title: Amide derivatives with pyrazole carboxylic acids of 5-amino-1,3,4-thiadiazole 2-sulfonamide as new carbonic anhydrase inhibitors: synthesis and investigation of inhibitory effects.
abstract: Pyrazole carboxylic acid amides of 5-amino-1,3,4-thiadiazole-2-sulfonamide were synthesized from 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carbonyl chloride and 4-benzoyl-1-(3-nitrophenyl)-5-phenyl-1H-pyrazole-3-carbonyl chloride. Carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from human erythrocyte cells by the affinity chromatography method. The inhibitory effects of 5-amino-1,3,4-thiadiazole-2-sulfonamide 1, acetazolamide 2 and new synthesized amides on these isozymes have been studied in vitro. The I(50) concentrations (the concentration of inhibitor producing a 50% inhibition of CA activity) against hydratase activity ranged from 1.2 to 2.2 nM for hCA-I and from 0.4 to 2 nM for hCA-II. The I(50) values against esterase activity ranged from 1.4 to 8 nM for hCA-I and from 1.3 to 6 nM for hCA-II. The K(i) values were observed between 8.2 x 10(- 5) to 6.2 x 10(- 4) M for hCA-I and between 2.9 x 10(- 4) to 8.2 x 10(- 4) M for hCA-II. The comparison of new synthesized amides to 5-amino-1,3,4-thiadiazole-2-sulfonamide 1, acetazolamide 2 indicated that the new synthesized compounds (18-23) inhibit CA activity more potently than the parent compounds.
authors.affiliation: Department of Chemistry, Faculty of Science and Arts, Dumlupinar University, Kutahya, Turkey. metinbulbul@yahoo.com
authors.forename: Metin
authors.initials: M
authors.lastname: Bülbül
authors.forename: Rahmi
authors.initials: R
authors.lastname: Kasimoğullari
authors.forename: O Irfan
authors.initials: OI
authors.lastname: Küfrevioğlu
mesh_terms: D000577:Amides / Q000737:chemistry*; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000737:chemistry*; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry*; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000577:Amides; D002257:Carbonic Anhydrase Inhibitors; D002264:Carboxylic Acids; D007527:Isoenzymes; D011720:Pyrazoles; D013449:Sulfonamides; D013830:Thiadiazoles; C404727:5-amino-1,3,4-thiadiazole-2-sulfonamide; C031280:pyrazole