US2014221371A1PendingUtilityA1
Heterocyclic compounds and their use as binding partners for 5-ht5 receptors
Est. expiryAug 21, 2025(expired)· nominal 20-yr term from priority
Inventors:Wilhelm AmbergAstrid NetzAndreas KlingMichael OchseUdo LangeCharles W. HutchinsFranciso Javier Garcia-LadonaWolfgang Wernet
C07D 401/04C07D 239/84C07D 491/056C07D 471/04A61P 25/00C07D 491/04C07D 405/06C07D 409/12A61P 25/28C07D 215/38C07D 409/04C07D 401/12
59
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The invention relates to compounds of general formula (I), corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof as well as pharmaceutically acceptable salts thereof and the prodrugs of said compounds. The invention also relates to the use of said compounds as binding partners for 5-HT5 receptors for treating diseases that are modulated by a 5-HT5 receptor activity, in particular, for treating neurodegenerative and neuropsychiatric disorders as well as signs, symptoms and dysfunctions.
Claims
exact text as granted — not AI-modified1 . A compound of general formula I
as well as corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, such that the stated radicals have the following definitions:
R 1 and R 2 independently of one another denote
hydrogen, a free electron pair, OH, CN or,
in each case optionally substituted, C 1 -C 6 alkyl, O—C 1 -C 6 alkyl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, CO—C 1 -C 6 alkyl, CO—O—C 1 -C 6 alkyl, SO 2 —C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-cycloalkyl, aryl, C 1 -C 4 alkylene-aryl, CO—O-arylalkyl, CO—C 1 -C 4 alkylene-aryl, CO-aryl, SO 2 -aryl, hetaryl, C 1 -C 4 alkylene-hetaryl, CO-hetaryl or SO 2 —C 1 -C 4 alkylene-aryl, heterocycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, indanyl or
R 1 and R 2 together with the nitrogen may form a three- to six-membered, optionally substituted, saturated or aromatic heterocycle, which may contain another heteroatom selected from the group consisting of O, N and S, such that the heterocycle may optionally be substituted once, twice or three times with the same or different substituents,
R 3 denotes
hydrogen, NO 2 , NH 2 , OH, CN, CF 3 , OCF 3 , CHF 2 , OCHF 2 , COOH, O—CH 2 —COOH, halogen, SH or,
in each case optionally substituted, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 2 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 2 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-hetaryl or C 1 -C 4 alkylene-aryl or
O—R 3 1 , CO—R 3 1 , S—R 3 1 , SO—R 3 1 , CO—O—R 3 1 , NR 3 4 —CO—O—R 3 1 , O—CH 2 —COO—R 3 1 , NR 3 2 R 3 3 , CONH 2 , SO 2 NH 2 , NR 3 4 —CO—R 3 1 , SO 2 —R 3 1 , NR 3 4 —SO 2 —R 3 1 , SO 2 —NR 3 2 R 3 3 or CO—NR 3 2 R 3 3
in which
R 3 1 denotes,
in each case optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-aryl, C 2 -C 6 alkylene-aryl or C 1 -C 6 alkylene-hetaryl;
R 3 2 denotes
hydrogen, OH, CN or,
in each case optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 4 alkylene-C 3 -C 2 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-hetaryl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl, CO—C 1 -C 6 alkyl, CO-aryl, CO-hetaryl, CO—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-hetaryl, CO—O—C 1 -C 6 alkyl, CO—O-aryl, CO—O—C 1 -C 4 alkylene-aryl, CO—O-hetaryl, CO—O—C 1 -C 4 alkylene-hetaryl, SO 2 —C 1 -C 6 alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 —C 1 -C 4 alkylene-aryl or SO 2 —C 1 -C 4 alkylene-hetaryl;
R 3 3 denotes,
in each case optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 4 alkylene-C 3 -C 2 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-hetaryl, C 1 -C 6 alkylene-O—C 1 -C 6 -alkyl, CO—C 1 -C 6 alkyl, CO-aryl, CO-hetaryl, CO—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-hetaryl, CO—O—C 1 -C 6 alkyl, CO—O-aryl, CO—O—C 1 -C 4 alkylene-aryl, CO—O-hetaryl,
CO—O—C 1 -C 4 alkylene-hetaryl, SO 2 —C 1 -C 6 alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 —C 1 -C 4 alkylene-aryl or SO 2 —C 1 -C 4 alkylene-hetaryl;
or the radicals R 3 2 and R 3 3 together with the nitrogen may form a three- to seven-membered, optionally substituted, saturated or aromatic heterocycle, which may contain one, two or three additional heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S, such that optionally two of the substituted radicals on this heterocycle together may form an anellated, optionally substituted, saturated, unsaturated or aromatic carbocycle or heterocycle, such that the heterocycle may contain up to three heteroatoms that are the same or different and are selected from the groups consisting of O, N and S and the cyclic group thereby formed may optionally be substituted and/or another optionally substituted cyclic group may be condensed onto this cyclic group;
R 3 4 denotes
hydrogen or,
in each case optionally substituted C 1 -C 6 alkyl, C 1 -C 6 alkenyl-O—C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 12 alkynyl, CO—C 1 -C 6 alkyl, CO—O—C 1 -C 6 alkyl, SO 2 —C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl, C 1 -C 4 alkylene-aryl, CO—O-arylalkyl, CO—O—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-aryl, CO-aryl, SO 2 -aryl, hetaryl, CO-hetaryl or SO 2 —C 1 -C 4 alkylene-aryl;
R 4 denotes
a bond in the ring to X 5 while maintaining a C═C double bond for the case when X 5 ═C or for the case when X 5 ═N, it may denote a radical selected from the group consisting of hydrogen, CN, CF 3 , CHF 2 , COOH, halogen or, in each case optionally
substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 2 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 2 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 2 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-hetaryl or C 1 -C 4 alkylene-aryl; or
R 3 and R 4 together with the respective carbon atom to which they are bound may form a three-membered, optionally substituted carbocycle,
R 5 denotes
hydrogen, a free electron pair or
in each case optionally substituted O—C 1 -C 6 alkyl, C 1 -C 6 alkyl, CO—C 1 -C 6 alkyl or —CO—O—C 1 -C 6 alkyl;
X 1 denotes C or N,
X 2 denotes C or N,
X 3 denotes C or N,
X 4 denotes C or N,
such that at most one of radicals X 1 through X 4 may denote N at the same time,
in which
R 6 , R 7 , R 8 and R 9 denote,
each independently of one another, a free electron pair when bound to a nitrogen atom (N), or when bound to a carbon atom (C), then they may denote, each independently of one another, the same or different radicals selected from groups 1), 2), 3), 4), 5), 6) or 7) above, which may be the same or different, such that groups 1) through 7) have the following meanings:
1) hydrogen, halogen, CN, CF 3 , CHF 2 , —OCF 3 , —NH 2 , —OH or optionally substituted C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl or NR Q 7 R Q 8 or NHR Q 7 ,
where R Q 7 and R Q 8 are defined below;
2) phenyl, which may be substituted with one, two or three radicals selected from the group consisting of R Q 2 , R Q 3 and R Q 4 such that
R Q 2 , R Q 3 and R Q 4 , each independently of one another, denotes a substituent from the following group:
hydrogen, NO 2 , NH 2 , OH, CN, CF 3 , CHF 2 , OCF 3 , OCHF 2 , COOH, O—CH 2 —COOH, SH, halogen or
in each case optionally substituted aryl, hetaryl, heterocycloalkyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 2 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 2 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, C 1 -C 4 alkylene-aryl or C 1 -C 4 alkylene-hetaryl or
O—R Q 5 , S—R Q 5 , NR Q 7 R Q 8 , CO—OR Q 6 , NR Q 7 —CO—O—R Q 6 , O—CH 2 —COO—R Q 6 , NR Q 7 —CO—R Q 6 , SO 2 —R Q 6 , NR Q 7 —SO 2 —R Q 6 , SO 2 NH 2 , CONH 2 , SO 2 —NR Q 7 R Q 8 or CO—NR Q 7 R Q 8 or
two radicals selected from the group consisting of R Q 2 , R Q 3 and R Q 4 together may form a three- to seven-membered, optionally substituted, saturated, unsaturated or aromatic carbocycle or an optionally substituted, saturated, unsaturated aromatic heterocycle that may contain one, two or three additional heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S and optionally two substituted radicals on this heterocycle together may form an anellated, optionally substituted, saturated, unsaturated or aromatic carbocycle or heterocycle, such that the heterocycle may contain one, two or three heteroatoms that are the same or different and are selected from the group consisting of O, N and S, and the resulting cyclic group may optionally be substituted and/or another optionally substituted cyclic group may be condensed onto this cyclic group;
R Q 5 denotes in each case optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, heterocycloalkyl or hetaryl or C 1 -C 4 alkyl that is optionally substituted once or more with one or more substituents that may be the same or different and are selected from the group consisting of halogen, NO 2 , NH 2 , OH, CN, CF 3 , CHF 2 , OCF 3 , OCHF 2 , NH—(C 1 -C 6 alkyl) and N(C 1 -C 6 alkyl) 2 ;
R Q 6 denotes in each case optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl or C 1 -C 6 alkylene-O—C 1 -C 6 alkyl;
R Q 7 denotes, independently of the respective incidence, hydrogen, CN or in each case optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl, CO—C 1 -C 6 alkyl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-hetaryl, CO-aryl, CO-hetaryl, CO—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-hetaryl, CO—O—C 1 -C 6 alkyl, CO—O-aryl, CO—O—C 1 -C 4 alkylene-aryl, CO—O-hetaryl, CO—O—C 1 -C 4 alkylene-hetaryl, SO 2 —C 1 -C 6 alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 —C 1 -C 4 alkylene-aryl or SO 2 —C 1 -C 4 alkylene-hetaryl;
R Q 8 denotes, independently of the respective incidence, in each case optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl, CO—C 1 -C 6 alkyl, CO-aryl, CO-hetaryl, CO—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-hetaryl, CO—O—C 1 -C 6 alkyl, CO—O-aryl, CO—O—C 1 -C 4 alkylene-aryl, CO—O-hetaryl, CO—O—C 1 -C 4 alkylene-hetaryl, SO 2 —C 1 -C 6 alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 —C 1 -C 4 alkylene-aryl or SO 2 —C 1 -C 4 alkylene-hetaryl;
or the radicals R Q 7 and R Q 8 together with the nitrogen may form a three- to seven-membered, optionally substituted, saturated or aromatic heterocycle that may contain one, two or three other heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S; and
optionally two substituted radicals on this heterocycle together may form an anellated, optionally substituted, saturated, unsaturated or aromatic carbocycle or heterocycle, such that the heterocycle may contain one, two or three heteroatoms that are the same or different and are selected from the group consisting of O, N and S, and the cyclic group thereby formed may optionally be substituted or another optionally substituted cyclic group may be condensed onto this cyclic group;
3) a five- or six-membered hetaryl radical, optionally substituted once or twice with substituents that are the same or different and are selected from the group consisting of:
2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-pyrimidyl, 6-pyrimidyl, 3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl, 6-pyridazinyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, thiadiazolyl, oxadiazolyl or triazinyl or their anellated derivatives indazolyl, benzothiophenyl, benzofuranyl, indolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, quinolinyl and isoquinolinyl, such that the substituents are preferably selected from the group consisting of halogen, NO 2 , NH 2 , OH, CN, CF 3 , OCF 3 , CHF 2 , OCHF 2 , C 1 -C 6 alkyl, O—C 1 -C 6 alkyl, NH—(C 1 -C 6 alkyl), N(C 1 -C 6 alkyl) 2 , NHCO—C 1 -C 4 alkyl, NHSO 2 —C 1 -C 4 alkyl and SO 2 —C 1 -C 4 alkyl;
4) two of the radicals R 6 , R 7 , R 8 or R 9 together form a four- to seven-membered, optionally substituted, partially or fully saturated carbocyclic group or a five- or six-membered, optionally substituted, partially or fully saturated heterocyclic group, which may contain one, two or three heteroatoms that are the same or different and are selected from the group consisting of O, N and S;
5) an optionally substituted C 3 -C 8 monocyclic saturated hydrocarbon radical;
6) an optionally substituted four- to seven-membered mono- or bicyclic, partially or fully saturated heterocyclic group, which may contain one, two or three heteroatoms that may be the same or different and are selected from the group consisting of O, N and S, such that this cyclic group may be substituted one or more times. For the case when the heterocyclic group contains a nitrogen atom, this nitrogen atom may be substituted with an R Q 7 radical as defined above;
such that the following, optionally substituted radicals azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, pyrrolin-1-yl, pyrrolin-3-yl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, 1,2,3,6-tetrahydropyridin-1-yl, 1,2,3,6-tetrahydropyridin-4-yl, piperidin-1-yl,
piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, tetrahydro-2H-pyran-4-yl, tetrahydrofuran-3-yl, azepan-4-yl, azepan-3-yl, azepan-2-yl, 1,4-diazepan-5-yl, morpholinyl or piperazinyl are preferred;
such that the following, optionally substituted radicals
are especially preferred;
