Synthesis and biological activity of chiral dihydropyrazole: Potential lead for drug design

Mini-Reviews in Medicinal Chemistry

Volumn 11, Issue 9, 2011, Pages 771-821

  Liu, X H ^a,b   Ruan, B F ^a   Li, J ^b   Chen, F H ^b   Song, B A ^c   Zhu, H L ^a   Bhadury, P S ^c   Zhao, J ^a  

^a NANJING UNIVERSITY   (China)

^b ANHUI MEDICAL UNIVERSITY   (China)

^c GUIZHOU UNIVERSITY   (China)

Author keywords

Biological activities; Dihydropyrazole; Lead; SAR

Indexed keywords

(4,5 DIHYDROPYRAZOL 1 YL) CHLOROQUINE DERIVATIVE; 2 [1 [5, 8 DIHYDRO QUINOXALINO(2,3 B)INDOLOACETYL] 3 (1 BENZOFURAN 2 YL) 4,5 DIHYDRO 1H PYRAZOL 5 YL]PHENYL DERIVATIVE; 2 [4 [3 (2,4 DIHYDROXYPHENYL) 1 (2 HYDROXYBENZOYL 4,5 DIHYDRO 1H 5 PYRAZOLYL] 2 METHOXYPHENOXY]ACETIC ACID DERIVATIVE; 4 METHYL 5 TRIFLUOROMETHYL 5 HYDROXY 4,5 DIHYDRO 1H PYRAZOLE METHYL ESTER; 5 (2 BROMOVINYL) 2' DEOXYURIDINE; 5 ARYL 1 ISONICOTINOYL 3 (PYRIDIN 2 YL) 4,5 DIHYDRO 1H PYRAZOLE DERIVATIVE; 5 METHOXY 3 PHENYL 4,5 DIHYDROPYRAZOL; AMOXICILLIN; ANALGESIC AGENT; ANTIBIOTIC AGENT; ANTICONVULSIVE AGENT; ANTIMALARIAL AGENT; ANTINEOPLASTIC AGENT; ANTIVIRUS AGENT; CHLOROQUINE; CIDOFOVIR; DIPYRONE; FLUOROURACIL; GANCICLOVIR; IBIPINABANT; ISONIAZID; KANAMYCIN; MORPHINE; NALOXONE; PENICILLIN G; PYRAZOLE DERIVATIVE; RIBAVIRIN; RIMONABANT; SPARFLOXACIN; THIOSULFATE ARYLPYRAZOLE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANOREXIA; ANTIBIOTIC RESISTANCE; ANTICONVULSANT ACTIVITY; ANTICONVULSANT THERAPY; ANTIINFLAMMATORY ACTIVITY; ANTIMALARIAL ACTIVITY; ANTIMICROBIAL ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; ARTHRITIS; ATAXIA; BACILLUS SUBTILIS; BINDING AFFINITY; BIOLOGICAL ACTIVITY; BREAST CANCER; CANDIDA ALBICANS; CELL PROLIFERATION; CELL PROTECTION; CHEMOTHERAPY; CHIRALITY; COLON CANCER; COMPETITIVE INHIBITION; CRYSTAL STRUCTURE; DEPRESSION; DROWSINESS; DRUG CYTOTOXICITY; DRUG DESIGN; DRUG INDUCED HEADACHE; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER; ENZYME ACTIVE SITE; ESCHERICHIA COLI; GASTROINTESTINAL SYMPTOM; HIRSUTISM; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYDROGEN BOND; HYDROPHILICITY; IC 50; KIDNEY CANCER; KLEBSIELLA PNEUMONIAE; LEUKEMIA; LIVER TOXICITY; LUNG CANCER; MELANOMA; MINIMUM INHIBITORY CONCENTRATION; MOLECULAR DOCKING; MULTIDRUG RESISTANCE; MYCOBACTERIUM TUBERCULOSIS; NOCICEPTION; NONHUMAN; OVARY CANCER; PAIN; PARKINSON DISEASE; PHARMACOPHORE; PLASMODIUM FALCIPARUM; PROSTATE CANCER; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS FLUORESCENS; REVIEW; SEIZURE; STAPHYLOCOCCUS AUREUS; STRUCTURE ACTIVITY RELATION;

ANALGESICS; ANTI-INFECTIVE AGENTS; ANTI-INFLAMMATORY AGENTS; ANTICONVULSANTS; ANTINEOPLASTIC AGENTS; DRUG DESIGN; MONOAMINE OXIDASE; NITRIC OXIDE SYNTHASE; PYRAZOLES; RECEPTOR, CANNABINOID, CB1; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79960578786     PISSN: 13895575     EISSN: 18755607     Source Type: Journal    
DOI: 10.2174/138955711796355285     Document Type: Review

References (89)

1. Kumar, S.; Bawa, S.; Drabu, Sushma.; Kumar, R.; Gupta, Himanshu. Biological activities of pyrazoline derivatives -a recent development. Recent Pat. Anti-Infect. Drug Discovery., 2009, 4, 154-163.
