COMBINATION OF A CHOLINESTERASE INHIBITOR AND A COMPOUND WITH 5-HT6 RECEPTOR AFFINITY
First Claim
Patent Images
1. An active substance combination that comprises:
- as component (A) at least one compound with 5-HT6 receptor affinity, andas component (B) at least one cholinesterase inhibitor,wherein an active substance combination comprising as component (A) the 5-HT6 antagonist SB271046 and as component (B) the cholinesterase inhibitor donepezil hydrochloride is excluded.
1 Assignment
0 Petitions
Accused Products
Abstract
The present invention relates to an active substance combination comprising at least one compound with 5-HT6 receptor affinity, and at least one cholinesterase inhibitor, a medicament comprising said active substance combination, and the use of said active substance combination for the manufacture of a medicament.
-
Citations
35 Claims
-
1. An active substance combination that comprises:
-
as component (A) at least one compound with 5-HT6 receptor affinity, and as component (B) at least one cholinesterase inhibitor, wherein an active substance combination comprising as component (A) the 5-HT6 antagonist SB271046 and as component (B) the cholinesterase inhibitor donepezil hydrochloride is excluded. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)
-
2. The combination according to claim 1, wherein component (A) has a Ki value for binding to the 5-HT6-receptor of below or equal to 1 μ
- M.
-
3. The combination according to claim 1, wherein component (A) acts as agonist or inverse agonist of the 5-HT6 receptor, preferably the compound with 5-HT6 receptor affinity acts as agonist of the 5-HT6 receptor.
-
4. The combination according to claims 1, wherein component (B) has an IC50 for the inhibition of acetylcholinesterase in erythrocytes below or equal to 1 μ
- M.
-
5. The combination according to claim 1, wherein the cholinesterase inhibitor is selected from the group consisting of reversible cholinesterase inhibitors and pseudo-reversible cholinesterase inhibitors.
-
6. The combination according to claim 1, wherein component (A) is selected from the group consisting of the benzoxazinone-derived sulfonamide compounds of general formula (Ia)
wherein R1a, R2a, R3a and R4a, independently of one another, each represent a hydrogen atom; - halogen;
an unbranched or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as ring member containing cycloaliphatic radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
an unsubstituted or at least mono-substituted aryl- or heteroaryl radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ringsystem;
nitro;
cyano;
—
O—
R10a;
—
O—
(C═
O)—
R11a;
—
(C═
O)—
OR11a;
—
SR12a;
—
SOR12a;
—
SO2R12a;
—
NH—
SO2R12a;
—
SO2NH3 or —
NR13aR14a;
R5a represents a hydrogen atom;
an unbranched or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical or a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as ring member containing cycloaliphatic radical;R6a, R7a, R8a, R9a, independetly of one another, each represent a hydrogen atom;
an unbranched or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as ring member containing cycloaliphatic radical;
a cyano group or a —
C(═
O)—
OR15a moiety;Wa represents an unbranched or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as ring member containing cycloaliphatic radical, which may be bonded via an optionally mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene or alkenylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; a —
NR16aR17a moiety, ora —
C(═
O)—
R18a moiety;R10a represents a hydrogen atom;
an unbranched or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as ring member containing cycloaliphatic radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R11a represents a hydrogen atom;
an unbranched or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as ring member containing cycloaliphatic radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R12a represents an unbranched or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as ring member containing cycloaliphatic radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R13a and R14a, independently of one another, each represent a hydrogen atom;
an unbranched or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as ring member containing cycloaliphatic radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;or R13a and R14a together with the bridging nitrogen atom form a saturated, unsaturated or aromatic heterocyclic ring, which is unsubstituted or at least mono-substituted and/or which may contain at least one further heteroatom as a ring member; R15a represents a hydrogen atom;
an unbranched or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as ring member containing cycloaliphatic radical or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R16a represents an unbranched or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; R17a represents an unbranched or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical, and R18a represents an unsubstituted or at least mono-substituted aryl radical; optionally in form of one of its stereoisomers, preferably enantiomers or diastereomers, its racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a solvate, respectively; indole-derived sulfonamide compounds of general formula (Ib) wherein R1b represents a hydrogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical,which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
a —
(CH2)mb—
NR13bR14b moiety with mb=0, 1, 2, 3, 4 or 5;
a —
C(═
O)—
R8b moiety;
a —
S(═
O)2—
R9b moiety;
or a —
S(═
O)2—
C(H)AbBb moiety;R2b represents a hydrogen atom;
—
F;
—
Cl;
—
Br;
—
I;
—
NO2;
—
NH2;
—
SH;
—
OH;
—
CN;
—
C(═
O)—
OH;
—
O—
R10b;
—
C(═
O)—
OR12b;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a chain member containing aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R3b represents a hydrogen atom;
—
F;
—
Cl;
—
Br;
—
I;
—
NO2;
—
CN;
—
O—
R10b;
—
S—
R11b;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
a —
CH(OC2H5)—
CH2—
NR13bR14b moiety or a —
(CH2)nb—
NR13bR14b moiety with nb=0, 1, 2, 3, 4 or 5;
a —
S(═
O)2—
R9b moiety;
a —
S(═
O)2—
C(H)AbBb moiety;
or a —
C(═
O)—
(CH2)pb—
C(═
O)—
N-DbEb moiety with pb=0, 1, 2, 3, 4 or 5;R4b;
R5b;
R6b and R7b, independently of one another, each represent a hydrogen atom;
—
NO2;
—
NH2;
—
SH;
—
OH;
—
CN;
—
C(═
O)—
OH;
—
C(═
O)—
H;
—
S(═
O)2—
OH;
—
C(═
O)—
NH2;
—
S(═
O)2—
NH2;
—
C(═
O)—
R8b;
—
S(═
O)2—
R9b;
—
O—
R10b;
—
S—
R11b;
C(═
O)—
OR12b;
—
N(R15b)—
S(═
O)2R16b;
—
NH—
R17b;
—
NR18bR19b;
—
C(═
O)—
NHR20b, —
C(═
O)—
NR21bR22b;
—
S(═
O)2—
NHR23b;
—
S(═
O)2—
