Benzimidazole: a medicinally important heterocyclic moiety

Andries K, Moermans M, Grevers T, Willebrords R, Sommen C, Lacrampe J, Janssens F, Wyde PR (2003) Substituted benzimidazoles with nanomolar activity against respiratory syncytial virus. Antivir Res 60:209–219

Andrzejewska M, Pagona MA, Meggio F, Brunati AM, Kazimierczuk Z (2003) Polyhalogenobenzimidazoles: synthesis and their inhibitory activity against casein kinases. Bioorg Med Chem 11:3997–4002

Andrzejewska M, Yepez-Mulia L, Tapia A, Cedillo-Rivera R, Laudy AE, Starosciak BJ, Kazimierczuk Z (2004) Synthesis, and antiprotozoal and antibacterial activities of S-substituted 4,6-dibromo- and 4,6-dichloro-2-mercaptobenzimidazoles. Eur J Pharm Sci 21:323–329

Beaulieu C, Wang Z, Denis D, Greig G, Lamontagne S, ONeill G, Slipetz D, Wang J (2004) Benzimidazoles as new potent and selective DP antagonists for the treatment of allergic rhinitis. Bioorg Med Chem Lett 14:3195–3199

Clerq ED, Naesens L (2006) In search of effective anti-HHV-6 agents. J Clin Virol 1:S82–S86

Cui JJ, Araldi GL, Reiner JE, Reddy KM, Kemp SJ, Ho JZ, Siev DV, Mamedova L, Gibson TS, Gaudette JA, Minami NK, Anderson SM, Bradbery AE, Nolan TG, Semple JE (2002) Non-covalent thrombin inhibitors featuring P3-heterocycles with P1-Bicyclic arginine surrogates. Bioorg Med Chem Lett 12:2925–2930

Dong Y, Roberge JY, Wang Z, Wang X, Tamasi J, Dell V, Golla R, Corte JR, Liu Y, Fang T, Anthony MN, Schnur DM, Agler ML, Dickson JK, Lawrence RM, Prack MM, Seethala R, Feyen JHM (2004) Characterization of a new class of selective nonsteroidal progesterone receptor agonists. Steroids 69:201–217

Estrada-Soto S, Villalobos-Molina R, Aguirre-Crespo F, Vergara-Galicia J, Moreno-Diaz H, Torres-Piedra M, Navarrete-Vazquez G (2006) Relaxant activity of 2-(substituted phenyl)-1H-benzimidazoles on isolated rat aortic rings: design and synthesis of 5-nitro derivatives. Life Sci 79:430–435

Fletcher SR, Mc-Iver E, Lewis S, Burkamp F, Leech C, Mason G, Boyce S, Morrison D, Richards G, Sutton K, Jones AB (2006) The search for novel TRPV1-antagonists: from carboxamides to benzimidazoles and indazolones. Bioorg Med Chem Lett 16:2872–2876

Goker H, Kus C, Boykin D, Yildiz S, Altanlar N (2002) Synthesis of some new 2-substituted-phenyl-1H-benzimidazole-5-carbonitriles and their potent activity against candida species. Bioorg Med Chem 10:2589–2596

Goker H, Ozden S, Yildiz S, Boykin DW (2005) Synthesis and potent antibacterial activity against MRSA of some novel 1,2-disubstituted-1H-benzimidazole-N-alkylated-5-carboxamidines. Eur J Med Chem 40:1062–1069

Gumus F, Pamuk I, Ozden T, Yildiz S, Dirl N, Oksuzoglu E, Gur S, Ozkul A (2003) Synthesis, characterization and in vitro cytotoxic, mutagenic and antimicrobial activity of platinum(II) complexes with substituted benzimidazole ligands. J Inorg Biochem 94:255–262

Hamaguchi T, Takahashi A, Kagamizono T, Manaka A, Sato M, Osada H (2000) Synthesis and characterization of a potent and selective protein tyrosine phosphatase inhibitor, 2-[(4-methylthiopyridin-2-yl)methylsulfinyl]benzimidazole. Bioorg Med Chem Lett 10:2657–2660

