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ID: ALA1141968

Journal: Bioorg Med Chem Lett

Title: A lead compound for the development of ABA 8'-hydroxylase inhibitors.

Authors: Ueno K, Yoneyama H, Saito S, Mizutani M, Sakata K, Hirai N, Todoroki Y.

Abstract: (1'S*,2'S*)-(+/-)-6-Nor-2',3'-dihydro-4'-deoxo-ABA (2) was designed and synthesized as a candidate lead compound for developing a potent and specific inhibitor of ABA 8'-hydroxylase. This compound acted as an effective competitive inhibitor of the enzyme, with a K(I) value of 0.40microM, without exhibiting ABA activity. However, compound 2 also functioned as an enzyme substrate, making it a short-lived inhibitor. The 8'-difluorinated derivative of 2 (4) was synthesized as a long-lasting alternative. Compound 4 resisted 8'-hydroxylation, but inhibited ABA 8'-hydroxylation as effectively as 2. These results suggest that compound 2 is a useful lead compound for the future design and development of an ideal ABA 8'-hydroxylase inhibitor.

CiteXplore: 16169217

DOI: 10.1016/j.bmcl.2005.08.042