Autotaxin inhibitors

Patent metadata

Field	Value
Publication number	US-9630945-B2
Application number	US-201314653649-A
Country	US
Kind code	B2
Filing date	Dec 17, 2013
Priority date	Dec 19, 2012
Publication date	Apr 25, 2017
Grant date	Apr 25, 2017

Abstract

The present invention relates to novel compounds of formula (I) (I) that are autotaxin inhibitors, processes for their preparation, pharmaceutical compositions and medicaments containing them and to their use in the treatment of an ATX-dependent or ATX-mediated disease or condition.

First claim

The invention claimed is:

1. A method of treating a disease or condition mediated by Autotaxin, wherein the disease or condition is selected from fibrosis, pruritus, cirrhosis, cancer, diabetes, kidney diseases, pain, asthma and COPD, in a subject comprising: administering to said subject a therapeutically effective amount of a The compound of formula (IV)

or a pharmaceutically acceptable salt thereof, wherein
A is selected from

Y 1 is —(CH 2 ) m —;
X is C(═O)—NH—;
Y 2 is —(CH 2 ) n —;
m is selected from 2, 3 and 4, and n is selected from 0 and 1;
Y 3 is O—(CH 2 )—,
R 1a , R 1b , R 1c , R 1d and R 1e are defined according to
(a) R 1b and R 1d is chloro and R 1a , R 1c and R 1e are H; or
(b) R 1b is CN; R 1d is CF 3 or OCF 3 ; and R 1a , R 1c and R 1e are H.

2. The method according to claim 1 or pharmaceutically acceptable salt thereof, wherein
m is 3 or 4, and n is 0; and
(b) R 1b is CN; R 1d is CF 3 ; and R 1a , R 1c and R 1e are H.

3. The method according to claim 1 , selected from
3,5-Dichlorobenzyl 4-(4-(1H-1,2,3-triazol-4-yl)butanamido)piperidine-1-carboxylate,
3,5-Dichlorobenzyl 4-(3-(1H-1,2,3-triazol-4-yl)propanamido)piperidine-1-carboxylate,
3,5-Dichlorobenzyl 4-(5-(1H-1,2,3-triazol-4-yl)pentanamido)piperidine-1-carboxylate,
3,5-Dichlorobenzyl 4-((4-(1H-1,2,3-triazol-5-yl)butanamido)methyl)piperidine-1-carboxylate,
3,5-Dichlorobenzyl 4-((3-(1H-1,2,3-triazol-5-yl)propanamido)methyl)piperidine-1-carboxylate,
3,5-Dichlorophenethyl 4-(4-(1H-1,2,3-triazol-4-yl)butanamido)piperidine-1-carboxylate,
3,5-Dichlorobenzyl 4-(2-((2-(1H-1,2,3-triazol-4-yl)ethyl)amino)-2-oxoethyl)piperidine-1-carboxylate,
3-Cyano-5-(trifluoromethyl)benzyl 4-(4-(1H-1,2,3-triazol-4-yl)butanamido)piperidine-1-carboxylate,
3-Cyano-5-(trifluoromethoxy)benzyl 4-(4-(1H-1,2,3-triazol-4-yl)butanamido)piperidine-1-carboxylate, and
or a pharmaceutically acceptable salt thereof.

4. The method according to claim 1 , wherein the disease or condition is idiopathic pulmonary fibrosis or pruritus.

Assignees

• Furminger Vikki
• Hughes Owen Rhys
• Le Grand Darren Mark
• Stanley Emily
• Thomson Christopher
• Novartis Ag

Inventors

• Furminger Vikki
• Hughes Owen Rhys
• Le Grand Darren Mark
• Stanley Emily
• Thomson Christopher

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• A61P29/00

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

• A61P17/04

  Antipruritics · CPC title