SK186599A3 - 2-substituted 4,5-diaryl imidazoles, process for their preparation, pharmaceutical composition containing them and their use - Google Patents
2-substituted 4,5-diaryl imidazoles, process for their preparation, pharmaceutical composition containing them and their use Download PDFInfo
- Publication number
- SK186599A3 SK186599A3 SK1865-99A SK186599A SK186599A3 SK 186599 A3 SK186599 A3 SK 186599A3 SK 186599 A SK186599 A SK 186599A SK 186599 A3 SK186599 A3 SK 186599A3
- Authority
- SK
- Slovakia
- Prior art keywords
- group
- carbon atoms
- pyridyl
- fluorophenyl
- imidazole
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 13
- 238000002360 preparation method Methods 0.000 title claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 65
- -1 alkylcycloalkenyl Chemical group 0.000 claims abstract description 57
- 125000001424 substituent group Chemical group 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 150000002148 esters Chemical group 0.000 claims abstract description 20
- 239000002253 acid Substances 0.000 claims abstract description 17
- 125000002619 bicyclic group Chemical group 0.000 claims abstract description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 14
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims abstract description 13
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 12
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 6
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 5
- 125000004665 trialkylsilyl group Chemical group 0.000 claims abstract description 5
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims abstract description 4
- 125000005110 aryl thio group Chemical group 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 64
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 15
- 150000007942 carboxylates Chemical class 0.000 claims description 15
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 6
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- 239000003018 immunosuppressive agent Substances 0.000 claims description 6
- 150000002576 ketones Chemical class 0.000 claims description 6
- KLHHFYHTAPSQFN-UHFFFAOYSA-N 2-[[5-(4-fluorophenyl)-4-pyridin-4-ylimidazol-1-yl]methoxy]ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCN1C=NC(C=2C=CN=CC=2)=C1C1=CC=C(F)C=C1 KLHHFYHTAPSQFN-UHFFFAOYSA-N 0.000 claims description 5
- 150000001299 aldehydes Chemical class 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000005936 piperidyl group Chemical group 0.000 claims description 5
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 4
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
- YXKXKUHMIZHMLM-UHFFFAOYSA-N 2,3,5,6-tetrafluoro-4-[4-(4-fluorophenyl)-5-pyridin-4-yl-1h-imidazol-2-yl]pyridine Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)NC(C=2C(=C(F)N=C(F)C=2F)F)=N1 YXKXKUHMIZHMLM-UHFFFAOYSA-N 0.000 claims description 4
- RTEHHLKYFIUUEN-UHFFFAOYSA-N 2-[[4-(4-fluorophenyl)-5-pyridin-4-ylimidazol-1-yl]methoxy]ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCN1C=NC(C=2C=CC(F)=CC=2)=C1C1=CC=NC=C1 RTEHHLKYFIUUEN-UHFFFAOYSA-N 0.000 claims description 4
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
- XIMIGUBYDJDCKI-UHFFFAOYSA-N diselenium Chemical compound [Se]=[Se] XIMIGUBYDJDCKI-UHFFFAOYSA-N 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 4
- 150000004820 halides Chemical class 0.000 claims description 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 4
- 229960003444 immunosuppressant agent Drugs 0.000 claims description 4
- 230000001861 immunosuppressant effect Effects 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Chemical group 0.000 claims description 4
