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US 2006/0052383 A1Published application
New dihydropteridione derivatives, process for their manufacture and their use as medicament
AssigneeBoehringer Ingelheim International GmbH
InventorsMatthias Grauert, Matthias Hoffmann, Martin Steegmaier, Christian Eickmeier, Gisela Schnapp, Norbert Redemann, Flavio Solca, Jens Quant
Life of this patent
Estimating the term…
Abstract
Disclosed are new dihydropteridinones of general formula (I) whereby the groups L, R1, R2, R3, R4 and R5 have the meanings given in the claims and specification, the isomers thereof, processes for preparing these dihydropteridinones and their use as pharmaceutical compositions.
Claims11
A Compound of the formula (I)
- wherein
- L denotes a single bond, or a bridging double-bonded group selected from among C1-C6-alkylene, C2-C6-alkenylene, C2-C6-alkynylene, C3-C7-cycloalkylene, C1-C4-alkylene-C6-C10-arylene-C1-C4-alkylene, C1-C4-alkylene-C6-C10-arylene, —O, —O—C1-C6-alkylene, —O—C3-C6-alkenylene, —O—C3-C6-alkynylene, —O—C3-C7-cycloalkylene, —O—C1-C4-alkylene-C6-C10-arylene-C1-C4-alkylene, —O—C1-C4-alkylene-C6-C10-arylene, —NR7— and —NR7—C1-C6-alkylene, —NR7-C3-C6-alkenylene, —NR7—C3-C6-alkynylene, —NR7—C3-C7-cycloalkylene, —NR7—C1-C4-alkylene-C6-C10-arylene-C1-C4-alkylene, —NR7—C1-C4-alkylene-C6-C10-arylene, which may optionally be substituted by one or more groups R9;
- R1 and R2, which may be identical or different, denote hydrogen, or a group selected from among C1-C6-alkyl, C2-C6-alkenyl and C2-C6-alkynyl, which may optionally be mono- or polysubstituted by one or more groups R9, or
- R1 and R2 together denote C2-C6-alkylene, in which optionally one or two methylene groups may be replaced by one of the groups —O or —NR7, and which may optionally be mono- or polysubstituted by one or more groups R9;
- R3 denotes hydrogen or a group selected from C1-C8-alkyl, C2-C8-alkenyl, C2-C8-alkynyl, C3-C8-cycloalkyl and C6-C14-aryl, which may optionally be mono- or polysubstituted by one or more groups R9;
- or
- R3 and R2 or R3 and R1 together denote C2-C6-alkylene which may optionally be mono- or polysubstituted by one or more groups R9;
- R4 denotes hydrogen, halogen, CN, OH, —NR7R8 or a group selected from among C1-C6-alkyl, C1-C6-alkyloxy, C2-C6-alkenyl, C2-C6-alkenyloxy, C2-C6-alkynyl and C2-C6-alkynyloxy, which may optionally be mono- or polysubstituted by one or more groups R10;
- R5 denotes phenyl, which may optionally be mono- or polysubstituted by one or more groups R11, or
- R5 denotes phenyl which is monosubstituted by a group R6, or
- R5 denotes C1-C4-alkyl which may optionally be mono- or polysubstituted by one or more groups R9, or
- R6 denotes —NR7R8 or a 5-10-membered heterocycloalkyl group which may contain one, two or three heteroatoms selected from among nitrogen, oxygen and sulphur, preferably nitrogen or oxygen, and which may optionally be mono- or polysubstituted by one or more of the groups R12;
- R7 and R8, which may be identical or different, denote hydrogen or C1-C6-alkyl,
- R9 denotes halogen, C1-C4-alkyl, C1-C4-alkyloxy, CN, OH or CF3;
- R10 denotes halogen, OH, CN, ═O, C1-C6-alkyloxy, COOR7, NR7R8, CONR7R8, SO2R7, CHF2 or CF3;
- R11 denotes halogen, OH, CN, C1-C4-alkyl, C1-C4-alkyloxy, COOR7, CONR7R8, SO2R7, CHF2, CF3, C6-C10-aryl or C1-C6-alkylene-C6-C10-aryl;
- R12 denotes halogen, CF3, C1-C6-alkyl, C1-C6-alkylene-C6-C10-aryl, C3-C8-cycloalkyl or C1-C6-alkylene-C3-C8-cycloalkyl;
- optionally in the form of the tautomers, racemates, enantiomers, diastereomers and mixtures thereof, and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and/or hydrates thereof.
