1
CLAIMS
1-Products of the following general formula (I):
inwhich
- Z3 represents aheteroaryl radical constituted of 5 or 6 ring members with1 to 4 heteroatoms selected from N,S or Obound to the carboline unit either by a C or by an N belonging toZ3,Z3optionally being mono- or polysubstituted;
- Z6isselected from:
- H;
- halogen
- -OH
- alkoxy in which the alkyl moiety is optionally mono-, di- or trisubstituted;
- -Y-alkyl (Y = S,SO,SO2), linear or branched, optionally mono-, di- or trisubstituted;
- -X-aryl (X = O,S,SO,SO2)optionally mono-, di- or trisubstituted;
- -X-heteroaryl (X = O,S,SO,SO2,heteroaryl with 5 or 6 ring members with1 to 4 heteroatoms selected from N,S or Obound to X either by a C or an N)optionally mono-, di- or trisubstituted;
- -NH2,
- -NH(alkyl),-N(alkyl)2linear,branched orcyclic in which the alkyl moiety is optionally mono-, di- or trisubstituted;
- -NH(aryl) in which the aryl moiety is optionally mono-, di- or trisubstituted;
- -NH(heteroaryl)in which the heteroaryl moiety (heteroaryl with 5 or 6 ring members with1 to 4 heteroatoms selected from N,S or Obound to the nitrogen atom either by a C or by an N)isoptionally mono-, di- or trisubstituted;
- -N(alkyl)(aryl)in which the alkyl (linear, branched or cyclic) and aryl moieties are optionally mono-, di- or trisubstituted;
- -N(alkyl)(heteroaryl)in which the alkyl (linear, branched or cyclic) and heteroaryl (heteroaryl with 5 or 6 ring members with 1 to 4 heteroatoms selected from N, S or O bound to the nitrogen atom either by a C or an N) moieties are optionally mono-, di- or trisubstituted;
- -C(O)OH
- -C(O)Oalkyl, linear, branched or cyclic, optionally mono-, di- or trisubstituted;
- -C(O)Oaryl optionally mono-, di- or trisubstituted;
- -C(O)Oheteroaryl (heteroaryl with 5 or 6 ring members with1 to 4 heteroatoms selected from N,S or Obound to the oxygen by a C atom)optionally mono-, di- or trisubstituted;
- -CONH2
- -CO-heterocycloalkyl mono-, di- or trisubstituted
- -CONH(alkyl),CON(alkyl)2linear,branched orcyclic in which the alkyl moiety is optionally mono-, di- or trisubstituted;
- -CON(alkyl)(aryl), alkyllinear, branchedor cyclic in which the alkyl and aryl moieties are optionally mono-, di- or trisubstituted;
- -CON(alkyl)(heteroaryl), linear, branchedor cyclicalkyl and heteroaryl with 5 or 6 ring members with1 to 4 heteroatoms selected from N,S or Obound to the nitrogen atom either by a C or by an N)in which the alkyl and heteroaryl moieties are optionally mono-, di- or trisubstituted;
- -C1-C10alkyl, linear, branched or cyclic, optionally comprising a heteroatom andoptionally mono-, di- or trisubstituted
- aryl optionally mono-, di- or trisubstituted
- heteroaryl (5 or 6 ring memberswith1 to 4 heteroatoms selected from N,S or O)bound to the carboline unit either by a C or by an N belonging toZ6,Z6optionally being mono- or polysubstituted;
- heterocycloalkyl optionally mono- or polysubstituted;
- -C2-C6 alkenyl optionally mono- or disubstituted;
- -C2-C6 alkynyl optionally substituted;
saidproducts of formula (I)being in all possible isomeric forms,racemic, enantiomeric and diastereoisomeric, as well as the salts of addition of said products of formula (I) with mineral and organic acids or with mineral and organic bases.
