Design, synthesis and antihypertensive screening of novel pyridazine substituted s-triazin-2-imine/one/thione derivatives

Figures & data

Figure 1.  Structures of positive inotropic agents possessing pyridazine nucleus.

Scheme 1.   Synthesis protocol for various 7-substituted-phenyl-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine/one/thione derivatives.

Table 1.  Percent reduction in mean arterial blood pressure (mm Hg) in rats.

Compound (20mg/kg)	% Reduction in mean arterial blood pressure
	1 h	3 h	6 h	12 h	24 h	48 h	72 h	96 h	120 h
Propranolol	41.40	41.40	38.71	33.75	29.55	23.86	17.10	10.66	4.72
Hydralazine	40.76	40.73	39.28	35.62	31.44	22.50	15.78	12.00	5.40
4a	23.85	22.98	20.77	17.50	14.46	10.42	6057	4.66	2.70
4b	28.65	27.96	25.76	22.50	19.49	16.82	13.15	8.00	4.78
4c	34.12	3295	30.13	26.25	23.27	19.38	13.81	9.33	4.72
4d	36.30	34.35	30.10	26.15	20.75	16.18	12.50	8.66	4.72
4e	32.46	32.10	29.43	25.46	21.38	17.46	11.84	9.20	6.08
4f	36.14	32.98	27.83	25.00	20.44	14.90	10.13	7.60	4.05
4g	24.50	22.36	20.77	19.37	17.61	12.98	6.57	4.00	1.35
4h	26.48	24.21	22.02	20.50	18.23	15.54	9.93	7.33	3.37
4i	28.52	26.91	24.46	22.50	17.61	12.85	9.21	6.66	4.05
4j	40.88	39.71	36.86	27.65	22.01	18.10	11.71	7.00	3.37
4k	36.82	36.21	35.47	30.00	25.78	20.70	15.78	12.00	5.00
4l	38.06	36.58	34.86	31.80	29.55	21.30	15.13	11.25	6.08
4m	40.98	39.47	36.20	25.67	20.12	15.67	11.18	8.53	4.05
4n	37.92	37.39	36.91	31.50	24.71	18.74	12.76	7.73	2.70
4o	32.64	32.53	29.68	26.12	19.37	14.77	10.26	7.46	2.02
4p	42.04	38.28	33.82	29.46	22.01	13.62	7.89	5.33	3.37
4q	30.15	29.06	25.90	25.00	21.38	15.29	10.03	7.20	4.18
4r	31.64	30.99	28.88	23.67	18.23	14.52	9.86	6.53	3.78
4s	24.12	22.21	20.00	18.60	16.98	14.33	11.05	6.93	1.35
4t	26.17	24.21	19.52	15.00	13.13	11.70	7.50	5.24	2.36
4u	18.52	15.83	13.04	12.50	11.63	9.48	6.44	4.46	2.22

^a Dose of Propranolol was taken as 14 mg/kg. ^b Dose of Hydralazine was taken as 2.6 mg/kg. All values were expressed as mean ± SEM (*p ≤ 0.05), each group comprised of four animals (i.e. n = 4). Toxic control group was compared with control group. All the treatment groups were compared with toxic control group and p < 0.05 was considered to be significant. ^** p < 0.01; ^* p < 0.05