Multitarget FAAH and COX inhibitors and therapeutical uses thereof

Patent metadata

Field	Value
Publication number	US-9630914-B2
Application number	US-201314420237-A
Country	US
Kind code	B2
Filing date	Aug 1, 2013
Priority date	Aug 6, 2012
Publication date	Apr 25, 2017
Grant date	Apr 25, 2017

Abstract

Multitarget inhibitors of the enzymes Fatty Acid Amide Hydrolase (FAAH), Cyclooxygenase-1 (COX-1) and/or Cyclooxygenase-2 (COX-2) having a specific carbamate moiety on the meta or ortho position of the A ring of a substituted biphenyl core and having an halogen in the ortho position of the B ring of the biphenyl core. Also concerns the therapeutical application of the multitarget inhibitors, in particular, in the prevention and treatment of cancer.

First claim

What is claimed is:

1. A compound that simultaneously inhibits the enzymes Fatty Acid Amide Hydrolase (FAAH), Cyclooxygenase-1 (COX-1) and/or Cyclooxygenase-2 (COX-2) having the formula (la)

or pharmaceutically acceptable salts thereof,
wherein
the phenyl ring A is substituted in the meta or ortho position with the carbamoyl group,
R 1 is halogen,
R 2 is a group —CHR 5 —(C═O)—R 6
wherein R 5 is (C 1 -C 6 )_alkyl, and R 6 is —OH, and R 3 and R 4 are independently selected from a group consisting of H, (C 1 -C 10 ) _alkyl, (C 3 -C 9 ) cycloalkyl (C 0 -C 4 ) alkyl, phenyl (C 0 -C 4 ) alkyl, phenyl and (C 3 -C 9 )_cycloalkyl.

2. A compound according to claim 1 , wherein R 1 is F and R 2 is
a group —CHR 5 —(C═O)—R 6 , wherein R 5 is (C 1 -C 6 )_alkyl, and R 6 is —OH.

3. A compound according to claim 1 , wherein R 3 and R 4 are independently selected from a group consisting of (C 1 -C 10 )_alkyl, (C 3 -C 9 ) cycloalkyl_(C 0 -C 4 )_alkyl, and phenyl (C 0 -C 4 )_alkyl.

4. A compound according to claim 1 , wherein
R 3 is H, and
R 4 is (C 1 -C 10 ) alkyl, (C 3 -C 9 ) cycloalkyl (C 0 -C 4 ) alkyl, or phenyl (C 0 -C 4 ) alkyl.

5. A compound according to claim 1 , wherein
R 1 is F; R 2 is —CHR 5 —(C═O)—R 6 wherein R 5 is CH 3 , R 6 is OH,
R 3 is H, and
R 4 is (C 1 -C 10 ) alkyl, (C 3 -C 9 ) cycloalkyl (C 0 -C 4 )_alkyl, or phenyl (C 0 -C 4 )alkyl.

6. A pharmaceutical composition comprising a compound of formula (la) or a pharmaceutically acceptable salt thereof of claim 1 and a pharmaceutical acceptable carrier and/or excipient.

Assignees

• Fond St Italiano Tecnologia
• Univ California
• Alma Mater Studiorum—Universita' di Bologna

Inventors

• De Vivo Marco
• Scarpelli Rita
• Cavalli Andrea
• Migliore Marco
• Piomelli Daniele
• Habrant Damien
• Favia Angelo

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P5/38

  of the suprarenal hormones · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title