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- JEWOUZJICLJHPM-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)-5-pyridin-4-yl-1h-imidazol-2-yl]cyclohexan-1-amine Chemical compound N=1C(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)NC=1C1(N)CCCCC1 JEWOUZJICLJHPM-UHFFFAOYSA-N 0.000 claims description 3
- UNIZPJWWWZTLDS-UHFFFAOYSA-N 3,5,6-trifluoro-4-[4-(4-fluorophenyl)-5-pyridin-4-yl-1h-imidazol-2-yl]pyridin-2-amine Chemical compound NC1=NC(F)=C(F)C(C=2NC(=C(N=2)C=2C=CC(F)=CC=2)C=2C=CN=CC=2)=C1F UNIZPJWWWZTLDS-UHFFFAOYSA-N 0.000 claims description 3
- STRAIBOPIVXLQO-UHFFFAOYSA-N 3,5-difluoro-4-[4-(4-fluorophenyl)-5-pyridin-4-yl-1h-imidazol-2-yl]pyridine-2,6-diamine Chemical compound NC1=NC(N)=C(F)C(C=2NC(=C(N=2)C=2C=CC(F)=CC=2)C=2C=CN=CC=2)=C1F STRAIBOPIVXLQO-UHFFFAOYSA-N 0.000 claims description 3
- 206010061218 Inflammation Diseases 0.000 claims description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
- DKNOJZGVJQZILW-UHFFFAOYSA-N 1-[4-(4-fluorophenyl)-5-pyridin-4-yl-1h-imidazol-2-yl]cyclohexan-1-ol Chemical compound N=1C(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)NC=1C1(O)CCCCC1 DKNOJZGVJQZILW-UHFFFAOYSA-N 0.000 claims description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 2
- CIWPUIAGXFUHHK-UHFFFAOYSA-N 4-[2-(4-butoxy-1-methylpiperidin-4-yl)-4-(4-fluorophenyl)-1h-imidazol-5-yl]pyridine Chemical compound N=1C(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)NC=1C1(OCCCC)CCN(C)CC1 CIWPUIAGXFUHHK-UHFFFAOYSA-N 0.000 claims description 2
- OIENJEGEDXPCRZ-UHFFFAOYSA-N 4-[2-(cyclohexen-1-yl)-4-(4-fluorophenyl)-1h-imidazol-5-yl]pyridine Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)NC(C=2CCCCC=2)=N1 OIENJEGEDXPCRZ-UHFFFAOYSA-N 0.000 claims description 2
- SIQUUVQVHIMYKO-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-5-pyridin-4-yl-1h-imidazol-2-yl]-1-methylpiperidin-4-ol Chemical compound C1CN(C)CCC1(O)C1=NC(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)N1 SIQUUVQVHIMYKO-UHFFFAOYSA-N 0.000 claims description 2
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- 229910005965 SO 2 Inorganic materials 0.000 claims description 2
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical class 0.000 claims description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000004546 quinazolin-4-yl group Chemical group N1=CN=C(C2=CC=CC=C12)* 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 229910052711 selenium Inorganic materials 0.000 claims description 2
- 239000011669 selenium Substances 0.000 claims description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 229910052714 tellurium Inorganic materials 0.000 claims description 2
- PORWMNRCUJJQNO-UHFFFAOYSA-N tellurium atom Chemical compound [Te] PORWMNRCUJJQNO-UHFFFAOYSA-N 0.000 claims description 2
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 2
- LVAKKFLGFCZOFC-UHFFFAOYSA-N 4-[2-(1,2-dicyclopropylethyl)-4-(4-fluorophenyl)-1h-imidazol-5-yl]pyridine Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)NC(C(CC2CC2)C2CC2)=N1 LVAKKFLGFCZOFC-UHFFFAOYSA-N 0.000 claims 1
- ZOAVMSMTFGCRQW-UHFFFAOYSA-N 4-[2-(cyclopropylmethyl)-4-(4-fluorophenyl)-1h-imidazol-5-yl]pyridine Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)NC(CC2CC2)=N1 ZOAVMSMTFGCRQW-UHFFFAOYSA-N 0.000 claims 1
- JVDIQZGPSNGXBD-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-2-phenylselanyl-1h-imidazol-5-yl]pyridine Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)NC([Se]C=2C=CC=CC=2)=N1 JVDIQZGPSNGXBD-UHFFFAOYSA-N 0.000 claims 1
- FOBNCXUJWKQKQI-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-2-phenylsulfanyl-1h-imidazol-5-yl]pyridine Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)NC(SC=2C=CC=CC=2)=N1 FOBNCXUJWKQKQI-UHFFFAOYSA-N 0.000 claims 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims 1
- 125000000000 cycloalkoxy group Chemical group 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 125000006413 ring segment Chemical group 0.000 claims 1
