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US 2003/0114452 A1Published application
Novel substituted imidazole compounds
AssigneeSmithKline Beecham Corporation
InventorsJerry L. Adams, Ralph F. Hall
Life of this patent
Estimating the term…
Abstract
Novel 1,4,5-substituted imidazole compounds and compositions for use in therapy as CSBP/p38 kinase inhibitors.
Claims34
A compound represented by the formula:
- 17
- wherein
- R1 is 4-pyridyl, pyrimidinyl, 4pyridazinyl, 1,2,4-triazin-5-yl, quinolyl, isoquinolinyl, or quinazolin-4-yl ring, which ring is substituted with Y-Ra and optionally with an additional independent substituent selected from C1-4 alkyl, halogen, hydroxyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylsulfinyl, CH2OR12, amino, mono and di-C1-6 alkyl substituted amino, an N-heterocyclyl ring which ring has from 5 to 7 members and optionally contains an additional heteroatom selected from oxygen, sulfur or NR15, N(R10)C(O)Rb or NHRa;
- Y is oxygen or sulfur;
- R4 is phenyl, naphth-1-yl or naphth-2-yl, or a heteroaryl, which is optionally substituted by one or two substituents, each of which is independently selected, and which, for a 4-phenyl, 4-naphth-1-yl, 5-naphth-2-yl or 6-naphth-2-yl substituent, is halogen, cyano, nitro, C(Z)NR7R17, C(Z)OR16, (CR10R20)vCOR12, SR5, SOR5, OR12 halo-substituted-C1-4 alkyl, C1-4 alkyl, ZC(Z)R12, NR10C(Z)R16, or (CR10R20)vNR10R20 and which, for other positions of substitution, is halogen, cyano, C(Z)NR13R14, C(Z)OR3, (CR10R20)m″COR3, S(O)mR3, OR3, halo-substituted-C1-4 alkyl, C1-4 alkyl, (CR10R20)m″NR10C(Z)R3, NR10S(O)m′R8, NR10S(O)m′NR7R17, ZC(Z)R3 or (CR10R20)m″NR13R14;
- Z is oxygen or sulfur;
- n is an integer having a value of 1 to 10;
- m is 0, or the integer 1 or 2;
- m′ is an integer having a value of 1 or 2,
- m″ is 0, or an integer having a value of 1 to 5;
- v is 0, or an integer having a value of 1 or 2;
- R2 is —C(H)(A)(R22);
- A is an optionally substituted aryl, heterocyclyl, or heteroaryl ring, or A is a substituted C1-10alkyl;
- R22 is an optionally substituted C1-10 alkyl;
- Ra is aryl, arylC1-6alkyl, heterocyclic, heterocyclylC1-6 alkyl, heteroaryl, heteroarylC1-6alkyl, wherein each of these moieties may be optionally substituted;
- Rb is hydrogen, C1-6 alkyl, C3-7 cycloalkyl, aryl, arylC1-4 alkyl, heteroaryl, heteroarylC1-4alkyl, heterocyclyl, or heterocyclylC1-4 alkyl, wherein each of these moieties may be optionally substituted;
- R3 is heterocyclyl, heterocyclylC1-10alkyl or R8;
- R5 is hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl or NR7R17, excluding the moieties SR5 being SNR7R17 and SOR5 being SOH;
- R6 is hydrogen, a pharmaceutically acceptable cation, C1-10 alkyl, C3-7 cycloalkyl, aryl, arylC1-4 alkyl, heteroaryl, heteroarylC1-4alkyl, heterocyclyl, aroyl, or C1-10 alkanoyl;
- R7 and R17 is each independently selected from hydrogen or C1-4 alkyl or R7 and R17 together with the nitrogen to which they are attached form a heterocyclic ring of 5 to 7 members which ring optionally contains an additional heteroatom selected from oxygen, sulfur or NR15;
- R8 is C1-10 alkyl, halo-substituted C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-7 cycloalkyl, C5-7 cycloalkenyl, aryl, arylC1-10 alkyl, heteroaryl, heteroarylC1-10 alkyl, (CR10R20)nOR11, (CR10R20)nS(O)mR18, (CR10R20)nNHS(O)2R18, (CR10R20)nNR13R14;