15 more elements
A compound of the formula (A8)
- wherein
- R1 and R2, which may be identical or different, denote hydrogen, or a group selected from among C1-C6-alkyl, C2-C6-alkenyl and C2-C6-alkynyl, which may optionally be mono- or polysubstituted by one or more groups R9, or
- R1 and R2 together denote C2-C6-alkylene, in which optionally one or two methylene groups may be replaced by one of the groups —O or —NR7, and which may optionally be mono- or polysubstituted by one or more groups R9;
- R3 denotes hydrogen or a group selected from C1-C8-alkyl, C2-C8-alkenyl, C2-C8-alkynyl, C3-C8-cycloalkyl and C6-C14-aryl, which may optionally be mono- or polysubstituted by one or more groups R9;
- or
- R3 and R2 or R3 and R1 together denote C2-C6-alkylene which may optionally be mono- or polysubstituted by one or more groups R9;
- R4 denotes hydrogen, halogen, CN, OH, —NR7R8 or a group selected from among C1-C6-alkyl, C1-C6-alkyloxy, C2-C6-alkenyl, C2-C6-alkenyloxy, C2-C6-alkynyl and C2-C6-alkynyloxy, which may optionally be mono- or polysubstituted by one or more groups R10;
- R5 denotes phenyl, which may optionally be mono- or polysubstituted by one or more groups R11, or
- R5 denotes phenyl which is monosubstituted by a group R6, or
- R5 denotes C1-C4-alkyl which may optionally be mono- or polysubstituted by one or more groups R9, or
- R6 denotes —NR7R8 or a 5-10-membered heterocycloalkyl group which may contain one, two or three heteroatoms selected from among nitrogen, oxygen and sulphur, preferably nitrogen or oxygen, and which may optionally be mono- or polysubstituted by one or more of the groups R12;
- R7 and R8, which may be identical or different, denote hydrogen or C1-C6-alkyl,
- R9 denotes halogen, C1-C4-alkyl, C1-C4-alkyloxy, CN, OH or CF3;
- R10 denotes halogen, OH, CN, ═O, C1-C6-alkyloxy, COOR7, NR7R8, CONR7R8, SO2R7, CHF2 or CF3;
- R11 denotes halogen, OH, CN, C1-C4-alkyl, C1-C4-alkyloxy, COOR7, CONR7R8, SO2R7, CHF2, CF3, C6-C10-aryl or C1-C6-alkylene-C6-C10-aryl;
- R12 denotes halogen, CF3, C1-C6-alkyl, C1-C6-alkylene-C6-C10-aryl, C3-C8-cycloalkyl or C1-C6-alkylene-C3-C8-cycloalkyl;
- optionally in the form of the tautomers, racemates, enantiomers, diastereomers and mixtures thereof, and optionally in the form of the acid addition salts, solvates and/or hydrates thereof.
14 more elements
A compound of the formula (A7a)
- wherein
- R1 and R2, which may be identical or different, denote hydrogen, or a group selected from among C1-C6-alkyl, C2-C6-alkenyl and C2-C6-alkynyl, which may optionally be mono- or polysubstituted by one or more groups R9, or
- R1 and R2 together denote C2-C6-alkylene, in which optionally one or two methylene groups may be replaced by one of the groups —O or —NR7, and which may optionally be mono- or polysubstituted by one or more groups R9;
- R3 denotes hydrogen or a group selected from C1-C8-alkyl, C2-C8-alkenyl, C2-C8-alkynyl, C3-C8-cycloalkyl and C6-C14-aryl, which may optionally be mono- or polysubstituted by one or more groups R9;
- or
- R3 and R2 or R3 and R1 together denote C2-C6-alkylene which may optionally be mono- or polysubstituted by one or more groups R9;
- R4 denotes hydrogen, halogen, CN, OH, —NR7R8 or a group selected from among C1-C6-alkyl, C1-C6-alkyloxy, C2-C6-alkenyl, C2-C6-alkenyloxy, C2-C6-alkynyl and C2-C6-alkynyloxy, which may optionally be mono- or polysubstituted by one or more groups R10;
- R5 denotes phenyl, which may optionally be mono- or polysubstituted by one or more groups R11, or
- R5 denotes phenyl which is monosubstituted by a group R6, or
- R5 denotes C1-C4-alkyl which may optionally be mono- or polysubstituted by one or more groups R9, or
- R6 denotes —NR7R8 or a 5-10-membered heterocycloalkyl group which may contain one, two or three heteroatoms selected from among nitrogen, oxygen and sulphur, preferably nitrogen or oxygen, and which may optionally be mono- or polysubstituted by one or more of the groups R12;
- R7 and R8, which may be identical or different, denote hydrogen or C1-C6-alkyl,
- R9 denotes halogen, C1-C4-alkyl, C1-C4-alkyloxy, CN, OH or CF3;
- R10 denotes halogen, OH, CN, ═O, C1-C6-alkyloxy, COOR7, NR7R8, CONR7R8, SO2R7, CHF2 or CF3;
- R11 denotes halogen, OH, CN, C1-C4-alkyl, C1-C4-alkyloxy, COOR7, CONR7R8, SO2R7, CHF2, CF3, C6-C10-aryl or C1-C6-alkylene-C6-C10-aryl;
- R12 denotes halogen, CF3, C1-C6-alkyl, C1-C6-alkylene-C6-C10-aryl, C3-C8-cycloalkyl or C1-C6-alkylene-C3-C8-cycloalkyl;
- and wherein PG denotes an amino protecting group, optionally in the form of the tautomers, racemates, enantiomers, diastereomers and mixtures thereof, and optionally in the form of the acid addition salts, solvates and/or hydrates thereof.