2-Products of general formula (I)as defined in Claim 1 in which the optional substituents of Z3,i.e. the groupsR2a,R2b,R2c,R2d or R2e,are selected independently of one another from:
- F;
- Cl;
- Br;
- I;
- -C1-C10alkyl, linear or branched, optionally mono- or polysubstituted(R3a,R3b,R3c);
- -C3-C7cycloalkyl optionally mono- or polysubstituted(R3a,R3b,R3c),
- -OH;
- -O-alkyl(C1-C10), linear or branched, optionally mono- or polysubstituted(R3a,R3b,R3c);
- -Y-alkyl (Y = S,SO,SO2), linear or branched, optionally mono-, di- or trisubstituted(R3a,R3b,R3c);
- -O-cycloalkyl (C3-C7)optionally mono- or polysubstituted(R3a,R3b,R3c);
- -O-aryl optionally mono- or polysubstituted(R3a,R3b,R3c);
- aryl optionally mono- or polysubstituted(R3a,R3b,R3c);
- heteroaryl (5 or 6 ring memberswith1 to 4 heteroatoms selected from N,S or O) boundeither by a C or by an N)optionally mono- or polysubstituted(R3a,R3b,R3c);
- heterocycloalkyl optionally mono- or polysubstituted(R3a,R3b,R3c);
- -NO2;
- -NH2;
- -NH-(alkyl(C1-C10)or cycloalkyl(C3-C7)or heterocycloalkyl)eachgroup optionally mono- or polysubstituted(R3a,R3b,R3c);
- -N(alkyl(C1-C10)orcycloalkyl(C3-C7))2eachgroupoptionally being mono- or polysubstituted(R3a,R3b,R3c);
- -NHaryl or NH heteroaryl optionally mono- or polysubstituted
- -NHC(O)substituted(R3a,R3b,R3c);
- -N(alkyl(C1-C10)C(O)substituted(R3a,R3b,R3c);
- -NHS(O2)substituted(R3a,R3b,R3c);
- -N(alkyl(C1-C10)S(O2)substituted(R3a,R3b,R3c);
- -CO2substituted(R3a,R3b,R3c);
- –S substituted (R3a,R3b,R3c);
- -S(O2)substituted(R3a,R3b,R3c);
- -S(O) substituted(R3a,R3b,R3c);
- oxo (O double bond);
- -C2-C6 alkenyl optionally mono- or disubstituted (R3a,R3b);
- -C2-C6 alkynyl optionally substituted((R3a);
the groups R3a,R3b,R3c, or the substituents of the groups R2a,R2b,R2c,R2d or R2e,are selected independently of one another from:
- F;
- Cl;
- Br;
- I;
- -C1-C10alkyl, linear or branched, optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -C3-C7cycloalkyl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -OH;
- -O-alkyl(C1-C10), linear or branched, optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -Y-alkyl (Y = S,SO,SO2), linear or branched, optionally mono-, di- or trisubstituted with R4a,R4b,R4c;
- -O-cycloalkyl (C3-C7)optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -O-aryl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- aryl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- heteroaryl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- heterocycloalkyl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -NO2;
- -NH2;
- -NH-(alkyl(C1-C10)or cycloalkyl(C3-C7)or heterocycloalkyl)eachgroup optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -N(alkyl(C1-C10)orcycloalkyl(C3-C7))2eachgroupoptionally being mono- or polysubstitutedwith R4a,R4b,R4c;
- -NHaryl or NH heteroaryl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -NHC(O)substituted with R4a,R4b,R4c;
- -N(alkyl(C1-C10)C(O)substituted with R4a,R4b,R4c;
- -NHS(O2)substituted with R4a,R4b,R4c;
- -N(alkyl(C1-C10)S(O2) substituted with R4a,R4b,R4c;
- -CO2 substituted with R4a,R4b,R4c;
