2-Methoxyethoxymethyl ethers stable

Roxithromycin (18), a methoxyethoxymethyl ether oxime derivative of 11, is more stable than 1 in acidic media. The E orientation of the oxime and the chain length that bears oxygen atoms, such as methoxyethoxymethyl, are important for increased in vitro and in vivo activity. The structural characteristics of 18 obtained by X-ray and NMR analyses have been compared with those of 1 [8, 9]. The modification of 1 at the 9-oxime decreased its affinity for R-450, which reflects reduced interaction with hepatic mono-oxygenase in vitro and in vivo [10]. The change in physicochemical properties such as the octanol-water partition coefficient of 18 (P = 408, log P = 2.61, 37°C, pH 7.40) indicated a more lipophilic character than that of 1 (P = 50, log P — 1.70), which can be linked with its good tissue penetration [11]. 

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