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A rational design, synthesis, characterization, and antihypertensive activities of some new substituted benzimidazoles

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Abstract

A series of 5-substituted benzimidazoles were designed, synthesized, and evaluated for in vivo antihypertensive activity by acute renal hypertension on guinea pig. All the compounds of the series elicit remarkable activity in comparison to standard drug (losartan). The activity is found to be relatively better in substituted alkylamino group at 5-position of benzimidazole. The maximum activity that is almost equipotent with losartan is observed with four compounds DR-13, DR-14, DR-15, and DR-16.

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References

  • Balasubramanian N, Dhake A, Mourya VK (2007) QSAR studies of 4,5-dihydro-4-oxo-3H-imidazo[4,5-c]pyridines as potent angiotensin II receptor antagonists by MLR and NLR analysis. Arkivoc 1:189–204

    Google Scholar 

  • Bali A, Bansal Y, Sugumaran M, Saggu JS, Balakumar P, Kaur G, Bansal G, Sharma A, Singh M (2005) Design, synthesis, and evaluation of novelly substituted benzimidazole compounds as angiotensin II receptor antagonists. Bioorg Med Chem Lett 15:3962–3965

    Article  PubMed  CAS  Google Scholar 

  • Belvisi L, Bravi G, Catalano G, Mabiliab M, Salimbeni A, Scolastico C (1996) A 3D QSAR CoMFA study of nonpeptide angiotensin II receptor antagonists. J Comput Aided Mol Des 10:567–582. doi:10.1007/BF00134180

    Article  PubMed  CAS  Google Scholar 

  • Carini DJ, Dunica JV, Aldrich PE, Chiu AT, Johnson AL, Pieerce ME, Price WA, Santella JB, Wells GJ, Wexler RR, Wong PC, Yoo S, Timmermans PBMWM (1991) Nonpeptide angiotensin II receptor antagonist: the discovery of series of n-(biphenylmethyl) imidazoles as potent, orally-active antihypertensive. J Med Chem 34:2525–2527

    Article  PubMed  CAS  Google Scholar 

  • Cherinet A, Tesfaye T, Abebe A, Hassen TS, Dawit A, Kelbessa U (2002) Antihypertensive activity of residue from “gebo arekei” locally distilled medicinal spirit from a brew containing lupines albus seeds in renovascular hypertensive guinea pig. Ethio J Health Sci 12:25–31

    Google Scholar 

  • Cockcroft JR, Sciberras DG, Goldberg MR, Ritter MJ (1993) Comparision of angiotensin converting enzyme inhibition with angiotensin II receptor antagonism in the human forearm. J Cardiovasc Pharm 22:579–584

    Article  CAS  Google Scholar 

  • Datar PA, Coutinho EC, Srivastava S (2004a) Comparative study of 3D-QSAR techniques on angiotensin II receptor (AT1) antagonists. Lett Drug Design Disc 1(6):115–120

    Google Scholar 

  • Datar PA, Desai PV, Coutinho EC (2004b) A 3D-QSAR of angiotensin II (AT1) receptor antagonistsbased on receptor surface analysis. J Chem Inf Model 44:210–220. doi:10.1021/ci0341520

    Article  CAS  Google Scholar 

  • Ellingboe JW, Antane M, Nguyen TT, Collini MD, Antane S, Bender R, Hartupee D, White V, McCallum J, Park CH (1994) Pyrido[2,3-d]pyrimidine angiotensin II antagonists. J Med Chem 37:542–550. doi:10.1021/jm00030a013

    Article  PubMed  CAS  Google Scholar 

  • Ferrario CM (1990) The renin-angiotensin system: importance in physiology. J Cardiovasc Pharm 15:S1–S5

    Article  Google Scholar 

  • Gilani AH, Jabeen Q, Ghayur MN, Janbaz KH, Akhtar MS (2005) Studies on the antihypertensive, antispasmodic, bronchodilator and hepatoprotective activities of the Carum copticum seed extract. J Ethnopharmacol 98:127–135

    Article  PubMed  CAS  Google Scholar 

  • Hauser SD, Stade M, Schmidt S, Hanauer G (2005) Cardiovascular parameters in anaesthetized guinea pigs: A safety pharmacology screening model. J Pharmacol Toxicol Methods 52:106–114

    Article  PubMed  CAS  Google Scholar 

  • Jain A, Chaturvedi SC (2008) Rationalization of physicochemical property of some substituted benzimidazole bearing acidic heterocyclic towards angiotensin II antagonist: a QSAR approach. Asian J Biochem 5:330–336

    Article  Google Scholar 

  • Jain A, Chaturvedi SC (2009a) QSAR study on 6- substituted benzimidazole: an insight into the structural requirement for the angiotensin II AT1 receptor antagonist. Sci Pharm 77:555–565

    Article  CAS  Google Scholar 

  • Jain A, Chaturvedi SC (2009) QSAR modeling of some substituted benzimidazole as angiotensin II AT1 receptor antagonist. Med Chem Res doi:10.1007/s00044-009-9182-z

  • Jason LM, Stephen MT, Vadim AS (2005) An efficient and operationally convenient general synthesis of tertiary amines by direct alkylation of secondary amines with alkyl halides in the presence of Huenig’s base. ARKIVOC 287–292

  • Jat RK, Jat JL, Pathak DP (2006) Synthesis of benzimidazole derivatives: as anti-hypertensive agents. Eur J Chem 13:278–285

    Google Scholar 

  • Kaur N, Kaur A, Bansal Y, Shah DI, Bansal G, Singh M (2008) Design, synthesis, and evaluation of 5-sulfamoyl benzimidazole derivatives as novel angiotensin ii receptor antagonists. Bioorg Med Chem 16:10210–10215

