Abstract
Silicon chemistry has been demonstrated to be a novel source of chemical diversity in drug design. The carbon/silicon switch strategy, i.e., the strategic replacement of a carbon atom with a silicon atom (sila-substitution) within a well-known drug, with the rest of the molecule being identical, is one of the methods that are currently used for the design and development of new silicon-based drugs. Some of the fundamental differences between carbon and silicon (e.g., differences in the covalent radii and electronegativities) can lead to marked alterations in the physicochemical and biological properties of the sila-drugs. In general, the sila-analogues share the same mode of action as the parent carbon compounds but may have altered biological properties. Incorporation of silicon into a drug can affect and, ideally, improve the pharmacological potency and selectivity, the pharmacodynamics, and the pharmacokinetics. Examples resulting from the carbon/silicon switch strategy are sila-venlafaxine, sila-haloperidol, and disila-bexarotene, the silicon analogues of the serotonin/noradrenaline reuptake inhibitor venlafaxine, the dopamine antagonist haloperidol, and the retinoid agonist bexarotene, respectively. Using these particular examples, the basic principles of the carbon/silicon strategy in drug design are illustrated in this review.
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References
Fessenden RJ, Fessenden JS (1967) Adv Drug Res 4:95
Voronkov MG, Lukevics E (1969) Russ Chem Rev 38:975
Garson LR, Kirchner LK (1971) J Pharm Sci 60:1113
Tacke R, Wannagat U (1979) Top Curr Chem 84:1
Voronkov MG (1979) Top Curr Chem 84:77
Tacke R, Zilch H (1986) Endeavour. New Series 10:191
Tacke R, Becker B (1987) Main Group Met Chem 10:169
Tacke R, Linoh H (1989) Bioorganosilicon chemistry In: Patai S, Rappoport Z (eds) The chemistry of organic silicon compounds, part 2. Wiley, Chichester, p 1143
Bains W, Tacke R (2003) Curr Opin Drug Discovery Dev 6:526
Showell GA, Mills JS (2003) Drug Discovery Today 8:551
Mills JS, Showell GA (2004) Expert Opin Investig Drugs 13:1149
Pooni PK, Showell GA (2006) Mini-Rev Med Chem 6:1169
Sieburth SMcN, Chen C-A (2006) Eur J Org Chem 311
Gately S, West R (2007) Drug Dev Res 68:156
Franz AK (2007) Curr Opin Drug Discovery Dev 10:654
Meanwell NA (2011) J Med Chem 54:2529
Franz AK, Wilson SO (2013) J Med Chem 56:388
Sieburth SMcN (2014) Top Med Chem. doi:10.1007/7355_2014_80
Fessenden RJ, Coon MD (1965) J Med Chem 8:604
Fessenden RJ, Ahlfors C (1967) J Med Chem 10:810
Fessenden RJ, Rittenhouse R (1968) J Med Chem 11:1070
Fessenden RJ, Hartman RA (1970) J Med Chem 13:52
Klapötke TM, Krumm B, Ilg R, Troegel D, Tacke R (2007) J Am Chem Soc 129:6908
Evangelisti C, Klapötke TM, Krumm B, Nieder A, Berger RJF, Hayes SA, Mitzel NW, Troegel D, Tacke R (2010) Inorg Chem 49:4865
Klapötke TM, Krumm B, Nieder A, Richter O, Troegel D, Tacke R (2012) Z Anorg Allg Chem 638:1075
Daiss JO, Burschka C, Mills JS, Montana JG, Showell GA, Warneck JBH, Tacke R (2006) Organometallics 25:1188
Tacke R, Daiss J (2003) International Patent Application WO2003 037905
Daiss JO, Penka M, Burschka C, Tacke R (2004) Organometallics 23:4987
Showell GA, Miller D, Mandal AK, Tacke R, Daiss J (2004) International Patent Application WO2004 094436
Showell GA, Barnes MJ, Daiss JO, Mills JS, Montana JG, Tacke R, Warneck JBH (2006) Bioorg Med Chem Lett 16:2555
Warneck JB, Cheng FHM, Barnes MJ, Mills JS, Montana JG, Naylor RJ, Ngan M-P, Wai M-K, Daiss JO, Tacke R, Rudd JA (2008) Toxicol Appl Pharmacol 232:369
Tacke R, Heinrich T, Bertermann R, Burschka C, Hamacher A, Kassack MU (2004) Organometallics 23:4468
Tacke R, Heinrich T (2003) UK Patent Application GB2003 2 382 575
Tacke R, Popp F, Müller B, Theis B, Burschka C, Hamacher A, Kassack MU, Schepmann D, Wünsch B, Jurva U, Wellner E (2008) ChemMedChem 3:152