- -CONH2
- -CONH(alkyl),CON(alkyl)2linear,branched orcyclic in which the alkyl moiety is optionally mono-, di- or trisubstituted with R4a,R4b,R4c;
- -C(O)heterocycloalkyl optionally mono-, di- or trisubstituted with R4a,R4b,R4c;
- -S substituted with R4a,R4b,R4c;
- -S(O2) substituted with R4a,R4b,R4c;
- -S(O)substituted with R4a,R4b,R4c;
- oxo (O double bond);
- -C2-C6 alkenyl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -C2-C6 alkynyl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
the groups R4a,R4b,R4c, or the substituents of the groups R3a,R3b and R3c,are selected independently of one another from:
- F;
- Cl;
- Br;
- I;
- -CF3;-CHF2
- -C1-C10alkyllinearorbranched;
- -C3-C7cycloalkyl;
- -OH;
- -O-alkyl(C1-C10)linearorbranched;
- -Y-alkyl (Y = S,SO,SO2)linearorbranched;
- -O-cycloalkyl (C3-C7);
- -O-aryl;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- -NO2;
- -NH2;
- -NH-(alkyl(C1-C10)or cycloalkyl(C3-C7)or heterocycloalkyl);
- -N(alkyl(C1-C10)orcycloalkyl(C3-C7))2;
- -NHaryl or NH heteroaryl;
- -NHS(O2)alkyl;
- -N(alkyl(C1-C10)S(O2)alkyl;
- -CO2alkyl;
- -CONH2
- -CONH(alkyl),CON(alkyl)2linear,branched orcyclic;
- -C(O)heterocycloalkyl;
- –S-alkyl;
- -S(O2)alkyl;
- -S(O)alkyl;
- oxo (O double bond);
- -C2-C6 alkenyl linearorbranched;
- -C2-C6 alkynyl linearorbranched;
saidproducts of formula (I)being in all possible isomeric forms,racemic, enantiomeric and diastereoisomeric, as well as the salts of addition of said products of formula (I) with mineral and organic acids or with mineral and organic bases.
3-Products of general formula (I)as defined in Claim 1 in which the optional substituents of Z6,i.e. thegroupsR2a,R2b,R2c,R2d or R2e,are selected independently of one another from:
- F;
- Cl;
- Br;
- I;
- -C1-C10alkyl, linear or branched, optionally mono- or polysubstituted(R3a,R3b,R3c);
- -C3-C7cycloalkyl optionally mono- or polysubstituted(R3a,R3b,R3c),
- -OH;
- -O-alkyl(C1-C10), linear or branched, optionally mono- or polysubstituted(R3a,R3b,R3c);
- -Y-alkyl (Y = S,SO,SO2), linear or branched, optionally mono-, di- or trisubstituted(R3a,R3b,R3c);
- -O-cycloalkyl (C3-C7)optionally mono- or polysubstituted(R3a,R3b,R3c);
- -O-aryl optionally mono- or polysubstituted(R3a,R3b,R3c);
- aryl optionally mono- or polysubstituted(R3a,R3b,R3c);
- heteroaryl (5 or 6 ring memberswith1 to 4 heteroatoms selected from N,S or O) boundeither by a C or by an N)optionally mono- or polysubstituted(R3a,R3b,R3c);
- heterocycloalkyl optionally mono- or polysubstituted(R3a,R3b,R3c);
- -NO2;
- -NH2;
- -NH-(alkyl(C1-C10)or cycloalkyl(C3-C7)or heterocycloalkyl)eachgroup optionally mono- or polysubstituted(R3a,R3b,R3c);
- -N(alkyl(C1-C10)orcycloalkyl(C3-C7))2eachgroupoptionally being mono- or polysubstituted(R3a,R3b,R3c);
- -NHaryl or NH heteroaryl optionally mono- or polysubstituted
- -NHC(O)substituted(R3a,R3b,R3c);
- -N(alkyl(C1-C10)C(O)substituted(R3a,R3b,R3c);
- -NHS(O2)substituted(R3a,R3b,R3c);
- -N(alkyl(C1-C10)S(O2)substituted(R3a,R3b,R3c);
- -CO2substituted(R3a,R3b,R3c);
- –S substituted (R3a,R3b,R3c);
- -S(O2)substituted(R3a,R3b,R3c);
