US2017037016A1PendingUtilityA1
Guanidine compounds and use thereof as binding partners for 5-ht5 receptors
Est. expiryFeb 19, 2024(expired)· nominal 20-yr term from priority
Inventors:Astrid NetzWilhelm AmbergUdo LangeMichael OchseCharles W. HutchinsFrancisco-Xavier Garcia-LadonaWolfgang WernetAndreas Kling
A61P 35/00A61P 39/02A61P 9/10A61P 43/00A61P 25/22A61P 25/18A61P 25/28A61P 25/32A61P 25/24A61P 25/30A61P 25/04A61P 25/06A61P 25/00A61P 25/08C07D 285/135C07D 513/04C07D 277/82C07D 285/08C07D 237/22C07D 417/04C07D 263/28C07D 417/12C07D 235/30C07D 231/56A61P 19/02C07D 277/60C07D 249/14C07D 261/14C07D 277/48C07D 263/48C07D 333/36
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Claims
Abstract
The present invention relates to guanidine compounds of the general formula I corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof as well as pharmaceutically acceptable salts thereof. The present compound further relates to the use of guanidine compounds as binding partners for 5-HT5 receptors for the treatment of diseases which are modulated by a 5-HT5 receptor activity, in particular for the treatment of neurodegenerative and neuropsychiatric disorders as well as the associated signs, symptoms and dysfunctions.
Claims
exact text as granted — not AI-modified1 . Guanidine compound of the general formula I
corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof, as well as pharmaceutically acceptable salts thereof, wherein the given moieties have the following definitions:
W:
a moiety of the general formula W1 or W2
wherein
A:
NO 2 , NH 2 , OH, CN, CF 3 , OCF 3 , CHF 2 , OCHF 2 , COOH, O—CH 2 —COOH, halogen, SH, or
each 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-heterocyclo-alkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 -alkylene-hetatyl or C 1 -C 4 -alkylene-aryl, or
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 , CONH 2 , SO 2 NH 2 , 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 or CO—NR A 2 R A 3 ;
R A 1 :
each 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-heterocyclo-alkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 -alkylene-aryl, C 2 -C 6 -alkenylene-aryl or C 1 -C 6 -alkylene-hetaryl;
R A 2 :
hydrogen, OH, CN, or
each 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 :
each 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 the moieties R A 2 and R A 3 form, together with the nitrogen, a 3 to 7-membered, optionally substituted, saturated or aromatic heterocycle which can contain one, two or three different or same heteroatoms from the group O, N, S; wherein optionally two moieties substituted on this heterocycle can together form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or same heteroatoms O, N, S, and wherein the cycle formed can optionally be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
R A 4 :
hydrogen or
each 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-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:
hydrogen or as moiety A is defined,
or each independently of one another, two of the moieties A, B or R w 1 form, together with a 3 to 7-membered, optionally substituted, saturated or unsaturated carbocycle or an optionally substituted, saturated or unsaturated or aromatic heterocycle which can contain one, two or three further different or same heteroatoms from the group O, N, S; wherein optionally two of the moieties substituted on this carbo- or heterocycle can together form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or same heteroatoms O, N, S, and wherein the cycle formed can optional be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
R w 1 :
hydrogen, OH, halogen, NO 2 , NH 2 , CN, CF 3 , CHF 2 , O—CF 3 , O—CHF 2 , or each 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;
D:
as moiety A is defined;
Z:
a moiety of the general formula Z1
with the indices
a=0-4
b=0, 1
c=0-4
wherein the sum of a, b and c is at least 1 and no more than 5;
R Z 1 , R Z 2 , R Z 3 , R Z 4 independently of one another:
hydrogen, halogen, OH, or
each optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkylene-C 3 -C 7 -cycloalkyl, C 3 -C 7 -cycloalkyl, aryl, C 1 -C 4 -alkylene-aryl, het-aryl or C 1 -C 4 -alkylene-hetaryl, or
each independently of one another, two moieties R z 1 and R z 2 or R z 3 and R z 4 together form a 3 to 7-membered, optionally substituted, saturated or unsaturated carbo- or heterocycle, wherein the heterocycle can contain up to three heteroatoms from the group O, N or S;
V Z :
—CO—, —CO—NR z 5 -, —NR z 5 —CO—, —O—, —S—, —SO—, —SO 2 —, —SO 2 —NR z 5 -, —NR z 5 —SO 2 —, —CS—, —CS—NR z 5 -, —NR z 5 —CS—, —CS—O—, —O—CS—, —CO—O—, —O—CO—, —O—, ethynylene, —C(═CR Z 6 R z 7 )—, —CR Z 6 ═CR Z 7 —, —NR z 5 —CO—NR z 5 -, —O—CO—NR z 5 -, —NR z 5 —;
R Z 5 , R Z 5 * independently of one another:
hydrogen or
each 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;
R Z 6 , R Z 7 independently of one another:
hydrogen, OH or
each optionally substituted C 1 -C 6 -alkyl, C 1 -C 4 -alkoxy, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -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;
R 1 , R 2 , R 3 independently of one another:
hydrogen, OH, CN, or
each 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 3 -C 7 -cycloalkyl, O—C 3 -C 7 -cycloalkyl, aryl, hetaryl, C 1 -C 4 -alkylene-aryl, C 1 -C 4 -alkylene-hetaryl, O-aryl, O—C 1 -C 4 -alkylene-aryl, O-hetaryl, O—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, CO—O-aryl, CO—O-hetaryl, CO—O—C 1 -C 4 -alkylene-aryl, SO 2 —C 1 -C 6 -alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 —C 1 -C 4 -alkylene-aryl, OCO—C 1 -C 6 -alkyl, OCO-aryl, OCO-hetaryl, OCO—C 1 -C 4 -alkylene-aryl, OCO—C 1 -C 4 -alkylene-hetaryl, SO 2 —C 1 -C 6 -alkyl, SO 2 -aryl, SO 2 -hetaryl or SO 2 —C 1 -C 4 -alkylene-aryl, or
each independent from the third moiety two moieties of R 1 , R 2 or R 3 together form a 5 to 7-membered, optionally substituted, saturated or unsaturated carbocycle or an optionally substituted, saturated or unsaturated heterocycle which can contain one, two or three further different or same heteroatoms from the group O, N, S, wherein optionally two moieties substituted on this carbo- or heterocycle together can form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or same heteroatoms O, N, S, and wherein the cycle formed can be optionally substituted or a further, optionally substituted cycle can be condensed onto this cycle;