2. Lange, J. H. M; Vliet, V. B. J. Fluoro-substituted 3,4-diaryl-4,5- dihydro-1H-pyrazole-1-carboxamidine derivatives having CB1 antagonistic activity. 2010, Patent WO2010003760.
3. Coleman, P. J.; Cox, C. D. Mitotic kinesin inhibitors. 2009, Patent US2009042966.
4. Jeske, M.; Flamme, I. New substituted dihydropyrazole-3-thione compounds are hypoxia inducible factor-prolyl-4-hydroxylase inhibitor, useful for preparing medicament to treat and/or prevent e.g. cardiovascular diseases, wound healing and anemia. 2009, Patent DE102007048447.
5. Kim, J. D.; Yoon, H. C.; Kin, I. W. novel benzoimidazole derivative and a pharmaceutical composition comprising the same. 2007, Patent WO2006080821.
6. Bakker, W. I. I.; Venhorst, J.; Loevezijn, A.V. arylsulfonyl pyrazoline carboxamidine derivatives as 5-HT antagonists. 2009, Patent AU2009226956.
7. Bandodkar, B. S.; Schmitt, S. Prazoline derivatives for the treatment of turberculosis. 2010, Patent US2010179161.
8. Yenes-Minguez, S.; Torrens-Jover, A.; Esteve, L. D. Substituted compounds with ACAT inhibition activity. 2010, Patent US2010099712.
9. Banday, A. H.; Mir, B. P.; Lone, I. H.; Suri, K. A.; Sampath Kumar, H.M. Studies on novel D-ring substituted steroidal pyrazolines as potential anticancer agents. Steroids, 2010, 75, 805-809.
10. Hayat, Faisal.; Salahuddin, A.; Umar, S.; Azam, A. Synthesis, characterization, antiamoebic activity and cytotoxicity of novel series of pyrazoline derivatives bearing quinoline tail. Eur. J. Med. Chem., 2010, 45, 4669-4675.
11. Girisha, K. S.; Kalluraya, B.; Vijaya, N.; Padmashree. Synthesis and pharmacological study of 1-acetyl/propyl-3-aryl-5-(5-chloro-3- methyl-1-phenyl-1H-pyrazol-4-yl)-2-Pyrazoline. Eur. J. Med. Chem., 2010, 45, 4640-4644.
12. Cuberes, A.R.; Frigola, C.J.; Mangues, B.R.; Casanova, R.I. Pyrazoline derivatives useful for the treatment of cancer. 2005, WO Patent 2005077910.
13. Abdou, I. M.; Saleh, A. M.; Zohdi, H. F. Synthesis and antitumor activity of 5-trifluoromethyl-2, 4-dihydropyrazol-3-one nucleosides. Mol., 2004, 9, 109-116.
14. Manna, F.; Chimenti, F.; Fioravanti, R.; Bolasco, A.; Secci, D.; Chimenti, Paola.; Ferlinib, C.; Scambia, G. Synthesis of some pyrazole derivatives and preliminary investigation of their affinity binding to P-glycoprotein. Bioorg. Med. Chem. Lett., 2005, 15, 4632-4635.
