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

Luigi Piero Stasi; 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

doi:10.1016/j.bmcl.2011.08.102

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. Epub 2011 Sep 1.

Authors

Luigi Piero Stasi¹, 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

Affiliation

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.

MeSH terms

Benzoxepins / chemical synthesis*
Benzoxepins / chemistry
Benzoxepins / pharmacology*
Drug Evaluation, Preclinical
Humans
In Vitro Techniques
Models, Molecular*
Receptors, Prostaglandin E, EP4 Subtype / antagonists & inhibitors*

Substances

10,11-dihydrodibenzo(b,f)oxepine-4-carboxamide
Benzoxepins
Receptors, Prostaglandin E, EP4 Subtype