- -S(O) substituted(R3a,R3b,R3c);
- oxo (O double bond);
- -C2-C6 alkenyl optionally mono- or disubstituted (R3a,R3b);
- -C2-C6 alkynyl optionally substituted((R3a);
the groups R3a,R3b,R3c, or the substituents of the groups R2a,R2b,R2c,R2d or R2e,are selected independently of one another from:
- F;
- Cl;
- Br;
- I;
- -C1-C10alkyl, linear or branched, optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -C3-C7cycloalkyl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -OH;
- -O-alkyl(C1-C10), linear or branched, optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -Y-alkyl (Y = S,SO,SO2), linear or branched, optionally mono-, di- or trisubstituted with R4a,R4b,R4c;
- -O-cycloalkyl (C3-C7)optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -O-aryl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- aryl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- heteroaryl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- heterocycloalkyl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -NO2;
- -NH2;
- -NH-(alkyl(C1-C10)or cycloalkyl(C3-C7)or heterocycloalkyl)eachgroup optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -N(alkyl(C1-C10)orcycloalkyl(C3-C7))2eachgroupoptionally being mono- or polysubstitutedwith R4a,R4b,R4c;
- -NHaryl or NH heteroaryl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -NHC(O)substituted with R4a,R4b,R4c;
- -N(alkyl(C1-C10)C(O)substituted with R4a,R4b,R4c;
- -NHS(O2)substituted with R4a,R4b,R4c;
- -N(alkyl(C1-C10)S(O2) substituted with R4a,R4b,R4c;
- -CO2 substituted with R4a,R4b,R4c;
- -CONH2
- -CONH(alkyl),CON(alkyl)2linear,branched orcyclic in which the alkyl moiety is optionally mono-, di- or trisubstituted with R4a,R4b,R4c;
- -C(O)heterocycloalkyl optionally mono-, di- or trisubstituted with R4a,R4b,R4c;
- -S substituted with R4a,R4b,R4c;
- -S(O2) substituted with R4a,R4b,R4c;
- -S(O)substituted with R4a,R4b,R4c;
- oxo (O double bond);
- -C2-C6 alkenyl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -C2-C6 alkynyl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
the groups R4a,R4b,R4c, or the substituents of the groups R3a,R3b and R3c,are selected independently of one another from:
- F;
- Cl;
- Br;
- I;
- -CF3;-CHF2
- -C1-C10alkyllinearorbranched;
- -C3-C7cycloalkyl;
- -OH;
- -O-alkyl(C1-C10)linearorbranched;
- -Y-alkyl (Y = S,SO,SO2)linearorbranched;
- -O-cycloalkyl (C3-C7);
- -O-aryl;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- -NO2;
- -NH2;
- -NH-(alkyl(C1-C10)or cycloalkyl(C3-C7)or heterocycloalkyl);
- -N(alkyl(C1-C10)orcycloalkyl(C3-C7))2;
- -NHaryl or NH heteroaryl;
- -NHS(O2)alkyl;
- -N(alkyl(C1-C10)S(O2)alkyl;
- -CO2alkyl;
- -CONH2
- -CONH(alkyl),CON(alkyl)2linear,branched orcyclic;
- -C(O)heterocycloalkyl;
- –S-alkyl;
- -S(O2)alkyl;
- -S(O)alkyl;
- oxo (O double bond);
- -C2-C6 alkenyl linearorbranched;
- -C2-C6 alkynyl linearorbranched;
saidproducts of formula (I)being in all possible isomeric forms,racemic, enantiomeric and diastereoisomeric, as well as the salts of addition of said products of formula (I) with mineral and organic acids or with mineral and organic bases.