15. Havrylyuk, D.; Zimenkovsky, B.; Vasylenko, O.; Zaprutko, L.; Gzella, A.; Lesyk, R. Synthesis of novel thiazolone-based compounds containing pyrazoline moiety and evaluation of their anticancer activity. Eur. J. Med. Chem., 2009, 44, 1396-1404.
16. Liu, X. H.; Bai, L. S.; Pan, C. X.; Song, B. A.; Zhu, H. L. Novel 5- methyl-2 [(un)substituted phenyl]-4-{4,5-dihydro-3- [(un)substituted phenyl]-5-(1, 2, 3, 4 -tetrahydroisoquinoline-2- yl)pyrazol-1-yl}-oxazole derivatives: Synthesis and anticancer activity. Chin. J. Chem., 2009, 27, 19571-961.
17. Shaharyar, M.; Abdullah, M. M.; Bakht, M. A.; Majeed, J. Pyrazoline bearing benzimidazoles: search for anticancer agent. Eur. J. Med. Chem., 2010, 45, 114-119.
18. Liu, X. H.; Liu, H. F.; Song, B. A.; Zhu, H. L.; Bai, L. S.; Pan, C. X.; Liu, J. X.; Yang, Y.; Qi, X. B. Synthesis and molecular docking study of novel coumarin derivatives containing 4,5- dihydropyrazole moiety as potential antitumor agents. Bioorg. Med. Chem. Lett., 2010, 20, 5705-5708.
19. Cai, Z. Y.; Yang, Y.; Liu, X. H.; Qi, X. B. Novel 3-(1-acetyl-5- (substituted- phenyl)-4,5-dihydro-1H-pyrazol-3-yl)-7-fluoro-2Hchromen- 2-one derivatives: synthesis and anticancer activity. Lett. Drug Des. Discov., 2010, 7, 640-643.
20. Insuasty, B.; Tigreros, A.; Orozco, F.; Quiroga, J.; Abonía, R.; Nogueras, M.; Sanchez, A.; Cobo, J. Synthesis of novel pyrazolic analogues of chalcones and their 3-aryl-4-(3-aryl-4,5-dihydro-1Hpyrazol- 5-yl)-1-phenyl-1H-pyrazole derivatives as potential antitumor agents. Bioorg. Med. Chem., 2010, 18, 4965-4974.
21. Lv, P. C.; Li, H. Q.; Sun, Juan.; Zhou, Yang.; Zhu, H. L. Synthesis and biological evaluation of pyrazole derivatives containing thiourea skeleton as anticancer agents. Bioorg. Med. Chem., 2010, 18, 4606-4614.
22. Mamolo, M. G.; Zampieri, V. F.; Vio, L.; Banfi, E. Synthesis and antimycobacterial activity of 5-aryl-1-isonicotinoyl-3-(pyridin-2- yl)-4,5-dihydro-1H-pyrazolderivatives. Il Farmaco. 2001, 56, 593-599.
23. Azarifar, D.; Shaebanzadeh, M. Synthesis and characterization of new 3, 5-dinaphthyl substituted 2-pyrazolines and study of their antimicrobial activity. Mol. 2002, 7, 885-895.
24. Liu, X. H.; Lv, P. C.; Li, B.; Zhu, H. L.; Song, B. A. Synthesis, structure, and antibacterial activity of novel 5-arylpyrazole derivatives. Aust. J. Chem., 2008, 61, 223-230.
25. Liu, X. H.; Cui, P.; Song, B. A.; Bhadury, P. S.; Zhu, H. L.; Wang, S. F. Synthesis, structure and antibacterial antivity of novel 1-(5- substituted-4,5-dihydropyrazol-1-yl)ethanone oxime ester derivatives. Bioorg. Med. Chem., 2008, 16, 4075-4082.
26. Silva, P. E. A.; Ramos, D. F.; Bonacorso, H. G.; Iglesia, A. I.; Oliveira, M. R.; Coelho, T.; Navarin, J.; Morbidoni, H. R.; Zanatta, N.; Martins, M. A. P. Synthesis and in vitro antimycobacterial activity of 3-substituted 5-hydroxy-5-trifluoro[chloro]methyl-4,5- dihydro-1H-1-(isonicotinoyl) pyrazoles. Int. J. Antimicrob. Ag., 2008, 32, 139-144.
