Substituted benzoxazoles

Patent metadata

Field	Value
Publication number	US-9493472-B2
Application number	US-201414895793-A
Country	US
Kind code	B2
Filing date	May 30, 2014
Priority date	Jun 3, 2013
Publication date	Nov 15, 2016
Grant date	Nov 15, 2016

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

The invention claimed is:

1. A 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. The compound of 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. The compound of 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. The compound of 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. The compound of 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

• Allerheiligen Swen
• Buchmüller Anja
• Engel Karen
• Gerdes Christoph
• Gericke Kersten Matthias
• Gerisch Michael
• Heitmeier Stefan
• Hillisch 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

• A61P9/02

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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61K31/495

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title