2. Academic Validation
  3. Identification of potent CNS-penetrant thiazolidinones as novel CGRP receptor antagonists

Identification of potent CNS-penetrant thiazolidinones as novel CGRP receptor antagonists

  • Bioorg Med Chem Lett. 2014 Feb 1;24(3):845-9. doi: 10.1016/j.bmcl.2013.12.089.
Pramod Joshi 1,  Corey Anderson 1,  Hayley Binch 1,  Sabine Hadida 1,  Sanghee Yoo 2,  Danielle Bergeron 2,  Caroline Decker 3,  Ernst terHaar 4,  Jonathan Moore 4,  Miguel Garcia-Guzman 5,  Andreas Termin 6
Affiliations

Affiliations

  • 1 Vertex Pharmaceuticals Inc., Department of Chemistry and Drug Innovation, 11010 Torreyana Road, San Diego, CA 92121, United States.
  • 2 Vertex Pharmaceuticals Inc., Department of Biology, 11010 Torreyana Road, San Diego, CA 92121, United States.
  • 3 Vertex Pharmaceuticals Inc., Department of Drug Metabolism and Pharmacokinetics, 11010 Torreyana Road, San Diego, CA 92121, United States.
  • 4 Vertex Pharmaceuticals Inc., Department of Structural Biology, 130 Waverly Street, Cambridge, MA 02139, United States.
  • 5 Aspyrian Therapeutics Inc., 11189 Sorrento Valley Rd, San Diego CA 92121, United States. Electronic address: Miguel_Guzman@aspyriantherapeutics.com.
  • 6 Vertex Pharmaceuticals Inc., Department of Chemistry and Drug Innovation, 11010 Torreyana Road, San Diego, CA 92121, United States. Electronic address: andreas_termin@vrtx.com.
PMID: 24405707 DOI: 10.1016/j.bmcl.2013.12.089
Abstract

Calcitonin gene-related peptide (CGRP) has been implicated in acute migraine pathogenesis. In an effort to identify novel CGRP Receptor antagonists for the treatment of migraine, we have discovered thiazolidinone 49, a potent (Ki=30 pM, IC50=1 nM), orally bioavailable, CNS-penetrant CGRP antagonist with good pharmacokinetic properties.

Keywords

CGRP antagonists; Migraine; Thiazolidinone.

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