27. Liu, X. H.; Zhi, L. P.; Song, B. A.; Xu, H. L. Synthesis, characterization and antibacterial activity of new 5-aryl pyrazole oxime ester derivatives. Chem. Res. Chinese U., 2008, 24, 454-458.
28. Liu, X. H.; Song, B. A.; Zhu, H. L.;Zuo, R. B. Synthesis, characterization and antibacterial activity of new 5-(o- Chlorophenyl)-3-(o,p-dichlorophenyl)-4,5- dihydro-pyrazol-1-yl oxime ester derivatives. Chin. J. Chem., 2008, 26, 505-509.
29. 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.
30. Manna, K.; Agrawal, Y. K. Microwave assisted synthesis of new indophenazine 1, 3, 5 -trisubstruted pyrazoline derivatives of benzofuran and their antimicrobial activity. Bioorg. Med. Chem. Lett., 2009, 19, 2688-2692.
31. Liu, X. H.; Zhu, J.; Zhou, A. N.; Song, B. A.; Zhu, H. L.; Bai, L. S.; Bhadury, P. S.; Pan C. X. Synthesis, structure and antibacterial activity of new 2-(1-(2-(subsititiuted-phenyl)-5-methyloxazol-4- yl)-3-(2-substituted-phenyl)-4,5-dihydro-1H-pyrazol-5-yl)-7- substituted-1,2,3,4-tetrahydroisoquinoline derivatives. Bioorg. Med. Chem., 2009, 17, 1207-1213.
32. Bai, L. S.; Wang, Y.; Liu, X. H.; Zhu, H. L.; Song, B. A. Novel dihydropyrazole derivatives linked with multi(hetero)aromatic ring: synthesis and antibacterial activity. Chin. Chem. Lett., 2009, 20, 427-430.
33. Cunico, W.; Cechinel, C. A.; Bonacorso, H. G.; Martins, M. A. P.; Zanatta, N.; Souza, M. V. N.; Freitas, I. O.; Soares, R. P. P.; Krettli, A. U. Antimalarial activity of 4-(5-trifluoromethyl-1Hpyrazol- 1-yl)-chloroquine analogues. Bioorg. Med. Chem. Lett., 2006, 16, 649-653.
34. Acharya, B. N.; Saraswat, D.; Tiwari, M.; Shrivastava, A. K.; Ghorpade, R.; Bapna, S.; Kaushik, M. P. Synthesis and antimalarial evaluation of 1,3,5-trisubstituted pyrazolines. Eur. J. Med. Chem., 2010, 45, 430-438.
35. Wanare, G.; Aher, R.; Kawathekar, N.; Ranjan, R.; Kaushik, N. K.; Sahal, D. Synthesis of novel α-pyranochalcones and pyrazoline derivatives as Plasmodium falciparum growth inhibitors. Bioorg. Med. Chem. Lett., 2010, 20, 4675-4678.
36. De Souza, F.R.; Figuera, M.R.; Lima, T.T.F.; Bastiani, J.; Barcellos, I.B.; Almeida, C.E.; Oliveira, M.R.; Bonacorso, H.G.; Flores, A.E.; Mello, C.F. 3-Methyl 5-hydroxy-5- trichloromethyl- 1H-1-pyrazolcarboxyamide (MPCA) induces antinociception. Pharmacol. Biochem. Be., 2001, 68, 525-530.
37. 2-Adrenoceptors and 5-HT receptors mediate the antinociceptive effect of new pyrazoles, but not of dipyrone. Eur. J. Pharmacol., 2004, 496, 93-97.
38. Tabarelli, Z.; Berlese, D.B.; Sauzem, P.D.; Rubin, M.A.; Missio, T.P.; Teixeira, M.V.; Sinhorin, A.P.; Martins, M.A.P.; Zanatta, N.; Bonacorso, H.G.; Mello, C.F. Antinociceptive effect of novel pyrazolines in mice. Braz. J. Med. Bio. Res., 2004, 37, 1531-1540.
