1413930-58-1Relevant articles and documents
Carbonic anhydrase inhibitors. Regioselective synthesis of novel series 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides and their inhibition of the human cytosolic isozymes i and II and transmembrane cancer-associated isozymes IX and XII
Brzozowski, Zdzislaw,Slawinski, Jaroslaw,Vullo, Daniela,Supuran, Claudiu T.
, p. 282 - 291,10 (2012/12/11)
A series of novel 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides 4-6, 9-17 and 21-31 have been synthesized and investigated as inhibitors of four isoforms of zinc enzyme carbonic anhydrase (CA.EC 4.2.1.1), that is the cytosolic CA I and II, and cancer-associated isozymes CA IX and XII. Against the human isozymes hCA I the new compounds showed KIs in the range of 224-4830 nM, whereas toward hCA II, KIs = 318-873 nM. Isozyme hCA IX was inhibited with KIs = 11.8-93.4 nM, and hCA XII with 23.5-82.3 nM. Compounds 12-14, 27 and 29-31 have an activity against hCA I (KIs = 224-889 nM) which is comparable to the clinically used sulfonamide DCP (K Is = 1200 nM). Several of new compounds, including 9, 10, 21, 24, 26-28 and 30 have an activity against hCA IX (KIs = 11.8-38.6 nM) which is comparable or more effective than the clinically used sulfonamides AAZ, MZA, EZA, DCP and IND (KIs = 24-50 nM). Compounds 9, 10, 13, 21-23, 26 and 27 were also very effective hCA XII inhibitors, with inhibition constants ranged from 23.5 to 47.2 nM comparable or more effective than sulfonamides EZA (KIs = 22 nM) or DCP (KIs = 50 nM), respectively.
