thiourea/urea derivatives. Eur. J. Pharm. Sci., 2005, 26 (1), 97-103.
16. Trilok, C.; Neha, G.; Suman, L.; Saxena, K.K.; Ashok, K. Synthesis of substituted acridinyl pyrazoline derivatives and their evaluation for anti-inflammatory activity. Eur. J. Med. Chem., 2010, 45, 1772-1776.
17. Gouda, M.A.; Berghot, M.A.; Abd El-Ghani, G.E.; Khalil, A.M. Synthesis and antimicrobial activities of some new thiazole and pyrazole derivatives based on 4,5,6,7-tetrahydrobenzothiophene moiety Eur. J. Med. Chem., 2010, 45, 1338-1345.
18. Bekhit, A.A.; Fahmy, H.T.Y.; Rostom, S.A.F.; Baraka, A.M. Design and synthesis of some substituted 1H-pyrazolyl-thiazolo[4,5- d]pyrimidines as anti-inflammatory/antimicrobial agents. Eur. J. Med. Chem., 2003, 38, 27-36.
19. Khanna, I.K.; Yu, Y.; Huff, R.M.; Weier, R.M.; Xu, X.; Koszyk, F.J.; Collins, P.W.; Cogburn, J.N.; Isakson, P.C.; Koboldt, C.M.; Masferrer, J.L.; Perkins, W.E.; Seibert, K.; Veenhuizen, A.W.; Yuan, J.; Yang, D.C.; Zhang, Y.Y. Selective cyclooxygenase-2 inhibitors: Heteroaryl modified 1,2-diarylimidazoles are potent, orally active anti-inflammatory agents. J. Med. Chem., 2000, 43, 3168-3185.
20. Ataya, S.; Tarnawski, A.S.; Dubois, A. Eicosanoids and the stomach. Prostaglandins. Other Lipid Metab., 2000, 61, 105-124.
21. Khanapure, S.P.; Letts, L.G. In: The Eicosanoids, Curtis-Prior, P. B., Ed.; John Wiley & Sons: London, 2003, pp. 131-162.
22. Narumiya, S.; Sugimoto, Y.; Ushikubi, F. Prostanoid receptors: Structures, properties, and functions. Physiol. Rev. 1999, 79, 1193-1226.
23. Ford-Hutchinson, A.W. Leukotriene B4 and neutrophil function. Crit. Rev. Immunol., 1990, 10, 1-12.
24. Taylor, P.C. Anti-cytokines and cytokines in the treatment of rheumatoid arthritis. Curr. Pharm. Des., 2003, 9, 1095-1106.
25. Long, S.F.; Shargel, L.; Mutnick, A.H.; Souney, P.F.; Swanson, L.N. Comprehensive Pharmacy Review. Lippincott Williams and Wilkins, Philadelphia, 2001, pp. 289-291.
26. Scheiman, J.M. Effects of nonsteroidal anti-inflammatory drugs, including COX-2 specific inhibitors, on the GI tract. Clin. Updat, 2005, 12, 1-4.
27. Fiorucci, S.; Santucci, L.; Distrutti, E. NSAIDs, coxibs, CINOD and H2S-releasing NSAIDs: What lies beyond the horizon? Dig. Liver Dis., 2007, 39, 1043-1051.
28. Kosegarten, D.C.; LaSala, E.F.; Long, S.F. In: Comprehensive Pharmacy Review, Shargel, Mutnick, Souney, Swanson, Block, Eds., Lippincott Williams and Wilkins, Philadelphia; 2001. pp. 289-291.
29. Griffin, M.R.; Yared, A.; Ray, W.A. Nonsteroidal antiinflammatory drugs and acute renal failure in elderly persons. Am. J. Epidemiol., 2000, 151, 488-496.
30. Singh, G.; Triadafilopoulos, G. Epidemiology of NSAID induced gastrointestinal complications. J. Rheumatol., 1999; 26,18-2624.
