Substituted benzimidazolone derivatives, medicaments comprising them and their use
View Patent ↗The present invention relates to novel benzimidazolone derivatives of the general formula (I) in which the substituents R 1 , R 2 , R 3 , A 1 , A 2 , and B are as defined in claim 1 , medicaments comprising these, and the use thereof for the prophylaxis and/or treatment of vasopressin-dependent diseases.
1. A benzimidazolone compound of the general formula (I)
in which
A 1 is hydrogen, in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkenyl or C 1 -C 4 -alkylene-phenyl, or
an aromatic, heteroaromatic, partly aromatic or partly heteroaromatic mono- or bicyclic ring having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms as ring members, which may besides additionally comprise 0, 1, 2, 3 or 4 identical or different heteroatoms independently of one another selected from the group consisting of nitrogen, oxygen and sulfur as ring members, and which may be substituted by one, two or three radicals R A 11 , R A 12 and/or R A 13 which are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, bromine, chlorine, iodine, fluorine, CN, CF 3 , OCF 3 , OCHF 2 , OH, COOH, CO—NH 2 , NH 2 , NH—CO—NH or in each case optionally substituted C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, O—C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkenyl, C 1 -C 4 -alkylene-aryl, NH—(C 1 -C 6 -alkyl), N(C 1 -C 6 -alkyl), C 1 -C 4 —NH 2 , C 1 -C 4 -alkylene-NH—(C 1 -C 6 -alkyl), C 1 -C 4 -alkylene-N(C 1 -C 6 -alkyl) 2 , C 1 -C 4 -alkylene-OH, C 1 -C 4 alkylene-O—C 1 -C 6 -alkyl, CO—C 1 -C 6 -alkyl, CO—O—C 1 -C 6 -alkyl, CO—NH(C 1 -C 6 -alkyl), CO—N(C 1 -C 6 -alkyl) 2 , NH—CO—C 1 -C 6 -alkyl, NH—CO—N(C 1 -C 6 -alkyl) 2 , N(C 1 -C 6 -alkyl)-CO—C 1 -C 6 -alkyl;
A 2 is hydrogen or in each case optionally substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkenyl, C 1 -C 6 -alkynyl or C 3 -C 6 -cycloalkyl;
or where the radicals A 1 and A 2 may form together with the carbon atom to which they are bonded an in each case optionally substituted 3- to 7-membered carbocyclic ring (spiro linkage) which may additionally comprise a heteroatom as ring member selected from the group consisting of O, S and NR A 14 in which R A 14 is a radical selected from the group consisting of hydrogen and in each case optionally substituted C 1 -C 6 -alkyl, aryl and C 1 -C 4 -alkylene-aryl, and where the ring formed in this way may be substituted by one, two or three radicals R A 11 , R A 12 and/or R A 13 which may independently of one another and independently of their respective occurrence assume the aforementioned meanings;
B is an aromatic, heteroaromatic, partly aromatic or partly heteroaromatic mono- or bicyclic ring having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms as ring members, which may additionally comprise 0, 1, 2, 3 or 4 identical or different heteroatoms independently of one another selected from the group consisting of nitrogen, oxygen and sulfur as ring members, and which may be substituted by one, two or three radicals R B 1 , R B 2 and/or R B 3 , where R B 1 , R B 2 and R B 3 are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, chlorine, bromine, fluorine, CN, CF 3 , OCF 3 , OCHF 2 , OCH 2 F, OCH 2 CF 3 , OCH 2 —CHF 2 , OH, and in each case optionally substituted O—C 1 -C 4 -alkyl, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl and C 2 -C 4 -alkynyl,
R 1 is selected from the group consisting of hydrogen, bromine, chlorine, fluorine, iodine, CN, CF 3 , OCF 3 , OCHF 2 , and in each case O—C 1 -C 4 -alkyl, C 1 -C 4 -alkyl, C 1 -C 4 -alkenyl and C 2 -C 4 -alkynyl; NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NO 2 , NHCHO, NHCO(C 1 -C 4 -alkyl) or NHCONH 2
R 2 is selected from the group consisting of hydrogen, and in each case optionally substituted C 1 -C 4 -alkyl, O—C 1 -C 4 -alkyl, chlorine, fluorine, difluoromethyl (CHF 2 ) and trifluoromethyl;
R 3 is a radical (X)—(Y), where
