Synthesis and bioactivity of several new hetaryl sulfonamides

Figures & data

Table 1. The synthesis route of hetaryl sulfonamides 1–12.

Compounds	R1	Z	X
1	H	COOCH2CH3	C6H5
2	CH3	COCH3	C6H5
3	CH3	COCH3	C6H4OH
4	CH3	COOCH2CH2CH3	CH3C6H4
5	CH3	COOC2H4OCOCCH2CH3	C6H5
6	OC2H5	COOC2H5	CH3
7	OCH3	COOC2H5	CH3
8	CH3	COOC2H5	CH3
9	CH3	COOC2H5	C6H5
10	OC2H5	COCH3	CH3
11	CH3	COCH3	CH3
12	OC2H5	COOC2H5	C6H5

Table 2. Physical and chemical characteristics of hetaryl sulfonamides 1–12.

No	Z	R^1	X	Yield (%)	Mp (^oС)	Brutto formula	Element analysis, Found/Calculated (%)		Spectrum analysis
							N	S
1	2	3	4	6	7	8	9	10	11
1	COOCH2CH3	H	C6H5	70.1	254–256	C13H13N2O4S2			^1H NMR (300 MHz, (DMSO-d6, δ): 1.30 (t, 3H, CH3); 3.98 (q, 2H, CH2); 7.20–7.44 (m, 4H, CH–Ar); 9.73 (bs, 1H, NH).13C NMR (75 MHz, DMSO-d6): 24.3; 55.1; 61.7; 111.6; 128.6; 142.9; 184.7. IR ν, sm^−1: 3313; 1672; 1574; 3175 (NH); 1588–1696 (C = O); 1094 (C = S); 1190–1458 (SO2N)
2	COCH3	CH3	C6H5	45.5	190–192	C13H14N2O3S2			^1H NMR (300 MHz, (DMSO-d6, δ): 1.27 (s, 3H, CH3); 2.43 (s, 3H, CH3); 5.06–5.17 (dd, 2H, CH2); 7.25 (d, 2H, 2CH–Ar); 7.30 (t, 2H, 2CH–Ar); 2.33 (s, 3H, Ar–CH3); 7.77 (s, 1H, NH). ^13C NMR (75 MHz, DMSO-d6) 24.3; 27; 52.8; 104.5; 126.8; 150.0; 196. IR ν, sm^−1: 3714; 3672; 3565; 3236; 3109; 2510; 1699 (C = O); 1599 (–OCO); 1462 (SO2N); 1090 (C = S)
3	COCH3	CH3	C6H4OH	68.6	208–210	C13H15N2O4S2			^1H NMR (300 MHz, (DMSO-d6, δ): 1.11 (t, 3H, CH3); 6.61–7.04 (m, 4H, CH–Ar); 2.33 (s, 3H, Ar–CH3); 8.90 (d, 1H, OH); 9.20 (s, 1H, NH). ^13C NMR (75 MHz, DMSO-d6): 12; 24.3; 27.0; 46.6; 104.5; 115.7; 122.8; 128.3; 136.7; 141.6; 150.0; 196.5.IR ν, sm^−1: 1570; 3185; 1650–1680 (C = O); 1076–1493 (SO2N); 3300 (NH)
4	COOCH2CH2CH3	CH3	CH3C6H4	35.8	205	C16H17N2O4S2			^1H NMR (300 MHz, (DMSO-d6, δ): 1.18 (m, 3H, CH3); 2.06 (s, 3H, CH3); 2.35 (s, 3H, CH3); 4.10 (m, 2H, CH2); 7.35 (m, 2H, CH2); 7.81 (s, 1H, CH–Ar); 6.34 (s, 1H, CH–Ar); 5.76 (s, 1H, CH–Ar); 5.70 (s, 1H, CH–Ar); 2.33 (s, 3H, Ar–CH3); 5.43 (s, 1H, NH). ^13C NMR (75 MHz, DMSO-d6): 11.9; 17.9; 24.3; 54.6; 104.2; 128.6; 125.2; 141.6; 143.2; 152.3.IR ν, sm^−1: 3237, 3116, 2973, 1687 (C = O), 1076, 1493 (SO2N)
5	COOC2H4OCOCCH2CH3	CH3	C6H5	44.3	171–172	C18H20N2O6S2			^1H NMR (300 MHz, (DMSO-d6, δ): 1.17 (m, 3H, CH3); 2. 34 (s, 3H, CH3); 4.09 (m, 2H, CH2); 7.30 (m, 2H, CH2); 7.64 (s, 1H, CH–Ar); 7.12 (m, 1H, CH–Ar); 6.32 (s, 1H, CH–Ar); 5.74 (s, 1H, CH–Ar); 2.33 (s, 3H, Ar–CH3); 5.78 (m, 2H, =CH2); 5.40 (s, 1H, NH).13C NMR (75 MHz, DMSO-d6): 17.9; 24.3; 64.0; 111.6; 125.2; 129.3; 136.7; 141.6; 185.IR ν, sm^−1: 3418 (NH); 1702 (C = O); 1093; 1403 (SO2N)
