US 2009/0291963 A1 · SUBSTITUTED INDOLES

Abstract

Substituted indoles of the formula (I) and physiologically acceptable derivatives and salts thereof, in which R1, D, E, R12, p, X1, E, G, X2 and Z are as defined in claim 1, exhibit particular actions on the central nervous system, especially 5HT reuptake-inhibiting and 5 HTx-agonistic and/or -antagonistic actions and in particular serotonin-agonistic and -antagonistic properties and can be employed as antipsychotics, neuroleptics, antidepressants, anxiolytics and/or antihypertonics. They can furthermore be employed as excitatory amino acid antagonists for combating neurodegenerative diseases, including cerebrovascular diseases, epilepsy, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's disease, cerebral ischaemia, infarction or psychoses

Compounds of the formula I

in which
R1 is H, A or SO2A,
A is straight-chain or branched alkyl having from 1 to 10 carbon atoms, alkenyl having from 2 to 10 carbon atoms or alkoxyalkyl having from 2 to 10 carbon atoms, and
D-E is R2C═CR4 or R2R3C—CR4R5,
in which
R2, R3, R4 and R5 are selected, independently, from H, A, cycloalkyl having from 3 to 7 carbon atoms, Hal, CH2Hal, CH(Hal)2, C(Hal)3, NO2, (CH2)nCN, (CH2)nN(R6)2, (CH2)nN(R6)Ar, (CH2)nN(R66)Het, (CH2)nN(Ar)2, (CH2)nN(Het)2, (CH2)nCOOR6 (CH2)nCOOAr, (CH2)nCOOHet, (CH2)nCON(R6)2, (CH2)nCON(R6)Ar, (CH2)nCON(R6)Het, (CH2)nCON(Ar)2, (CH2)nCON(Het)2, (CH2)nNR6COR6, (CH2)nNR6CON(R6)2, (CH2)nNR6SO2A, (CH2)nSO2N(R6)2, (CH2)nSO2NR6(CH2)mAr, (CH2)nSO2NR6(CH2)mHet, (CH2)nS(O)wR6, (CH2)nS(O)wAr, (CH2)nS(O)wHet, (CH2)nOOCR6 (CH2)nHet, (CH2)nAr, (CH2)nCOR6, (CH2)nCO(CH2)mAr, (CH2)nCO(CH2)mHet, (CH2)nCOO(CH2)mAr, (CH2)nCOO(CH2)mHet, (CH2)nOR6, (CH2)nO(CH2)mAr, (CH2)nO(CH2)mHet, (CH2)nSR6, (CH2)nS(CH2)mAr, (CH2)nS(CH2)mHet, (CH2)nN(R6)(CH2)mAr, (CH2)nN(R6)(CH2)mHet, (CH2)nSO2N(R6)(CH2)mAr, (CH2)nN(R6)SO2(CH2)mAr, (CH2)nSO2N(R6)(CH2)mHet, (CH2)nN(R6)SO2(CH2)mHet, (CH2)nCON(R6)(CH2)mAr, (CH2)nN(R6)CO(CH2)mAr, (CH2)nCON(R6)(CH2)mHet, (CH2)nN(R6)CO(CH2)mHet, CH═N—OA, CH2CH═N—OA, (CH2)nNHOA, (CH2)nCH═N-Het, (CH2)OCOR6, (CH2)nOC(O)N(R6)2, (CH2)nOC(O)NR6(CH2)mAr, (CH2)nOC(O)NR6(CH2)mHet, (CH2)nNR6COOR6, (CH2)nNR6COO(CH2)mAr, (CH2)nNR6COO(CH2)mHet, (CH2)nN(R6)CH2CH2OR6, (CH2)nN(R6)CH2CH2OCF3, (CH2)nN(R6)C(R6)HCOOR6, (CH2)nN(R6)CH2COHet, (CH2)nN(R6)CH2Het, (CH2)nN(R6)CH2CH2N(R6)CH2COOR6, (CH2)nN(R6)CH2CH2N(R6)2, CH═CHCOOR6, CH═CHCH2NR6Het, CH═CHCH2N(R6)2, CH═CHCH2OR6, (CH2)nN(COOR66)COOR6, (CH2)nN(CONH2)COOR6 (CH2)nN(CONH2)CONH2, (CH2)nN(CH2COOR6)COOR6, (CH2)nN(CH2CONH2)COOR6, (CH2)nN(CH2CONH2)CONH2, (CH2)nCHR6COR6, (CH2)nCHR6COOR6, (CH2)nCHR6CH2OR6, (CH2)nOCN or (CH2)nNCO, in which