X is CO, SO, or (C═NH),
Y is selected from the group consisting of
OH, NH 2 , NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NH(C 2 -C 4 -alkylene-OH), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-OH), NH(C 2 -C 4 -alkylene-O—C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-O—C 1 -C 4 -alkyl), NH(C 3 -C 7 -cycloalkyl), N(C 1 -C 4 -alkyl)(C 3 -C 7 -cyclo-alkyl), NH(C 1 -C 4 -haloalkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -haloalkyl), N(R Y 5 )(C 1 -C 4 -alkylene)-R Y 3 , and radical R Y 1 ;
R Y 1 is selected independently of its respective occurrence from the group consisting of the respective individual radicals mentioned below
where n is independently of its occurrence the integer 1 or 2,
where the aforementioned radicals may independently of one another each have one or two substituents R Y 12 and/or R Y 13 which are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, fluorine, OH, in each case optionally substituted O—C 1 -C 4 -alkyl, phenyl and C 1 -C 4 -alkyl;
R Y 11 is a radical selected from the group consisting of hydrogen, in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl;
R Y 2 is a radical selected from the group consisting of hydrogen, in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, phenyl, C 1 -C 4 -alkylene-phenyl, C 1 -C 4 -haloalkyl, C 3 -C 7 -cycloalkyl, pyridine, pyrimidine, pyrazine, pyridazine, furan, thiophene, pyrrole, oxazole, isoxazole, thiazole, imidazole, pyrazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, triazole, 1,3,5-triazine, tetrazole, (C 2 -C 4 -alkylene)-R Y 3 and ring radical R Y 22 , where
R Y 22 is selected independently of its respective occurrence from the group consisting of the respective individual radicals
where the aforementioned radicals may independently of one another in each case have one or two substituents R Y 222a and/or R Y 223a which are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, fluorine, OH and in each case optionally substituted O—C 1 -C 4 -alkyl, phenyl and C 1 -C 4 -alkyl;
R Y 221 is a radical selected from the group consisting of hydrogen, and in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl and C 1 -C 4 -alkylene-phenyl, in particular hydrogen, and in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl;
R Y 3 is a radical selected from the group consisting of hydrogen, NH 2 , N(R Y 3a )R Y 3b , NH(C 2 -C 4 -alkylene)-R Y 8 , N(R Y 7 )(C 2 -C 4 -alkylene)-R Y 8 , N(R Y 7 )R Y 9 , N(R Y 7 )CH 2 R Y 9 , a radical R Y 33 , a radical CH 2 R Y 33 and an aromatic radical, selected from phenyl, pyridine, pyrimidine, pyrazine, pyridazine, furan, thiophene, pyrrole, oxazole, isoxazole, thiazole, isothiazole, imidazole, pyrazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, triazole, 1,3,5-triazine and tetrazole, the aromatic radical being substituted or carrying 1 or 2 substitutens R Y 331 and/or R Y 332 , where
R Y 33 is independently of its respective occurrence a radical selected from the group consisting of the respective individual radicals
where n is independently of its occurrence the integer 1 or 2,
where the aforementioned radicals R 33 may independently of one another in each case have one or two substituents R Y 331 and/or R Y 332 ,
R Y 331 , R Y 332 are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, fluorine, OH, and in each case optionally substituted O—C 1 -C 4 -alkyl, phenyl and C 1 -C 4 -alkyl,
R Y 333 is a radical selected from the group consisting of hydrogen and in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, phenyl and C 1 -C 4 -alkylene-phenyl;
R Y 3a is a radical selected from the group consisting of hydrogen, and in each case optionally substituted C 1 -C 6 -alkyl, C 3 -C 7 -cycloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, phenyl and C 1 -C 4 -alkylene-phenyl;
R Y 3b is a radical selected from the group consisting of in each case optionally substituted C 1 -C 6 -alkyl and C 1 -C 4 -alkylene-phenyl;
