P3 SAR exploration of biphenyl carbamate based Legumain inhibitors

  • Bioorg Med Chem Lett. 2014 Jun 1;24(11):2521-4. doi: 10.1016/j.bmcl.2014.04.002.
Catherine Higgins  1 ,  Samira Bouazzaoui  1 ,  Kishore Gaddale  1 ,  Zenobia D'Costa  1 ,  Amy Templeman  1 ,  Martin O'Rourke  2 ,  Andrew Young  3 ,  Christopher Scott  4 ,  Tim Harrison  5 ,  Paul Mullan  1 ,  Rich Williams  6
Affiliations
  • 1. CCRCB Drug Discovery Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, UK.
  • 2. Almac Discovery, Almac House, 20 Seagoe Industrial Estate, Craigavon BT63 5QD, UK.
  • 3. School of Pharmacy, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, UK.
  • 4. CCRCB Drug Discovery Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, UK; School of Pharmacy, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, UK.
  • 5. CCRCB Drug Discovery Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, UK; Almac Discovery, Almac House, 20 Seagoe Industrial Estate, Craigavon BT63 5QD, UK.
  • 6. CCRCB Drug Discovery Group, Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, UK. Electronic address: [email protected].
PMID: 24775305 DOI: 10.1016/j.bmcl.2014.04.002
Abstract

This Letter describes the further development and SAR exploration of a novel series of Legumain inhibitors. Based upon a previously identified Legumain Inhibitor from our group, we explored the SAR of the carbamate phenyl ring system to probe the P3 pocket of the enzyme. This led to the identification of a sub-nanomolar inhibitor of Legumain.

Keywords
Cancer; Cyano warhead; Legumain; Protease inhibitor.
Products