1. A heterocyclic compound of the formula (I)
the stereoisomers, N-oxides, prodrugs, tautomers andor physiologically tolerated acid addition salts thereof, and the compounds of the general formula I, wherein at least one of the atoms has been replaced by its stable, non-radioactive isotope, wherein
A is selected from the group consisting of CRA1RA2 and NRB; where
RA1 and RA2 are independently of each other selected from the group consisting of hydrogen, C1-C2-alkyl, C1-C2-haloalkyl, NH2 and OH; and
RB is selected from hydrogen, C1-C4-alkyl and C1-C4-haloalkyl;
X1 and X2 are independently of each other selected from the group consisting of CR2 and N;
X3, X4, X5 and X6 are independently of each other selected from the group consisting of CR3, CR4 and N;
with the proviso that no more than two of X3, X4, X5 and X6 are CR4;
Y1, Y2, Y3 and Y4 are independently of each other selected from the group consisting of CR4, CR5 and N;
with the proviso that at most one of Y1, Y2, Y3 and Y4 is N and with the proviso that at most one of Y1, Y2, Y3 and Y4 is CR4; and
with the proviso that one of Y1, Y2, Y3 and Y4 is CR4 or C\u2014CF3 if none of X3, X4, X5 and X6 is CR4;
R1 is selected from hydrogen, C1-C4-alkyl and C1-C4-haloalkyl;
each R2 is independently selected from the group consisting of hydrogen, OH, halogen, CN, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy and NRaRb;
or two radicals R2 bonded at the carbon atoms of groups X1 and X2, together with the carbon atoms to which they are bonded, form a 5- or 6-membered saturated or unsaturated ring which may contain 1 or 2 heteroatoms as ring members selected from the group consisting of N, O and S and which optionally carries 1, 2 or 3 substituents R6;
each R3 is independently selected from the group consisting of hydrogen, CN, NRaRb, OH, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C3-C7-cycloalkyl, C3-C7-halocycloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C1-C6-alkoxy, C1-C6-haloalkoxy, formyl, C1-C6-alkylcarbonyl, C1-C6-haloalkylcarbonyl, C1-C6-alkoxycarbonyl, C1-C6-haloalkoxycarbonyl, C1-C6-alkyl-NRaRb and an aromatic radical Ar, which is selected from the group consisting of phenyl and a 5- or 6-membered N- or C-bound heteroaromatic radical comprising one nitrogen atom and optionally 1, 2 or 3 further heteroatoms independently selected from O, S and N as ring members, wherein Ar is unsubstituted or carries one or two radicals R7 and wherein Ar may also be bonded via a CH2 group;
R4 is a C-bound saturated or partially unsaturated monocyclic 3-, 4-, 5-, 6- or 7-membered heterocyclic ring containing 1, 2 or 3 heteroatoms or heteroatom-containing groups selected from O, N, S, NO, SO and SO2 as ring members, where the heterocyclic ring optionally carries 1, 2 or 3 C- or N-bound substituents R8;
R5 is selected from the group consisting of hydrogen, CN, NRaRb, OH, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C3-C7-cycloalkyl, C3-C7-halocycloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C1-C6-alkoxy, C1-C6-haloalkoxy, formyl, C1-C6-alkylcarbonyl, C1-C6-haloalkylcarbonyl, C1-C6-alkoxycarbonyl, C1-C6-haloalkoxycarbonyl, C1-C6-alkyl-NRaRb and an aromatic radical Ar, which is selected from the group consisting of phenyl and a 5- or 6-membered N- or C-bound heteroaromatic radical comprising one nitrogen atom and optionally 1, 2 or 3 further heteroatoms independently selected from O, S and N as ring members, wherein Ar is unsubstituted or carries one or two radicals R7 and wherein Ar may also be bonded via a CH2 group;