6	COOC2H5	OC2H5	CH3	9.20	145–146	C10H16N2O5S2			^1H NMR (300 MHz, (DMSO-d6, δ): 1.12 (3H, CH3); 2.02 (s, 3H, CH3); 4.02 (2H, CH2); 8.13 (s, 1H, NH); 7.42–7.05 (m, 4H, Ar–CH).13C NMR (75 MHz, DMSO-d6): 166.5; 152.7; 149.8; 144.4; 137.9; 135.6; 130.0; 129.9; 129.1; 128.0; 126.6; 103.9; 53.4; 51.6; 21.1; 18.5.IR ν, sm^−1: 3472; 1694; 1211; 1076; 1712 (C = O); 1090; 1412 (SO2N)
7	COOC2H5	OCH3	CH3	17.5	158–159	C9H14N2O5S2			^1H NMR (300 MHz, (DMSO-d6, δ): 1.08 (t, 3H, CH3), 2.23 (s, 3H, CH3), 3.80 (q, 2H, CH2), 7.31 (m, 1H, CH–Ar), 9.19 (s, 1H, NH); 3.58 (s, 3H, OCH3). ^13C NMR (75 MHz, DMSO-d6): 183.6; 167.2; 152.3; 144.4; 137.9; 135.6; 130.0; 129.9; 129.1; 128.0; 126.6; 103.9; 53.4; 51.6; 21.1; 18.5. IR ν, sm^−1: 3175 (NH); 1709 (C = O); 1092 (C = S); 756; 852; 974; 1230
8	COOC2H5	CH3	CH3	89.80	212	C9H14N2O4S2			^1H NMR (300 MHz, (DMSO-d6, δ): 1.13 t (3H, CH3); 2.47 t (3H, CH3); 2.64–2.89 m (2H, CH2); 7.31 m (1H, NH); 3.03 m (1H, CH). ^13C NMR (75 MHz, DMSO-d6): 18.6; 53.3; 57.6; 36.2; 184.7. IR ν, sm^−1: 3223; 3126; 2931; 1719 (C = O); 1070–1450 (SO2N)
9	COOC2H5	CH3	C6H5	90.67	220	C14H16N2O4S2			^1H NMR (300 MHz, (DMSO-d6, δ): 1.10 (t, 3H, CH3); 2.31 (s, 3H, CH3); 4.00 (q, 2H, OCH2); 6.92–7.50 (m, 4H, CH–Ar); 9.50 (s, 1H, NH). ^13C NMR (75 MHz, DMSO-d6): 24; 65.0; 113; 126.2; 128.3; 137; 146; 195. IR ν, sm^−1: 3325; 3177; 1674; 1726 (C = O); 1087–1459 (SO2N)
10	COCH3	OC2H5	CH3	26.3	198–199	C9H14N2O4S2			^1H NMR (300 MHz, (DMSO-d6, δ): 1.14 (t, 3H, CH3); 2.35 (s, 3H, CH3); 4.03 (q, 2H, CH2); 6.84–7.20 (m, 4H, CH–Ar); 8.60 (s, 1H, NH). ^13C NMR (75 MHz, DMSO-d6): 19; 23; 68.0; 116; 122; 136.7; 140.6; 180. IR ν, sm^−1: 3220; 3100–2900; 1680 (C = O); 1093; 1403 (SO2N)
11	COCH3	CH3	CH3	23.30	168	C8H12N2O3S2			^1H NMR (300 MHz, (DMSO-d6, δ): 1.05 (m, 3H, CH3); 2.29 (s, 3H, CH3), 3.33 (s, 3H, CH3), 7.09 (s, 1H, NH), 7.81 (s, 1H, CH–Ar); 2.33 (s, 3H, Ar–CH3). ^13C NMR (75 MHz, DMSO-d6): 186, 162, 153, 144, 139, 135.6, 130.0, 129, 105, 54, 51, 21. IR ν, sm^−1: 3196, 2980, 1750, 1690 (C = O), 1093, 1403 (SO2N)
12	COOC2H5	OC2H5	C6H5	19.2	226	C15H18N2O5S2			^1H NMR (300 MHz, (DMSO-d6, δ): 1.13 (m, 3H, CH3); 2.42 (s, 3H, CH3), 2.98 (q, 2H, CH2); 4.02 (s, 2H, CH2); 7.20 (m, 1H, CH–Ar); 9.73 (s, 1H, NH). ^13C NMR (75 MHz, DMSO-d6): 23.4; 51.5; 67.1; 74.5; 116.1; 128.6; 140.9; 171.7; 184.7. IR ν, sm^−1: 3214; 1682; 1564; 3185 (NH); 1699 (C = O); 1599 (OCO); 1144–1462 (SO2N)

Scheme 1. The synthesis routes of the 1-(4-methylsulfonyl)-2-thione-4-aryl-5-Z-6-methyl and oxyalkyl-imidazoles.