R Y 5 is a radical selected from the group consisting of hydrogen and in each case optionally substituted C 1 -C 4 -alkyl;
R Y 6 is a radical selected from the group consisting of hydrogen and in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, phenyl and C 1 -C 4 -alkylene-phenyl;
R Y 7 is a radical selected from the group consisting of hydrogen and in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, phenyl and C 1 -C 4 -alkylene-phenyl;
R Y 8 is a radical elected from the group consisting of OH, NH 2 , and in each case optionally substituted NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 alkyl), NH(C 2 -C 4 -alkylene-OH), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-OH), NH(C 2 -C 4 -alkylene-O-C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-O—C 1 -C 4 -alkyl), NH(C 3 -C 7 -cycloalkyl), N(C 1 -C 4 -alkyl)(C 3 -C 7 -cycloalkyl), NH(C 1 -C 4 haloalkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -haloalkyl), O—C 1 -C 4 -alkyl, and the ring radical R Y 81 , where
R Y 81 is a radical independently of its respective occurrence selected from the group consisting of the respective individual radicals
R Y 9 is a 5- or 6-membered heteroaromatic radical having 2, 3, 4 or 5 carbon atom as ring members and 1, 2 or 3 heteroatoms, selected from O, S and N, wherein the 5- or 6-membered heteroaromatic radical may be unsubstituted or may have one or two substituents R Y 331 and/or R Y 332 ,
the tautomeric, enantiomeric and/or diastereomeric forms thereof, and the physiologically tolerated salts of the aforementioned compound or compounds,
with the proviso that R 1 ≠H (is not hydrogen) when A 1 =A 2 =hydrogen,
and with the proviso that R 1 is halogen, cyano, or in each case optionally substituted C 1 -C 6 -alkoxy and C 1 -C 6 -alkyl when A 1 =A 2 =hydrogen.
2. The compound according to claim 1 , wherein,
A 1 is an aromatic, heteroaromatic, partly aromatic or partly heteroaromatic mono- or bicyclic ring having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms as ring members, which may besides additionally comprise 0, 1, 2, 3 or 4 identical or different heteroatoms independently of one another selected from the group consisting of nitrogen, oxygen and sulfur as ring members, and which may be substituted by one, two or three radicals R A 11 , R A 12 and/or R A 13 which are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, bromine, chlorine, iodine, fluorine, CN, CF 3 , OCF 3 , OCHF 2 , OH, COOH, CO—NH 2 , NH 2 , NH—CO—NH 2 or in each case optionally substituted C 1 -C 6 -alkyl, O—C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, O—C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkenyl, C 1 -C 4 -alkylene-aryl, NH—(C 1 -C 6 -alkyl), N(C 1 -C 6 -alkyl) 2 , C 1 -C 4 —NH 2 , C 1 -C 4 -alkylene-NH—(C 1 -C 6 -alkyl), C 1 -C 4 -alkylene-N(C 1 -C 6 -alkyl) 2 , C 1 -C 4 -alkylene-OH, C 1 -C 4 alkylene-O—C 1 -C 6 -alkyl, CO—C 1 -C 6 -alkyl, CO—O—C 1 -C 6 -alkyl, CO—NH(C 1 -C 6 -alkyl), CO—N(C 1 -C 6 -alkyl) 2 , NH—CO—C 1 -C 6 -alkyl, NH—CO—N(C 1 -C 6 -alkyl) 2 , N(C 1 -C 6 -alkyl)-CO—C 1 -C 6 -alkyl;
A 2 is hydrogen or in each case optionally substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkenyl, C 1 -C 6 -alkynyl or C 3 -C 6 -cycloalkyl;
or where the radicals A 1 and A 2 may form together with the carbon atom to which they are bonded an in each case optionally substituted 3- to 7-membered carbocyclic ring (spiro linkage) which may additionally comprise a heteroatom as ring member selected from the group consisting of O, S and NR A 14 in which R A 14 is a radical selected from the group consisting of hydrogen and in each case optionally substituted C 1 -C 6 -alkyl, aryl and C 1 -C 4 -alkylene-aryl, and where the ring formed in this way may be substituted by one, two or three radicals R A 11 , R A 12 and/or R A 13 which may independently of one another and independently of their respective occurrence assume the aforementioned meanings;