R6 and R8, independently of each other and independently of each occurrence, are selected from the group consisting of CN, NRaRb, OH, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C3-C7-cycloalkyl, C3-C7-halocycloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C1-C6-alkoxy, C1-C6-haloalkoxy, formyl, C1-C6-alkylcarbonyl, C1-C6-haloalkylcarbonyl, C1-C6-alkoxycarbonyl, C1-C6-haloalkoxycarbonyl, C1-C6-alkyl-NRaRb and an aromatic radical Ar, which is selected from the group consisting of phenyl and a 5- or 6-membered N- or C-bound heteroaromatic radical comprising one nitrogen atom and optionally 1, 2 or 3 further heteroatoms independently selected from O, S and N as ring members, wherein Ar is unsubstituted or carries one or two radicals R7 and wherein Ar may also be bonded via a CH2 group;
each R7 is independently selected from the group consisting of halogen, CN, C1-C6-alkyl, C1-C6-haloalkyl, C3-C6-cycloalkyl, C3-C6-halocycloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, NRaRb, a phenyl group and a 5- or 6-membered heteroaromatic radical comprising one nitrogen atom and optionally 1, 2 or 3 further heteroatoms independently selected from O, S and N as ring members, wherein phenyl and the heteroaromatic radical are, independently of each other, unsubstituted or substituted by 1, 2, 3 or 4 radicals selected from halogen, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-haloalkoxy; and
Ra and Rb are independently of each other selected from the group consisting of hydrogen, C1-C6-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylcarbonyl and C1-C4-haloalkylcarbonyl;
or Ra and Rb form, together with the nitrogen atom to which they are bonded, a 3-, 4-, 5-, 6- or 7-membered saturated or unsaturated aromatic or non-aromatic N-heterocyclic ring, which may contain 1 further heteroatom or heteroatom containing group selected from the group consisting of O, S, SO, SO2 and N as a ring member.
2. The heterocyclic compound of claim 1, wherein either one of X3, X4, X5 and X6 is CR4 and none of Y1, Y2, Y3 and Y4 is CR4, or one of Y1, Y2, Y3 and Y4 is CR4 and none of X3, X4, X5 and X6 is CR4.
3. The heterocyclic compound of claim 1, wherein one of Y1, Y2, Y3 and Y4 is CR4 if none of X3, X4, X5 and X6 is CR4.
4. The heterocyclic compound of claim 1, wherein one of Y1, Y2, Y3 and Y4 is C\u2014CF3 if none of X3, X4, X5 and X6 is CR4.
5. The heterocyclic compound of claim 1, wherein R4 is selected from a C-bound saturated or partially unsaturated monocyclic 4-, 5- or 6-membered heterocyclic ring containing 1 or 2 or 3 heteroatoms selected from O, N, S and SO, as ring members, where the heterocyclic ring optionally carries 1, 2 or 3 substituents R8.
6. The heterocyclic compound of claim 5, wherein R4 is selected from C-bound oxetanyl, thietanyl, azetidinyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydrothienyl-1-oxide, pyrrolidinyl, pyrrolinyl, pyrazolidinyl, pyrazolinyl, imidazolidinyl, imidazolinyl, tetrahydropyranyl, dihydropyranyl, piperidinyl, tetrahydropyridinyl, dihydropyridinyl, piperazinyl and morpholinyl, where the heterocyclic ring optionally carries 1, 2 or 3 substituents R8.
7. The heterocyclic compound of claim 6, wherein R4 is selected from C-bound oxetanyl, azetidinyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydrothienyl-1-oxide, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, dihydropyranyl, piperidinyl, tetrahydropyridinyl, dihydropyridinyl, piperazinyl and morpholinyl, where the heterocyclic ring optionally carries 1, 2 or 3 substituents R8.
