Synthesis and Biological Evaluation of Potent Antihypertensive Activity: 2-[(Substituted-phenyl amino)-phenyl-methyl]-1-[2'-(1H-tetrazol-5-yl) biphenyl-3-ylmethyl]-1H-benzoimidazol-5-ylamine Derivatives

Authors

  • M. C.Sharma Department of Pharmaceutical Sciences Dr.Hari Singh Gour University Sagar (M.P) 470003 India
  • D.V.Kohli Department of Pharmaceutical Sciences Dr.Hari Singh Gour University Sagar (M.P) 470003 India
  • Smita Sharma Department of Chemistry Yadhunath Mahavidyalya, Bhind (M.P) 477001 India

Keywords:

Benzimidazoles, Biphenyl tetrazole, Angiotension-II, antihypertensive agents

Abstract

Some new 2-[(Substituted-phenyl amino)-phenyl-methyl]-1-[2'-(1Htetrazol-5-yl) biphenyl-3-ylmethyl]-1H-benzoimidazol-5-ylamine Derivatives were synthesised by 2-( α -hydroxy benzyl) benzimidazole was converted to 2-(α-bromo benzyl) benzimidazole by reacting with Con.Nitric acid, sulphuric acid HBr and Anhydrous ZnCl2 Schiff bases react with ortho position attach biphenyl tetrazole with different substituents amino group cyclocondensation with appropriate reagents. Different from the previously reported and related compounds in that they produce a potent hypertensive effect the compounds synthesised were identified by 1H NMR, 13C NMR, FAB Mass and FT-IR spectroscopic techniques. All compounds studied in this work were screened for their antihypertensive activity by tail cuff method and direct method measurement.

References

Wexler R.R, Greenlee W.J, Irvin J.D,

Goldberg M.R, Prendergast K, Smith R.D,

Timmermans P.B. Nonpeptide angiotensin

II receptor antagonists: the next generation

in antihypertensive therapy. J Med

Chem1996; 39: 625–656.

Brunner H.R, Nussberger J, Waeber B.

The present molecules of converting

enzyme inhibitors. J Cardiovasc

Pharmacol. 1985; 7 Suppl 1:S2–S11.

Goodfriend T.L, Elliott M.E, Catt K.J.

Angiotensin receptors and their

antagonists. N Engl J Med. 1996; 334:

–1654.

Tuccinardi T, Calderone V, Rapposelli S,

Martinelli A. Proposal of a new binding

orientation for non-peptide AT1

antagonists. J Med Chem 2006; 49:4305–

Kubo K, Kohar Y, Yoshimura Y, Shibouta

Y, Furukawa Y . Nonpeptide angiotensin

II receptor antagonists. Synthesis and

biological activity of potential prodrugs of

benzimidazole-7-carboxylic acids. J Med

Chem 1993; 36:2343–2349.

Smith R.D, Chiu A.T, Wong P.C, Herblin

W.F, Timmermans P.B.M.W.M.

Pharmaco doi:10.1021/jm00068a011logy

of Nonpeptide Angiotensin-II Receptor

Antagonists. Ann Rev Pharmacol

Toxicol.1992; 32: 135–165.

Timmermans P.B, Chiu A.T, Herblin W.F,

Wong P.C, Smith R.D. Angiotensin II

receptor subtypes. Am J Hypertens1992;

: 406–410.

Bernhart C.A, Perreaut P.M, Ferrari B.P,

Muneaux Y.A, Assens J.L, Clement J,

Haudricourt F, Muneaux C.F,Taillades

J.E, Vignal M.A . A new series of

imidazolones: highly specific and potent

nonpeptide AT1 angiotensin II receptor

antagonists. J Med Chem 1993; 36:3371–

Buhl M.P, Furet P, Criscione L, de G. M,

Schimidilin T.S, LAttman R, W. J

.Valsartan: a potent orally active

angiotensin ii antagonist developed from a

structurally new amino acid series. Bioorg

Med Chem Lett 1994; 4:29–34.