B is an aromatic, heteroaromatic, partly aromatic or partly heteroaromatic mono- or bicyclic ring having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms as ring members, which may additionally comprise 0, 1, 2, 3 or 4 identical or different heteroatoms independently of one another selected from the group consisting of nitrogen, oxygen and sulfur as ring members, and which may be substituted by one, two or three radicals R B 1 , R B 2 and/or R B 3 , where R B 1 , R B 2 and R B 3 are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, chlorine, bromine, fluorine, CN, CF 3 , OCF 3 , OCHF 2 , OCH 2 F, OCH 2 CF 3 , OCH 2 —CHF 2 , OH, and in each case optionally substituted O—C 1 -C 4 -alkyl, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl and C 2 -C 4 -alkynyl,
R 1 is selected from the group consisting of hydrogen, bromine, chlorine, fluorine, iodine, N, CF 3 , OCF 3 , OCHF 2 , and in each case O—C 1 -C 4 -alkyl, C 1 -C 4 -alkyl, C 1 -C 4 -alkenyl and C 2 -C 4 -alkynyl; NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NO 2 , NHCHO, NHCO(C 1 -C 4 alkyl) or NHCONH 2
R 2 is selected from the group consisting of hydrogen, and in each case optionally substituted C 1 -C 4 -alkyl, O—C 1 -C 4 -alkyl, chlorine, fluorine, difluoromethyl (CHF 2 ) and trifluoromethyl;
R 3 is a radical (X)—(Y), where
X is CO, SO 2 or (C═NH),
Y is selected from the group consisting of
OH, NH 2 , NH(C 1 -C 4 -alkyl), N(C 1 -C 4 alkyl)(C 1 -C 4 alkyl), NH(C 2 -C 4 -alkylene-OH), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-OH), NH(C 2 -C 4 -alkylene-O—C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-O—C 1 -C 4 -alkyl), NH(C 1 -C 7 -cycloalkyl), N(C 1 -C 4 -alkyl)(C 3 -C 7 -cycloalkyl), NH(C 1 -C 4 haloalkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -haloalkyl), N(R Y 5 )(C 1 -C 4 -alkylene)-R Y 3 , and radical R Y 1 ;
R Y 1 is selected independently of its respective occurrence from the group consisting of the respective individual radicals mentioned below
where the aforementioned radicals may independently of one another each have one or two substituents R Y 12 and/or R Y 13 which are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, fluorine, OH, in each case optionally substituted O—C 1 -C 4 -alkyl, phenyl and C 1 -C 4 -alkyl;
R Y 11 is a radical selected from the group consisting of hydrogen, in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl;
R Y 2 is a radical selected from the group consisting of hydrogen, in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, phenyl, C 1 -C 4 -alkylene-phenyl, C 1 -C 4 -haloalkyl, C 3 -C 7 cycloalkyl, pyridine, pyrimidine, pyrazine, pyridazine, furan, thiophene, pyrrole, oxazole, isoxazole, thiazole, imidazole, pyrazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, triazole, 1,3,5-triazine, tetrazole, (C 2 -C 4 -alkylene)-R Y 3 and ring radical R Y 22 , where
R Y 22 is selected independently of its respective occurrence from the group consisting of the respective individual radicals
where the aforementioned radicals may independently of one another in each case have one or two substituents R Y 222a and/or R Y 223a which are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, fluorine, OH and in each case optionally substituted O—C 1 -C 4 -alkyl, phenyl and C 1 -C 4 -alkyl;
R Y 221 is a radical selected from the group consisting of hydrogen, and in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl;
R Y 3 is a radical selected from the group consisting of hydrogen, NH 2 and in each case optionally substituted NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NH(C 2 -C 4 -alkylene-OH), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-OH), NH(C 2 -C 4 -alkylene-O—C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-O—C 1 -C 4 -alkyl), NH(C 3 -C 7 -cycloalkyl), N(C 1 -C 4 -alkyl)(C 3 -C 7 -cycloalkyl), NH(C 1 -C 4 -haloalkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -haloalkyl), phenyl, pyridine, pyrimidine, pyrazine, pyridazine, furan, thiophene, pyrrole, oxazole, isoxazole, thiazole, imidazole, pyrazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, triazole, 1,3,5-triazine, tetrazole, NH(C 2 -C 4 -alkylene)-R Y 8 , N(R Y 7 )(C 2 -C 4 -alkylene)-R Y 8 and a ring radical R Y 33 , where
