NEW DIAZASPIROCYCLOALKANE AND AZASPIROCYCLOALKANE

• US 20170029425A1
• Filed: 10/13/2016
• Published: 02/02/2017
• Est. Priority Date: 06/13/2012
• Status: Active Grant

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Hunziker, Daniel, Mattei, Patrizio, Mauser, Harald, Prunotto, Marco, Ullmer, Christoph
• Granted Patent: US 10,633,384 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07D 205/12 condensed with carbocyclic rings or ring systems
• CPC Class Codes: C07D 249/18 Benzotriazoles
• CPC Class Codes: C07D 401/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 471/10 Spiro-condensed systems
• CPC Class Codes: C07D 487/10 Spiro-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

Compounds having the general formula (I)

wherein R¹, R², Y and W are as described herein, compositions including the compounds and methods of using the compounds as autotaxin inhibitors.

Claims

1. A compound of formula (I)

2. The compound of claim 1, wherein R¹ is substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylcycloalkyl, substituted phenylalkenyl, substituted phenylalkynyl, substituted pyridinylalkyl, substituted thiophenylalkyl, substituted 2,3-dihydro-1H-isoindol-2-yl, substituted 1H-indol-2-yl or substituted benzofuran-2-yl, wherein substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylcycloalkyl, substituted phenylalkenyl, substituted pyridinylalkyl, substituted thiophenylalkyl, substituted 2,3-dihydro-1H-isoindol-2-yl, substituted 1H-indol-2-yl and substituted benzofuran-2-yl are substituted with R⁸, R⁹ and R¹⁰.

3. The compound of claim 1, wherein R¹ is substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylcycloalkyl or substituted phenylalkenyl, wherein substituted phenyl, substituted phenylalkyl, substituted phenoxyalkyl, substituted phenylcycloalkyl and substituted phenylalkenyl are substituted with R⁸, R⁹ and R¹⁰.

4. The compound of claim 1, wherein R¹ is phenylalkyl substituted with R⁸, R⁹ and R¹⁰.

5. The compound of claim 1, wherein R² is —

C(O)—

R³.

6. The compound of claim 1, wherein Y is —

OC(O)—

or —

C(O)—

, wherein in case R¹ is substituted phenylalkenyl, substituted pyridinylalkenyl or substituted thiophenylalkenyl, then Y is not —

OC(O)—

.

7. The compound of claim 1, wherein Y is —

OC(O)— and

R¹ is not substituted phenylalkenyl, substituted pyridinylalkenyl or substituted thiophenylalkenyl.

8. The compound of claim 1, wherein W is selected from one of the ring systems A, C, D, H, I, J, L, M, N, O, Q and R.

9. The compound of claim 1, wherein W is the ring system A.

10. The compound of claim 1, wherein R³ is substituted phenyl, substituted pyridinyl or substituted thiophenyl, wherein substituted phenyl, substituted pyridinyl and substituted thiophenyl are substituted with R¹¹, R¹² and R¹³.

11. The compound of claim 1, wherein R⁸ is haloalkoxy, halogen or alkylsulfonyl.

12. The compound of claim 1, wherein R⁹ is alkyl, haloalkyl or halogen.

13. The compound of claim 1, wherein R¹⁰ is H.

14. A process to prepare a compound of claim 1 comprising

a) the reaction of a compound of formula (II) in the presence of a compound of formula (III);

15. A pharmaceutical composition comprising a compound of claim 1 and a therapeutically inert carrier.

16. A method for the treatment or prophylaxis a renal condition selected from the group consisting of renal conditions, liver conditions, inflammatory conditions, conditions of the nervous system, fibrotic diseases and acute and chronic organ transplant—

rejection, which method comprises administering an effective amount of a compound of claim 1.