Ellingboe J.W, Antane M, Nguyen T.T,

Collini M.D, Antane S, Bender R,

Hartupee D, White V, McCallum J, Park

C.H. Pyrido[2,3-d]pyrimidine angiotensin

II antagonists. J Med Chem 1994;37:542–

Judd D.B, Dowle M.D, Middlemiss D,

Scopes D.I, Ross B.C, Jack T.I, Pass M,

Tranquillini E, Hobson J.E, Panchal T.A.

Bromobenzofuran-based nonpeptide

antagonists of angiotensin II: A potent

antihypertensive agent with high oral

bioavailability. J Med Chem1994;

:3108–3120.

Keenan R.M, Weinstock J, Finkelstein

J.A, Franz R.G, Gaitanopoulos D.E,

Girard G.R, Hill D.T, Morgan T.M,

Samanen J.M, Peishoff C.E. Potent

nonpeptide angiotensin II receptor

antagonists. 2. 1- (Carboxybenzyl)

imidazole-5-acrylic acids. J Med Chem

;36:1880–1892.

Middlemiss D, Drew G.M, Ross B.C,

Robertson M.J, Scopes D.I.C, Dowle M.D,

Akers J, Cardwell K, Clark K.L, Coote S,

Idred C.D, Hamblett J, Hilditch A, Hirst

G.C, Jack T, Motana J, Panchal T.A, Paton

J.M.S, Shah P, Stuart G, Travers A. (1991)

Benzobromofurans: a new class of potent

non peptide antagonists of angiotensin II.

Bioorg Med Chem Lett 1991; 1:711–716.

Carini D. J, Duncia J. V, AldrichP. E,

Chiu A. T, Johnson A.L, Pierce M. E,

Price W. A, Santella J. B, Wells G. J,

WexlerR. R, Wong P. C, Yoo S.E,

Timmermans P. B. M. W. M.Nonpeptide

Angiotensin II Receptor Antagonists: The

Discovery of a Series of N-

(Biphenylylmethyl)imidazoles as Potent,

Orally Active Antihypertensive. J Med

Chem 1991; 34, 2525-2547.

Bali A, Bansal Y, Sugumaran M, Saggu

J.S, Balakumar P, Kaur G, Bansal G,

Sharma A, Singh M. Design, synthesis and

evaluation of novelly substituted

benzimidazole compounds as angiotensin

II receptor antagonists. Bioorg Med Chem

Lett 2005;15,3962-3965.

Dhvanit I. S, Sharma M, Bansal Y,Bansal

G, M. Singh. Angiotensin II AT1 receptor

antagonists: Design, synthesis and

evaluation of substituted carboxamido

benzimidazole derivatives European

Journal of Medicinal Chemistry 2008;43,

-1812.

Jat R.K,Jat J.L, Pathak D.P.Synthesis of

Benzimidazole Derivatives: As Antihypertensive Agents.E Journal of

Chemistry 2006;3:(13), 278-285.

Preston, Heterocyclic Compounds:

Benzimidazoles and Congeneric Tricyclic

compounds, Part-I, Vol-40, p-7.

Solomon Marmor, Laboratory methods in

Organic Chemistry, 1986, Surjeet

publications,p-284-285.

Badyal D.K, Lata H, Dadhich A.P, Animal

models of hypertension and effect of

drugs. Indian J of Pharmacology 2003;

(66), 349-362.

Bunag R.D, McCubbin J.W, Page I.H.

Lack of correlation between direct and

indirect measurements of arterial pressure

in unanaesthetized rats. Cardiovasc Res

;5(1): 24-31.

Gupta S.K.Drug Screening methods,

Jaypee Brothers Medical Publisher, New

Delhi,2004; pp 236-246.

Shreenivas M.T, Chetan B.P, Bhat A.R,

Synthesis and Pharmacological Evaluation

of Certain Schiff Bases and Thiazoldine

Derivatives as AT1 Angiotension-II (AII)

Receptor Antagonists. Journal of

Pharmaceutical Science and Technology

; 1 (2), 88-94.

A.A.Siddiqui, M.S.Wani. Indian. j.

chemistry. 43B, 1574, 1579(2004).

R.D.Bunag.J.W.McCubbin, I.H.Page.

Lack of correlation between direct and

indirect measurements of arterial pressure

in unanaesthetized rats. Cardiovascular

Res. 5(1): 24-31 (1971).

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09/30/2010

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