R6 is selected, independently, from H, A or cycloalkyl having from 3 to 7 carbon atoms,
Het is a saturated, unsaturated or aromatic mono- or bicyclic heterocyclic radical which is unsubstituted or mono- or polysubstituted by A, Hal, NO2, CN, OR6, N(R6)2, COOR6, CON(R6)2, NR6COR6, NR6CON(R6)2, NR6SO2A, COR6, SO2N(R6)2, S(O)wA and/or OOCR6,
Ar is an aromatic hydrocarbon radical having from 6 to 14 carbon atoms which is unsubstituted or mono- or polysubstituted by A, Hal, NO2, CN, OR6, N(R6)2, COOR6, CON(R6)2, NR6COR6, NR6CON(R6)2, NR6SO2A, COR6, SO2N(R6)2, S(O)wA and/or OOCR6,
w is 0, 1, 2 or 3, and
n and m, independently of one another, are 0, 1, 2, 3, 4 or 5;
X1 is (CHR7)g or (CHR7)h-Q-(CHR8)k, in which
Q is selected from O, S, N—R6, (O—CHR7)g, (CHR7—O)g, CR9═CR10, (O—CHR9CHR10)g, (CHR9CHR10—O)g, C═O, C═S, C═NR6, CH(OR6), C(OR6)(OR6), C(═O)O, OC(═O), OC(═O)O, C(═O)N(R6), N(R6)C(═O), C(═S)N(R6), N(R6)C(═S), OC(═O)N(R6), N(R6)C(═O)O, CH═N—O, CH═N—NR6, OC(O)NR6, NR6C(O)O, S═O, SO2, SO2NR6 and NR6SO2,
g is 1, 2, 3, 4, 5 or 6,
h and k, independently of one another, are 0, 1, 2, 3, 4, 5 or 6, and
R7, R8, R9, R10 and R12, independently of one another, are as defined for R2 to R5;
p is 0, 1, 2 or 3
E is H, A, (CH2)nHet, (CH2)nAr or cycloalkyl having from 3 to 7 carbon atoms,
G is an optionally substituted alkylene radical having from 1 to 4 carbon atoms, where the substituents are selected from the meanings indicated for R4,
or
E and
G, together with the N atom to which they are bonded, are an unsubstituted or substituted 5-, 6- or 7-membered, mono- or bicyclic heterocyclic radical, which may have 1, 2 or 3 further heteroatoms selected from N, O and S,
X2 is a bond or is selected, independently, from the meanings indicated for X1,
Z is H or is a saturated, mono- or polyethylenically unsaturated or aromatic carbocyclic radical having from 5 to 10 carbon atoms or a saturated, mono- or polyethylenically unsaturated or aromatic heterocyclic radical having from 4 to 9 carbon atoms, where the carbocyclic or heterocyclic radical may be mono- or polysubstituted, where the substituents are selected, independently of one another, from the meanings of R2 to R5 other than H, and where the heterocyclic radical contains from 1 to 4 heteroatoms selected, independently of one another, from N, O and S,
and
Hal is F, Cl, Br or I,
and pharmaceutically usable derivatives, salts, solvates and stereoisomers and mixtures thereof.

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Substituted indoles

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Substituted indoles

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Abstract

Claims19