Q:
a doubly substituted 5-membered hetaryl moiety chosen from Q1 to Q7
E: O, N—R Q 1 or S;
R Q 1 :
hydrogen or
each optionally substituted C 1 -C 4 -alkyl, CO—C 1 -C 4 -alkyl, SO 2 —C 1 -C 4 -alkyl, CO—O—C 1 -C 4 -alkyl, aryl, C 1 -C 4 -alkylene-aryl, CO-aryl, CO-hetaryl, SO 2 -aryl, SO 2 -hetaryl, CO—O-aryl, CO—C 1 -C 4 -alkylene-aryl, SO 2 —C 1 -C 4 -alkylene-aryl or CO—O—C 1 -C 4 -alkylene-aryl;
R 4 , R 5 each independently of one another a moiety chosen from the groups 1.), 2.), 3.), 4.), 5.), 6.) or 7.):
1.) hydrogen, halogen, CN, CF 3 , CHF 2 , or
each optionally substituted C 1 -C 10 -alkyl, C 2 -C 10 -alkenyl, C 2 -C 10 -alkynyl, C 3 -C 7 -cycloalkyl, C 1 -C 6 -alkylene-C 3 -C 7 -cycloalkyl, C 1 -C 4 -alkylene-aryl, C 1 -C 4 -alkylene-hetaryl, C 1 -C 6 -alkylene-O—C 1 -C 6 -alkyl, C 1 -C 6 -alkylene-O-aryl, COO—C 1 -C 4 -alkyl or C 1 -C 4 -alkylene-COO—C 1 -C 4 -alkyl;
2.) Phenyl or naphthyl, which are each substituted with R Q 2 , R Q 3 and R Q 4 , wherein
R Q 2 , R Q 3 and R Q 4 each independently of one another represent 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
each optionally substituted aryl, hetaryl, heterocycloalkyl, 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, 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 8 —CO—O—R Q 6 , O—CH 2 —COO—R Q 6 , NR Q 8 —CO—R Q 6 , SO 2 —R Q 6 , NR Q 8 —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 6 , or
two of the moieties R Q 2 , R Q 3 or R Q 4 together form a 3 to 7-membered, optionally substituted, saturated, unsaturated or aromatic carbocycle or a an optionally substituted, saturated, unsaturated aromatic heterocycle which can contain up to three further different or same heteroatoms O, N, S and optionally two of the moieties substituted on this heterocycle can together form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or same heteroatoms O, N, S and the cycle formed can be optionally substituted or a further, optionally substituted cycle can be condensed onto this cycle;
R Q 5 each optionally substituted 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 6 -alkyl, which is optionally substituted with a substituent 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 each 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 hydrogen, OH, CN, or
each 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 hydrogen or
each 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 moieties R Q 7 and R Q 8 , together with the nitrogen, form a 3 to 7-membered, optionally substituted, saturated or aromatic heterocycle, which can contain one, two or three further different or same heteroatoms O, N, S; and optionally two of the moieties substituted on this heterocycle can together form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S, and the cycle formed can optionally be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
3.) a 5- or 6-membered hetaryl moiety optionally substituted with 1 or 2 substituents, the hetaryl moiety chosen from the group consisting of:
2-pyrrolyl, 3-pyrrolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-pyrimidyl, 4-pyrimidyl, 5-pyrimidyl, 6-pyrimidyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 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, benzthiazolyl, benzoxazolyl, chinolinyl and isochinolinyl; or
2-thienyl or 3-thienyl optionally substituted with one or two substituents, wherein the substituents are chosen from the group consisting of halogen, NO 2 , NH 2 , OH, CN, CF 3 , OCF 3 , CHF 2 , O—CHF 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.) both moieties R 4 and R 5 together form a 4 to 7-membered, optionally substituted, saturated or unsaturated or aromatic carbocycle or a 5- or 6-membered optionally substituted, saturated or unsaturated or aromatic heterocycle, which can contain up to three further different or identical heteroatoms O, N, S; and can be substituted with up to two further moieties, wherein optionally two moieties substituted on this carbo or hetero cycle can together form an anellated, saturated, unsaturated or aromatic carbo cycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S and wherein the cycle formed can be optionally substituted or a further, optionally substituted cycle can be condensed onto this cycle;
5.) a C 5 -C 18 - bi- or tricyclic, saturated hydrocarbon moiety;
6.) each optionally substituted C 1 -C 8 -Alkyl-NH 2 , C 1 -C 8 -Alkyl-NR Q 7 R Q 8 , C 1 -C 8 -Alkyl-CO—NR Q 7 R Q 8 , C 1 -C 8 -Alkyl-SO 2 NR Q 7 R Q 8 , C 1 -C 8 -Alkyl-CO—NH 2 , C 1 -C 8 -Alkyl-SO 2 NH 2 , CO—NH 2 , CO—NR Q 7 R Q 8 , SO 2 NH 2 , SO 2 NR Q 7 R Q 8 , NR Q 7 R Q 8 ;
7.) a 4-7-membered mono- or bicyclic saturated or unsaturated heterocycle, which can contain up to two different or identical heteroatoms from the group O, N or S, wherein this cycle can also be multiply substituted. For the case that the heterocycle contains an N-atom, this can be substituted with a moiety R Q 7 .
2 . Guanidine compound of the general formula I
corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof as well as pharmaceutically acceptable salts thereof, wherein the given moieties have the following definitions:
W:
a moiety of the general formula W1 or W2
A:
NO 2 , NH 2 , OH, CN, CF 3 , OCF 3 , CHF 2 , OCHF 2 , COOH, O—CH 2 —COOH, halogen, SH, or
each 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-heterocyclo-alkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 -alkylene-hetaryl or C 1 -C 4 -alkylene-aryl, or
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 , CONH 2 , SO 2 NH 2 , 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 or CO—NR A 2 R A 3 ;
R A 1 :
each 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-heterocyclo-alkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 -alkylene-aryl, C 2 -C 6 -alkenylene-aryl or C 1 -C 6 -alkylene-hetaryl;
R A 2 :
hydrogen, OH, CN, or
each 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 5 -alkyl, CO-aryl, CO-hetaryl, CO—C 1 -C 4 -alkylene-aryl, CO—C 1 -C 4 -alkylene-hetaryl, CO—O—C 1 -C 4 -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 .
