COMPUTER PREDICTION AND SYNTHESIS OF NEW OXAZOLES BASED ON AN 8-THIOSUBSTITUTED 1,3,7-TRIMETHYLXANTHINE SKELETON
AbstractThe synthesis of new oxazole derivatives was carried out under Davidson synthesis conditions from O-acylacyloins with an 8-thiosubstituted 1,3,7-trimethylxanthine skeleton and ammonium acetate in a 1:10 ratio in glacial acetic acid media. The starting O-acylacyloins were obtained as products from the interaction of the sodium salt of 2-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)acetic acid and a-haloketones. The structures of the new compounds were proven by microanalyses and spectral data. The PASS online web application was used to predict the biological activity spectra of the obtained derivatives and to determine the most promising biological effects for further experimental testing. Thus, it has been shown that the synthesized compounds are a promising class for the creation of substances with a wide range of biological activity. The substrate/metabolite specificity of the tested compounds was also predicted using SMP web-service. The studied compounds were considered to perform most probably with CYP2 substrate activity.
Bezhentsev V.M., Tarasova O.A., Dmitriev A.V., Rudik A.V., Lagunin A.A., Filimonov D.A., Poroikov V.V. (2016). Computer-aided prediction of xenobiotics metabolism in the human organism. Russ. Chem. Rev., 85 (8) 854-879.
Ceylan, S.; Bektas, H.; Bayrak, H.; Demirbas, N.; Alpay-Karaoglu, S.; Ulker, S. (2013), Syntheses and biological activities of new hybrid molecules containing different heterocyclic moieties. Arch. Pharm., 346(10), 743-756.
Davidson, D.; Weiss, M.; Jelling, M. (1937), The action of ammonia on benzoin, J. Org. Chem. 2(4), 328–334.
Filimonov D.A., Lagunin A.A., Gloriozova T.A., Rudik A.V., Druzhilovskiy D.S., Pogodin P.V., Poroikov V.V. (2014). Prediction of the biological activity spectra of organic compounds using the PASS online web resource. Chemistry of Heterocyclic Compounds, 50 (3), 444-457.
Georgieva M., Mitkov J., Peikova L., Peikov P., Zlatkov Al. (2016), Synthesis evaluation and quantum mechanical characterization of cyclohexylamine containing derivatives of methylxanthine. CBU International Conference Proceedings, 4, 879 – 887.
Harris P. A., Cheung M., Hunter III R. N., Brown M. L., Veal J. M., Nolte R. T., Wang L., Liu W., Crosby R. M., Johnson J. H., Epperly A. H., Kumar R., Luttrell D.K., Stafford J. A. (2005), Discovery and Evaluation of 2-Anilino-5-aryloxazoles as a Novel Class of VEGFR2 Kinase Inhibitors. J. Med. Chem. 48, 1610-1619.
Kus, C., Uğurlu, E., Ozdamar, E. D., Eke B. C. (2017), Synthesis and Antioxidant Properties of New Oxazole-5(4H)-one Derivatives. Turkish Journal of Pharmaceutical Sciences, 14(2), 174-178.
Mitkov J., Danchev N., Nikolova I., Zlatkov Al. (2007), Synthesis and brain antihypoxic activity of some aliphatic and arylaliphatic amides of caffeine-8-thioglycolic acid, Acta Pharm., 57(3), 361-370.
Mitkov J., Nikolova L., Nikolova I., Danchev N., Zlatkov Al. (2010), Synthesis and brain antihypoxic activity of some aminoalcoholic derivatives of caffeine-8-thioglycolic acid, Compt. Rend. Bulg. Acad. Sci., 63(7), 1075-1082.
Mitkov, J., Georgieva, M., Zlatkov, Al. (2012), Development of an optimized synthetic approach for Synthesis of caffeine-8-thioglycolic acid and its ester derivatives, Pharmacia, 59(1-4), 17-23.
Name Reactions in Heterocyclic Chemistry II. Ed. Jie Jack Li, (2011), John Wiley & Sons, Inc., Hoboken, New Jersey, 221-224.
Nayana M.R.S., Sekhar Y.N., Kumari N.S., Mahmood S.K., Ravikumar M. (2008). CoMFA and docking studies on triazolopyridine oxazole derivatives as p38 MAP kinase inhibitors. European Journal of Medicinal Chemistry. 43(6), 1261-1269.
PASSOnline retrieved from http://www.way2drug.com/PASSOnline/.
Poroikov V. V., Filimonov D. A. (2002), How to acquire new biological activities in old compounds by computer prediction, J. Comput. Aid. Molec., 16(11), 819–824.
Rawat, B. S., Shukla, S. K. (2016), Synthesis and evaluation of some new thiazole / oxazole derivatives for their biological activities. World Journal of Pharmacy and Pharmaceutical Sciences. 5 (8), 1473-1482.
Shallal, M. A. H. (2017), Synthesis, Coordination ,Chemical Analysis, Biological Activity of Ligands (Imidazole, Oxazole, thaizole) Derivatives with Zn. International Journal Of Advanced Research In Medical & Pharmaceutical Sciences(IJARMPS), 2(8), 5-18.
SMP retrieved from http://www.way2drug.com/SMP/.
Strydom, B., Bergh, J. J., Petzer, J. P. (2011) 8-Aryl- and alkyloxycaffeine analogues as inhibitors of monoamine oxidase. European Journal of Medicinal Chemistry, 46(8), 3474-3485.
Swellmeen, L. (2016), 1,3-Oxazole Derivatives: A Review of Biological Activities as Antipathogenic. Der Pharma Chemica, 8(13), 269-286.
Undem B. J., Lichtenstein L. M: (2001), Drugs used in the treatment of asthma. In: Goodman and Gilman’s the Pharmacological Basis of Therapeutics. Ed. Hardman J. G., Limbird L. E., 10th edn. Mc Graw-Hill Medical Publishing Division, International Edition, New York, 743–744.
Valkova, I., Zlatkov, Al., Nedza, K., Doytchinova, I. (2012), Synthesis, 5-HT1A and 5-HT2A receptor affinity and QSAR study of 1-benzhydryl-piperazine derivatives with xanthine moiety at N4, Med Chem Res, 21(4), 477-486.
Yamada, K., Kamimura, N., Kunishima M. (2017), Development of a method for the synthesis of 2,4,5- trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid. Beilstein J. Org. Chem. 13, 1478–1485.
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License (Creative Commons Attribution License 3.0 - CC BY 3.0) that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
firstname.lastname@example.org, www.iseic.cz, ojs.journals.cz