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US 6,638,933 B2Granted
Bicyclic imidazo-3-yl-amine derivatives
AssigneeGruenenthal GmbH
InventorsMatthias Gerlach, Corinna Maul
Life of this patent
Estimating the term…
Abstract
Substituted bicyclic imidazo-3-yl-amines and medicaments comprising these compounds, useful, inter alia, as analgesics.
Claims12
A compound of formula I:
- wherein
- X and Y each separately denote CH or N, with the proviso that X and Y do not simultaneously denote N;
- R1 denotes tert-butyl, (CH2)nCN, where n=4, 5 or 6, optionally substituted phenyl, C4-C8-cycloalkyl, CH2CH2R (R=4-morpholino), 1,1,3,3-tetramethylbutyl, or CH2Ra wherein Ra represents hydrogen, OH, branched or unbranched C1-C8-alkyl, optionally substituted phenyl, CO(OR′) wherein R′=unbranched C1-C4-alkyl or branched C1-C5-alkyl, PO(OR′)2 wherein R′=unbranched C1-C4-alkyl or branched C1-C5-alkyl, or Si(RxRyRz) wherein Rx, Ry and Rz are each selected independently of one another from branched or unbranched C1-C4-alkyl, C4-C8-cycloalkyl, and phenyl;
- R2 denotes hydrogen, CORb, wherein Rb represents branched or unbranched C1-C4-alkyl or C3-C8-cycloalkyl, CH2CH2CO(ORc), wherein Rc represents branched or unbranched C1-C4-alkyl, adamantyl, optionally substituted phenyl, optionally substituted 1-naphthyl, optionally substituted 2-naphthyl, optionally substituted 2-pyridyl, optionally substituted 3-pyridyl, optionally substituted 4-pyridyl, optionally substituted thiazolyl, optionally substituted furoyl, benzyl, CH2CH2Rd wherein Rd represents optionally substituted phenyl, or CONHRe wherein Re represents branched or unbranched C1-C8-alkyl, C3-C8-cycloalkyl, or optionally substituted phenyl;
- R3 denotes methyl, ethyl, tert-butyl, C3-C8-cycloalkyl, phenyl wherein said phenyl is optionally monosubstituted in the 3-, 5- or 6-position, or wherein said phenyl is optionally at least di-substituted in the 4-position and additionally in at least one of the 2-, 3-, 5-, and 6-positions, phenoxy, optionally substituted naphthyl, optionally substituted pyrrole, optionally substituted pyridyl, optionally substituted furan, optionally substituted thiophene, optionally substituted anthracene, optionally substituted phenanthrene, or optionally substituted quinoline;
- wherein any radical denoted optionally substituted is unsubstituted, or is at least mono-substituted with a moiety selected from the group consisting of OH, nitro, amino, amido, cyano, CO—C1-C8-alkyl, CO—O—C1-C8-alkyl, CO2H, O—C1-C8-alkyl, O-heteroalkyl, halogen, branched or unbranched C1-C8-alkyl, C3-C8-cycloalkyl, C3-C8-heterocyclyl, unsubstituted or substituted phenyl, unsubstituted or substituted heteroaryl, wherein any ring, aromatic or unsaturated, may be fused to other rings, any moeity optionally has one or more double or triple bonds, and any alkyl or aromatic moiety is unsubstituted or is substituted with a moiety selected from this group;
- with the proviso that if R1 is tert-butyl, n-propyl, n-butyl, 1,1,3,3-tetramethylbutyl, cyclohexyl, CH2CH2R wherein R=4-morpholino, monosubstituted phenyl, 2,6-dimethylphenyl or benzyl, and R2 is hydrogen or —CO(methyl), R3 is not n-propyl, cyclohexyl, unsubstituted phenyl, or phenyl monosubstituted in the 3-position with a carboxylic acid amide group;
- with the further proviso that if R1 denotes benzyl, and R3 is methyl, R2 is not hydrogen;
- with the further proviso that if R1 is CH2C(O)tert-butyl, and R3 is unsubstituted phenyl, R2 is not hydrogen;
- or a pharmaceutically acceptable salt thereof.