R Y 33 is independently of its respective occurrence a radical selected from the group consisting of the respective individual radicals
where the aforementioned radicals may independently of one another in each case have one or two substituents R Y 331 and/or R Y 332 which are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, fluorine, OH, and in each case optionally substituted O—C 1 -C 4 -alkyl, phenyl and C 1 -C 4 -alkyl;
R Y 333 is a radical selected from the group consisting of hydrogen and in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, phenyl and C 1 -C 4 -alkylene-phenyl;
R Y 5 is a radical selected from the group consisting of hydrogen and in each case optionally substituted C 1 -C 4 -alkyl;
R Y 6 is a radical selected from the group consisting of hydrogen and in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, phenyl and C 1 -C 4 -alkylene-phenyl;
R Y 7 is a radical selected from the group consisting of hydrogen and in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, phenyl and C 1 -C 4 -alkylene-phenyl;
R Y 8 is a radical selected from the group consisting of OH, NH 2 , and in each case optionally substituted NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NH(C 2 -C 4 -alkylene-OH), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-OH), NH(C 2 -C 4 -alkylene-O—C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-O—C 1 -C 4 -alkyl), NH(C 3 -C 7 -cycloalkyl), N(C 1 -C 4 -alkyl)(C 3 -C 7 -cycloalkyl), NH(C 1 -C 4 -haloalkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -haloalkyl), O—C 1 -C 4 -alkyl, and the ring radical R Y 81 where
R Y 81 is a radical independently of its respective occurrence selected from the group consisting of the respective individual radicals
the tautomeric, enantiomeric and/or diastereomeric forms thereof, and the physiologically tolerated salts of the aforementioned compounds.
3. The compounds according to claim 1 , in which
A 1 is an aromatic, heteroaromatic, partly aromatic or partly heteroaromatic mono- or bicyclic ring having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms as ring members, which may besides additionally comprise 0, 1, 2, 3 or 4 identical or different heteroatoms independently of one another selected from the group consisting of nitrogen, oxygen and sulfur as ring members, and which may be substituted by one, two or three radicals R A 11 , R A 12 and/or R A 13 which are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, bromine, chlorine, fluorine, CN, CF 3 , OCF 3 , OCHF 2 , OH, and in each case optionally substituted O—C 1 -C 4 -alkyl and C 1 -C 4 -alkyl;
or in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkenyl, C 1 -C 4 -alkylene-phenyl;
A 2 is hydrogen or in each case optionally substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkenyl, C 1 -C 6 -alkynyl and C 3 -C 6 -cycloalkyl;
or where
A 1 and A 2 form together with the carbon atom to which they are bonded an in each case optionally substituted 3- to 7-membered carbocyclic ring (spiro linkage) which may additionally comprise a heteroatom as ring member selected from the group consisting of O, S and NR A 14 in which R A 14 is a radical selected from the group consisting of hydrogen and in each case optionally substituted C 1 -C 6 -alkyl, aryl and C 1 -C 4 -alkylene-aryl, and where the carbo- or heterocarbocyclic ring formed in this way may be substituted by one, two or three radicals R A 11 , R A 12 and/or R A 13 which may independently of one another and independently of their respective occurrence assume the aforementioned meanings;
