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Synthesis and Characterization of Impurities in Rasagiline: A Novel MAO-B Inhibitor in Parkinson’s Disease Therapy
Corresponding Author(s) : N. Maruthi Raju
Asian Journal of Chemistry,
Vol. 29 No. 6 (2017): Vol 29 Issue 6
Abstract
Rasagiline (1) is indicated as adjunctive therapy and monotherapy for treatment of Parkinson’s disease approved by the FDA. During the process development of rasagiline, few processes related impurities were observed along with the final API. These impurities were identified as indanol (2), indanamine (3), allyl (4), keto (7), other isomer (6) and chloro allyl (5,5a) impurities. The present work describes the synthesis of all these impurities and characterized by 1H NMR and Mass spectral analysis.
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- Y. Akao, W. Maruyama, H. Yi, M. Shamoto-Nagai, M.B.H. Youdim and M. Naoi, Neurosci. Lett., 326, 105 (2002); https://doi.org/10.1016/S0304-3940(02)00332-4.
- F. Stocchi, C. Fossati and M. Torti, Expert Opin. Pharmacother., 16, 2231 (2015); https://doi.org/10.1517/14656566.2015.1086748.
- I.N. Glazkov, N.L. Bochkareva and I.A. Revelskil, J. Anal. Chem., 60, 107 (2005); https://doi.org/10.1007/s10809-005-0003-3.
- International Conference on Harmonization [ICH] Guidelines, Q3A [R] Impurities in New Drug Substances, February (2002).
- M.B.H. Youdim, J.P.M. Finberg, R. Levy, J. Sterling, D. Lerner, T. Berger-Paskin, H. Yellin and A. Veinberg, R-enantiomer of N-Propargyl-1-aminoindan, Salts, Compositions and Uses Thereof, US Patent US5532415 (1996).
- A.L. Gutman, I. Zaltzman, V. Ponomarev, M. Sotrihin and G. Nisnevich, Process for the Preparation of Rasagiline and its Salts Patent, WO 200202068376 A1 (2002).
- O.P. Goel, Process for the Resolution of 1-Aminoindanes, US Patent US4833273 (1989).
- R. Levy, M.B.H. Youdim, J.P.M. Finberg, S. Cohen and J. Sterling, Pharmaceutical Compositions Comprising S-(-)-N-Propargyl-1-Aminoindan, US Patent US 6277886 B1 (2001).
- M.B.H. Youdim, J.P.M. Finberg, R. Levy, J. Sterling, D. Lerner, T. Berger-Paskin and H. Yellin, R-enantiomers of N-Propargyl-aminoindan Compounds, Their Preparation and Pharmaceutical Compositions Containing Them, US Patent US5457133 A (1995).
- L.T. Boulton, I.C. Lennon and E. Bahar, Process for the Synthesis of Enantiomeric Indanylamine Derivatives, US Patent US7476757 B2 (2009).
- M.W. Gittos, J.W. James and L.F. Wiggins, Methods of Lowering Blood Pressure in Animals by Administering Secondary and Tertiary Amines, US Patent US3513244 A (1970).
- P. Falus, Z. Boros, G. Hornyánszky, J. Nagy, F. Darvas, L. Ürge and L. Poppe, Tetrahedron Lett., 52, 1310 (2011); https://doi.org/10.1016/j.tetlet.2011.01.062.
- Patent WO2009/81148 A1 (2009).
- L. Minuti, A. Taticchi, E. Gacs-Baitz and A. Marrocchi, Tetrahedron, 51, 8953 (1995); https://doi.org/10.1016/0040-4020(95)00504-2.
- P. Macchi, W. Jing, R. Guidetti-Grept and R. Keese, Tetrahedron, 69, 2479 (2013); https://doi.org/10.1016/j.tet.2013.01.016.
- Y. Arai, T. Kontani and T. Koizumi, Chem. Lett., 20, 2135 (1991); https://doi.org/10.1246/cl.1991.2135.
References
Y. Akao, W. Maruyama, H. Yi, M. Shamoto-Nagai, M.B.H. Youdim and M. Naoi, Neurosci. Lett., 326, 105 (2002); https://doi.org/10.1016/S0304-3940(02)00332-4.
F. Stocchi, C. Fossati and M. Torti, Expert Opin. Pharmacother., 16, 2231 (2015); https://doi.org/10.1517/14656566.2015.1086748.
I.N. Glazkov, N.L. Bochkareva and I.A. Revelskil, J. Anal. Chem., 60, 107 (2005); https://doi.org/10.1007/s10809-005-0003-3.
International Conference on Harmonization [ICH] Guidelines, Q3A [R] Impurities in New Drug Substances, February (2002).
M.B.H. Youdim, J.P.M. Finberg, R. Levy, J. Sterling, D. Lerner, T. Berger-Paskin, H. Yellin and A. Veinberg, R-enantiomer of N-Propargyl-1-aminoindan, Salts, Compositions and Uses Thereof, US Patent US5532415 (1996).
A.L. Gutman, I. Zaltzman, V. Ponomarev, M. Sotrihin and G. Nisnevich, Process for the Preparation of Rasagiline and its Salts Patent, WO 200202068376 A1 (2002).
O.P. Goel, Process for the Resolution of 1-Aminoindanes, US Patent US4833273 (1989).
R. Levy, M.B.H. Youdim, J.P.M. Finberg, S. Cohen and J. Sterling, Pharmaceutical Compositions Comprising S-(-)-N-Propargyl-1-Aminoindan, US Patent US 6277886 B1 (2001).
M.B.H. Youdim, J.P.M. Finberg, R. Levy, J. Sterling, D. Lerner, T. Berger-Paskin and H. Yellin, R-enantiomers of N-Propargyl-aminoindan Compounds, Their Preparation and Pharmaceutical Compositions Containing Them, US Patent US5457133 A (1995).
L.T. Boulton, I.C. Lennon and E. Bahar, Process for the Synthesis of Enantiomeric Indanylamine Derivatives, US Patent US7476757 B2 (2009).
M.W. Gittos, J.W. James and L.F. Wiggins, Methods of Lowering Blood Pressure in Animals by Administering Secondary and Tertiary Amines, US Patent US3513244 A (1970).
P. Falus, Z. Boros, G. Hornyánszky, J. Nagy, F. Darvas, L. Ürge and L. Poppe, Tetrahedron Lett., 52, 1310 (2011); https://doi.org/10.1016/j.tetlet.2011.01.062.
Patent WO2009/81148 A1 (2009).
L. Minuti, A. Taticchi, E. Gacs-Baitz and A. Marrocchi, Tetrahedron, 51, 8953 (1995); https://doi.org/10.1016/0040-4020(95)00504-2.
P. Macchi, W. Jing, R. Guidetti-Grept and R. Keese, Tetrahedron, 69, 2479 (2013); https://doi.org/10.1016/j.tet.2013.01.016.
Y. Arai, T. Kontani and T. Koizumi, Chem. Lett., 20, 2135 (1991); https://doi.org/10.1246/cl.1991.2135.