8. The heterocyclic compound of claim 7, wherein R4 is selected from azetidin-3-yl, tetrahydrofuran-3-yl, pyrrolidin-3-yl, pyrrolin-3-yl, tetrahydropyran-4-yl, tetrahydropyran-3-yl, dihydropyran-4-yl, dihydropyran-3-yl, piperidin-4-yl, 1,2,5,6-tetrahydropyridin-4-yl and 1,2-dihydropyridin-4-yl, where the heterocyclic ring optionally carries 1, 2 or 3 substituents R8.
9. The heterocyclic compound of claim 1, wherein R8 is selected from C1-C6-alkyl, C1-C6-haloalkyl, C3-C7-cycloalkyl, C3-C7-halocycloalkyl, C2-C4-alkenyl, C2-C4-haloalkenyl, C1-C6-alkoxy, C1-C6-haloalkoxy, formyl, C1-C6-alkylcarbonyl, C1-C6-haloalkylcarbonyl, C1-C6-alkoxycarbonyl, C1-C6-haloalkoxycarbonyl and benzyl and is preferably C1-C6-alkyl, C1-C6-haloalkyl or C1-C6-alkoxycarbonyl.
10. The heterocyclic compound of claim 1, wherein R8 is N-bound.
11. The heterocyclic compound of claim 1, wherein R4 is selected from following structures:
where
R8a is hydrogen or has one of the meanings given in claim 1 for R8; and
# is the attachment point to the remainder of the molecule.
12. The heterocyclic compound of claim 1, wherein at most one of X1, X2, X3, X4, X5 and X6 is N.
13. The heterocyclic compound of claim 12, wherein X1 and X2 are CR2 and X3, X4, X5 and X6 are CR3 or CR4, or where X1 and X2 are CR2, X3 is N and X4, X5 and X6 are CR3 or CR4.
14. The heterocyclic compound of claim 1, wherein Y1, Y2, Y3 and Y4 are CR4 or CR5 or Y2 is N and Y3 and Y4 are CR4 or CR5.
15. The heterocyclic compound of claim 1, wherein A is NRB, preferably NH.
16. The heterocyclic compound of claim 1, wherein R1 is hydrogen or methyl, preferably hydrogen.
17. The heterocyclic compound of claim 1, wherein R2 is hydrogen.
18. The heterocyclic compound of claim 1, wherein R3 is selected from hydrogen, CN, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C3-C7-cycloalkyl, C3-C7-halocycloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, formyl, C1-C6-alkylcarbonyl, C1-C6-haloalkylcarbonyl, C1-C6-alkoxycarbonyl and C1-C6-haloalkoxycarbonyl and is preferably selected from hydrogen, CN, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy and C1-C6-haloalkoxy.
19. The heterocyclic compound of claim 1, wherein 0, 1 or 2 of the radicals R3 are different from hydrogen.
20. The heterocyclic compound of claim 1, wherein R5 is selected from hydrogen, CN, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C3-C7-cycloalkyl, C3-C7-halocycloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, formyl, C1-C6-alkylcarbonyl, C1-C6-haloalkylcarbonyl, C1-C6-alkoxycarbonyl and C1-C6-haloalkoxycarbonyl and is preferably selected from hydrogen, halogen, C1-C4-haloalkyl, C3-C7-cycloalkyl and C3-C7-halocycloalkyl and in particular from hydrogen, fluorinated C1-C2-alkyl and C3-C6-cycloalkyl.
21. The heterocyclic compound of claim 1, wherein at most one of the radicals R5 is different from hydrogen.
22. The heterocyclic compound of claim 1, of formula I-1
where
X3 is N or CH;
Y2 is N or CH;
R31 has one of the meanings given in claim 1, for R3 except for hydrogen, and is preferably halogen, C1-C4-alkyl or C1-C4-alkoxY;
R4 has one of the meanings given in claim 1;
R51 has one of the meanings given in claim 1, for R5 except for hydrogen;
a is 0, 1 or 2; and
b, c and d are independently of each other 0 or 1, with the proviso that one of b and c is 1.