each 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 moieties R A 2 and R A 3 form, together with the nitrogen, a 3 to 7-membered, optionally substituted, saturated or aromatic heterocycle, which can contain one, two or three further different or identical heteroatoms from the group O, N, S; wherein optionally two of the moieties substituted on this heterocycle can together form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms 0, N, S and wherein the so-formed cycle can be optionally substituted or a further, optionally substituted cycle can be condensed onto this cycle;
R A 4 :
hydrogen, or
each 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-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:
hydrogen or as moiety A is defined,
or each independently of one another, two of the moieties A, B or R w 1 together form a 3 to 7-membered, optionally substituted, saturated or unsaturated carbocycle or an optionally substituted, saturated or unsaturated or aromatic heterocycle which can contain one, two or three further different or identical heteroatoms from the group O, N, S; wherein optionally two moieties substituted on this carbo- or heterocycle can together form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S and wherein the cycle formed can optionally be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
R w 1 :
hydrogen, OH, halogen, NO 2 , NH 2 , CN, CF 3 , CHF 2 , O—CF 3 , O—CHF 2 , or each 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;
D:
as moiety A is defined;
Z:
a moiety of the general formula Z1
with the indices
a=0-4
b=0, 1
c=0-4
wherein the sum of a, b and c is at least 1 and no more than 5;
R Z 1 , R Z 2 , R Z 3 , R Z 4 independently of one another:
hydrogen, halogen, OH, or
each optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -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 two moieties are R Z 1 and R Z 2 or R Z 3 and R Z 4 together form a 3 to 7-membered, optionally substituted, saturated or unsaturated carbo- or heterocycle, wherein the heterocycle can contain up to three heteroatoms from the group O, N, or S;
V Z :
—CO—, —CO—NR z 5 -, —NR z 5 —CO—, —O—, —S—, —SO—, —SO 2 —, —SO 2 —NR z 5 —, —NR z 5 —SO 2 —, —CS—, —CS—NR z 5 —, —NR z 5 —CS—, —CS—O—, —O—CS—, —CO—O—, —O—CO—, —O—, ethynylene, —C(═CR Z 6 R z 7 )—, —CR Z 6 ═CR Z 7 —, —NR z 5 —CO—NR z 5 *—, —O—CO—NR z 5 —, —NR z 5 —;
R Z 5 , R Z 5 * independently of one another:
hydrogen or
each 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;
R Z 6 , R Z 7 independently of one another:
hydrogen, OH or
each optionally substituted C 1 -C 6 -alkyl, C 1 -C 4 -alkoxy, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -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;
R 1 , R 2 , R 3 independently of one another:
hydrogen, OH, CN, or
each 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 3 -C 7 -cycloalkyl, O—C 3 -C 7 -cycloalkyl, aryl, hetaryl, C 1 -C 4 -alkylene-aryl, C 1 -C 4 -alkylene-hetaryl, O-aryl, O—C 1 -C 4 -alkylene-aryl, O-hetaryl, O—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, CO—O-aryl, CO—O-hetaryl, CO—O—C 1 -C 4 -alkylene-aryl, SO 2 —C 1 -C 6 -alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 — C 1 -C 4 -alkylene-aryl, OCO—C 1 -C 6 -alkyl, OCO-aryl, OCO-hetaryl, OCO—C 1 -C 4 -alkylene-aryl, OCO—C 1 -C 4 -alkylene-hetaryl, SO 2 —C 1 -C 6 -alkyl, SO 2 -aryl, SO 2 -hetaryl or SO 2 —C 1 -C 4 -alkylene-aryl, or
each independently of the third moiety, two moieties of R 1 , R 2 or R 3 together form a 5 to 7-membered, optionally substituted, saturated or unsaturated carbocycle or an optionally substituted, saturated or unsaturated heterocycle which can contain one, two or three further different or identical heteroatoms from the group O, N, S, wherein optionally two of the moieties substituted on this carbo- or heterocycle can together form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S and wherein the cycle formed is optionally substituted or a further, optionally substituted cycle is condensed onto this cycle;
Q:
a doubly substituted 5-membered hetaryl moiety chosen from Q1 to Q6
E: O, N—R Q 1 or S;
R Q 1 :
hydrogen, or
each optionally substituted C 1 -C 4 -alkyl, CO—C 1 -C 4 -alkyl, SO 2 —C 1 -C 4 -alkyl, CO—O—C 1 -C 4 -alkyl, aryl, C 1 -C 4 -alkylene-aryl, CO-aryl, CO-hetaryl, SO 2 -aryl, SO 2 -hetaryl, CO—O-aryl, CO—C 1 -C 4 -alkylene-aryl, SO 2 —C 1 -C 4 -alkylene-aryl or CO—O—C 1 -C 4 -alkylene-aryl;
R 4 , R 5 each independently of one another a moiety chosen from the groups 1.), 2.), 3.), 4.) or 5.):
1.) hydrogen, halogen, CN, CF 3 , CHF 2 , or
each optionally substituted C 1 -C 10 -alkyl, C 2 -C 10 -alkenyl, C 2 -C 10 -alkynyl, C 3 -C 7 -cycloalkyl, C 1 -C 6 -alkylene-C 3 -C 7 -cycloalkyl, C 1 -C 4 -alkylene-aryl, C 1 -C 4 -alkylene-hetaryl, C 1 -C 6 -alkylene-O—C 1 -C 6 -alkyl, C 1 -C 6 -alkylene-O-aryl, COO—C 1 -C 4 -alkyl or C 1 -C 4 -alkylene-COO—C 1 -C 4 -alkyl;
2.) Phenyl or naphthyl, which are each substituted with R Q 2 , R Q 3 and R Q 4 , wherein
R Q 2 , R Q 3 and R Q 4 each independently of one another represent 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
each optionally substituted aryl, hetaryl, heterocycloalkyl, 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, 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 8 —CO—O—R Q 6 , O—CH 2 —COO—R Q 6 , NR Q 8 —CO—R Q 6 , SO 2 —R Q 6 , NR Q 8 —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 of the moieties R Q 2 , R Q 3 or R Q 4 together form a 3 to 7-membered, optionally substituted, saturated, unsaturated or aromatic carbocycle or an optionally substituted, saturated or unsaturated aromatic heterocycle, which can contain up to three further different or identical heteroatoms O, N, S and optionally two moieties substituted on this heterocycle can together form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S and the cycle formed can optionally be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
R Q 5 each optionally substituted 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 6 -alkyl, which is optionally substituted with a substituent 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 each 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 hydrogen, OH, CN, or
each 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 each 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 moieties R Q 7 and R Q 8 form, together with the nitrogen, a 3 to 7-membered, optionally substituted, saturated or aromatic heterocycle which can contain one, two or three further or different identical heteroatoms O, N, S; and optionally two moieties substituted on this heterocycle can form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S and the cycle formed can optionally be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
3.) a 5- or 6-membered hetaryl moiety optionally substituted with one or two substituents from the group consisting of:
2-pyrrolyl, 3-pyrrolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-pyrimidyl, 4-pyrimidyl, 5-pyrimidyl, 6-pyrimidyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 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, benzthiazolyl, benzoxazolyl, chinolinyl and isochinolinyl; or
2-thienyl or 3-thienyl optionally substituted with one or two substituents, wherein the substituents are chosen from the group consisting of halogen, NO 2 , NH 2 , OH, CN, CF 3 , OCF 3 , CHF 2 , O—CHF 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;
5.) both moieties R 4 and R 5 together form a 4 to 7-membered, optionally substituted, saturated or unsaturated or aromatic carbocycle or a 5- or 6-membered optionally substituted, saturated or unsaturated or aromatic heterocycle, which can contain up to three further different or identical heteroatoms O, N, S and can be substituted with up to two further moieties, wherein optionally two moieties substituted on this carbo- or heterocycle can form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S and wherein the cycle formed can be optionally substituted or a further, optionally substituted cycle can be condensed onto this cycle;
6.) a C 5 -C 18 - bi- or tricyclic, saturated hydrocarbon moiety.
