JP4865702B2 - サイトカイン阻害剤 - Google Patents
サイトカイン阻害剤 Download PDFInfo
- Publication number
- JP4865702B2 JP4865702B2 JP2007511450A JP2007511450A JP4865702B2 JP 4865702 B2 JP4865702 B2 JP 4865702B2 JP 2007511450 A JP2007511450 A JP 2007511450A JP 2007511450 A JP2007511450 A JP 2007511450A JP 4865702 B2 JP4865702 B2 JP 4865702B2
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- methyl
- optionally
- alkoxy
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 102000004127 Cytokines Human genes 0.000 title description 44
- 108090000695 Cytokines Proteins 0.000 title description 44
- 239000003112 inhibitor Substances 0.000 title description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 244
- 150000001875 compounds Chemical class 0.000 claims description 99
- 125000003545 alkoxy group Chemical group 0.000 claims description 81
- -1 hydroxy, hydroxy Chemical group 0.000 claims description 75
- 229910052739 hydrogen Inorganic materials 0.000 claims description 56
- 239000001257 hydrogen Substances 0.000 claims description 54
- 125000000623 heterocyclic group Chemical group 0.000 claims description 48
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 42
- 150000002431 hydrogen Chemical class 0.000 claims description 39
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 150000002825 nitriles Chemical class 0.000 claims description 36
- 125000002252 acyl group Chemical group 0.000 claims description 35
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 35
- 125000001072 heteroaryl group Chemical group 0.000 claims description 34
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 150000002367 halogens Chemical class 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 125000003342 alkenyl group Chemical group 0.000 claims description 29
- 125000003282 alkyl amino group Chemical group 0.000 claims description 29
- 125000004043 oxo group Chemical group O=* 0.000 claims description 29
- 125000003386 piperidinyl group Chemical group 0.000 claims description 28
- 125000002757 morpholinyl group Chemical group 0.000 claims description 27
- 125000004076 pyridyl group Chemical group 0.000 claims description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
- 125000004193 piperazinyl group Chemical group 0.000 claims description 23
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 23
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 22
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
- 125000002883 imidazolyl group Chemical group 0.000 claims description 17
- JNFIHXJPZSKVII-UHFFFAOYSA-N 1-methyl-7-pyridin-4-yloxyindole-2-carboxylic acid Chemical compound C=12N(C)C(C(O)=O)=CC2=CC=CC=1OC1=CC=NC=C1 JNFIHXJPZSKVII-UHFFFAOYSA-N 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 125000004423 acyloxy group Chemical group 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 16
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 15
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 14
- 125000004442 acylamino group Chemical group 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000001425 triazolyl group Chemical group 0.000 claims description 13
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 12
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 11
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 11
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 11
- 150000001356 alkyl thiols Chemical class 0.000 claims description 10
