N‐Aril‐N'‐Heteroaril‐Substitue Üre Türevlerinin Sentezi

Yıl 2016, Cilt: 16 Sayı: 2, 222 - 229, 30.04.2016

Şengül Dilem Doğan

Öz

Bu çalışmada, biyolojik aktif bileşikler grubunda yer alan benzimidazol, tiyazol ve üre grubunu aynı

molekülde içeren N‐[4‐(1H‐benzimidazol‐2‐il)‐2‐tiyazolil]‐N'‐fenil‐üre türevleri, o‐fenilendiamin

bileşiğinden çıkılarak, ilk defa sentezlenmiştir. Sentezlenen bileşiklerin yapılarını aydınlatmak için IR, LCMS,

1H ve 13CNMR spektroskopisi yöntemleri kullanılmıştır.

Anahtar Kelimeler

Benzimidazol, Üre, Tiyazol, Açil Azit, Izosiyanat

Kaynakça

• Allen D. R., A. Bolt, G. A. Chapman, R. L. Knight, J. W. G. Meissner, D. A. Owen and R. J. Watson (2007). Identification and structure–activity relationships of 1‐aryl‐3‐piperidin‐4‐yl‐urea derivatives as CXCR3 receptor antagonists, Bioorganic & Medicinal Chemistry Letters 17(3): 697‐701.
• Ansari K. F. and C. Lal (2009). Synthesis and evaluation of some new benzimidazole derivatives as potential antimicrobial agents, European Journal of Medicinal Chemistry 44(5): 2294‐2299.
• Budriesi R., P. Ioan, A. Locatelli, S. Cosconati, A. Leoni, M. P. Ugenti, A. Andreani, R. Di Toro, A. Bedini, S. Spampinato, L. Marinelli, E. Novellino and A. Chiarini (2008). Imidazo[2,1‐ b]thiazole System: A Scaffold Endowing Dihydropyridines with Selective Cardiodepressant Activity, Journal of Medicinal Chemistry 51(6): 1592‐1600.
• Cole A. G., I. L. Stroke, M.‐R. Brescia, S. Simhadri, J. J. Zhang, Z. Hussain, M. Snider, C. Haskell, S. Ribeiro, K. C. Appell, I. Henderson and M. L. Webb (2006). Identification and initial evaluation of 4‐N‐aryl‐[1,4]diazepane ureas as potent CXCR3 antagonists, Bioorganic & Medicinal Chemistry Letters 16(1): 200‐203.
• Dai Y., K. Hartandi, Z. Ji, A. A. Ahmed, D. H. Albert, J. L. Bauch, J. J. Bouska, P. F. Bousquet, G. A. Cunha and K. B. Glaser (2007). Discovery of N‐(4‐(3‐Amino‐1 Hindazol‐ 4‐yl) phenyl)‐N'‐(2‐fluoro‐5‐ methylphenyl) urea (ABT‐869), a 3‐ Aminoindazole‐Based Orally Active Multitargeted Receptor Tyrosine Kinase Inhibitor, Journal of medicinal chemistry 50(7): 1584‐1597.
• de Oliveira Lopes R., N. C. Romeiro, C. K. F. de Lima, L. L. da Silva, A. L. P. de Miranda, P. G. B. Nascimento, F. Q. Cunha, E. J. Barreiro and L. M. Lima (2012). Docking, synthesis and pharmacological activity of novel ureaderivatives designed as p38 MAPK inhibitors, European journal of medicinal chemistry 54: 264‐271.
• Demain A. L. and S. Sanchez (2009). Microbial drug discovery: 80 years of progress, The Journal of antibiotics 62(1): 5‐16. Doğan S. D., E. Demirpolat, M. B. Y. Aycan and M. Balci (2015). Synthesis of new 4‐azaindoles via acyl azides, Tetrahedron 71(2): 252‐258.
• Garudachari B., M. N. Satyanarayana, B. Thippeswamy, C. K. Shivakumar, K. N. Shivananda, G. Hegde and A. M. Isloor (2012). Synthesis, characterization and antimicrobial studies of some new quinoline incorporated benzimidazole derivatives, European Journal of Medicinal Chemistry 54: 900‐906.
• Hodge C. N., P. E. Aldrich, L. T. Bacheler, C.‐H. Chang, C. J. Eyermann, S. Garber, M. Grubb, D. A. Jackson, P. K. Jadhav, B. Korant, P. Y. S. Lam, M. B. Maurin, J. L. Meek, M. J. Otto, M. M. Rayner, C. Reid, T. R. Sharpe, L. Shum, D. L. Winslow and S. Erickson‐Viitanen (1996).
