152628-03-0Relevant articles and documents
Design, synthesis and evaluation of novel angiotensin II receptor 1 antagonists with antihypertensive activities
Bao, Xiao-Lu,Zhu, Wei-Bo,Shan, Tian-Li,Wu, Zhuo,Zhang, Rui-Jing,Liao, Ping-Yong,Zheng, Mei-Zhen,Tang, He-Sheng,Yan, Yi-Jia,Chen, Zhi-Long
, p. 26401 - 26410 (2017)
A series of novel angiotensin II receptor 1 antagonists (1a-f, 2a-f) were designed, synthesized and evaluated. Radioligand binding assays showed that all these prepared compounds displayed nanomolar affinity for angiotensin II type 1 receptor, among which compound 1f was more affinitive than telmisartan at the same order of magnitude with an IC50 value of 1.13 ± 1.68 nM. The antihypertensive effects showed that all these compounds could decrease blood pressure in a dose dependent manner on spontaneously hypertensive rats. And compound 2-(4-((2-butyl-4-methyl-6-(oxazolo[4,5-b]pyridine-2-yl)benzimidazole-1-yl)methyl)-1H-indol-1-yl) benzoic acid (1f), showed efficient and long-lasting effects in reducing blood pressure, with a maximal response lowered 55.98 ± 4.74 mmHg at 10 mg kg-1 and 35.82 ± 6.20 mmHg at 5 mg kg-1, the antihypertensive effect of it lasted beyond 24 h which was better than telmisartan. In the single-dose pharmacokinetic experiments, compound 1f was absorbed efficiently and metabolized smoothly in Wistar rats. The values of Cmax, Tmax, AUC0-72, MRT0-72 and T1/2 were 17.92 ± 10.85 ng mL-1, 2.60 ± 3.05 h, 252.85 ± 144.59 ng mL-1 h, 18.75 ± 0.43 h and 17.16 ± 4.24 h respectively. Compound 1f was distributed into tissues rapidly and extensively after oral administration and the level of it was the highest in the liver, followed by in the kidney, and the lowest in brain. The acute toxicity assays in ICR rats of 1f showed that it had low acute toxicity with an LD50 value of 1459.89 mg kg-1. These encouraging results make 1f an efficient, long-acting and safe antihypertensive drug candidate and deserving of further investigation.
Preparation method of telmisartan intermediate
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Paragraph 0021; 0029; 0031; 0032; 0034; 0035; 0037; 0038, (2019/02/21)
The invention relates to a preparation method of a telmisartan intermediate, namely 2-n-propyl-4-methyl-6-Benzimidazolecarboxylic acid. The preparation method of the 2-n-propyl-4-methyl-6-Benzimidazolecarboxylic acid comprises the following steps: firstly, ethanol hydrochloride acts with butyronitrile and anhydrous hydrogen chloride within the range of 0-35 DEG C; the mixture obtained in the firststep reacts with 3-methyl-4-aminobenzoic acid and ice vinegar within the range of pH 5.0-11.0 at the controlled temperature of 10-40 DEG C, and an intermediate shown in the formula II is obtained; and then the intermediate shown in the formula II reacts with a sodium hypochlorite solution, and the 2-n-propyl-4-methyl-6-Benzimidazolecarboxylic acid is obtained. The intermediate preparation processis suitable for industrial production, and meanwhile the product quality is improved.
Design, synthesis and biological evaluation of AT1 receptor blockers derived from 6-substituted aminocarbonyl benzimidazoles
Wu, Zhuo,Anh, Nguyen Thi Phuong,Yan, Yi-Jia,Xia, Ming-Bao,Wang, Yan-Hui,Qiu, Yan,Chen, Zhi-Long
, (2019/08/01)
A series of new 6-substituted aminocarbonyl benzimidazole derivatives with 1, 4-disubsituted or 1, 5-disubsituted indole moiety and benzoic acid moiety were designed, synthesized and pharmacologically evaluated. Most of the synthesized compounds could bind to the AT1 receptor and decrease blood pressure significantly. Notably, 2e and 1h could obviously decrease MBP in a dose dependent manner. The maximal response lowered 57.9 ± 2.3 mmHg (2e) and 57.6 ± 1.9 mmHg (1h) of MBP at 10 mg/kg after oral administration, and the antihypertensive effect lasted beyond 24 h, which performed better than Losartan (Fig. 1). These results indicate that 2e and 1h are effective and long-lasting anti-hypertension drug candidates and deserve further investigation for therapeutic application.
