Carbonic anhydrase inhibitors. Inhibition of human tumor-associated isozymes IX and cytosolic isozymes I and II with some 1,3,4-oxadiazole-thiols

Figures & data

Scheme 1 Reagents and conditions: i) Aq. 5% NaOH, ether, stirring at RT for 6 h; ii) H₂SO₄ / ethanol, refluxing for 11 h; iii) NH₂-NH₂.H₂O / ethanol (absolute), refluxing for 9 h; iv) CS₂ / KOH, ethanol, refluxing for 16.5 h. (v) Et₃N, DMAP, CH₃Cl(dry), benzyl bromide, stirring at 30–70°C for 5 h.

Table I.  Inhibition data for compounds 4-6 reported in the present paper and standard sulfonamide CA inhibitors, against isozymes I, II, and IX, by a stopped-flow, CO₂ hydration assay [32].

Inhibitor	KI*
hCA I^a (μM)	hCA II^a (μM)	hCA IX^b (μM)
AAZ	0.31	0.012	0.025
MZA	0.78	0.014	0.027
EZA	0.025	0.008	0.034
DCP	1.20	0.038	0.050
IND	0.031	0.015	0.024
4k	1059	9092	10.0
4m	1440	1266	9.9
5a	501	552	1381
5b	390	566	1203
5d	170	720	820
5e	129	1783	560
5f	552	1486	10.1
5 g	678	1314	9.9
5j	1088	1215	1467
5k	1675	1364	1509
5m	1110	1665	1187
6b	1250	3960	2830

*Errors in the range of 5–10% of the reported value (from 3 different assays).

^a Human (cloned) isozymes, by the CO₂ hydration method;

^b Catalytic domain of human, cloned isozyme [30,31], by the CO₂ hydration method [32].

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