- 230000009466 transformation Effects 0.000 claims 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 abstract description 13
- 201000010099 disease Diseases 0.000 abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 13
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 abstract description 5
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 abstract description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 5
- 108010002352 Interleukin-1 Proteins 0.000 abstract description 4
- 102000000589 Interleukin-1 Human genes 0.000 abstract description 4
- 230000001404 mediated effect Effects 0.000 abstract description 4
- 102000043136 MAP kinase family Human genes 0.000 abstract description 3
- 108091054455 MAP kinase family Proteins 0.000 abstract description 3
- 208000001132 Osteoporosis Diseases 0.000 abstract description 3
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 abstract description 3
- 230000004097 bone metabolism Effects 0.000 abstract description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 239000003795 chemical substances by application Substances 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- 102100040247 Tumor necrosis factor Human genes 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 11
- 239000013078 crystal Substances 0.000 description 11
- 238000011282 treatment Methods 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 238000003556 assay Methods 0.000 description 8
- 150000001540 azides Chemical class 0.000 description 8
- 239000002158 endotoxin Substances 0.000 description 8
- 229920006008 lipopolysaccharide Polymers 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 208000023275 Autoimmune disease Diseases 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 230000001363 autoimmune Effects 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- MAOSUPNJVJGJEU-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-1h-imidazol-5-yl]pyridine Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)NC=N1 MAOSUPNJVJGJEU-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 208000027866 inflammatory disease Diseases 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- RINDIXSOILAVRZ-UHFFFAOYSA-N 4-[1-(diethoxymethyl)-5-(4-fluorophenyl)imidazol-4-yl]pyridine Chemical compound CCOC(OCC)N1C=NC(C=2C=CN=CC=2)=C1C1=CC=C(F)C=C1 RINDIXSOILAVRZ-UHFFFAOYSA-N 0.000 description 3
- ACRZFHMXFZBHRV-UHFFFAOYSA-N 4-[3-(diethoxymethyl)-5-(4-fluorophenyl)imidazol-4-yl]pyridine Chemical compound CCOC(OCC)N1C=NC(C=2C=CC(F)=CC=2)=C1C1=CC=NC=C1 ACRZFHMXFZBHRV-UHFFFAOYSA-N 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 3
- 230000006433 tumor necrosis factor production Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- VTFWVPMEQJEWSR-UHFFFAOYSA-N 2-bromo-1-(4-fluorophenyl)-2-pyridin-4-ylethanone;hydrobromide Chemical compound Br.C1=CC(F)=CC=C1C(=O)C(Br)C1=CC=NC=C1 VTFWVPMEQJEWSR-UHFFFAOYSA-N 0.000 description 2
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 206010006895 Cachexia Diseases 0.000 description 2
- 101100026251 Caenorhabditis elegans atf-2 gene Proteins 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 206010040070 Septic Shock Diseases 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 229940125721 immunosuppressive agent Drugs 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- XTGOWLIKIQLYRG-UHFFFAOYSA-N 2,3,4,5,6-pentafluoropyridine Chemical compound FC1=NC(F)=C(F)C(F)=C1F XTGOWLIKIQLYRG-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 1
- 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- CJHFNCCERODIHE-UHFFFAOYSA-N 4-fluoro-1-[[4-(4-fluorophenyl)-5-pyridin-4-yl-1h-imidazol-2-yl]methyl]cyclohexa-2,4-dien-1-ol Chemical compound N=1C(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)NC=1CC1(O)CC=C(F)C=C1 CJHFNCCERODIHE-UHFFFAOYSA-N 0.000 description 1