Han X, Pin SS, Buriris K, Fung LK, Huang S, Taber MT, Zhang J, Dubowchi KGM (2005) Synthesis and structure–activity relationship of imidazo[1,2-a] benzimidazoles as corticotropin-releasing factor 1 receptor antagonists. Bioorg Med Chem Lett 15:4029–4032

He W, Hanney B, Myers MR, Condon S, Beeker MR, Spada AP, Burns C, Brown K, Colussi D, Chu V (2002) Benzimidazoles and isosteric compounds as potent and selective factor Xa inhibitors. Bioorg Med Chem Lett 12:919–922

He Y, Wu B, Yang J, Robinson D, Risen L, Ranken R, Blyn L, Sheng S, Swayze EE (2003) 2-Piperidin-4-yl-benzimidazoles with broad spectrum antibacterial activities. Bioorg Med Chem Lett 13:3253–3256

He Y, Yang J, Wu B, Risen L, Swayze EE (2004) Synthesis and biological evaluations of novel benzimidazoles as potential antibacterial agents. Bioorg Med Chem Lett 14:1217–1220

Huang ST, Hsei IJ, Chen C (2006) Synthesis and anticancer evaluation of bis(benzimidazoles), bis(benzoxazoles), and benzothiazoles. Bioorg Med Chem 14:6106–6119

Ishida T, Suzuki T, Hirashima S, MIzutani K, Adachi T, Hashimoto H (2006) Benzimidazole inhibitors of hepatitis C virus NS5B polymerase: identification of 2-[(4-diarylmethoxy)phenyl]-benzimidazole. Bioorg Med Chem Lett 16:1859–1863

Ismail MA, Brun R, Wenzler T, Tanious FA, Wilson WD, Boykin DW (2004) Dicationic biphenyl benzimidazole derivatives as antiprotozoal agents. Bioorg Med Chem 12:5405–5413

Jin S, Kim JS, Sim SP, Liu A, Pilch DS, Liu FL, Lavoie EJ (2000) Design and structure–activity relationship of 3-benzimidazol-2-yl-1H-indazoles as inhibitors of receptor tyrosine kinases. Bioorg Med Chem Lett 10:719–723

Jordan AD, Vidya AH, Rosenthal DI, Dubinsky B, Kordik CP, Sanifilippo PJ, Wu W, Reitz AB (2002) Potential anxiolytic agents. Part 4: novel orally-active N5-substituted pyrido[1,2-a]benzimidazoles with high GABA-A receptor affinity. Bioorg Med Chem Lett 12:2381–2386

Kawasaki K, Masubachi M, Morikami K, Sogebe S, Aoyama T, Ebiike H, Niizuma S, Hayase M, Fujii T, Sakata K, Shindoh H, Shiratori Y, Aoki Y, Ohtsuka T, Shimma N (2003) Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 3. Bioorg Med Chem Lett 13:87–91

Klimesova V, Pour M, Stachel J, Waisser K, Kaustova J (2002) Synthesis and preliminary evaluation of benzimidazole derivatives as antimicrobial agents. Eur J Med Chem 37:409–418

Kumar D, Jacob MR, Reynolds MB, Kerwin SM (2002) Synthesis and evaluation of anticancer benzoxazoles and benzimidazoles related to UK-1. Bioorg Med Chem 10:3997–4004

Kumar BVS, Vidya SD, Kumar RV, Bhirud SB, Mane RB (2006) Synthesis and anti-bacterial activity of some novel 2-(6-fluorochroman-2-yl)-1-alkyl/acyl/aroyl-1H-benzimidazoles. Eur J Med Chem 41:599–604

Li Y, Wang G, Huang W, Tang W, Feng C, Shi L, Ren Y, Zuo J, Lu W (2007) Identification of 1-isopropylsulfonyl-2-amine benzimidazoles as a new class of inhibitors of hepatitis B virus. Eur J Med Chem 42:1358–1364