4 -Products of general formula (I)as defined in any one of the preceding claims inwhich
- Z3 represents aheteroaryl radical with 5 or 6 ring members with1 to 4 heteroatoms selected from N,S or Obound to the carboline unit either by a C or by an N belonging toZ3,Z3optionally being mono- or polysubstitutedwith R2a,R2b,R2c,R2d,R2e,which may be identical or different;
- Z6isselected from:
- H;
- halogen;
- -OH
- alkoxy in which the alkyl moiety is optionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- -Y-alkyl (Y = S,SO,SO2), linear or branched, optionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- -X-aryl (X = O,S,SO,SO2)optionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- -X-heteroaryl (X = O,S,SO,SO2,heteroaryl with 5 or 6 ring members with1 to 4 heteroatoms selected from N,S or Obound to X either by a C or an N)optionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- -NH2,
- -NH(alkyl),-N(alkyl)2linear,branched orcyclic in which the alkyl moiety is optionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- -NH(aryl) in which the aryl moiety is optionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- -NH(heteroaryl)in which the heteroaryl moiety (heteroaryl with 5 or 6 ring members with1 to 4 heteroatoms selected from N,S or Obound to the nitrogen atom either by a C or by an N)isoptionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- -N(alkyl)(aryl)in which the alkyl (linear, branched or cyclic) and aryl moieties are optionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- -N(alkyl)(heteroaryl)in which the alkyl (linear, branched or cyclic) and heteroaryl (heteroaryl with 5 or 6 ring members with 1 to 4 heteroatoms selected from N, S or O bound to the nitrogen atom either by a C or an N) moieties are optionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- -C(O)OH
- -C(O)Oalkyl, linear, branched or cyclic, optionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- -C(O)Oaryl optionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- -C(O)Oheteroaryl (heteroaryl with 5 or 6 ring members with1 to 4 heteroatoms selected from N,S or Obound to the oxygen by a C atom)optionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- -CONH2
- -CO-heterocycloalkyl mono-, di- or trisubstituted
- -CONH(alkyl),CON(alkyl)2linear,branched orcyclic in which the alkyl moiety is optionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- -CON(alkyl)(aryl), alkyllinear, branchedor cyclic in which the alkyl and aryl moieties are optionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- -CON(alkyl)(heteroaryl), alkyllinear, branchedor cyclicand heteroaryl with 5 or 6 ring members with1 to 4 heteroatoms selected from N,S or Obound to the nitrogen atom either by a C or by an N)in which the alkyl and heteroaryl moieties are optionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- -C1-C10alkyl, linear, branched or cyclic, optionally comprising a heteroatom andoptionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- aryl optionally mono-, di- or trisubstituted with R2a,R2b,R2c,which may be identical or different;
- heteroaryl (5 or 6 ring memberswith1 to 4 heteroatoms selected from N,S or O)bound to the carboline unit either by a C or by an N belonging toZ6,Z6optionally being mono- or polysubstitutedwith R2a,R2b,R2c,R2d,R2e which may be identical or different;
- heterocycloalkyl optionally mono- or polysubstitutedwith R2a,R2b,R2c,which may be identical or different;
- -C2-C6 alkenyl optionally mono- or disubstituted with R2a,R2b,which may be identical or different;
- -C2-C6 alkynyl optionally substituted with R2a;
the groups R2a,R2b,R2c,R2d or R2e are selected independently of one another from:
- F;
- Cl;
- Br;
- I;
- -C1-C10alkyl, linear or branched, optionally mono- or polysubstitutedwith R3a,R3b,R3c,which may be identical or different
- -C3-C7cycloalkyl optionally mono- or polysubstitutedwith R3a,R3b,R3c,which may be identical or different,
- -OH;
- -O-alkyl(C1-C10), linear or branched, optionally mono- or polysubstitutedwith R3a,R3b,R3c,which may be identical or different;
- -Y-alkyl (Y = S,SO,SO2), linear or branched, optionally mono-, di- or trisubstituted with R3a,R3b,R3c,which may be identical or different;
- -O-cycloalkyl (C3-C7)optionally mono- or polysubstitutedwith R3a,R3b,R3c,which may be identical or different;
- -O-aryl optionally mono- or polysubstitutedwith R3a,R3b,R3c,which may be identical or different;
- aryl optionally mono- or polysubstitutedwith R3a,R3b,R3c,which may be identical or different;
- heteroaryl constituted of 5 or 6 ring members with1 to 4 heteroatoms selected from N,S or O boundeither by a C or by an N)optionally mono- or polysubstitutedwith R3a,R3b,R3c,which may be identical or different;
- heterocycloalkyl optionally mono- or polysubstitutedwith R3a,R3b,R3c,which may be identical or different;
- -NO2;
- -NH2;
- -NH-(alkyl(C1-C10)or cycloalkyl(C3-C7)or heterocycloalkyl)eachgroup optionally mono- or polysubstitutedwith R3a,R3b,R3c,which may be identical or different;
- -N(alkyl(C1-C10)orcycloalkyl(C3-C7))2eachgroupoptionally being mono- or polysubstitutedwith R3a,R3b,R3c,which may be identical or different;
- -NHaryl or NH heteroaryl optionally mono- or polysubstitutedwith R3a,R3b,R3c,which may be identical or different
- -NHC(O) substituted with R3a,R3b,R3c,which may be identical or different;
- -N(alkyl(C1-C10)C(O) substituted with R3a,R3b,R3c,which may be identical or different;
- -NHS(O2) substituted with R3a,R3b,R3c,which may be identical or different;
- -N(alkyl(C1-C10)S(O2) substituted with R3a,R3b,R3c,which may be identical or different;
- -CO2 substituted with R3a,R3b,R3c,which may be identical or different;
- –S substituted with R3a,R3b,R3c,which may be identical or different;
- -S(O2) substituted with R3a,R3b,R3c,which may be identical or different;
- -S(O)substituted with R3a,R3b,R3c,which may be identical or different;
- oxo (O double bond);
- -C2-C6 alkenyl optionally mono- or disubstituted with R3a,R3bwhich may be identical or different;
- -C2-C6 alkynyl optionally substituted with R3a;
the groups R3a,R3b,R3c, or the substituents of the groups R2a,R2b,R2c,R2d or R2e,are selected independently of one another from:
- F;
- Cl;
- Br;
- I;
- -C1-C10alkyl, linear or branched, optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -C3-C7cycloalkyl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -OH;
- -O-alkyl(C1-C10), linear or branched, optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -Y-alkyl (Y = S,SO,SO2), linear or branched, optionally mono-, di- or trisubstituted with R4a,R4b,R4c;
- -O-cycloalkyl (C3-C7)optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -O-aryl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- aryl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- heteroaryl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- heterocycloalkyl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -NO2;
- -NH2;
- -NH-(alkyl(C1-C10)or cycloalkyl(C3-C7)or heterocycloalkyl)eachgroup optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -N(alkyl(C1-C10)orcycloalkyl(C3-C7))2eachgroupoptionally being mono- or polysubstitutedwith R4a,R4b,R4c;
- -NHaryl or NH heteroaryl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -NHC(O)substituted with R4a,R4b,R4c;
- -N(alkyl(C1-C10)C(O)substituted with R4a,R4b,R4c;
