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US 8,138,187 B2Granted
Substituted heteroaryl derivatives
AssigneeGruenenthal GmbH
InventorsSaskia Zemolka, Stefan Schunk, Werner Englberger, Babette-Yvonne Kögel, Klaus Linz, Hans Schick, Helmut Sonnenschein, Heinz Graubaum, Claudia Hinze
Life of this patent
Estimating the term…
Abstract
The invention relates to substituted heteroaryl derivatives, to methods for the production thereof, to medicaments containing said compounds and to the use of substituted heteroaryl derivatives for producing medicaments.
Claims17
Substituted heteroaryl derivatives of the formula I
- wherein
- A represents N or CR7-10, wherein A represents N at most twice
- W represents O, S or NR4
- with the proviso that if W represents O or S, A denotes CR7-10;
- one of the radicals B or C represents H;
- C1-8-alkyl, in each case saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted, COR12;
- SO2R12;
- aryl, C3-8-cycloalkyl or heteroaryl bonded via C1-3-alkyl and in each case mono- or polysubstituted or unsubstituted, aryl or heteroaryl, in each case mono- or polysubstituted or unsubstituted;
- C3-8-cycloalkyl, in each case mono- or polysubstituted or unsubstituted;
- and the other particular radical B or C represents
- wherein
- represents a single bond or a double bond,
- R1 and R2 independently of one another represent H;
- C1-5-alkyl, in each case saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted, except that neither R1 nor R2 may represent alkyl substituted by unsubstituted or substituted O-phenyl;
- C3-8-cycloalkyl, in each case mono- or polysubstituted or unsubstituted;
- aryl or heteroaryl, in each case mono- or polysubstituted or unsubstituted;
- or aryl, C3-8-cycloalkyl or heteroaryl, bonded via C1-3-alkyl and in each case mono- or polysubstituted or unsubstituted;
- or the radicals R1 and R2 together represent CH2CH2OCH2CH2, CH2CH2NR11CH2CH2 or (CH2)3-6,
- wherein R11 denotes H;
- C1-5-alkyl, in each case saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted;
- C3-8-cycloalkyl, in each case mono- or polysubstituted or unsubstituted;
- aryl or heteroaryl, in each case mono- or polysubstituted or unsubstituted;
- or aryl, C3-8-cycloalkyl or heteroaryl, bonded via C1-3-alkyl and in each case mono- or polysubstituted or unsubstituted;
- C(O)phenyl, C(O)heteroaryl, C(O)C1-5-alkyl, in each case substituted or unsubstituted;
- and
- R3 represents C1-8-alkyl, in each case saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted;
- C3-8-cycloalkyl, in each case mono- or polysubstituted or unsubstituted;
- aryl or heteroaryl, in each case unsubstituted or mono- or polysubstituted;
- aryl, heteroaryl or C3-8-cycloalkyl, bonded via C1-3-alkyl group and in each case unsubstituted or mono- or polysubstituted;
- R4 represents H;
- C1-5-alkyl, saturated or unsaturated, branched or unbranched, unsubstituted or mono- or polysubstituted;
- aryl, or heteroaryl, in each case substituted or unsubstituted;
- aryl, heteroaryl or cycloalkyl, bonded via a C1-3-alkyl group and in each case mono- or polysubstituted or unsubstituted;
- COR12;
- SO2R12,
- wherein R12 denotes H;
- C1-5-alkyl, in each case saturated or unsaturated, branched or unbranched, mono- or polysubstituted or unsubstituted;
- C3-8-cycloalkyl, in each case saturated or unsaturated, mono- or polysubstituted or unsubstituted;
- aryl or heteroaryl, in each case mono- or polysubstituted or unsubstituted;
- or aryl, C3-8-cycloalkyl or heteroaryl, bonded via C1-3-alkyl and in each case mono- or polysubstituted or unsubstituted;
- OR13;
- NR14R15;
- R7, R8, R9 and R10 independently of one another represent
- H, F, Cl, Br, I, NO2, CF3, OR13, SR13, SO2R13, SO2OR13, CN, COOR13, NR14R15, NHC(O)NHR13, NHC(O)R13, NH(CNR13)NHR13, SO2NHR13;
- C1-5-alkyl, C3-8-cycloalkyl, unsubstituted or mono- or polysubstituted;
- aryl or heteroaryl, unsubstituted or mono- or polysubstituted;
- or aryl, C3-8-cycloalkyl or heteroaryl, bonded via C1-3-alkyl and unsubstituted or mono- or polysubstituted;
- wherein R13 denotes H;
- C1-5-alkyl, in each case saturated or unsaturated, branched or unbranched, unsubstituted or mono- or polysubstituted;
- C3-8-cycloalkyl, in each case saturated or unsaturated, unsubstituted or mono- or polysubstituted;
- aryl or heteroaryl, unsubstituted or mono- or polysubstituted;
- or aryl, C3-8-cycloalkyl or heteroaryl, bonded via C1-3-alkyl and unsubstituted or mono- or polysubstituted;
- or R7, R8 and R9 have the abovementioned meaning and R10 together with B represents —CH2CH2CH2— and R10 and B therefore form a six-membered ring,
- R14 and R15 independently of one another denote H;
- C1-5-alkyl, in each case saturated or unsaturated, branched or unbranched, unsubstituted or mono- or polysubstituted;
- or C3-8-cycloalkyl, in each case saturated or unsaturated, unsubstituted or mono- or polysubstituted;
- aryl or heteroaryl, unsubstituted or mono- or polysubstituted;
- or aryl, C3-8-cycloalkyl or heteroaryl, bonded via C1-3-alkyl and unsubstituted or mono- or polysubstituted;
- or R14 and R15 together form CH2CH2OCH2CH2, CH2CH2NR16CH2CH2 or (CH2)3-6,
- wherein R16 denotes H;
- C1-5-alkyl, saturated or unsaturated, branched or unbranched, unsubstituted or mono- or polysubstituted;
- in the form of the racemate;
- of the enantiomers, diastereomers, mixtures of the enantiomers or diastereomers or of an individual enantiomer or diastereomer;
- of the bases and/or salts of physiologically acceptable acids.
61 more elements
Process for the preparation of substituted heteroaryl derivatives of the formula Ic
- comprising reacting ketones of the formula B with heteroaromatics of the formula A in organic solvents or solvent mixtures with the addition of an organic or inorganic acid, or without a solvent in an organic or inorganic acid or acid mixtures at temperatures of between 0° C. and 150° C., optionally using microwave irradiation, and then reacting with the addition of an organic or inorganic reducing agent at temperatures of between 0° C. and 150° C., optionally using microwave irradiation.
Process for the preparation of substituted heteroaryl derivatives of the general formula Id or Ie
- comprising reacting heteroaromatics of the formula A or A′ with cyclohexanones of the formula B in organic solvents or solvent mixtures with the addition of an organic or inorganic acid at temperatures of between 0° C. and 150° C., optionally using microwave irradiation;
- or reacting heteroaromatics of the formula A or A′ with cyclohexanones of the formula B with the addition of a base in an organic solvent at temperatures of between 20 and 100° C.
Process for the preparation of substituted heteroaryl derivatives of the formulae Ic or If
- comprising reducing compounds Id or Ie by means of hydrogen in the form of HBr/glacial acetic acid/Sn or HCl/Sn (nascent hydrogen) or H2 in the presence of a metal catalyst in a suitable solvent or solvent mixture at temperatures of between 0° C. and 150° C.
Dependencies are inferred from the claim text.