7) a radical of general formula V
—(CR V 1 R V 2 ) d —(Y) e —(CR V 3 R V 4 ) f —R V 5 V
having the indices
d=0, 1, 2, 3 or 4
e=0 or 1
f=0, 1, 2, 3 or 4
where the sum of d, e and f is 1, 2, 3, 4, 5, 6, 7 or 8;
R V 1 , R V 2 , R V 3 , R V 4 independently of one another denote
hydrogen, halogen, OH or
in each case optionally substituted C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkyl, aryl, C 1 -C 4 alkylene-aryl, hetaryl or C 1 -C 4 alkylene-hetaryl or
independently of one another, two radicals R V 1 and R V 2 or R V 3 and R V 4 together may form a three- to seven-membered, optionally substituted, saturated or unsaturated carbocyclic or heterocyclic group, such that the heterocyclic group may contain one, two or three heteroatoms selected from the group consisting of O, N and S;
R V 5 denotes
a radical as defined above in one of the groups 1), 2), 3), 5) or 6):
Y denotes
—CO—, —O—, —S—, —SO—, —SO 2 —, —CS—NR Y 5 —, —COO—, —O—CO—, —CO—NR Y 5 , —NR Y 5 —CO—, —SO 2 —NR Y 5 , —NR Y 5 —SO 2 —;
such that
R Y 5 denotes
hydrogen or
optionally substituted C 1 -C 6 alkyl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 12 alkynyl, CO—C 1 -C 6 alkyl, CO—O—C 1 -C 6 alkyl, SO 2 —C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl, C 1 -C 4 alkylene-aryl, CO—O—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-aryl, CO-aryl, SO 2 aryl, hetaryl, CO-hetaryl or SO 2 —C 1 -C 4 alkylene-aryl;
X 5 denotes
C or N,
Z denotes
a radical of general formula Z1
where
a=1, 2, 3 or 4,
preferably a=1 or 2,
especially preferably a=1,
R Z 1 , R Z 2 independently of one another denote
hydrogen, halogen, OH or
in each case optionally substituted C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkyl, aryl, C 1 -C 4 alkylene-aryl, hetaryl or C 1 -C 4 alkylene-hetaryl or
each independently of one another denote two radicals R Z i and R Z 2 which together form a three- to seven-membered, optionally substituted, saturated or unsaturated carbocyclic or heterocyclic group, such that the heterocyclic group may contain one, two or three heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S, such that preferably R Z 1 and R Z 2 should not both be OH at the same time,
W denotes a radical of general formula W
in which
A denotes OH, CN, OCF 3 , CHF 2 , CF 3 , OCHF 2 , COOH, O—CH 2 —COOH, SH, C 1 -C 4 alkylene-OH, NR A 4 —COOH,
or
R A 1 , O—R A 1 , CO—R A 1 , S—R A 1 , SO—R A 1 , CO—O—R A 1 , NR A 4 —CO—O—R A 1 , O—CH 2 —COO—R A 1 , NR A 2 R A 3 , NR A 4 —CO—R A 1 , SO 2 —R A 1 , NR A 4 —SO 2 —R A 1 , SO 2 —NR A 2 R A 3 , CO—NR A 2 R A 3 , C 1 -C 4 alkylene-NR A 2 R A 3 , C 1 -C 4 alkylene-CO—NR A 2 R A 3 , C 1 -C 4 alkylene-NR A 2 R A 3 , C 1 -C 4 alkylene-CO—NR A 2 R A 3 or C 1 -C 4 alkylene-O—R A 1 ;
preferably A=optionally substituted —O—C 1 -C 3 alkyl or —O—C 1 -C 3 haloalkyl, —N(C 1 -C 3 alkyl) 2 , piperidinyl or morpholinyl,
especially preferably A=optionally substituted —O—C 1 -C 3 alkyl or —O—C 1 -C 3 alkyl substituted with one, two, three, four or five halogen atoms that may be the same or different and are selected from the group consisting of fluorine, chlorine, bromine and iodine;
most especially preferred is A=-O—CH 3 , —OCF 3 , —OCHF 2 , —OCH 2 F, —O—CH 2 —CH 3 , —O—CH 2 —CF 3 , —O—CH 2 —CHF 2 , —O—CH 2 —CH 2 F or O-isopropyl;
even more preferably A=-O—CH 3 , —O—CH 2 —CH 3 , —O—CH 2 —CF 3 , —O—CH 2 —CHF 2 or —O—CH 2 —CH 2 F;
most preferred is A=-O—CH 3 ;
in which
R A 1 denotes
independently of the respective occurrence, in each case optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-aryl, C 2 -C 6 alkylene-aryl, C 1 -C 6 alkylene-hetaryl, C 1 -C 4 alkylene-NR A 2 R A 3 or C 1 -C 4 alkylene-O—C 1 -C 6 alkyl;
R A 2 denotes
independently of their respective occurrence, hydrogen, OH, CN
or
in each case optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-hetaryl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl; CO—C 1 -C 6 alkyl, CO-aryl, CO-hetaryl, CO—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-hetaryl, CO—O—C 1 -C 6 alkyl, CO—O-aryl, CO—O—C 1 -C 4 alkylene-aryl, CO—O-hetaryl, CO—O—C 1 -C 4 alkylene-hetaryl, SO 2 —C1-C6 alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 —C 1 -C 4 alkylene-aryl or SO 2 —C 1 -C 4 alkylene-hetaryl;
R A 3 denotes
independently of the respective occurrence, hydrogen or in each case optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-hetaryl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl; CO—C 1 -C 6 alkyl, CO-aryl, CO-hetaryl, CO—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-hetaryl, CO—O—C 1 -C 6 alkyl, CO—O-aryl, CO—O—C 1 -C 4 alkylene-aryl, CO—O-hetaryl, CO—O—C 1 -C 4 alkylene-hetaryl, SO 2 —C 1 -C 6 alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 —C 1 -C 4 alkylene-aryl or SO 2 —C 1 -C 4 alkylene-hetaryl;
or the radicals R A 2 and R A 3 together with the nitrogen to which they are attached may form a three- to seven-membered, optionally substituted, saturated or aromatic heterocycle, which may contain one, two or three additional heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S; such that two optionally substituted radicals on this heterocycle together may form an anellated, optionally substituted, saturated, unsaturated or aromatic carbocycle or heterocycle, such that the heterocycle may contain one, two or three heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S and such that the cyclic group thereby formed may optionally be substituted and/or another optionally substituted cyclic group may be condensed onto this cyclic group;
R A 4 denotes
independently of the respective occurrence, hydrogen or in each case optionally substituted C 1 -C 6 alkyl, C 1 -C 6 alkenyl-O—C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 12 alkynyl, CO—C 1 -C 6 alkyl. CO—O—C 1 -C 6 alkyl, SO 2 —C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl, C 1 -C 4 alkylene-aryl, CO—O-arylalkyl, CO—C 1 -C 4 alkylene-aryl, CO-aryl, SO 2 -aryl, hetaryl, CO-hetaryl or SO 2 —C 1 -C 4 alkylene-aryl;
B denotes
hydrogen, NO 2 , NH 2 , OH, CN, OCF 3 , CHF 2 , CF 3 , OCHF 2 , COOH, O—CH 2 —COOH, halogen, SH, C 1 -C 4 alkylene-OH, NR A 4 —COOH,
or
in each case optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-hetaryl, C 1 -C 4 alkylene-aryl, O—R A 1 , CO—R A 1 , S—R A 1 , SO—R A 1 , CO—O—R A 1 , NR A 4 —CO—O—R A 1 , O—CH 2 —COO—R A 1 , NR A 2 R A 3 , NR A 4 —CO—R A 1 , SO 2 —R A 1 , NR A 4 —SO 2 —R A 1 , SO 2 —NR A 2 R A 3 , CO—NR A 2 R A 3 , C 1 -C 4 alkylene-NR A 2 R A 3 , C 1 -C 4 alkylene-CO—NR A 2 R A 3 , C 1 -C 4 alkylene-SO 2 —NR A 2 R A 3 or C 1 -C 4 alkylene-O—R A 1 ;
or independently of one another, two of the radicals A, B or R W together with the respective carbon atom to which they are attached may form a five- to seven-membered, optionally substituted, saturated or unsaturated carbocycle or a five- to seven-membered, optionally substituted, saturated or unsaturated or aromatic heterocycle that may contain one, two or three additional heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S; such that optionally two substituted radicals on this carbocycle or heterocycle together may form an anellated, optionally substituted, saturated, unsaturated or aromatic carbocycle or heterocycle, such that the heterocycle may contain one, two or three heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S, and such that the cyclic group thus formed may optionally be substituted and/or another optionally substituted cyclic group may be condensed onto this cyclic group;
R W denotes
hydrogen, OH, halogen, NO 2 , NH 2 , CN, CF 3 , CHF 2 , OCF 3 , OCHF 2
or
in each case optionally substituted C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl, C 1 -C 6 thioalkyl, aryl, hetaryl, O—C 1 -C 6 alkyl, O-aryl, O—C 1 -C 4 alkylene-aryl, O-benzyl, C 1 -C 6 alkylamino, C 1 -C 6 dialkylamino, pyrrolidinyl, piperidinyl, morpholinyl, CO—C 1 -C 6 alkyl, SO 2 —C 1 -C 6 alkyl, CO-aryl, SO 2 -aryl, CO—C 1 -C 4 alkylene-aryl, SO 2 —C 1 -C 4 alkylene-aryl, SO-aryl, CONH 2 , CONH—C 1 -C 6 alkyl, SO 2 NH—C 1 -C 6 alkyl, CON—(C 1 -C 6 alkyl) 2 , SO 2 N—(C 1 -C 6 alkyl) 2 , NH—SO 2 —C 1 -C 6 alkyl or NH—CO—C 1 -C 6 alkyl;
optionally preferably with one, two, three, four or five measures selected from the group consisting of measures (i), (ii), (iii), (iv) and (v):
measure (i): according to a preferred embodiment, at least one compound of general formula I, in which the radicals R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , X 1 , X 2 , X 3 , X 4 , X 5 , Z and W have the meanings given above, with the provision that when X 5 ═N, then R 3 and R 4 are each hydrogen and/or
measure (ii): according to another preferred embodiment, at least one compound of general formula I, in which the radicals R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , X 1 , X 2 , X 3 , X 4 , X 5 , Z and W have the meanings given above, with the provision that when X 2 ═N and X 5 ═C, R 8 is not bound to the 1,6-naphthyridine ring by a nitrogen, oxygen or sulfur atom and/or
measure (iii): according to another preferred embodiment, at least one compound of general formula I, in which the radicals R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , X 1 , X 2 , X 3 , X 4 , X 5 , Z and W have the meanings given above, with the provision that when X 4 ═N and X 5 ═C then R 8 is not bound to the 1,8-naphthyridine ring by a nitrogen atom and/or
measure (iv): according to another preferred embodiment, at least one compound of general formula I, in which the radicals R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , X 1 , X 2 , X 3 , X 4 , X 5 , Z and W have the meanings given above, with the provision that when X 1 , X 2 , X 3 , X 4 and X 5 each equal C, then R 3 does not denote COOH, COOR 3 or a pharmaceutically acceptable acid mimetic as defined in U.S. Patent Application No. US 2005/0101568, paragraph [0088], pages 6 and 7 and/or
measure (v): according to a preferred embodiment, at least one compound of general formula I, in which the radicals R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , X 1 , X 2 , X 3 , X 4 , X 5 , Z and W have the meanings given above, with the provision that formula I does not denote 2-({2-[(2-benzoyl-4-chlorophenyl)amino]-6-chloro-4-phenylquinolin-3-yl}methyl)benzoic acid or 3-[2-(methoxymethyl)benzyl]-3,4-dihydroquinazolin-2-amine.
2 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
R 1 and R 2 independently of one another denote hydrogen, a free electron pair, OH, CN or optionally substituted O—C 1 -C 6 alkyl, C 1 -C 6 alkyl, CO—C 1 -C 6 alkyl, CO—OC 1 -C 6 alkyl.
3 . A one compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
A denotes OH, —O—C 1 -C 6 alkyl, —OCF 3 , —OCHF 2 or optionally substituted —NH—C 1 -C 6 alkyl, —NH—CO—C 1 -C 6 alkyl, —NH—SO 2 —C 1 -C 6 alkyl, —N(C 1 -C 6 alkyl) 2 , piperidinyl, morpholinyl, —N(C 1 -C 6 alkyl)-CO—C 1 -C 6 alkyl or
—N(C 1 -C 6 alkyl)-SO 2 —C 1 -C 6 alkyl, C 1 -C 4 alkylene-CO—N(CH 3 ) 2 , C 1 -C 4 alkylene-CO—N-piperidyl, C 1 -C 4 alkylene-CO—N-morpholinyl, C 1 -C 4 alkylene-SO 2 —N(CH 3 ) 2 , C 1 -C 4 alkylene-SO 2 —N-piperidyl, C 1 -C 4 alkylene, SO 2 —N-morpholinyl or C 1 -C 4 alkyl-O—C 1 -C 4 alkyl and
B denotes hydrogen, CN, CF 3 , OCF 3 , OCHF 2 , CHF 2 , COOH, halogen, or optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-hetaryl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-NR A 2 R A 3 , C 1 -C 4 alkylene-CO—NR A 2 R A 3 , C 1 -C 4 alkylene-SO 2 —NR A 2 R A 3 , NR A 4 —CO—R A 1 , NR A 4 —SO 2 —R A 1 , or C 1 -C 4 alkylene-O—R A 1 , —O—R A 1 or —NR A 2 R A 3 ; in which R A 1 denotes
independently of its respective occurrence, optionally substituted C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, C 1 -C 4 alkylene-aryl, C 1 -C 6 alkylene-hetaryl, C 1 -C 4 alkylene-NR A 2 R A 3 , C 1 -C 4 alkylene-CO—NR A 2 R A 3 or C 1 -C 4 alkylene-O—C 1 -C 6 alkyl;
R A 2 denotes
independently of its respective occurrence, hydrogen, CN or optionally substituted C 1 -C 6 alkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-hetaryl, CO—C 1 -C 6 alkyl, CO-aryl, CO-hetaryl, CO—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-hetaryl, CO—O—C 1 -C 6 alkyl, SO 2 -aryl or SO 2 -hetaryl;
R A 3 denotes
independently of its respective occurrence, hydrogen or optionally substituted C 1 -C 6 alkyl;
or the radicals R A 2 and R A 3 together with the nitrogen may form a five- or six-membered, optionally substituted, saturated or
aromatic heterocycle that may contain another heteroatom that may be the same or different and is selected from the group O, N, S;
R A 4 denotes
hydrogen or
optionally substituted C 1 -C 6 alkyl;
R W denotes hydrogen, CN, CF 3 , OCF 3 or
optionally substituted C 1 -C 6 alkyl or O—C 1 -C 6 alkyl or independently of one another, two radicals selected from the group consisting of A, B, or R W together with the respective carbon atom to which they are attached may form a five- or six-membered, optionally substituted, saturated or unsaturated carbocycle or a five- or six-membered, optionally substituted, saturated or unsaturated or aromatic heterocycle, which may contain one, two or three other heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S.
