Pyrazole compounds and methods of making and using same

Patent metadata

Field	Value
Publication number	US-10093630-B2
Application number	US-201515312998-A
Country	US
Kind code	B2
Filing date	May 20, 2015
Priority date	May 21, 2014
Publication date	Oct 9, 2018
Grant date	Oct 9, 2018

Abstract

Provided herein are pyrazole compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of one or more of MAGL, ABHD6, and FAAH. Furthermore, the subject compounds and compositions are useful for the treatment of, for example, pain, solid tumors and/or obesity.

First claim

We claim:

1. A compound of Formula (I):

wherein:
R 1 is optionally substituted phenyl;
R 2 is phenyl optionally substituted with one or more groups independently selected from alkyl, —O— alkyl, alkenyl, alkynyl, halo, fluoroalkyl, cyano, nitro, aryl, —O-aryl, aralkyl, —O-aralkyl, carbocyclyl, heterocyclyl, heterocyclylalkyl, and heteroaryl;
R 3 is H; and
R 4 is phenyl optionally substituted with one or more groups independently selected from alkyl, halo, and fluoroalkyl;
or a solvate, hydrate, tautomer, N-oxide, or pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, or pharmaceutically acceptable salt thereof, wherein R 4 is phenyl substituted with one or more groups independently selected from alkyl, halo, and fluoroalkyl.

3. The compound of claim 2 , or a solvate, hydrate, tautomer, N-oxide, or pharmaceutically acceptable salt thereof, wherein R 4 is phenyl substituted with one group selected from alkyl, halo, and fluoroalkyl.

4. The compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, or pharmaceutically acceptable salt thereof, wherein R 4 is phenyl substituted with one halo.

5. The compound of claim 2 , or a solvate, hydrate, tautomer, N-oxide, or pharmaceutically acceptable salt thereof, wherein R 2 is phenyl optionally substituted with one or two groups independently selected from alkyl, —O-alkyl, halo, fluoroalkyl, aryl, —O-aryl, aralkyl, —O— aralkyl, heterocyclyl, and heterocyclylalkyl.

6. The compound of claim 5 , or a solvate, hydrate, tautomer, N-oxide, or pharmaceutically acceptable salt thereof, wherein R 2 is phenyl substituted with one or two groups independently selected from alkyl, halo, and fluoroalkyl.

7. The compound of claim 6 , or a solvate, hydrate, tautomer, N-oxide, or pharmaceutically acceptable salt thereof, wherein R 2 is phenyl substituted with one halo.

8. The compound of claim 6 , or a solvate, hydrate, tautomer, N-oxide, or pharmaceutically acceptable salt thereof, wherein R 1 is phenyl optionally substituted with one or more groups independently selected from alkyl, halo, and fluoroalkyl.

9. The compound of claim 6 , or a solvate, hydrate, tautomer, N-oxide, or pharmaceutically acceptable salt thereof, wherein R 1 is phenyl substituted with one or more groups independently selected from alkyl, halo, and fluoroalkyl.

10. The compound of claim 6 , or a solvate, hydrate, tautomer, N-oxide, or pharmaceutically acceptable salt thereof, wherein R 1 is phenyl substituted with one or two groups independently selected from alkyl, halo, and fluoroalkyl.

11. The compound of claim 6 , or a solvate, hydrate, tautomer, N-oxide, or pharmaceutically acceptable salt thereof, wherein R 1 is phenyl substituted with one group selected from alkyl, halo, and fluoroalkyl.

12. The compound of claim 6 , or a solvate, hydrate, tautomer, N-oxide, or pharmaceutically acceptable salt thereof, wherein R 1 is unsubstituted phenyl.

13. The compound of claim 1 selected from:

or a solvate, hydrate, tautomer, N-oxide, or pharmaceutically acceptable salt thereof.

14. A pharmaceutical composition comprising a compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

15. A method of therapeutically treating a disorder selected from the group consisting of a solid tumor cancer, obesity, Down's syndrome, Alzheimer's disease, and inflammation, in a patient in need thereof, comprising administering a therapeutically effective amount of a compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, or a pharmaceutically acceptable salt thereof, to the patient.

16. A method of therapeutically treating pain in a patient in need thereof, comprising administering a therapeutically effective amount of a compound of claim 1 , or a solvate, hydrate, tautomer, N-oxide, or a pharmaceutically acceptable salt thereof, to the patient.

Assignees

• Abide Therapeutics Inc
• Scripps Research Inst

Inventors

• Boger Dale L
• Otrubova Katerina
• Cisar Justin S
• Grice Cheryl A
• Jones Todd K

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• C07D231/16

  Halogen atoms or nitro radicals · CPC title

• C07D231/14 Primary

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title

• C07D401/12

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