39. Prokopp, C.R.; Rubin, M.A.; Sauzem, P.D.; Souza, A.H.; Berlese, D.B.; Lorega, R.V.; Muniz, M.N.; Bonacorso, H.G.; Zanatta, N.; Martins, M.A.P.; Mello, C.F. A pyrazolylthiazole derivative causes antinociception in mice. Braz. J. Med. Bio. Res., 2006, 39, 795-799.
40. 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 andmicrowave-4,5-dihydro-1H-pyrazoles: Novel agents with analgesic and aninflammatory properties. Eur. J. Med. Chem., 2008, 43, 1237-1247.
41. Milano, J.; Oliveira, S.M.; Rossato, M.F.; Machado, P.; Beck, P.; Zanatta, N.; Martins, M.A.P.; Mello, C.F.; Rubim, M.A.; Ferreira, J.; Bonacorso, H.G. Antinociceptive effect of novel trihalomethylsubstituted pyrazole methyl esters in mice. Eur. J. Phar., 2008, 581, 86-96.
42. Tortorici, V.; Vanegas, H. Opioid tolerance induced by metamizol (dipyrone) microinjections into the periaqueductal grey of rats. Eur. J. Neurosci. 2000, 12, 4074-4080.
43. Kaplancikli, Z. A.; Zitouni, G. T.; Özdemir, A.; Can, Ö. D.; Chevallet, P. Synthesis and antinociceptive activities of some pyrazoline derivatives. Eur. J. Med. Chem., 2009, 44, 2606-2610.
44. Puig-Basagoiti, F.; Tilgner, M.; Forshey, B.M. Triaryl pyrazoline compound inhibits flavivirus rna replication. Antimicrob. Agents Che., 2006, 50, 1320-1329.
45. Goodell, J.R.; Puig-Basagoiti, F.; Forshey, B.M.; Shi, P.Y.; Ferguson, D.M. Identification of compounds with anti-west nile virus activity. J. Med. Chem., 2006, 49, 2127-2137.
46. Yar, M.S.; Bakht, M.A.; Siddiqui, A.A.; Abdullah, M.M.; Clercq, E.D. Synthesis and evaluation of in vitro antiviral activity of novel phenoxy acetic acid derivatives. J. Enzym. Inhib. Med. Chem., 2009, 24, 876-882.
47. El-Sabbagh, O. I.; Baraka, M. M.; Ibrahim, S. M.; Pannecouque, G. A.; Snoeck, R.; Balzarini, J.; Rashad, A. A. Synthesis and antiviral activity of new pyrazole and thiazole derivatives. Eur. J. Med. Chem., 2009, 44, 3746-3753.
48. Lange, J. H. M.; Coolen, H. K. A. C.; Stuivenberg, H. H. V.; Dijksman, J. A. R.; Herremans, A. H. J.; Ronken, E.; Keizer, H. G.; Tipker, K.; McCreary, A. C.; Veerman, W.; Wals, H. C.; Stork, B.; Verveer, P. C.; Hartog, A. P. D.; Jong, N. M. J. D.; Adolfs, T. J. P.; Hoogendoorn, J.; Kruse, C. G. Synthesis, Biological Properties, and Molecular Modeling Investigations of Novel 3,4- diarylpyrazolines as potent and selective CB1 cannabinoid receptor antagonists. J. Med. Chem., 2004, 47, 627-643.
49. Lange, J. H. M; Stuivenberg, H. H.; Veerman, W. Novel 3,4- diarylpyrazolines as potent cannabinoid CB1 receptor antagonists with lower lipophilicity. Bioorg. Med. Chem. Lett., 2005, 15, 4794-4798.