NR24bR25b;
—
O—
C(═
O)—
R26b;
—
NH—
C(═
O)—
R27b;
—
NR28b—
C(═
O)—
R29b;
NH—
C(═
O)—
O—
R30b;
NR31b—
C(═
O)—
O—
R32b;
—
S(═
O)2—
O—
R33b;
a halogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group;with the proviso that at least one of the substituents R4b, R5b, R6b and R7b represents a —
N(R15b—
S(═
O)2—
R16b moiety;R8b, R12b, R17b, R18b, R19b, R20b, R21b, R22b, R23b, R24b, R25b, R26b, R27b, R28b, R29b, R30b, R31b, R32b and R33b, independently of one another, each represent a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene, alkenylene or alkinylene group;R9b represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R10b and R11b, independently of one another, each represent a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group;R13b and R14b, independently of one another, each represent a hydrogen atom;
or a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;R13b and R14b together with the bridging nitrogen form an unsubstituted or at least mono-substituted, saturated, unsaturated or aromatic heterocyclic ring which may contain at least one further heteroatom as a ring member and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; R15b represents a hydrogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical or a —
S(═
O)2—
R16b moiety;R16b represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;Ab and Bb together with the bridging carbon form an unsubstituted or at least mono-substituted, saturated or unsaturated cycloaliphatic ring which may contain at least one further heteroatom as a ring member and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; Db and Eb together with the bridging nitrogen form an unsubstituted or at least mono-substituted, saturated, unsaturated or aromatic heterocyclic ring which may contain at least one further heteroatom as a ring member and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
orDb and Eb, independently of one another, each represent a hydrogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, respectively;
indazolyl- and (2,3)-dihydro-indolyl-derived sulfonamide compounds of general formula (Ic)wherein Xc—
Yc from left to right represents CR1c═
N and Zc is N[(CH2)ncR6c] orXc—
Yc from left to right represents CR7c═
N, Zc is NH, R7c represents the following moietyAc represents CH or N and Bc represents NR8c, O or S; Xc—
Yc from left to right represents C[(CH2)ncR9c═
N and Zc is NR10c orXc—
Yc represents CH2—
CH2 and Zc is N[(CH2)ncR11c];nc is 0, 1, 2, 3 or 4; R1c represents a hydrogen atom;
NO2;
—
NH2;
—
SH;
—
OH;
—
CN;
—
C(═
O)—
R12c;
—
OR13c;
—
SR14c;
—
F;
—
Cl, —
Br;
—
I;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R2c, R3c, R4c and R5c, independently of one another, each represent a hydrogen atom;
—
NO2;
—
NH2;
—
SH;
—
OH;
—
CN;
—
C(═
O)—
H;
—
C(═
O)—
R12c;
—
OR13c;
—
SR14c;
—
N(R15c)—
S(═
O)2—
R16c;
—
NH—
R17c;
—
NR18cR19c;
—
F;
—
Cl, —
Br;
—
I;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;with the proviso that at least one of the substituents R2c, R3c, R4c and R5c represents a —
N(R15c)—
S(═
O)2—
R16c moiety;R6c, R9c and R11c, independently of one another, each represent a —
NR20cR21c radical ora saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; R8c represents —
C(═
O)—
R22c;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R10c represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical-;
or a —
S(═
O)2—
R23c moiety;R12c, R13c, R14c, R17c, R18c and R19c, independently of one another, each represent a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R15c represents a hydrogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or a —
S(═
O)2—
R24c moiety;R16c and R24c, independently of one another, each represent an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; R20c and R21c, independently of one another, each represent a hydrogen atom;
or a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;or R20c and R21c together with the bridging nitrogen form an unsubstituted or at least mono-substituted, saturated, unsaturated or aromatic heterocyclic ring which may contain at least one further heteroatom as a ring member and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; R22c represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; andR23c represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, respectively; phenyl-piperazine-derived compounds of general formula (Id) wherein Xd represents a —
NR1dR2d moiety t or a —
OR3d moiety;R1d represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; an unsubstituted or at least mono-substituted radical selected from the group consisting of adamantyl, bicyclo[2.2.1]heptyl and bicyclo[3.1.1]heptyl, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group which may contain 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as chain member(s); a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system and/or which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group which may contain 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as chain member(s); or a —
C(═
O)—
R12d moiety;R2d represents a hydrogen atom or a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
orR1d and R2d together with the bridging nitrogen form an optionally at least mono-substituted, saturated, unsaturated or aromatic heterocyclic ring which may contain at least one further heteroatom as a ring member and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; R3d represents or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system and/or which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group; R4d, R5d and R6d, independently of one another, each represent a hydrogen atom or a halogen atom;
orR4d and R5d together with the bridging carbon atoms form an unsubstituted 5- or 6-membered heterocyclic ring which contains 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as ring member(s) and which together with the phenyl ring which it is fused with forms a 9- or 10-membered bicyclic aromatic ring system; R7d and R8d, independently of one another, each represent a hydrogen atom or a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; R9d and R10d, independently of one another, each represent a hydrogen atom or a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; R11d represents a hydrogen atom;
or a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical, which may contain 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as chain member(s);or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system and/or which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group; -a-C(═
O)—
R13d moiety or a —