B is an aromatic, heteroaromatic, partly aromatic or partly heteroaromatic mono- or bicyclic ring having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms as ring members, which may additionally comprise 0, 1, 2, 3 or 4 identical or different heteroatoms independently of one another selected from the group consisting of nitrogen, oxygen and sulfur as ring members, and which may be substituted by one, two or three radicals R B 1 , R B 2 and/or R B 3 , where R B 1 , R B 2 and R B 3 are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, chlorine, bromine, fluorine, CN, CF 3 , OCF 3 , OCHF 2 , OCH 2 F, OCH 2 CF 3 , OCH 2 —CHF 2 , OH, and in each case optionally substituted O—C 1 -C 4 -alkyl, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl and C 2 -C 4 -alkynyl,
R 1 is a radical selected from the group consisting of hydrogen, bromine, chlorine, fluorine, iodine, CN, CF 3 , OCF 3 , OCHF 2 , and/or in each case optionally substituted O—C 1 -C 4 -alkyl, C 1 -C 4 -alkyl, C 1 -C 4 -alkenyl, C 2 -C 4 -alkynyl; NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NO 2 , NHCHO, NHCO(C 1 -C 4 alkyl) and NHCONH 2 ;
R 2 is a radical selected from the group consisting of hydrogen, chlorine, fluorine and trifluoromethyl and/or in each case optionally substituted C 1 -C 4 -alkyl and O—C 1 -C 4 -alkyl;
R 3 is a radical (X)—(Y), where
X is CO, SO 2 or (C═NH),
Y is a radical selected from the group consisting of
OH, NH 2 , and/or in each case optionally substituted NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NH(C 2 -C 4 -alkylene-OH), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-OH), NH(C 2 -C 4 -alkylene-O—C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-O—C 1 -C 4 -alkyl), NH(C 3 -C 7 -cycloalkyl), N(C 1 -C 4 -alkyl)(C 3 -C 7 -cycloalkyl), NH(C 1 -C 4 -haloalkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -haloalkyl), N(R Y 5 )(C 1 -C 4 -alkylene)-R Y 3 , and the radical R Y 1 ; in which
R Y 1 is independently of its respective occurrence a radical selected from the group consisting of the respective individual radicals mentioned below
where the aforementioned radicals may in each case have one or two substituents R Y 12 and/or R Y n which are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, fluorine, OH, and/or in each case optionally substituted O—C 1 -C 4 -alkyl, phenyl and C 1 -C 4 -alkyl;
R Y 11 is a radical selected from the group consisting of hydrogen, and/or in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl or C 2 -C 6 -alkynyl;
R Y 2 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, phenyl, C 1 -C 4 -alkylene-phenyl, C 1 -C 4 -haloalkyl, C 3 -C 7 -cycloalkyl, pyridine, pyrimidine, pyrazine, pyridazine, furan, thiophene, pyrrole, oxazole, isoxazole, thiazole, imidazole, pyrazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, triazole, 1,3,5-triazine, tetrazole, (C 2 -C 4 -alkylene)R Y 3 and the ring radical R Y 22 , where
R Y 22 irrespective of its respective occurrence is a radical selected from the group consisting of the respective individual radicals mentioned below
where the aforementioned radicals may in each case have one or two substituents R Y 222a and/or R Y 223a which are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, fluorine, OH, and/or in each case optionally substituted O—C 1 -C 4 -alkyl, phenyl and C 1 -C 4 -alkyl; and where
R Y 221 is a radical selected from the group consisting of hydrogen, and/or in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl;
R Y 3 is a radical selected from the group consisting of hydrogen, NH 2 , and/or in each case optionally substituted NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NH(C 2 -C 4 -alkylene-OH), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-OH), NH(C 2 -C 4 -alkylene-O—C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-O—C 1 -C 4 -alkyl), NH(C 3 -C 7 -cycloalkyl), N(C 1 -C 4 -alkyl)(C 3 -C 7 -cycloalkyl), NH(C 1 -C 4 -haloalkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -haloalkyl), NH(C 2 -C 4 -alkylene)-R Y 8 , N(R Y 7 )(C 2 -C 4 -alkylene)-R Y 8 , N(R Y 7 )R Y 9 , N(R Y 7 )CH 2 R Y 9 , a radical R Y 33 , a radical CH 2 R Y 33 and an aromatic radical, selected from phenyl, pyridine, pyrimidine, pyrazine, pyridazine, furan, thiophene, pyrrole, oxazole, isoxazole, thiazole, isothiazole, imidazole, pyrazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, triazole, 1,3,5-triazine and tetrazole, the aromatic radical being substituted or carrying 1 or 2 substitutens R Y 331 and/or R Y 332 , in which
