Design, synthesis and biological evaluation of N-(5-methyl-isoxazol-3-yl/1,3,4-thiadiazol-2-yl)-4-(3-substitutedphenylureido) benzenesulfonamides as human carbonic anhydrase isoenzymes I, II, VII and XII inhibitors

Figures & data

Figure 1. Sulfonamides CA inhibitors (acetazolamide, methazolamide and SLC-0111), sulfadrugs (sulfadiazine and sulfapyridine) and the designed novel compounds 15–26.

Scheme 1. Synthesis of N-(5-methyl-isoxazol-3-yl/1,3,4-thiadiazol-2-yl)-4-(3-substituted phenylureido)benzenesulfonamide derivatives. Reagent and conditions: A. Dried DMF reflux, 5–6 h.

Table 1. hCA I, II, VII and XII inhibition with compounds 15–26, with AAZ as standard.

	KI (μM)
Compound	hCA I	hCA II	hCA VII	hCA XII
15	73.7	>100	85.8	>100
16	>100	>100	>100	>100
17	>100	>100	>100	>100
18	>100	>100	>100	>100
19	>100	96.0	>100	>100
20	>100	>100	>100	>100
21	>100	>100	>100	>100
22	>100	>100	>100	>100
23	>100	>100	>100	>100
24	>100	>100	>100	>100
25	>100	87.8	>100	>100
26	>100	>100	>100	>100
AAZ	0.25	0.012	0.005	0.006

Table

Compound number	R-Group	R1-Group
15		H
16		4-Fluoro
17		4-Chloro
18		4-Methyl
19		4-Methoxy
20		Benzyl
21		H
22		4-Fluoro
23		4-Chloro
24		4-Methyl
25		4-Methoxy
26		Benzyl