4 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
Z denotes —CH 2 —, —CH(C 1 -C 3 alkyl), optionally C 1 -C 3 alkyl-substituted C 1 -C 3 alkylene or —CH 2 —C—(CH 2 —CH 2 )—CH 2 —.
5 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
Z denotes —CH 2 —, —CH 2 —CH 2 — or —CH 2 —CH 2 —CH 2 —.
6 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
Z denotes —CH 2 —.
7 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which the stated radicals are defined as follows:
W denotes, with the provision that A denotes optionally substituted —O—C 1 -C 6 alkyl, —OCF 3 , —OCHF 2 , —N(C 1 -C 3 alkyl) 2 , piperidinyl, morpholinyl and B denotes
hydrogen, CN, CF 3 , OCF 3 , —OCHF 2 , CHF 2 , COOH, halogen, or optionally substituted C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-NR A 2 R A 3 , C 1 -C 4 alkylene-CO—NR A 2 R A 3 , C 1 -C 4 alkylene-SO 2 —NR A 2 R A 3 , NR A 4 —CO—R A 1 , NR A 4 —SO 2 —R A 1 or C 1 -C 4 alkylene-O—R A 1 , —O—R A 1 or —NR A 2 R A 3 ,
in which
R A 1 denotes
independently of its respective occurrence, optionally substituted C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, phenyl, pyridyl, C 1 -C 4 alkylene-NR A 2 R A 3 or C 1 -C 4 alkylene-O—C 1 -C 6 alkyl;
R A 2 denotes
independently of its respective occurrence, hydrogen, CN or optionally substituted C 1 -C 6 alkyl, phenyl or pyridyl;
R A 3 denotes
independently of its respective occurrence, hydrogen or optionally substituted C 1 -C 6 alkyl;
or the radicals R A 2 and R A 3 together with the nitrogen atom to which they are attached may form a five- or six-membered, optionally substituted, saturated heterocycle, which may contain another heteroatom which may be the same or different and is selected from the group consisting of O, N, S;
R A 4 denotes
independently of its respective occurrence, hydrogen or
optionally substituted C 1 -C 6 alkyl;
R W denotes hydrogen or
independently of one another, two radicals selected from the group consisting of A, B and R W together with the respective carbon atom
to which they are attached may form a five- or six-membered, optionally substituted, saturated or unsaturated or aromatic heterocycle, which may contain one or two or more heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S.
8 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, such that formula I has one of the following meanings IIa, IIb or IIc (dihydroquinazoline compound), depending on the meaning of R 1 , R 2 , R 4 and R 5
in which the radicals R 1 , R 2 , R 5 , R 6 , R 7 , R 8 , R 9 , X 1 , X 2 , X 3 , X 4 , Z and W, unless otherwise described above, have the same meanings as in claim 1 and in which the stated radicals are defined as follows:
R 3 denotes hydrogen and
R 4 denotes hydrogen.
9 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof,
such that formula I has one of the following meanings IIa, IIb or IIc (dihydroquinazoline compound), depending on the meaning of R 1 , R 2 , R 4 and R 5
in which the radicals R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , Z and W, unless otherwise described above, have the same meanings as in claim 1 and in which the stated radicals are defined as follows:
X 1 denotes C,
X 2 denotes C,
X 3 denotes C,
X 4 denotes C.
10 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, such that formula I has one of the following meanings IIa, IIb or IIc (dihydroquinazoline compound), depending on the meaning of R 1 , R 2 , R 4 and R 5
in which the radicals R 1 , R 2 , R 3 , R 4 , R 5 , X 2 , X 2 , X 3 , X 4 , Z and W, unless otherwise described above, have the same meanings as in claim 1 and in which the stated radicals are defined as follows:
R 6 , R 7 , R 8 and R 9 denote each independently of one another, a radical selected from groups 1), 2), 3), 4), 5), 6) or 7), which may the same or different where groups 1) through 7) have the following meanings:
1) hydrogen, halogen, CN, CF 3 , —OCF 3 , or optionally substituted C 1 -C 4 alkyl, C 2 -C 4 alkenyl or NR Q 7 R Q 8 or NHR Q 7 ,
in which R Q 7 and R Q 8 are defined as shown below
2) phenyl optionally substituted with one, two or three radicals which may be the same or different and are selected from the group consisting of R Q 2 , R Q 3 and R Q 4 in which
R Q 2 , R Q 3 and R Q 4 , each independently of one another, denote a substituent from the following group:
hydrogen, NO 2 , NH 2 , OH, CN, CF 3 , CHF 2 , OCF 3 , OCHF 2 , COOH, O—CH 2 —COOH, SH, halogen or
optionally substituted hetaryl, heterocycloalkyl, C 1 -C 4 alkyl, O—R Q 5 , NR Q 7 R Q 8 , or
two of the radicals selected from the group consisting of R Q 2 , R Q 3 and R Q 4 together with the respective atom to which they are attached may form a five- or six-membered, optionally substituted, saturated, unsaturated or aromatic heterocycle, which may contain one or two other different or same
heteroatoms selected from the group consisting of O, N and S;
R Q 5 denotes optionally substituted C 1 -C 4 alkyl;
R Q 7 denotes, independently of its respective occurrence, hydrogen or optionally substituted C 1 -C 4 alkyl;
R Q 8 denotes, independently of the respective occurrence, optionally substituted C 1 -C 4 alkyl, aryl or hetaryl;
or the radicals R Q 7 and R Q 8 together with the nitrogen atom to which they are attached may form a five- or six-membered, optionally substituted, saturated or aromatic heterocycle, which may contain one or two additional heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S;
3) a five- or six-membered hetaryl radical, optionally having one or two substituents that may be the same or different and are selected from the group consisting of:
2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, in which the substituents are preferably selected from the group consisting of halogen, CN, CF 3 , OCF 3 , or optionally substituted C 1 -C 3 alkyl, O—C 1 -C 4 alkyl, NH—(C 1 -C 4 alkyl), N(C 1 -C 4 alkyl) 2 ;
4) two radicals selected from the group consisting of R 6 , R 7 , R 8 and R 9 together with the respective atom to which they are attached may form a five- or six-membered, optionally substituted, partially or fully saturated carbocycle or a five- or six-membered, optionally substituted, partially or fully saturated heterocycle, which may have one or two heteroatoms that are the same or different and are selected from the group consisting of O, N and S;
5) an optionally substituted C 3 -C 5 monocyclic saturated hydrocarbon radical;
6) an optionally substituted five- or six-membered monocyclic, partially or fully saturated heterocycle selected from the following group:
in which the radical R Q 7 is defined as described above, independently of its occurrence;
7) a radical of general formula V
—(CR V 1 R V 2 ) d —(Y) e —(CR V 3 R V 4 ) f —R V 5 V
with the indices
d=0 or 1,
e=0 or 1,
f=0 or 1,
in which the sum of d, e and f is 1, 2 or 3;
R V 1 , R V 2 , R V 3 , R V 4 independently of one another denote
hydrogen or C 1 -C 4 alkyl,
R V 5 denotes a radical selected from the radicals as defined above in groups 1), 2), 3), 5) or 6);
Y denotes —CO—, —O—, —S—, —NR Y 5 —, —CO—NR Y 5 , —NR Y 5 —CO—, —SO 2 —NR Y 5 , —NR Y 5 —SO 2 —;
in which
R Y 5 denotes
hydrogen or
optionally substituted C 1 -C 6 alkyl.
11 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, such that formula I has one of the following meanings IIa, IIb or IIc (dihydroquinazoline compound), depending on the meaning of R 1 , R 2 , R 4 and R 5
in which the radicals R 1 , R 2 , R 3 , R 4 , R 5 , X 1 , X 2 , X 3 , X 4 , Z and W, unless otherwise described above, have the same meanings as in claim 1 and in which the stated radicals are defined as follows:
R 6 , R 7 , R 8 and R 9 denote
each independently of one another, a radical selected from the same or different radicals of groups 1), 2), 3), 4), 5), 6) or 7), in which groups 1) through 7) have the following meanings:
1) hydrogen, Cl, F, CN, CF 3 , —OCF 3 , or
optionally substituted C 1 -C 4 alkyl or NR Q 7 R Q 8
in which R Q 7 and R Q 8 are defined as shown below
2) phenyl optionally substituted with one, two or three radicals selected from the group consisting of R Q 2 , R Q 3 and R Q 4 in which
R Q 2 , R Q 3 and R Q 4 , each independently of one another, denote a substituent that may be the same or different and is selected from the following group:
hydrogen, CN, CF 3 , Cl, F or
optionally substituted C 1 -C 4 alkyl, O—R Q 5 , NR Q 7 R Q 8 ;
R Q 5 denotes optionally substituted C 1 -C 2 alkyl;
R Q 7 denotes, independently of its respective occurrence, hydrogen
or
optionally substituted C 1 -C 2 alkyl;
R Q 8 denotes, independently of its respective occurrence, optionally substituted C 1 -C 2 alkyl;
3) optionally substituted 2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-pyridyl, 3-pyridyl or 4-pyridyl;
4) two of the radicals R 6 , R 1 , R 8 or R 9 together with the respective atom to which they are attached may form an optionally substituted 1,3-dioxolane ring;
5) optionally substituted cyclopropyl or cyclopentyl;
6) a six-membered monocyclic, optionally substituted heterocycle selected from the following group:
in which the radical R Q 7 is defined as above, independently of its occurrence;
7) an optionally substituted radical of general formula V
—(CR V 1 R V 2 ) d —(Y) e —(CR V 3 R V 4 ) f —R Y 5 V
with the indices
d=0 or 1,
e=0 or 1,
f=0 or 1,
in which the sum of d, e and f is 1 or 2;
R V 1 , R V 2 , R V 3 and R V 4 each denotes hydrogen,
R V 5 denotes, independently of its occurrence, a radical selected from radicals as defined above in groups 1), 2), 3), 5) or 6);
Y denotes
—CO—,—O—,—NR Y 5 —;
in which
R Y 5 denotes
hydrogen or methyl.
12 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, such that formula I has one of the following meanings IIa, IIb or IIc (dihydroquinazoline compound), depending on the meaning of R 1 , R 2 , R 4 and R 5
in which the radicals R 1 , R 2 , R 3 , R 4 , R 5 , X 2 , X 2 , X 3 , X 4 , Z and W, unless otherwise described above, have the same meanings as in claim 1 and in which the stated radicals are defined as follows:
R 6 , R 7 , R 8 and R 9 denote
each independently of one another, a radical that may be the same or different selected from the group consisting of:
hydrogen, Cl, F, CN, CF 3 , —OCF 3 , C 1 -C 4 alkyl, NMe 2 , methoxy, ethoxy; phenyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, morpholinyl or N-methylpiperazinyl which may optionally be substituted once, twice or three times with Cl, F, methyl or methoxy, where the substituents may be the same or different.
13 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, such that formula I has one of the following meanings IIa, IIb or IIc (dihydroquinazoline compound), depending on the meaning of R 1 , R 2 , R 4 and R 5
in which the radicals R 3 , R 4 , R 6 , R 7 , R 8 , R 9 , Z and W, unless otherwise described above, have the same meanings as in claim 1 and in which the stated radicals are defined as follows:
R 2 denotes hydrogen
R 2 denotes hydrogen and
R 5 denotes hydrogen or a free electron pair.
14 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, such that formula I has one of the following meanings IIIa, IIIb or IIIc (quinoline compound), depending on the meaning of R 1 , R 2 and R 5
and R 1 , R 2 , R 5 , R 6 , R 7 , R 8 , R 9 , X 1 , X 2 , X 3 , X 4 , Z and W, unless otherwise described above, have the same meanings as in claim 1 and in which the stated radicals are defined as follows:
R 3 denotes hydrogen, CN, CF 3 , Cl, F, methoxy, ethoxy, methyl, ethyl,
optionally substituted phenyl.
15 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, such that formula I has one of the following meanings IIIa, IIIb or IIIc (quinoline compound), depending on the meaning of R 1 , R 2 and R 5
and R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , Z and W, unless otherwise described above, have the same meanings as in claim 1 and in which the stated radicals are defined as follows:
X 2 denotes C,
X 2 denotes C or N,
X 3 denotes C or N,
X 4 denotes C.