3 . Guanadine compound according to claim 1 or 2 , wherein the given moieties have the following definition:
W: W1;
A: halogen, OH, CN, CF 3 , CHF 2 , OCF 3 , OCHF 2 , or
each optionally substituted C 1 -C 6 -alkyl or C 2 -C 6 -alkenyl, O—CH 2 —COO—R A 1 , O—R A 1 , S—R A 1 , NR A 2 R A 3 , NR A 4 —CO—R A 1 or CO—NR A 4 R A 1 ;
R A 1 : each optionally substituted C 1 -C 4 -alkyl, C 3 -C 7 -cycloalkyl, phenyl or benzyl;
R A 2 : hydrogen, or
each optionally substituted C 1 -C 4 -alkyl, phenyl, benzyl, phenethyl, CO—C 1 -C 4 -alkyl, CO-aryl, CO—O—C 1 -C 4 -alkyl, SO 2 —C 1 -C 4 -alkyl, SO 2 -aryl, SO 2 -hetaryl or SO 2 —C 1 -C 4 -alkylene-aryl;
R A 3 : each optionally substituted C 1 -C 4 -alkyl, phenyl, benzyl, phenethyl, CO—C 1 -C 4 -alkyl, CO-aryl, CO—O—C 1 -C 4 -alkyl, SO 2 —C 1 -C 4 -alkyl, SO 2 -aryl, SO 2 -hetaryl, or SO 2 —C 1 -C 4 -alkylene-aryl;
or the moieties R A 2 and R A 3 together form an optionally substituted 5- or 6-membered saturated or unsaturated ring, which can contain up to two identical or different heteroatoms from the group O and N;
R A 4 : hydrogen or an optionally substituted C 1 -C 4 -alkyl moiety;
B: hydrogen or as moiety A is defined;
R w 1 : hydrogen, F, Cl, CN, CF 3 , O—CF 3 , or
each optionally substituted C 1 -C 4 -alkyl, aryl, C 1 -C 6 -alkylamino or C 1 -C 6 -dialkylamino;
in the formula Z1 the sum of a, b and c is 1, 2 or 3;
R Z 1 , R Z 2 , R Z 3 , R Z 4 independently of one another:
hydrogen, halogen, OH, optionally substituted C 1 -C 6 -alkyl;
V z : —CO—, —CO—NR z 5 —, —NR z 5 —CO—, —O—, —S—;
R Z 5 : hydrogen, CH 3 ;
R 1 , R 2 , R 3 independently of one another:
hydrogen, OH, CN, C 1 -C 4 -alkyl, C 1 -C 6 -alkylene-O—C 1 -C 6 -alkyl, substituted aryl, benzyl, CO—C 1 -C 6 -alkyl, CO-aryl, CO—C 1 -C 4 -alkylene-aryl, OCO—C 1 -C 6 -alkyl, OCO-aryl or OCO—C 1 -C 4 -alkylene-hetaryl;
Q is chosen from the group consisting of Q1, Q2 and Q3;
R Q 1 : hydrogen, optionally substituted C 1 -C 4 -alkyl, in the aryl moiety optionally substituted benzyl, CO—C 1 -C 4 -alkyl, optionally substituted benzoyl, SO 2 —C 1 -C 4 -alkyl or in the aryl moiety optionally substituted SO 2 -aryl.
4 . Guanidine compound according to at least one of the claims 1 to 3 , wherein the given moieties have the following definitions:
A: OH, F, Cl, OCF 3 , OCHF 2 , optionally substituted C 1 -C 4 -alkyl, O—C 1 -C 4 -alkyl or S—C 1 -C 4 -alkyl;
B: hydrogen, OH, F, Cl, CF 3 , OCF 3 , OCHF 2 , optionally substituted C 1 -C 4 -alkyl, O—C 1 -C 4 -alkyl or S—C 1 -C 4 -alkyl;
R w 1 : hydrogen, F, Cl, CN, CF 3 or O—CF 3 ;
Z: each optionally substituted C 1 -C 4 -alkyl or C 1 -C 4 -alkylene-O—C 1 -C 4 -alkyl;
R Z 1 , R Z 2 , R Z 3 , R Z 4 each independently of one another:
hydrogen, F, CH 3 ;
R 1 , R 2 , R 3 independently of one another:
hydrogen, OH, CN, O-methyl, O-phenyl, acetyl, benzoyl, O-acetyl, O-benzoyl;
Q is chosen from the group consisting of
R Q 1 : hydrogen, CH 3 , methanesulfonyl, phenylsulfonyl or tosyl.
5 . Guanidine compound according to at least one of the claims 1 to 4 , wherein the given moieties have the following definitions:
A: OH, OCF 3 , OCH 3 , O-ethyl, O-propyl or O-i-propyl;
Z: —CH 2 —, —CH 2 —O—, —CH 2 —CH 2 — or —CH 2 —CH 2 —O—;
two of the moieties R 1 , R 2 , or R 3 , are hydrogen, and the third moiety is hydrogen, OH, acetyl or benzoyl;
Q:
6 . Guanidine compound according to at least one of the claims 1 to 5 , wherein R 4 and/or R 5 each independently of one another represents a moiety chosen from the groups 1.), 2.), 3.), 4.) or 5.):
1.) hydrogen, F, Cl, CN, CF 3 , or
each optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 1 -C 6 -alkylene-O—C 1 -C 6 -alkyl or C 3 -C 7 -cycloalkyl;
2.) R Q 1 , R Q 2 and R Q 3 independently of one another
hydrogen, CN, CF 3 , CHF 2 , OCF 3 , OCHF 2 , F, Cl, OH or each optionally substituted phenyl or hetaryl, C 1 -C 4 -alkyl, C 5 -C 7 -cycloalkyl, O—R Q 5 , NR Q 7 R Q 8 , CO—OR Q 6 , NR Q 8 —CO—O—R Q 6 , O—CH 2 —COO—R Q 6 , NR Q 8 —CO—R Q 6 , SO 2 —R Q 6 , NR Q 8 —SO 2 —R Q 6 , NR Q 8 —CO—O—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 ;
R Q 5 : C 1 -C 4 -Alkyl, which is optionally substituted with a substituent from the group consisting of F, Cl, OH, CN, CF 3 , OCF 3 , NH—(C 1 -C 4 -alkyl) and N(C 1 -C 4 -alkyl) 2 ;
R Q 6 : each optionally substituted C 1 -C 6 -alkyl, aryl, hetaryl or phenyl;
R Q 7 : hydrogen, each optionally substituted C 1 -C 4 -alkyl, allyl, aryl, hetaryl, benzyl, phenethyl or CH 2 -hetaryl;
R Q 8 : each optionally substituted C 1 -C 4 -alkyl, allyl, aryl, hetaryl, benzyl, phenethyl or CH 2 -hetaryl;
or R Q 7 und R Q 8 form an optionally substituted 3- or 7-membered saturated or unsaturated ring which can contain up to two identical or different hetero
atoms from the group O and N;
3.) benzothiophenyl, benzofuranyl, chinolinyl or isochinolinyl;
4.) both moieties R 4 and R 5 together form one of the following rings:
wherein R Q 2 and R Q 3 are as defined under 2.);
5.) Adamantyl.