50. Srivastava, B. K.; Joharapurkar, A.; Raval, S.; Patel, J. Z.; Soni, R.; Raval, P.; Gite, A.; Goswami, A.; Sadhwani, N.; Gandhi, N.; Patel, H.; Mishra, B.; Solanki, M.; Pandey, B.; Jain, M. R.; Patel, P. R. Diaryl Dihydropyrazole-3-carboxamides with significant in vivo antiobesity activity related to CB1 receptor antagonism: synthesis, biological evaluation, and molecular modeling in the homology model. J. Med. Chem., 2007, 50, 5951-5966
51. Lange, J.H.M.; Zilaout, H.; Van-vliet, B. 5-aryl-4,5-dihydro-(1H)- pyrazoles as cannabinoid CB1 receptor agonists.2009, WO Patent 2009037244.
52. Yildirim, M.; Wals, H. C.; Van vliet, B.J.; Lange, J. H. M. 4,5- dihydro-(1H)-pyrazole derivatives as cannabinoid CB1 receptor modulators. 2008, Patent WO2008152086.
53. Buschmann, H. H.; Torrens-Jover, A.; Mas-Prio, J.; Yenes- Minguez, S. Sulfonamide substituted pyrazole compounds, their preparation and used as CB1 modulators. 2008, Patent WO2008043544.
54. Lange, J. H. M.; Iwema, B.W.; Van Der Neut, M. A. W.; Van Vliet, B. J. 4,5-dihydro-(1H)-pyrazole derivatives as cannabinoid CB1 Receptor modulators. 2007, Patent WO2007071662.
55. Buschmann, H. H. CB1 antagonists or inverse antagonists as therapeutical agents for the treatment of inflammation involving gene expression. 2007, Patent WO2007017125.
56. Buschmann, H. H.; Torrens-Jover, A.; Mas-Prio, J.; Yenes- Minguez, S. Thiocarbonyl-substituted pyrazoline compounds, their preparation and used as CB1 modulators. 2007, Patent WO2007009688.
57. Dordal, Z. A.; Buschmann, H. H.; Torrens-Jover, A.; Mas-Prio, J.; Quintana, R. J. R. Carbonyl substituted pyrazoline compounds, their preparation and used as CB1 modulators. 2007, Patent WO2007009687.
58. Lange, J. H. M. 5-aryl-4,5-dihydro-(1H)-pyrazoles as cannabinoid CB1 Receptor agonists. 2009, Patent US20090082396.
59. Ali, M. A.; Yar, M. S. Antitubercular activity of novel substituted 4, 5-dihydro-1H-1-pyrazolylmethanethiones. J. Enzy. Inhi. Med. Chem. 2007, 22, 183-189.
60. Zampieri, D.; Mamolo, M. G.; Laurini, E.; Scialino, G.; Banfi, E.; Vio, L. Antifungal and antimycobacterial activity of 1-(3,5-diaryl- 4,5-dihydro-1H-pyrazol-4-yl)-1H-imidazole derivatives. Bioor. Med. Chem. 2008, 16, 4516-4522.
61. Manna, K.; Agrawal, Y. K. Potent in vitro and in vivo antitubercular activity of certain newly synthesized indophenazine 1,3,5-trisubstituted pyrazoline derivatives bearing benzofuran. Med. Chem. Res. 2010, DOI:10.1007/s00044-010-9322-5
62. Manna, K.; Agrawal, Y. K. Design, synthesis, and antitubercular evaluation of novel series of 3- benzofuran- 5- aryl- 1- pyrazolylpyridylmethanone and 3- benzofuran- 5- aryl- 1- pyrazolylcarbonyl- 4- oxo- naphthyridin analogs. Eur. J. Med. Chem., 2010, 45, 3831-3839.
63. Randall, R. W.; Eakins, K. E. Higgs, G. A.; Salmon, J. A.; Tateson, J. E. Inhibition of Arachidonic Acid Cyelo-Oxygenase and Lipoxygenase activities of leukocytes by indomethacin and compound BW755C. Agents. Actions., 1980, 10, 553-555.
64. Rovnyak, G. C.; Milloig, R. C.; Schwartz, J. Shu, V. Synthesis and antiinflammatory activity of hexahydrothiopyrano [4,3-C] pyrazoles and related analogues. J. Med. Chem., 1982, 25, 1482-1488.