• Improved cyclic urea inhibitors of the HIV‐1 protease: synthesis, potency, resistance profile, human pharmacokinetics and X‐ray crystal structure of DMP 450, Chemistry & Biology 3(4): 301‐314.
• Kashaw S. K., V. Kashaw, P. Mishra, N. K. Jain and J. P. Stables (2009). Synthesis, anticonvulsant and CNS depressant activity of some new bioactive 1‐(4‐substituted‐phenyl)‐3‐(4‐oxo‐2‐ phenyl/ethyl‐4H‐quinazolin‐3‐yl)‐urea, European Journal of Medicinal Chemistry 44(11): 4335‐4343.
• Kryshchyshyn A., D. Atamanyuk and R. Lesyk (2012). Fused thiopyrano [2, 3‐d] thiazole derivatives as potential anticancer agents, Scientia pharmaceutica 80(3): 509.
• Lam P., P. Jadhav, C. J. Eyermann, C. N. Hodge, Y. Ru, L. T. Bacheler, J. L. Meek, M. J. Otto, M. M. Rayner and Y. N. Wong (1994). Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease inhibitors, Science 263(5145): 380‐384.
• Luzina E. L. and A. V. Popov (2009). Synthesis and anticancer activity of Nbis( trifluoromethyl)alkyl‐N′‐thiazolyl and Nbis( trifluoromethyl)alkyl‐N′‐benzothiazolyl ureas, European Journal of Medicinal Chemistry 44(12): 4944‐4953.
• Malla Reddy V. and K. Ravinder Reddy (2010). Synthesis and antimicrobial activity of some novel 4‐(1H‐benz [d] imidazol‐2yl)‐1, 3‐ thiazol‐2‐amines, Chemical and Pharmaceutical Bulletin 58(7): 953‐956.
• Millan D. S., M. E. Bunnage, J. L. Burrows, K. J. Butcher, P. G. Dodd, T. J. Evans, D. A. Fairman, S. J. Hughes, I. C. Kilty, A. Lemaitre, R. A. Lewthwaite, A. Mahnke, J. P. Mathias, J. Philip, R. T. Smith, M. H. Stefaniak, M. Yeadon and C. Phillips (2011). Design and Synthesis of Inhaled p38 Inhibitors for the Treatment of Chronic Obstructive Pulmonary Disease, Journal of Medicinal Chemistry 54(22): 7797‐ 7814.
• Motohashi N., M. Kawase, T. Kurihara, A. Hever, S. Nagy, I. Ocsocvszki, M. Tanaka and J. Molnar (1995). Synthesis and antitumor activity of 1‐[2‐(chloroethyl)‐3‐(2‐substituted‐ 10H‐phenothiazin‐10‐yl) alkyl‐1‐urea s as potent anticancer agents, Anticancer research 16(5A): 2525‐2532.
• Özcan S., E. Şahin and M. Balci (2007). The synthesis of unusual isocoumarin derivatives: the chemistry of homophthalic acid, Tetrahedron letters 48(12): 2151‐2154.
• Ramprasad J., N. Nayak, U. Dalimba, P. Yogeeswari, D. Sriram, S. K. Peethambar, R. Achur and H. S. S. Kumar (2015). Synthesis and biological evaluation of new imidazo[2,1‐ b][1,3,4]thiadiazole‐benzimidazole derivatives, European Journal of Medicinal Chemistry 95: 49‐63.
• Reddy T. S., H. Kulhari, V. G. Reddy, V. Bansal, A. Kamal and R. Shukla (2015). Design, synthesis and biological evaluation of 1,3‐diphenyl‐1Hpyrazole derivatives containing benzimidazole skeleton as potential anticancer and apoptosis inducing agents, European Journal of Medicinal Chemistry 101: 790‐805.
• Regan J., S. Breitfelder, P. Cirillo, T. Gilmore, A. G. Graham, E. Hickey, B. Klaus, J. Madwed, M. Moriak, N. Moss, C. Pargellis, S. Pav, A. Proto, A. Swinamer, L. Tong and C. Torcellini (2002). Pyrazole Urea‐Based Inhibitors of p38 MAP Kinase: From Lead Compound to Clinical Candidate, Journal of Medicinal Chemistry 45(14): 2994‐3008.