16 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, such that formula I has one of the following meanings IIIa, IIIb or IIIc (quinoline compound), depending on the meaning of R 1 , R 2 and R 5
and R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , Z and W, unless otherwise described above, have the same meanings as in claim 1 , and in which the stated radicals are defined as follows:
X 1 denotes C,
X 2 denotes C,
X 3 denotes C,
X 4 denotes C.
17 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, such that formula I has one of the following meanings IIIa, IIIb or IIIc (quinoline compound), depending on the meaning of R 1 , R 2 and R 5
in which the radicals R 1 , R 2 , R 3 , R 5 , X 2 , X 2 , X 3 , X 4 , Z and W, unless otherwise described above, have the same meanings as in claim 1 and in which the stated radicals are defined as follows:
R 6 , R 7 , R 8 and R 9 denote
each independently of the others, a radical that may be the same or different is selected from the same or different radicals of the groups 1), 2), 3), 4), 5), 6) or 7), in which groups 1) through 7) have the following meanings:
1) hydrogen, halogen, CN, CF 3 , —OCF 3 , or
optionally substituted C 1 -C 4 alkyl, C 2 -C 4 alkenyl or NR Q 7 R Q 8
in which R Q 7 and R Q 8 are defined as shown below
2) phenyl optionally substituted with one, two or three radicals which may be the same or different and are selected from the group consisting of R Q 2 , R Q 3 and R Q 4 in which
R Q 2 , R Q 3 and R Q 4 , independently of one another each denote a substituent that may be the same or different and is selected from the following group:
hydrogen, NO 2 , NH 2 , OH, CN, CF 3 , CHF 2 , OCF 3 , OCHF 2 , COOH, O—CH 2 —COOH, SH, halogen or
optionally substituted hetaryl, heterocycloalkyl, C 1 -C 4 alkyl, O—R Q 5 , NR Q 7 R Q 8 or
two of the radicals from R Q 2 , R Q 3 or R Q 4 together with the carbon atom to which they are attached may form a five- or six-membered, optionally substituted, saturated, unsaturated or aromatic heterocycle that may contain one or two additional different or the same heteroatoms selected from the group consisting of O, N and S, in which
R Q 5 denotes optionally substituted C 1 -C 4 alkyl;
R Q 7 denotes, independently of its respective occurrence, hydrogen
or
in each case optionally substituted C 1 -C 4 alkyl;
R Q 8 denotes, independently of its respective occurrence, optionally substituted C 1 -C 4 alkyl, aryl or hetaryl;
or the radicals R Q 7 and R Q 8 together with the nitrogen atom to which they are attached may form a five- or six-membered, optionally substituted, saturated or aromatic heterocycle, which may contain one or two additional heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S;
3) a five- or six-membered hetaryl radical, which may optionally be substituted once or twice with substituents that may be the same or different and are selected from the group consisting of:
2-thienyl, 3-thienyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 1-imidazolyl,
2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, in which the substituents are preferably selected from the group consisting of halogen, CN, CF 3 , OCF 3 , or optionally substituted C 1 -C 3 alkyl, O—C 1 -C 4 alkyl, NH—(C 1 -C 4 alkyl), N(C 1 -C 4 alkyl) 2 ;
4) two of the radicals R 6 , R 7 , R 8 or R 9 together may form a five- or six-membered, optionally substituted, partially or fully saturated carbocycle or a five- or six-membered, optionally substituted, partially or fully saturated heterocycle, which may contain one or two heteroatoms that are the same or different and are selected from the group consisting of O, N and S;
5) an optionally substituted C 3 -C 5 monocyclic saturated hydrocarbon radical;
6) an optionally substituted five- or six-membered monocyclic, partially or fully saturated heterocycle selected from the following group:
in which the radical R Q 7 , independently of its occurrence, is defined as above;
7) a radical of general formula V
—(CR V 1 R V 2 ) d —(Y) e —(CR V 3 R V 4 ) f —R V 5 V
with the indices
d=0 or 1,
e=0 or 1,
f=0 or 1,
in which the sum of d, e and f is 1, 2 or 3;
R V 1 , R V 2 , R V 3 , R V 4 independently of one another denote
hydrogen or optionally substituted C 1 -C 4 alkyl,
R V 5 denotes
a radical selected from radicals as defined above in one or more of the groups 1), 2), 3), 5) or 6);
Y denotes
—CO—, —O—, —S—, —NR Y 5 —, —CO—NR Y 5 , —NR Y 5 —CO—, —SO 2 —NR Y 5 , —NR Y 5 —SO 2 —;
in which
R Y 5 denotes
hydrogen or
optionally substituted C 1 -C 6 alkyl.
18 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, such that formula I has one of the following meanings IIIa, IIIb or IIIc (quinoline compound), depending on the meaning of R 1 , R 2 and R 5
in which the radicals R 1 , R 2 , R 3 , R 5 , X 2 , X 2 , X 3 , X 4 , Z and W, unless otherwise described above, have the same meanings as in claim 1 and in which the stated radicals are defined as follows:
R 6 , R 7 , R 8 and R 9 denote
each independently of one another, a radical selected from the groups 1), 2), 3), 4), 5), 6) or 7) which may be the same or different, such that groups 1) through 7) have the following meanings:
1) hydrogen, Cl, F, CN, CF 3 , —OCF 3 , or
optionally substituted C 1 -C 4 alkyl or NR Q 7 R Q 8
in which R Q 7 and R Q 8 are defined as shown below,
2) phenyl which may substituted with one, two or three radicals that may be the same or different and are selected from the group consisting of R Q 2 , R Q 3 and R Q 4 in which
R Q 2 , R Q 3 and R Q 4 each independently of one another denotes a substituent that may be the same or different and is selected from the following group:
hydrogen, CN, CF 3 , CHF 2 , OCF 3 , OCHF 2 , Cl, F or
optionally substituted hetaryl, heterocycloalkyl, C 1 -C 4 alkyl, O—R Q 5 , NR Q 7 R Q 8 or
two of the radicals from R Q 2 , R Q 3 or R Q 4 together with the carbon atom to which they are attached may form a five- or six-membered, optionally substituted, saturated, unsaturated or aromatic heterocycle, which may contain one or two additional heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S;
R Q 5 denotes optionally substituted C 1 -C 4 alkyl;
R Q 7 denotes, independently of its respective occurrence, hydrogen
or
in each case optionally substituted C 1 -C 4 alkyl;
R Q 8 denotes, independently of its respective occurrence, optionally substituted C 1 -C 4 alkyl, aryl or hetaryl;
or the radicals R Q 7 and R Q 8 together with the nitrogen atom to which they are attached may form a five- or six-membered, optionally substituted, saturated or aromatic heterocycle, which may contain another heteroatom selected from the group consisting of O, N and S;
3) a five- or six-membered hetaryl radical, optionally substituted once or twice with substituents that may be the same or different and are selected from the group consisting of:
2-thienyl, 3-thienyl, 2-thiazolyl, 1-pyrazolyl, 1-imidazolyl, 2-imidazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, in which the substituents are preferably selected from the group consisting of Cl, F, CN, CF 3 , OCF 3 , or optionally substituted C 1 -C 3 alkyl, O—C 1 -C 4 alkyl, NH—(C 1 -C 4 alkyl), N(C 1 -C 4 alkyl) 2 ;
4) two of the radicals R 6 , R 7 , R 8 or R 9 together with the respective atom to which they are attached may form an optionally substituted 1,3-dioxolane or morpholine ring;
5) optionally substituted cyclopropyl or cyclopentyl;
6) a five- or six-membered, optionally substituted monocyclic, partially or fully saturated heterocycle selected from the following group:
where the R Q 7 radical, independently of its occurrence, is defined as above;
7) a radical of general formula V
—(CR V 1 R V 2 ) d —(Y) e —(CR V 3 R V 4 ) f —R V 5 V
with the indices
d=0 or 1,
e=0 or 1,
f=0 or 1,
in which the sum of d, e and f is 1 or 2;
R V 1 , R V 2 , R V 3 and R V 4 each denotes hydrogen,
R V 5
denotes a radical selected from the radicals as defined above in one or more of groups 1), 2), 3), 5) or 6);
Y denotes
—CO—, —O—, —NR Y 5 —;
in which
R Y 5 denotes
hydrogen or methyl.
19 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, such that formula I has one of the following meanings IIIa, IIIb or IIIc (quinoline compound), depending on the meaning of R 1 , R 2 and R 5
in which the radicals R 1 , R 2 , R 3 , R 5 , X 2 , X 2 , X 3 , X 4 , Z and W, unless otherwise described above, have the same meanings as in claim 1 and in which the stated radicals are defined as follows:
R 6 , R 7 , R 8 and R 9 denote
each independently of one another, a radical selected from the group:
hydrogen, Cl, F, CN, CF 3 , —OCF 3 , optionally substituted C 1 -C 4 alkyl, dimethylamino, diethylamino, methoxy, ethoxy, propoxy, isopropoxy, pyrrolidinyl, piperidinyl, morpholinyl or N-methylpiperazinyl or
aryl or hetaryl, optionally substituted once or more with substituents that may be the same or different and are selected from Cl, F, methyl or methoxy, the aryl or hetaryl being selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-thiazolyl, 1-imidazolyl, 1-pyrazolyl, 2-pyridyl, 3-pyridyl or 4-pyridyl.
20 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, such that formula I has one of the following meanings IIIa, IIIb or IIIc (quinoline compound), depending on the meaning of R 1 , R 2 and R 5
in which the radicals R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , Z and W, unless otherwise described above, have the same meanings as in claim 1 and in which the stated radicals are defined as follows:
R 1 denotes hydrogen,
R 2 denotes hydrogen and
R 5 denotes hydrogen or a free electron pair.
21 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
R 1 and R 2 independently of one another denote hydrogen, a free electron pair, OH, CN or optionally substituted O—C 1 -C 6 alkyl, C 1 -C 6 alkyl, CO—C 1 -C 6 alkyl, CO—O—C 1 -C 6 alkyl, R 3 denotes hydrogen, CN, CF 3 , Cl, F, methoxy, ethoxy, methyl, ethyl, optionally substituted phenyl, R 4 denotes a bond to X 5 while preserving a C═C double bond, R 5 denotes hydrogen or a free electron pair, R 6 , R 7 , R 8 and R 9
denote each independently of one another, a radical selected from the group consisting of hydrogen, Cl, F, CN, CF 3 , —OCF 3 , optionally substituted C 1 -C 4 alkyl, dimethylamino, diethylamino, methoxy, ethoxy, propoxy, isopropoxy, pyrrolidinyl, piperidinyl, morpholinyl or N-methylpiperazinyl or
aryl or hetaryl selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-thiazolyl, 1-imidazolyl, 1-pyrazolyl, 2-pyridyl, 3-pyridyl or 4-pyridyl, each optionally substituted once or more with substituents that may be the same or different and are selected from Cl, F, methyl or methoxy;
X 1 denotes C, X 2 denotes C, X 3 denotes C, X 4 denotes C, X 5 denotes C, Z denotes —CH 2 —, —CH 2 —CH 2 — or —CH 2 —CH 2 —CH 2 — and W with A denotes optionally substituted —O—C 1 -C 6 alkyl, —OCF 3 , —OCHF 2 , —NH—C 1 -C 6 alkyl, —NH—CO—C 1 -C 6 alkyl, —NH—SO 2 —C 1 -C 6 alkyl, —N(C 1 -C 6 alkyl) 2 , piperidinyl, morpholinyl, —N(C 1 -C 6 alkyl)-CO—C 1 -C 6 alkyl or —N(C 1 -C 6 alkyl)-SO 2 —C 1 -C 6 alkyl, C 1 -C 4 alkylene-CO—N(CH 3 ) 2 , C 1 -C 4 alkylene-CO—N-piperidyl, C 1 -C 4 alkylene-CO—N-morpholinyl, C 1 -C 4 alkylene-SO 2 —N(CH 3 ) 2 , C 1 -C 4 alkylene-SO 2 —N-piperidyl, C 1 -C 4 alkylene, SO 2 —N-morpholinyl or C 1 -C 4 alkyl-O—C 1 -C 4 alkyl and B denotes hydrogen, CN, CF 3 , OCF 3 , —OCHF 2 , CHF 2 , COOH, halogen, or optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-hetaryl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-NR A 2 R A 3 , C 1 -C 4 alkylene-CO—NR A 2 R A 3 , C 1 -C 4 alkylene-SO 2 —NR A 2 R A 3 , NR A 4 —CO—R A 1 , NR A 4 —SO 2 —R A 1 , or C 1 -C 4 alkylene-O—R A 1 , —O—R A 1 or —NR A 2 R A 3 ; in which R A 1 denotes
optionally substituted C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, C 1 -C 4 alkylene-aryl, C 1 -C 6 alkylene-hetaryl, C 1 -C 4 alkylene-NR A 2 R A 3 , C 1 -C 4 alkylene-CO—NR A 2 R A 3 or C 1 -C 4 alkylene-O—C 1 -C 6 alkyl;
R A 2 denotes
hydrogen, CN or
optionally substituted C 1 -C 6 alkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-hetaryl, CO—C 1 -C 6 alkyl, CO-aryl, CO-hetaryl, CO—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-hetaryl, CO—O—C 1 -C 6 alkyl, SO 2 -aryl or SO 2 -hetaryl;
R A 3 denotes
hydrogen or optionally substituted C 1 -C 6 alkyl;
or the radicals R A 2 and R A 3 together with the nitrogen atom to which they are attached may form a five- or six-membered, optionally substituted, saturated or aromatic heterocycle, which may contain another heteroatom that may be the same or different and is selected from the group consisting of O, N and S;
R A 4 denotes
hydrogen or
optionally substituted C 1 -C 6 alkyl;
R W denotes hydrogen, CN, CF 3 , OCF 3 or
optionally substituted C 1 -C 6 alkyl or O—C 1 -C 6 alkyl
or, independently of one another, two of the radicals A, B, or R W together with the carbon atom to which they are attached may form a five- or six-membered, optionally substituted, saturated or unsaturated carbocycle or a five- or six-membered, optionally substituted, saturated or unsaturated or aromatic heterocycle, which may contain one, two or three additional heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S.
