- Synthesis, characterization of benzimidazole carboxamide derivatives as potent anaplastic lymphoma kinase inhibitor and antioxidant activity
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Novel benzimidazole carboxamide derivatives have been synthesized and characterized by FTIR, NMR, and mass spectral analysis. The synthesized compounds 7a, 7d, and 7f showed excellent scavenging capacity against DPPH radical and the results are comparable with ascorbic acid. In-silico molecular docking studies exhibited compounds 7a, 7d, and 7f had a good affinity towards the active pocket and the results indicated the ability of potent and selective inhibition of anaplastic lymphoma kinase (ALK) receptor. The theoretical investigation of MEPs, HOMO, LUMO, and the energy gap of HOMO-LUMO were calculated by B3LYP/6-31G method and reactivity descriptors were also computed.
- Sam Daniel Prabu,Lakshmanan, Sivalingam,Ramalakshmi,Thirumurugan,Govindaraj, Dharman,Antony, S. Arul
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p. 266 - 278
(2019/01/19)
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- Nonpeptide Angiotensin II Receptor Antagonists. Synthesis and Biological Activity of Benzimidazolecarboxylic Acids
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A series of 2-substituted-1--1H-benzimidazole-7-carboxylic acids was prepared from the key intermediate 3-amino-2-amino>benzoate (6a-c) in order to clarify the structure-activity relationships of various analogues of 2-butyl-1-methyl>-1H-benzimidazole-7-carboxylic acid (CV-11194), a potent and long acting angiotensin II (AII) receptor antagonist.The AII antagonistic activity of the benzimidazoles was investigated by in vitro assays, which included an AII receptor binding assay and AII-induced vasocontraction assay, as well as by in vivo assays such as an AII-induced pressor response in rats.Most of the benzimidazoles showed high affinity for the AII receptor (IC50 value, 10-6-1--7 M) and inhibited the AII-induced pressor response at 1 or 3 mg/kg po, and the effects were more potent than those of CV-11194 and DuP 753.The structure-activity relationship studies on the binding affinity and the inhibition of AII-induced pressor response suggested that straight chains of a certain length (e.g., ethoxy groups, ethyl groups) were the best as substituents at the 2-position and that their steric factors, lipohilicity, and electronic effects affected the potency of the AII antagonistic action.Both a carboxyl group at the 7-position and a tetrazole ring at the 2'-position were particularly important for potent and orally active AII antagonistic activity and a long-acting hypotensive effect.The representative compound, 2-ethoxy-1-methyl>-1H-benzimidazole-7-carboxylic acid (26b, CV-11974), inhibited the specific binding of AII to bovine adrenal cortical membrane with an IC50 value of 1.1*10-7 M.The AII-induced contraction of rabbit aortic strips was antagonized by CV-11974 (IC50 value, 3.0*1--10 M).Oral administration of CV-11974 to conscious normatensive rats at 1 mg/kg resulted in long-lasting inhibition of the AII-induced pressor response.CV-11974 at 0.1-1 mg/kg iv reduced blood pressure dose-dependently in spontaneously hypertensive rats.
- Kubo, Keiji,Kohara, Yasuhisa,Imamiya, Eiko,Sugiura, Yoshihiro,Inada, Yoshiyuki,et al.
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p. 2182 - 2195
(2007/10/02)
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- Benzimidazole derivatives and their use
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Novel imidazole derivatives of the formula (I): STR1 wherein R1 is an optionally substituted alkyl group, R2 and R3 are independently a group capable of forming an anion or a group which can be changed thereinto, ring A is a benzene ring optionally having, besides the group shown by R2, further substituents, and X shows linkage of phenylene group and phenyl group directly or through a spacer whose atomic length is not more than 2 and a salt thereof, show antagonistic actions to angiotensin II, thus being useful as therapeutics for cardiovascular diseases.
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