Atypical Elements in Drug Design by Jacob Schwarz

By Jacob Schwarz

Medicinal chemistry is either technological know-how and paintings. The technological know-how of medicinal chemistry deals mankind considered one of its most sensible hopes for making improvements to the standard of lifestyles. The artwork of medicinal chemistry maintains to problem its practitioners with the necessity for either instinct and event to find new medications. for that reason sharing the adventure of drug study is uniquely useful to the sector of medicinal chemistry. Drug learn calls for interdisciplinary team-work on the interface among chemistry, biology and medication. hence, the topic-related sequence themes in Medicinal Chemistry covers all correct points of drug examine, e.g. pathobiochemistry of illnesses, id and validation of (emerging) drug pursuits, structural biology, drugability of ambitions, drug layout techniques, chemogenomics, man made chemistry together with combinatorial equipment, bioorganic chemistry, ordinary compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions at the molecular point, structure-activity relationships, drug absorption, distribution, metabolism, removing, toxicology and pharmacogenomics. more often than not, exact volumes are edited by means of popular visitor editors.

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Genin E, Reboud-Ravaux M, Vidal J (2010) Curr Top Med Chem 10:232 99. Adams J, Behnke M, Chen SW, Cruickshank AA, Dick LR, Grenier L, Klunder JM, Ma YT, Plamondon L, Stein RL (1998) Bioorg Med Chem Lett 8:333 100. Richardson PG, Sonneveld P, Schuster MW, Stadtmauer EA, Facon T, Harousseau J-L, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, Blade J, Boccadoro M, Cavenagh JD, Boral AL, Esseltine D-L, Wen PY, Amato AA, Anderson KC, San Miguel J (2009) Br J Haematol 144:895 101. Adams JM, Cory S (2007) Oncogene 26:1324 102.

3 Sila-Substitution of Drugs: Selected Examples . . . . . . . . . . . . . . . . . . . . . . . 1 Sila-Venlafaxine: A Silicon Analogue of the Serotonin/Noradrenaline Reuptake Inhibitor Venlafaxine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Sila-Haloperidol: A Silicon Analogue of the Dopamine Antagonist Haloperidol . . 3 Disila-Bexarotene: A Silicon Analogue of the Retinoid Agonist Bexarotene .

30 31 32 32 37 45 53 55 56 57 1 Introduction Over the past five decades, many biologically active organosilicon compounds have been synthesized, and silicon chemistry has been demonstrated to be a novel source of chemical diversity in drug design (for reviews, see [1–17]). There are two different approaches that can be used for the design of silicon-based drugs: (1) synthesizing a silicon analogue of a known drug in which at least one carbon atom has been replaced by a silicon atom, with the rest of the molecule being identical (carbon/silicon exchange, carbon/silicon switch, sila-substitution) and (2) synthesizing completely new silicon-based classes of compounds (the carbon analogues of which are unknown or do not exist for principal reasons) that exploit specific features of silicon chemistry to address a well-validated target.

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