22 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
R 1 denotes hydrogen, R 2 denotes hydrogen and R 3 denotes hydrogen, CN, CF 3 , Cl, F, methoxy, ethoxy, methyl, ethyl, optionally substituted phenyl, R 4 denotes a bond to X 5 while preserving a C═C double bond, R 5 denotes hydrogen or a free electron pair, R 6 , R 7 , R 8 and R 9
denote, each independently of one another, a radical that may be the same or different and is selected from the group consisting of
hydrogen, Cl, F, CN, CF 3 , —OCF 3 , C 1 -C 4 alkyl, dimethylamino, diethylamino, methoxy, ethoxy, propoxy, isopropoxy, pyrrolidinyl, piperidinyl, morpholinyl or N-methylpiperazinyl or
aryl or hetaryl selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-thiazolyl, 1-imidazolyl, 1-pyrazolyl, 2-pyridyl, 3-pyridyl and 4-pyridyl, optionally substituted once or more with substituents that may be the same or different and are selected from Cl, F, methyl or methoxy;
X 1 denotes C, X 2 denotes C, X 3 denotes C, X 4 denotes C, X 5 denotes C, Z denotes —CH 2 —, and W with A denotes optionally substituted —O—C 1 -C 6 alkyl, —OCF 3 , —OCHF 2 , —N(C 1 -C 3 alkyl) 2 , piperidinyl or morpholinyl and B denotes hydrogen, CN, CF 3 , OCF 3 , —OCHF 2 , CHF 2 , COOH, halogen or
optionally substituted C 1 -C 6 alkyl, C 3 -C 2 cycloalkyl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-NR A 2 R A 3 , C 1 -C 4 alkylene-CO—NR A 2 R A 3 , C 1 -C 4 alkylene-SO 2 —NR A 2 R A 3 , NR A 4 —CO—R A 1 , NR A 4 —SO 2 —R A 1 or C 1 -C 4 alkylene-O—R A 1 , —O—R A 1 or —NR A 2 R A 3 ; in which
R A 1 denotes
optionally substituted C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, phenyl, pyridyl, C 1 -C 4 alkylene-NR A 2 R A 3 or C 1 -C 4 alkylene-O—C 1 -C 6 alkyl;
R A 2 denotes
hydrogen, CN or optionally substituted C 1 -C 6 alkyl, phenyl or pyridyl;
R A 3 denotes
hydrogen or optionally substituted C 1 -C 6 alkyl;
or the radicals R A 2 and R A 3 together with the nitrogen atom to which they are attached may form a five- to six-membered saturated heterocycle, which may contain another heteroatom that may be the same or different and is selected from the group consisting of O, N and S;
R A 4 denotes
hydrogen or optionally substituted C 1 -C 6 alkyl;
R W denotes hydrogen
or independently of one another, two of the radicals A, B, or R W together with the carbon atom to which they are attached may form a five- or six-membered, optionally substituted, saturated or unsaturated or aromatic heterocycle that may contain one or two or three additional
heteroatoms that are the same or different and are selected from the group consisting of O, N and S.
23 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
R 1 denotes hydrogen, R 2 denotes hydrogen and R 3 denotes hydrogen, CN, CF 3 , Cl, F, methoxy, ethoxy, methyl, ethyl, optionally substituted phenyl, R 4 denotes a bond to X 5 while preserving a C═C double bond, R 5 denotes hydrogen or a free electron pair, R 6 , R 7 , R 8 and R 9
denote each independently of one another, a radical that may be the same or different and is selected from the group consisting of
hydrogen, Cl, F, CN, CF 3 , —OCF 3 , optionally substituted C 1 -C 4 alkyl, dimethylamino, diethylamino, methoxy, ethoxy, propoxy, isopropoxy, pyrrolidinyl, piperidinyl, morpholinyl or N-methylpiperazinyl or
aryl or hetaryl selected from the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-thiazolyl, 1-imidazolyl, 1-pyrazolyl, 2-pyridyl, 3-pyridyl and 4-pyridyl, optionally substituted once or more with substituents that may be the same or different and are selected from Cl, F, methyl or methoxy;
X 1 denotes C, X 2 denotes C, X 3 denotes C, X 4 denotes C, X 5 denotes C, Z denotes —CH 2 —, and W with A denotes optionally substituted —O—C 1 -C 6 alkyl, —OCF 3 , —OCHF 2 , —N(C 1 -C 3 alkyl) 2 , piperidinyl or morpholinyl and B denotes hydrogen, CN, CF 3 , OCF 3 , —OCHF 2 , CHF 2 , halogen or optionally substituted C 1 -C 6 alkyl, C 3 -C 2 cycloalkyl, C 1 -C 4 alkylene-NR A 2 R A 3 , NR A 4 —CO—R A 1 , NR A 4 —SO 2 —R A 1 or C 1 -C 4 alkylene-O—R A 1 , —O—R A 1 or —NR A 2 R A 3 ; in which R A 1 denotes
optionally substituted C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, phenyl, pyridyl, C 1 -C 4 alkylene-NR A 2 R A 3 or C 1 -C 4 alkylene-O—C 1 -C 6 alkyl;
R A 2 denotes
hydrogen, CN or optionally substituted C 1 -C 6 alkyl, phenyl or pyridyl;
R A 3 denotes
hydrogen or optionally substituted C 1 -C 6 alkyl;
or the radicals R A 2 and R A 3 together with the nitrogen atom to which they are attached may form a five- to six-membered, optionally substituted, saturated heterocycle, which may contain another heteroatom that may be the same or different and is selected from the group consisting of O, N and S;
R A 4 denotes
hydrogen or methyl;
R W denotes hydrogen.
24 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
R 1 and R 2 independently of one another denotes hydrogen, a free electron pair, OH or optionally substituted O—C 1 -C 6 alkyl, C 1 -C 6 alkyl, CO—C 1 -C 6 alkyl, CO—O—C 1 -C 6 alkyl, R 3 denotes hydrogen, R 4 denotes hydrogen, R 5 denotes hydrogen or a free electron pair, R 6 , R 7 , R 8 and R 9
each independently of one another denotes a radical selected from the group consisting of
hydrogen, Cl, F, CN, CF 3 , —OCF 3 , C 1 -C 4 alkyl, NMe 2 , methoxy, ethoxy;
phenyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, morpholinyl or N-methylpiperazinyl, optionally substituted once or more with substituents that may be the same or different and are selected from Cl, F, methyl or methoxy;
X 1 denotes C, X 2 denotes C, X 3 denotes C, X 4 denotes C, X 5 denotes C, Z denotes —CH 2 —, and W with A denotes optionally substituted —O—C 1 -C 6 alkyl, —OCF 3 , —OCHF 2 , —NH—C 1 -C 6 alkyl, —NH—CO—C 1 -C 6 alkyl, —NH—SO 2 —C 1 -C 6 alkyl, —N(C 1 -C 6 alkyl) 2 , piperidinyl, morpholinyl, —N(C 1 -C 6 alkyl)-CO—C 1 -C 6 alkyl or —N(C 1 -C 6 alkyl)-SO 2 —C 1 -C 6 alkyl, C 1 -C 4 alkylene-CO—N(CH 3 ) 2 , C 1 -C 4 alkylene-CO—N-piperidyl, C 1 -C 4 alkylene-CO—N-morpholinyl, C 1 -C 4 alkylene-SO 2 —N(CH 3 ) 2 , C 1 -C 4 alkylene-SO 2 —N-piperidyl, C 1 -C 4 alkylene, SO 2 —N-morpholinyl or C 1 -C 4 alkyl-O—C 1 -C 6 alkyl and B denotes hydrogen, CN, CF 3 , OCF 3 , —OCHF 2 , CHF 2 , COOH, halogen, or optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 2 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 2 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-hetaryl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-NR A 2 R A 3 , C 1 -C 4 alkylene-CO—NR A 2 R A 3 , C 1 -C 4 alkylene-SO 2 —NR A 2 R A 3 , NR A 4 —CO—R A 1 , NR A 4 —SO 2 —R A 1 , or C 1 -C 4 alkylene-O—R A 1 , —O—R A 1 or —NR A 2 R A 3 ; in which R A 1 denotes
optionally substituted C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, C 1 -C 4 alkylene-aryl, C 1 -C 6 alkylene-hetaryl, C 1 -C 4 alkylene-NR A 2 R A 3 , C 1 -C 4 alkylene-CO—NR A 2 R A 3 or C 1 -C 4 alkylene-O—C 1 -C 6 alkyl;
R A 2 denotes
hydrogen, CN or optionally substituted C 1 -C 6 alkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-hetaryl, CO—C 1 -C 6 alkyl, CO-aryl, CO-hetaryl, CO—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-hetaryl, CO—O—C 1 -C 6 alkyl, SO 2 -aryl or SO 2 -hetaryl;
R A 3 denotes
hydrogen or optionally substituted C 1 -C 6 alkyl;
or the radicals R A 2 and R A 3 together with the nitrogen atom to which they are attached may form a five- or six-membered, optionally substituted, saturated or aromatic heterocycle, which may contain another heteroatom that may be the same or different and is selected from the group consisting of O, N and S;
R A 4 denotes
hydrogen or optionally substituted C 1 -C 6 alkyl;
R W denotes hydrogen, CN, CF 3 , OCF 3 or
optionally substituted C 1 -C 6 alkyl or O—C 1 -C 6 alkyl
or independently of one another, two of the radicals A, B or R W together with the carbon atom to which they are attached may form a five- or six-membered, optionally substituted, saturated or unsaturated carbocycle or a five- or six-membered, optionally substituted, saturated or unsaturated or aromatic heterocycle, which may contain one, two or three additional heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S.
25 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
R 1 denotes hydrogen, R 2 denotes hydrogen, R 3 denotes hydrogen, R 4 denotes hydrogen, R 5 denotes hydrogen or a free electron pair, R 6 , R 7 , R 8 and R 9
each independently of one another denotes a radical that may be the same or different and is selected from the group consisting of
hydrogen, Cl, F, CN, CF 3 , —OCF 3 , C 1 -C 4 alkyl, NMe 2 , methoxy, ethoxy;
phenyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, morpholinyl or N-methylpiperazinyl, optionally substituted once or more with substituents that may be the same or different and are selected from Cl, F, methyl or methoxy;
X 1 denotes C, X 2 denotes C, X 3 denotes C, X 4 denotes C, X 5 denotes N, Z denotes —CH 2 —, and W with A denotes —O—C 1 -C 6 alkyl, —OCF 3 , —OCHF 2 , —N(C 1 -C 3 alkyl) 2 , piperidinyl or morpholinyl and B denotes hydrogen, CN, CF 3 , OCF 3 , —OCHF 2 , CHF 2 , COOH, halogen, or optionally substituted C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-NR A 2 R A 3 , C 1 -C 4 alkylene-CO—NR A 2 R A 3 , C 1 -C 4 alkylene-SO 2 —NR A 2 R A 3 , NR A 4 —CO—R A 1 , NR A 4 —SO 2 —R A 1 or C 1 -C 4 alkylene-O—R A 1 , —O—R A 1 , —NR A 2 R A 3 ; in which R A 1 denotes
optionally substituted C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, phenyl, pyridyl, C 1 -C 4 alkylene-NR A 2 R A 3 or C 1 -C 4 alkylene-O—C 1 -C 6 alkyl;
R A 2 denotes
hydrogen, CN or optionally substituted C 1 -C 6 alkyl, phenyl or pyridyl;
R A 3 denotes
hydrogen or optionally substituted C 1 -C 6 alkyl;
or the radicals R A 2 and R A 3 together with the nitrogen atom to which they are attached may form a five- or six-membered, optionally substituted, saturated heterocycle, which may contain another heteroatom that may be the same or different and is selected from the group consisting of O, N and S;
R A 4 denotes
hydrogen or optionally substituted C 1 -C 6 alkyl;
R W denotes hydrogen
or independently of one another, two of the radicals A, B or R W together with the carbon atom to which they are attached may form a five- or six-membered, optionally substituted, saturated or unsaturated or aromatic heterocycle that may contain one or two additional heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S.