23. The heterocyclic compound of claim 1, of formula I-2
where
Y2 is N or preferably CH;
R31 has one of the meanings given in claim 1 for R3 except for hydrogen, and is preferably selected from the group consisting of halogen, trifluoromethyl, cyano or methoxy;
R4 has one of the meanings given in claim 1;
a is 0, 1 or 2;
b is 0 or 1.
24. The heterocyclic compound of claim 23, where Y2 is CH, b is 0 and a is 0, 1 or 2 and where R31, if present, is selected from the group consisting of halogen, trifluoromethyl, cyano and methoxy.
25. A heterocyclic compound selected from the group consisting of
1-(6-(3,6-dihydro-2H-pyran-4-yl)pyridin-2-yl)-3-(8-fluoroquinolin-4-yl)urea,
1-(8-fluoroquinolin-4-yl)-3-(6-(tetrahydro-2H-pyran-4-yl)pyridin-2-yl)urea,
1-(6-(3,4-dihydro-2H-pyran-5-yl)pyridin-2-yl)-3-(8-fluoroquinolin-4-yl)urea,
1-(6-(3,6-dihydro-2H-pyran-4-yl)pyridin-2-yl)-3-(7-methoxyquinolin-4-yl)urea,
1-(6-(3,4-dihydro-2H-pyran-5-yl)quinolin-4-yl)-3-(6-(trifluoromethyl)pyridin-2-yl)-urea,
1-(7-(3,6-dihydro-2H-pyran-4-yl)quinolin-4-yl)-3-(6-(trifluoromethyl)pyridin-2-yl)-urea,
1-(6-(tetrahydro-2H-pyran-4-yl)quinolin-4-yl)-3-(6-(trifluoromethyl)pyridin-2-yl)-urea,
1-(7-methoxyquinolin-4-yl)-3-(6-(tetrahydro-2H-pyran-4-yl)pyridin-2-yl)urea,
1-(7-(tetrahydro-2H-pyran-4-yl)quinolin-4-yl)-3-(6-(trifluoromethyl)pyridin-2-yl)-urea,
1-(6-(tetrahydro-2H-pyran-3-yl)quinolin-4-yl)-3-(6-(trifluoromethyl)pyridin-2-yl)-urea,
1-(7-(3,6-dihydro-2H-pyran-4-yl)quinolin-4-yl)-3-(pyrazin-2-yl)urea,
1-(6-(3,4-dihydro-2H-pyran-5-yl)pyridin-2-yl)-3-(7-methoxyquinolin-4-yl)urea,
1-(7-methoxyquinolin-4-yl)-3-(6-(tetrahydro-2H-pyran-3-yl)pyridin-2-yl)urea,
1-(pyrazin-2-yl)-3-(7-(tetrahydro-2H-pyran-4-yl)quinolin-4-yl)urea,
1-(7-(3,4-dihydro-2H-pyran-5-yl)quinolin-4-yl)-3-(6-(trifluoromethyl)pyridin-2-yl)-urea,
1-(6-bromo-quinolin-4-yl)-3-(6-trifluoromethyl-pyridin-2-yl)-urea,
1-(6-(trifluoromethyl)pyridin-2-yl)-3-quinolin-4-yl-urea,
1-(6,8-difluoroquinolin-4-yl)-3-(6-trifluoromethyl-pyridin-2-yl)-urea,
1-(7-bromoquinolin-4-yl)-3-(6-trifluoromethyl-pyridin-2-yl)-urea,
1-(7-trifluoromethylquinolin-4-yl)-3-(6-trifluoromethyl-pyridin-2-yl)-urea,
1-(7-methoxyquinolin-4-yl)-3-(6-trifluoromethyl-pyridin-2-yl)-urea,