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 208000032467 Aplastic anaemia Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 206010071155 Autoimmune arthritis Diseases 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 208000018083 Bone metabolism disease Diseases 0.000 description 1
- JVDJXNBSVNTQGF-UHFFFAOYSA-N C1=CC(F)=CC=C1C(C=1C=CN=CC=1)C(=O)C(C=1C=CC(F)=CC=1)C1=CC=NC=C1 Chemical compound C1=CC(F)=CC=C1C(C=1C=CN=CC=1)C(=O)C(C=1C=CC(F)=CC=1)C1=CC=NC=C1 JVDJXNBSVNTQGF-UHFFFAOYSA-N 0.000 description 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 206010060742 Endocrine ophthalmopathy Diseases 0.000 description 1
- 206010014824 Endotoxic shock Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101150106931 IFNG gene Proteins 0.000 description 1
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 238000011795 OF1 mouse Methods 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 206010065159 Polychondritis Diseases 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 208000010399 Wasting Syndrome Diseases 0.000 description 1
- 208000016807 X-linked intellectual disability-macrocephaly-macroorchidism syndrome Diseases 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 208000002205 allergic conjunctivitis Diseases 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- ZHGASCUQXLPSDT-UHFFFAOYSA-N cyclohexanesulfonic acid Chemical compound OS(=O)(=O)C1CCCCC1 ZHGASCUQXLPSDT-UHFFFAOYSA-N 0.000 description 1
- 125000002243 cyclohexanonyl group Chemical group *C1(*)C(=O)C(*)(*)C(*)(*)C(*)(*)C1(*)* 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexyloxide Natural products O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004983 dialkoxyalkyl group Chemical group 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- KAKKHKRHCKCAGH-UHFFFAOYSA-L disodium;(4-nitrophenyl) phosphate;hexahydrate Chemical compound O.O.O.O.O.O.[Na+].[Na+].[O-][N+](=O)C1=CC=C(OP([O-])([O-])=O)C=C1 KAKKHKRHCKCAGH-UHFFFAOYSA-L 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 208000016036 idiopathic nephrotic syndrome Diseases 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 206010023332 keratitis Diseases 0.000 description 1
- 201000010666 keratoconjunctivitis Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 208000009928 nephrosis Diseases 0.000 description 1
- 231100001027 nephrosis Toxicity 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000004768 organ dysfunction Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 206010035653 pneumoconiosis Diseases 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 238000001896 rotating frame Overhauser effect spectroscopy Methods 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000002884 skin cream Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 208000018464 vernal keratoconjunctivitis Diseases 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9713726.9A GB9713726D0 (en) | 1997-06-30 | 1997-06-30 | Organic compounds |
| PCT/EP1998/003930 WO1999001449A1 (en) | 1997-06-30 | 1998-06-26 | 2-substituted 4,5-diaryl imidazoles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK186599A3 true SK186599A3 (en) | 2000-06-12 |
Family
ID=10815101
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1865-99A SK186599A3 (en) | 1997-06-30 | 1998-06-26 | 2-substituted 4,5-diaryl imidazoles, process for their preparation, pharmaceutical composition containing them and their use |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US6300347B1 (no) |
| EP (2) | EP0993456B1 (no) |
| JP (1) | JP3704362B2 (no) |
| KR (1) | KR20010013215A (no) |
| CN (1) | CN1261885A (no) |
| AR (1) | AR014886A1 (no) |
| AT (1) | ATE275557T1 (no) |
| AU (1) | AU744411B2 (no) |
| BR (1) | BR9810955A (no) |
| CA (1) | CA2291758A1 (no) |
| CO (1) | CO4940462A1 (no) |