31. Penning, T.D.; Talley, J.J.; Bertenshaw, S.R.; Carter, J.S.; Collins, P.W.; Docter, S.; Graneto, M.J.; Lee, L.F.; Malecha, J.W.; Miyashiro, J.M.; Rogers, R.S.; Rogier, D.J.; Yu, S.S.; Anderson, G.D.; Burton, E.G.; Cogburn, J.N.; Gregory, S.A.; Koboldt, C.M.; Perkins, W.E.; Seibert, K.; Veenhuizen, A.W.; Zhang, Y.Y.; Isakson, P.C. Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors. J. Med. Chem., 1997, 40, 1347-1365.
32. ®, 4-(4 - methylsulfonylphenyl)-3-phenyl-2(5H)-furanone], an orally active cyclooxygenase-2 inhibitor. Bioorg. Med. Chem. Lett.,1999, 9, 1773-1778.
33. Talley, J.A.; Brown, D.L.; Carter, J.S.; Masferrer, M.J.; Perkins,W.E.; Rogers, R.S.; Shaffer, A.F.; Zhang, Y.Y.; Zweifel, B.S.; Seibert, K. 4-[5-Methyl-3-phenylisoxazol-4-yl]- benzenesulfonamide, valdecoxib: A potent and selective inhibitor of COX-2. J. Med. Chem., 2000, 43, 775-777.
34. Deeks, J.J.; Smith, L.A.; Bradley, M.D. Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomized controlled trials. Br. Med. J., 2002, 325, 619-623.
35. Palomer, A.; Cabre, F.; Pascual, J.; Campos, J.; Trujillo, M.A.; Entrena, A.; Callo, M.A.; Garcia, L.; Mauleón, D.; Espinosa, A.: Identification of novel cyclooxygenase-2 selective inhibitors using pharmacophore models. J. Med. Chem., 2002, 45, 1402-1411.
36. Comber, R.N.; Gray, R.J.; Secrist, J.A. Acyclic analogues of pyrazofurin: syntheses and antiviral evaluation. Carbohydr. Res., 1991, 216, 441-452.
37. Raphael, R.A. Acetylenic compounds in organic synthesis. Academic Press, Inc.:New York, 1955.
38. Escribano, F.G.; Alcántara, M.P.D.; Gómez-Sánchez, A. Heterocycle formation from 1,3-dinitroalkanes: A novel pyrazole synthesis. Tetrahedron Lett., 1988, 29(46), 6001-6004.
39. Ahmed, M.S.M.; Kobayashi, K.; Mori, A. One-pot construction of pyrazoles and isoxazoles with palladium-catalyzed four-component coupling. Org. Lett., 2005, 7, 4487-4489.
40. Martin, R.; Rivero, M.R.; Buchwald, S.L. Domino Cu-catalyzed C- N coupling/hydroamidation: A highly efficient synthesis of nitrogen heterocycles. Angew. Chem. Int. Ed., 2006, 45, 7079-7082.
41. Gosselin, F.; O'Shea, P.D.; Webster, R.A.; Reamer, R.A.; Tillyer, R.D.; Grabowski, E.J.J. Highly regioselective synthesis of 1-aryl- 3,4,5-substituted pyrazoles. Synlett, 2006, 19, 3267-3270.
42. Heller, S.T.; Natarajan, S.R. 1,3-Diketones from acid chlorides and ketones: A rapid and general one-pot synthesis of pyrazoles. Org. Lett., 2006, 8, 2675-2678.
43. Deng, X.; Mani, N.S. Reaction of N-monosubstituted hydrazones with nitroolefins: A novel regioselective pyrazole synthesis. Org. Lett., 2006, 8, 3505-3508.
44. Dang, T.T.; Dang, T.T.; Langer, P. One-pot synthesis of pyrazole- 5-carboxylates by cyclization of hydrazone 1,4-dianions with diethyl oxalate. Tetrahedron Lett., 2007, 48, 3591-3593.
45. Doebel, K.J. The chemistry of non-steroidal anti-inflammatory agents. Pure Appl. Chem., 1969, 19, 49-75.
46. Lagishetty, C.V.; Naik, S.R. Polyamines; potential antiinflammatory agents and their possible mechanism of action. Indian J. Pharmacol., 2008, 40(3), 121-125.