1-(8-trifluoromethylquinolin-4-yl)-3-(6-trifluoromethyl-pyridin-2-yl)-urea,
1-(8-cyanoquinolin-4-yl)-3-(6-trifluoromethyl)pyridin-2-yl)-urea,
1-(8-iodoquinolin-4-yl)-3-(6-trifluoromethyl)pyridin-2-yl)-urea,
1-(8-cyanoquinolin-4-yl)-3-pyrazin-2-yl-urea,
1-(7-methoxyquinolin-4-yl)-3-pyrazin-2-yl-urea,
tert-butyl 4-{4-3-(6-trifluoromethyl-pyridin-2-yl)-ureido-quinolin-6-yl}-3,6-dihydro-2H-pyridine-1-carboxylate,
1-6-(1,2,3,6-tetrahydro-pyridin-4-yl)-quinolin-4-yl-3-(6-trifluoromethyl-pyridin-2-yl)-urea,
1-(6-(piperidin-4-yl)quinolin-4-yl)-3-(6-(trifluoromethyl)pyridin-2-yl)urea,
1-6-(1-methyl-1,2,3,6-tetrahydro-pyridin-4-yl)-quinolin-4-yl-3-(6-trifluoromethyl-pyridin-2-yl)-urea,
1-6-(1-methyl-piperidin-4-yl)-quinolin-4-yl-3-(6-trifluoromethyl-pyridin-2-yl)-urea,
1-{6-1-(2-fluoro-ethyl)-piperidin-4-yl-quinolin-4-yl}-3-(6-trifluoromethyl-pyridin-2-yl)-urea,
1-{6-1-(2,2-difluoro-ethyl)-piperidin-4-yl-quinolin-4-yl}-3-(6-trifluoromethyl-pyridin-2-yl)-urea,
1-6-(3,6-dihydro-2H-pyran-4-yl)-quinolin-4-yl-3-(6-trifluoromethyl-pyridin-2-yl)-urea,
1-6-(3,6-dihydro-2H-pyran-4-yl)-quinolin-4-yl-3-pyrazin-2-yl-urea,
tert-butyl 4-4-(3-pyrazin-2-ylureido)quinolin-6-yl-5,6-dihydropyridine-1(2H)-carboxylate,
1-pyrazin-2-yl-3-6-(1,2,3,6-tetrahydro-pyridin-4-yl)-quinolin-4-yl-urea,
1-(6-piperidin-4-yl-quinolin-4-yl)-3-pyrazin-2-yl-urea,
1-{6-1-(2-fluoro-ethyl)-piperidin-4-yl-quinolin-4-yl}-3-pyrazin-2-yl-urea,
1-6-(1-methyl-piperidin-4-yl)-quinolin-4-yl-3-pyrazin-2-yl-urea,
tert-butyl 4-{4-3-(6-cyclopropyl-pyrazin-2-yl)-ureido-quinolin-6-yl}-3,6-dihydro-2H-pyridine-1-carboxylate,
tert-butyl 4-{4-3-(6-cyclopropyl-pyrazin-2-yl)-ureido-quinolin-6-yl}-piperidine-1-carboxylate,
1-(6-cyclopropyl-pyrazin-2-yl)-3-(6-piperidin-4-yl-quinolin-4-yl)-urea,
1-(6-cyclopropyl-pyrazin-2-yl)-3-6-(1-methyl-piperidin-4-yl)-quinolin-4-yl-urea,
tert-butyl 3-{4-3-(6-Trifluoromethyl-pyridin-2-yl)-ureido-quinolin-6-yl}-2,5-dihydropyrrole-1-carboxylate,
1-6-(2,5-dihydro-1H-pyrrol-3-yl)-quinolin-4-yl-3-(6-trifluoromethyl-pyridin-2-yl)-urea,
1-6-(3,6-dihydro-2H-pyran-4-yl)-pyridin-2-yl-3-(8-fluoro-quinolin-4-yl)-urea,
1-(8-fluoro-quinolin-4-yl)-3-6-(tetrahydro-pyran-4-yl)-pyridin-2-yl-urea,