26 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
R 1 denotes hydrogen, R 2 denotes hydrogen, R 3 denotes hydrogen, R 4 denotes hydrogen, R 5 denotes hydrogen or a free electron pair, R 6 , R 7 , R 8 and R 9
each independently of one another denotes a radical selected from the group consisting of
hydrogen, Cl, F, CN, CF 3 , —OCF 3 , C 1 -C 4 alkyl, NMe 2 , methoxy, ethoxy;
phenyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, morpholinyl or N-methylpiperazinyl, optionally substituted once or more with substituents that may be the same and are selected from Cl, F, methyl or methoxy; X 1 denotes C, X 2 denotes C, X 3 denotes C, X 4 denotes C, X 5 denotes N, Z denotes —CH 2 —, and W with A denotes optionally substituted —O—C 1 -C 6 alkyl, —OCF 3 , —OCHF 2 , —N(C 1 -C 3 alkyl) 2 , piperidinyl or morpholinyl and B denotes hydrogen, CN, CF 3 , OCF 3 , —OCHF 2 , CHF 2 , halogen, or optionally substituted C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-NR A 2 R A 3 , NR A 4 —CO—R A 1 , NR A 4 —SO 2 —R A 1 or C 1 -C 4 alkylene-O—R A 1 , —O—R A 1 , —NR A 2 R A 3 ; in which R A 1 denotes
optionally substituted C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, phenyl, pyridyl, C 1 -C 4 alkylene-NR A 2 R A 3 or C 1 -C 4 alkylene-O—C 1 -C 6 alkyl;
R A 2 denotes
hydrogen, CN or
optionally substituted C 1 -C 6 alkyl, phenyl or pyridyl;
R A 3 denotes
hydrogen or optionally substituted C 1 -C 6 alkyl;
or the radicals R A 2 and R A 3 together with the nitrogen atom to which they are attached may form a five- to six-membered, optionally substituted, saturated heterocycle, which may contain an additional heteroatom that may be the same or different and is selected from the group consisting of O, N and S;
R A 4 denotes
hydrogen or methyl;
R W denotes hydrogen.
27 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
A denotes optionally substituted —O—C 1 -C 3 alkyl, —O—C 1 -C 3 haloalkyl, —N(C 1 -C 3 alkyl) 2 , piperidinyl or morpholinyl.
28 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
A denotes optionally substituted —O—C 1 -C 3 alkyl or —O—C 1 -C 3 alkyl that is substituted with one, two, three, four or five halogen atoms that are the same or different and are selected from the group consisting of fluorine, chlorine, bromine and iodine.
29 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
A denotes —O—CH 3 , —OCF 3 , —OCHF 2 , —OCH 2 F, —O—CH 2 —CH 3 , —O—CH 2 —CF 3 , —O—CH 2 —CHF 2 , —O—CH 2 —CH 2 F or O-isopropyl.
30 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
A denotes —O—CH 3 , —O—CH 2 —CH 3 , —O—CH 2 —CF 3 , —O—CH 2 —CHF 2 or —O—CH 2 —CH 2 F.
31 . A compound of general formula I according to claim 1 , corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) thereof, in which:
A denotes —O—CH 3 .
32 . (canceled)
33 . A pharmaceutical composition containing at least one compound of general formula I according to claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof and/or the active ingredient precursors (prodrugs) and optionally at least one pharmaceutically acceptable vehicle and/or diluent.
34 . A method for the treatment and/or the prevention of at one disease that can be treated and/or prevented prophylactically by modulation of the 5-HT 5 receptor activity, said method comprising administering an effective amount of at least one compound of general formula I according to claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof to a patient in need of such treatment and/or prevention.
35 . A method for the treatment and/or the prevention of at one disease that can be treated and/or prevented prophylactically by modulation of the 5-HT 5 receptor activity with simultaneous binding affinity for the 5-HT 5A receptor of less than or equal to 10 μM (Ki) in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof to a patient in need of such treatment and/or prevention.
36 . A method for the treatment and/or the prevention of at one disease selected from the group consisting of neuropathological, neuropsychiatric and neurodegenerative disorders; neuropathological, neuropsychiatric and neurodegenerative symptoms and neuropathological, neuropsychiatric and neurodegenerative dysfunctions in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof to a patient in need of such treatment and/or prevention.
37 . A method for the treatment and/or the prevention of migraines and brain injuries in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof to a patient in need of such treatment and/or prevention.
38 . A method for the treatment and/or the prevention of at least one neuropathological, neuropsychiatric and neurodegenerative disease selected from the group consisting of cerebral ischemia, stroke, epilepsy and seizures in general, psychoses, schizophrenia, autism, OCD syndrome, cognitive disorders, attention disorders, depression, bipolar and/or unipolar depression, anxiety, dementia, senile dementia, Alzheimer's disease, demyelinizing diseases, multiple sclerosis and brain tumors in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof to a patient in need of such treatment and/or prevention.
39 . A method for the treatment and/or the prevention of at least one disease selected from the group consisting of cerebrovascular disorders, pain, pain-induced disorders, addiction, drug-induced disorders, amnesia, alcoholism, drug abuse, disorders of the circadian rhythm and Cushing's syndrome in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof to a patient in need of such treatment and/or prevention.
40 .- 41 . (canceled)
42 . A method for the treatment and/or prevention is based on a binding affinity the 5-HT 5A receptor of less than or equal to 300 nM (K i ), determined according to a suitable test mode comprising administering an effective amount of at least one compound of general formula I according claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof, determined according to a suitable test model.
43 . (canceled)
44 . A method for the treatment and/or prevention of CNS diseases or CNS-related diseases in a patient comprising administering an effective amount of at least one compound of general formula I
corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof to a patient in need thereof,
where the radicals listed have the following definitions:
R 1 and R 2 independently of one another denote
hydrogen, a free electron pair, OH, CN or,
optionally substituted, C 1 -C 6 alkyl, O—C 1 -C 6 alkyl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 12 alkynyl, CO—C 1 -C 6 alkyl, CO—O—C 1 -C 6 alkyl, SO 2 —C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl, C 1 -C 4 alkylene-aryl, CO—O-arylalkyl, CO—C 1 -C 4 alkylene-aryl, CO-aryl, SO 2 -aryl, hetaryl, CO-hetaryl or SO 2 —C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-hetaryl, C 1 -C 4 alkylene-heterocycloalkyl, heterocycloalkyl, C 1 -C 4 cycloalkyl, indanyl or
R 1 and R 2 together with the nitrogen atom to which they are attached may form a three- to six-membered, optionally substituted, saturated or aromatic heterocycle, which may contain another heteroatom selected from the group consisting of O, N and S, such that the heterocycle may optionally have one, two or three substituents which may be the same or different,
R 3 denotes
hydrogen, NO 2 , NH 2 , OH, CN, CF 3 , OCF 3 , CHF 2 , OCHF 2 , COOH, O—CH 2 —COOH, halogen, SH or,
optionally substituted, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl,
aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-hetaryl or C 1 -C 4 alkylene-aryl or optionally substituted
O—R 3 1 , CO—R 3 1 , S—R 3 1 , SO—R 3 1 , CO—O—R 3 1 , NR 3 4 —CO—O—R 3 1 , O—CH 2 —COO—R 3 1 , NR 3 2 R 3 3 , CONH 2 , SO 2 NH 2 , NR 3 4 —CO—R 3 1 , SO 2 —R 3 1 , NR 3 4 —SO 2 —R 3 1 , SO 2 —NR 3 2 R 3 3 or CO—NR 3 2 R 3 3
in which
R 3 2 denotes
optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-aryl, C 2 -C 6 alkylene-aryl or C 1 -C 6 alkylene-hetaryl;
R 3 2 denotes
hydrogen, OH, CN or,
optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 4 alkylene-C 3 -C 2 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-hetaryl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl, CO—C 1 -C 6 alkyl, CO-aryl, CO-hetaryl, CO—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-hetaryl, CO—O—C 1 -C 6 alkyl, CO—O-aryl, CO—O—C 1 -C 4 alkylene-aryl, CO—O-hetaryl, CO—O—C 1 -C 4 alkylene-hetaryl, SO 2 —C 1 -C 6 alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 —C 1 -C 4 alkylene-aryl or SO 2 —C 1 -C 4 alkylene-hetaryl;
R 3 3 denotes
optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-hetaryl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl, CO—C 1 -C 6 alkyl, CO-aryl, CO-hetaryl, CO—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-hetaryl, CO—O—C 1 -C 6 alkyl, CO—O-aryl, CO—O—C 1 -C 4 alkylene-aryl, CO—O-hetaryl, CO—O—C 1 -C 4 alkylene-hetaryl, SO 2 —C 1 -C 6 alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 —C 1 -C 4 alkylene-aryl or SO 2 —C 1 -C 4 alkylene-hetaryl;
or the radicals R 3 2 and R 3 3 together with the nitrogen atom to which they are attached may form a three- to seven-membered, optionally substituted, saturated or aromatic heterocycle that may contain one, two or three other heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S, such that two optionally substituted radicals on this heterocycle together with the respective atom to which they are attached may form an anellated, optionally substituted, saturated, unsaturated or aromatic carbocycle or heterocycle, such that the heterocycle may contain one, two or three heteroatoms that are the same or different and are selected from the group consisting of O, N and S and the cyclic group thereby formed may be optionally substituted and/or another optionally substituted cyclic group may be condensed onto this cyclic group;
R 3 4 denotes
hydrogen or
optionally substituted C 1 -C 6 alkyl, C 1 -C 6 alkenyl-O—C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 12 alkynyl, CO—C 1 -C 6 alkyl, CO—O—C 1 -C 6 alkyl, SO 2 —C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl, C 1 -C 4 alkylene-aryl, CO—O-arylalkyl, CO—C 1 -C 4 alkylene-aryl, CO-aryl, SO 2 -aryl, hetaryl, CO-hetaryl or SO 2 —C 1 -C 4 alkylene-aryl;
R 4 denotes
a bond in the ring to X 5 while maintaining a C═C double bond for the case when X 5 ═C or a radical selected from hydrogen, CN, CF 3 , CHF 2 , COOH, halogen or, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-hetaryl
or C 1 -C 4 alkylene-aryl,
for the case when X 5 ═N; or
R 3 and R 4 together with the atom to which they are bound may form an optionally substituted three-membered carbocycle,
R 5 denotes
hydrogen, a electron pair or
optionally substituted O—C 1 -C 6 alkyl, C 1 -C 6 alkyl, CO—C 1 -C 6 alkyl, —CO—O—C 1 -C 6 alkyl
X 1 denotes C or N,
X 2 denotes C or N,
X 3 denotes C or N,
X 4 denotes C or N,
such that at most one of radicals X 1 through X 4 may denote N at the same time,
in which
R 6 , R 7 , R 8 and R 9 denote,
each independently of one another, a radical that may be the same or different and is selected from the same or different moieties of the groups 1), 2), 3), 4), 5), 6) or 7), such that the groups 1) through 7) have the following meanings:
1) hydrogen, halogen, CN, CF 3 , CHF 2 , —OCF 3 , —NH 2 , —OH or optionally substituted C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl or NR Q 7 R Q 8 ,
in which R Q 7 and R Q 8 are defined as shown below;
2) phenyl, optionally substituted with one, two or three radicals that may be the same or different and are selected from the group consisting of R Q 2 , R Q 3 and R Q 4 in which
R Q 2 , R Q 3 and R Q 4 each independently of one another denotes a substituent from the following group:
hydrogen, NO 2 , NH 2 , OH, CN, CF 3 , CHF 2 , OCF 3 , OCHF 2 , COOH, O—CH 2 —COOH, SH, halogen or
optionally substituted aryl, hetaryl, heterocycloalkyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 2 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 2 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, C 1 -C 4 alkylene-aryl or C 1 -C 4 alkylene-hetaryl or
O—R Q 5 , S—R Q 5 , NR Q 7 R Q 8 , CO—OR Q 6 , NR Q 7 —CO—O—R Q 6 , O—CH 2 —COO—R Q 6 , NR Q 7 —CO—R Q 6 , SO 2 —R Q 6 , NR Q 7 —SO 2 —R Q 6 , SO 2 NH 2 , CONH 2 , SO 2 —NR Q 7 R Q 8 or CO—NR Q 7 R Q 8 or
two or the radicals R Q 2 , R Q 3 and R Q 4 together with the atom to which they are attached may form a three- to seven-membered, optionally substituted, saturated, unsaturated or aromatic carbocycle or a three- to seven-membered, optionally substituted, saturated, unsaturated aromatic heterocycle that may contain one, two or three additional heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S and
optionally two substituted radicals on this heterocycle together may form an anellated, optionally substituted, saturated, unsaturated or aromatic carbocycle or heterocycle, such that the heterocycle may contain one, two or three heteroatoms that are the same or different and are selected from the group consisting of O, N and S, and the resulting cyclic group may optionally be substituted or another optionally substituted cyclic group may be condensed onto this cyclic group;