- -NHS(O2)substituted with R4a,R4b,R4c;
- -N(alkyl(C1-C10)S(O2) substituted with R4a,R4b,R4c;
- -CO2 substituted with R4a,R4b,R4c;
- -CONH2
- -CONH(alkyl),CON(alkyl)2linear,branched orcyclic in which the alkyl moiety is optionally mono-, di- or trisubstituted with R4a,R4b,R4c;
- -C(O)heterocycloalkyl optionally mono-, di- or trisubstituted with R4a,R4b,R4c;
- -S substituted with R4a,R4b,R4c;
- -S(O2) substituted with R4a,R4b,R4c;
- -S(O)substituted with R4a,R4b,R4c;
- oxo (O double bond);
- -C2-C6 alkenyl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
- -C2-C6 alkynyl optionally mono- or polysubstitutedwith R4a,R4b,R4c;
the groups R4a,R4b,R4c, or the substituents of the groups R3a,R3b and R3c,are selected independently of one another from:
- F;
- Cl;
- Br;
- I;
- -CF3;-CHF2
- -C1-C10alkyllinearorbranched;
- -C3-C7cycloalkyl;
- -OH;
- -O-alkyl(C1-C10)linearorbranched;
- -Y-alkyl (Y = S,SO,SO2)linearorbranched;
- -O-cycloalkyl (C3-C7);
- -O-aryl;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- -NO2;
- -NH2;
- -NH-(alkyl(C1-C10)or cycloalkyl(C3-C7)or heterocycloalkyl);
- -N(alkyl(C1-C10)orcycloalkyl(C3-C7))2;
- -NHaryl or NH heteroaryl;
- -NHS(O2)alkyl;
- -N(alkyl(C1-C10)S(O2)alkyl;
- -CO2alkyl;
- -CONH2
- -CONH(alkyl),CON(alkyl)2linear,branched orcyclic;
- -C(O)heterocycloalkyl;
- –S-alkyl;
- -S(O2)alkyl;
- -S(O)alkyl;
- oxo (O double bond);
- -C2-C6 alkenyl linearorbranched;
- -C2-C6 alkynyl linearorbranched;
saidproducts of formula (I)being in all possible isomeric forms,racemic, enantiomeric and diastereoisomeric, as well as the salts of addition of said products of formula (I) with mineral and organic acids or with mineral and organic bases.
5 -Products of formula (I)as defined in any one of the preceding claims with the following names:
- 6-methoxy-3-(pyridin-3-yl)-9H-beta-carboline
- 3-(pyridin-3-yl)-9H-beta-carboline
- 6-bromo-3-(pyridin-3-yl)-9H-beta-carboline
- methyl 3-(pyridin-3-yl)-9H-beta-carboline-6-carboxylate
- 6-methoxy-3-(5-methoxypyridin-3-yl)-9H-beta-carboline
- 5-(6-methoxy-9H-beta-carbolin-3-yl)pyridin-2-amine
- 3-(pyrimidin-5-yl)-9H-beta-carboline
- 6-methoxy-3-(6-methoxypyridin-3-yl)-9H-beta-carboline
- 6-methoxy-3-[6-(methylsulphanyl)pyridin-3-yl]-9H-beta-carboline
- 3-(pyridin-3-yl)-6-(trifluoromethyl)-9H-beta-carboline
- 3-(pyridin-3-yl)-6-(trifluoromethoxy)-9H-beta-carboline
- 6-fluoro-3-(pyridin-3-yl)-9H-beta-carboline
-N,N-diethyl-2-{4-[3-(pyridin-3-yl)-9H-beta-carbolin-6-yl]-1H-pyrazol-1-yl}ethanamine
- N,N-diethyl-2-{4-[3-(1-methyl-1H-pyrazol-4-yl)-9H-beta-carbolin-6-yl]-1H-pyrazol-1-yl}ethanamine
- 6-{4-[3-(piperidin-1-yl)propoxy]phenyl}-3-(pyridin-3-yl)-9H-beta-carboline
- 3-(1-methyl-1H-pyrazol-4-yl)-6-{4-[3-(piperidin-1-yl)propoxy]phenyl}-9H-beta-carboline
- 6-(difluoromethoxy)-3-(pyridin-3-yl)-9H-beta-carboline
- 6-(difluoromethoxy)-3-(1-methyl-1H-pyrazol-4-yl)-9H-beta-carboline
- 6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-9H-beta-carboline
6 -Method for preparing theproducts of formula (I)as defined in thepreceding claims,characterizedby the following general scheme:
inwhichthesubstituents Z3andZ6have the meanings given for the products of formula (I)in any one of the preceding claims,theoptionally reactive functions of Z3andZ6beingoptionally protected by known protecting groups.
7-Asmedicinal products,theproducts of formula (I)as defined in Claims 1 to 4 as well astheir prodrugs, saidproducts of formula (I)being in all possible isomeric forms, racemic, enantiomeric and diastereoisomeric, as well as the salts of addition of said products of formula (I)with pharmaceutically acceptable mineral and organic acids or mineral and organic bases.