47. Ezawa, M.; Garvey, D.S.; Janero, D.R.; Khanapure, S.P.; Letts, L.G.; Martino, A.; Ranatunge, R.R.; Schwalb, D.J.; Young, D.V. Design of a heteroaryl modified 1,5-disubstituted pyrazole cyclooxygenase-2 (COX-2) selective inhibitor. Lett. Drug Des. Discov., 2005, 2, 40-43.
48. Thilagavathi, R.; Chakraborti, A.K. Importance of alignment in developing 3-D QSAR models of 1,5-diaryl pyrazoles for prediction of COX-2 inhibitory activity. Internet Electron. J. Mol. Des., 2005, 4, 603-612.
49. Chakraborti, A.K.; Thilagavathi, R. Computer-aided design of non sulphonyl COX-2 inhibitors: An improved comparative molecular field analysis incorporating additional descriptors and comparative molecular similarity indices analysis of 1,3-diaryl isoindole derivatives. Bioorg. Med. Chem., 2003, 11, 3989-3996.
50. Khode, S.; Maddi, V.; Aragade, P.; Palkar, M.; Ronad, P.K.; Mamledesai, S.; Thippeswamy, A.H.M.; Satyanarayana, D. Synthesis and pharmacological evaluation of a novel series of 5-(substituted) aryl-3-(3-coumarinyl)-1-phenyl-2-pyrazolines as novel antiinflammatory and analgesic agents; Eur. J. Med. Chem., 2009, 44,1682-1688.
51. Amir, M.; Kumar, H.; Khan, S.A. Synthesis and pharmacological evaluation of pyrazoline derivatives as new anti-inflammatory and analgesic agents. Bioorg. Med. Chem. Lett., 2008, 18, 918-922.
52. Chowdhury, M.A.; Abdellatif, K.R.A.; Dong, Y.; Das, D.; Suresh, M.R.; Knaus, E.E. Synthesis of celecoxib analogs that possess a N- hydroxypyrid-2(1H)one 5-lipoxygenase pharmacophore: Biological evaluation as dual inhibitors of cyclooxygenases and 5- lipoxygenase with anti-inflammatory activity. Bioorg. Med. Chem. Lett., 2008, 18, 6138-6141.
53. Abdellatif, K.R.A.; Chowdhury, M.A.; Dong, Y.; Velázquez, C.; Das, D.; Suresh, M.R.; Knaus, E.E. Diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of 5-(4-hydroxymethylphenyl)-1-(4- aminosulfonylphenyl)-3-trifluoromethyl-1H-pyrazole and its methanesulfonyl analog: Synthesis, biological evaluation and nitric oxide release studies. Bioorg. Med. Chem., 2008, 16, 9694-9698.
54. Chowdhury, M.A.; Abdellatif, K.R.A.; Dong, Y.; Knaus, E.E. Synthesis of new 4-[2-(4-methyl(amino)sulfonylphenyl)-5-trifluo- romethyl-2H-pyrazol-3-yl]-1,2,3,6-tetrahydropyridines: A search for novel nitric oxide donor anti-inflammatory agents. Bioorg. Med. Chem., 2008, 16, 8882-8888.
55. Abdellatif, K.R.A.; Chowdhury, M.A.; Dong, Y.; Knaus, E.E.: Diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of 1- (4-methanesulfonylphenyl)-5-aryl-1H-pyrazol-3-carboxylic acids: Synthesis, nitric oxide release studies and anti-inflammatory activities. Bioorg. Med. Chem., 2008, 16, 6528-6534.
56. Shaaban, M.R.; Saleh, T.S.; Mayhoub, A.S.; Mansour, A.; Farag, A.M. Synthesis and analgesic/anti-inflammatory evaluation of fused heterocyclic ring systems incorporating phenylsulfonyl moiety. Bioorg. Med. Chem., 2008, 16, 6344-6352.
57. Sauzem, P.D.; Machado, P.; Rubin, M.A.; Sant'anna G.S.; Faber, H.B.; de Souza, A.H.; Mello, C.F.; Beck, P.; Burrow, R.A.; Bonacorso, H.G.; Zanatta, N.; Martins, M.A.P. Design and microwaveassisted synthesis of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles: Novel agents with analgesic and anti-inflammatory properties. Eur. J. Med. Chem., 2008, 43, 1237-1247.
