Inhibitors for soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FAAH)

Patent metadata

Field	Value
Publication number	US-11873288-B2
Application number	US-202017112713-A
Country	US
Kind code	B2
Filing date	Dec 4, 2020
Priority date	Mar 15, 2016
Publication date	Jan 16, 2024
Grant date	Jan 16, 2024

Abstract

The present invention provides compounds that are dual inhibitors of soluble epoxide hydrolase and fatty acid amide hydrolase. The present invention also provides methods of using the compounds to inhibit soluble epoxide hydrolase and fatty acid amide hydrolase, and to treat cancer.

First claim

What is claimed is:

1. A method for inhibiting a soluble epoxide hydrolase and fatty acid amide hydrolase, the method comprising contacting the soluble epoxide hydrolase and fatty acid amide hydrolase with a therapeutically effective amount of a compound having Formula II:

or a pharmaceutically acceptable salt or isomer thereof, thereby inhibiting the soluble epoxide hydrolase and fatty acid amide hydrolase,

wherein
each R 1 is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, hydroxy, C 1-6 hydroxyalkyl, halogen, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, —CN, —C(O)R 1a , —C(O)OR 1a , —OC(O)R 1a , —C(O)N(R 1a )(R 1b ), —N(R 1b )C(O)R 1a , —C(O)N(R 1a )CH 2 C(O)OR 1b , —N(R 1a )(R 1b ), —S(O) 2 R 1a , —S(O) 2 N(R 1a )(R 1b ), —N(R 1b )S(O) 2 R 1a , C 3-8 cycloalkyl, C 5-10 heterocycloalkyl, C 6-12 aryl and C 5-12 heteroaryl;
R 1a is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 hydroxyalkyl, and C 1-6 alkyl-C 6-12 aryl;
R 1b is selected from the group consisting of hydrogen and C 1-6 alkyl;
R 2 is selected from the group consisting of C 3-8 cycloalkyl, C 3-10 heterocycloalkyl, C 6-12 aryl, and C 5-12 heteroaryl, optionally substituted with 1 to 2 R a groups;
each R 2a is independently selected from the group consisting of hydrogen, C 1-6 alkyl, halogen, C 1-6 haloalkyl, C 1-6 alkoxy, and C 1-6 haloalkoxy;
L 1 is selected from the group consisting of C 1-6 alkylene, C 3-8 cycloalkylene, C 3-10 heterocycloalkylene, C 6-12 arylene, and C 5-12 heteroarylene;
R 3 is selected from the group consisting of hydrogen and C 1-6 alkyl, or is combined with L 1 and the nitrogen to which they are attached to form a C 5-8 heterocycloalkyl having 1 to 2 additional heteroatoms each independently selected from N, O and S;
X is selected from the group consisting of CH and N; and
subscript n is an integer from 1 to 4.

2. The method of claim 1 , wherein the compound has a structure according to Formula IIa:

or a pharmaceutically acceptable salt or isomer thereof,

wherein
R 2a is selected from the group consisting of hydrogen, C 1-6 alkyl, halogen, C 1-6 haloalkyl, C 1-6 alkoxy and C 1-6 haloalkoxy.

3. The method of claim 1 , wherein the compound has a structure according to Formula IIb:

or a pharmaceutically acceptable salt or isomer thereof,

wherein
R 1 is selected from the group consisting of hydrogen, C 1-6 alkyl, hydroxy, C 1-6 hydroxyalkyl, C 1-6 alkoxy, —CN, —C(O)R 1a , —C(O)OR 1a , —OC(O)R 1a , —C(O)N(R 1a )(R 1b ), —C(O)N(R 1a )CH 2 C(O)OR 1b , and C 5-12 heteroaryl.

4. The method of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt or isomer thereof.

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

or a pharmaceutically acceptable salt or isomer thereof.

6. The method of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt or isomer thereof.

Assignees

• Univ California

Inventors

• Hammock Bruce
• Kodani Sean

Classifications

• C07D401/06 Primary

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07C275/28

  having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton · CPC title

• C07C275/34

  having nitrogen atoms of urea groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring · CPC title

• C07C275/36

  with at least one of the oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. N-aryloxyphenylureas · CPC title