الفهرس | Only 14 pages are availabe for public view |
Abstract A general survey about the inflammation, anti-inflammatory drugs and their mechanism of action, as well as a survey about the methods of synthesis of N-aryl pyrazoles. Finally, a small introduction about different approaches of computer aided drug design. A series of 3,4-bis-chalcone-N-arylpyrazoles IIIa-k was prepared from diacetyl pyrazoles IIa-e. The reaction of IId,e with hydrazine hydrate gave pyrazolo[3,4-d]pyridazine derivatives IVa,b. Furthermore, the reaction of IIa-e with thiosemicarbazide afforded pyrazolo[3,4-d]pyridazine thiocyanate salts Va-e. The synthesized compounds were subjected to in vivo antiinflammatory and ulcerogenic activities in addition to their in vitro Cox selectivity to give a full profile about their anti-inflammatory activity. Compounds IIIc, IIIf, IIIi and IIIe showed a significant anti-inflammatory activity among the synthesized compounds. Moreover, docking studies were performed to give an explanation for their anti-inflammatory activity through COX selectivity. The present investigation involves the synthesis of the following new intermediates: 1) 3,4-Diacetyl-1(4-fluorophenyl)5-methylpyrazole. 2) 3,4-Diacetyl-1(4-bromophenyl)5-methylpyrazole. The present study also comprises the synthesis of the following new compounds: 1) 1-(4-Phenyl)-3,4-bis(2,4dichlorocinnamoyl)-5-methylpyrazole. 2) 1-(4-Methylphenyl)-3,4-bis(2,4-dichlorocinnamoyl)-5- methylpyrazole. vi 3) 1-(4-Chlorophenyl)-3,4-bis(4-methoxycinnamoyl)-5-methylpyrazole. 4) 1-(4-Chlorophenyl)-3,4-bis(2,4-dichlorocinnamoyl)-5- methylpyrazole. 5) 1-(4-Chlorophenyl)-3,4-bis(3-(furan-2-yl)acryloyl)-5-methylpyrazole. 6) 1-(4-Fluorophenyl)-3,4-bis(4-methoxycinnamoyl)-5-methylpyrazole. 7) 1-(4-Fluorophenyl)-3,4-bis(2,4-dichlorocinnamoyl)-5-methylpyrazole. 8) 1-(4-Fluorophenyl)-3,4-bis(3-(furan-2-yl)acryloyl)-5-methylpyrazole. 9) 1-(4-Bromophenyl)-3,4-bis(4-methoxycinnamoyl)-5-methylpyrazole. 10) 1-(4-Bromophenyl)-3,4-bis(2,4-dichlorocinnamoyl)-5- methylpyrazole. 11) 1-(4-Bromophenyl)-3,4-bis(3-(furan-2-yl)acryloyl)-5- methylpyrazole. 12) 2-(4-Fluorophenyl)-3,4,7-trimethyl-2H-pyrazolo[3,4-d]pyridazine. 13) 2-(4-Bromophenyl)-3,4,7-trimethyl-2H-pyrazolo[3,4-d]pyridazine. 14) 3,4,7-Trimethyl-2-phenyl-2H-pyrazolo[3,4-d]pyridazin-5-ium isothiocyanate. 15) 3,4,7-Trimethyl-2-(p-tolyl)-2H-pyrazolo[3,4-d]pyridazin-5-ium isothiocyanate. 16) 2-(4-Chlorophenyl)-3,4,7-trimethyl-2H-pyrazolo[3,4-d]pyridazin-5- ium isothiocyanate. 17) 2-(4-Fluorophenyl)-3,4,7-trimethyl-2H-pyrazolo[3,4-d]pyridazin-5- ium isothiocyanate. 18) 2-(4-Bromophenyl)-3,4,7-trimethyl-2H-pyrazolo[3,4-d]pyridazin-5- ium isothiocyanate. |