Carbamate compounds and methods of making and using same

Patent metadata

Field	Value
Publication number	US-9957242-B2
Application number	US-201615272313-A
Country	US
Kind code	B2
Filing date	Sep 21, 2016
Priority date	Jan 6, 2012
Publication date	May 1, 2018
Grant date	May 1, 2018

Abstract

This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition.

First claim

What is claimed is:

1. A compound represented by:

wherein
L 3 is —CH 2 —;
R 7 is

R i and R j are independently selected from the group consisting of: H, halogen, CH 3 , C 2-6 alkyl (optionally substituted by one, two, or three moieties independently selected from R c ), and phenyl (optionally substituted by one, two, or three moieties independently selected from R c );
R i2 and R j2 are independently selected from the group consisting of: H, halogen, CH 3 , C 2-6 alkyl (optionally substituted by one, two, or three halogens), and phenyl (optionally substituted by one, two, or three moieties independently selected from R c ); and
R c is selected from the group consisting of halogen, C 1-6 alkyl (optionally substituted by one, two, or three halogens), and C 1-6 alkoxy;

or a pharmaceutically acceptable salt or stereoisomer thereof.

2. The compound of claim 1 , represented by a formula selected from the group consisting of:

3. The compound of claim 2 , represented by:

4. The compound of claim 2 , represented by:

5. The compound of claim 2 , represented by:

6. A compound selected from the group consisting of:
1,1,1,3,3,3-hexafluoropropan-2-yl 4-((5-(4-methoxyphenyl)isoxazol-3-yl)methyl)piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-((5-phenylisoxazol-3-yl)methyl)piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-((3-methyl-1-phenyl-1H-pyrazol-4-yl)methyl)piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-((1-methyl-3-phenyl-1H-pyrazol-5-yl)methyl)piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-((1-methyl-3-phenyl-1H-pyrazol-4-yl)methyl)piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-((4-bromo-1-methyl-1H-pyrazol-5-yl)methyl)piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[3-(2-chlorophenyl)-1-methyl-1H-pyrazol-4-yl]methyl]piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[3-phenyl-1-(propan-2-yl)-1H-pyrazol-4-yl]methyl]piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[3-(2-chlorophenyl)-1-(propan-2-yl)-1H-pyrazol-4-yl]methyl]piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[2-methyl-6-(2-methylphenyl)pyridin-3-yl]methyl]piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[6-(2-fluorophenyl)-2-methylpyridin-3-yl]methyl]piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[2-methyl-6-(3-methylphenyl)pyridin-3-yl]methyl]piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[6-(3-fluorophenyl)-2-methylpyridin-3-yl]methyl]piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[6-methyl-5-(2-methylphenyl)pyridin-2-yl]methyl]piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[5-(3-fluorophenyl)pyridin-2-yl]methyl]piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[5-(2-fluorophenyl)-6-methylpyridin-2-yl]methyl]piperazine-1-carboxylate,
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[5-(3-fluorophenyl)-6-methylpyridin-2-yl]methyl]piperazine-1-carboxylate,
and
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[6-methyl-5-(3-methylphenyl)pyridin-2-yl]methyl]piperazine-1-carboxylate;
or a pharmaceutically acceptable salt thereof.

7. A pharmaceutically acceptable composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

8. A method of treating pain in a patient in need thereof, comprising administering to the patient in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

9. A pharmaceutically acceptable composition comprising a compound of claim 6 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

10. A method of treating pain in a patient in need thereof, comprising administering to the patient in need thereof an effective amount of a compound of claim 6 , or a pharmaceutically acceptable salt thereof.

Assignees

• Abide Therapeutics Inc
• Scripps Research Inst

Inventors

• Cisar Justin S
• Grice Cheryl A
• Jones Todd K
• Niphakis Micah J
• Chang Jae Won
• Lum Kenneth M
• Cravatt Benjamin F

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · 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

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title