- wherein the aryl, arylalkyl, heteroaryl, heteroaryl alkyl may be optionally substituted;
- R9 is hydrogen, C(Z)R11 or optionally substituted C1-10 alkyl, S(O)2R18, optionally substituted aryl or optionally substituted aryl-C1-4 alkyl;
- R10 and R20 is each independently selected from hydrogen or C1-4 alkyl;
- R11 is hydrogen, C1-10 alkyl, C3-7 cycloalkyl, heterocyclyl, heterocyclyl C1-10alkyl, aryl, arylC1-10 alkyl, heteroaryl or heteroarylC1-10 alkyl, wherein these moieites may be optionally substituted;
- R12 is hydrogen or R16;
- R13 and R14 is each independently selected from hydrogen or optionally substituted C1-4 alkyl, optionally substituted aryl or optionally substituted aryl-C1-4 alkyl, or together with the nitrogen which they are attached form a heterocyclic ring of 5 to 7 members which ring optionally contains an additional heteroatom selected from oxygen, sulfur or NR9;
- R15 is R10 or C(Z)—C1-4 alkyl;
- R16 is C1-4 alkyl, halo-substituted-C1-4 alkyl, or C3-7 cycloalkyl;
- R18 is C1-10 alkyl, C3-7 cycloalkyl, heterocyclyl, aryl, aryl1-10alkyl, heterocyclyl, heterocyclyl-C1-10alkyl, heteroaryl or heteroaryl1-10alkyl;
- or a pharmaceutically acceptable salt thereof.
28 more elements
A compound, or pharmaceutically acceptable salt thereof, which is:
- 2 22 R1 R2 methyl hydroxymethyl ethyl hydroxymethyl isopropyl hydroxymethyl 2-(methyl)propyl hydroxymethyl phenyl hydroxymethyl benzyl hydroxymethyl phenethyl hydroxymethyl methyl dimethylaminomethyl ethyl dimethylaminomethyl isopropyl dimethylaminomethyl 2-(methyl)propyl dimethylaminomethyl phenyl dimethylaminomethyl benzyl dimethylaminomethyl phenethyl dimethylaminomethyl methyl carboxy ethyl carboxy isopropyl carboxy 2-(methyl)propyl carboxy phenyl carboxy benzyl carboxy phenethyl carboxy methyl —CONH2 methyl —CONHMe methyl —CONMe2
A compound, or pharmaceutically acceptable salt thereof, which is:
- 3 23 R1 R2 methyl methoxymethyl methyl phenoxymethyl methyl benzyloxymethyl methyl carbamoyl methyl carbamoylmethyl methyl aminomethyl methyl N-(methyl)aminomethyl methyl N-(dimethyl)aminomethyl methyl N-(benzyl)aminomethyl methyl acetamidomethyl methyl benzamidomethyl methyl methanesulfonamidomethyl methyl benzenesulfonamidomethyi methyl phenylmethylsulfonamidomethyl methyl N′-ethylureidomethyl methyl N′-phenylureidomethyl methyl —CH2OCH2CH2Ph methyl —CONHPh methyl —CONHBn methyl —CH2OCH2(4-MePh) methyl —CH2OCH2(4-FPh) methyl —CH2OCH2(4-ClPh) methyl —CH2OCH2(3-ClPh) methyl —CH2O(4-MePh) methyl —CH2O(4-FPh) methyl —CH2O(4-ClPh) methyl —CH2O(3-ClPh) ethyl —CONH2 ethyl —CONHMe ethyl CONMe2 ethyl methoxymethyl ethyl phenoxymethyl ethyl benzyloxymethyl ethyl carbamoylmethyl ethyl carbamoylmethyl ethyl aminomethyl ethyl N-(methyl)aminomethyl ethyl N-(dimethyl)aminomethyl ethyl N-(benzyl)aminomethyl ethyl acetamidomethyl ethyl benzamidomethyl ethyl methanesulfonamidomethyl ethyl benzenesulfonamidomethyl ethyl phenylmethylsulfonamidomethyl ethyl N′-ethylureidomethyl ethyl N′-phenylureidomethyl ethyl —CH2OCH2CH2Ph ethyl —CONHPh ethyl —CONHBn ethyl —CH2OCH2(4-MePh) ethyl —CH2OCH2(4-FPh) ethyl —CH2OCH2(4-ClPh) ethyl —CH2OCH2(3-ClPh) ethyl —CH2O(4-MePh) ethyl —CH2O(4-FPh) ethyl —CH2O(4-ClPh) ethyl —CH2O(3-ClPh)
Dependencies are inferred from the claim text.