Tacke R, Nguyen B, Burschka C, Lippert WP, Hamacher A, Urban C, Kassack MU (2010) Organometallics 29:1652
Johansson T, Weidolf L, Popp F, Tacke R, Jurva U (2010) Drug Metab Dispos 38:73
Daiss JO, Burschka C, Mills JS, Montana JG, Showell GA, Fleming I, Gaudon C, Ivanova D, Gronemeyer H, Tacke R (2005) Organometallics 24:3192
Montana JG, Showell GA, Fleming I, Tacke R, Daiss J (2004) International Patent Application WO2004 048390
Büttner MW, Nätscher JB, Burschka C, Tacke R (2007) Organometallics 26:4835
Luger P, Weber M, Hübschle C, Tacke R (2013) Org Biomol Chem 11:2348
Lippert WP, Burschka C, Götz K, Kaupp M, Ivanova D, Gaudon C, Sato Y, Antony P, Rochel N, Moras D, Gronemeyer H, Tacke R (2009) ChemMedChem 4:1143
Bauer JB, Lippert WP, Dörrich S, Tebbe D, Burschka C, Christie VB, Tams DM, Henderson AP, Murray BA, Marder TB, Przyborski SA, Tacke R (2011) ChemMedChem 6:1509
Büttner MW, Burschka C, Daiss JO, Ivanova D, Rochel N, Kammerer S, Peluso-Iltis C, Bindler A, Gaudon C, Germain P, Moras D, Gronemeyer H, Tacke R (2007) ChemBioChem 8:1688
Tacke R, Müller V, Büttner MW, Lippert WP, Bertermann R, Daiß JO, Khanwalkar H, Furst A, Gaudon C, Gronemeyer H (2009) ChemMedChem 4:1797
Gluyas JBG, Burschka C, Dörrich S, Vallet J, Gronemeyer H, Tacke R (2012) Org Biomol Chem 10:6914
Tacke R, Kornek T, Heinrich T, Burschka C, Penka M, Pülm M, Keim C, Mutschler E, Lambrecht G (2001) J Organomet Chem 640:140
Tacke R, Handmann VI, Kreutzmann K, Keim C, Mutschler E, Lambrecht G (2002) Organometallics 21:3727
Tacke R, Handmann VI, Bertermann R, Burschka C, Penka M, Seyfried C (2003) Organometallics 22:916
Heinrich T, Buschka C, Warneck J, Tacke R (2004) Organometallics 23:361
Tacke R, Schmid T, Penka M, Burschka C, Bains W, Warneck J (2004) Organometallics 23:4915
Ilg R, Burschka C, Schepmann D, Wünsch B, Tacke R (2006) Organometallics 25:5396
Barnes MJ, Burschka C, Büttner MW, Conroy R, Daiss JO, Gray IC, Hendrick AG, Tam LH, Kuehn D, Miller DJ, Mills JS, Mitchell P, Montana JG, Muniandy PA, Rapley H, Showell GA, Tebbe D, Tacke R, Warneck JBH, Zhu B (2011) ChemMedChem 6:2070
Wang J, Ma C, Wu Y, Lamb RA, Pinto LH, DeGrado WF (2011) J Am Chem Soc 133:13844
Reddy GD, Park S-J, Cho HM, Kim T-J, Lee ME (2012) J Med Chem 55:6438
Tacke R, Bertermann R, Burschka C, Dörrich S, Fischer M, Müller B, Meyerhans G, Schepmann D, Wünsch B, Arnason I, Bjornsson R (2012) ChemMedChem 7:523
Fujii S, Miyajima Y, Masuno H, Kagechika H (2013) J Med Chem 56:160
Nakamura M, Makishima M, Hashimoto Y (2013) Bioorg Med Chem 21:1643
Büttner MW, Penka M, Doszczak L, Kraft P, Tacke R (2007) Organometallics 26:1295
Doszczak L, Kraft P, Weber H-P, Bertermann R, Triller A, Hatt H, Tacke R (2007) Angew Chem 119:3431; (2007) Angew Chem Int Ed 46:3367
Büttner MW, Burschka C, Junold K, Kraft P, Tacke R (2007) ChemBioChem 8:1447
Büttner MW, Metz S, Kraft P, Tacke R (2007) Organometallics 26:3925
Tacke R, Metz S (2008) Chem Biodiversity 5:920
Metz S, Nätscher JB, Burschka C, Götz K, Kaupp M, Kraft P, Tacke R (2009) Organometallics 28:4700
Sunderkötter A, Lorenzen S, Tacke R, Kraft P (2010) Chem Eur J 16:7404
Geyer M, Bauer J, Burschka C, Kraft P, Tacke R (2011) Eur J Inorg Chem 2769
Dörrich S, Bauer JB, Lorenzen S, Mahler C, Schweeberg S, Burschka C, Baus JA, Tacke R, Kraft P (2013) Chem Eur J 19:11396
Förster B, Bertermann R, Kraft P, Tacke R (2014) Organometallics 33:338
Friedrich J, Dörrich S, Berkefeld A, Kraft P, Tacke R (2014) Organometallics 33:796
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Tacke, R., Dörrich, S. (2014). Drug Design Based on the Carbon/Silicon Switch Strategy. In: Schwarz, J. (eds) Atypical Elements in Drug Design. EGC 2015. Topics in Medicinal Chemistry, vol 17. Springer, Cham. https://doi.org/10.1007/7355_2014_55
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DOI: https://doi.org/10.1007/7355_2014_55
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