Synthesis, pharmacophore modeling and in vitro activity of 10,11-dihydrodibenzo[b,f]oxepine-4-carboxamide derivatives as novel and potent antagonists of the prostaglandin EP4 receptor

  • Bioorg Med Chem Lett. 2011 Nov 1;21(21):6336-40. doi: 10.1016/j.bmcl.2011.08.102.
Luigi Piero Stasi  1 ,  Kanji Bhimani ,  Manuela Borriello ,  Luca Canciani ,  Gianfranco Caselli ,  Fabrizio Colace ,  Cristian Ferioli ,  Mehul Kaswala ,  Laura Mennuni ,  Tiziana Piepoli ,  Sabrina Pucci ,  Matteo Salvi ,  Vikas Shirsath ,  Tiziano Zanelli ,  Silvia Zerbi
Affiliations
  • 1. Rottapharm Madaus, Medicinal Chemistry Department, via Valosa di Sopra 9, Monza 20900, Italy. [email protected]
PMID: 21930381 DOI: 10.1016/j.bmcl.2011.08.102
Abstract

The construction of a EP(4) antagonists pharmacophore model and the discovery of a highly potent oxepinic series of EP(4) antagonists is discussed. Compound 1a exhibits an excellent selectivity profile toward EP(2) receptor subtype and low Cytochrome P450 inhibition potential.