Isaac Scientific Publishing

Modern Organic Chemistry Research

The Stability Study of a Novel Phenylpiperazine Derivative

Download PDF (828.9 KB) PP. 1 - 12 Pub. Date: February 1, 2019

DOI: 10.22606/mocr.2019.41001

Author(s)

  • Monika TARSA1, Małgorzata STAREK2*
    1Department of Organic Chemistry
  • Monika DĄBROWSKA2, Marzena BARAN1
    2Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St, 30-688 Krakow, Poland
  • Agnieszka CZARNY3, Marek CEGŁA1
    3Department of Organic Chemistry, Faculty of Chemistry, Jagiellonian University Medical College, 3 Ingardena St, 30-060 Krakow, Poland

Abstract

N-phenylpiperazine compounds are a very large class of chemicals, and some of them have the ability to cross the blood-brain barrier due to the small size and the lipohilic nature. This group of compounds shows an interesting spectrum of biological activities. The chemical stability of the drugs determines the quality of the drug, affects safety, efficacy and storage conditions. The active compounds have diverse molecular structure and are susceptible to many variable degradation pathways, such as hydrolysis, oxidation, photodegradation, isomerization, elimination, dehydration and interaction with others substances. A hydrolysis degradation process is one of the most common destructive processes for chemical structures. It depends on various conditions e.g. temperature, pH and the chemical properties of a substance. The aims of this investigation were to study the stability testing of 2-[(4-phenylpiperazino)methyl]-2,3-dihydro-5H-[1,3]oxazolo[3,2-a]pyridine-5-one, a new oxazolopyridonyl derivative of phenylpiperazine. A probable pathway of its chemical degradation was designated, based on the kinetic parameters and the identification products by the chromatographic methods.

Keywords

N-phenylpiperazine; stability; spectrophotometry; chromatography

References

[1] Fagiolini, A. Comandini, M. Catena Dell’Osso and S. Kasper, “Rediscovering trazodone for the treatment of major depressive disorder”, CNS Drugs, vol. 26, pp. 1033-1049, 2012.

[2] G. Neves, R. Fenner, A.P. Meckler, A.F. Viana, L. Tasso, R. Menegatti, C.A.H. Fraga, E.J. Barreiro, T. Dalla-Costa and S.M.K. Rates, “Dopaminergic profile of new heterocyclic N-phenylpiperazine derivatives”, Braz. J. Med. Biol. Res., vol. 36, pp. 625-629, 2003.

[3] K.S. Jain, J.B. Bariwal, M.K. Kathiravan, M.S. Phoujdar, R.S. Sahne, B.S. Chauhan, A.K. Shah and M.R. Yada, “Recent advances in selective alpha1-adrenoreceptor antagonists as antihypertensive agents”, Bioorg. Med. Chem., vol. 16, pp. 4759-4800, 2008.

[4] J. Handzlik, M. Bajda, M. Zygmunt, D. Maciag, M. Dybala, M. Bednarski, B. Filipek, B. Malawska and K. Kiec-Kononowicz, “Antiarrhythmic properties of phenylpiperazine derivatives of phenytoin with α1-adrenoceptor affinities”, Bioorg. Med. Chem., vol. 20, pp. 2290-2303, 2012.

[5] Y.B. Lee, Y.D. Gong, D.J. Kim, C.H. Ahn, J.Y. Kong and N.S. Kang, “Synthesis, anticancer activity and pharmacokinetic analysis of 1-[(substituted 2-alkoxyquinoxalin-3-yl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives”, Bioorg. Med. Chem., vol. 20, pp. 1303-1309, 2012.

[6] A. Blaser, B.D. Palmer, H.S. Sutherland, I. Kmentova, S.G. Franzblau, B. Wan, Y. Wang, Z. Ma, A.M. Thompson and W.A. Denny, “Structure-activity relationships for amide-, carbamate-, and urea-linked analogues of the tuberculosis drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824)”, J. Med. Chem., vol. 55, pp. 312-326, 2012.

[7] J. Handzlik, D. Maciag, M. Kubacka, S. Mogilski, B. Filipek, K. Stadnicka and K. Kiec-Kononowicz, “Synthesis, α1-adrenoceptor antagonist activity, and SAR study of novel arylpiperazine derivatives of phenytoin”, Bioorg. Med. Chem., vol. 16, pp. 5982-5998, 2008.

[8] J. Handzlik, A.J. Bojarski, G. Satala, M. Kubacka, B. Sadek, A. Ashoor, A. Siwek, M. Wiecek, K. Kucwaj, B. Filipek and K. Kiec-Kononowicz, “SAR-studies on the importance of aromatic ring topologies in search for selective 5-HT7 receptor ligands among phenylpiperazine hydantoin derivatives”, Eur. J. Med. Chem., vol. 78, pp. 324-339, 2014.

[9] R. Romagnoli, P.G. Baraldi, M.D. Carrion, C.L. Cara, O. Cruz-Lopez, M.K. Salvador, D. Preti, M.A. Tabrizi, A.R. Moorman, F. Vincenzi, P.A. Borea and K. Varani, “Synthesis and Biological Evaluation of 2-Amino-3-(4-chlorobenzoyl)-4-[(4-arylpiperazin-1-yl)methyl]-5-substituted-thiophenes. Effect of the 5-Modification on Allosteric Enhancer Activity at the A1 Adenosine Receptor”, J. Med. Chem., vol. 55, pp. 7719-7735, 2012.