1-(8-chloro-6-methyl-quinolin-4-yl)-3-6-(tetrahydro-pyran-4-yl)-pyridin-2-yl-urea,
1-(6,8-dichloro-quinolin-4-yl)-3-6-(tetrahydro-pyran-4-yl)-pyridin-2-yl-urea,
1-(6,8-difluoro-quinolin-4-yl)-3-6-(tetrahydro-pyran-4-yl)-pyridin-2-yl-urea,
1-(8-chloro-quinolin-4-yl)-3-6-(tetrahydro-pyran-4-yl)-pyridin-2-yl-urea,
1-1,5naphthyridin-4-yl-3-6-(tetrahydro-pyran-4-yl)-pyridin-2-yl-urea,
1-(5,8-difluoro-quinolin-4-yl)-3-6-(tetrahydro-pyran-4-yl)-pyridin-2-yl-urea,
1-(8-fluoro-6-methoxy-quinolin-4-yl)-3-6-(tetrahydro-pyran-4-yl)-pyridin-2-yl-urea,
1-6-(5,6-dihydro-4H-pyran-3-yl)-pyridin-2-yl-3-(8-fluoro-quinolin-4-yl)-urea,
1-(8-fluoro-quinolin-4-yl)-3-6-(tetrahydro-pyran-3-yl)-pyridin-2-yl-urea,
1-6-(3,6-dihydro-2H-pyran-4-yl)-pyridin-2-yl-3-1,5naphthyridin-4-yl-urea,
tert-butyl-6-3-(8-fluoro-quinolin-4-yl)-ureido-3\u2032,6\u2032-dihydro-2\u2032H-2,4\u2032bipyridinyl-1\u2032-carboxylate,
1-(8-fluoro-quinolin-4-yl)-3-(1\u2032,2\u2032,3\u2032,6\u2032-tetrahydro-2,4\u2032bipyridinyl-6-yl)-urea,
tert-butyl-6-3-(8-fluoro-quinolin-4-yl)-ureido-3\u2032,4\u2032,5\u2032,6\u2032-tetrahydro-2\u2032H-2,4\u2032bipyridinyl-1\u2032-carboxylate,
1-(8-fluoro-quinolin-4-yl)-3-(1\u2032,2\u2032,3\u2032,4\u2032,5\u2032,6\u2032-hexahydro-2,4\u2032bipyridinyl-6-yl)-urea,
1-(8-fluoro-quinolin-4-yl)-3-(1\u2032-methyl-1\u2032,2\u2032,3\u2032,4\u2032,5\u2032,6\u2032-hexahydro-2,4\u2032bipyridinyl-6-yl)-urea,
1-1\u2032-(2-fluoro-ethyl)-1\u2032,2\u2032,3\u2032,4\u2032,5\u2032,6\u2032-hexahydro-2,4\u2032bipyridinyl-6-yl-3-(8-fluoroquinolin-4-yl)-urea,
1-1\u2032-(2,2-difluoro-ethyl)-1\u2032,2\u2032,3\u2032,4\u2032,5\u2032,6\u2032-hexahydro-2,4\u2032bipyridinyl-6-yl-3-(8-fluoroquinolin-4-yl)-urea,
1-(8-fluoro-quinolin-4-yl)-3-(1\u2032-isopropyl-1\u2032,2\u2032,3\u2032,4\u2032,5\u2032,6\u2032-hexahydro-2,4\u2032bipyridinyl-6-yl)-urea,
1-(8-fluoro-quinolin-4-yl)-3-5-(tetrahydro-pyran-4-yl)-pyridin-2-yl-urea,
tert-butyl-3-4-(3-pyrazin-2-yl-ureido)-quinolin-6-yl-2,5-dihydro-pyrrole-1-carboxylate,
tert-butyl-3-4-(3-pyrazin-2-yl-ureido)-quinolin-6-yl-pyrrolidine-1-carboxylate,
1-pyrazin-2-yl-3-(6-pyrrolidin-3-yl-quinolin-4-yl)-urea,
the stereoisomers, N-oxides, prodrugs, tautomers or physiologically tolerated acid addition salts thereof.