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 9
- 125000002971 oxazolyl group Chemical group 0.000 claims description 9
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 9
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 9
- 125000000335 thiazolyl group Chemical group 0.000 claims description 9
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 9
- WCNFFKHKJLERFM-UHFFFAOYSA-N thiomorpholinyl sulfone group Chemical group N1(CCSCC1)S(=O)(=O)N1CCSCC1 WCNFFKHKJLERFM-UHFFFAOYSA-N 0.000 claims description 9
- ZCAGUOCUDGWENZ-UHFFFAOYSA-N thiomorpholinyl sulfoxide group Chemical group N1(CCSCC1)S(=O)N1CCSCC1 ZCAGUOCUDGWENZ-UHFFFAOYSA-N 0.000 claims description 9
- 150000001408 amides Chemical class 0.000 claims description 7
- 125000004069 aziridinyl group Chemical group 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 7
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 7
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- FFFYPQJYPMJWJY-UHFFFAOYSA-N 1-methyl-7-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]oxyindole-2-carboxylic acid Chemical compound C1CN(C)CCN1C1=CC(OC=2C=3N(C)C(C(O)=O)=CC=3C=CC=2)=CC=N1 FFFYPQJYPMJWJY-UHFFFAOYSA-N 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 5
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 5
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 claims description 5
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 claims description 5
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 5
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
- 125000004276 dioxalanyl group Chemical group 0.000 claims description 5
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 5
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 5
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 5
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 5
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 5
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 5
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 5
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 5
- ISXOBTBCNRIIQO-UHFFFAOYSA-N tetrahydrothiophene 1-oxide Chemical compound O=S1CCCC1 ISXOBTBCNRIIQO-UHFFFAOYSA-N 0.000 claims description 5
- BUGOPWGPQGYYGR-UHFFFAOYSA-N thiane 1,1-dioxide Chemical compound O=S1(=O)CCCCC1 BUGOPWGPQGYYGR-UHFFFAOYSA-N 0.000 claims description 5
- NNLBRYQGMOYARS-UHFFFAOYSA-N thiane 1-oxide Chemical compound O=S1CCCCC1 NNLBRYQGMOYARS-UHFFFAOYSA-N 0.000 claims description 5
- YFHICDDUDORKJB-UHFFFAOYSA-N trimethylene carbonate Chemical compound O=C1OCCCO1 YFHICDDUDORKJB-UHFFFAOYSA-N 0.000 claims description 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 4
- 125000003435 aroyl group Chemical group 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000005605 benzo group Chemical group 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- PJQFFBWOBHJRSE-UHFFFAOYSA-N n-(5-tert-butyl-2-methylpyridin-3-yl)-1-methyl-7-pyridin-4-yloxyindole-2-carboxamide Chemical compound CC1=NC=C(C(C)(C)C)C=C1NC(=O)C1=CC2=CC=CC(OC=3C=CN=CC=3)=C2N1C PJQFFBWOBHJRSE-UHFFFAOYSA-N 0.000 claims description 2
- FNYZOSLTEFIJEE-UHFFFAOYSA-N n-(5-tert-butyl-2-methylsulfinylphenyl)-1-methyl-7-pyridin-4-yloxyindole-2-carboxamide Chemical compound C=12N(C)C(C(=O)NC=3C(=CC=C(C=3)C(C)(C)C)S(C)=O)=CC2=CC=CC=1OC1=CC=NC=C1 FNYZOSLTEFIJEE-UHFFFAOYSA-N 0.000 claims description 2