| DE (1) | DE69826127T2 (no) |
| ES (1) | ES2226164T3 (no) |
| GB (1) | GB9713726D0 (no) |
| HU (1) | HUP0003351A3 (no) |
| ID (1) | ID23385A (no) |
| IL (1) | IL133034A0 (no) |
| NO (1) | NO996429L (no) |
| NZ (1) | NZ501275A (no) |
| PE (1) | PE99999A1 (no) |
| PL (1) | PL337057A1 (no) |
| PT (1) | PT993456E (no) |
| RU (1) | RU2214408C2 (no) |
| SK (1) | SK186599A3 (no) |
| TR (1) | TR199903278T2 (no) |
| TW (1) | TW429258B (no) |
| WO (1) | WO1999001449A1 (no) |
| ZA (1) | ZA985656B (no) |
Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998007425A1 (en) | 1996-08-21 | 1998-02-26 | Smithkline Beecham Corporation | Imidazole compounds, compositions and use |
| US7301021B2 (en) | 1997-07-02 | 2007-11-27 | Smithkline Beecham Corporation | Substituted imidazole compounds |
| EP1119254A4 (en) | 1998-10-07 | 2004-05-12 | Smithkline Beecham Corp | STROKE TREATMENT |
| IL143236A0 (en) * | 1998-12-16 | 2002-04-21 | Warner Lambert Co | Treatment of arthritis with mek inhibitors |
| AU765473B2 (en) * | 1999-04-23 | 2003-09-18 | Takeda Pharmaceutical Company Limited | 5-pyridyl-1,3-azole compounds, process for producing the same and use thereof |
| ATE425142T1 (de) * | 1999-04-23 | 2009-03-15 | Vertex Pharma | Inhibitoren von c-jun n-terminal kinasen (jnk) |
| US6291457B1 (en) | 1999-07-01 | 2001-09-18 | Merck & Co., Inc. | Compounds having cytokine inhibitory activity |
| US7122666B2 (en) | 1999-07-21 | 2006-10-17 | Sankyo Company, Limited | Heteroaryl-substituted pyrrole derivatives, their preparation and their therapeutic uses |
| ES2254238T3 (es) * | 1999-10-27 | 2006-06-16 | Novartis Ag | Compuestos de tiazol e imidazo(4,5-b)piridina y su uso farmaceutico. |
| PT1140939E (pt) | 1999-11-10 | 2005-05-31 | Ortho Mcneil Pharm Inc | 2-aril-3-(heteroaril)- imidazo [1,2-alfa] pirimidinas substituidas, e formulacoes farmaceuticas e metodos relacionados |
| US6808902B1 (en) | 1999-11-12 | 2004-10-26 | Amgen Inc. | Process for correction of a disulfide misfold in IL-1Ra Fc fusion molecules |
| WO2001037835A1 (en) * | 1999-11-22 | 2001-05-31 | Smithkline Beecham Plc. | Novel compounds |
| WO2001038312A1 (en) | 1999-11-23 | 2001-05-31 | Smithkline Beecham Corporation | 3,4-DIHYDRO-(1H)QUINAZOLIN-2-ONE COMPOUNDS AS CSBP/p38 KINASE INHIBITORS |
| US7612065B2 (en) | 2000-04-21 | 2009-11-03 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-JUN N-terminal kinases (JNK) |
| ES2251582T3 (es) | 2001-03-09 | 2006-05-01 | Pfizer Products Inc. | Compuestos antiinflamatorios de bencimidazol. |
| ATE323701T1 (de) | 2001-03-09 | 2006-05-15 | Pfizer Prod Inc | Triazolopyridine als entzündungshemmende mittel |
| ATE304009T1 (de) | 2001-04-04 | 2005-09-15 | Pfizer Prod Inc | Neue benzotriazole mit entzündungshemmender wirkung |
| YU103003A (sh) | 2001-06-26 | 2006-05-25 | Abgenix Inc. | Antitela za opgl |
| MXPA04003729A (es) * | 2001-10-22 | 2004-07-23 | Tanabe Seiyaku Co | Compuestos de 4-imidazolin-2-ona. |
| AR039241A1 (es) | 2002-04-04 | 2005-02-16 | Biogen Inc | Heteroarilos trisustituidos y metodos para su produccion y uso de los mismos |
| DE10222103A1 (de) * | 2002-05-17 | 2003-11-27 | Merckle Gmbh Chem Pharm Fabrik | 2-Thio-substituierte Imidazolderivate und ihre Verwendung in der Pharmazie |
| DE60310730T2 (de) | 2002-07-09 | 2007-05-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmazeutische zusammensetzungen aus anticholinergica und p38 kinase hemmern zur behandlung von erkrankungen der atemwege |
| US6949652B2 (en) | 2002-08-30 | 2005-09-27 | Pfizer, Inc. | Crystalline forms of 3-isopropyl-6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-[1,2,4]triazolo-[4,3-A]pyridine |
| US7012143B2 (en) | 2002-08-30 | 2006-03-14 | Dombroski Mark A | Cycloalkyl-[4-(difluorophenyl)-oxazol-5-yl]-triazolo-pyridines |
