Synthesis of N-benzenesulfonamide-1H-pyrazoles bearing arylsulfonyl moiety: Novel celecoxib analogs as potent anti-inflammatory agents.
In: European Journal of Medicinal Chemistry, Jg. 80 (2014-06-10), S. 416-422
Online
academicJournal
Zugriff:
The reaction of arylsulfones 11a–d with hydrazonoyl chloride derivative 13 furnished celecoxib analogs 4-(3-acetyl-5-aryl-4-(arylsulfonyl)-1H-pyrazol-1-yl)benzenesulfonamides 15a–d, respectively. Oximes 16a, b and hydrazones 17a, b were prepared by reacting sulfones 11a, b with hydroxyl amine and phenyl hydrazine, respectively. The anti-inflammatory activity of the synthesized compounds showed that, 5-(4-bromophenyl)-4-(phenylsulfonyl)pyrazole 15c and 5-(4-bromophenyl)-4-(4-tolylsulfonyl)pyrazole 15d exhibited excellent anti-inflammatory activity with ED50 = 68 ± 2.2 and 51 ± 0.7 μM/kg, respectively, higher than that of celecoxib (ED50 = 86 ± 1.1 μM/kg) after 3 h with acceptable ulcer index. In addition, the LD50 of 15c and 15d is 7.1 mM/kg for each, and 9.8 mM/kg for celecoxib. Compound 15d appeared selectivity index (COX-2/COX-1) almost the half of celecoxib while 15c is non-selective for COX-2. Compound 15c with ED50 = 80 ± 2.8 μM/kg showed a significant analgesic activity when compared with celecoxib (ED50 = 70 ± 3.9 μM/kg) after 2 h whereas 15b (ED50 = 50 ± 1.2 μM/kg) and 15d (ED50 = 69 ± 2.7 μM/kg) seemed to be more potent than celecoxib (ED50 = 156 ± 4.8 μM/kg) but with a shorter duration (0.5 h). [ABSTRACT FROM AUTHOR]
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Synthesis of N-benzenesulfonamide-1H-pyrazoles bearing arylsulfonyl moiety: Novel celecoxib analogs as potent anti-inflammatory agents.
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Autor/in / Beteiligte Person: | Abdel-Aziz, Hatem A. ; Al-Rashood, Khalid A. ; ElTahir, Kamal Eldin H. ; Suddek, Ghada M. |
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Zeitschrift: | European Journal of Medicinal Chemistry, Jg. 80 (2014-06-10), S. 416-422 |
Veröffentlichung: | 2014 |
Medientyp: | academicJournal |
ISSN: | 0223-5234 (print) |
DOI: | 10.1016/j.ejmech.2014.04.065 |
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