[10] M. Leopoldo, E. Lacivita, F. Berardi, R. Perrone and P.B. Hedlund, “Serotonin 5-HT7 receptor agents: Structure-activity relationships and potential therapeutic applications in central nervous system disorders”, Pharmacol. Ther., vol. 129, pp. 120-148, 2011.

[11] G. Romeo, L. Materia, G. Marucci, M. Modica, M. Pittalá, L. Salerno, M.A. Siracusa, M. Buccioni, P. Angeli and K.P. Minneman, “New pyrimido[5,4-b]indoles and [1]benzothieno[3,2-d]pyrimidines: High affinity ligands for the α1-adrenoceptor subtypes”, Bioorg. Med. Chem. Lett., vol. 16, pp. 6200-6203, 2006.

[12] J. Buch, “Urapidil, a dual-acting antihypertensive agent: Current usage considerations”, Adv. Ther., vol. 27, pp. 426-443, 2010.

[13] J.J. Lehot, E. Bonnefoy, J.P. Dalmas, S. Filley, O. Basttien and M. George, “Role of urapidil in the treatment of acute hypertension”, Cah. Anesthesiol., vol. 43, pp. 67-76, 1995.

[14] J.H. Bremner, B. Coban, R. Griffith, K.M. Groenewoud and B.F. Yates, “Ligand design for α1 adrenoceptor subtype selective antagonists”, Bioorg. Med. Chem., vol. 8, pp. 201-214, 2000.

[15] T.E.T. Pompeu, F.R.S. Alves, C.D.M. Figueiredo, C.B. Antonio, V. Herzfeldt, B.C. Moura, S.M.K. Rates, E.J. Barreiroe, C.A.M. Fraga and F. Noël, “Synthesis and pharmacological evaluation of new N-phenylpiperazine derivatives designed as homologues of the antipsychotic lead compound LASSBio-579”, Eur. J. Med. Chem., vol. 66, pp. 122-134, 2013.

[16] V. Pittalà, M.A. Siracusa, M.N. Modica, L. Salerno, A. Pedretti, G. Vistoli, A. Cagnotto, T. Mennini and G. Romeo, “Synthesis and molecular modeling of 1H-pyrrolopyrimidine-2,4-dione derivatives as ligands for the α1-adrenoceptors”, Bioorg. Med. Chem., vol. 19, pp. 5260-5276, 2011.

[17] G. Romeo, L. Materia, M.N. Modica, V. Pittalà, L. Salerno, M.A. Siracusa, F. Manetti, M. Botta and K.P. Minneman, “Novel 4-phenylpiperidine-2,6-dione derivatives. Ligands for α1-adrenoceptor subtypes”, Eur. J. Med. Chem.,vol. 46, pp. 2676-2690, 2011.

[18] Bang-Andersen, T. Ruhland, M. Jorgensen, G. Smith, K. Frederiksen, K. Gjervig Jensen, H. Zhong, S. Moller Nielsen, S. Hogg, A. Mork and T.B. Stensbol, “Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder”, J. Med. Chem., vol. 54, pp. 3206-3221, 2011.

[19] M. Baran, E. Kepczyńska, M. Zylewski, A. Siwek, M. Bednarski and M.T. Cegla, “Studies on novel pyridine and 2-pyridone derivatives of N-arylpiperazine as α-adrenoceptor ligands”, Med. Chem., vol. 10, pp. 144-153, 2014.

[20] J.G. Lombardino and J.A. Lowe, “The role of the medicinal chemist in drug discovery--then and now”, Nat. Rev. Drug Discov., vol. 3, pp. 853-862, 2004.

[21] D.A. Smith, B.C. Jones and D.K. Walker, “Design of drugs involving the concepts and theories of drug metabolism and pharmacokinetics”, Med. Res. Rev., vol. 16, pp. 243-266, 1996.

[22] H. Van De Waterbeemd, D.A. Smith, K. Beaumont and D.K. Walker, “Property-based design: optimization of drug absorption and pharmacokinetics”, J. Med. Chem., vol. 44, pp. 1313-1333, 2001.

[23] T. Loftsson, Drug Stability for Pharmaceutical Scientists, Amsterdam: Academic Press, 2014.

[24] S.R. Khan, M. Tawakkul, V.A. Sayeed, P. Faustino and M.A. Khan, “Stability characterization, kinetics and mechanism of degradation of dantrolene in aqueous solution: effect of pH and temperature”, Pharmacol. Pharm., vol. 3, pp. 281-290, 2012.

[25] M. Blessy, R.D. Patel, P.N. Prajapati and Y.K. Agrawal, “Development of forced degradation and stability indicating studies of drugs-A review”, J. Pharm. Anal., vol. 4, pp. 159-165, 2014.

[26] M.I. Walash and M.E.K. Wahba, “A validated liquid chromatographic method for the determination of fluphenazine hydrochloride in the presence of its degradation products: application to degradation kinetics”, Anal. Meth., vol. 6, pp. 6727-6735, 2014.

[27] M. Cegla, M. Baran, A. Czarny, M. Zylewski, J. Potaczek, J. Klenc and L.J. Strekowski, “The -NH-(C=)-Br functionality of heteroaromatic compounds as a synthon for fused dihydrooxazoles”, J. Heterocyclic Chem., vol. 48, pp. 720-723, 2011.

[28] J. Gajewska and S. Pietras, Physicochemical Guide, Warszawa: WNT, 1974.