R Q 5 denotes optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, heterocycloalkyl or hetaryl or C 1 -C 4 alkyl optionally substituted with one, two or three substituents selected, independently of one another, from the group consisting of halogen, NO 2 , NH 2 , OH, CN, CF 3 , CHF 2 , OCF 3 , OCHF 2 or optionally substituted NH—(C 1 -C 6 alkyl) and N(C 1 -C 6 alkyl) 2 ;
R Q 6 denotes optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl or C 1 -C 6 alkylene-O—C 1 -C 6 alkyl;
R Q 7 denotes, independently of its respective occurrence, hydrogen, CN or optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl, CO—C 1 -C 6 alkyl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-hetaryl, CO-aryl, CO-hetaryl, CO—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-hetaryl, CO—O—C 1 -C 6 alkyl, CO—O-aryl, CO—O—C 1 -C 4 alkylene-aryl, CO—O-hetaryl, CO—O—C 1 -C 4 alkylene-hetaryl, SO 2 —C 1 -C 6 alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 —C 1 -C 4 alkylene-aryl or SO 2 —C 1 -C 4 alkylene-hetaryl;
R Q 8 denotes, independently of its respective occurrence, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl, CO—C 1 -C 6 alkyl, CO-aryl,
CO-hetaryl, CO—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-hetaryl, CO—O—C 1 -C 6 alkyl, CO—O-aryl, CO—O—C 1 -C 4 alkylene-aryl, CO—O-hetaryl, CO—O—C 1 -C 4 alkylene-hetaryl, SO 2 —C 1 -C 6 alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 —C 1 -C 4 alkylene-aryl or SO 2 —C 1 -C 4 alkylene-hetaryl;
or the radicals R Q 7 and R Q 8 together with the nitrogen atom to which they are attached may form a three- to seven-membered, optionally substituted, saturated or aromatic heterocycle that may contain one, two or three other heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S; and optionally two substituted radicals on this heterocycle together may form an anellated, optionally substituted, saturated, unsaturated or aromatic carbocycle or heterocycle, such that the heterocycle may contain one, two or three heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S, and the resulting cyclic group may optionally be substituted and/or another cyclic group, optionally substituted, may be condensed onto this cyclic group;
3) a five- or six-membered hetaryl radical, optionally substituted once or twice with substituents that may be the same or different and are selected from the group consisting of:
2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-pyrimidyl, 6-pyrimidyl, 3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl, 6-pyridazinyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, thiadiazolyl, oxadiazolyl or triazinyl or the anellated derivatives thereof indazolyl,
benzothiophenyl, benzofuranyl, indolinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, quinolinyl and isoquinolinyl, such that the substituents are preferably selected from the group consisting of halogen, NO 2 , NH 2 , OH, CN, CF 3 , OCF 3 , CHF 2 , O—CHF 2 , optionally substituted C 1 -C 6 alkyl, O—C 1 -C 6 alkyl, NH—(C 1 -C 6 alkyl), N(C 1 -C 6 alkyl) 2 , NHCO—C 1 -C 4 alkyl, NHSO 2 —C 1 -C 4 alkyl and SO 2 —C 1 -C 4 alkyl;
4) two of the radicals R 6 , R 7 , R 8 or R 9 together with the respective atom to which they are attached may form a four- to seven-membered, optionally substituted, fully or partially saturated carbocycle or a five- or six-membered, optionally substituted, fully or partially saturated heterocycle that may contain two or three heteroatoms that are the same or different and are selected from the group consisting of O, N and S;
5) an optionally substituted C 3 -C 8 monocyclic saturated hydrocarbon radical;
6) an optionally substituted four- to seven-membered mono- or bicyclic, fully or partially saturated heterocycle that may contain one or two heteroatoms that are the same or different and are selected from the group consisting of O, N and/or S, such that this cyclic group may also contain one, two, three or more substituents, and in the event the heterocycle contains a nitrogen atom, this nitrogen atom may be substituted with an R Q 7 radical, which may have one of the meanings defined above, independently of its occurrence,
such that preferably the following, optionally substituted radicals are
azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, pyrrolin-1-yl, pyrrolin-3-yl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, 1,2,3,6-tetrahydropyridin-1-yl,
1,2,3,6-tetrahydropyridin-4-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, tetrahydro-2H-pyran-4-yl, tetrahydrofuran-3-yl, azepan-4-yl, azepan-3-yl, azepan-2-yl, 1,4-diazepan-5-yl, morpholinyl, piperazinyl,
such that the following optionally substituted radicals preferably include:
7) a radical of general formula V
—(CR V 1 R V 2 ) d —(Y) e —(CR V 3 R V 4 ) f —R V 5 V
having the indices
d=0, 1, 2, 3 or 4
e=0 or 1
f=0, 1, 2, 3 or 4,
such that the sum of d, e and f is 1, 2, 3, 4, 5, 6, 7 or 8;
R V 1 , R V 2 , R V 3 , R V 4 each independently denotes
hydrogen, halogen, OH or
optionally substituted C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkyl, aryl, C 1 -C 4 alkylene-aryl, hetaryl or C 1 -C 4 alkylene-hetaryl or,
independently of one another, two radicals R V 1 and R V 2 or R V 3 and R V 4 together with the carbon atom to which they are attached may form a three- to seven-membered, optionally substituted, saturated or unsaturated carbocycle or heterocycle in which the heterocycle may contain one, two or three heteroatoms selected from the group consisting of O, N and S;
R V 5 denotes
a radical selected from the radicals as defined above in the same or different moieties of groups 1), 2), 3), 5) or 6):
Y denotes
—CO—, —O—, —S—, —SO—, SO 2 —, CS—, —NR Y 5 —, —COO—, —O—CO—, —CO—NR Y 5 , —NR Y 5 —CO—, —SO 2 —NR Y 5 , —NR Y 5 , SO 2 —;
in which
R Y 5 denotes
hydrogen or
optionally substituted C 1 -C 6 alkyl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 12 alkynyl, CO—C 1 -C 6 alkyl, CO—O—C 1 -C 6 alkyl, SO 2 —C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl, C 1 -C 4 alkylene-aryl,
CO—O—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-aryl, CO-aryl, SO 2 aryl, hetaryl, CO-hetaryl or SO 2 —C 1 -C 4 alkylene-aryl;
X 5 denotes
C or N
Z denotes
a radical of general formula Z1
where
a=1, 2, 3 or 4,
preferably a=1 or 2,
especially preferably a=1,
R Z 1 , R Z 2 independently of one another denote
hydrogen, halogen, OH or
optionally substituted C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkylene-C 3 -C 2 cycloalkyl, C 3 -C 2 cycloalkyl, aryl, C 1 -C 4 alkylene-aryl, hetaryl or C 1 -C 4 alkylene-hetaryl or
independently of one another, two radicals R Z 1 and R Z 2 together with the carbon atom to which they are attached may form a three- to seven-membered, optionally substituted, saturated or unsaturated carbocycle or heterocycle, such that the heterocycle may contain one, two or three heteroatoms selected from the group consisting of O, N and S, such that preferably R Z 1 and R Z 2 should not both denote OH at the same time;
W denotes a radical of general formula W
in which
A denotes
OH, CN, OCF 3 , CHF 2 , CF 3 , OCHF 2 , COOH, O—CH 2 —COOH, SH, SO 2 H, C 1 -C 4 alkylene-OH, NR A 4 —SO 2 H, NR A 4 —COOH, SOH,
or optionally substituted
O—R A 1 , CO—R A 1 , S—R A 1 , SO—R A 1 , CO—O—R A 1 , NR A 4 —CO—O—R A 1 , O—CH 2 —COO—R A 1 , NR A 2 R A 3 , NR A 4 —CO—R A 1 , SO 2 —R A 1 , NR A 4 —SO 2 —R A 1 , SO 2 —NR A 2 R A 3 , CO—NR A 2 R A 3 , C 1 -C 4 alkylene-NR A 2 R A 3 , C 1 -C 4 alkylene-CO—NR A 2 R A 3 , C 1 -C 4 alkylene-SO 2 —NR A 2 R A 3 or C 1 -C 4 alkylene-O—R A 1 ;
preferably A=optionally substituted —O—C 1 -C 3 alkyl or —O—C 1 -C 3 haloalkyl, —N(C 1 -C 3 alkyl) 2 , piperidinyl or morpholinyl,
especially preferably A=optionally substituted —O—C 1 -C 3 alkyl or —O—C 1 -C 3 alkyl substituted with one, two, three, four or five halogen atoms that may be the same or different and are selected from the group consisting of fluorine, chlorine, bromine and iodine;
most especially preferably A=-O—CH 3 , —OCF 3 , —OCHF 2 , —OCH 2 F, —O—CH 2 —CH 3 , —O—CH 2 —CF 3 , —O—CH 2 —CHF 2 , —O—CH 2 —CH 2 F or O-isopropyl;
even more preferably A=-O—CH 3 , —O—CH 2 —CH 3 , —O—CH 2 —CF 3 , —O—CH 2 —CHF 2 or —O—CH 2 —CH 2 F;
most preferred is A=-O—CH 3 ,
R A 1 denotes
independently of its respective occurrence, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-aryl, C 2 -C 6 alkylene-aryl, C 1 -C 6 alkylene-hetaryl, C 1 -C 4 alkylene-NR A 2 R A 3 , C 1 -C 4 alkylene-CO—NR A 2 R A 3 or C 1 -C 4 alkylene-O—C 1 -C 6 alkyl;
R A 2 denotes
independently of its respective occurrence, hydrogen, OH, CN
or
optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-hetaryl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl; CO—C 1 -C 6 alkyl, CO-aryl, CO-hetaryl, CO—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-hetaryl, CO—O—C 1 -C 6 alkyl, CO—O-aryl, CO—O—C 1 -C 4 alkylene-aryl, CO—O-hetaryl, CO—O—C 1 -C 4 alkylene-hetaryl, SO 2 —C 1 -C 6 alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 —C 1 -C 4 alkylene-aryl or SO 2 —C 1 -C 4 alkylene-hetaryl;
R A 3 denotes
independently of its respective occurrence, hydrogen or optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-aryl, C 1 -C 4 alkylene-hetaryl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl; CO—C 1 -C 6 alkyl, CO-aryl, CO-hetaryl, CO—C 1 -C 4 alkylene-aryl, CO—C 1 -C 4 alkylene-hetaryl, CO—O—C 1 -C 6 alkyl, CO—O-aryl, CO—O—C 1 -C 4 alkylene-aryl, CO—O-hetaryl, CO—O—C 1 -C 4 alkylene-hetaryl, SO 2 —C 1 -C 6 alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 —C 1 -C 4 alkylene-aryl or SO 2 —C 1 -C 4 alkylene-hetaryl;
or the radicals R A 2 and R A 3 together with the nitrogen atom to which they are attached may form a three- to seven-membered, optionally substituted, saturated or aromatic heterocycle that may contain one, two or three additional heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S; such that optionally two substituted radicals on this heterocycle together may form an anellated, optionally substituted, saturated, unsaturated or aromatic carbocycle or heterocycle, such that the heterocycle may contain one, two or three heteroatoms that are the same or different and are selected from the group consisting of O, N and S and such that the resulting cyclic group may optionally be substituted and/or another optionally substituted cyclic group may be condensed onto this cyclic group;
R A 4 denotes
independently of its respective occurrence, hydrogen or optionally substituted C 1 -C 6 alkyl, C 1 -C 6 alkenyl-O—C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 12 alkynyl, CO—C 1 -C 6 alkyl, CO—O—C 1 -C 6 alkyl, SO 2 —C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, aryl, C 1 -C 4 alkylene-aryl, CO—O-arylalkyl, CO—C 1 -C 4 alkylene-aryl, CO-aryl, CO-aryl, SO 2 -aryl, hetaryl, CO-hetaryl or SO 2 —C 1 -C 4 alkylene-aryl;
B denotes
hydrogen, NO 2 , NH 2 , OH, CN, OCF 3 , CHF 2 , CF 3 , OCHF 2 , COOH, O—CH 2 —COOH, halogen, SH or
optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-C 3 -C 7 cycloalkyl, C 1 -C 4 alkylene-heterocycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 alkylene-hetaryl, C 1 -C 4 alkylene-aryl, O—R A 1 , CO—R A 1 , S—R A 1 , SO—R A 1 , CO—O—R A 1 , NR A 4 —CO—O—R A 1 , O—CH 2 —COO—R A 1 , NR A 2 R A 3 , NR A 4 —CO—R A 1 , SO 2 —R A 1 , NR A 4 —SO 2 —R A 1 , SO 2 —NR A 2 R A 3 , CO—NR A 2 R A 3 ,
C 1 -C 4 alkylene-NR A 2 R A 3 , C 1 -C 4 alkylene-CO—NR A 2 R A 3 , C 1 -C 4 alkylene-SO 2 —NR A 2 R A 3 or C 1 -C 4 alkylene-O—R A 1 ;
or, independently of one another, two of the radicals A, B or R W together with the carbon atom to which they are each attached may form a five- to seven-membered, optionally substituted, saturated or unsaturated carbocycle or a five- to seven-membered, optionally substituted, saturated or unsaturated or aromatic heterocycle, which may have one, two or three additional heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S; such that optionally two substituted radicals on this carbocycle or heterocycle together may form an anellated, optionally substituted, saturated, unsaturated or aromatic carbocycle or heterocycle, such that the heterocycle may have one, two or three heteroatoms, which may be the same or different and are selected from the group consisting of O, N and S and such that the cyclic group thus formed may optionally be substituted and/or another optionally substituted cyclic group may be condensed onto this cyclic group;
R W denotes
hydrogen, OH, halogen, NO 2 , NH 2 , CN, CF 3 , CHF 2 , OCF 3 , OCHF 2
or
optionally substituted C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 1 -C 6 alkylene-O—C 1 -C 6 alkyl, C 1 -C 6 thioalkyl, aryl, hetaryl, O—C 1 -C 6 alkyl, O-aryl, O-benzyl, C 1 -C 6 alkylamino, C 1 -C 6 dialkylamino, pyrrolidinyl, piperidinyl, morpholinyl, CO—C 1 -C 6 alkyl, SO 2 —C 1 -C 6 alkyl, CO-aryl, SO 2 -aryl, CO—C 1 -C 4 alkylene-aryl, SO 2 —C 1 -C 4 alkylene-aryl, SO-aryl, CONH 2 , CONH—C 1 -C 6 alkyl, SO 2 NH—C 1 -C 6 alkyl, CON—(C 1 -C 6 alkyl) 2 , SO 2 N—(C 1 -C 6 alkyl) 2 , NH—SO 2 —C 1 -C 6 alkyl or NH—CO—C 1 -C 6 alkyl;
for treatment and/or prevention and/or production of a medication for treatment and/or prevention of CNS diseases or CNS-related diseases in a patient requiring such treatment and/or prevention.
45 . The method according to claim 44 in which:
A denotes optionally substituted —O—C 1 -C 3 alkyl, —O—C 1 -C 3 haloalkyl, —N(C 1 -C 3 alkyl) 2 , piperidinyl or morpholinyl.