58. Grayer, R.J.; Harborne, J.B. A survey of antifungal compounds from higher plants. Phytochemistry, 1994, 37, 19-42.
59. Irob, O.N.; Moo-Young, M.; Anderson, W.A. Antimicrobial activity of Annatto (Bixa orellana) extract. Int. J. Pharm., 1996, 34, 87-90.
60. Jayashankara, B.; Rai, K.M.L. Synthesis and antimicrobial studies of new series of pyrazoline bearing bis-heterocycles via 1,3-dipolar cycloaddition reactions. E-J. Chem., 2008, 5(2), 309-315.
61. Argade, N.D.; Kalrale, B.K; Gill, C.H. Microwave assisted improved method for the synthesis of pyrazole containing 2,4- disubstituted oxazole-5-one and their antimicrobial activity. E- J. Chem., 2008, 5(1), 120-129.
62. Abunada, N.M.; Hassaneen, H.M.; Kandile, N.J.; Miqdad, O.D. Synthesis and antimicrobial activity of some new pyrazole, fused pyrazolo[3,4-d]-pyrimidine and pyrazolo[4,3-e][1,2,4]-triazolo[1,5- c]pyrimidine derivatives. Molecules, 2008, 13, 1501-1517.
63. Chovatia, P.T.; Akabari, J.D.; Kachhadia, P.K.; Zalavadia, P.D.; Joshi, H.S. Synthesis and selective antitubercular and antimicrobial inhibitory activity of 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)- pyrazole derivatives. J. Serb. Chem. Soc., 2007, 71 (7), 713-720.
64. Abdel-Wahab, B.F.; Abdel-Aziz, H.A.; Ahmed, E.M. Synthesis and antimicrobial evaluation of 1-(benzofuran-2-yl)-4-nitro-3- arylbutan-1-ones and 3-(benzofuran-2-yl)-4,5-dihydro-5-aryl-1-[4- (aryl)-1, 3-thiazol-2-yl]-1H-pyrazoles. Eur. J. Med. Chem., 2009, 44, 2632-2635.
65. Abdel-Wahab, B.F.; Abdel-Aziz, H.A.; Ahmed, E.M. Convenient synthesis and antimicrobial activity of new 3-substituted 5- (benzofuran-2-yl)-pyrazole derivatives. Arch. Pharm. Chem. Life Sci., 2008, 341, 734 - 739.
66. Leal, B.; Afonso, I.F.; Rodrigues, C.R; Abreu, P.A.; Garrett, R.; Pinheiro, L.C.S.; Azevedo, A.R.; Borges, J.C.; Vegi, P.F.; Santos, C.C.C.; da Silveira, F.C.A.; Cabral, L.M.; Frugulhetti, I.C.C.P.; Bernardino, A.M.R.; Santos, D.O.; Castro, H.C. Antibacterial profile against drug-resistant Staphylococcus epidermidis clinical strain and structure-activity relationship studies of 1H- pyrazolo[3,4-b]pyridine and thieno[2,3-b]pyridine derivatives. Bioorg. Med. Chem., 2008, 16, 8196-8204.
67. Rai, N.S.; Kalluraya, B.; Lingappa, B.; Shenoy, S.; Puranic, V.G. Convenient access to 1,3,4-trisubstituted pyrazoles carrying 5- nitrothiophene moiety via 1,3-dipolar cycloaddition of sydnones with acetylenic ketones and their antimicrobial evaluation. Eur. J. Med. Chem., 2008, 43, 1715-1720.
68. Abunada, N.M.; Hassaneen, H.M.; Kandile, N.G.; Miqdad, O.E. Synthesis and biological activity of some new pyrazoline and pyrrolo[3,4-c]pyrazole-4,6-dione derivatives: Reaction of nitrilimines with some dipolarophiles. Molecules, 2008, 13, 1011-1024.
69. Farag, A.M.; Mayhoub, A.S.; Barakat, S.E.; Bayomic, A.H. Synthesis of new N-phenylpyrazole derivatives with potent antimicrobial activity. Bioorg. Med. Chem., 2008, 16, 4569-4578.
70. Bekhit, A.A.; Fahmy, H.T.Y. Design and synthesis of some substituted 1H-pyrazolyl-oxazolidines or 1H-pyrazolyl-thiazolidines as anti-inflammatory-antimicrobial agents. Arch. Pharm. Pharm. Med. Chem., 2003, 2, 111-118.
