Substituted oxindole derivatives, drugs containing said derivatives and the use thereof
View Patent ↗The invention relates to novel oxindol derivative of general formula (I), wherein substituents R 1 , R 2 , A, B and Y are such as defined in a claim 1 . Drugs containing said derivatives and the use thereof for preventing and/or treating vassopress-and/or oxytocin-dependent-diseases are also disclosed.
1. A method for treating stress-dependent anxiety disorders, anxiety, or depressive disorders, the method comprising administering an effective amount of at least one compound of the formula (I),
in which
A is an aromatic, heteroaromatic, partly aromatic or partly heteroaromatic mono- or bicyclic radical which consists of 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms and 0, 1, 2, 3 or 4 nitrogen atoms and/or 0, 1 or 2 oxygen atoms and/or 0, 1 or 2 sulfur atoms, and which is substituted by the radical R A 1 and may be additionally substituted by 1, 2 or 3 radicals R A 11 , R A 12 and/or R A 13 which are selected independently of one another and independent of their respective occurrence from the group consisting of hydrogen, chlorine, bromine, iodine, fluorine, CN, CF 3 , OCF 3 , OCHF 2 , CO—NH 2 , CO—NH(C 1 -C 4 -alkyl), CO—N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NH 2 , NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NHCHO, NH—CO—NH 2 , NH—CO(C 1 -C 4 -alkyl), NO 2 , OH, O—C 1 -C 4 -alkyl, O—C 0 -C 4 -alkylene-phenyl, phenyl, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl,
in which
R A 1 is R A 2 -(C 1 -C 4 -alkylene)-R A 4 ,
R A 2 is selected from the group consisting of
(C 0 -C 4 -alkylene)-O, (C 0 -C 4 -alkylene)-NR A 5 , (C 0 -C 4 -alkylene)-S, (C 0 -C 4 -alkylene)-SO, (C 0 -C 4 -alkylene)-SO 2 , (C 0 -C 4 -alkylene)-CO, (C 0 -C 4 -alkylene)-NR A 5 -SO 2 , (C 0 -C 4 -alkylene)-CO—NR A 5 , (C o -C 4 -alkylene)-CO—O, (C 0 -C 4 -alkylene)-NR A 5 —SO 2 , (C 0 -C 4 -alkylene)-SO 2 —NR A 5 , (C 0 -C 4 -alkylene)-NR A 5 —CO—NR A 6 , (C 0 -C 4 -alkylene)-O—CO—NR A 5 , (C 0 -C 4 -alkylene)-NR A 5 -CO—O and single bond,
R A 4 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 1 -C 4 -alkylene-O—C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkylene-O—C 1 -C 4 -alky) NH—CHO, N(C 1 -C 4 -alkyl)-CHO, NH—CO—NH 2 , N(C 1 -C 4 -alkyl)-CO—NH 2 , NH—CO—C 1 -C 4 -alkyl, N(C 1 -C 4 -alkyl)-CO—C 1 -C 4 -alkyl, NH—SO 2 -C 1 -C 4 -alkyl, N(C 1 -C 4 -alkyl)-SO 2 -C 1 -C 4 -alkyl and ring R A 8 ,
R A 5 , R A 6 , R A 9 are selected independently of one another and independent of their respective occurrence from the group consisting of hydrogen, C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl,
R A 8 is selected from the group consisting of the respective individual radicals
B is an aromatic, heteroaromatic, partly aromatic or partly heteroaromatic mono- or bicyclic radical which consists of 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms and 0, 1, 2, 3 or 4 nitrogen atoms and/or 0, 1 or 2 oxygen atoms and/or 0, 1 or 2 sulfur atoms, and which may be substituted by 1, 2 or 3 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 independent of their respective occurrence from the group consisting of hydrogen, chlorine, bromine, iodine, fluorine, CN, CF 3 , OCF 3 , OCHF 2 , CO—NH 2 , CO—NH(C 1 -C 4 -alkyl), CO—N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NH 2 , NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NH—CHO, NH—CO—NH 2 , NH—CO—C 1 -C 4 -alkyl, NO 2 , OH, O—C 1 -C 4 -alkyl, O—C 0 -C 4 -alkylenephenyl, phenyl, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl,
R 1 is selected from the group consisting of hydrogen, chlorine, bromine, iodine, fluorine, CN, CF 3 , OCF 3 , OCHF 2 , CO—NH 2 , CO—NH(C 1 -C 4 -alkyl), CO—N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NH 2 , NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NH—CHO, NH—CO—NH 2 , NH—CO—C 1 -C 4 -alkyl, NO 2 , OH, O—C 1 -C 4 -alkyl, O—C 0 -C 4 -alkylenephenyl, phenyl, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl,
R 2 is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, O—C 1 -C 4 -alkyl, chlorine and fluorine,
Y is a radical
in which
R Y 1 is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl,
R Y 2 is selected from the group consisting of hydrogen; phenyl; phenyl substituted by 1, 2, 3, 4 or 5 radicals R Ph l , R Ph 2 , R Ph 3 , R Ph 4 and/or R Ph 5 which are selected independently of one another from the group consisting of hydrogen, halogen, C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy; C 1 -C 6 -alkyl; C 3 -C 7 -cycloalkyl and C 1 -C 6 -haloalkyl,
in which R Y 1 and R Y 2 may also form together with the atoms to which they are bonded a 4-, 5-, 6- or 7-membered, saturated or unsaturated ring which may, instead of a ring C atom, also include a heteroatom selected from the group consisting of O, S and NR Y 5 ring member, where R Y 5 independent of its respective occurrence is hydrogen, C 1 -C 4 -alkyl or CO—C 1 -C 4 -alkyl, and where the ring may have one or two substituents R Y 6 and R Y 7 which are selected independently of one another and independent of their respective occurrence from the group consisting of the radicals hydrogen, chlorine, bromine, iodine, fluorine, CN, CF 3 , OCF 3 , OCHF2, CO—NH 2 , CO—NH(C 1 -C 4 -alkyl), CO—N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NH 2 , NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl)(C 1 -C 4 -alkyl), NH—CHO, NH—CO—NH 2 , NH—CO—C 1 -C 4 -alkyl, OH, O—C 1 -C 4 -alkyl, O—CO—C 1 -C 4 -alkyl, O—(CH 2 ) 0-2 -phenyl, phenyl, C 1 -C 6 -alkyl,
or
R Y 6 and R Y 7 may also independent of their respective occurrence form together with the C atoms to which they are bonded a fused phenyl ring or a fused 5- or 6-membered, aromatic heterocycle which, besides C atoms, includes as ring members 1, 2, 3 or 4 identical or different heteroatoms as ring members which may be selected independently of one another from the group consisting of nitrogen, oxygen and sulfur,
R Y 3 is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl,
R Y 4 is selected from the group consisting of hydrogen, CO—NR Y 21 R Y 22 , CO—C 1 -C 4 -alkyl, COOH and CO—O—C 1 -C 4 -alkyl,
R Y 21 , R Y 22 are selected independently of one another and independent of their respective occurrence from the group consisting of hydrogen, C 1 -C 4 -alkyl and C 1 -C 4 -haloalkyl,
or R Y 21 and R Y 22 may also independent of their respective occurrence form together with the nitrogen atom to which they are bonded a 4-, 5- or 6-membered, saturated or wholly or partly unsaturated N-heterocyclic ring.
2. The method of claim 1 , where the patient is a mammal.
3. The method of claim 2 , wherein the patient is a human.