7 . Guanidine compound according to claim 1 or 2 , wherein the given moieties have the following definitions:
W: W1;
A: halogen, OH, CN, CF 3 , CHF 2 , OCF 3 , OCHF 2 , or
each optionally substituted C 1 -C 6 -alkyl or C 2 -C 6 -alkenyl, O—CH 2 —COO—R A 1 , O—R A 1 , S—R A 1 , NR A 2 R A 3 , NR A 4 —CO—R A 1 , SO 2 NH 2 , NR A 4 —SO 2 —R A 1 , SO 2 —NR A 2 R A 3 or CO—NR A 4 R A 1 ;
R A 1 : each optionally substituted C 1 -C 4 -alkyl, C 3 -C 7 -cycloalkyl, phenyl or benzyl;
R A 2 : hydrogen, or
each optionally substituted C 1 -C 4 -alkyl, phenyl, benzyl, phenethyl, CO—C 1 -C 4 -alkyl, CO-aryl, CO—O—C 1 -C 4 -alkyl, SO 2 —C 1 -C 4 -alkyl, SO 2 -aryl, SO 2 -hetaryl or SO 2 —C 1 -C 4 -alkylene-aryl;
R A 3 : each optionally substituted C 1 -C 4 -alkyl, phenyl, benzyl, phenethyl, CO—C 1 -C 4 -alkyl, CO-aryl, CO—O—C 1 -C 4 -alkyl, SO 2 —C 1 -C 4 -alkyl, SO 2 -aryl, SO 2 -hetaryl, or SO 2 —C 1 -C 4 -alkylene-aryl;
or the moieties R A 2 and R A 3 together form an optionally substituted 5- or 6-membered saturated or unsaturated ring, which can contain up to two identical or different heteroatoms from the group O and N;
R A 4 : hydrogen or an optionally substituted C 1 -C 4 -alkyl moiety;
B: hydrogen or as moiety A is defined;
R w 1 : hydrogen, F, Cl, CN, CF 3 , O—CF 3 , or
each optionally substituted C 1 -C 4 -alkyl, aryl, C 1 -C 6 -alkylamino or C 1 -C 6 -dialkylamino;
in the formula Z1 the sum of a, b and c is 1, 2 or 3;
R Z 1 , R Z 2 , R Z 3 , R Z 4 independently of one another:
hydrogen, halogen, OH, optionally substituted C 1 -C 6 -alkyl;
V Z : —CO—, —CO—NR z 5 —, —NR z 5 —CO—, —O—, —S—;
R Z 5 : hydrogen, CH 3 ;
R 1 , R 2 , R 3 independently of one another:
hydrogen, OH, CN, C 1 -C 4 -alkyl, C 1 -C 6 -alkylene-O—C 1 -C 6 -alkyl, substituted aryl, benzyl, CO—C 1 -C 6 -alkyl, CO-aryl, CO—C 1 -C 4 -alkylene-aryl, OCO—C 1 -C 6 -alkyl, OCO-aryl or OCO—C 1 -C 4 -alkylene-hetaryl;
Q is chosen from the group consisting of Q1, Q2, Q3 and Q5;
R Q 1 : hydrogen, optionally substituted C 1 -C 4 -alkyl, in the aryl moiety optionally substituted benzyl, CO—C 1 -C 4 -alkyl, optionally substituted benzoyl, SO 2 —C 1 -C 4 -alkyl or in the aryl moiety optionally substituted SO 2 -aryl.
8 . Guanidine compound according to at least one of claims 1 , 2 or 7 , wherein the given moieties have the following definitions:
A: OH, F, Cl, OCF 3 , OCHF 2 , optionally substituted C 1 -C 4 -alkyl, O—C 1 -C 4 -alkyl or S—C 1 -C 4 -alkyl;
B: hydrogen, OH, F, Cl, CF 3 , OCF 3 , OCHF 2 , optionally substituted C 1 -C 4 -alkyl, O—C 1 -C 4 -alkyl or S—C 1 -C 4 -alkyl;
R w 1 : hydrogen, F, Cl, CN, CF 3 or O—CF 3 ;
Z: each optionally substituted C 1 -C 4 -alkyl or C 1 -C 4 -alkylene-O—C 1 -C 4 -alkyl;
R Z 1 , R Z 2 , R Z 3 , R Z 4 each independently of one another:
hydrogen, F, CH 3 ;
R 1 , R 2 , R 3 independently of one another:
hydrogen, OH, CN, O-methyl, O-phenyl, acetyl, benzoyl, O-acetyl, O-benzoyl;
Q is chosen from the group consisting of
R Q 1 : hydrogen, CH 3 , phenyl, benzyl, methanesulfonyl, phenylsulfonyl or tosyl.
9 . Guanidine compound according to at least one of the claims 1 , 2 , 7 or 8 , wherein the given moieties have the following definitions:
A: OH, OCF 3 , OCH 3 , O-ethyl, O-propyl or O-i-propyl;
Z: —CH 2 —, —CH 2 —O—, —CH 2 —CH 2 — or —CH 2 —CH 2 —O—;
two of the moieties R 1 , R 2 , or R 3 are hydrogen, and the third moiety is hydrogen, OH, acetyl or benzoyl;
Q:
R Q 1 : hydrogen, CH 3 , phenyl, benzyl, methanesulfonyl, phenylsulfonyl or tosyl.
10 . Guanidine compound according to at least one of the claims 1 , 2 or 7 to 9 , wherein R 4 and/or R 5 each independently from one another represent a moiety chosen from the groups 1.), 2.), 3.), 4.), 5.) or 7.):
1.) hydrogen, F, Cl, CN, CF 3 , or
each optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 1 -C 6 -alkylene-O—C 1 -C 6 -alkyl or C 3 -C 7 -cycloalkyl;
2.) R Q 1 , R Q 2 and R Q 3 independently of one another hydrogen, CN, CF 3 , CHF 2 , OCF 3 , OCHF 2 , F, Cl, OH or each optionally substituted phenyl or hetaryl, C 1 -C 4 -alkyl, C 5 -C 7 -cycloalkyl, O—R Q 5 , NR Q 7 R Q 8 , CO—OR Q 6 , NR Q 8 —CO—O—R Q 6 , O—CH 2 —COO—R Q 6 , NR Q 8 —CO—R Q 6 , SO 2 —R Q 6 , NR Q 8 —SO 2 —R Q 6 , NR Q 8 —CO—O—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 ;
R Q 5 : C 1 -C 4 -alkyl, which is optionally substituted with a substituent from the group consisting of F, Cl, OH, CN, CF 3 , OCF 3 , NH—(C 1 -C 4 -alkyl) and N(C 1 -C 4 -alkyl) 2 ;
R Q 6 : each optionally substituted C 1 -C 6 -alkyl, aryl, hetaryl or phenyl;
R Q 7 : hydrogen, each optionally substituted C 1 -C 4 -alkyl, allyl, aryl, hetaryl, benzyl, phenethyl or CH 2 -hetaryl;
R Q 8 : hydrogen, each optionally substituted C 1 -C 4 -alkyl, allyl, aryl, hetaryl, benzyl, phenethyl or CH 2 -hetaryl;
or R Q 7 and R Q 8 form an optionally substituted 3- or 7-membered saturated or unsaturated ring, which can contain up to two identical or different heteroatoms from the group O and N;
3.) benzothiophenyl, benzofuranyl, chinolinyl or isochinolinyl;
4.) both moieties R 4 and R 5 together form one of the following rings:
wherein R Q 2 and R Q 3 are defined as under 2.); or together can form an anellated 5- or 6-membered ring;
5.) adamantyl;
7.) each optionally substituted azetidine-3-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, tetrahydro-2H-pyrane-4-yl, tetrahydrofuran-3-yl, azepan-4-yl, azepan-3-yl, azepan-2-yl, 1,4-diazepane-5-yl, 1,2,3,6-tetrahydropyridine-4-yl, 2,5-dihydro-1H-pyrrol-3-yl.