| PA8579601A1 (es) | 2002-08-30 | 2004-05-07 | Pfizer Prod Inc | Compuestos antiinflamatorios de di y trifloruro-triazolo-piridinas |
| US7005523B2 (en) | 2002-08-30 | 2006-02-28 | Pfizer Inc. | Cycloalkyl-[4-(trifluorophenyl)-oxazol-5yl]-triazolo-pyridines |
| US7037923B2 (en) | 2002-08-30 | 2006-05-02 | Pfizer, Inc. | Alkyl-[4-(trifluorophenyl)-oxazol-5-yl]-triazolo-pyridines |
| UA80295C2 (en) | 2002-09-06 | 2007-09-10 | Biogen Inc | Pyrazolopyridines and using the same |
| AU2003299652A1 (en) * | 2002-12-06 | 2004-06-30 | Scios Inc. | Methods for treating diabetes |
| JP2006516548A (ja) | 2002-12-30 | 2006-07-06 | アンジオテック インターナショナル アクツィエン ゲゼルシャフト | 迅速ゲル化ポリマー組成物からの薬物送達法 |
| JP2006522128A (ja) * | 2003-04-03 | 2006-09-28 | メルク エンド カムパニー インコーポレーテッド | 代謝調節型グルタミン酸受容体−５のモジュレーターとしての４環イミダゾール誘導体 |
| US7344716B2 (en) * | 2003-05-13 | 2008-03-18 | Depuy Spine, Inc. | Transdiscal administration of specific inhibitors of pro-inflammatory cytokines |
| US20040229878A1 (en) * | 2003-05-13 | 2004-11-18 | Depuy Spine, Inc. | Transdiscal administration of specific inhibitors of P38 kinase |
| US8273347B2 (en) * | 2003-05-13 | 2012-09-25 | Depuy Spine, Inc. | Autologous treatment of degenerated disc with cells |
| US7553827B2 (en) * | 2003-08-13 | 2009-06-30 | Depuy Spine, Inc. | Transdiscal administration of cycline compounds |
| US8361467B2 (en) | 2003-07-30 | 2013-01-29 | Depuy Spine, Inc. | Trans-capsular administration of high specificity cytokine inhibitors into orthopedic joints |
| US7253164B2 (en) * | 2003-07-31 | 2007-08-07 | Irm Llc | Bicyclic compounds and compositions as PDF inhibitors |
| JP2007507540A (ja) | 2003-10-02 | 2007-03-29 | アイアールエム・リミテッド・ライアビリティ・カンパニー | タンパク質キナーゼ阻害剤としての化合物および組成物 |
| US8895540B2 (en) | 2003-11-26 | 2014-11-25 | DePuy Synthes Products, LLC | Local intraosseous administration of bone forming agents and anti-resorptive agents, and devices therefor |
| WO2005063716A1 (en) | 2003-12-22 | 2005-07-14 | Janssen Pharmaceutica, N.V. | Imidazoles and their use cck-1 receptor modulators |
| US20060035893A1 (en) | 2004-08-07 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders |
| US7713998B2 (en) | 2004-11-10 | 2010-05-11 | Ono Pharmaceutical Co., Ltd. | Nitrogenous heterocyclic compound and pharmaceutical use thereof |
| PE20060777A1 (es) | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas |
| ATE469893T1 (de) * | 2005-02-28 | 2010-06-15 | Merckle Gmbh | 2-sulfinyl- und 2-sulfonyl-substituierte imidazolderivate und deren verwendung als cytokininhibitoren |
| US7968572B2 (en) | 2005-10-03 | 2011-06-28 | Ono Pharmaceuticals Co., Ltd. | Nitrogen-containing heterocyclic compound and pharmaceutical application thereof |
| JP5324785B2 (ja) | 2005-10-28 | 2013-10-23 | 武田薬品工業株式会社 | 複素環アミド化合物及びその用途 |
| ES2301380B1 (es) | 2006-08-09 | 2009-06-08 | Laboratorios Almirall S.A. | Nuevos derivados de 1,7-naftiridina. |
| ES2320955B1 (es) | 2007-03-02 | 2010-03-16 | Laboratorios Almirall S.A. | Nuevos derivados de 3-((1,2,4)triazolo(4,3-a)piridin-7-il)benzamida. |
| ES2329639B1 (es) | 2007-04-26 | 2010-09-23 | Laboratorios Almirall S.A. | Nuevos derivados de 4,8-difenilpoliazanaftaleno. |
| EP1992344A1 (en) | 2007-05-18 | 2008-11-19 | Institut Curie | P38 alpha as a therapeutic target in pathologies linked to FGFR3 mutation |
| AU2008261030A1 (en) * | 2007-06-05 | 2008-12-11 | Western States Biopharmaceuticals, Inc. | T-cell cytokine-inducing surface molecules and methods of use |
| US8986696B2 (en) * | 2007-12-21 | 2015-03-24 | Depuy Mitek, Inc. | Trans-capsular administration of p38 map kinase inhibitors into orthopedic joints |
| US20090162351A1 (en) * | 2007-12-21 | 2009-06-25 | Depuy Spine, Inc. | Transdiscal administration of inhibitors of p38 MAP kinase |