R Y 33 irrespective of its respective occurrence is a radical selected from the group consisting of the respective individual radicals mentioned below
where the aforementioned radicals may in each case have one or two substituents R Y 331 and/or R Y 332 which are selected independently of one another and independently of their respective occurrence from the group consisting of hydrogen, fluorine, OH, and/or in each case optionally substituted O—C 1 -C 4 -alkyl, phenyl and C 1 -C 4 alkyl;
R Y 333 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, phenyl and C 1 -C 4 alkylene-phenyl;
R Y 5 is a radical selected from the group consisting of hydrogen and optionally substituted C 1 -C 4 -alkyl;
R Y 6 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, phenyl and C 1 -C 4 -alkylene-phenyl;
R Y 7 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, phenyl and C 1 -C 4 -alkylene-phenyl;
R Y 8 is a radical selected from the group consisting of OH, NH 2 , and/or in each case optionally substituted NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NH(C 2 -C 4 -alkylene-OH), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-OH), NH(C 2 -C 4 -alkylene-O—C 1 -C 4 alkyl), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-O—C 1 -C 4 -alkyl), NH(C 3 -C 7 -cyclo-alkyl), N(C 1 -C 4 -alkyl)(C 3 -C 7 -cycloalkyl), NH(C 1 -C 4 haloalkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -haloalkyl), O—C 1 -C 4 -alkyl, and the ring radical R Y 81 , in which
R Y 81 is independently of its respective occurrence a radical selected from the group consisting of the respective individual radicals mentioned below
R Y 9 is a 5- or 6-membered heteroaromatic radical having 2, 3, 4 or 5 carbon atom as ring members and 1, 2 or 3 heteroatoms, selected from O, S and N, wherein the 5- or 6-membered heteroaromatic radical may be unsubstituted or may have one or two substituents R Y 331 and/or R Y 332 .
4. The compounds according to claim 1 , wherein the radical R 1 and the radical R 2 have the following meanings:
R 1 is hydrogen, fluorine, chlorine, iodine, CN or ethynyl,
and
R 2 is hydrogen
and the tautomeric, enantiomeric and/or diastereomeric forms thereof, and the physiologically tolerated salts thereof.
5. The compounds according to claim 1 , wherein R 3 is C(O)—Y.
6. The compounds according to claim 1 , wherein R 3 is a radical (X)—(Y),
X is CO and wherein Y is a radical R Y 1 .
7. The compounds according to claim 6 , wherein the radical R Y 1 is selected from a cyclic radical of the formulae
wherein R Y 2 and R Y 3 are as defined in claim 1 .
8. The compounds according to claim 7 , wherein the radical R Y 3 is selected from the group consisting of NH 2 , NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NH(C 2 -C 4 -alkylene-OH), N(C 1 -C 4 -alkyl)(C 2 -C 4 -alkylene-OH), NH(C 2 -C 4 -alkylene-O—C 1 -C 4 alkyl), N(C 1 -C 4 -alkyl)(C 2 -C 4 alkylene-O—C 1 -C 4 alkyl), NH(C 3 -C 7 -cycloalkyl), N(C 1 -C 4 -alkyl)(C 3 -C 7 -cycloalkyl), NH(C 1 -C 4 -haloalkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -haloalkyl), N(R Y 7 )R Y 9 , N(R Y 7 )CH 2 R Y 9 , a radical R Y 33 , a radical CH 2 R Y 33 and an aromatic radical, selected from pyridine.
9. The compounds according to claim 1 , wherein R 3 is a radical (X)—(Y), X is CO and wherein Y is selected from the following radicals:
wherein n is 1 or 2, R is hydrogen or methyl, and wherein R Y 6 , R Y 7 , R Y 221 , R Y 222 and R Y 223 are as defined in claim 1 .