14 more elements
A compound of the formula (A7b)
- wherein
- R1 and R2, which may be identical or different, denote hydrogen, or a group selected from among C1-C6-alkyl, C2-C6-alkenyl and C2-C6-alkynyl, which may optionally be mono- or polysubstituted by one or more groups R9, or
- R1 and R2 together denote C2-C6-alkylene, in which optionally one or two methylene groups may be replaced by one of the groups —O or —NR7, and which may optionally be mono- or polysubstituted by one or more groups R9;
- R3 denotes hydrogen or a group selected from C1-C8-alkyl, C2-C8-alkenyl, C2-C8-alkynyl, C3-C8-cycloalkyl and C6-C14-aryl, which may optionally be mono- or polysubstituted by one or more groups R9;
- or
- R3 and R2 or R3 and R1 together denote C2-C6-alkylene which may optionally be mono- or polysubstituted by one or more groups R9;
- R4 denotes hydrogen, halogen, CN, OH, —NR7R8 or a group selected from among C1-C6-alkyl, C1-C6-alkyloxy, C2-C6-alkenyl, C2-C6-alkenyloxy, C2-C6-alkynyl and C2-C6-alkynyloxy, which may optionally be mono- or polysubstituted by one or more groups R10;
- R5 denotes phenyl, which may optionally be mono- or polysubstituted by one or more groups R11, or
- R5 denotes phenyl which is monosubstituted by a group R6, or
- R5 denotes C1-C4-alkyl which may optionally be mono- or polysubstituted by one or more groups R9, or
- R6 denotes —NR7R8 or a 5-10-membered heterocycloalkyl group which may contain one, two or three heteroatoms selected from among nitrogen, oxygen and sulphur, preferably nitrogen or oxygen, and which may optionally be mono- or polysubstituted by one or more of the groups R12;
- R7 and R8, which may be identical or different, denote hydrogen or C1-C6-alkyl,
- R9 denotes halogen, C1-C4-alkyl, C1-C4-alkyloxy, CN, OH or CF3;
- R10 denotes halogen, OH, CN, ═O, C1-C6-alkyloxy, COOR7, NR7R8, CONR7R8, SO2R7, CHF2 or CF3;
- R11 denotes halogen, OH, CN, C1-C4-alkyl, C1-C4-alkyloxy, COOR7, CONR7R8, SO2R7, CHF2, CF3, C6-C10-aryl or C1-C6-alkylene-C6-C10-aryl;
- R12 denotes halogen, CF3, C1-C6-alkyl, C1-C6-alkylene-C6-C10-aryl, C3-C8-cycloalkyl or C1-C6-alkylene-C3-C8-cycloalkyl;
- optionally in the form of the tautomers, racemates, enantiomers, diastereomers and mixtures thereof, and optionally in the form of the acid addition salts, solvates and/or hydrates thereof.
14 more elements
A compound of the formula (A5)
- R1 and R2, which may be identical or different, denote hydrogen, or a group selected from among C1-C6-alkyl, C2-C6-alkenyl and C2-C6-alkynyl, which may optionally be mono- or polysubstituted by one or more groups R9, or
- R1 and R2 together denote C2-C6-alkylene, in which optionally one or two methylene groups may be replaced by one of the groups —O or —NR7, and which may optionally be mono- or polysubstituted by one or more groups R9;
- R3 denotes hydrogen or a group selected from C1-C8-alkyl, C2-C8-alkenyl, C2-C8-alkynyl, C3-C8-cycloalkyl and C6-C14-aryl, which may optionally be mono- or polysubstituted by one or more groups R9;
- or
- R7 denotes hydrogen or C1-C6-alkyl,
- R9 denotes halogen, C1-C4-alkyl, C1-C4-alkyloxy, CN, OH or CF3;
- optionally in the form of the tautomers, racemates, enantiomers, diastereomers and mixtures thereof, and optionally in the form of the acid addition salts, solvates and/or hydrates thereof.
4 more elements
Dependencies are inferred from the claim text.