11 . Guanidine compound according to at least one of the claims 1 to 10 , wherein one moiety from R 4 and R 5 is chosen from group 1.), and the other moiety from R 4 and R 5 is chosen from the group 1.), 2.) or 3.).
12 . Guanidine compound according to at least one of the claims 1 to 11 as a medicament.
13 . Pharmaceutical composition, comprising at least one guanidine compound according to one of the claims 1 to 12 , as well as a pharmaceutically acceptable carrier or dilution agent.
14 . Use of compounds of the general formula IVA for the preparation of 5HT5A receptor ligands:
W—Z—NH 2 IVA
15 . Use according to claim 14 for the preparation of the guanidine compounds according to one of the claims 1 to 12 .
16 . Use of a guanidine compound of the general formula IA
of the corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof as well as pharmaceutically acceptable salts thereof
wherein the given moieties have the following definitions:
W:
a moiety of the general formula W1 or W2
A:
NO 2 , NH 2 , OH, CN, CF 3 , OCF 3 , CHF 2 , OCHF 2 , COOH, O—CH 2 —COOH, halogen, SH, or
each 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 or C 1 -C 4 -alkylene-hetero-cycloalkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 -alkylene-hetaryl or C 1 -C 4 -alkylene-aryl, or
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 , CONH 2 , SO 2 NH 2 , NR A 4 —CO—R A 1 , SO 2 —R A 1 , NR A 4 —SO—R A 1 , SO 2 —NR A 2 R A 3 or CO—NR A 2 R A 3 ;
R A 1 :
each 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-heterocyclo-alkyl, aryl, hetaryl, heterocycloalkyl, C 1 -C 4 -alkylene-aryl, C 2 -C 6 -alkenylene-aryl or C 1 -C 6 -alkylene-hetaryl;
R A 2 :
hydrogen, OH, CN, or
each 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 :
each 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 moieties R A 2 and R A 3 form, together with the nitrogen, a 3 to 7-membered, optionally substituted, saturated or aromatic heterocycle, which can contain one, two or three further different or identical heteroatoms from the group O, N, S; wherein optionally two moieties substituted on this heterocycle can together form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms, O, N, S and wherein the so-formed cycle can optionally be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
R A 1 :
hydrogen, or
each 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-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:
hydrogen or as moiety A is defined,
or each independently of one another two of the moieties A, B or R w 1 together form a 3 to 7-membered, optionally substituted, saturated or unsaturated carbocycle with an optionally substituted, saturated or unsaturated or aromatic heterocycle which can contain one, two or three further different or identical heteroatoms from the group O, N, S; wherein optionally two moieties substituted on this carbo- or heterocycle can form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S and wherein the cycle formed can optionally be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
R w 1 :
hydrogen, OH, halogen, NO 2 , NH 2 , CN, CF 3 , CHF 2 , O—CF 3 , O—CHF 2 , or each 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 -alkylene-S—C 1 -C 6 -alkyl, 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;
D:
as moiety A is defined;
Z:
a moiety of the general formula Z1
with the indices
a=0-4
b=0, 1
c=0-4
wherein the sum of a, b and c is no more than 5;
R Z 1 , R Z 2 , R Z 3 , R Z 4 independently of one another:
hydrogen, halogen, OH, or
each optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -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 two moieties R Z 1 , and R Z 2 or R Z 3 and R Z 4 together form a 3 to 7-membered, optionally substituted, saturated or unsaturated carbo- or heterocycle, which can contain up to three heteroatoms from the group O, N or S;
V z :
—CO—, —CO—NR z 5 —, —NR z 5 —CO—, —O—, —S—, —SO—, —SO 2 —, —SO 2 —NR z 5 —, —NR z 5 —SO 2 —, —CS—, —CS—NR z 5 —, —NR z 5 —CS—, —CS—O—, —O—CS—, —CO—O—, —O—CO—, —O—, ethynylene, —C(═CR Z 6 R z 7 )—, —CR Z 6 ═CR Z 7 —, —NR z 5 —CO—NR z 5 *—, —O—CO—NR z 5 —, —NR z 5 —;
R Z 5 , R Z 5 * independently of one another:
hydrogen, or
each 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;
R Z 6 , R Z 7 independently of one another:
hydrogen, OH, or
each optionally substituted C 1 -C 6 -alkyl, C 1 -C 4 -alkoxy, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -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;
R 1 , R 2 , R 3 independently of one another:
hydrogen, OH, CN, or
each 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 3 -C 7 -cycloalkyl, O—C 3 -C 7 -cycloalkyl, aryl, hetaryl, C 1 -C 4 -alkylene-aryl, C 1 -C 4 -alkylene-hetaryl, O-aryl, O—C 1 -C 4 -alkylene-aryl, O-hetaryl, O—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, CO—O-aryl, CO—O-hetaryl, CO—O—C 1 -C 4 -alkylene-aryl, SO 2 —C 1 -C 6 -alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 —C 1 -C 4 -alkylene-Aryl, OCO—C 1 -C 6 -alkyl, OCO-aryl, OCO-hetaryl, OCO—C 1 -C 4 -alkylene-aryl, OCO—C 1 -C 4 -alkylene-hetaryl, SO 2 —C 1 -C 6 -alkyl, SO 2 -aryl, SO 2 -hetaryl or SO 2 —C 1 -C 4 -alkylene-aryl, or
each independently from the third moiety two moieties of R 1 , R 2 or R 3 together form a 5 to 7-membered, optionally substituted, saturated or unsaturated carbocycle or an optionally substituted, saturated or unsaturated, which can contain one, two or three further different or identical heteroatoms from the group O, N, S, wherein optionally two moieties substituted on this carbo- or heterocycle can together form an anellated, saturated, unsaturated, or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S and wherein the cycle formed can be optionally substituted or a further, optionally substituted cycle can be condensed onto this cycle;
Q:
a doubly substituted 5-membered hetaryl moiety, chosen from Q1 to Q7
E: O, N—R Q 1 or S;
R Q 1 :
hydrogen, or
each optionally substituted C 1 -C 4 -alkyl, CO—C 1 -C 4 -alkyl, SO 2 —C 1 -C 4 -alkyl, CO—O—C 1 -C 4 -alkyl, aryl, C 1 -C 4 -alkylene-aryl, CO-aryl, CO-hetaryl, SO 2 -aryl, SO 2 -hetaryl, CO—O-aryl, CO—C 1 -C 4 -alkylene-aryl, SO 2 —C 1 -C 4 -alkylene-aryl or CO—O—C 1 -C 4 -alkylene-aryl;
R 4 , R 5 each independently of one another, a moiety chosen from the groups 1.), 2.), 3.), 4.), 5.), 6.) or 7.):
1.) hydrogen, halogen, CN, CF 3 , CHF 2 , or
each optionally substituted C 1 -C 10 -alkyl, C 2 -C 10 -alkenyl, C 2 -C 10 -alkynyl, C 3 -C 7 -cycloalkyl, C 1 -C 6 -alkylene-C 3 -C 7 -cycloalkyl, C 1 -C 4 -alkylene-aryl, C 1 -C 4 -alkylene-hetaryl, C 1 -C 6 -alkylene-O—C 1 -C 6 -alkyl, C 1 -C 6 -alkylene-O-aryl, COO—C 1 -C 4 -alkyl or C 1 -C 4 -alkylene-COO—C 1 -C 4 -alkyl;
3.) phenyl or naphthyl, which are substituted with R Q 2 , R Q 3 and R Q 4 , wherein
R Q 2 , R Q 3 and R Q 4 each independently of one another represent 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