S(═
O)2—
R14d moiety;R12d represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system and/or which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group; and R13d and R14d, independently of one another, each represent a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system and/or which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group which may contain 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as chain member(s);optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, respectively; and phenyl-piperazine-derived compounds of general formula (Ie) wherein Xe represents —
CN, —
C(═
O)—
OH, —
C(═
O)—
OR4e, —
O—
R5e, —
NH2, —
NR6e—
C(═
O)—
R7e, —
NH—
S(═
O)2—
R8e or —
NH—
R9e;R1 represents a hydrogen atom; a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system and/or which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group which may contain 1, 2 or 3 heteroatom(s) independently selected from the group consisting of nitrogen, oxygen and sulfur as chain member(s); R2e represents a hydrogen atom or a —
C(═
O)—
R10e moiety;
orR1e and R2e together with the bridging nitrogen form a nitro (NO2)-group or an unsubstituted or at least mono-substituted 5- or 6-membered heteroaryl radical which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; R3e represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; R4e represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; R5e represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
oran unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system and/or which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group; R6e represents a hydrogen atom or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system and/or which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group; R7e represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; R8e represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system and/or which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group; R9e represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system and/or which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group; and R10e represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, respectively; and tetrahydroisoquinoline-derived sulfonamide compounds of general formula (If) wherein R1f represents a hydrogen atom;
a —
C(═
O)—
OR37f moiety;a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R2f, R3f, R4f and R5f, independently of one another, each represent a hydrogen atom;
F, Cl, Br, I, —
NO2;
—
NH2;
—
SH;
—
OH;
—
CN;
—
C(═
O)—
OH;
—
C(═
O)—
H;
—
S(═
O)2—
OH;
—
C(═
O)—
NH2;
—
S(═
O)2—
NH2;
—
C(═
O)—
R6f;
—
S(═
O)—
R7f;
—
S(═
O)2—
R7f;
—
OR8f;
—
SR9f;
—
C(═
O)—
OR10f;
—
N(R11f)—
S(═
O)2—
R12f;
—
NR13fR14f;
—
NH—
R15f;
—
C(═
O)—
NR16fR17f;
C(═
O)—
NHR18f;a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene, alkenylene or alkinylene group and which may be condensed with an unsubstituted or at least mono-substituted saturated, unsaturated or aromatic mono- or bicyclic ring system; or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene, alkenylene or alkinylene group and which may be condensed with an unsubstituted or at least mono-substituted saturated or unsaturated, but not aromatic, mono- or bicyclic ring system; with the proviso that at least one of the substituents R2f, R3f, R4f and R5f represents a —
N(R11f)—
S(═
O)2—
R12f moiety;R6f, R7f, R8f, R9f, R10f, R13f, R14f, R15f, R16f, R17f and R18f, independently of one another, each represent a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene, alkenylene or alkinylene group and which may be condensed with an unsubstituted or at least mono-substituted saturated, unsaturated or aromatic mono- or bicyclic ring system; or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene, alkenylene or alkinylene group and which may be condensed with an unsubstituted or at least mono-substituted saturated or unsaturated, but not aromatic, mono- or bicyclic ring system; R11f represents a hydrogen atom or a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; R12frepresents a phenyl radical of general formula (Af), wherein R19f, R20f, R21f, R22f and R38f, independently of one another, each represent a hydrogen atom;
F, Cl, Br, I, —
NO2;
—
NH2;
—
SH;
—
OH;
—
CN;
—
C(═
O)—
OH;
—
C(═
O)—
H;
—
S(═
O)2—
OH;
—
C(═
O)—
NH2;
—
S(═
O)2—
NH2;
—
C(═
O)—
R23f;
—
S(═
O)—
R24f;
—
S(═
O)2—
R24f;
—
OR25f;
—
SR26f;
—
C(═
O)—
OR27f;
—
N(R28f)—
S(═
O)2—
R29f;
—
NH—
S(═
O)2—
R30f;
—
NR31fR32f;
—
NH—
R33f;
—
C(═
O)—
NHR34f;
—
C(═
O)—
NR35fR36f;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system and/or which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group; or a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be condensed with an unsubstituted or at least mono-substituted saturated, unsaturated or aromatic mono- or bicyclic ring system; R23f, R27f, R28f, R29f and R30f, independently of one another, each represent a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene, alkenylene or alkinylene group and which may be condensed with an unsubstituted or at least mono-substituted saturated, unsaturated or aromatic mono- or bicyclic ring system; or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene, alkenylene or alkinylene group and which may be condensed with an unsubstituted or at least mono-substituted saturated or unsaturated, but not aromatic, mono- or bicyclic ring system; R24f, R26f, R31f, R32f and R33f, each represent a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene, alkenylene or alkinylene group and which may be condensed with an unsubstituted or at least mono-substituted saturated, unsaturated or aromatic mono- or bicyclic ring system; or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be condensed with an unsubstituted or at least mono-substituted saturated or unsaturated, but not aromatic, mono- or bicyclic ring system; R25f, R34f, R35f and R36f, represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; and R37f represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene, alkenylene or alkinylene group and which may be condensed with an unsubstituted or at least mono-substituted saturated, unsaturated or aromatic mono- or bicyclic ring system; or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene, alkenylene or alkinylene group and which may be condensed with an unsubstituted or at least mono-substituted saturated or unsaturated, but not aromatic, mono- or bicyclic ring system; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a salt thereof, or a corresponding solvate thereof.