Lopez-Vallezo F, Medina-Franco JS, Hernandez-Campos A, Rodriguez-Morales S, Yepez L, Cedillo R, Castillo R (2007) Molecular modeling of some 1H-benzimidazole derivatives with biological activity against Entamoeba histolytica: a comparative molecular field analysis study. Bioorg Med Chem 15:1117–1126

Mader M, Dios A, Shih C, Bonjouklian R, Li T, White W, Uralde BL, Sanchez-Martinez C, Prado M, Jaramillo C, Diego E, Cabrejas LMM, Dominguez C, Montero C, Shepherd T, Dally R, Toth JE, Chatterjee A, Pleite S, Blanco-Urgoiti J, Perez L, Barberis M, Lorite MJ, Jambrina E, Nevill CR, Lee PA, Schultz RC, Wolos JA, Li LC, Campbell RM, Anderson BD (2008) Imidazolyl benzimidazoles and imidazo[4,5-b]pyridines as potent p38α MAP kinase inhibitors with excellent in vivo antiinflammatory properties. Bioorg Med Chem Lett 18:179–183

Mavrova AT, Anichina KK, Vuchev DI, Issenov JA, Denkova PS, Kondeva MS, Micheva MK (2006) Antihelminthic activity of some newly synthesized 5(6)-(un)substituted-1H-benzimidazol-2-ylthioacetylpiperazine derivatives. Eur J Med Chem 41:1412–1420

McBride CM, Renhowe PA, Heise C, Jansen JM, Lapointe G, Ma S, Pineda R, Vora J, Wiesmann M, Shafer CM (2006) Design and structure–activity relationship of 3-benzimidazol-2-yl-1H-indazoles as inhibitors of receptor tyrosine kinases. Bioorg Med Chem Lett 16:3595–3599

Middleton T, Lim HB, Montgomery D, Rockway T, Tang H, Cheng X, Lu L, Mo H, Kohlbrenner WE, Molla A, Kati WM (2004) Inhibition of human immunodeficiency virus type I integrase by naphthamidines and 2-aminobenzimidazoles. Antivir Res 64:35–45

Minoura H, Takeshita S, Ita M, Hirosumi J, Mabuchi M, Kawamura I, Nakajima S, Nakayama O, Kayakiri H, Oku T, Ohkubo-Suzuki A, Fukagawa M, Kojo H, Hanioka K, Yamasaki N, Imoto T, Kobayashi Y, Mutoh S (2004) Pharmacological characteristics of a novel nonthiazolidinedione insulin sensitizer, FK614. Eur J Pharmacol 494:273–281

Ng RA, Guan J, Alford VC, Lanter JC, Allan GF, Sbriscia T, Lundeen SG, Sui Z (2007a) 2-(2,2,2-Trifluoroethyl)-5,6-dichlorobenzimidazole derivatives as potent androgen receptor antagonists. Bioorg Med Chem Lett 17:955–958

Ng RA, Lanter JC, Alford VC, Allan GF, Sbriscia T, Lundeen SG, Sui Z (2007b) Synthesis of potent and tissue-selective androgen receptor modulators (SARMs): 2-(2,2,2)-trifluoroethyl-benzimidazole scaffold. Bioorg Med Chem Lett 17:1784–1787

Nokano H, Inoque T, Kawasaki N, Miyataka H, Matsumoto H, Taguchi T, Inagaki N, Nagai H, Satoh T (2000) Synthesis and biological activities of novel antiallergic agents with 5-lipoxygenase inhibiting action. Bioorg Med Chem 8:373–380

Pagona MA, Meggio F, Ruzzene M, Andrzejewska M, Kazimierczuk Z, Pinna LA (2004) 2-Dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole: a novel powerful and selective inhibitor of protein kinase CK2. Biochem Biophys Res Commun 321:1040–1044