Table 3. The inhibition profiles of a dozen 1-(4-methylsulfonyl)-2-thione-4-aryl-5-Z-6-methyl and oxyalkyl-imidazoles 1–12 against human carbonic anhydrase isoenzymes I and II (hCA I and II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes.

	IC50 (nM)								KI (nM)
Compounds	hCA I	r^2	hCA II	r^2	AChE	r^2	BChE	r^2	hCA I	hCA II	AChE	BChE
1	4.33	0.9899	3.37	0.8518	3.17	0.9746	6.24	0.9674	1.43 ± 0.09	2.85 ± 0.58	1.14 ± 0.26	2.02 ± 0.45
2	4.31	0.9540	3.14	0.9338	2.62	0.9426	5.50	0.9827	5.74 ± 2.89	2.44 ± 0.62	0.44 ± 0.01	2.24 ± 0.19
3	4.51	0.9325	3.19	0.9216	2.77	0.9737	5.97	0.9661	4.31 ± 2.43	1.72 ± 0.62	0.94 ± 0.17	3.51 ± 1.04
4	4.78	0.9925	6.60	0.9745	0.76	0.9817	5.87	0.9827	2.31 ± 0.88	5.86 ± 0.99	0.21 ± 0.04	2.45 ± 0.32
5	4.61	0.9755	5.49	0.9771	0.95	0.9546	5.25	0.9868	1.92 ± 0.26	3.62 ± 0.87	0.20 ± 0.05	2.59 ± 0.34
6	4.99	0.9911	7.69	0.9821	1.59	0.9625	7.88	0.9637	1.42 ± 0.24	6.97 ± 2.25	0.49 ± 0.17	5.92 ± 1.63
7	6.03	0.9930	7.22	0.9834	1.95	0.9666	8.06	0.9941	4.27 ± 0.53	4.59 ± 1.74	0.47 ± 0.21	5.53 ± 0.91
8	4.08	0.8833	2.86	0.9349	2.21	0.9939	4.71	0.9709	5.62 ± 1.33	3.35 ± 1.16	0.46 ± 0.04	2.75 ± 0.45
9	3.61	0.9704	6.29	0.9679	1.54	0.9943	7.29	0.9656	3.46 ± 0.49	6.34 ± 3.12	0.72 ± 0.21	2.75 ± 0.38
10	5.06	0.9729	5.47	0.9836	1.12	0.9539	7.53	0.9782	4.39 ± 1.50	5.31 ± 2.07	0.38 ± 0.11	1.55 ± 0.44
11	4.50	0.9970	6.42	0.9355	1.60	0.9595	6.79	0.9613	6.58 ± 2.01	7.41 ± 2.32	0.39 ± 0.13	2.17 ± 0.66
12	5.37	0.9838	6.03	0.9611	2.06	0.9810	6.03	0.9703	5.21 ± 1.07	6.47 ± 2.21	0.62 ± 0.23	1.87 ± 0.25
AZA	46.19	0.9925	34.65	0.9947	–	–	–	–	43.69 ± 6.44	31.67 ± 8.39	–	–
TAC	–	–	–	–	62.43	0.9984	86.63	0.9721	–	–	25.75 ± 3.39	37.82 ± 2.08

Table 4. Determination of the half maximal concentrations (IC₅₀, μg/mL) of Fe²⁺chelating of several new hetaryl sulfonamides 1–12 and standard compounds including BHA, BHT, α-Tocopherol, Trolox and EDTA.

Antioxidant compounds	Fe^2+ chelating (IC50)	r^2
BHA	46.20	0.9984
BHT	76.96	0.9664
α-Tocopherol	40.76	0.9421
Trolox	31.13	0.9442
EDTA	9.36	0.9773
1	173.25	0.9727
2	196.11	0.9866
3	72.32	0.9694
4	169.02	0.9341
5	43.31	0.9170
6	135.88	0.9766
7	97.65	0.9782
8	86.63	0.9092
9	115.40	0.9912
10	76.95	0.9636
11	131.50	0.9626
12	95.86	0.9689