- halogen;
-
7. The combination according to claim 6, wherein the indole-derived sulfonamide is selected from the group consisting of compounds of general formula (Ih)
wherein R1h represents a hydrogen atom; - a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or a —
(CH2)mh—
NR13hR14h moiety with mh=0, 1, 2, 3, 4 or 5;
R2h represents a hydrogen atom;
—
F;
—
Cl;
—
Br;
—
I;
—
NO2;
—
CN;
—
O—
R10h;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R3h represents a hydrogen atom;
—
F;
—
Cl;
—
Br;
—
I;
—
NO2;
—
CN;
—
O—
R10h;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or a —
(CH2)nh—
NR13hR14h moiety with nh=0, 1, 2, 3, 4 or 5;R4h, R5h and R7h, independently of one another, each represent a hydrogen atom;
—
NO2;
—
CN;
—
O—
R10h;
—
C(═
O)—
OR12h;
a halogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group;R10h represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group;R13h and R14h, independently of one another, each represent a hydrogen atom;
or a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
orR13h and R14h together with the bridging nitrogen form an unsubstituted or at least mono-substituted, saturated, unsaturated or aromatic heterocyclic ring which may contain at least one further heteroatom as a ring member and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; R15h represents a hydrogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical or a —
S(═
O)2—
R16h moiety;and R16h represents an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, respectively; and compounds of general formula (Ik) wherein R1k represents a hydrogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
an unsubstituted or at least mono-substituted phenyl radical or an unsubstituted or at least mono-substituted benzyl radical;R3k represents a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or a —
(CH2)nk—
NR13kR14k moiety with nk=0, 1, 2, 3, 4 or 5;R13k and R14k, independently of one another, each represent a hydrogen atom;
or a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
orR13k and R14k together with the bridging nitrogen form an unsubstituted or at least mono-substituted, saturated, unsaturated or aromatic heterocyclic ring which may contain at least one further heteroatom as a ring member and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; R15k represents a hydrogen atom;
or a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;and R16k represents an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, respectively; compounds of general formula (Im) wherein R1m represents a hydrogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or a —
(CH2)mm—
NR13mR14m moiety with mm=0, 1, 2, 3, 4 or 5;R2m represents a hydrogen atom;
—
F;
—
Cl;
—
Br;
—
I;
—
NO2;
—
CN;
—
O—
R10m;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R3m represents a hydrogen atom;
—
F;
—
Cl;
—
Br;
—
I;
—
NO2;
—
CN;
—
O—
R10m;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or a —
(CH2)nm—
NR13mR14m moiety with nm=0, 1, 2, 3, 4 or 5;R4m, R6m and R7m, independently of one another, each represent a hydrogen atom;
—
NO2;
—
CN;
—
O—
R10m;
a halogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group;R10m represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group;R13m and R14m, independently of one another, each represent a hydrogen atom;
or a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
orR13m and R14m together with the bridging nitrogen form an unsubstituted or at least mono-substituted, saturated, unsaturated or aromatic heterocyclic ring which may contain at least one further heteroatom as a ring member and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; R15m represents a hydrogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical or a —
S(═
O)2—
R16m moiety;and R16m represents an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, respectively; and compounds of general formula (In) wherein R1n represents a hydrogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or a —
(CH2)mn—
NR13nR14n moiety with mn=0, 1, 2, 3, 4 or 5;R2n represents a hydrogen atom;
—
F;
—
Cl;
—
Br;
—
I;
—
NO2;
—
CN;
—
O—
R10n;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R3n represents a hydrogen atom;
—
F;
—
Cl;
—
Br;
—
I;
—
NO2;
—
CN;
—
O—
R10n;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or a —
(CH2)nn—
NR13nR14n moiety with nn=0, 1, 2, 3, 4 or 5;R5n, R6n and R7n, independently of one another, each represent a hydrogen atom;
—
NO2;
—
CN;
—
O—
R10n;
a halogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group;R10n represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group;R13n and R14n, independently of one another, each represent a hydrogen atom;
or a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
orR13n and R14n together with the bridging nitrogen form an unsubstituted or at least mono-substituted, saturated, unsaturated or aromatic heterocyclic ring which may contain at least one further heteroatom as a ring member and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; R15n represents a hydrogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical or a —
S(═
O)2—
R16n moiety;R16n represents an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, respectively; and compounds of general formula (Io) wherein R1o represents a hydrogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or a —
(CH2)mo—
NR13oR14o moiety with mo=0, 1, 2, 3, 4 or 5;R2o represents a hydrogen atom;
—
F;
—
Cl;
—
Br;
—
I;
—
NO2;
—
CN;
—
O—
R10o;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R3o represents a hydrogen atom;
—
F;
—
Cl;
—
Br;
—
I;
—
NO2;
—
CN;
—
O—
R10o;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