26. The heterocyclic compound of claim 1, wherein at least one of the atoms has been replaced by its stable, non-radioactive isotope, and preferably wherein at least one hydrogen atom has been replaced by a deuterium atom.
27. A pharmaceutical composition comprising at least one heterocyclic compound of claim 1, a stereoisomer, N-oxide, prodrug, tautomer andor physiologically tolerated acid addition salt thereof or comprising at least one heterocyclic compound as defined in any of the preceding claims wherein at least one of the atoms has been replaced by its stable, non-radioactive isotope, preferably wherein at least one hydrogen atom has been replaced by a deuterium atom, and at least one physiologically acceptable carrier andor auxiliary substance.
28. The heterocyclic compounds of claim 1 or the stereoisomers, N-oxides, prodrugs, tautomers or physiologically tolerated acid addition salts thereof for use as a medicament.
29. The heterocyclic compounds of claim 1 or the stereoisomers, N-oxides, prodrugs, tautomers or physiologically tolerated acid addition salts thereof for the treatment of a medical disorder susceptible to the treatment with a compound that modulates, preferably inhibits, the activity of glycogen synthase kinase 3\u03b2.
30. The use of the heterocyclic compound of claim 1 or of a stereoisomer, N-oxide, prodrug, tautomer or physiologically tolerated acid addition salt thereof for the preparation of a medicament for the treatment of a medical disorder susceptible to the treatment with a compound that modulates, preferably inhibits, the activity of glycogen synthase kinase 3\u03b2.
31. A method for treating a medical disorder susceptible to treatment with a compound that modulates, preferably inhibits, glycogen synthase kinase 3\u03b2 activity, said method comprising administering an effective amount of at least one heterocyclic compound of claim 1 or of a stereoisomer, prodrug, N-oxide, tautomer or physiologically tolerated acid addition salt thereof or of a pharmaceutical composition of claim 1 to a subject in need thereof.
32. The heterocyclic compounds of claim 29, wherein the medical disorder is a neurodegenerative disorder or an inflammatory disorder.
33. The heterocyclic compounds or the use or the method of claim 32, wherein the medical disorder is selected from schizophrenia, Alzheimer’s disease, behavioural and psychiatric symptoms of dementia, Parkinson’s disease, tauopathies, vascular dementia, acute stroke and other traumatic injuries, cerebrovascular accidents, brain and spinal cord trauma, peripheral neuropathies, bipolar disorders, retinopathies, glaucoma, pain, rheumatoid arthritis and osteoarthritis.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A radiation imaging apparatus comprising:
an area sensor arranged with pixels in a matrix, each pixel having a conversion element for converting incident radiation into an electric signal;
a driving circuit unit for applying a driving signal to a driving line and driving a plurality of the pixels connected in common to the driving line;
a read out circuit unit reading out the electric signal from the pixel driven by the driving circuit unit and outputting the electric signal as image data;
a processing unit for executing a process for producing image data for correction based on partial image data for correction, wherein the partial image data for correction is read out by the read out circuit unit as an electric signal from one or more of the plurality of pixels in the area sensor without the incident radiation while the one or more of the pixels are driven by the driving circuit unit and the other pixels are not driven by the driving circuit unit, and then outputted from the read out circuit unit; and
an arithmetic operation unit for subjecting radiation image data to an arithmetic operation processing using the image data for correction, wherein the radiation image data is read out by the read out circuit unit as an electric signal from the pixels driven by the driving circuit unit based on the incident radiation, and then outputted from the read out circuit unit.
2. The radiation imaging apparatus according to claim 1, wherein the processing unit synthesizes first partial image data for correction output from the read out circuit unit after the processing unit reads out the electric signal in a state in which the radiation is not incident from the pixel included in a first pixel group partially driven by the driving circuit unit, after the radiation image data is output, and second partial image data for correction output from the read out circuit after the processing unit reads out the electric signal in a state in which the radiation is not incident from the pixel included in a second pixel group different from the first pixel group partially driven by the driving circuit unit, before the radiation image data is output, thereby to generate the image data for correction.
