Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-04-23
2002-09-17
Chang, Ceila (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C544S333000
Reexamination Certificate
active
06451805
ABSTRACT:
The present invention relates to new substituted pyrazole derivatives, processes for their preparation and their use as medicaments, in particular as medicaments for the treatment of cardiovascular disorders.
It has already been disclosed that 1-benzyl-3-(substituted heteroaryl)-fused pyrazole derivatives inhibit platelet aggregation (cf. EP 667 345 A1).
The present invention relates to new substituted pyrazole derivatives of the general formula (I)
in which
R
1
represents a saturated or aromatic 5- or 6-membered heterocycle having up to 3 heteroatoms from the group consisting of S, N and/or O, which can be bonded via a nitrogen atom and which is optionally substituted up to 3 times identically or differently by amino, azido, formyl, mercaptyl, carboxyl, hydroxyl, straight-chain or branched acyl, alkoxy, alkylthio or alkoxycarbonyl each having up to 6 carbon atoms, nitro, cyano, halogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms, which for its part can be substituted by hydroxyl, amino, azido, carboxyl, straight-chain or branched acyl. alkoxy, alkoxycarbonyl or acylamino each having up to 5 carbon atoms or by a radical of the formula —OR
4
,
in which
R
4
denotes straight-chain or branched acyl having up to 5 carbon atoms or a group of the formula —SiR
5
R
6
R
7
,
in which
R
5
, R
6
and R
7
are identical or different and denote aryl having 6 to 10 carbon atoms or alkyl having up to 6 carbon atoms,
and/or is substituted by a radical of the formula
—S(O)
c
—NR
9
R
10
,
in which
a, b and b′ are identical or different and denote a number 0, 1, 2 or 3,
R
8
denotes hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms,
c denotes a number 1 or 2 and
R
9
and R
10
are identical or different and denote hydrogen or straight-chain or branched alkyl having up to 10 carbon atoms, which can optionally be substituted by cycloalkyl having 3 to 8 carbon atoms or by aryl having 6 to 10 carbon atoms, which for its part can be substituted by halogen, or
denote aryl having 6 to 10 carbon atoms, which is optionally substituted by halogen, or
denote cycloalkyl having 3 to 7 carbon atoms, or
R
9
and R
10
, together with the nitrogen atom, form a 5- to 7-membered saturated heterocycle which can optionally contain a further oxygen atom or a radical —NR
11
, in which
R
11
denotes hydrogen, straight-chain or branched alkyl having up to 4 carbon atoms or a radical of the formula
or denotes benzyl or phenyl, where the ring systems are optionally substituted by halogen,
R
2
and R
3
, including the double bond, form a 6-membered saturated or aromatic heterocycle having up to 3 heteroatoms from the group consisting of N. S and/or O, which is optionally substituted up to 3 times identically or differently by formyl, carboxyl, hydroxyl, mercaptyl, straight-chain or branched acyl, alkylthio or alkoxycarbonyl each having up to 6 carbon atoms, nitro, cyano, halogen or straight-chain or branched alkyl or alkoxy each having up to 6 carbon atoms, which for its part can be substituted by hydroxyl, amino. carboxyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl each having up to 5 carbon atoms,
and/or the heterocycle is optionally substituted by a group of the formula —NR
12
R
13
or —S(O)
c′
NR
9′
R
10′
, in which
R
12
and R
13
are identical or different and denote hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms, or
R
12
denotes hydrogen and
R
13
denotes formyl
c′, R
9′
and R
10′
have the meaning of c, R
9
and R
10
indicated above and are identical to or different from these
and/or the heterocycle is optionally substituted by phenyl which for its part can be substituted up to 2 times identically or differently by halogen or by straight-chain or branched alkyl or alkoxy each having up to 6 carbon atoms
and/or the heterocycle is optionally substituted by a group of the formula —N═CH—NR
14
R
15
, in which
R
14
and R
15
are identical or different and denote hydrogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms,
A represents a 5- or 6-membered aromatic or saturated heterocycle having up to 3 heteroatoms from the group consisting of S, N and/or O or phenyl, each of which is optionally substituted up to 3 times identically or differently by amino. mercaptyl, hydroxyl, formyl, carboxyl, straight-chain or branched acyl, alkylthio, alkyloxyacyl, alkoxy or alkoxycarbonyl each having up to 6 carbon atoms, nitro, cyano, trifluoromethyl, azido, halogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms, which for its part can be substituted by hydroxyl, carboxyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl each having up to 5 carbon atoms,
and/or is substituted by a group of the formula —(CO)
d
—NR
16
R
17
,
in which
d denotes a number 0 or 1,
R
16
and R
17
are identical or different and
denote hydrogen, phenyl, benzyl or straight-chain or branched alkyl or acyl each having up to 5 carbon atoms,
and their isomeric forms and salts.
