BIOMAT Database Logo BIOMAT Database Logo

Design, synthesis and biological evaluation of new 5-nitro benzimidazole derivatives as AT1 antagonists with anti-hypertension activities. 2014

Weibo Zhu, and Yajing Da, and Dan Wu, and Huiling Zheng, and Linfeng Zhu, and Li Wang, and Yijia Yan, and Zhilong Chen
Department of Pharmaceutical Science and Technology, College of Chemistry and Biology, Donghua University, 2999 North Renmin Road, Shanghai 201620, China.

The design, synthesis, in vitro and in vivo evaluation of 5-nitro benzimidazole with 1,4-disubsituted or 1,5-disubsituted indole derivatives as novel angiotensin II receptor antagonist is outlined. Radioligand binding assays showed that 2-(4-((2-butyl-5-nitro-1H-benzo[d]imidazol-1-yl)methyl)-1H-indol-1-yl)benzoic acid, compound 3, displayed a high affinity for the angiotensin II type 1 receptor with IC50 value of 1.03±0.26nM. The biological evaluation on spontaneously hypertensive rats and renal hypertensive rats showed that 3 could cause significant decrease on MBP in a dose dependent manner, whose maximal response lowered 30mmHg of MBP at 5mg/kg and 41mmHg of MBP at 10mg/kg after oral administration, and the significant antihypertensive effect lasted beyond 24h, which is better than Losartan. Taken together 3 could be considered as an effective and durable anti-hypertension drug candidate. These encouraging results are deserved of further investigation towards its use for therapeutic benefit.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011918 Rats, Inbred SHR A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke. Rats, Spontaneously Hypertensive,Rats, SHR,Inbred SHR Rat,Inbred SHR Rats,Rat, Inbred SHR,Rat, SHR,Rat, Spontaneously Hypertensive,SHR Rat,SHR Rat, Inbred,SHR Rats,SHR Rats, Inbred,Spontaneously Hypertensive Rat,Spontaneously Hypertensive Rats
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000959 Antihypertensive Agents Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. Anti-Hypertensive,Anti-Hypertensive Agent,Anti-Hypertensive Drug,Antihypertensive,Antihypertensive Agent,Antihypertensive Drug,Anti-Hypertensive Agents,Anti-Hypertensive Drugs,Anti-Hypertensives,Antihypertensive Drugs,Antihypertensives,Agent, Anti-Hypertensive,Agent, Antihypertensive,Agents, Anti-Hypertensive,Agents, Antihypertensive,Anti Hypertensive,Anti Hypertensive Agent,Anti Hypertensive Agents,Anti Hypertensive Drug,Anti Hypertensive Drugs,Anti Hypertensives,Drug, Anti-Hypertensive,Drug, Antihypertensive,Drugs, Anti-Hypertensive,Drugs, Antihypertensive
D001562 Benzimidazoles Compounds with a BENZENE fused to IMIDAZOLES.
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

Related Publications

Weibo Zhu, and Yajing Da, and Dan Wu, and Huiling Zheng, and Linfeng Zhu, and Li Wang, and Yijia Yan, and Zhilong Chen
Design, synthesis and biological evaluation of novel fluoro-substituted benzimidazole derivatives with anti-hypertension activities.
August 2020, Bioorganic chemistry,
Weibo Zhu, and Yajing Da, and Dan Wu, and Huiling Zheng, and Linfeng Zhu, and Li Wang, and Yijia Yan, and Zhilong Chen
Design, synthesis and biological evaluation of 6-substituted aminocarbonyl benzimidazole derivatives as nonpeptidic angiotensin II AT1 receptor antagonists.
March 2012, European journal of medicinal chemistry,
Weibo Zhu, and Yajing Da, and Dan Wu, and Huiling Zheng, and Linfeng Zhu, and Li Wang, and Yijia Yan, and Zhilong Chen
Design, synthesis, and pharmacological evaluation of 5-oxo-1,2,4-oxadiazole derivatives as AT1 antagonists with antihypertension activities.
January 2016, Clinical and experimental hypertension (New York, N.Y. : 1993),
Weibo Zhu, and Yajing Da, and Dan Wu, and Huiling Zheng, and Linfeng Zhu, and Li Wang, and Yijia Yan, and Zhilong Chen
Angiotensin II--AT1 receptor antagonists: design, synthesis and evaluation of substituted carboxamido benzimidazole derivatives.
September 2008, European journal of medicinal chemistry,
Weibo Zhu, and Yajing Da, and Dan Wu, and Huiling Zheng, and Linfeng Zhu, and Li Wang, and Yijia Yan, and Zhilong Chen
Design, Synthesis, and Biological Evaluation of 6-Benzoxazole Benzimidazole Derivatives with Antihypertension Activities.
January 2019, ACS medicinal chemistry letters,
Weibo Zhu, and Yajing Da, and Dan Wu, and Huiling Zheng, and Linfeng Zhu, and Li Wang, and Yijia Yan, and Zhilong Chen
Design, synthesis, and evaluation of 5-sulfamoyl benzimidazole derivatives as novel angiotensin II receptor antagonists.
December 2008, Bioorganic & medicinal chemistry,
Weibo Zhu, and Yajing Da, and Dan Wu, and Huiling Zheng, and Linfeng Zhu, and Li Wang, and Yijia Yan, and Zhilong Chen
Design, synthesis and biological evaluation of 3',4',5'-trimethoxy flavonoid benzimidazole derivatives as potential anti-tumor agents.
February 2018, MedChemComm,
Weibo Zhu, and Yajing Da, and Dan Wu, and Huiling Zheng, and Linfeng Zhu, and Li Wang, and Yijia Yan, and Zhilong Chen
Benzimidazole derivatives. Part 5: design and synthesis of new benzimidazole-arylpiperazine derivatives acting as mixed 5-HT1A/5-HT3 ligands.
October 2004, Bioorganic & medicinal chemistry,
Weibo Zhu, and Yajing Da, and Dan Wu, and Huiling Zheng, and Linfeng Zhu, and Li Wang, and Yijia Yan, and Zhilong Chen
Synthesis and biological evaluation of new fluorine substituted derivatives as angiotensin II receptor antagonists with anti-hypertension and anti-tumor effects.
December 2012, Bioorganic & medicinal chemistry,
Weibo Zhu, and Yajing Da, and Dan Wu, and Huiling Zheng, and Linfeng Zhu, and Li Wang, and Yijia Yan, and Zhilong Chen
Design, Synthesis, and Biological Evaluation of Benzimidazole Derivatives as Potential Lassa Virus Inhibitors.
February 2023, Molecules (Basel, Switzerland),
Copied contents to your clipboard!