7 more elements
A method of alleviating pain in a patient in need thereof, comprising administering to said patient an effective pain alleviating amount of at least one compound of formula I:
- wherein
- X and Y each separately denote CH or N, with the proviso that X and Y do not simultaneously denote N;
- R1 denotes tert-butyl, (CH2)nCN, where n=4, 5 or 6, optionally substituted phenyl, C4-C8-cycloalkyl, CH2CH2R (R=4-morpholino), 1,1,3,3-tetramethylbutyl, or CH2Ra wherein Ra represents hydrogen, OH, branched or unbranched C1-C8-alkyl, optionally substituted phenyl, CO(OR′) wherein R′=unbranched C1-C4-alkyl or branched C1-C5-alkyl, PO(OR′)2 wherein R′=unbranched C1-C4-alkyl or branched C1-C5-alkyl, or Si(RxRyRz) wherein Rx, Ry and Rz are each selected independently of one another from branched or unbranched C1-C4-alkyl, C4-C8-cycloalkyl, and phenyl;
- R2 denotes hydrogen, CORb, wherein Rb represents branched or unbranched C1-C4-alkyl or C3-C8-cycloalkyl, CH2CH2CO(ORc), wherein Rc represents branched or unbranched C1-C4-alkyl, adamantyl, optionally substituted phenyl, optionally substituted 1-naphthyl, optionally substituted 2-naphthyl, optionally substituted 2-pyridyl, optionally substituted 3-pyridyl, optionally substituted 4-pyridyl, optionally substituted thiazolyl, optionally substituted furoyl, benzyl, CH2CH2Rd wherein Rd represents optionally substituted phenyl, or CONHRe wherein Re represents branched or unbranched C1-C8-alkyl, C3-C8-cycloalkyl, or optionally substituted phenyl;
- R3 denotes methyl, ethyl, tert-butyl, C3-C8-cycloalkyl, phenyl wherein said phenyl is optionally monosubstituted in the 3-, 5- or 6-position, or wherein said phenyl is optionally at least di-substituted in the 4-position and additionally in at least one of the 2-, 3-, 5-, and 6-positions, phenoxy, optionally substituted naphthyl, optionally substituted pyrrole, optionally substituted pyridyl, optionally substituted furan, optionally substituted thiophene, optionally substituted anthracene, optionally substituted phenanthrene, or optionally substituted quinoline;
- wherein any radical denoted optionally substituted is unsubstituted, or is at least mono-substituted with a moiety selected from the group consisting of OH, nitro, amino, amido, cyano, CO—C1-C8-alkyl, CO—O—C1-C8-alkyl, CO2H, O—C1-C8-alkyl, O-heteroalkyl, halogen, branched or unbranched C1-C8-alkyl, C3-C8-cycloalkyl, C3-C8-heterocyclyl, unsubstituted or substituted phenyl, unsubstituted or substituted heteroaryl, wherein any ring, aromatic or unsaturated, may be fused to other rings, any moeity optionally has one or more double or triple bonds, and any alkyl or aromatic moiety is unsubstituted or is substituted with a moiety selected from this group;
- with the proviso that if R1 is tert-butyl, n-propyl, n-butyl, 1,1,3,3-tetramethylbutyl, cyclohexyl, CH2CH2R wherein R=4-morpholino, monosubstituted phenyl, 2,6-dimethylphenyl or benzyl, and R2 is hydrogen or CO(methyl), R3 is not n-propyl, cyclohexyl, unsubstituted phenyl, or phenyl monosubstituted in the 3-position with a carboxylic acid amide group;
- with the further proviso that if R1 denotes benzyl, and R3 is methyl, R2 is not hydrogen;
- with the further proviso that if R1 is CH2C(O)tert-butyl, and R3 is unsubstituted phenyl, R2 is not hydrogen;
- or a pharmaceutically acceptable salt thereof.
7 more elements
Dependencies are inferred from the claim text.