The compounds of the general formula (I) according to the invention can also be present in the form of their salts. In general, salts with organic or inorganic bases or acids may be mentioned here.
In the context of the present invention, physiologically acceptable salts are preferred. Phvsiologically acceptable salts of the compounds according to the invention can be salts of the substances according to the invention with mineral acids, carboxylic acids or sulphonic acids. Particularly preferred salts are, for example, those with hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, ethanesulphonic acid, toluenesulphonic acid, benzenesulphonic acid naphthalenedisulphonic acid, acetic acid, propionic acid, lactic acid, tartaric acid, citric acid, fumaric acid, maleic acid or benzoic acid.
Physiologically acceptable salts can also be metal or ammonium salts of the compounds according to the invention which have a free carboxyl group. Those particularly preferred are, for example, sodium, potassium, magnesium or calcium salts, and also ammonium salts which are derived from ammonia, or organic amines such as, for example, ethylamine, di- or triethylamine, di- or triethanolamine, dicyclohexylamine, dimethylaminoethanol, arginine, lysine or ethylenediamine.
The compounds according to the invention can exist in stereoisomeric forms which either behave as image and mirror image (enantiomers), or which do not behave as image and mirror image (diastereomers). The invention relates both to the enantiomers or diastereomers and their respective mixtures. Like the diastereomers, the racemic forms can also be separated into the stereoisomerically uniform constituents in a known manner.
Heterocycle in the context of the invention, depending on the abovementioned substituents, in general represents a saturated or aromatic 5- or 6-membered heterocycle which can contain up to 3 heteroatoms from the group consisting of S, N and/or O and which in the case of a nitrogen atom can also be bonded via this. Examples which may be mentioned are: oxadiazolyl, thiadiazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyridazinyl. pyrazinyl, thienyl, furyl, pyrrolyl, tetrahydropyranyl, tetrahydroturanyl, 12,3-triazolyl, thiazolyl, oxazolyl, imidazolyl, morpholinyl or piperidyl. Thiazolyl, furyl, oxazolyl, pyrazolyl triazolyl, pyridyl, pyrimidinyl, pyridazinyl and tetrahydropyranyl are preferred.
Preferred compounds of the general formula (I) according to the invention are those
in which
R
1
represents pyrimidinyl, pyridazinyl, pyridyl, pyrazinyl, tetrahydropyranyl, tetrahydrofuranyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, 1.2.3-triazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, isoxazolyl, isothiazolyl, pyranyl or morpholinyl, each of which is optionally substituted up to 3 times identically or differently by amino, formyl, mercaptyl, carboxyl, hydroxyl, straight-chain or branched acyl, alkoxy, alkylthio or alkoxycarbonyl
Dembowsky Klaus
Feurer Achim
Fürstner Chantal
Hütter Joachim
Jaetsch Thomas
Bayer Aktiengesellschaft
Chang Ceila
Norris & McLaughlin & Marcus
Wright Sonya
LandOfFree
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