each optionally substituted aryl, hetaryl, heterocycloalkyl, 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, 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 8 —CO—O—R Q 6 , O—CH 2 —COO—R Q 6 , NR Q 8 —CO—R Q 6 , SO 2 —R Q 6 , NR Q 8 —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 of the moieties R Q 2 , R Q 3 or R Q 4 together form a 3 to 7-membered, optionally substituted, saturated, unsaturated carbocycle or an optionally substituted, saturated, unsaturated aromatic heterocycle which can contain up to three further different or identical heteroatoms O, N, S, and optionally two moieties substituted on this heterocycle can form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S, and the cycle formed may optionally be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
R Q 5 each 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, aryl or hetaryl;
R Q 6 each 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 hydrogen, OH, CN, or
each 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 hydrogen or
each 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 both moieties R Q 7 and R Q 8 form, together with the nitrogen, a 3 to 7-membered, optionally substituted, saturated or aromatic heterocycle,
which can contain one, two or three different or identical heteroatoms O, N, S; and optionally two moieties substituted on this heterocycle can together form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S, and the cycle formed can be optionally substituted or a further, optionally substituted cycle can be condensed onto this cycle;
3.) a 5- or 6-membered, hetaryl moiety, optionally substituted with 1 or 2 substituents from the group consisting of:
2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-pyrimidyl, 4-pyrimidyl, 5-pyrimidyl, 6-pyrimidyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl, 6-pyridazinyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, thiadiazolyl, oxadiazolyl or triazinyl or their anellated derivatives indazolyl, indolyl, benzothiophenyl, benzofuranyl, indolinyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, chinolinyl and isochinolinyl;
4.) both moieties R 4 and R 5 together form a 4 to 7-membered, optionally substituted, saturated or unsaturated or aromatic carbocycle or a 5- or 6-membered optionally substituted, saturated or unsaturated or aromatic heterocycle, which can contain up to three further different or identical heteroatoms O, N, S, and which can be substituted with up to two further moieties, wherein optionally two moieties substituted on this carbo- or heterocycle together form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S and wherein the cycle formed can optionally be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
5.) a C 6 -C 10 - bi- or tricyclyc, saturated hydrocarbon moiety;
6.) each optionally substituted C 1 -C 8 -alkyl-NH 2 , C 1 -C 8 -alkyl-NR Q 7 R Q 8 , C 1 -C 8 -alkyl-CO—NR Q 7 R Q 8 , C 1 -C 8 -alkyl-SO 2 NR Q 7 R Q 8 , C 1 -C 8 -alkyl-CO—NH 2 , C 1 -C 8 -alkyl-SO 2 NH 2 , CO—NH 2 , CO—NR Q 7 R Q 8 , SO 2 NH 2 , SO 2 NR Q 7 R Q 8 , NR Q 7 R Q 8 ;
7.) a 4-7-membered mono- or bicyclic saturated or unsaturated heterocycle, which can contain up to two different or identical heteroatoms from the group O, N or S, wherein this cycle can also be multiply substituted. For the case that the heterocycle contains an N-atom, this can be substituted with an R Q 7 moiety.
for the preparation of a medicament for the treatment of diseases modulated by a 5-HT5 receptor activity.
17 . Use of a guanidine compound of the general formula IA
of the corresponding enantiomeric, diastereomeric and/or tautomeric forms thereof as well as pharmaceutically acceptable salts thereof,
wherein the given moieties have the following definitions:
W:
a moiety of the general formula W1 or W2
A:
NO 2 , NH 2 , OH, CN, CF 3 , OCF 3 , CHF 2 , OCHF 2 , COOH, O—CH 2 —COOH, halogen, SH, or
each 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 or 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 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 , CONH 2 , SO 2 NH 2 , 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 or CO—NR A 2 R A 3 ;
R A 1 :
each 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 -alkenylene-aryl or C 1 -C 6 -alkylene-hetaryl;
R A 2 :
hydrogen, OH, CN, or
each 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 :
each 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 moieties R A 2 and R A 3 form, together with the nitrogen, a 3 to 7-membered, optionally substituted, saturated or aromatic heterocycle, which can contain one, two or three further different or identical heteroatoms from the group O, N, S; wherein optionally two moieties substituted on this heterocycle together can form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S, and wherein the so-formed cycle can optionally be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
R A 4 :
hydrogen, or
each 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-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:
hydrogen or as moiety A is defined,
or each independently from another, two of the moieties A, B or R w 1 together form a 3 to 7-membered, optionally substituted, saturated or unsaturated carbocycle or an optionally substituted, saturated or unsaturated or aromatic heterocycle, which can contain one, two or three further different or identical heteroatoms from the group O, N, S; wherein optionally two moieties substituted on this carbo- or heterocycle can together form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S and wherein the heterocycle formed can optionally be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
R w 1 :
hydrogen, OH, halogen, NO 2 , NH 2 , CN, CF 3 , CHF 2 , O—CF 3 , O—CHF 2 , or each 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 -alkylene-S—C 1 -C 6 -alkyl, 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;
D:
as moiety A is defined;
Z:
a moiety of the general formula Z1
with the indices
a=0-4
b=0, 1
c=0-4
wherein the sum of a, b and c is no more than 5;
R Z 1 , R Z 2 , R Z 3 , R Z 4 independently of one another:
hydrogen, halogen, OH, or
each optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -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, two moieties R Z 1 and R Z 2 or R Z 3 and R Z 4 together form a 3 to 7-membered, optionally substituted, saturated or unsaturated carbo- or heterocycle, which can contain up to three heteroatoms from the group O, N or S;
V z :
—CO—, —CO—NR z 5 —, —NR z 5 —CO—, —O—, —S—, —SO—, —SO 2 —, —SO 2 —NR z 5 —, —NR z 5 —SO 2 —, —CS—, —CS—NR z 5 —, —NR z 5 —CS—, —CS—O—, —O—CS—, —CO—O—, —O—CO—, —O—, ethynylene, —C(═CR Z 6 R z 7 )—, —CR Z 6 ═CR z 7 —, —NR z 5 —CO—NR z 5 *—, —O—CO—NR z 5 —, —NR z 5 —;
R Z 5 , R Z 5 * independently of one another:
hydrogen, or
each 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;
R Z 6 , R Z 7 independently of one another:
hydrogen, OH, or