65. Nugent, R. A.; Murphy, M.; Schlachter, S. T.; Dunn, C. J.; Smith, R. J.; Staite, N. D.; Galinet, L. A.; Shields, S. K. Aspar, D. A.; Richard, K. A.; Rohloff, N. A. Pyrazoline bisphosphonate esters as novel antiinflammatory and antiarthritic agents. J. Med. Chem., 1993, 36, 134-139.
66. Gusar, N. I.; Gul'ko, L. I.; Gorodetskova, N. R.; Klebanov, B. M. Synthesis and pharmacological activity of 1-aryl-3-amino-2- pyrazoline derivatives. Phar. Chem. Jour., 1994, 28, 255-260.
67. Burguete, A.; Pontiki, E.; Hadjipavlou-Litina, D.; Villar, R.; Vicente, E.; Solano, B.; Ancizu, S.; Pérez-Silanes, S.; Aldana, I.; Monge, A. Synthesis and anti-inflammatory/antioxidant activities of some new ring substituted 3-phenyl-1-(1,4-di-Noxidequinoxalin- 2-yl)-2-propen-1-one derivatives and of their 4,5- dihydro-(1H)-pyrazole analogues. Bioorg. Med. Chem. Lett., 2007, 17, 6439-6443.
68. 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
69. 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 anti-inflammatory and analgesic agents. Eur. J. Med. Chem., 2009, 44, 1682-1688.
70. Shoman, M. E.; Abdel-Aziz, M.; Aly, O. M.; Farag, H. H.; Morsy, M. A. Synthesis and investigation of anti- inflammatory activity and gastric ulcerogenicity of novel nitric oxide- donating pyrazoline derivatives. Eur. J. Med. Chem., 2009, 44, 3068-3076.
71. Sauzem, P. D.; Anna, G. d. S. S.; Machado, P.; Duarte, M. M. M. F.; Ferreira, J.; Mello, C. F.; Beck, P.; Bonacorso, H. G.; Zanatta, N.; Martins, M. A. P.; Rubin, M. A. Effect of 5-trifluoromethyl- 4,5-dihydro-1H-pyrazoles on chronic inflammatory pain model in rats. Eur. J. Phar., 2009, 616, 91-100.
72. Rathish, I. G.; Javed, K.; Ahmad, S. Synthesis and antiinflammatory activity of some new 1,3,5-trisubstituted pyrazolines bearing benzene sulfonamide. Bioorg. Med. Chem. Lett., 2009, 19, 255-258.
73. Palaska, E.; Erol, D.; Demirdamar, R. Synthesis and antidepressant activities of some 1,3,5-triphenyl-2-pyrazolines. Eur. J. Med. Chem., 1996, 31, 43-47.
74. Manna, F.; Chimenti, F.; Bolasco, A.; Secci, D.; Bizzarri, B.; Befani, O.; Turini, P.; Mondovi, B.; Alcaro, S.; Tafi, A. Inhibition of amine oxidases activity by 1- acetyl- 3, 5- diphenyl- 4, 5- dihydro- (1H)- pyrazole derivatives. Bioorg. Med. Chem. Lett., 2002, 12, 3629-3633.
75. France, C.; Adriana, B.; Fedele, M.; Daniela, S.; Paola, C.; Olivia, B.; Paola, T.; Valentina, G.; Bruno, M.; Roberto, C.; Francesco, L. T. Synthesis and selective inhibitory activity of 1- acetyl- 3, 5- diphenyl- 4, 5- dihydro- (1H)- pyrazole derivatives against monoamine oxidase. J. Med. Chem., 2004, 47, 2071-2074.
76. Franco, C.; Elias, M.; Daniela, S.; Adriana, B.; Paola, C.; Arianna, G.; Olivia, B.; Paola, T.; Stefano, A.; Francesco, O.; Roberto, C.; Francesco, L. T.; Maria, C. C.; Simona, D. 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.
77. Nesrin, G. K.; Samiye, Y.; Esra, K.; Umut, S.; Özen, Ö.; Gülberk, U.; Erdem, Y.; Engin, K.; Akgül, Y.; Altan, B. A. A new therapeutic approach in Alzheimer disease: Some novel pyrazole derivatives as dual MAO-B inhibitors and antiinflammatory analgesics. Bioorg. Med. Chem., 2007, 15, 5775-5786.