46 . The method according to claim 44 in which:
A denotes optionally substituted —O—C 1 -C 3 alkyl, —O—C 1 -C 3 alkyl substituted with 1, 2, 3, 4 or 5 halogen atoms that may be the same or different and are selected from the group comprising fluorine, chlorine, bromine and iodine.
47 . The method according to claim 44 in which:
A denotes —O—CH 3 , —OCF 3 , —OCHF 2 , —OCH 2 F, —O—CH 2 —CF 3 , —O—CH 2 —CHF 2 , —O—CH 2 —CH 2 F or O-isopropyl.
48 . The method according to claim 44 in which:
A denotes —O—CH 3 , —O—CH 2 —CH 3 , —O—CH 2 —CF 3 , —O—CH 2 —CHF 2 or —O—CH 2 —CHF 2 .
49 . The method according to claim 44 in which:
A denotes —O—CH 3 .
50 . The method according to claim 44 in which:
X 5 denotes C and
R 4 denotes a bond in the ring to X 5 while maintaining a C═C double bond.
51 . A method for the treatment and/or prevention of CNS diseases or CNS-related diseases in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 to a patient in need of such treatment and/or prevention without any and/or any significant simultaneous nitrogen monoxide modulation (nitric oxide modulation).
52 . A method for the treatment and/or prevention of CNS diseases or CNS-related diseases in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 to a patient in need of such treatment and/or prevention without any and/or any significant simultaneous interacting or binding to the SH3 protein domain or homologs thereof.
53 . A method for the treatment and/or prevention of CNS diseases or CNS-related diseases in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 to a patient in need of such treatment and/or prevention without or without any significant simultaneous antagonism of the chemokine receptor in particular without antagonizing the chemokine receptor CCR4 and/or CCR5.
54 . The method of claim 34 wherein the treatment and/or prevention is accomplished by modulation of the 5-HT 5 receptor activity in the patient.
55 . The method of claim 34 wherein the treatment and/or prevention is accomplished by modulation of the 5-HT 5 receptor activity but without or without any significant simultaneous nitric oxide modulation in the patient.
56 . The method of claim 34 wherein the treatment and/or prevention is accomplished by modulation of the 5-HT 5 receptor activity but without or without any significant simultaneous interacting or binding to the SH3 protein domain or homologs thereof in the patient.
57 . The method of claim 34 wherein the treatment and/or prevention is accomplished by modulation of the 5-HT 5 receptor activity but without or without any significant simultaneous antagonism of the chemokine receptor in particular without antagonizing the chemokine receptor CCR4 and/or CCR5 in the patient.
58 . The method of claim 44 , characterized in that the CNS disease or CNS-related disease is a disease selected from the group comprising neuropathological, neuropsychiatric and neurodegenerative disorders, neuropathological, neuropsychiatric and neurodegenerative symptoms and/or neuropathological, neuropsychiatric and neurodegenerative dysfunctions.
59 . The method of claim 44 characterized in that the CNS diseases or CNS-related diseases are treated by modulation of the 5-HT 5 receptor activity.
60 . The method of claim 44 characterized in that the CNS diseases or CNS-related diseases are treated by modulation of the 5-HT 5 receptor activity but without or without any significant simultaneous nitric oxide modulation.
61 . The method of claim 44 characterized in that the CNS diseases or CNS-related diseases are treated by modulation of the 5-HT 5 receptor activity but without or without any significant simultaneous interacting or binding to the SH3 protein domain or homologs thereof.
62 . The method of claim 44 characterized in that the CNS diseases or CNS-related diseases are treated by modulation of the 5-HT 5 receptor activity but without or without any significant simultaneous antagonism of the chemokine receptor in particular without antagonizing the chemokine receptor CCR4 and/or CCR5.
63 . The method of claim 44 , characterized in that the CNS disease or CNS-related disease is a disease selected from the group comprising neuropathological, neuropsychiatric and/or neurodegenerative disorders, symptoms and/or dysfunctions are migraines and/or brain injuries.
64 . A method for treatment and/or prevention of one or more of the aforementioned CNS diseases, CNS-related diseases, neuropathological, neuropsychiatric and/or neurodegenerative disorders, symptoms and/or dysfunctions in conjunction with migraines and/or brain injuries by modulation of the 5-HT 5 receptor activity in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof to a patient in need of such treatment and/or prevention.
65 . A method for treatment and/or prevention of one or more of the aforementioned CNS diseases, CNS-related diseases, neuropathological, neuropsychiatric and/or neurodegenerative disorders, symptoms and/or dysfunctions in conjunction with migraines and/or brain injuries by modulation of the 5-HT 5 receptor activity but without or without any significant simultaneous nitric oxide modulation, without or without any significant simultaneous interacting or binding to the SH3 protein domain or homologs thereof and/or without or without any significant simultaneous antagonism of the chemokine receptor in particular without antagonizing the chemokine receptor CCR4 and/or CCR5 in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof to a patient in need of such treatment and/or prevention.
66 . A method characterized in that the CNS disease and/or CNS-related disease and/or neuropathological, neuropsychiatric and/or neurodegenerative disorders, symptoms and/or dysfunctions are selected from the group comprising cerebral ischemia, stroke, epilepsy and seizures in general, Psychoses, schizophrenia, autism, OCD syndrome, cognitive disorders, attention disorders, depression, bipolar and unipolar depression, anxiety, dementia, senile dementia, Alzheimer's dementia, demyelinizing diseases, multiple sclerosis and brain tumors in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof to a patient in need of such treatment and/or prevention.
67 . A method for the treatment and/or prevention of CNS diseases, CNS-related diseases, neuropathological, neuropsychiatric and/or neurodegenerative disorders, symptoms and/or dysfunctions selected from the group comprising cerebral ischemia, stroke, epilepsy and seizures in general, psychoses, schizophrenia, autism, OCD syndrome, cognitive disorders, attention disorders, depression, bipolar and unipolar depression, anxiety, dementia, senile dementia, Alzheimer's dementia, demyelinizing diseases, multiple sclerosis and brain tumors by modulation of the 5-HT 5 receptor activity in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof to a patient in need of such treatment and/or prevention.
68 . A method for the treatment and/or prevention of CNS diseases, CNS-related diseases, neuropathological, neuropsychiatric and/or neurodegenerative disorders, symptoms and/or dysfunctions selected from the group comprising cerebral ischemia, stroke, epilepsy and seizures in general, psychoses, schizophrenia, autism, OCD syndrome, cognitive disorders, attention disorders, depression, bipolar and unipolar depression, anxiety, dementia, senile dementia, Alzheimer's dementia, demyelinizing diseases, multiple sclerosis and brain tumors by modulation of the 5-HT 5 receptor activity but without or without any significant simultaneous nitric oxide modulation, without or without any significant simultaneous interacting or binding to the SH3 protein domain or homologs thereof and/or without or without any significant simultaneous antagonism of the chemokine receptor in particular without antagonizing the chemokine receptor CCR4 and/or CCR5 in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof to a patient in need of such treatment and/or prevention.
69 . A method characterized in that the CNS disease and/or CNS-related disease and/or neuropathological, neuropsychiatric and/or neurodegenerative disorders, symptoms and/or dysfunctions are selected from the group comprising cerebral vascular disorders, pain, pain-related disorders, addiction, drug-related disorders, amnesia, alcoholism, drug abuse, disturbances in the circadian rhythm and Cushing's syndrome in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof to a patient in need of such treatment and/or prevention.
70 . A method characterized in that the CNS disease and/or CNS-related disease and/or neuropathological, neuropsychiatric and/or neurodegenerative disorders, symptoms and/or dysfunctions are selected from the group comprising cerebral vascular disorders, pain, pain-related disorders, addiction, drug-related disorders, amnesia, alcoholism, drug abuse, disturbances in the circadian rhythm and Cushing's syndrome by modulation of the 5-HT 5 receptor activity in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof to a patient in need of such treatment and/or prevention.
71 . A method characterized in that the CNS disease and/or CNS-related disease and/or neuropathological, neuropsychiatric and/or neurodegenerative disorders, symptoms and/or dysfunctions are selected from the group comprising cerebral vascular disorders, pain, pain-related disorders, addiction, drug-related disorders, amnesia, alcoholism, drug abuse, disturbances in the circadian rhythm and Cushing's syndrome by modulation of the 5-HT 5 receptor activity but without or without any significant simultaneous nitric oxide modulation, without or without any significant simultaneous interacting or binding to the SH3 protein domain or homologs thereof and/or without or without any significant simultaneous antagonism of the chemokine receptor in particular without antagonizing the chemokine receptor CCR4 and/or CCR5 in a patient comprising administering an effective amount of at least one compound of general formula I according to claim 1 and/or corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof and/or the pharmaceutically acceptable salts thereof to a patient in need of such treatment and/or prevention.
72 . A method characterized in that the treatment and/or prevention is based on a binding affinity for the 5-HT 5A receptor of less than or equal to 10 μM (Ki), determined according to a suitable test model.
73 . The method of claim 34 characterized in that the treatment and/or prevention is based on a binding affinity for the 5-HT 5A receptor of less than or equal to 300 nM (Ki), determined according to a suitable test model.
74 . The method of claim 34 characterized in that the treatment and/or prevention is based modulation of the 5-HT 5 receptor activity and additionally on a certain binding affinity for the 5-HT 5 receptor in a patient.
75 . Synthesis of at least one optionally substituted 2-amino-3-benzylquinoline derivative according to general formula I according to claim 1 , characterized by the reaction of optionally substituted 2-aminobenzaldehyde derivatives and optionally substituted 3-arylpropionitrile derivatives under basic or acidic reaction conditions by means of a reaction related to the Friedlander reaction.
76 . Synthesis of at least one optionally substituted 2-amino-3-benzylquinoline derivative according to claim 75 , characterized by the steps of reaction of an optionally substituted (2-chloroquinolin-3-yl)(aryl)methanone compound by reaction with primary, secondary amines or ammonia and then reduction of the 3-carboxy group (e.g., under Wolff-Kishner conditions).
77 . Synthesis of at least one optionally substituted 2-amino-3-benzylquinoline derivative according to claim 75 , characterized by the steps of reaction of an optionally substituted 2-chloroquinoline compound by orthometallization in position 3, reaction with benzaldehyde derivatives, oxidation to the corresponding optionally substituted chloroquinolin-3-yl(aryl)methanone compound, reaction of primary, secondary amines or ammonia and then reduction of the 3-carboxy groups (e.g., under Wolff-Kishner conditions).
78 . Synthesis of at least one optionally substituted 3-benzyl-3,4-dihydroquinazolin-2-amine derivative according to general formula I according to claim 1 , characterized by the steps of reaction of optionally substituted 2-nitrobenzoic acid derivatives by peptide linkage with an optionally substituted benzylamine derivative, then production of the amide thus formed to the secondary amine followed by reduction of the nitro group and then cyclization with cyanogen bromide.
79 . Synthesis of at least one optionally substituted 3-benzyl-3,4-dihydroquinazolin-2-amine derivative according to claim 78 , characterized by the steps of reaction of an optionally substituted 2-nitrobenzaldehyde derivative by reductive alkylation with an optionally substituted benzylamine derivative, follows by reduction of the nitro group, cyclization to yield the corresponding 3-aryl-2-(methylthio)-3,4-dihydroquinazoline derivatives with carbon disulfide and methyl iodide and subsequent reaction with primary, secondary amines or ammonia.
80 .- 81 . (canceled)
82 . A method for the treatment of diseases modulated by a 5-HT 5 receptor activity, such that the diseases are one or more diseases selected from the group comprising neuropathological, neuropsychiatric and neurodegenerative disorders, symptoms and dysfunctions in a patient comprising administering an effective amount of at least one quinoline and/or dihydroquinazoline compound of general formula (I) according to claim 1 for the production of a medication for a patient in need of such treatment and/or prevention.
83 . A method for the treatment of diseases modulated by a 5-HT 5 receptor activity, such that the diseases are one or more diseases selected from the group comprising neuropathological, neuropsychiatric and neurodegenerative disorders, symptoms and dysfunctions, in particular the treatment of migraines and brain injuries and/or disorders in a patient comprising administering an effective amount of at least one quinoline and/or dihydroquinazoline compound of general formula (I) according to claim 1 to a patient in need of such treatment and/or prevention.
84 . A method for the treatment of diseases modulated by a 5-HT 5 receptor activity, such that the diseases are one or more diseases selected from the group comprising neuropathological, neuropsychiatric and neurodegenerative disorders, symptoms and dysfunctions, in particular brain damage and/or disorders selected from the group comprising cerebral ischemia, stroke, epilepsy and seizures in general, psychoses, schizophrenia, autism, OCD syndrome, cognitive disorders, attention disorders, depression, bipolar and/or unipolar depression, anxiety, dementia, senile dementia, Alzheimer's dementia, demyelinizing diseases, multiple sclerosis and brain tumors in a patient comprising administering an effective amount of at least one quinoline and/or dihydroquinazoline compound of general formula (I) according to claim 1 to a patient in need of such treatment and/or prevention.
85 . A method for the treatment of diseases modulated by a 5-HT5 receptor activity, such that the diseases include one or more diseases selected from the group comprising cerebrovascular disorders, pain, pain-related disorders, addiction, drug-related disorders, amnesia, alcoholism, drug abuse, disorders of the circadian rhythm and Cushing's syndrome in a patient comprising administering an effective amount of at least one quinoline and/or dihydroquinazoline compound of general formula (I) according to claim 1 to a patient in need of such treatment and/or prevention.Join the waitlist — get patent alerts
Track US2014221371A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.