Design,synthesis and biological evaluation of new 5-nitro benzimidazole derivatives as AT1 antagonists with anti-hypertension activities |
| |
| Affiliation: | 1. Department of Radiation Oncology, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA;2. Department of Medicine, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA;3. Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, CA 90502, USA;4. Department of Physiology and Biophysics, University of California Irvine, 1001 Health Sciences Road, Irvine, CA 92697, USA;1. Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, India;2. ISOM, Universidad Politecnia de Madrid, 28040, Spain;3. Physics and Energy Harvesting Group, National Physical Laboratory, New Delhi 110012, India;1. Institute of Physical and Organic Chemistry of Southern Federal University, StachkiProsp. 194/2, 344090 Rostov-on-Don, Russian Federation;2. N.S. Kurnakov Institute of General and Inorganic Chemistry of Russian Academy of Sciences, LeninskyProsp. 31, 119991 Moscow, Russian Federation;3. Southern Scientific Center of Russian Academy of Sciences, Chekhova str. 41, 344006 Rostov-on-Don, Russian Federation;1. Pharmaceutical Chemistry, Institute of Pharmacy, Universität Innsbruck, Innrain 80-82, 6020, Innsbruck, Austria;2. Pharmaceutical Chemistry, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise Str. 2+4, 14195, Berlin, Germany;3. Computer-Aided Drug Design, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise Str. 2+4, 14195, Berlin, Germany;4. Institute of Pharmacology, Center for Cardiovascular Research, Charité Universitätsmedizin Berlin, Hessische Str. 3-4, 10115, Berlin, Germany |
| |
| Abstract: | ![]()
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 ± 0.26 nM. 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 30 mmHg of MBP at 5 mg/kg and 41 mmHg of MBP at 10 mg/kg after oral administration, and the significant antihypertensive effect lasted beyond 24 h, 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. |
| |
| Keywords: | 5-Nitro benzimidazole derivatives Synthesis Anti-hypertension |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
