Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
2001-07-31
2003-04-29
McKane, Joseph K. (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
C564S123000, C564S160000
Reexamination Certificate
active
06555580
ABSTRACT:
The invention relates to novel amino- and amido-diphenyl ethers, processes for their preparation and their use in pharmaceuticals, in particular for the indications of arteriosclerosis and hypercholesterolaemia.
European Application 580 550 A (Ciba Geigy; 1994) describes oxamic acid derivatives having cholesterol-lowering properties in mammals. This application describes an in vitro test based on the binding to thyroid hormone cell receptors (so-called T
3
nuclear receptors). The pharmacological property which is stressed is the reduction in plasma cholesterol, in particular LDL cholesterol. Cholesterol-lowering effects are also described in the European Application EP-A-188 351 (SKF; 1986) for certain diphenyl ethers with thyroid hormone-like effects.
It has now been found that the compounds of the general formula (I)
in which
R
1
represents nitro, amino, acetamido or represents a group of the formula —NH—CO—CO—A or —NH—CH
2
—CO—A, in which
A represents hydroxyl or (C
1
-C
4
)-alkoxy,
R
2
and R
3
are identical or different and denote halogen, C
1
-C
4
-alkyl or trifluoromethyl,
R
4
represents a group of the formula
in which
E represents straight-chain or branched (C
1
-C
4
)-alkyl,
R
6
and R
7
are identical or different and, independently of one another, represent straight-chain or branched (C
1
-C
10
)-alkyl which can be substituted one or more times, identically or differently, by (C
3
-C
8
)-cycloalkyl, (C
1
-C
6
)-alkoxy, amino, mono- or di-(C
1
-C
6
)-alkyl amino, (C
1
-C
4
)-alkoxycarbonyl amino, aminocarbonyl, (C
1
-C
6
)-alkoxycarbonyl, or by (C
6
-C
10
)-aryl or 5 to 6-membered saturated or aromatic heterocyclyl with up to three heteroatoms from the series N, O and/or S, where aryl and heterocyclyl in turn are optionally substituted one or more times, identically or differently, by (C
1
-C
4
)-alkyl, aminocarbonyl, (C
1
-C
4
)-alkanoylamino or halogen,
represent (C
6
-C
10
)-aryl or (C
3
-C
8
)-cycloalkyl, each of which can be substituted by (C
1
-C
4
)-alkoxy, or
represent a 4- to 8-membered saturated heterocycle with up to two heteroatoms from the series N, O and/or S, which can be substituted one or more times, identically or differently, by (C
1
-C
4
)-alkoxycarbonyl, oxo or (C
1
-C
4
)-alkyl, or
R
6
and R
7
form, together with the nitrogen atom to which they are bonded, a 4- to 7-membered saturated heterocycle which optionally contains up to two other heteroatoms from the series N, O and/or S,
R
8
represents straight-chain or branched (C
1
-C
10
)-alkyl which can be substituted by (C
3
-C
8
)-cycloalkyl, phenyl or phenoxy, or represents (C
3
-C
8
)-cycloalkyl, (C
6
-C
10
)-aryl, biphenylyl or (C
1
-C
6
)-alkoxy,
R
9
represents straight-chain or branched (C
1
-C
8
)-alkyl whose carbon chain can be interrupted by —O— and which can be substituted by (C
3
-C
8
)-cycloalkyl or phenyl, or represents (C
3
-C
8
)-cycloalkyl, (C
2
-C
6
)-alkenyl, phenyl or pyridyl,
where the aromatic ring systems mentioned both in R
8
and in R
9
can, in each case independently of one another, in turn be substituted by trifluoromethyl, halogen, (C
1
-C
4
)-alkoxy, (C
1
-C
4
)-alkyl or amino, or
R
8
and R
9
form, together with the nitrogen atom and the carbonyl group to which they are bonded, a 4- to 7-membered saturated heterocycle which optionally contains up to two other heteroatoms from the series N, O and/or S,
R
10
represents straight-chain or branched (C
1
-C
15
)-alkyl which can be substituted by (C
3
-C
8
)-cycloalkyl, (C
1
-C
4
)-alkoxy, phenyl, phenoxy or benzyloxy, where the said aromatic radicals can in turn each be substituted up to three times, identically or differently, by halogen, (C
1
-C
6
)-alkyl or (C
1
-C
4
)-alkoxy,
represents (C
3
-C
8
)-cycloalkyl which can be substituted by (C
1
-C
4
)-alkoxy or phenyl,
represents (C
6
-C
10
)-aryl which can be substituted up to three times, identically or differently, by (C
1
-C
6
)-alkyl, (C
1
-C
6
)-alkoxy, halogen, cyano, amino, trifluoromethyl or phenyl, or
represents a 5- to 6-membered saturated or aromatic, optionally benzo-fused heterocycle with up to two heteroatoms from the series N, O and/or S, or
