University of California

Università Degli Studi Di Parma

Fondazione Istituto Italiano Di Technologia

Università Degli Studi Di Urbino "Carlo Bo"

Fondazione Istituto Italiano Di Tecnologia

Neurosciences Research Foundation, Inc.

Universita Degli Studi Di Urbino

Other

The University of Chicago

Alma Mater Studiorum-Universitá Di Bologna

Universita Degl Studi Di Parma

Daniele Piomelli

Marco Mor

Giorgio Tarzia

Tiziano Bandiera

Rita Scarpelli

Andrea Duranti

Andrea Tontini

Fabio Bertozzi

Daniela Pizzirani

Chiara Pagliuca

Marco De Vivo

Antonio Calignano

Anders Bach

Angelo Mario Reggiani

Andrea Cavalli

Fernando Rodríguez De Fonseca

Giovanna La Rana

Natalia Realini

Massimiliano Beltramo

Andrea Nuzzi

Annalisa Fiasella

Marco Migliore

Stefano Ponzano

Andrea Guiffrida

Guillermo Moreno-Sanz

Roger Heim

Giovanni Bottegoni

Angelo Danilo Favia

Sonyuan Lin

Alexandros Makriyannis

Laurin Melzig

Jason R Clapper

Damien Habrant

Gian Filippo Ruda

Alessio De Simone

Miguel Garcia-Guzmàn

Angelo Favia

Jason Clapper

Georgio Tarzia

Andrea Giuffrida

Disclosed herein, inter alia, are compositions and methods for modulating the activity of N-acylethanolamine acid amidase for the treatment of a pathological state, including pain, an inflammatory condition, or a neurodegenerative disorder.

Piperazinyl methanone NAAA inhibitors

Described herein, inter alia, are compositions and methods useful for inhibiting fatty acid amide hydrolase.

Inhibitors of fatty acid amide hydrolase (FAAH) enzyme with improved oral bioavailability and their use as medicaments

Compounds and pharmaceutical compositions are contemplated that inhibit N-acyl-ethanolamine-hydrolyzing acid amidase (NAAA) to so increase the concentration of the substrate of NAAA, palmitoylethanolamide (PEA). NAAA inhibition is contemplated to be effective to alleviate conditions associated with a reduced concentration of PEA. Among other uses, various NAAA inhibitors are especially contemplated as therapeutic agents in the treatment of inflammatory diseases.

Compositions and methods of inhibiting N-acylethanolamine-hydrolyzing acid amidase

The present invention relates to benzoxazolone derivatives as acid ceramidase inhibitors, pharmaceutical compositions containing these inhibitors and methods of inhibiting acid ceramidase for the treatment of disorders in which modulation of the levels of ceramide is clinically relevant. The invention also provides benzoxazolone derivatives for use as a medicament in the treatment of cancer, inflammation, pain, inflammatory pain or pulmonary diseases.

Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments

The present invention relates to substituted benzoxazolone derivatives as acid ceramidase inhibitors, pharmaceutical compositions containing these inhibitors and methods of inhibiting acid ceramidase for the treatment of disorders in which modulation of the levels of ceramide is clinically relevant. The invention also provides substituted benzoxazolone derivatives for use in the treatment of cancer, inflammation, pain, inflammatory pain or pulmonary diseases.

Substituted benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments

Described herein are compounds and pharmaceutical compositions which inhibit N-acylethanolamine acid amidase (NAAA). Described herein are methods for synthesizing the compounds set forth herein and methods for formulating these compounds as pharmaceutical compositions which include these compounds. Also described herein are methods of inhibiting NAAA in order to sustain the levels of palmitoylethanolamide (PEA) and other N-acylethanolamines (NAE) that are substrates for NAAA, in conditions characterized by reduced concentrations of NAE. Also, described here are methods of treating and ameliorating pain, inflammation, inflammatory diseases, and other disorders in which modulation of fatty acid ethanolamides is clinically or therapeutically relevant or in which decreased levels of NAE are associated with the disorder.

Amide derivatives of lactam based N-acylethanolamine acid amidase (NAAA) inhibitors

Carbamate derivatives of lactam based N-acylethanolamine acid amidase (NAAA) inhibitors

The invention provides compounds of Formula (I) or pharmaceutically acceptable salts thereof 

Phenyl carbamates and their use as inhibitors of the fatty acid amide hydrolase (FAAH) enzyme and modulators of the D3 dopamine receptor (D3DR)

The present invention provides methods of making and using peripherally restricted inhibitors of fatty acid amide hydrolase (FAAH). The present invention provides compounds and compositions that suppress FAAH activity and increases anandamide levels outside the central nervous system (CNS). The present invention also sets forth methods for inhibiting FAAH as well as methods for treating conditions such as, but not limited to, pain, inflammation, immune disorders, dermatitis, mucositis, the over reactivity of peripheral sensory neurons, neurodermatitis, and an overactive bladder. Accordingly, the invention also provides compounds, methods, and pharmaceutical compositions for treating conditions in which the selective inhibition of peripheral FAAH (as opposed to CNS FAAH) would be of benefit.

Meta-substituted biphenyl peripherally restricted FAAH inhibitors

Multitarget inhibitors of the enzymes Fatty Acid Amide Hydrolase (FAAH), Cyclooxygenase-1 (COX-1) and/or Cyclooxygenase-2 (COX-2) having a specific carbamate moiety on the meta or ortho position of the A ring of a substituted biphenyl core and having an halogen in the ortho position of the B ring of the biphenyl core. Also concerns the therapeutical application of the multitarget inhibitors, in particular, in the prevention and treatment of cancer.

Multitarget FAAH and COX inhibitors and therapeutical uses thereof

The present invention concerns, in a first aspect, compounds of Formula I as defined herein, pharmaceutically acceptable salts thereof and pharmaceutical compositions containing such compounds. The present invention also relates to compounds of Formula I for use as acid ceramidase inhibitors, and in the treatment of cancer and other disorders in which modulation of the levels of ceramide is clinically relevant.

Acid ceramidase inhibitors and their use as medicaments

The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.

Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)

Peripherally restricted inhibitors of fatty acid amide hydrolase (FAAH) are provided. The compounds can suppress FAAH activity and increases anandamide levels outside the central nervous system (CNS). Despite their relative inability to access brain and spinal cord, the compounds attenuate behavioral responses indicative of persistent pain in rodent models of inflammation and peripheral nerve injury, and suppresses noxious stimulus-evoked neuronal activation in spinal cord regions implicated in nociceptive processing. CBi receptor blockade prevents these effects. Accordingly, the invention also provides methods, and pharmaceutical compositions for treating conditions in which the inhibition of peripheral FAAH would be of benefit. The compounds of the invention are according to the formula (I): in which Ris a polar group. In some embodiments, Ris selected from the group consisting of hydroxy and the physiologically hydro lysable esters thereof. Rand Rare independently selected from the group consisting of hydrogen and substituted or unsubstituted hydrocarbyl; each Ris independently selected from the group consisting of halogen and substituted or unsubstituted hydrocarbyl and n is an integer from 0 to 4; each Ris independently selected from the group consisting of halo and substituted or unsubstituted hydrocarbyl and m is an integer from 0 to 3; and Ris substituted or unsubstituted cyclohexyl; and the pharmaceutically acceptable salts thereof. 

Peripherally restricted FAAH inhibitors

Growing community of inventors

Irvine, CA, United States of America

Daniele Piomelli