| EP2108641A1 (en) | 2008-04-11 | 2009-10-14 | Laboratorios Almirall, S.A. | New substituted spiro[cycloalkyl-1,3'-indo]-2'(1'H)-one derivatives and their use as p38 mitogen-activated kinase inhibitors |
| EP2113503A1 (en) | 2008-04-28 | 2009-11-04 | Laboratorios Almirall, S.A. | New substituted indolin-2-one derivatives and their use as p39 mitogen-activated kinase inhibitors |
| TWI435874B (zh) * | 2008-10-31 | 2014-05-01 | Toray Industries | 環己烷衍生物及其醫藥用途 |
| EP2322176A1 (en) | 2009-11-11 | 2011-05-18 | Almirall, S.A. | New 7-phenyl-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one derivatives |
| EP2516668B1 (en) * | 2009-12-22 | 2016-04-06 | Csir | Inhibition of the activity of kinase and synthetase enzymes |
| US20130018039A1 (en) * | 2010-03-31 | 2013-01-17 | Bodmer Vera Q | Imidazolyl-imidazoles as kinase inhibitors |
| WO2017151409A1 (en) | 2016-02-29 | 2017-09-08 | University Of Florida Research Foundation, Incorporated | Chemotherapeutic methods |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69322254T2 (de) * | 1992-01-13 | 1999-04-29 | Smithkline Beecham Corp., Philadelphia, Pa. 19101 | Pyridyl-substituierte imidazole |
| IL104369A0 (en) * | 1992-01-13 | 1993-05-13 | Smithkline Beecham Corp | Novel compounds and compositions |
| US5916891A (en) | 1992-01-13 | 1999-06-29 | Smithkline Beecham Corporation | Pyrimidinyl imidazoles |
| ZA945363B (en) * | 1993-07-21 | 1995-03-14 | Smithkline Beecham Corp | Novel compounds |
| US5620999A (en) * | 1994-07-28 | 1997-04-15 | Weier; Richard M. | Benzenesulfonamide subtituted imidazolyl compounds for the treatment of inflammation |
| US5717100A (en) * | 1995-10-06 | 1998-02-10 | Merck & Co., Inc. | Substituted imidazoles having anti-cancer and cytokine inhibitory activity |
| JP3382951B2 (ja) * | 1995-10-06 | 2003-03-04 | メルク エンド カムパニー インコーポレーテッド | 抗がん活性及びサイトカン阻害活性を有する置換イミダゾール |
| US5965583A (en) | 1997-04-24 | 1999-10-12 | Ortho-Mcneil Pharmaceutical, Inc. | Substituted imidazoles useful in the treatment of inflammatory disease |
| CZ9904452A3 (cs) | 1997-06-12 | 2002-02-13 | Rhone-Poulenc Rorer Limited | Cyklické acetaly imidazolylu, způsob jejich přípravy, jejich pouľití a farmaceutický prostředek, který je obsahuje |
| US6610695B1 (en) | 1997-06-19 | 2003-08-26 | Smithkline Beecham Corporation | Aryloxy substituted pyrimidine imidazole compounds |
| KR20010014288A (ko) | 1997-06-30 | 2001-02-26 | 오르토-맥네일 파마슈티칼, 인코퍼레이티드 | 염증성 질환의 치료에 유용한 2-치환된 이미다졸 |
| AU8381098A (en) | 1997-07-02 | 1999-01-25 | Smithkline Beecham Corporation | Novel cycloalkyl substituted imidazoles |
| TW517055B (en) | 1997-07-02 | 2003-01-11 | Smithkline Beecham Corp | Novel substituted imidazole compounds |
| AR016294A1 (es) | 1997-07-02 | 2001-07-04 | Smithkline Beecham Corp | Compuesto de imidazol sustituido, composicion farmaceutica que la contiene, su uso en la fabricacion de un medicamento y procedimiento para supreparacion |
| FR2772377B1 (fr) | 1997-12-12 | 2000-01-07 | Synthelabo | Derives de 1-(1-h-imidazol-2-yl)pyrrolidines et 1-(1-h-imidazol-2-ylpiperidines), leur preparation et leur application en therapeutique |
-
1997
- 1997-06-30 GB GBGB9713726.9A patent/GB9713726D0/en active Pending
-
1998
- 1998-06-11 TW TW087109301A patent/TW429258B/zh active
- 1998-06-25 CO CO98036362A patent/CO4940462A1/es unknown
- 1998-06-26 CA CA002291758A patent/CA2291758A1/en not_active Abandoned
- 1998-06-26 EP EP98939541A patent/EP0993456B1/en not_active Expired - Lifetime
- 1998-06-26 EP EP03026996A patent/EP1396491A3/en not_active Withdrawn
- 1998-06-26 AU AU88015/98A patent/AU744411B2/en not_active Ceased
- 1998-06-26 US US09/446,885 patent/US6300347B1/en not_active Expired - Fee Related
- 1998-06-26 NZ NZ501275A patent/NZ501275A/en unknown
- 1998-06-26 ID IDW991681A patent/ID23385A/id unknown
- 1998-06-26 PT PT98939541T patent/PT993456E/pt unknown
