Substituted benzoxazoles

Patent metadata

Field	Value
Publication number	US-2016137647-A1
Application number	US-201414895793-A
Country	US
Kind code	A1
Filing date	May 30, 2014
Priority date	Jun 3, 2013
Publication date	May 19, 2016
Grant date	—

Abstract

The invention relates to substituted benzoxazoles and to processes for their preparation and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular of cardiovascular disorders, preferably of thrombotic or thromboembolic disorders.

First claim

1 . Compound of the formula

in which
R 1 represents a group of the formula

where * is the point of attachment to the carbonyl group,
X represents an oxygen atom, a sulphur atom or CH—R 6 ,
where
R 6 represents hydroxyl,

R 2 represents hydrogen, C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl or phenyl,
where alkyl and cycloalkyl may be substituted by a substituent selected from the group consisting of hydroxy, methoxy, cyano, hydroxycarbonyl, aminocarbonyl, methylsulphonyl, difluoromethoxy and trifluoromethoxy,
or
where alkyl and cycloalkyl may be substituted by 1 to 3 fluorine substituents,

R 3 represents hydrogen or C 1 -C 4 -alkyl,
or
R 2 and R 3 together with the carbon atom to which they are attached form a cyclopropyl ring, cyclobutyl ring or cyclopentyl ring,
where the cyclobutyl ring and the cyclopentyl ring may be substituted by a hydroxyl substituent,

R 4 represents hydrogen or C 1 -C 6 -alkyl,
where alkyl may be substituted by a hydroxyl substituent,

R 5 represents C 1 -C 4 -alkyl,
or
R 4 and R 5 together with the carbon atom to which they are attached form a cyclopropyl ring, cyclobutyl ring or cyclopentyl ring,
where the cyclobutyl ring and the cyclopentyl ring may be substituted by a hydroxyl substituent,

R 7 represents hydrogen or C 1 -C 6 -alkyl,
where alkyl may be substituted by a hydroxyl or cyano substituent,
or
where alkyl may be substituted by 1 to 3 fluorine substituents,

R 8 represents hydrogen,
R 9 represents hydrogen or C 1 -C 6 -alkyl,
where alkyl may be substituted by a hydroxyl or cyano substituent,
or
where alkyl may be substituted by 1 to 3 fluorine substituents,

R 10 represents hydrogen,
R 11 represents C 1 -C 4 -alkyl,
where alkyl may be substituted by a hydroxyl substituent,

R 12 represents hydrogen or C 1 -C 4 -alkyl,
or
R 11 and R 12 together with the carbon atom to which they are attached form a cyclopropyl ring, cyclobutyl ring or cyclopentyl ring,
where the cyclobutyl ring and the cyclopentyl ring may be substituted by a hydroxyl substituent,

R 13 represents hydroxymethyl or hydroxyethyl,
R 14 represents methoxy or ethoxy,

or one of the salts thereof, solvates thereof or solvates of the salts thereof.

2 . Compound according to claim 1 , characterized in that
R 1 represents a group of the formula

where * is the point of attachment to the carbonyl group,
X represents an oxygen atom or CH—R 6 ,
where
R 6 represents hydroxyl,

R 2 represents hydrogen, C 1 -C 4 -alkyl or C 3 -C 6 -cycloalkyl,
where alkyl may be substituted by a hydroxyl or hydroxycarbonyl substituent,
and
where cycloalkyl may be substituted by a hydroxyl substituent,

R 3 represents hydrogen or C 1 -C 4 -alkyl,
or
R 2 and R 3 together with the carbon atom to which they are attached form a cyclobutyl ring,
where the cyclobutyl ring may be substituted by a hydroxyl substituent,

R 4 represents hydrogen or C 1 -C 4 -alkyl,
where alkyl may be substituted by a hydroxyl substituent,

R 5 represents C 1 -C 4 -alkyl,
R 7 represents hydrogen or C 1 -C 4 -alkyl,
R 8 represents hydrogen,
R 9 represents hydrogen or C 1 -C 4 -alkyl,
where alkyl may be substituted by a hydroxyl substituent,

R 10 represents hydrogen,
R 11 and R 12 together with the carbon atom to which they are attached form a cyclobutyl ring,
R 13 represents hydroxymethyl or hydroxyethyl,
R 14 represents methoxy or ethoxy,

or one of the salts thereof, solvates thereof or solvates of the salts thereof.

3 . Compound according to claim 1 , characterized in that
R 1 represents a group of the formula

where * is the point of attachment to the carbonyl group,
X represents an oxygen atom,
R 2 represents methyl, ethyl or cyclobutyl,
where methyl and ethyl are substituted by a hydroxyl substituent,
and
where cyclobutyl is substituted by a hydroxyl substituent,

R 3 represents hydrogen,
R 4 represents hydrogen or methyl,
and
R 5 represents methyl,
or
R 2 represents methyl,
R 3 represents hydrogen or methyl,
R 4 represents methyl, ethyl or propyl,
where methyl, ethyl and propyl are substituted by a hydroxyl substituent,

and
R 5 represents methyl,
or
R 2 and R 3 together with the carbon atom to which they are attached form a cyclobutyl ring,
where the cyclobutyl ring is substituted by a hydroxyl substituent,

R 4 represents hydrogen or methyl,
and
R 5 represents methyl,

or one of the salts thereof, solvates thereof or solvates of the salts thereof.

4 . Compound according to claim 1 , characterized in that
R 1 represents a group of the formula

where * is the point of attachment to the carbonyl group,
X represents an oxygen atom,
R 2 represents methyl or ethyl,
where methyl and ethyl are substituted by a hydroxyl substituent,

R 3 represents hydrogen,
or
R 2 and R 3 together with the carbon atom to which they are attached form a cyclobutyl ring,
where the cyclobutyl ring is substituted by a hydroxyl substituent,

R 4 represents hydrogen or methyl,
R 5 represents methyl,
R 7 represents hydrogen or methyl,
R 8 represents hydrogen,

or one of the salts thereof, solvates thereof or solvates of the salts thereof.

5 . Compound according to claim 1 , characterized in that
R 1 represents a group of the formula

where * is the point of attachment to the carbonyl group,
X represents an oxygen atom,
R 2 represents methyl or ethyl,
where methyl and ethyl are substituted by a hydroxyl substituent,

R 3 represents hydrogen,
or
R 2 and R 3 together with the carbon atom to which they are attached form a cyclobutyl ring,
where the cyclobutyl ring is substituted by a hydroxyl substituent,

R 4 represents hydrogen or methyl,
R 5 represents methyl,

or one of the salts thereof, solvates thereof or solvates of the salts thereof.

6 . (2-{[(1S)-1-(3-Chlorophenyl)-2-fluoroethyl]amino}-7-methoxy-1,3-benzoxazol-5-yl)[(2S,5S)-5-(2-hydroxyethyl)-2-methylmorpholin-4-yl]methanone according to claim 1 of the formula below

or one of the salts thereof, solvates thereof or solvates of the salts thereof.

7 . (2-{[(1S)-1-(3-Chl

Assignees

• Bayer Pharma AG

Inventors

• Allerheillgen Swen
• Buchmüller Anja
• Engel Karen
• Gerdes Christoph
• Gericke Kersten Matthias
• Gerisch Michael
• Heitmeier Stefan
• Hilllsch Alexander
• Kinzel Tom
• Lienau Philip
• Riedl Bernd
• Röhrig Susanne
• Schmidt Martina Victoria
• Strassburger Julia
• Tersteegen Adrian

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

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/02

  Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives · CPC title

• C07D417/06

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