Novel CGRP receptor antagonists from central amide replacements causing a reversal of preferred chirality.
| Autor: | Wood MR; Department of Medicinal Chemistry, Merck & Co., Inc., PO Box 4, 770 Sumneytown Pike, West Point, PA 19486, United States., Schirripa KM, Kim JJ, Bednar RA, Fay JF, Bruno JG, Moore EL, Mosser SD, Roller S, Salvatore CA, Vacca JP, Selnick HG |
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| Jazyk: | angličtina |
| Zdroj: | Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Nov 15; Vol. 20 (22), pp. 6827-30. Date of Electronic Publication: 2010 Aug 26. |
| DOI: | 10.1016/j.bmcl.2010.08.105 |
| Abstrakt: | A previously utilized quinoline-for-N-phenylamide replacement strategy was employed against a central amide in a novel class of CGRP receptor antagonists. A unique and unexpected substitution pattern was ultimately required to maintain reasonable affinity for the CGRP receptor, while at the same time predicting acceptable heterocycle positioning for related analogs. Subsequently, specific quinoline and naphthyridine compounds were prepared which supported these structural predictions by displaying CGRP binding affinities in the 0.037-0.15 nM range. (Copyright © 2010 Elsevier Ltd. All rights reserved.) |
| Databáze: | MEDLINE |
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