each optionally substituted C 1 -C 6 -alkyl, C 1 -C 4 -alkoxy, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -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;
R 1 , R 2 , R 3 independently of one another:
hydrogen, OH, CN, or
each 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 3 -C 7 -cycloalkyl, O—C 3 -C 7 -cycloalkyl, aryl, hetaryl, C 1 -C 4 -alkylene-aryl, C 1 -C 4 -alkylene-hetaryl, O-aryl, O—C 1 -C 4 -alkylene-aryl, O-hetaryl, O—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, CO—O-aryl, CO—O-hetaryl, CO—O—C 1 -C 4 -alkylene-aryl, SO 2 —C 1 -C 6 -alkyl, SO 2 -aryl, SO 2 -hetaryl, SO 2 —C 1 -C 4 -alkylene-aryl, OCO—C 1 -C 6 -alkyl, OCO-aryl, OCO-hetaryl, OCO—C 1 -C 4 -alkylene-aryl, OCO—C 1 -C 4 -alkylene-hetaryl, SO 2 —C 1 -C 6 -alkyl, SO 2 -aryl, SO 2 -hetaryl or SO 2 —C 1 -C 4 -alkylene-aryl, or
each independently of the third moiety, two moieties of R 1 , R 2 or R 3 together form a 5 to 7-membered, optionally substituted, saturated or unsaturated carbocycle, or an optionally substituted, saturated or unsaturated, which can contain one, two or three different or identical heteroatoms from the group O, N, S, wherein optionally two moieties substituted on this carbo- or heterocycle can together form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle may contain up to three different or identical heteroatoms O, N, S and wherein the cycle formed can optionally be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
Q:
a doubly substituted 5-membered hetaryl moiety, chosen from Q1 to Q6
E: O, N—R Q 1 or S;
R Q 1 :
hydrogen, or
each optionally substituted C 1 -C 4 -alkyl, CO—C 1 -C 4 -alkyl, SO 2 —C 1 -C 4 -alkyl, CO—O—C 1 -C 4 -alkyl, aryl, C 1 -C 4 -alkylene-aryl, CO-aryl, CO-hetaryl, SO 2 -aryl, SO 2 -hetaryl, CO—O-aryl, CO—C 1 -C 4 -alkylene-aryl, SO 2 —C 1 -C 4 -alkylene-aryl or CO—O—C 1 -C 4 -alkylene-aryl;
R 4 , R 5 each independently of one another a moiety chosen from the groups 1.), 2.), 3.), 4.) or 5.):
1.) hydrogen, halogen, CN, CF 3 , CHF 2 , or
each optionally substituted C 1 -C 10 -alkyl, C 2 -C 10 -alkenyl, C 2 -C 10 -alkynyl, C 3 -C 7 -cycloalkyl, C 1 -C 6 -alkylene-C 3 -C 7 -cycloalkyl, C 1 -C 4 -alkylene-aryl, C 1 -C 4 -alkylene-hetaryl, C 1 -C 6 -alkylene-O—C 1 -C 6 -alkyl, C 1 -C 6 -alkylene-O-aryl, COO—C 1 -C 4 -alkyl or C 1 -C 4 -alkylene-COO—C 1 -C 4 -alkyl;
4.) Phenyl or naphthyl, which are each substituted with R Q 2 , R Q 3 and R Q 4 , wherein
R Q 2 , R Q 3 and R Q 4 each independently from one another represent 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
each optionally substituted aryl, hetaryl, heterocycloalkyl, 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, 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 8 —CO—O—R Q 6 , O—CH 2 —COO—R Q 6 , NR Q 8 —CO—R Q 6 , SO 2 —R Q 6 , NR Q 8 —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 of the moieties R Q 2 , R Q 3 or R Q 4 together form a 3 to 7-membered, optionally substituted, saturated, unsaturated carbocycle or an optionally substituted, saturated, unsaturated aromatic heterocycle, which can contain up to three further different or identical heteroatoms O, N, S, and optionally two moieties substituted on this heterocycle together can form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S, and the cycle formed can optionally be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
R Q 5 each 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, aryl or hetaryl;
R Q 6 each 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 hydrogen, OH, CN, or
each 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 each 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 both moieties R Q 7 and R Q 8 form, together with the nitrogen, a 3 to 7-membered, optionally substituted, saturated or aromatic heterocycle, which can contain one, two or three further different or identical heteroatoms O, N, S; and optionally two moieties substituted on this heterocycle can together form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or same heteroatoms O, N, S and the cycle formed can optionally be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
3.) a 5- or 6-membered, hetaryl moiety, optionally substituted with one or two substituents from the group consisting of:
2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-pyrimidyl, 4-pyrimidyl, 5-pyrimidyl, 6-pyrimidyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl, 6-pyridazinyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, thiadiazolyl, oxadiazolyl or triazinyl or their anellated derivatives indazolyl, indolyl, benzothiophenyl, benzofuranyl, indolinyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, chinolinyl and isochinolinyl;
4.) both moieties R 4 and R 5 together form a 4 to 7-membered, optionally substituted, saturated or unsaturated or aromatic carbocycle or a 5- or 6-membered optionally substituted, saturated or unsaturated or aromatic heterocycle, which can contain up to three further different or identical heteroatoms O, N, S, and can be substituted with up to two further moieties, wherein optionally two moieties substituted on this carbo- or heterocycle can together form an anellated, saturated, unsaturated or aromatic carbocycle or heterocycle, wherein the heterocycle can contain up to three different or identical heteroatoms O, N, S and wherein the cycle formed can optionally be substituted or a further, optionally substituted cycle can be condensed onto this cycle;
5.) a C 6 -C 10 - bi- or tricyclyc, saturated hydrocarbon moiety;
for the manufacture of a medicament for the treatment of diseases which are modulated by a 5-HT5 receptor activity.
18 . Use according to claim 16 , wherein R 4 and/or R 5 have the following meanings:
2-pyridyl, 3-pyridyl, 4-pyridyl, 2-thienyl, 3-thienyl, benzothiophenyl, benzofuranyl, chinolinyl or isochinolinyl, which may optionally be substituted with 1 or 2 moieties.
19 . Use according to claim 16 or 17 for the treatment of neuropathological, neuropsychiatric and neurodegenerative disorders, symptoms and dysfunctions.
20 . Use according to at least one of the claims 16 to 18 for the treatment of migraine and brain damage.
21 . Use according to claim 18 for the treatment of neuropathological, neuropsychiatric and neurodegenerative diseases, selected from the group consisting of cerebral ischemia, stroke, epilepsy and seizures in general, psychoses, schizophrenia, autism, OCD-syndrome, cognitive diseases, attention disorders, depressions, bipolar- and/or unipolar depressions, states of anxiety, dementia, senile dementia, Alzheimer dementia, demyelinizing diseases, multiple sclerosis and brain tumors.
22 . Use according to claim 16 or 17 for the treatment of diseases chosen from the group consisting of cerebral vascular disorders, pain, disorders due to pain, addiction, disorders due to drugs, amnesia, alcohol abuse, drug abuse, disorders of the circadian rhythm and Cushing syndrome.Join the waitlist — get patent alerts
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