301533-59-5Relevant articles and documents
Design, Synthesis, and Biological Evaluation of 6-Benzoxazole Benzimidazole Derivatives with Antihypertension Activities
Wu, Zhuo,Bao, Xiao-Lu,Zhu, Wei-Bo,Wang, Yan-Hui,Phuong Anh, Nguyen Thi,Wu, Xiao-Feng,Yan, Yi-Jia,Chen, Zhi-Long
, p. 40 - 43 (2019/01/14)
A series of new angiotensin II receptor 1 antagonists were prepared. They displayed nanomolar affinity to AT1 receptor and could decrease blood pressure efficiently in spontaneously hypertensive rats. Among them, compounds 1b and 2b could reduce the blood pressure with more or equal potency compared to Losartan. So, compounds 1b and 2b could be considered as potential antihypertension drug candidates.
N-Phenyl indole derivatives as AT1 antagonists with anti-hypertension activities: Design, synthesis and biological evaluation
Zhu, Weibo,Bao, Xiaolu,Ren, He,Da, Yajing,Wu, Dan,Li, Fuming,Yan, Yijia,Wang, Li,Chen, Zhilong
, p. 161 - 178 (2016/04/05)
The design, synthesis, in vitro and in vivo evaluation of 6-substituted benzimidazole with 1, 4-disubsituted or 1, 5-disubsituted indole derivatives as novel angiotensin II receptor antagonists are outlined. Radioligand binding assays showed that several 6-substituted benzimidazole derivatives displayed high affinities binding to the angiotensin II type 1 receptor at the same order of magnitude to telmisartan. The biological evaluation on spontaneously hypertensive rats showed that 2-[4-[[2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole-1-yl]methyl]-1H-indol-1-yl]benzoic acid, 1c, could cause significant decrease on MBP in a dose dependent manner. Its maximal response lowered 53 mmHg of MBP at 5 mg/kg and 64 mmHg of MBP at 10 mg/kg after oral administration, and the significant antihypertensive effect lasted beyond 24 h, which was better than both losartan and telmisartan. A study designed to determine acute toxicity showed that 1c had low acute toxicity with no significant changes in the weight and no obvious untoward reactions. The encouraging results make 1c an effective and durable anti-hypertension drug candidate and deserve further investigation for therapeutic application.
Facile Synthesis of Novel Nonpeptide Angiotensin II Receptor Antagonists
Yang, Ling-Chun,Qi, Chuan-Min,Zhang, Guan-Xin,Zou, Nan-Zhi
, p. 1107 - 1112 (2007/10/03)
A series of Losartan analogues 1-12 with different functional groups were synthesized and characterized. In comparison with the previous reports, the synthetic procedures described in this paper have been optimized as follows below: 1) preparation of aromatic amine 15 and 18 through hydrogenation by employing Raney Ni and hydrazine as catalysts in place of palladium; 2) preparation of nitro-compound 17 by using pure fuming nitric acid at -20 - -15°C; 3) alkylation of 21 with 22 or 23 in the presence of sodium hydride in place of potassium tert-butylate; 4) preparation of carboxylic acid 4 by ester cleavage rather than hydrolysis of cyano group.
6-Substituted benzimidazoles as new nonpeptide angiotensin II receptor antagonists: Synthesis, biological activity, and structure-activity relationships
Ries,Mihm,Narr,Hasselbach,Wittneben,Entzeroth,Van Meel,Wienen,Hauel
, p. 4040 - 4051 (2007/10/02)
Starting from the recently reported nonpeptidic angiotensin II (AII) receptor antagonists DuP 753 (1) and Exp 7711 (2), we have designed and investigated novel substituted benzimidazoles. Systematic variation of several substituents at the benzimidazole ring positions 4-7 led to the finding that substitution in position 6 with acylamino groups results in highly active AII antagonists. Compounds with 6-membered lactam or sultam substituents in position 6 of benzimidazole showed receptor activities in the low nanomolar range but were only weakly active when given orally to rats. In contrast, analogous substitution of the benzimidazole moiety with basic heterocycles resulted in potent AII antagonists which were also well absorbed after oral application. The most active compound of this series, 33 (BIBR 277), was selected as a candidate for clinical development. On the basis of molecular modeling studies a binding model of this new class of AII antagonists to the AT1 receptor is proposed.
