Synthesis and Evaluation of New Phthalazine Urea and Thiourea Derivatives as Carbonic Anhydrase Inhibitors

Abstract

A new series of phthalazine substituted urea and thiourea derivatives were synthesized, and their inhibitory effects on the activity of purified human carbonic anhydrases (hCAs I and II) were evaluated. 2H-Indazolo[2,1-b]phthalazine-trione derivative(1)was prepared with 4-nitrobenzaldehyde, dimedone, and phthalhydrazide in the presence of TFA in DMF, and nitro group was reduced to amine derivative(2)with SnCl2·2H2O. The compound was reacted with isocyanates and isothiocyanates to get the final products(3a–p). The results showed that all the synthesized compounds inhibited the CA isoenzymes activity.3a(IC50= 6.40 µM for hCA I and 6.13 µM for hCA II) has the most inhibitory effect. The synthesized compounds are very bulky to be able to bind near the zinc ion, and they much more probably bind as the coumarin derivatives.

In vitro inhibition of purified human carbonic anhydrase I and II by novel fluorene derivatives

“…In summary, enzyme inhibition is an important issue for drug design and biochemical applications [41][42][43][44][45]. Our results suggest that these novel compounds are likely to be adopted as candidates for the treatment of glaucoma and that they should be further evaluated in in vivo studies.…”

Synthesis of new series of thiazol‐(2(3H)‐ylideneamino)benzenesulfonamide derivatives as carbonic anhydrase inhibitors

“…DMF, dimethylformamide; THF, tetrahydrofuran Thiourea derivatives were carried out by conventional synthesis, involving reaction of sulfanilamide, with different thioisocyanates in THF. [33] After thiourea synthesis, 3-phenylthiazol-(2(3H)-ylideneamino) benzenesulfonamide (5a-s) compounds were prepared using α-haloacetophenone derivatives in EtOH-DMF mixture (Scheme 1). [34] The structures of the compounds were deduced from their IR, 1 H NMR, 13 C NMR, and mass spectrometry.…”

Multicomponent chemistry in the synthesis of carbonic anhydrase inhibitors

“…Beber and colleagues 24,25 from Sakaraya University reported the use of modified Biginelly-type reaction employing phtalazine as a 1,2-nucleophile in order to obtain indazolophtalazinetrione 20. This scaffold provided convenient access to two types of CA inhibitor, such as (thio)urea derivatives 22 and b-lactam phtalazines 23.…”