Naproxen structure

A number of drugs have been successfully separated using MIPs. Naproxen , (S)-6-methoxy-a-methyl-2-naphthaleneacetic acid, is a nonsteroidal anti-inflammatory drug (NSAID) that is administered as the S enantiomer. Naproxen (structure 16.20) will be used to illustrate the MIP sequence. Naproxen has both polar and nonpolar domains. It also has a fused-ring aromatic site. 

NSAIDs are of diverse chemical structures salicylates (aspirin, sulphasalazine), indole acetic acids (indomethacin, etodolac), heteroaryl acetic acids (diclofenac), arylpropionic acids (ibuprofen, naproxen), anthranilic acids (mefenamic acid) and enolic acids (piroxicam, meloxicam). 

The ratio of THF and 4-vinylpyridine is important because both assemble around the naproxen. If there are many solvent molecules present, the cocoon cavity will not be sufficient to retain the template molecule imprint. If the concentration of vinylpyridine is very high, the cocoon structure will be complete and prevent both the exit of the target molecule and entrance of other naproxen molecules during the separation procedure. 

Nabumetone is the only nonacid NSAID in current use it is converted to the active acetic acid derivative in the body. It is given as a ketone prodrug that resembles naproxen in structure (Figure 36-1). Its half-life of more than 24 hours (Table 36-1) permits once-daily dosing, and the drug does not appear to undergo enterohepatic circulation. Renal impairment results in a doubling of its half-life and a 30% increase in the area under the curve. 

Polyphosphazenes are a relatively new class of biodegradable polymers. Their hydrolytic stability or instability is determined not by changes in the backbone structure but by changes in the side groups attached to an unconventional macromolecular backbone. Synthetic flexibility and versatile adaptability of polyphosphazenes make them unique for drug delivery applications. For example, Veronese et al.18 prepared polyphos-phazene microspheres with phenylalanine ethyl ester as a phosphorous substituent and loaded it with succinylsulphathiazole or naproxen. The kinetics of release from these matrices were very convenient in yielding local concentrations of the two drugs that are useful per se or when mixed with hydroxyapatite for better bone formation. Polyphosphazene matrices are also considered as potential vehicles for the delivery of proteins and vaccines.19... 

B. Busqewski, M. El Mouelhi, K. Albert, and E. Bayer, Influence of the Structure of chemically binded C18 phases on HPLC separation in naproxen glucuronide diastreoisomers, J. Liquid Chromatogr., 73 505 (1990). 

Silica-base stationary phases have also been employed for enantiomeric separations in CEC [6,72-81]. In the initial work on chiral CEC, commercially available HPLC materials were utilized, including cyclodextrins [6,74,81] and protein-type selectors [73,75,80] such as human serum albumin [75] and ai-acid glycoprotein [73]. Fig. 4.9, for example, depicts the structure of a cyclodextrin-base stationary phase used in CEC and the separation of mephobarbital enantiomers by capillary LC and CEC in a capillary column packed with such a phase. The column operated in the CEC mode affords higher separation efficiency than in the capillary LC mode. Other enantiomeric selectors are also use in CEC, including the silica-linked or silica-coated macrocyclic antibiotics vancomycin [82,83] and teicoplanin [84], cyclodextrin-base polymer coated silicas [72,78], and weak anion-exchage type chiral phases [85]. Relatively high separation efficiency and excellent resolution for a variety of compounds have also been achieved using columns packed with naproxen-derived and Whelk-0 chiral stationary phases linked to 3 pm silica particles [79]. Fig. 4.10 shows the... 

Although nitrile hydratases tend not to be stereoselective, examples of enantioselective enzymes are known [103, 106, 107, 114]. Of particular interest is the possibility to selectively hydrolyse 2-phenylproprionitriles, the core structure for ibuprofen and many other profens [103, 107, 114, 115]. This enables the enantioselective synthesis of the amides of ketoprofen and naproxen (Scheme 6.39). 

Figure 22-24. CSP for enantiomeric separation of Naproxen. Chemical structure (left) and a CPK model (right). (Adapted from reference 98, with permission.)...

S)-Naproxen is the aaive ingredient in the widely used pain relievers Naprosyn and Aleve. The three-dimensional orientation of two atoms at a single carbon in naproxen determines its therapeutic properties. Changing the position of these two atoms converts this anti-inflammatory agent into a liver toxin. In Chapter 5 we learn more about stereochemistry and how small structural differences can have a large effect on the properties of a molecule. 

The importance of the three-dimensional structure in the pain reliever (S)-naproxen (Opener)... 

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