a —
CH(OC2H5)—
CH2—
NR13oR14o moiety or a —
(CH2)no—
NR13oR14o moiety with no=0, 1, 2, 3, 4 or 5;R4o, R5o and R6o, independently of one another, each represent a hydrogen atom;
—
NO2;
—
CN;
—
O—
R10o;
a halogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group;R10o represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group;R13o and R14o, independently of one another, each represent a hydrogen atom;
or a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
orR13o and R14o together with the bridging nitrogen form an unsubstituted or at least mono-substituted, saturated, unsaturated or aromatic heterocyclic ring which may contain at least one further heteroatom as a ring member and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; R15o represents a hydrogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical or a —
S(═
O)2—
R16o moiety;and R16o represents an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, respectively; compounds of general formula (Ip) wherein R1p represents a —
S(═
O)2—
R9p moiety or a —
S(═
O)2—
C(H)ApBp moiety;R2p represents a hydrogen atom;
—
F;
—
Cl;
—
Br;
—
I;
—
NO2;
—
OH;
—
CN;
—
O—
R10p;
—
S—
R11p;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R3p represents a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via an unsubstituted or at least mono-substituted alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or a —
(CH2)np—
NR13pR14p moiety with np=0, 1, 2, 3, 4 or 5;R4p, R5p, R6pand R7p, independently of one another, each represent a hydrogen atom;
—
NO2;
—
NH2;
—
OH;
—
CN;
—
C(═
O)—
R8p;
—
O—
R10p;
—
S—
R11p;
—
NH—
R17p;
—
NR18pR19p;
a halogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group;R8p represents a hydrogen atom or a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; R8p, R17p, R18pand R19p, independently of one another, each represent a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene, alkenylene or alkinylene group;R9p represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical; R10p and R11p, independently of one another, each represent a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group;R13p and R14p, independently of one another, each represent a hydrogen atom;
or a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
orR13p and R14p together with the bridging nitrogen form an unsubstituted or at least mono-substituted, saturated, unsaturated or aromatic heterocyclic ring which may contain at least one further heteroatom as a ring member and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; Ap and Bp together with the bridging carbon form an unsubstituted or at least mono-substituted, saturated or unsaturated cycloaliphatic ring which may contain at least one further heteroatom as a ring member and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, respectively; and compounds of general formula (Iq) wherein R1q represents a hydrogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical,which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
a —
C(═
O)—
R8q moiety;
a —
S(═
O)2—
R9q moiety;R2q represents a hydrogen atom;
—
F;
—
Cl;
—
Br;
—
I;
—
NO2;
—
NH2;
—
SH;
—
OH;
—
CN;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a chain member containing aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R4q, R5q, R6q and R7q, independently of one another, each represent a hydrogen atom;
—
NO2;
—
NH2;
—
SH;
—
OH;
—
CN;
—
C(═
O)—
OH;
—
C(═
O)—
H;
—
S(═
O)2—
OH;
—
C(═
O)—
NH2;
—
S(═
O)2—
NH2;
—
C(═
O)—
R8q;
—
S(═
O)2—
R9q;
—
O—
R10q;
—
S—
R11q;
—
C(═
O)—
OR12q;
—
N(R15q)—
S(═
O)2—
R16q;
—
NH—
R17q;
—
NR18qR19q;
—
C(═
O)—
NHR20g, —
C(═
O)—
NR21qR22q;
—
S(═
O)2—
NHR23q;
—
S(═
O)2—
NR24qR25q;
—
O—
C(═
O)—
R26q;
—
NH—
C(═
O)—
R27q;
—
NR28q—
C(═
O)—
R29q;
NH—
C(═
O)—
O—
R30q;
NR31q—
C(═
O)—
O—
R32q;
—
S(═
O)2—
O—
R33q;
a halogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group;with the proviso that at least one of the substituents R4q, R5q, R6q and R7q represents a —
N(R15q)—
S(═
O)2—
R16q moiety;R8q, R12q, R17q, R18q, R19q, R20q, R21q, R22q, R23q, R24q, R25q, R26q, R27q, R28q, R29q, R30q, R31q, R32q and R33q, independently of one another, each represent a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene, alkenylene or alkinylene group;R9q represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;R10q and R11q, independently of one another, each represent a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched alkylene group;R15q represents a hydrogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical or a —
S(═
O)2—
R16q moiety;R16q represents a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;Dq and Eq together with the bridging nitrogen form an unsubstituted or at least mono-substituted, saturated, unsaturated or aromatic heterocyclic ring which may contain at least one further heteroatom as a ring member and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
orDq and Eq, independently of one another, each represent a hydrogen atom;
a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
a saturated or unsaturated, unsubstituted or at least mono-substituted, optionally at least one heteroatom as a ring member containing cycloaliphatic radical, which may be bonded via a linear or branched alkylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;
or an unsubstituted or at least mono-substituted aryl or heteroaryl radical, which may be bonded via a linear or branched, unsubstituted or at least mono-substituted alkylene, alkenylene or alkinylene group and/or which may be condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system;optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, respectively.
