Arylboronic acids as dual-action FAAH and TRPV1 ligands

  • Bioorg Med Chem Lett. 2016 Mar 1;26(5):1401-5. doi: 10.1016/j.bmcl.2016.01.071.
Enrico Morera  1 ,  Vincenzo Di Marzo  2 ,  Ludovica Monti  3 ,  Marco Allarà  2 ,  Aniello Schiano Moriello  2 ,  Marianna Nalli  3 ,  Giorgio Ortar  3 ,  Luciano De Petrocellis  4
Affiliations
  • 1. Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, piazzale Aldo Moro 5, 00185 Roma, Italy. Electronic address: [email protected].
  • 2. Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, via Campi Flegrei 34, 80078 Pozzuoli (Napoli), Italy.
  • 3. Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, piazzale Aldo Moro 5, 00185 Roma, Italy.
  • 4. Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, via Campi Flegrei 34, 80078 Pozzuoli (Napoli), Italy. Electronic address: [email protected].
PMID: 26850005 DOI: 10.1016/j.bmcl.2016.01.071
Abstract

A series of 31 arylboronic acids designed on the basis of the pharmacophore model for a variety of TRPV1 antagonists was prepared and tested on FAAH and TRPV1 channel. Four of them, that is, compounds 3c, 4a, 5a,b acted as dual FAAH/TRPV1 blockers with IC50 values between 0.56 and 8.11μM whereas ten Others (compounds 1c,f-i, 2c-f, 4b) inhibited FAAH and activated/desensitized TRPV1.

Keywords
Boronic acids; Dual-ligands; FAAH; Fatty acid amide hydrolase; TRPV1; Transient receptor potential vanilloid type-1 channel.