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ID: ALA1156010
Journal: Bioorg Med Chem Lett
Title: Novel CGRP receptor antagonists through a design strategy of target simplification with addition of molecular flexibility.
Authors: Wood MR, Schirripa KM, Kim JJ, Quigley AG, Stump CA, Bell IM, Bednar RA, Fay JF, Bruno JG, Moore EL, Mosser SD, Roller S, Salvatore CA, Kane SA, Vacca JP, Selnick HG.
Abstract: A novel class of CGRP receptor antagonists was rationally designed by modifying a highly potent, but structurally complex, CGRP receptor antagonist. Initial modifications focused on simplified structures, with increased flexibility. Subsequent to the preparation of a less-potent but more flexible lead, classic medicinal chemistry methods were applied to restore high affinity (compound 22, CGRP Ki=0.035 nM) while maintaining structural diversity relative to the lead. Good selectivity against the closely related adrenomedullin-2 receptor was also achieved.
CiteXplore: 19703767