Thienomethylpiperazine derivatives as inhibitors of soluble epoxide hydrolase

Patent metadata

Field	Value
Publication number	US-9776991-B2
Application number	US-201415100608-A
Country	US
Kind code	B2
Filing date	Dec 2, 2014
Priority date	Dec 4, 2013
Publication date	Oct 3, 2017
Grant date	Oct 3, 2017

Abstract

The present invention relates to compounds of the formula (I), wherein R1, R2, R3, R4 and X have the meanings indicated in the claims. The compounds of formula I are valuable pharmacologically active compounds. They are highly potent and selective soluble epoxide hydrolase inhibitors and are suitable, for example, for the therapy and prophylaxis of renal failure, diabetic nephropathy, type 2 diabetes mellitus, cardiovascular diseases, inflammatory diseases or could show beneficial effects in pain, dyslipidemia, atherosclerosis wound healing and stroke. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

First claim

The invention claimed is:

1. A compound selected from the group consisting of:
5-[4-((R)-2-Hydroxy-3-methyl-butyryl)-piperazin-1-ylmethyl]-thiophene-2-carboxylic acid (2-methoxy-pyridin-4-ylmethyl)-amide;
5-[4-(2-Hydroxy-propionyl)-piperazin-1-ylmethyl]-thiophene-2-carboxylic acid 2-trifluoromethoxy-benzylamide;
5-[4-(2,4-Dimethyl-6-oxo-6H-pyran-3-carbonyl)-piperazin-1-ylmethyl]-thiophene-2-carboxylic acid 4-chloro-2-fluoro-benzylamide;
5-[4-(1-Amino-cyclopropanecarbonyl)-piperazin-1-ylmethyl]-thiophene-2-carboxylic acid 2-trifluoromethoxy-benzylamide;
5-[4-(2,6-Dimethyl-pyridin-4-yl)-piperazin-1-ylmethyl]-thiophene-2-carboxylic acid 2,4-dichloro-benzylamide;
5-[4-(3,5-Dimethyl-1H-pyrazole-4-carbonyl)-piperazin-1-ylmethyl]-thiophene-2-carboxylic acid (2-methoxy-pyridin-4-ylmethyl)-amide;
5-[4-(3,6-Difluoro-pyridine-2-carbonyl)-piperazin-1-ylmethyl]-thiophene-2-carboxylic acid (2-methoxy-pyridin-4-ylmethyl)-amide; and
2-[4-(2-Dimethylamino-propionyl)-piperazin-1-ylmethyl]-thiazole-5-carboxylic acid 2,4-dichloro-benzylamide,

or a stereoisomeric form thereof, or a physiologically tolerable salt of any of the foregoing.

2. A pharmaceutical composition comprising at least one compound of claim 1 , a stereoisomeric form thereof or a mixture of stereoisomeric forms thereof in any ratio, or a physiologically tolerable salt of any of the foregoing, and a pharmaceutically acceptable carrier.

Assignees

• Sanofi Sa

Inventors

• Mendez-Perez Maria
• Breitschopf Kristin
• Lorenz Katrin
• Strobel Hartmut
• Wang Li-Hsing
• Schiffer Alexander
• Goerlitzer Jochen

Classifications

• A61P9/12

  Antihypertensives · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• C07D333/48

  by oxygen atoms · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D417/12

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