- 1998-06-26 BR BR9810955-3A patent/BR9810955A/pt not_active IP Right Cessation
- 1998-06-26 RU RU2000101820/04A patent/RU2214408C2/ru not_active IP Right Cessation
- 1998-06-26 SK SK1865-99A patent/SK186599A3/sk unknown
- 1998-06-26 IL IL13303498A patent/IL133034A0/xx unknown
- 1998-06-26 JP JP50628899A patent/JP3704362B2/ja not_active Expired - Fee Related
- 1998-06-26 PL PL98337057A patent/PL337057A1/xx unknown
- 1998-06-26 HU HU0003351A patent/HUP0003351A3/hu unknown
- 1998-06-26 PE PE1998000569A patent/PE99999A1/es not_active Application Discontinuation
- 1998-06-26 WO PCT/EP1998/003930 patent/WO1999001449A1/en not_active Application Discontinuation
- 1998-06-26 KR KR19997011203A patent/KR20010013215A/ko not_active Application Discontinuation
- 1998-06-26 AT AT98939541T patent/ATE275557T1/de not_active IP Right Cessation
- 1998-06-26 ES ES98939541T patent/ES2226164T3/es not_active Expired - Lifetime
- 1998-06-26 TR TR1999/03278T patent/TR199903278T2/xx unknown
- 1998-06-26 DE DE69826127T patent/DE69826127T2/de not_active Expired - Fee Related
- 1998-06-26 CN CN98806673A patent/CN1261885A/zh active Pending
- 1998-06-26 AR ARP980103093A patent/AR014886A1/es unknown
- 1998-06-29 ZA ZA985656A patent/ZA985656B/xx unknown
-
1999
- 1999-12-23 NO NO996429A patent/NO996429L/no not_active Application Discontinuation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK186599A3 (en) | 2-substituted 4,5-diaryl imidazoles, process for their preparation, pharmaceutical composition containing them and their use | |
| DE69723104T2 (de) | Piridin-2-yl-methylamin-derivate, verfahren zu deren herstellung und ihre verwendung als arzneimittel | |
| DE60003709T2 (de) | Substituierte azole | |
| JP3000674B2 (ja) | ジヒドロピラゾロピロール類 | |
| US6608072B1 (en) | Thiazole compounds and their pharmaceutical use | |
| DE69030206T2 (de) | Pyrazolopyridinverbindungen und Verfahren zu ihrer Herstellung | |
| TWI449696B (zh) | 以５員雜環為主之ｐ３８激酶抑制劑 | |
| DE69123784T2 (de) | Benzimidazolderivate, Verfahren zu deren Herstellung und Anwendung | |
| WO2000026209A1 (en) | Anti-inflammatory 4-phenyl-5-pyrimidinyl-imidazoles | |
| US4772596A (en) | Dihydropyridine derivatives, their preparation and their use | |
| DE69212346T2 (de) | Diazotierte heterocyclische Derivate aus Stickstoff, substituiert durch eine Biphenylgruppe, ihre Herstellung, und diese enthaltende pharmazeutische Zubereitungen | |
| DE69912618T2 (de) | NEUE THIENO[2,3-d]PYRIMIDINDIONE, VERFAHREN FÜR IHRE HERSTELLUNG UND IHRE VERWENDUNG IN DER THERAPIE | |
| KR20070007361A (ko) | 1-아미노-프탈라진 유도체, 이의 제조 방법 및 치료적 용도 | |
| DE60025848T2 (de) | Pyrimidin-derivate als selective inhibitoren von cox-2 | |
| EP2086551A2 (en) | Thrombopoietin mimetics | |
| SK182799A3 (en) | Azetidinylpropylpiperidine derivatives, intermediates and use as tachykinin antagonists | |
| DE60305053T2 (de) | Pyrimidinderivate als selektive cox-2-inhibitoren | |
| DE3852332T2 (de) | 4-Thiochinazolin-Derivate, Verfahren zu deren Herstellung und pharmazeutische Zusammenstellungen. | |
| DE60220779T2 (de) | Tetrahydropyridyl-alkyl-heterozykle, verfahren zu ihrer herstellung und pharmazeutische zusammensetzungen die sie enthalten | |
| CZ474199A3 (cs) | 4,5-diarylimidazoly substituované v poloze 2, způsob jejich přípravy a farmaceutické prostředky, které je obsahují | |
| KR20050018947A (ko) | 퀴나졸린 유도체 | |
| JPH0625250A (ja) | チエノ〔３，４−ｄ〕イミダゾール誘導体、その製造法およびそれを含有する循環器官用剤 | |
| HUT64056A (en) | Process for producing sulfonylbenzyl-substituted imidazolylpropenoic acid derivatives and pharmaceutical compositions comprising same | |
| MXPA99011411A (en) | 2-substituted 4,5-diaryl imidazoles | |
| DE69010772T2 (de) | 1,2,4-Triazolderivate, ihre Herstellung und ihre Verwendung in der Behandlung von Bluthochdruck oder von Atemwegserkrankungen. |