Piperidine derivatives

Patent metadata

Field	Value
Publication number	US-10172843-B2
Application number	US-201715612123-A
Country	US
Kind code	B2
Filing date	Jun 2, 2017
Priority date	Dec 2, 2014
Publication date	Jan 8, 2019
Grant date	Jan 8, 2019

Abstract

The invention relates to a compound of formula (I)

wherein A 1 , A 2 and R 1 to R 3 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

First claim

The invention claimed is:

1. A compound of formula (I)

wherein
R 1 is haloalkylsulfonyl, haloalkyl, alkylsulfonyl, phenylalkylsulfonyl, halogen or alkyl;
R 2 is hydrogen or halogen;
R 3 is hydrogen or halogen;
A 1 is 1H-imidazolyl optionally substituted with one or two substituents independently selected from alkyl, phenyl, phenylalkyl and alkoxyalkyl; and
A 2 is heterocyclyl or substituted heterocyclyl, wherein heterocyclyl is oxodihydroquinazolinyl, oxodihydrobenzoimidazolyl, 1H-pyrrolopyridine, oxodihydroindolyl, benzoimidazol-1-yl, 3-oxo-4H-benzo[1,4]oxazinyl, oxo-1H-imidazolyl, benzo[d]isoxazolyl, oxo-4H-[1,2,4]triazolyl, oxo-5H-imidazopyridinyl or oxopiperidinyl and wherein substituted heterocyclyl is heterocyclyl substituted with one or two substituents independently selected from alkyl, halogen, alkoxycarbonylalkyl, alkoxyalkyl, pyrrolidinyl, hydroxyalkyl, alkylcarbonyloxyalkyl, alkylsulfonylalkyl, morpholinyl, aminocarbonylalkyl, alkylaminocarbonylalkyl, alkylpiperazinyl, halophenyl and carboxyalkyl;
or a pharmaceutically acceptable salt or ester thereof.

2. A compound according to claim 1 , or a pharmaceutically acceptable salt or ester thereof, wherein R 1 is haloalkylsulfonyl, haloalkyl or alkylsulfonyl.

3. A compound according to claim 1 , or a pharmaceutically acceptable salt or ester thereof, wherein R 1 is trifluoromethylsulfonyl, trifluoromethyl or methylsulfonyl.

4. A compound according to claim 1 , or a pharmaceutically acceptable salt or ester thereof, wherein R 2 is hydrogen or chloro.

5. A compound according to claim 1 , or a pharmaceutically acceptable salt or ester thereof, wherein R 3 is hydrogen.

6. A compound according to claim 1 , or a pharmaceutically acceptable salt or ester thereof, wherein A 1 is alkyl-1H-imidazolyl or dialkyl-1H-imidazolyl.

7. A compound according to claim 1 , or a pharmaceutically acceptable salt or ester thereof, wherein A 1 is methyl-1H-imidazolyl, propyl-1H-imidazolyl or dimethyl-1H-imidazolyl.

8. A compound according to claim 1 , or a pharmaceutically acceptable salt or ester thereof, wherein A 2 is oxodihydroquinazolinyl, alkyloxodihydrobenzoimidazolyl, (alkylpyrrolidinyl)oxodihydrobenzoimidazolyl or 1H-pyrrolopyridine.

9. A compound according to claim 1 , or a pharmaceutically acceptable salt or ester thereof, wherein A 2 is oxodihydroquinazolinyl, methyloxodihydrobenzoimidazolyl, (methylpyrrolidinyl)oxodihydrobenzoimidazolyl or 1H-pyrrolopyridine.

10. A compound according to claim 1 selected from
3-{1-[5-Methyl-2-(4-trifluoromethanesulfonyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one;
1-Methyl-3-{1-[5-methyl-2-(4-trifluoromethanesulfonyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one;
3-{1-[2-(3-Chloro-4-trifluoromethyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one;
3-{1-[1,5-Dimethyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one;
3-{1-[2-(4-Methanesulfonyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one
3-{1-[5-Methyl-2-(4-phenylmethanesulfonyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one;
3-{1-[2-(3-Chloro-4-trifluoromethyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-7-fluoro-3,4-dihydro-1H-quinazolin-2-one;
(6-Chloro-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-acetic acid methyl ester;
1-(2-Methoxy-ethyl)-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one;
1-Methyl-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one;
3-{1-[2-(3-Fluoro-4-trifluoromethyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one;
5-Chloro-3-ethyl-1-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one;
3-{1-[5-Methyl-2-(4-trifluoromethanesulfonyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1H-pyrrolo [3,2-c]pyridine;
1-Methyl-3-{1-[5-methyl-2-(4-phenylmethanesulfonyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one;
1-{1-[2-(4-Methanesulfonyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3-methyl-1,3-dihydro-benzoimidazol-2-one;
7-Fluoro-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one;
1-{1-[5-Methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-6-pyrrolidin-1-yl-1,3-dihydro-benzoimidazol-2-one;
3-{1-[5-Methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one;
5-Chloro-3-methyl-1-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one;
6-Bromo-3-[1-[[2-[4(trifluoromethyl)phenyl]-1H-imidazol-5-yl]methyl]-4-piperidyl]-1,4-dihydroquinazolin-2-one;
5-Chloro-3-(2-methoxy-ethyl)-1-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one;
3-{1-[5-Benzyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one
5-Chloro-3-(2-hydroxy-ethyl)-1-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one;
1-{1-[2-(3-Chloro-4-trifluoromethyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3-methyl-1,3-dihydro-benzoimidazol-2-one;
5-Chloro-1-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one;
1-{1-[1,5-Dimethyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3-methyl-1,3-dihydro-benzoimidazol-2-one;
5-Chloro-3-(2-methanesulfonyl-ethyl)-1-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one;
Acetic acid 2-(6-chloro-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-ethyl ester;
1-Methyl-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1,3-dihydro-benzoimidazol-2-one;
3-{1-[2-(2-Chloro-4-trifluoromethyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one;
1-{1-[5-Methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-6-morpholin-4-yl-1,3-dihydro-benzoimidazol-2-one;
3-{1-[2-(3,4-Dichloro-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one;
3-{1-[5-Propyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one;
3-{1-[2-(3-Chloro-4-trifluoromethyl-phenyl)-5-methyl-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-1H-pyrrolo [2,3-b]pyridine;
2-(6-Chloro-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-acetamide;
3-{1-[1-(2-Methoxy-ethyl)-5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one;
2-(6-Chloro-3-{1-[5-methyl-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-N-methyl-acetamide;
3-{1-[5-(2-Methoxy-ethyl)-2-(4-trifluoromethyl-phenyl)-1H-imidazol-4-ylmethyl]-piperidin-4-yl}-3,4-dihydro-1H-quinazolin-2-one;
1-{1-[2-(3-Fluoro-4-trifluoromethyl-phenyl)-5-methyl-1H-

Assignees

• Hoffmann La Roche

Inventors

• Haap Wolfgang
• Kuehne Holger
• Mauser Harald

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P5/00

  Drugs for disorders of the endocrine system · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title