71. Bekhit, A.A.; Fahmy, H.T.Y.; Rostom, S.A.F.; Baraka, A.M. Design and synthesis of some substituted 1H-pyrazolyl-thiazolo[4,5- d]pyrimidines as anti-inflammatory/antimicrobial agents. Eur. J. Med. Chem., 2003, 38, 2728-2736.
72. Bekhit, A.A.; Abdel-Aziem, T. Design, synthesis and biological evaluation of some pyrazole derivatives as anti-inflammatory antimicrobial agents: Bioorg. Med. Chem., 2004, 12, 1935-1945.
73. Bekhit, A.A.; Ashour, H.M.A.; Guemei, A.A. Novel pyrazole derivatives as potential promising anti-inflammatory antimicrobial agents. Arch. Pharm. Chem. Life Sci., 2005, 338, 167-174.
74. Bekhit, A.A.; Ashour, H.M.A.; Bekhit, A.E.A.; Bekhit, S.A. Synthesis and biological evaluation of novel pyrazole derivatives as anti-inflammatory antimicrobial agents. Med. Chem., 2009, 5(2), 103-117.
75. Bekhit, A.A.; Abdel-Rahman, H.M.; Guemei, A.A. Synthesis and biological evaluation of some hydroxypyrazole derivatives as anti inflammatory-antimicrobial agents. Arch. Pharm. Chem. Life Sci., 2006, 339, 81-87.
76. Bekhit, A.A.; Ashour, H.M.A.; Bekhit, A.E.A.; Abdel-Rahman, H.M.; Bekhit, S.A. Synthesis of some pyrazolyl benzenesulfonamide derivatives as dual anti-inflammatory antimicrobial agents. J. Enzyme Inhib. Med. Chem., 2009, 24, 296-309.
77. Ahasan, N.B.; Islam, M.R. Cytotoxicity study of pyrazole derivatives. Bangladesh J. Pharmacol., 2007, 2, 81-87.
78. Solis, P.N.; Wright, C.W.; Anderson, M.M.; Gupta, M.P.; Phillipson, J.D. A microwell cytotoxicity assay using Artemia salina (brine shrimp). Planta Med., 1993, 59, 250-252.
79. Abd Allah, O.A. Synthesis and biological studies of some benzopyrano[2,3-c]pyrazole derivatives. Il Farmaco, 2000, 55, 641-649.
80. Shaha, G.C.; Khayer, K.; Islam, M.R.; Chowduri, M.S. Synthesis of thiocarbohydrazide, some thiocarbo-hydrazoenes and their cyclized products as probes for pharmacological studies. Indian J. Chem., 1992, 31B, 547.
81. Süleyman, H.; Büyükokuroǧlu, M.E. The effects of newly synthesized pyrazole derivatives on formaldehyde-, carrageenan-, and dextran-induced acute paw edema in rats. Biol. Pharm. Bull., 2001, 24, 1133-1136.
82. Amir, M.; Kumar, H.; Khan, A.S. Synthesis and pharmacological evaluation of pyrazoline derivatives as new anti-inflammatory and analgesic agents. Bioorg. Med. Chem. Lett., 2008, 18, 918-922.
83. Evarts, R.P.; Raab, M.M.; Haliday, E.; Brown, C. Pyrazole effects on mutagenicity and toxicity of dimethylnitrosamine in Wistar rats. Cancer Res., 1983, 43, 496-499.
84. Kojo, A.; Viitala, P.; Pasanen, M.; Pelkonen, O.; Raunio, H.; Juvonen, R. Induction of CYO2A5 by pyrazole and its derivatives in mouse primary heptaocytes. Arch. Toxicol., 1998, 72, 336-341.
85. Islam, M.R.; Khayer, K.; Ahmad, M.M. Synthesis of 3- methylpyrazoline-5-one and its 3,3-dimethyl-5,5-ethene-bis-2- pyrazoline-4,4-dione, substituted cyclic tri-azothione and N- acetylated derivatives. J. Bangladesh Chem. Soc., 2001, 14, 33-40.