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

Patent metadata

Field	Value
Publication number	US-9828338-B2
Application number	US-201514853634-A
Country	US
Kind code	B2
Filing date	Sep 14, 2015
Priority date	Mar 15, 2013
Publication date	Nov 28, 2017
Grant date	Nov 28, 2017

Abstract

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.

First claim

What is claimed is:

1. A compound having the structure of Formula I:

wherein:
R 1 and R 2 are each hydrogen,
R 3 is selected from the group consisting of hydrogen and alkyl;
R 4 is selected from the group consisting of alkylene, alkenylene, and alkynylene;
R 5 is selected from the group consisting of alkylene, alkenylene;
R 6 is 3 to 10 membered cycloalkyl;
or a pharmaceutically acceptable salt or ester thereof.

2. A compound of claim 1 , having the structure:

3. A compound of claim 1 , wherein R 4 is alkylene.

4. A compound of claim 1 , wherein R 4 is selected from the group consisting of methylene, ethylene, i-propylene, n-propylene, i-butylene, t-butylene, n-butylene, n-pentylene, i-pentylene, pentylene, hexylene, heptylene, octylene, nonylene, decylene, undecylene, and dodecylene.

5. A compound of claim 1 , wherein the compound is selected from the group consisting of

6. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, carrier or diluent.

7. A compound of claim 1 , wherein the compound is of the formula:

or a pharmaceutically acceptable salt thereof.

8. A compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

9. A compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

10. A compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

11. A compound of claim 1 , wherein R 4 -R 5 is ethylene, n-propylene, n-butylene, n-pentylene, or hexylene.

12. A compound of claim 1 , wherein R 4 -R 5 is n-propylene, n-butylene, or n-pentylene.

13. A compound of claim 1 , wherein R 3 is hydrogen.

14. A compound of claim 1 , wherein R 6 is cyclopentyl or cyclohexyl.

15. A compound of claim 1 , wherein R 6 is cyclohexyl.

Assignees

• Univ California
• Fondazione St Italiano Tecnologia
• Univ Degli Studi Di Parma
• Univ Degli Studi Di Urbino “Carlo Bo”
• Fondazione Istituto Italiano Di Tech

Inventors

• Piomelli Daniele
• Bandiera Tiziano
• Bertozzi Fabio
• Nuzzi Andrea
• Fiasella Annalisa
• Ponzano Stefano
• Pagliuca Chiara
• Reggiani Angelo Mario
• Mor Marco
• Tarzia Giorgio

Classifications

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D405/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D205/085 Primary

  with a nitrogen atom directly attached in position 3 · CPC title

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title