- a linear or branched, saturated or unsaturated, unsubstituted or at least mono-substituted aliphatic radical;
-
8. The combination according to claim 1, wherein component (A) is at least one compound selected from the group consisting of BVT-5182, EMDT, Ro 65-7199, Ro 04-6790, Ro 63-0563, MS-245, SB-271046, LY-483518, ALX-0440, WAY-181189, WAY-466, ALX-1175, ALX-1161, SB-271046, SB-258510, SB-357134, SB-214111, SB-399885, Ro 65-7674, SB-699929, Ro 43-68554, SB-742457, Ro 66-0074, [11C]GSK-215083,
[HT1] N,N-dimethyl-2-(1-(phenylsulfonyl)-1H-indol-3-yl)ethanamine, [HT2] 5-chloro-2-methyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole, [HT3] 2-(1-(5-(phenylsulfonamido)-1H-indol-3-yl)ethylidene)hydrazinecarboximidamide, [HT4] 5-fluoro-3-(3-fluorophenylsulfonyl)-1-(piperidin-3-yl)-1H-indole, [HT5] 2-((1-(4-aminophenylsulfonyl)-1H-indol-3-yl)methylene)hydrazinecarboximidamide, [HT6] 3-(phenylsulfonyl)-7-(2-(pyrrolidin-1-yl)ethoxy)-1H-indole, [HT7] N,N-dimethyl-2-(1-(phenylsulfonyl)-1H-indol-4-yloxy)ethanamin, [HT8] 1-(phenylsulfonyl)-3-(pyrrolidin-2-ylmethyl)-1H-indole, [HT9] 2-(3-benzyl-1H-indol-1-yl)-N,N-dimethylethanamine, [HT10] 4-(3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-1-ylsulfonyl)benzenamine, [HT12] (6S,7S)-7-(dimethylamino)-2-tosyl-2,6,7,8-tetrahydrobenzo[cd]indol-6-ol, [HT13] 2-(1-(phenylsulfonyl)-6,7-dihydro-1H-indol-4(5H)-ylidene)hydrazinecarboximidamide, [HT14] 6-(phenylsulfonyl)-2,3,4,9-tetrahydro-1H-carbazol-3-amine, [HT15] 3-(3-chlorophenylsulfonyl)-1-(pyrrolidin-2-ylmethyl)-1H-pyrrolo[2,3-b]pyridine, [HT16] 4-(5,6,7,8-tetrahydrocarbazol-9-ylsulfonyl)benzenamine, [HT17] 3-(2-aminoethyl)-1-(naphthalen-2-ylsulfonyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one, [HT18] 2-(4-(6-chloroimidazo[2,1-b]thiazol-5-ylsulfonyl)-4H-thieno[3,2-b]pyrrol-6-yl)-N,N-dimethylethanamine, [HT19] N,N-dimethyl-3-(phenylsulfonyl)-6,7,8,9-tetrahydro-3H-benzo[e]indol-8-amine, [HT20] N-(4-(piperidin-4-yl)-2H-chromen-6-yl)naphthalene-1-sulfonamide, [HT21] 2-(3-benzyl-3H-inden-1-yl)-N,N-dimethylethanamine, [HT22] N-(7-((3S,4S)-3-fluoropiperidin-4-yloxy)benzofuran-5-yl)-2-methoxy-5-methylbenzenesulfonamide, [HT23] 2-Methoxy-10-(1-methylpyrrolidin-3-yl)-5-thia-4b-aza-indeno[2,1-a]indene 5,5-dioxide, [HT24] 1-(6-(phenylsulfonyl)pyridin-3-yl)piperazine, [HT25] 1-(2-methoxy-5-(naphthalen-1-ylsulfonyl)phenyl)piperazine, [HT26] 1-(2-chloro-5-(phenylsulfonyl)phenyl)piperazine, [HT27] 8-methoxy-1-(3-methoxy-5-(piperazin-1-yl)benzyl)-3,4-dihydroquinolin-2(1H)-one, [HT28] 5-chloro-3-(3-chlorophenylsulfonyl)-7-(4-methylpiperazin-1-yl)-1H-indole, [HT29] 1-(4-(phenylsulfonypnaphthalen-1-yl)piperazine, [HT30] 3-(phenylsulfonyl)-7-(piperazin-1-yl)-1H-pyrrolo[3,2-b]pyridine, [HT31] 4-(2-chlorophenylsulfonyl)-6-methyl-8-(piperazin-1-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine, [HT32] 5-(4-methylpiperazin-1-yl)-3-(naphthalen-1-ylsulfonyl)-1H-indazole, [HT33] 4-(4-(4-(4,5-dihydro-1H-imidazol-2-yl)piperazin-1-yl)-1H-indol-1-ylsulfonyl)benzenamine, [HT34] 5-(4-benzylpiperazin-1-yl)-3-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine, [HT35] 2-(2,3-dichlorophenylsulfonyl)-5-(piperazin-1-yl)-1,2,3,4-tetrahydroisoquinoline, [HT36] 6-fluoro-4-(2-fluorobenzyl)-8-(piperazin-1-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one, [HT37] 2-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-indole, [HT38] 4-(4-(piperazin-1-yl)naphthalen-1-ylsulfonyl)benzenamine, [HT39] 8-(4-(4-fluorobenzyl)piperazin-1-yl)-3-(phenylsulfonyl)quinoline, [HT40] 2,3-dichloro-N-(2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)benzenesulfonamide, [HT41] 2-(methylthio)-3-(phenylsulfonyl)-4H-pyrido[1,2-a]pyrimidin-4-imine and [HT42] 8-(4-(3-fluoro-5-(trifluoromethypbenzyl)phenylsulfonyl)-N,N,3-trimethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-amine; salts thereof, free bases thereof, racemates thereof, enantiomers thereof, and combinations thereof.
