Lipid-lowering properties of 6-benzoyl-2(3H)-benzothiazolone and structurally related compounds

Figures & data

Figure 1 General structures of lipid-lowering compounds described in this study.

Table I.  Physico-chemical properties of compounds 1–7, 9–16 and 18.

Compd.	A	R1	R2	Yield (%)	m.p. (°C)	Crys. solvent	Formula
1	CO	H	C6H5	80	216–217	EtOH	C14H9NO2S
2	CO	CH3	C6H5	82	148	EtOH	C15H11NO2S
3	CO	H	C6H4Cl(4)	75	>270	EtOH	C14H8ClNO2S
4	CO	H	2-Thienyl	20	224	EtOH	C12H7NO2S
5	CO	H	C3H7	50	143–145	EtOH	C11H11NO2S
6	CO	CH3	C3H7	55	115–116	EtOH	C12H13NO2S
7	CO	H	n-C4H9	57	142–143	EtOH	C12H13NO2S
9	CO	H	3-Pyridyl	73	237–239	EtOH	C13H8N2O2S
10	CO	CH3	3-Pyridyl	76	176–178	EtOH	C14H10N2O2S
11	CO	H	(CH2)2CO2H	55	242	EtOH	C11H9NO4S
12	CO	H	CH2C(CH2)CO2H	30	227-230	EtOH	C12H9NO4S
13	CH2	H	n-C3H7	93	127–129	C6H12	C11H13NOS
14	CO	H	CH(CH2N(CH3)2)C2H5	88	160–162	EtOH	C14H18N2O2S
15	CO	H	C(CH2)C2H5	80	151–152	Toluene	C12H11NO2S
16	CO	H	CH(C2H5)CH2SC2H5	67		oil	C14H17NO2S2
18	CO	H		60	185–187	EtOH	C21H23N3O2S

Scheme 1 Synthesis of compounds 1–12.

Scheme 2 Synthesis of compounds 13–18.

Table II.  Effects of treatments (15 days) on plasma lipids, body and liver weights in mice receiving hypercholesterolemic diet.

Compd.	Body wt^a (g) day 15	Liver/body Wt^b (%)	Chol^c (g/l)	TG^d (g/l)	PL^e (g/l)	HDL-C/Chol^f (%)
Control n^g = 12	25.25 ± 2.73	7.52 ± 1.17	2.60 ± 0.37	0.77 ± 0.23	2.34 ± 0.36	37.88 ± 4.60
Fenofibrate n = 12	21.92 ± 2.07	11.22 ± 1.40****	1.87 ± 0.35****	0.47 ± 0.16****	2.68 ± 0.50****	60.92 ± 4.09***
1 n = 12	22.36 ± 2.42*	7.50 ± 1.37	2.05 ± 055****	0.57 ± 0.23****	2.55 ± 0.55*	63.61 ± 4.79***
2 n = 12	24.50 ± 2.00	9.27 ± 0.95 ***	2.88 ± 0.52***	0.65 ± 0.17****	2.32 ± 0.43	45.40 ± 4.67
3 n = 12	24.92 ± 2.09	8.56 ± 0.92*	3.12 ± 0.47****	0.71 ± 0.14****	2.19 ± 0.32***	31.95 ± 4.35
4 n = 12	24.50 ± 2.67	9.42 ± 0.95****	3.15 ± 0.53****	0.66 ± 0.18****	2.43 ± 0.39	39.23 ± 4.88
5 n = 11	21.91 ± 2.34	8.28 ± 1.11	2.19 ± 0.45****	0.63 ± 0.16****	2.10 ± 0.58**	41.12 ± 6.22
6 n = 12	25.75 ± 1.82	8.91 ± 1.29*	3.35 ± 0.52****	0.73 ± 0.14**	2.68 ± 0.37****	46.79 ± 5.63
7 n = 10	25.56 ± 2.92	7.28 ± 1.28	1.96 ± 0.33****	0.70 ± 0.20***	1.85 ± 0.33****	48.99 ± 4.38
9 n = 9	28.75 ± 2.59	5.65 ± 1.02***	2.05 ± 0.44****	0.78 ± 0.26	1.83 ± 0.30****	46.09 ± 5.39
10 n = 12	27.50 ± 3.03	6.84 ± 1.17	2.59 ± 0.50	0.73 ± 0.14**	2.25 ± 0.58	47.90 ± 4.56
11 n = 12	29.83 ± 1.80*	6.22 ± 0.90***	2.79 ± 0.38***	0.69 ± 0.18****	1.70 ± 0.30****	31.74 ± 4.70
12 n = 12	28.50 ± 2.54	6.47 ± 1.10****	2.56 ± 0.47	0.65 ± 0.15****	1.73 ± 0.37****	33.54 ± 5.13
13 n = 12	26.50 ± 1.98	7.66 ± 0.90	2.39 ± 0.21****	0.71 ± 0.14****	2.20 ± 0.39*	51.75 ± 3.98
15 n = 12	25.00 ± 2.04	10.14 ± 0.95****	2.68 ± 0.50	0.59 ± 0.15****	2.35 ± 0.37	49.03 ± 6.55
16 n = 12	27.92 ± 2.38	8.67 ± 0.90**	3.05 ± 0.48****	0.71 ± 0.21***	2.34 ± 0.48	41.21 ± 6.66
18 n = 12	27.42 ± 1.88	8.06 ± 0.87	2.90 ± 0.51***	0.64 ± 0.14****	2.05 ± 0.43****	41.62 ± 5.87

