7-Acylamino-3H-1,2-benzoxathiepine 2,2-dioxides as new isoform-selective carbonic anhydrase IX and XII inhibitors

Figures & data

Scheme 1. Reagents and conditions: (i) MePPh₃Br, tBuOK, THF, RT, 18 h, 65%; (ii) Net₃, CH₂Cl₂, 0 °C to RT, 4 h, 57%; (iii) 5, toluene, 70 °C, 4 h, 96%; (iv) Fe, AcOH, EtOH, H₂O, 75 °C, 1 h, 98%; (v) RCOCl, Net₃, CH₂Cl₂, 0 °C to RT, 4 h.

Table 1. Inhibition data of human CA isoforms CA I, II, IX and XII with 3H-1,2-benzoxathiepines 2,2-dioxide 8–17 using acetazolamide (AAZ) as a standard drug.

Cmpd	R	KI (nM)^a,b
		hCA I	hCA II	hCA IX	hCA XII
8	CH3	>100 µM	>100 µM	61.8	162.5
9	C6H5	>100 µM	>100 µM	208.6	370.1
10	4-CH3-C6H4	>100 µM	>100 µM	83.0	309.3
11	4-Br-C6H4	>100 µM	>100 µM	353.3	140.7
12	2-I-C6H4	>100 µM	>100 µM	45.4	643.7
13	2-Br-C6H4	>100 µM	>100 µM	66.8	96.2
14	2-F-C6H4	>100 µM	>100 µM	74.6	40.3
15	2-CF3-C6H4	>100 µM	>100 µM	19.7	8.7
16	thien-2-yl	>100 µM	>100 µM	177.5	73.2
17	furan-2-yl	>100 µM	>100 µM	210.1	134.4
AAZ	–	250	12	25	5.7

^aMean from three different assays, by a stopped flow technique (errors were in the range of ±5–10% of the reported values).

^bIncubation time 6 h.