-
9. The combination according to claim 1, wherein component (B) is at least one compound selected from the group consisting of
edrophonium, ganstigmine, demecarium, ambenonium, neostigmine bromide, dehydroevodiamine chloride, eseroline, imperatorin, scopoletin (SCT), huperizine A (Hup A), huperzine A, tacrine hydrochloride (CI-970, THA.HCl), 7-methoxytacrine (7-MEOTA), velnacrine maleate (HP-029, P83-6029A), rivastigmine tartrate (ENA-713, ENA-713D, ONO-2540, SDZ-212-713, SDZ-ENA-713), eptastigmine tartrate (L-693487), heptylstigmine tartrate (MF-201), donepezil hydrochloride (BNAG, E-2020), suronacrine maleate (HP-128), UCB-11056, SM-10888, stacofylline hydrochloride (S-9977, S-9977-2), berberine iodide, zifrosilone (MDL-73745), norpyridostigmine, quilostigmine (HP-290, NXX-066), E-2030, THB-013, F-3796, PD-142012, CI-1002, PD-142676, terestigmine tartrate (CHF-2060), thiacymserine, phenserine tartrate, galantamine hydrobromide (GP-37267), galantamine hydrobromide (R-113675), Ro-46-5934, P11012, MF-8615, MF-268 bitartrate, anseculin hydrochloride (KA-672.HCl), ensaculin hydrochloride, icopezil maleate (CP-118954, CP-118954-11), eserine salicylate, physostigmine salicylate, isovanihuperzine A (IVHA), JWS-USC-751X, FR-152558, UR-1827, P11467, P-10358, bis(7)-tacrine, HMR-2420, T-82, CP-126998, TV-3279, MSF, THA-C8, subergorgic acid, suberogorgin, SPH-1286, huperzine B (Hup B), pyridostigmine bromide (Ro-1-5130), huprine X, ER-127528, tolserine tartrate, huprine Y, coronaridine, RS-1233, kobophenol A, bis(12)-huperine, BGC-20-1259, RS-1259, NP-7557, ZT-1, ITH-4012, TK-19, T-81, TH-171, TH-185, distigmine bromide (BC-51), (− - )-9-dehydrogalanthaminium bromide, memoquin, NP-0361, scopoletin 7-O-beta-D-glucopyranoside (NSC-404560), scopolin (SCN), scopoloside, BW-284c51, SP-004, SP-04, withaferin A (NSC-101088), withaferine (NSC-273757), (+)-corynoline, corynoline, (S)-(−
)-oxypeucedanin, oxypeucedanin, (−
)-voacangine, carbomethoxyibogaine, voacangine, dieckol, phlorofucofuroeckol (PFF), phlorofucofuroeckol A, (−
)-3-O-acetylspectaline hydrochloride and rhaphiasaponin 1, salts thereof, free bases thereof, racemates thereof, enantiomers thereof, and combinations thereof.
- )-9-dehydrogalanthaminium bromide, memoquin, NP-0361, scopoletin 7-O-beta-D-glucopyranoside (NSC-404560), scopolin (SCN), scopoloside, BW-284c51, SP-004, SP-04, withaferin A (NSC-101088), withaferine (NSC-273757), (+)-corynoline, corynoline, (S)-(−
-
10. The combination according to claim 1, which comprises 1-99% by weight of component (A) and 99-1% by weight of component (B), preferably 70 to 95% by weight of component (A) and 30 to 5% by weight of component (B), more preferably 85 to 95% by weight of component (A) and 15 to 5% by weight of component (B), in each case referring to the total weight of both components (A) and (B).
-
11. An active substance combination as defined in claim 1 which is a pharmaceutical composition.
-
12. A method of administration of the combination of claim 1 for simultaneous acetylcholinesterase inhibition and 5-HT6-receptor regulation.
-
13. A method of administration of the active substance combination of claim 1 for regulation of appetite, for maintenance, increase or reduction of body weight, for prophylaxis and/or treatment of disorders related to food ingestion, preferably for prophylaxis and/or treatment of obesity, anorexia, cachexia, bulimia, diabetes, preferably type II diabetes (non-insulin-dependent diabetes mellitus), or for prophylaxis and/or treatment of gastrointestinal tract disorders, preferably of the irritable bowel syndrome, for prophylaxis and/or treatment of Metabolic Syndrome, Peripheral Nervous System Disorders, Central Nervous System Disorders, arthritis, epilepsy, anxiety, panic, depression, cognitive disorders, memory disorders, cardiovascular diseases, senile dementia processes, such as Alzheimer'"'"'s, Parkinson'"'"'s and/or Huntington'"'"'s Disease, schizophrenia, psychosis, infantile hyperkinesia (ADHD, attention deficit / hyperactivity disorder), pain, hypertensive syndrome, inflammatory diseases, immunologic diseases or for improvement of cognition.
-
14. A pharmaceutical formulation, characterized in that it comprises an active substance combination according to claim 1 and optionally one or more pharmacologically acceptable adjuvants.
-
15. The pharmaceutical formulation according to claim 14, which is in solid pharmaceutical forms selected from the group consisting of tablets, tablets, chewing tablets, chewing gums, dragé
- es, capsules, suppositories, powder preparations, transdermal therapeutic systems, and transmucosal therapeutic systems.
-
16. The pharmaceutical formulation according to claim 14, which is in the form of multiple particles, microtablets, microcapsules, microspheroids, granules, crystals or pellets, and is optionally compacted in a tablet, filled in a capsule or suspended in a suitable liquid.
-
17. The pharmaceutical formulation according to claim 14, which is for oral, intravenous, intramuscular, subcutaneous, intrathecal, epidural, buccal, sublingual, pulmonal, rectal, transdeitual, nasal or intracerebroventricular application.
-
18. The pharmaceutical formulation according to claim 14, wherein at least one of the components of the active substance combination (A) or (B) is present at least partially in sustained-release form.