• Regan J., A. Capolino, P. F. Cirillo, T. Gilmore, A. G. Graham, E. Hickey, R. R. Kroe, J. Madwed, M. Moriak, R. Nelson, C. A. Pargellis, A. Swinamer, C. Torcellini, M. Tsang and N. Moss (2003). Structure−Ac􀆟vity Rela􀆟onships of the p38α MAP Kinase Inhibitor 1‐(5‐tert‐ Butyl‐2‐p‐tolyl‐2H‐pyrazol‐3‐yl)‐3‐[4‐(2‐ morpholin‐4‐yl‐ethoxy)naph‐ thalen‐1‐yl]urea (BIRB 796), Journal of Medicinal Chemistry 46(22): 4676‐4686.
• Seenaiah D., P. R. Reddy, G. M. Reddy, A. Padmaja, V. Padmavathi and N. Siva krishna (2014). Synthesis, antimicrobial and cytotoxic activities of pyrimidinyl benzoxazole, benzothiazole and benzimidazole, European Journal of Medicinal Chemistry 77: 1‐7.
• Shingalapur R. V., K. M. Hosamani and R. S. Keri (2009). Synthesis and evaluation of in vitro anti‐microbial and anti‐tubercular activity of 2‐styryl benzimidazoles, European Journal of Medicinal Chemistry 44(10): 4244‐4248.
• Sobol E., B. Yagen, H. Steve White, K. S. Wilcox, J. G. Lamb, O. Pappo, B. J. Wlodarczyk, R. H. Finnell and M. Bialer (2006). Preclinical evaluation of 2,2,3,3‐ tetramethylcyclopropanecarbonyl‐urea, a novel, second generation to valproic acid, antiepileptic drug, Neuropharmacology 51(4): 933‐946.
• Trivedi B. K., A. Holmes, T. L. Stoeber, C. J. Blankley, W. H. Roark, J. A. Picard, M. K. Shaw, A. D. Essenburg, R. L. Stanfield and B. R. Krause (1993). Inhibitors of acyl‐ CoA:cholesterol acyltransferase. 4. A novel series of urea ACAT inhibitors as potential hypocholesterolemic agents, Journal of Medicinal Chemistry 36(22): 3300‐3307.
• Tunçbilek M., T. Kiper and N. Altanlar (2009). Synthesis and in vitro antimicrobial activity of some novel substituted benzimidazole derivatives having potent activity against MRSA, European Journal of Medicinal Chemistry 44(3): 1024‐1033.
• Vu C. B., J. E. Bemis, J. S. Disch, P. Y. Ng, J. J. Nunes, J. C. Milne, D. P. Carney, A. V. Lynch, J. J. Smith, S. Lavu, P. D. Lambert, D. J. Gagne, M. R. Jirousek, S. Schenk, J. M. Olefsky and R. B. Perni (2009). Discovery of Imidazo[1,2‐ b]thiazole Derivatives as Novel SIRT1 Activators, Journal of Medicinal Chemistry 52(5): 1275‐1283.
• Wilde R. G., J. D. Klaczkiewicz, J. T. Billheimer, R. R. Wexler and P. J. Gillies (1995). Acyl CoA:cholesterol acyltransferase (ACAT) inhibitors: heterocyclic bioisosteres for the urea group in DuP 128, Bioorganic & Medicinal Chemistry Letters 5(2): 177‐180.
• Yang Y., Y. Shen, H. Liu and X. Yao (2011). Molecular Dynamics Simulation and Free Energy Calculation Studies of the Binding Mechanism of Allosteric Inhibitors with p38α MAP Kinase, Journal of Chemical Information and Modeling 51(12): 3235‐3246.
• Zhang H.‐Z., G. L. V. Damu, G.‐X. Cai and C.‐H. Zhou (2013). Design, synthesis and antimicrobial evaluation of novel benzimidazole type of Fluconazole analogues and their synergistic effects with Chloromycin, Norfloxacin and Fluconazole, European Journal of Medicinal Chemistry 64: 329‐344.
• Zheng S., Q. Zhong, Y. Xi, M. Mottamal, Q. Zhang, R. L. Schroeder, J. Sridhar, L. He, H. McFerrin and G. Wang (2014). Modification and Biological Evaluation of Thiazole Derivatives as Novel Inhibitors of Metastatic Cancer Cell Migration and Invasion, Journal of Medicinal Chemistry 57(15): 6653‐6667.