Pharmaceutically solid-supported pharmaceuticals

Chemistry on solid support has gained tremendous importance during the last few years, mainly driven by the needs of the pharmaceutical sciences. Due to the robust and tolerable nature of the available catalysts, metathesis was soon recognized as a useful technique in this context. Three conceptually different, RCM-based strategies are outlined in Fig. 11. In the approach delineated in Fig. 1 la, a polymer-bound diene 353 is subjected to RCM. The desired product 354 is formed with concomitant traceless release from the resin. This strategy is very favorable, since only compounds with the correct functionality will be liberated, while unwanted by-products remain attached to the polymer. However, as the catalyst is captured in this process by the matrix (355), a higher catalyst loading will be required, or ancillary alkenes have to be added to liberate the catalyst. 

The simplest technique is the use of the 96-well collection plate format (analogous to the format used in SPE) in conjunction with a liquid handling robotic system it follows the same principle as bulk scale LLE. However, immobilization of the aqueous plasma sample on an inert solid support medium packed in a cartridge or in the individual wells of a 96-well plate and percolating a water-immiscible organic solvent to extract the analyte from this medium evoked significant enthusiasm from the pharmaceutical industry. 

Loidl-Stahlhofen, A., Eckert, A., Hartmann, T. and Schottner, M. (2001). Solid-supported lipid membranes as a tool for determination of membrane affinity high-throughput-screening of a physicochemical parameter, J. Pharmaceut. Sci., 90, 599-606. 

The present revised textbook on Pharmaceutical Drug Analysis caters for the much needed handbook and reference book, which is absolutely current with regard to the esteemed philosophy of analytical chemistry, an obvious solid support towards drug discovery, development, stability studies, bioavailability and pharmacokinetic studies, and above all the quality assurance of pure drugs together with their respective dosage forms. 

The search for new enantiopure molecules in industry have recently become more and more important especially in the pharmaceutical area. Until now there are only a few examples of asymmetric synthesis on solid supports. However, as the recovery of a polymer-supported chiral auxiliary by simple filtration techniques... 

Binding enzymes to solid supports can be achieved via covalent bonds, ionic interactions, or physical adsorption, although the last two options are prone to leaching. Enzymes are easily bound to several types of synthetic polymers, such as acrylic resins, as well as biopolymers, e.g., starch, cellulose [52], or chitosan [53,54]. Degussa s Eupergit resins, for example, are used as enzyme carriers in the production of semisynthetic antibiotics and chiral pharmaceuticals [55], Typically, these copolymers contain an acrylamide/methacrylate backbone, with epoxide side groups... 

The separation of enantiomers is especially important in the pharmaceutical field, because drag enantiomers may produce different effects in the body. Enantiomer separations by chromatography require one of the components of the phase system to be chiral. This can be achieved by (a) the addition of a chiral compound to the mobile phase, which is then used in combination with a nonchiral stationary phase, or (b) the use of a chiral stationary phase in combination with a nonchiral mobile phase. The chiral phase can either be a solid support physically coated with a chiral stationary phase liquid or a chemically bonded chiral phase. For mobile-phase compatibility reasons, a chiral stationary phase is preferred in LC-MS. However, most chiral stationary phases have stringent demands with respect to mobile-phase compositiorr, which in turn may lead to compatibility problems. Three types of phase systems are applied in LC-MS ... 

Solid-phase synthesis of peptides was pioneered by Bruce Merrifield in the early 1960s. This work, for which he won the Nobel Prize in 1984, set in motion the modern approach to drug discovery called combinatorial chemistry. Through combinatorial chemistry, millions of compounds are generated by the synthesis of libraries on solid supports and screened for therapeutic activity by high-throughput assays. The importance of this work is attested by the numerous combinatorial research units that are now an integral part of most major pharmaceutical companies. 

Enantiomers are distinguished on the basis of their interaction with a chiral selector. Development of chiral selectors or chiral stationary phases (CSPs) for GC, HPLC, and CE has rapidly opened a new dimension in the area of chiral drug separation techniques. There are different chiral selectors available for enantiomeric separation of drugs and pharmaceuticals. Finding a suitable chiral selector, whether immobilized on a solid support (GC, HPLC) or added to a running buffer (HPLC, CE), is still often based on trial and error. A few predictions can be made, however, if common structural elements are present. After a selector has been chosen, variables, such as the nature, ionic strength, and pH of buffer, can be varied, as can presence of organic modifiers, temperature, and so on. 

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