Diazaspirocycloalkane and azaspirocycloalkane

Patent metadata

Field	Value
Publication number	US-10633384-B2
Application number	US-201615293080-A
Country	US
Kind code	B2
Filing date	Oct 13, 2016
Priority date	Jun 13, 2012
Publication date	Apr 28, 2020
Grant date	Apr 28, 2020

Abstract

Compounds having the general formula (I)

wherein R 1 , R 2 , Y and W are as described herein, compositions including the compounds and methods of using the compounds as autotaxin inhibitors.

First claim

The invention claimed is:

1. A compound of formula (I)

wherein
R 1 is phenylalkyl or phenylalkenyl, each substituted with R 8 , R 9 and R 10 ;
R 2 is —(CR 4 R 5 ) n —R 3 , —C(O)—R 3 or —S(O) 2 —R 3 ;
Y is —OC(O)—;
W is selected from

R 3 is

R 4 and R 5 are each H;
R 7 is H;
R 8 , R 9 , and R 10 are independently selected from H, alkyl, hydroxyalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkoxy, cycloalkoxy, cycloalkoxyalkyl, cycloalkylalkoxyalkyl, alkoxy, alkoxyalkyl, haloalkoxy, haloalkoxyalkyl, alkoxyalkoxy, alkoxyalkoxyalkyl, halogen, hydroxy, cyano, alkylsulfonyl, cycloalkylsulfonyl, substituted aminosulfonyl, substituted amino and substituted aminoalkyl, wherein substituted aminosulfonyl, substituted amino and substituted aminoalkyl are substituted on the nitrogen atom with one to two substituents independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl and cycloalkylcarbonyl; and
n is zero or 1;
or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is phenylalkyl substituted with R 8 , R 9 and R 10 .

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is —C(O)—R 3 .

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein W is selected from

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein W is

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 8 is haloalkoxy, halogen or alkylsulfonyl.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 9 is alkyl, haloalkyl or halogen.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 10 is H.

9. A process to prepare a compound of claim 1 , or a pharmaceutically acceptable salt thereof, comprising:
a) the reaction of a compound of formula (II) in the presence of a compound of formula (III);

or
b) the reaction of a compound of formula (IV) in the presence of a compound of formula (V);

wherein in step b) R 2 is —C(O)—R 3 .

10. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

11. A method for inhibiting ATX which are inhibitors of LPA production which method comprises administering an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

12. The compound of claim 1 , selected from:

or a pharmaceutically acceptable salt thereof.

Assignees

• Hoffmann La Roche

Inventors

• Hunziker Daniel
• Mattei Patrizio
• Mauser Harald
• Prunotto Marco
• Ullmer Christoph

Classifications

• C07D401/12

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

• C07D249/18

  Benzotriazoles · CPC title

• C07D403/12 Primary

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

• C07D405/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D401/10

  linked by a carbon chain containing aromatic rings · CPC title