α- and γ-truxillic acid derivatives and pharmaceutical compositions thereof

Patent metadata

Field	Value
Publication number	US-11026910-B2
Application number	US-201916276920-A
Country	US
Kind code	B2
Filing date	Feb 15, 2019
Priority date	Jul 20, 2012
Publication date	Jun 8, 2021
Grant date	Jun 8, 2021

Abstract

The present invention provides a compound, and method of inhibiting the activity of a Fatty Acid Binding Protein (FABP) comprising contacting the FABP with a compound, having the structure:

First claim

What is claimed is:

1. A mixture of compounds having the structure:

wherein the mixture is enantiomerically enriched in a compound having the structure:

wherein
one of R 1 or R 2 is —C(═O)OR 13 ,
wherein R 13 is substituted C 1-10 alkyl, C 2-10 alkenyl or C 2-10 alkynyl; and

the other of R 1 or R 2 is —C(═O)OH,
wherein the substituted C 1-10 alkyl is substituted with halogen, alkoxy, heteroaryloxy, sulfonyl, nitro, mercapto, sulfanyl, cyano, amino, carbamoyl, carboxyl or acyl;

R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and R 12 are each independently, H, halogen, —NO 2 , —CN, —NHR 15 , —OR 15 or CF 3 ;
wherein R 15 is H, C 1-10 alkyl, C 2-10 alkenyl or C 2-10 alkynyl;

or a pharmaceutically acceptable salt thereof.

2. The mixture of claim 1 , wherein the mixture is enriched in a compound having the structure:

wherein
one of R 1 or R 2 is —C(═O)OR 13 ,
wherein R 13 is substituted C 1-10 alkyl, C 2-10 alkenyl or C 2-10 alkynyl; and

the other of R 1 or R 2 is —C(═O) OH,
wherein the substituted C 1-10 alkyl is substituted with halogen, alkoxy, heteroaryloxy, sulfonyl, nitro, mercapto, sulfanyl, cyano, amino, carbamoyl, carboxyl or acyl;

R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and R 12 are each independently, H, halogen, —NO 2 , —CN, —NHR 15 , —OR 15 , CF 3 ;
wherein R 15 is H, C 1-10 alkyl, C 2-10 alkenyl or C 2-10 alkynyl;

or a pharmaceutically acceptable salt thereof.

3. The mixture of claim 1 , wherein the mixture is enriched in a compound having the structure:

wherein
one of R 1 or R 2 is —C(═O)OR 13 ,
wherein R 13 is substituted C 1-10 alkyl, C 2-10 alkenyl or C 2-10 alkynyl; and

the other of R 1 or R 2 is —C(═O) OH,
wherein the substituted C 1-10 alkyl is substituted with halogen, alkoxy, heteroaryloxy, sulfonyl, nitro, mercapto, sulfanyl, cyano, amino, carbamoyl, carboxyl or acyl;

R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and R 12 are each independently, H, halogen, —NO 2 , —CN, —NHR 15 , —OR 15 , CF 3 ;
wherein R 15 is H, C 1-10 alkyl, C 2-10 alkenyl or C 2-10 alkynyl;

or a pharmaceutically acceptable salt thereof.

4. The mixture of claim 1 , wherein the mixture is enriched in a compound having the structure of:

or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition comprising the mixture of claim 1 and a pharmaceutically acceptable carrier.

6. A method of inhibiting the activity of a Fatty Acid Binding Protein (FABP) comprising contacting the FABP with the mixture of claim 1 .

7. The method of claim 6 , wherein the mixture inhibits binding of an FABP ligand to the FABP; or wherein the FABP ligand is an endocannabinoid ligand; or wherein the FABP ligand is anandamide (AEA) or 2-arachidonoylglycerol (2-AG).

Assignees

• Univ New York State Res Found

Inventors

• Ojima Iwao
• Deutsch Dale
• Kaczocha Martin
• Berger William T
• Rizzo Robert
• Balius Trent E

Classifications

• G01N2500/20

  cell-free systems · CPC title

• C07C67/48

  Separation; Purification; Stabilisation; Use of additives · CPC title

• C07B2200/07

  Optical isomers · CPC title

• C07C69/757

  having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, [IMAGE cpc-sch-C07C-0958.gif] groups,[IMAGE cpc-sch-C07C-0959.gif] groups, or[IMAGE cpc-sch-C07C-0960.gif] in the acid moiety · CPC title

• C07C233/11

  with carbon atoms of carboxamide groups bound to carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings · CPC title