2003 Enzyme inhibiting activity

Enzyme inhibiting activityX 0220 Improvement of Therapeutic Index of Phosphodiesterase Type IV Inhibitors as

Antiasthmatics. — A series of fifteen catechol hydrazines is prepared from isovanillin by known procedures in order to develop more potent and selective phosphodiesterease 4(PDE4) inhibitors with reduced side effects. Molecular modeling studies suggest that the (E)-isomers are about 3—4 times more potent than the (Z)-isomers. The catechol hydrazines are evaluated for PDE4 inhibitory activity as well as for binding affinity to the high affinity-rolipram binding site. Among the (E)-isomers, analogues (I) are the most potent compounds and show similar affinity to rolipram. With respect to retaining antiasthmatic activities and exhibiting minimum emetic side effect, analogue (Ia) shows the greatest improvement. — (KIM*, E.; CHUN, H.-O.; JUNG, S.-H.; KIM, J. H.; LEE, J.-M.; SUH, B.-C.; XIANG, M. X.; RHEE*, C. K.; Bioorg. Med. Chem. Lett. 13 (2003) 14, 2355-2358; Pharm. Anal. Chem. Res.,Kyonggido 467-120, S. Korea; Eng.) — H. Hoennerscheid

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