Investigation of novel alkyl/benzyl (4-sulphamoylphenyl)carbamimidothioates as carbonic anhydrase inhibitors

Figures & data

Scheme 1. Chemical structures of some selected examples of effective CA inhibitors 1–4.

Scheme 2. Reagents and conditions: (i) KSCN, aq. 3.5 M HCl, reflux, 3 h, 31%; (ii) DMF 20–100 °C, 2.5–24 h.

Table 1. Inhibition data of human CA isoforms CA I, II, VII, and XIII and bacterial β-CA isoforms MscCA, from Mammaliicoccus (Staphylococcus) sciuri, and StCA1 and StCA2, from Salmonella enterica (serovar Typhimurium), with compounds 8a–o using AAZ as standard drug.

Cmpd	R	KI (nM)^a
		hCA I	hCA II	hCA VII	hCA XIII	MscCA	StCA1	StCA2
8a	–CH3	90.4	85.8	18.9	97.5	759.9	87.4	270.2
8b	–(CH2)3CH3	76.4	73.6	13.8	341.6	889.8	91.7	347.8
8c	–(CH2)5CH3	78.8	2.5	2.3	92.2	946.7	82.5	897.8
8d	–(CH2)6CH3	69.6	9.3	2.7	925.9	3703	71.3	955.3
8e	–CH2CH = CH2	38.5	8.2	1.8	814.4	879.2	313.1	4987
8f	–CH2C≡CH	92.5	6.9	5.5	351.6	2479	79.8	7121
8g	–CH2C6H5	68.1	53.3	2.4	490.7	360.8	52.2	901.7
8h	CH2(4-Cl–C6H4)	73.2	34.4	2.0	892.0	618.9	89.7	6680
8i	–CH2(4-Br–C6H4)	60.0	29.9	2.1	907.3	8761	750.9	9697
8j	–CH2(4-CN–C6H4)	82.8	21.5	1.5	301.6	925.4	55.7	5194
8k	–CH2(4-NO2–C6H4)	77.2	9.0	2.6	855.7	934.3	86.2	6853
8l	–CH2(4-CF3–C6H4)	73.5	8.9	2.3	80.5	658.8	73.4	5894
8m	–CH2(3,5-diF–C6H3)	82.2	1.7	1.2	75.6	742.3	91.0	6306
8n	–CH2(3,4-diCl–C6H3)	40.5	9.4	7.7	69.3	7816	301.2	8705
8o	–CH2(3,5-diCH3–C6H3)	83.9	23.3	25.6	750.4	8455	281.8	7884
AAZ	–	250	12.5	2.5	16.0	625	59	84

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