Treated mice (300 mg/Kg per day) were compared to control mice receiving the same diet. *p < 0.05; **p < 0.02; ***p < 0.01; ****p < 0.001; results are mean ± SD.

a body weight

b liver/body weight ratio

c total cholesterol

d triglycerids

e phospholipids

f HDL cholesterol/total cholesterol ratio

g number of treated mice

Table III.  Effects of treatments (21 days) on plasma lipids, body and liver weights in mice receiving standard diet.

Compd.	Body wt^a (g) day 15	Liver/body Wt^b (%)	Chol^c (g/l)	TG^d (g/l)	PL^e (g/l)	HDL-C/Chol^f (%)
Control n^g = 12	29.75 ± 1.54	3.43 ± 0.26	1.04 ± 0.25	0.78 ± 0.23	1.73 ± 0.33	77.77 ± 5.34
Fenofibrate n = 12	31.75 ± 1.82	7.55 ± 0.30****	1.19 ± 0.22****	0.70 ± 0.27***	2.04 ± 0.28****	81.17 ± 5.82
1 n = 12	29.83 ± 1.34	4.40 ± 0.31****	1.06 ± 0.25	1.65 ± 0.35****	1.89 ± 0.42***	82.90 ± 5.20
2 n = 12	31.50 ± 1.57	3.79 ± 0.31****	1.05 ± 0.27	1.39 ± 0.35****	1.91 ± 0.37***	80.92 ± 5.57
3 n = 12	29.50 ± 1.38	3.92 ± 0.35****	0.91 ± 0.17****	1.16 ± 0.32****	1.67 ± 0.23
4 n = 12	32.50 ± 2.35	3.69 ± 0.40****	1.06 ± 0.22	1.48 ± 0.38****	1.87 ± 0.34***	83.11 ± 3.62
5 n = 11	28.92 ± 1.62	3.87 ± 0.33****	0.99 ± 0.20*	1.37 ± 0.36****	1.93 ± 0.27****	78.29 ± 5.42
6 n = 12	29.17 ± 1.59	3.79 ± 0.20****	1.11 ± 0.20***	1.37 ± 0.36**	1.93 ± 0.27****	78.29 ± 5.42
7 n = 10	31.25 ± 1.36	3.84 ± 0.34****	1.10 ± 0.20**	1.03 ± 0.38***	1.89 ± 0.33***	75.43 ± 4.69
9 n = 9	30.00 ± 2.05	4.41 ± 0.37****	1.35 ± 0.33****	1.18 ± 0.23****	2.37 ± 0.44****	76.42 ± 3.48
10 n = 12	29.90 ± 1.97	4.88 ± 0.29****	1.36 ± 0.30****	1.44 ± 0.38**	2.24 ± 0.46****	72.72 ± 4.99
11 n = 12	30.08 ± 1.44	3.45 ± 0.40	1.16 ± 0.30****	0.91 ± 0.18****	1.90 ± 0.39***	77.69 ± 3.47
12 n = 12	30.33 ± 1.72	3.70 ± 0.19****	1.01 ± 0.20	0.87 ± 0.23****	1.77 ± 0.30	74.58 ± 5.87
13 n = 12	31.17 ± 1.95	4.24 ± 0.31****	1.11 ± 0.20***	1.35 ± 0.38****	1.95 ± 0.26****	73.20 ± 4.64
15 n = 12	32.50 ± 2.35	3.69 ± 0.40****	1.23 ± 0.35****	0.92 ± 0.23****	2.00 ± 0.46****	86.26 ± 4.43
16 n = 12	29.08 ± 1.31	4.54 ± 0.26****	0.87 ± 0.15****	± 0.24***	1.35 ± 0.23****	77.66 ± 7.32
18 n = 12	29.09 ± 1.22	3.90 ± 0.26****	1.02 ± 0.20	0.61 ± 0.21****	1.73 ± 0.27	78.18 ± 5.59

Treated mice (300 mg/Kg per day) were compared to control mice receiving the same diet. *p < 0.05; **p < 0.02; ***p < 0.01; ****p < 0.001; results are mean ± SD.

a body weight

b liver/body weight ratio

c total cholesterol

d triglycerids

e phospholipids

f HDL cholesterol/total cholesterol ratio

g number of treated mice