Carbamate compounds and of making and using same

Patent metadata

Field	Value
Publication number	US-9487495-B2
Application number	US-201314369982-A
Country	US
Kind code	B2
Filing date	Jan 7, 2013
Priority date	Jan 6, 2012
Publication date	Nov 8, 2016
Grant date	Nov 8, 2016

Abstract

This disclosure provides compounds having the structure:

wherein L 3 , R 7 , R d and p are defined herein, which are modulators of MAGL and/or ABHD6. Further provided is the use of these compounds as medicinal agents, processes for their preparation, and pharmaceutical compositions that include the disclosed compounds. The disclosure also provides a 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
R a and R b together with the nitrogen to which they are attached, form a 4-6 membered heterocyclic ring which may have an additional heteroatom selected from O, S, and N; wherein the 4-6 membered heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, C 1-6 alkyl, —S(O) w —C 1-6 alkyl (where w is 0, 1 or 2), hydroxyl, —C(O)—C 1-6 alkyl, —NH 2 , and —NH—C(O)—C 1-6 alkyl;
L 3 is C 1 -C 6 alkylene, wherein C 1 -C 6 alkylene is substituted by an additional R 7 ;
R 7 is selected from the group consisting of:

wherein R 7 is optionally substituted by one, two, three or four moieties independently selected from R h ;
R e is selected from the group consisting of H and C 1-6 alkyl (optionally substituted by one, two or three halogens); and
R h is selected from the group consisting of: halogen, C 1-6 alkyl (optionally substituted by one, two or three halogens), C 1-6 alkoxy (optionally substituted by one, two or three halogens), and R a R b N—;

or a pharmaceutically acceptable salt or stereoisomer thereof.

2. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt or stereoisomer thereof.

3. A compound selected from the group consisting of:
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[bis(4-chlorophenyl)methyl]-3-methylpiperazine-1-carboxylate;
1,1,1,3,3,3-hexafluoropropan-2-yl 4-(bis(oxazol-4-yl)methyl)piperazine-1-carboxylate;
1,1,1,3,3,3-hexafluoropropan-2-yl 4-(bis(4-chloro-2-methylphenyl)methyl)piperazine-1-carboxylate;
1,1,1,3,3,3-hexafluoropropan-2-yl 4-(bis(1-methyl-1H-indazol-5-yl)methyl)piperazine-1-carboxylate; and
1,1,1,3,3,3-hexafluoropropan-2-yl 4-(di(pyridin-3-yl)methyl)piperazine-1-carboxylate;

or a pharmaceutically acceptable salt or stereoisomer thereof.

4. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 7 is optionally substituted on a free carbon by one, two, or three substituents independently selected from R h , and each R h is independently selected from the group consisting of halogen and C 1-6 alkyl (optionally substituted by one, two or three halogens).

5. The compound of claim 4 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 7 is substituted on a free carbon by one, two, or three substituents independently selected from R h , and each R h is independently selected from the group consisting of halogen, and C 1-6 alkyl (optionally substituted by one, two or three halogens).

6. The compound of claim 4 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 7 is

and R 7 is substituted by one or two substituents independently selected from R h , and each R h is independently selected from the group consisting of halogen and C 1-6 alkyl (optionally substituted by one, two or three halogens).

7. The compound of claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 7 is unsubstituted.

8. A pharmaceutically acceptable composition comprising a compound of any one of claims 1 , 2 , 3 , and 4 - 7 , or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable excipient.

9. A method of treating pain, comprising administering to a patient in need thereof an effective amount of a compound of any one of claims 1 , 2 , 3 , and 4 - 7 , or a pharmaceutically acceptable salt or stereoisomer thereof.

Assignees

• Abide Therapeutics Inc
• Scripps Research Inst
• The Scripts Res Inst
• Abide Therapeutics

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

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · 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

• A61P29/00

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