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An Efficient Synthesis of an αvβ3 Antagonist

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journal contribution
posted on 19.03.2004, 00:00 by Nobuyoshi Yasuda, Yi Hsiao, Mark S. Jensen, Nelo R. Rivera, Chunhua Yang, Kenneth M. Wells, James Yau, Michael Palucki, Lushi Tan, Peter G. Dormer, Ralph P. Volante, David L. Hughes, Paul J. Reider
A practical preparation of an αvβ3 antagonist is reported. The antagonist consists of three key components, a tetrahydronaphthyridine moiety, a β-alanine moiety, and a central imidazolidone moiety. The tetrahydronaphthyridine component was prepared using two different methods, both of which relied on variations of the Friedländer reaction to establish the desired regiochemistry. The β-alanine component was prepared using Davies' asymmetric 1,4-addition methodology as the key stereo-defining step. The central imidazolidone portion was created from these two components using an effective three-step cyclization protocol. Thus, a highly convergent process for the drug candidate was defined.

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