-
19. The pharmaceutical formulation according to claim 18, wherein the medicament has at least one coating or at least one matrix comprising at least one material, which sustains active substance release.
-
20. The pharmaceutical formulation according to claim 19, wherein the sustained-release material is based on optionally modified, water-insoluble, natural, semisynthetic or synthetic polymer, or a natural wax or fat or fatty alcohol or semisynthetic or synthetic fatty acid, or on a mixture of at least two of these afore mentioned components.
-
21. The pharmaceutical formulation according to claim 20, wherein the water-insoluble polymer is based on an acrylic resin, which is selected from the group consisting of poly(meth)acrylates, poly(C1-4)dialkylamino(C1-4)alkyl(meth)acrylates and/or copolymers thereof, mixtures thereof, and combinations thereof.
-
22. The pharmaceutical formulation according to claim 20, wherein the water-insoluble polymers are selected from the group consisting of cellulose derivatives, alkyl cellulose ethyl cellulose, and cellulose esters.
-
23. The pharmaceutical formulation according to claim 20, wherein the wax is selected from the group consiting of carnauba wax, beeswax, glycerol monostearate, glycerol monobehenate, glycerol ditripalmitostearate, microcrystalline wax a, mixtures thereof, and combinations thereof.
-
24. The pharmaceutical formulation according to claim 20, wherein the polymers are in combination with one or more plasticizers.
-
25. The pharmaceutical formulation according to claim 24, wherein that besides the sustained-release form, at least one of the active substance components (A) or (B) is present in a non-sustained-release form.
-
26. The combination according to claim 1, wherein component (A) has a Ki value for binding to the 5-HT6-receptor below or equal to 500 nM.
-
27. The combination according to claim 1, wherein component (A) has a Ki value for binding to the 5-HT6-receptor below or equal to 100 nM.
-
28. The combination according to claim 1, wherein component (A) has a Ki value for binding to the 5-HT6-receptor below or equal to 50 nM.
-
29. The combination according to claim 1, wherein component (A) has a Ki value for binding to the 5-HT6-receptor below or equal to 25 nM.
-
30. The combination according to claim 1 wherein component (B) has an IC50 for the inhibition of acetylcholinesterase in erythrocytes below or equal to 500 nM.
-
31. The combination according to claim 1 wherein component (B) has an IC50 for the inhibition of acetylcholinesterase in erythrocytes below or equal to 300 nM.
-
32. The combination according to claim 1 wherein component (B) has an IC50 for the inhibition of acetylcholinesterase in erythrocytes below or equal to 200 nM.
-
33. The combination according to claim 1 wherein component (B) has an IC50 for the inhibition of acetylcholinesterase in erythrocytes below or equal to 100 nM.
-
34. The pharmaceutical formulation according to claim 14, which is in liquid and semi-liquid pharmaceutical forms selected from the group consisting of drops, juice, sirup, solutions, emulsions, and suspensions.
-
35. The pharmaceutical formulation according to claim 34, which is in a form selected from the group consisting of tablets, capsules, drops or solution.
-
2. The combination according to claim 1, wherein component (A) has a Ki value for binding to the 5-HT6-receptor of below or equal to 1 μ
-
Specification
- Resources
Thank you for your request. You will receive a custom alert email when the Litigation Campaign Assessment is available.
×
-
Current AssigneeLaboratories Del Dr Esteve SA (Corporation Quimico Farmaceutica Esteve SA)
-
Original AssigneeLaboratories Del Dr Esteve SA (Corporation Quimico Farmaceutica Esteve SA)
-
InventorsBuschmann, Helmut Heinrich, Codony-Soler, Xavier
-
Application NumberUS12/305,516Publication NumberTime in Patent OfficeDaysField of SearchUS Class Current514/217.10CPC Class CodesA61K 2300/00 Mixtures or combinations of...A61K 31/445 Non condensed piperidines, ...A61K 45/06 Mixtures of active ingredie...A61P 1/00 Drugs for disorders of the ...A61P 1/04 for ulcers, gastritis or re...A61P 1/14 Prodigestives, e.g. acids, ...A61P 1/16 for liver or gallbladder di...A61P 11/00 Drugs for disorders of the ...A61P 15/00 Drugs for genital or sexual...A61P 15/08 for gonadal disorders or fo...A61P 15/10 for impotenceA61P 19/02 for joint disorders, e.g. a...A61P 19/06 Antigout agents, e.g. antih...A61P 25/00 Drugs for disorders of the ...A61P 25/02 for peripheral neuropathiesA61P 25/04 Centrally acting analgesics...A61P 25/08 Antiepileptics; Anticonvuls...A61P 25/14 for treating abnormal movem...A61P 25/16 Anti-Parkinson drugsA61P 25/18 Antipsychotics, i.e. neurol...A61P 25/22 : AnxiolyticsA61P 25/24 : AntidepressantsA61P 25/28 : for treating neurodegenerat...A61P 29/00 : Non-central analgesic, anti...A61P 3/00 : Drugs for disorders of the ...A61P 3/04 : Anorexiants; Antiobesity ag...A61P 3/06 : AntihyperlipidemicsA61P 3/10 : for hyperglycaemia, e.g. an...A61P 35/00 : Antineoplastic agentsA61P 37/02 : ImmunomodulatorsA61P 9/00 : Drugs for disorders of the ...A61P 9/04 : Inotropic agents, i.e. stim...A61P 9/06 : AntiarrhythmicsA61P 9/10 : for treating ischaemic or a...A61P 9/12 : Antihypertensives