8-Asmedicinal products,theproducts of formula (I)as defined in Claims 1 to4with the following names:
- 6-methoxy-3-(pyridin-3-yl)-9H-beta-carboline
- 3-(pyridin-3-yl)-9H-beta-carboline
- 6-bromo-3-(pyridin-3-yl)-9H-beta-carboline
- methyl 3-(pyridin-3-yl)-9H-beta-carboline-6-carboxylate
- 6-methoxy-3-(5-methoxypyridin-3-yl)-9H-beta-carboline
- 5-(6-methoxy-9H-beta-carbolin-3-yl)pyridin-2-amine
- 3-(pyrimidin-5-yl)-9H-beta-carboline
- 6-methoxy-3-(6-methoxypyridin-3-yl)-9H-beta-carboline
- 6-methoxy-3-[6-(methylsulphanyl)pyridin-3-yl]-9H-beta-carboline
- 3-(pyridin-3-yl)-6-(trifluoromethyl)-9H-beta-carboline
- 3-(pyridin-3-yl)-6-(trifluoromethoxy)-9H-beta-carboline
- 6-fluoro-3-(pyridin-3-yl)-9H-beta-carboline
- N,N-diethyl-2-{4-[3-(pyridin-3-yl)-9H-beta-carbolin-6-yl]-1H-pyrazol-1-yl}ethanamine
- N,N-diethyl-2-{4-[3-(1-methyl-1H-pyrazol-4-yl)-9H-beta-carbolin-6-yl]-1H-pyrazol-1-yl}ethanamine
- 6-{4-[3-(piperidin-1-yl)propoxy]phenyl}-3-(pyridin-3-yl)-9H-beta-carboline
- 3-(1-methyl-1H-pyrazol-4-yl)-6-{4-[3-(piperidin-1-yl)propoxy]phenyl}-9H-beta-carboline
- 6-(difluoromethoxy)-3-(pyridin-3-yl)-9H-beta-carboline
- 6-(difluoromethoxy)-3-(1-methyl-1H-pyrazol-4-yl)-9H-beta-carboline
- 6-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-9H-beta-carboline
9 -Pharmaceutical compositions containing, as active principle, a compound according to any oneof the preceding claims as well as at least one pharmaceutically compatible excipient.
10 -Pharmaceutical compositions according to the preceding claim used for thetreatment of cancer.
11-Asnovel industrial products,thesynthesis intermediates offormula(XIV)as defined in thegeneral scheme of Claim 6andhereunder:
inwhichthesubstituents Z3andZ6have the meanings given for the products of formula (I)in any one of the preceding claims,theoptionally reactive functions of Z3andZ6beingoptionally protected by known protecting groups.
PATENT
DISUBSTITUTED 9H-PYRIDINO[3,4-b]INDOLE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF
SANOFI-AVENTIS
Abstract
Products of formula (I):
inwhichZ3represents heteroaryl with 5 or 6 ring members with1 to 4 heteroatoms selected from N,S or O, optionally substituted;
Z6notablyrepresents H;Hal;OH;alkoxy;-Y-alkyl(Y = S,SO,SO2);-X-aryl or-X-heteroaryl (X = O,S,SO,SO2);-NH2,-NH(alkyl),-N(alkyl)2;-NH(aryl);-NH(heteroaryl);-N(alkyl)(aryl);-N(alkyl)(heteroaryl);-C(O)OH;linear -C(O)Oalkyl; -C(O)Oaryl;-C(O)Oheteroaryl;-CONH2;-CONH(alkyl),CON(alkyl)2;-CO-heterocycloalkyl;-CON(alkyl)(aryl);-CON(alkyl)(heteroaryl);-C1-C10alkyllinear, branchedor cyclic;aryl;heteroaryl;heterocycloalkyl;-C2-C6 alkenyl;-C2-C6 alkynyl;
alloptionally mono- or polysubstituted;
as well as theisomers andthesaltsof saidproducts of formula (I)andtheirapplicationin therapeuticsfor thetreatment of cancer.