    Article  PubMed  CAS  Google Scholar 

  • Kohara Y, Kubo K, Imamiya E, Wada T, Inada Y, Naka T (1996) Synthesis and angiotensin ii receptor antagonist activities of benzimidazole derivatives bearing acidic heterocycle as novel tetrazole bioisosteres. J Med Chem 39:5228–5235

    Article  PubMed  CAS  Google Scholar 

  • Kubo K, Kohara Y, Yoshimura Y, Inada Y, Shibouta Y, Furukawa Y, Kato T, Nishikawa K, Naka T (1993a) Nonpeptide angiotensin ii receptor antagonist. Synthesis and biological activity of benzimidazolecarboxylic acids. J Med Chem 36:2182–2195

    Article  PubMed  CAS  Google Scholar 

  • Kubo K, Kohara Y, Yoshimura Y, InadaY Shibouta Y, Furukawa Y, Kato T, Nishikawa K, Naka T (1993b) Nonpeptide angiotensin ii receptor antagonist. Synthesis and biological activity of benzimidazoles. J Med Chem 36:1172–1784

    Google Scholar 

  • Kurup A, Garg R, Carini DJ, Hansch C (2001) Comparative QSAR: angiotensin II antagonists. Chem Rev 101:2727. doi:10.1021/cr000025g

    Article  PubMed  CAS  Google Scholar 

  • Hardman JG, Limbird, LE (2001) Goodman and Gilman’s: the pharmacological basis of therapeutics. McGraw-Hill, New York

  • Mostafa MR, Mohamed AO, Tokuda H, Hoda IE (2007) Synthesis and inhibitory activity of new benzimidazole derivatives against Burkitt’lymphoma promotion. Bio Med Chem 6489–6496

  • Naka T, Kubo K (1999) a new class of diacidic nonpeptide angiotensin II receptor antagonists: candesartan cilexetil. Curr Pharm Des 6:453–472

    Google Scholar 

  • Pandya T, Chaturvedi SC (2004) QSAR study of a series of 2-, 3-, 6-substituted quinazolinones as AT1 selective angiotensin II receptor antagonists. Ind J Chem 4300300:2440–2445

    Google Scholar 

  • Pandya T, Chaturvedi SC (2005) Structure–activity relationship study of some triazolinone-based compounds with antagonistic balanced activity on angiotensin II receptor subtypes AT1 and AT2:a three-dimensional quantitative structure–activity relationship investigation. Arzneimittelforschung 55:265–270

    PubMed  CAS  Google Scholar 

  • Pandya T, Pandey SK, Tiwari M, Chaturvedi SC, Saxena AK (2001) 3-D QSAR studies of triazolinone based balanced AT1/AT2 receptor antagonists. Bioorg Med Chem 9:291–300

    Article  PubMed  CAS  Google Scholar 

  • Ries UJ, Mihm G, Narr B, Hasselbach KM, Wittneben H, Entzeroth M, Van Meel JC, Wienen W, Hauel NH (1993) 6-Substituted benzimidazoles as new nonpeptide angiotensin II receptor antagonists: synthesis, biological activity, and structure-activity relationships. J Med Chem 25:4040–4051

    Article  Google Scholar 

  • Shah DI, Sharma M, Bansal Y, Bansal G, Singh M (2008) Angiotensin II- AT1 receptor antagonist: design, synthesis and evaluation of substituted carboxamido benzimidazole derivatives. Euro J Med Chem 43:1808–1812

    Article  CAS  Google Scholar 

  • Xu JY, Zeng Y, Ran Q, Wei Z, Qian YB, Qiu HH, Wang J, Hu S, Zhang J, Tang MY, Huaa WY, Wua XM (2007) Synthesis and biological activity of 2-alkylbenzimidazole bearing a N-phenyl pyrrole moiety as novel angiotensin II AT1 receptor antagonists. Bioorg Med Chem Lett 17:2921–2926

    Google Scholar 

  • Yan PZ, Chen BC, Shi H, Jian HJ, Hai LW, Guo LS, Ru QY (2007) QSAR study of angiotensin II antagonists using robust boosting partial least squares regression. Anal Chim Acta 593:68–74. doi:10.1016/j.aca.2007.04.031

    Article  Google Scholar 

  • Yoo SE, Kim SK, Lee SH, Yi KY, Lee DW (1999) A comparative molecular field analysis and molecular modeling studies on pyridylimidazole type of angiotensin II antagonists. Bioorg Med Chem 7:2971–2976. doi:10.1016/S0968-0896(99)00245-X

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank the Head of the School of Pharmacy, Devi Ahilya Vishwavidyalaya, for providing the facilities for carrying out the study, and Mr. B. R. Nahata from the College of Pharmacy for his help in carrying out biological evaluation.

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Authors and Affiliations

  1. B. R. Nahata College of Pharmacy, Mandasur, 458001, MP, India

    Anurekha Jain

  2. School of Pharmacy, DAVV, Indore, MP, India

    Rajesh Sharma

  3. Aurbindo college of Pharmacy, Indore, MP, India

    S. C. Chaturvedi

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  1. Anurekha Jain
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  2. Rajesh Sharma
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  3. S. C. Chaturvedi
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Correspondence to Anurekha Jain.

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Jain, A., Sharma, R. & Chaturvedi, S.C. A rational design, synthesis, characterization, and antihypertensive activities of some new substituted benzimidazoles. Med Chem Res 22, 4622–4632 (2013). https://doi.org/10.1007/s00044-012-0462-7

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  • DOI: https://doi.org/10.1007/s00044-012-0462-7

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