3. The radiation imaging apparatus according to claim 2, wherein the first pixel group comprises a plurality of pixels connected to the odd-numbered driving lines among the plurality of the pixels inside the area sensor, and the second pixel group comprises the plurality of pixels connected to the even-numbered driving lines among the plurality of the pixels inside the area sensor.
4. The radiation imaging apparatus according to claim 3, wherein the first pixel group comprises the plurality of pixels connected to the odd-numbered driving lines given an interlace scanning by the driving circuit unit and the second pixel group comprises the plurality of pixels connected to the even-numbered driving lines given the interlace scanning by the driving circuit unit.
5. The radiation imaging apparatus according to claim 4, further comprising radiographing condition setting means for performing the setting of radiographing conditions, wherein, according to the radiographing conditions set by the radiographing condition setting means, the number of lines of the driving lines performing the interlace scanning is controlled.
6. The radiation imaging apparatus according to claim 5, wherein, according to the radiographing conditions set by the radiographing condition setting means, a pulse period, an energy, and an intensity of the radiation can be changed.
7. The radiation imaging apparatus according to claim 2, wherein the processing unit, when synthesizing the first partial image data for correction and the second partial image data for correction, performs the synthesis by applying a specific coefficient to both or either of them.
8. The radiation imaging apparatus according to claim 1, wherein the arithmetic operation means performs a subtraction as the arithmetic operation processing.
9. The radiation imaging apparatus according to claim 1, wherein, every time the radiation image data is output, the partial image data for correction is output from the read out circuit unit.
10. The radiation imaging apparatus according to claim 1, wherein the pixel comprises the conversion element and a switch element for transferring the electric signal of the conversion element on an insulating substrate, and control electrodes of the switch elements of a plurality of pixels arranged in a row direction are connected in common to the driving lines, and one electrode among main electrodes of the switch elements of the plurality of pixels arranged in a column direction is connected in common to the signal line, and another electrode among main electrodes of the switch elements is connected to the conversion element, and the signal line is connected to the read out circuit unit, and the conversion element includes a photoelectric conversion element comprising amorphous silicon as a main material and a wavelength converter for converting the radiation into a light perceptible by the photoelectric conversion element.
11. The radiation imaging apparatus according to claim 1, wherein the driving circuit unit comprises a shift resistor input with a start pulse, a shift clock and an output enable signal.
12. A radiation imaging system, comprising:
a radiation generator for generating radiation; and
a radiation imaging apparatus according to claim 1,
wherein the radiation generated by the radiation generator is incident upon the area sensor.
13. A driving method of a radiation imaging apparatus, which comprises an area sensor arranged with pixels in a matrix, each pixel having a conversion element for converting incident radiation into an electric signal, a driving circuit unit for applying a driving signal to a driving line and driving a plurality of the pixels connected in common to the driving line, and a read out circuit unit reading out the electric signal from the pixel driven by the driving circuit unit and outputting the electric signal as image data, comprising:
a step of outputting radiation image data from the read out circuit unit, wherein the radiation image data is read out by the read out circuit unit as an electric signal from pixels driven by a driving circuit unit based on the incident radiation, and then outputted from the read out circuit unit;
a step of outputting partial image data for correction from the read out circuit unit, wherein the partial image data for correction is read out by the read out circuit unit as an electric signal from one or more of the plurality of pixels in the area sensor without the incident radiation while the one or more of the pixels are driven by the driving circuit unit and the other pixels are not driven by the driving circuit unit, and then outputted from the read out circuit unit;
a step of generating image data for correction by using the partial image data for correction; and
a step of performing an arithmetic operation processing on the radiation image data by using the image data for correction.