10. The compounds according to claim 1 , wherein A 1 is a radical
in which
R A 11 is a radical selected from the group consisting of hydrogen, chlorine, fluorine, or in each case optionally substituted O—C 1 -C 4 -alkyl and C 1 -C 4 -alkyl.
11. The compounds according to claim 1 , wherein A 2 is hydrogen.
12. The compounds according to claim 1 , wherein B is selected from phenyl, 2-pyridyl, 8-quinolinyl, 2-thienyl and 3-thienyl, wherein the aromatic or heteroaromatic radical is unsubstituted or may carry 1 or 2 radicals R A 11 , R A 12 which are selected independently of each other from the group consisting of hydrogen, chlorine, fluorine, O—C 1 -C 4 -alkyl and C 1 -C 4 -alkyl.
13. The compounds according to claim 1 , wherein B is a radical selected from the group consisting of the respective individual radicals mentioned below:
14. The compound according to claim 1 , in which
A 1 is a radical selected from the group consisting of the in each case optionally substituted C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 3 -C 6 -cycloalkyl and the radical
in which
R A 11 is a radical selected from the group consisting of hydrogen, chlorine, fluorine, or in each case optionally substituted O—C 1 -C 4 -alkyl and C 1 -C 4 -alkyl;
A 2 is hydrogen;
B is a radical selected from the group consisting of the respective individual radicals mentioned below
R 1 is selected from the group consisting of chlorine, bromine, iodine, fluorine, CN and ethynyl;
R 2 is hydrogen
R 3 is a radical (X)—(Y), where
X is CO;
Y is a radical selected from the group consisting of the respective individual radicals mentioned below
in which n is 1 or 2, R is hydrogen or methyl,
R Y 6 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl;
R Y 7 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl;
R Y 221 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl;
R Y 222 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl; and
R Y 223 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl.
15. The compound according to claim 14 , wherein Y is a radical of the following formulae:
in which
R Y 222 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl; and
R Y 223 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl.
16. The compound according to claim 1 , in which
A 1 is a radical selected from the group consisting of the respective individual radicals mentioned below
A 2 is hydrogen;
B is a radical selected from the group consisting of the respective individual radicals mentioned below
R 1 is selected from the group consisting of chlorine, iodine, CN and ethynyl;
R 2 is hydrogen;
R 3 is a radical (X)—(Y), where
X is CO;
Y is a radical selected from the group consisting of the respective individual radicals mentioned below
in which n is 1 or 2, R is hydrogen or methyl,
R Y 6 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl;
R Y 7 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl;
R Y 221 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl;
R Y 222 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl; and
R Y 223 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl.
17. The compound according to claim 16 , wherein Y is a radical of the following formulae:
in which
R Y 222 is a radical selected from the group consisting of hydrogen, in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl;
R Y 223 is a radical selected from the group consisting of hydrogen, in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl;
the tautomeric, enantiomeric and/or diastereomeric forms thereof, and the physiologically tolerated salts of the aforementioned compound or compounds.
18. The compound according to claim 1 , in which
A 1 is a radical selected from the group consisting of the respective individual radicals mentioned below
A 2 is hydrogen;
B is a radical selected from the group consisting of the respective individual radicals mentioned below
R 1 is CN;
R 2 is hydrogen;
R 3 is a radical (X)—(Y), where
X is CO;
Y is a radical selected from the group consisting of the respective individual radicals mentioned below
in which n is 1 or 2, R is hydrogen or methyl,
R Y 6 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl;
R Y 7 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl;
R Y 221 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl;
R Y 222 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl; and
R Y 223 is a radical selected from the group consisting of hydrogen and/or in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl.
19. The compound according to claim 18 , wherein Y is a radical of the following formulae:
in which
R Y 222 is a radical selected from the group consisting of hydrogen, in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl;
R Y 223 is a radical selected from the group consisting of hydrogen, in each case optionally substituted C 1 -C 6 -alkyl and CH 2 -phenyl.
20. A pharmaceutical composition comprising at least one compound of the general formula (I) according to claim 1 , or a physiologically tolerated salt thereof, where appropriate with one or more physiologically tolerated excipients and/or additives.