denotes a group of the formula —OR
13
or NR
14
R
15
, in which
R
13
represents straight-chain or b ranched (C
1
-C
6
)-alkyl, and
R
14
and R
15
are identical or different and, independently of one another,
represent hydrogen, straight-chain or branched (C
1
-C
12
)-alkyl, which can be substituted by aminocarbonyl, a group of the formula —NR
16
R
17
, 5- to 6-membered heteroaryl which contains up to 3 heteroatoms selected from the series N, O and/or S or can be substituted by phenyl, where phenyl is optionally substituted up to twice, identically or differently, by halogen, (C
1
-C
4
)-alkyl, trifluoromethyl or (C
1
-C
4
)-alkoxy,
represent (C
3
-C
8
)-cycloalkyl which can be substituted by (C
1
-C
4
)-alkyl,
represent (C
6
-C
10
)-aryl which can be substituted up to three times, identically or differently, by halogen, (C
1
-C
4
)-alkyl, trifluoromethyl, (C
1
-C
4
)-alkoxy, amino, phenyl or phenoxy, or
represent a 5- to 7-membered, saturated or unsaturated heterocycle which contains one or two nitrogen atoms and which can be bonded via a carbon or nitrogen atom and is optionally substituted by (C
1
-C
4
)-alkyl or an oxo group, where
R
16
and R
17
are identical or different and, independently of one another, represent hydrogen, (C
1
-C
6
)-alkyl, phenyl or (C
6
-C
10
)-arylsulphonyl, or
form, together with the nitrogen atom to which they are bonded, a 3- to 7-membered saturated heterocycle which optionally contains up to two other heteroatoms from the series N, O and/or S, or
R
14
and R
15
form, together with the nitrogen atom to which they are bonded, a 4- to 7-membered saturated heterocycle which can contain up to two other heteroatoms from the series N, O and/or S and be substituted by amino, (C
1
-C
6
)-alkyl, (C
1
-C
4
)-alkanoyl, aminocarbonyl, (C
1
-C
4
)-alkoxycarbonyl, (C
1
-C
4
)-alkoxycarbonylamino, phenyl or pyridyl,
R
11
and R
12
are identical or different and, independently of one another,
represent hydrogen, straight-chain or branched (C
1
-C
6
)-alkyl, which can be substituted one or more times, identically or differently, by mono-(C
1
-C
6
)-alkylamino, di-(C
1
-C
6
)-alkylamino, (C
1
-C
4
)-alkoxy, (C
1
-C
6
)-alkoxycarbonyl, carboxyl, pyridyl or (C
6
-C
10
)-aryl, where the latter in turn is optionally substituted by halogen, trifluoromethyl, (C
1
-C
6
)-alkyl or (C
1
-C
6
)-alkoxy,
represent (C
3
-C
8
)-cycloalkyl or represent a 5- to 7-membered heterocycle which contains one to two nitrogen atoms and which can be bonded via a carbon or nitrogen atom, where cycloalkyl and heterocycle are optionally substituted by (C
1
-C
4
)-alkyl, or
R
11
and R
12
form, together with the nitrogen atom to which they are bonded, a 5- to 7-membered saturated, optionally benzo-fused heterocycle which can contain up to two other heteroatoms from the series N, O and/or S and be substituted by amino, (C
1
-C
6
)-alkyl, (C
1
-C
4
)-alkoxycarbonyl, (C
1
-C
4
)-alkoxy-carbonylamino or phenyl, and
R
5
denotes hydrogen, (C
1
-C
4
)-alkyl or (C
1
-C
4
)-alkanoyl,
and the respective salts and hydrates thereof show a pharmacological effect and can be used as pharmaceuticals or for producing pharmaceutical formulations.
Heteroaryl is intended to mean for the purposes of the invention in general a 5- to 8-membered aromatic, optionally benzo-fused heterocycle with up to 4 heteroatoms from the series S, N and/or O. Examples which may be mentioned are: pyridyl, thienyl, thiazolyl, oxazolyl, imidazolyl, triazolyl, tetrazolyl.
Heterocycles are intended to mean for the purposes of the invention generally a 5- to 8-membered, saturated, partially unsaturated or aromatic, optionally benzo-fused heterocycle with up to 4 heteroatoms from the series S, N and/or O, that is to say a heterocycle which may contain one or more double bonds and which is linked via a ring carbon atom or a ring nitrogen atom. Examples which may be mentioned are: tetrahydrofur-2-yl, tetrahydrofur-3-yl, pyrrolidin-1-yl, pyrrolidi
Bischoff Hilmar
Faeste Christiane
Haning Helmut
Kretschmer Axel
Pernerstorfer Josef
Bayer Aktiengesellschaft
Chiu Jerrie L.
McKane Joseph K.
Saeed Kamal
LandOfFree
Amino- and amido-diphenyl ethers does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Amino- and amido-diphenyl ethers, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Amino- and amido-diphenyl ethers will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3024313