78. Yabanoglu, S.; Ucar, G.; Gokhan, N.; Salgin, U.; Yesilada, A.; Bilgin, A. A. Interaction of rat lung SSAO with the novel 1- Nsubstituted thiocarbamoyl- 3- substituted phenyl- 5- (2- pyrolyl)- 2- pyrazoline derivatives. J. Neu. Tran., 2007, 114, 769-773.
79. Franco, C.; Rossella, F.; Adriana, B.; Fedele, M.; Paola, C.; Daniela, S.; Francesca, R.; Paola, T.; Francesco, O.; Stefano, A.; Maria, C. C. Synthesis, molecular modeling studies and selective inhibitory activity against MAO of N1-propanoyl-3,5-diphenyl-4,5- dihydro-(1H)-pyrazole derivatives. Eur. J. Med. Chem., 2008, 43, 2262-2267.
80. Jun, M. A.; Park, W. S.; Kang, S. K.; Kim, K. Y.; Kim, K. R.; Rhee, S. D.; Bae, M. A.; Kang, N. S.; Sohn, S. K.; Kim, S. G.; Lee, J. O.; Lee, D. H.; Cheon, H. G.; Kim, S. S.; Ahn, J. H. Synthesis and biological evaluation of pyrazoline analogues with b-amino acyl group as dipeptidyl peptidase IV inhibitors. Eur. J. Med. Chem., 2008, 43, 1889-1902.
81. Amr, A. E. G. E.; Maigail, S. S.; Abdulla, M. M. Synthesis, and analgesic and antiparkinsonian activities of thiopyrimidine, pyrane, pyrazoline, and thiazolopyrimidine derivatives from 2-chloro-6- ethoxy-4-acetylpyridine. Monatsh. Chem., 2008, 139, 1409-1405.
82. Can, Ö. D.; Özkay, Ü. D.; Kaplancikli, Z. A.; Öztürk, Y. Effects of some 1, 3, 5- trisubstitued- 2- pyrazoline derivatives on depression and anxiety parameters of Mice. Arch. Pharm. Res., 2009, 32, 1293-1299.
83. Sule, G.; Murat, D.; Ahmet, Ö.; Gülhan, T. Z. Evaluation of antidepressant-like effect of 2-pyrazoline derivatives. Med. Chem. Res., 2010, 19, 94-101.
84. Amnerkar, N. D.; Bhusari, K. P. Synthesis, anticonvulsant activity and 3D-QSAR study of some prop-2-eneamido and 1-acetylpyrazoline derivatives of aminobenzothiazole. Eur. J. Med. Chem., 2010, 45, 149-159.
85. Zhang, X.; Li, X.; Allan, G. F. Design, synthesis, and in vivo SAR of a novel series of pyrazolines as potent selective androgen receptor modulators. J. Med. Chem., 2007, 50, 3857-3869.
86. Jones, D. G.; Liang, X.; Stewart, E. L. Discovery of non-steroidal mifepristone mimetics: pyrazoline-based PR antagonists. Bioorg. Med. Chem. Lett., 2005, 15, 3203-3206.
87. Amr, A. G.; Abdel-Latif, N. A.; Abdalla, M. M. Synthesis and antiandrogenic activity of some new 3-substituted androstano[17,16-c]-5'-aryl-pyrazoline and their derivatives. Bioorg. Med. Chem., 2006, 14, 373-384.
88. Camacho, M. E.; León, J.; Entrena, A. 4,5-dihydro-1H-pyrazole derivatives with inhibitory nNOS activity in rat brain: Synthesis and structure-activity relationships. J. Med. Chem., 2004, 47, 5641-5650.
89. Carrión, M. D.; López, C. L. C.; Camacho, M. E. Pyrazoles and pyrazolines as neural and inducible nitric oxide synthase (nNOS and iNOS) potential inhibitors (III). Eur. J. Med. Chem., 2008, 43, 2579-2591.