Palma AMD, Heggermont W, Leyssen P, Purstinger G, Wimmer E, Clercq ED, Rao A, Monforte A, Chimirri A, Neyts J (2007) Anti-enterovirus activity and structure–activity relationship of a series of 2,6-dihalophenyl-substituted 1H,3H-thiazolo[3,4-a]benzimidazoles. Biochem Biophys Res Commun 353:628–632

Pinar A, Yurdakul P, Yildiz I, Temiz-Arpaci O, Acan NL, Aki-Sener E, Yalcin I (2004) Some fused heterocyclic compounds as eukaryotic topoisomerase II inhibitors. Biochem Biophys Res Commun 317:670–674

Ramla MM, Omar MA, Tokuda H, El-Diwani HI (2007) Synthesis and inhibitory activity of new benzimidazole derivatives against Burkitt’s lymphoma promotion. Bioorg Med Chem 15:6489–6496

Safonov IG, Heerding DA, Keenan RM, Price AJ, Erickson-Miller CL, Hopson CB, Levin JL, Lord KA, Tapley PM (2006) New benzimidazoles as thrombopoietin receptor agonists. Bioorg Med Chem Lett 16:1212–1216

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

Shao B, Huang J, Sun Q, Valenzano KJ, Schmid L, Nolan S (2005) 4-(2-Pyridyl)piperazine-1-benzimidazoles as potent TRPV1 antagonists. Bioorg Med Chem Lett 15:719–723

Snow RJ, Abeywardane A, Campbell A, Lord J, Kashem MA, Khine HH, King J, Kowalski JA, Puppen SS, Roma T, Roth GP, Sarco CR, Wilson NS, Winters MP, Wolak JP, Cywin CL (2007) Hit-to-lead studies on benzimidazole inhibitors of ITK: discovery of a novel class of kinase inhibitors. Bioorg Med Chem Lett 17:3660–3665

Sondhi SM, Rajavanshi S, Johar M, Bharti N, Azam A, Singh K (2002) Anti-inflammatory, analgesic and antiamoebic activity evaluation of pyrimido[1,6-a]benzimidazole derivatives synthesized by the reaction of ketoisothiocyanates with mono and diamines. Eur J Med Chem 37:835–843

Starcevic K, Kralj M, Ester K, Sabol I, Grce M, Pavelic K, Karminski-Zamola G (2007) Synthesis, antiviral and antitumor activity of 2-substituted-5-amidino-benzimidazoles. Bioorg Med Chem 15:4419–4426

Tatsuta M, Kataoka M, Yasoshima K, Sakakibara S, Shogase Y, Shimazaki M, Yura T, Li Y, Yamamoto N, Gupta J, Urbhans K (2005) Benzimidazoles as non-peptide luteinizing hormone-releasing hormone (LHRH) antagonists. Part 3: discovery of 1-(1H-benzimidazol-5-yl)-3-tert-butylurea derivatives. Bioorg Med Chem Lett 15:2265–2269

Vedula MS, Pulipaka AB, Venna C, Chintakunta VC, Jinnapally S, Kattuboina VA, Vallakati RK, Basetti V, Akella V, Rajgopal S, Reka AK, Teepireddy SK, Mamnoor PK, Rajagopalan R, Bulusu G, Khandelwal A, Upreti VV, Mamidi SR (2003) New styryl sulfones as anticancer agents. Eur J Med Chem 38:811–824

Wu W, Brunett DA, Caplen MA, Domalski MS, Bennet C, Greenlee WJ, Hawes BE, O’Neill K, Weig B, Weston D, Spar B, Kowalski T (2006) Design and synthesis of orally efficacious benzimidazoles as melanin-concentrating hormone receptor 1 antagonists. Bioorg Med Chem Lett 16:3674–3678

Zien P, Bretner M, Zastapilo K, Szyzyka R, Shugar D (2003) Selectivity of 4,5,6,7-tetrabromobenzimidazole as an ATP-competitive potent inhibitor of protein kinase CK2 from various sources. Biochem Biophys Res Commun 306:129–133