- RQKSFNAHXUEHEM-UHFFFAOYSA-N n-(5-tert-butyl-2-methylsulfonylphenyl)-1-methyl-7-pyridin-4-yloxyindole-2-carboxamide Chemical compound C=12N(C)C(C(=O)NC=3C(=CC=C(C=3)C(C)(C)C)S(C)(=O)=O)=CC2=CC=CC=1OC1=CC=NC=C1 RQKSFNAHXUEHEM-UHFFFAOYSA-N 0.000 claims description 2
- QXMRVSNDXLZRDT-UHFFFAOYSA-N n-(5-tert-butyl-2-oxo-1h-pyridin-3-yl)-1-methyl-7-pyridin-4-yloxyindole-2-carboxamide Chemical compound C=12N(C)C(C(=O)NC=3C(NC=C(C=3)C(C)(C)C)=O)=CC2=CC=CC=1OC1=CC=NC=C1 QXMRVSNDXLZRDT-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- 150000003536 tetrazoles Chemical class 0.000 claims description 2
- 150000003852 triazoles Chemical class 0.000 claims description 2
- 230000003796 beauty Effects 0.000 claims 2
- CDKZKAUOODOSCT-UHFFFAOYSA-N 1-methyl-7-[2-(4-methylpiperazin-1-yl)pyrimidin-4-yl]oxyindole-2-carboxylic acid Chemical compound C1CN(C)CCN1C1=NC=CC(OC=2C=3N(C)C(C(O)=O)=CC=3C=CC=2)=N1 CDKZKAUOODOSCT-UHFFFAOYSA-N 0.000 claims 1
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- SQLZBXYFLQKKFE-UHFFFAOYSA-N n-(2-tert-butyl-5-methoxypyridin-4-yl)-1-methyl-7-[2-(4-methylpiperazin-1-yl)pyrimidin-4-yl]oxyindole-2-carboxamide Chemical compound COC1=CN=C(C(C)(C)C)C=C1NC(=O)C1=CC2=CC=CC(OC=3N=C(N=CC=3)N3CCN(C)CC3)=C2N1C SQLZBXYFLQKKFE-UHFFFAOYSA-N 0.000 claims 1
- RGEHOVSPXMOFJS-UHFFFAOYSA-N n-(2-tert-butyl-5-methylsulfinylpyridin-4-yl)-1-methyl-7-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]oxyindole-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC(OC=2C=3N(C)C(C(=O)NC=4C(=CN=C(C=4)C(C)(C)C)S(C)=O)=CC=3C=CC=2)=CC=N1 RGEHOVSPXMOFJS-UHFFFAOYSA-N 0.000 claims 1
- FTPSXZOTFCPGEY-UHFFFAOYSA-N n-(5-tert-butyl-2-methylpyridin-3-yl)-1-methyl-7-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]oxyindole-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC(OC=2C=3N(C)C(C(=O)NC=4C(=NC=C(C=4)C(C)(C)C)C)=CC=3C=CC=2)=CC=N1 FTPSXZOTFCPGEY-UHFFFAOYSA-N 0.000 claims 1
- JGBCDDNLVNNVDP-UHFFFAOYSA-N n-(5-tert-butyl-2-methylpyridin-3-yl)-1-methyl-7-[2-(4-methylpiperazin-1-yl)pyrimidin-4-yl]oxyindole-2-carboxamide Chemical compound C1CN(C)CCN1C1=NC=CC(OC=2C=3N(C)C(C(=O)NC=4C(=NC=C(C=4)C(C)(C)C)C)=CC=3C=CC=2)=N1 JGBCDDNLVNNVDP-UHFFFAOYSA-N 0.000 claims 1
- VHPRXLOYYSAIRC-UHFFFAOYSA-N n-(5-tert-butyl-3-cyano-2-methoxyphenyl)-1-methyl-7-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]oxyindole-2-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(C#N)C(OC)=C1NC(=O)C1=CC2=CC=CC(OC=3C=C(N=CC=3)N3CCN(C)CC3)=C2N1C VHPRXLOYYSAIRC-UHFFFAOYSA-N 0.000 claims 1
- CWWSWNHORYIAPS-UHFFFAOYSA-N n-(5-tert-butyl-3-cyano-2-methoxyphenyl)-1-methyl-7-[2-(4-methylpiperazin-1-yl)pyrimidin-4-yl]oxyindole-2-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(C#N)C(OC)=C1NC(=O)C1=CC2=CC=CC(OC=3N=C(N=CC=3)N3CCN(C)CC3)=C2N1C CWWSWNHORYIAPS-UHFFFAOYSA-N 0.000 claims 1
- KZPVENRWOMYPGP-UHFFFAOYSA-N n-(5-tert-butyl-3-cyano-2-methoxyphenyl)-1-methyl-7-pyridin-4-yloxyindole-2-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(C#N)C(OC)=C1NC(=O)C1=CC2=CC=CC(OC=3C=CN=CC=3)=C2N1C KZPVENRWOMYPGP-UHFFFAOYSA-N 0.000 claims 1
- BXBOQEWXJKZESY-UHFFFAOYSA-N n-[3-(methanesulfonamido)-2-methoxy-5-(1-methylcyclopropyl)phenyl]-1-methyl-7-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]oxyindole-2-carboxamide Chemical compound C1=C(C2(C)CC2)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C(N(C1=2)C)=CC1=CC=CC=2OC(C=1)=CC=NC=1N1CCN(C)CC1 BXBOQEWXJKZESY-UHFFFAOYSA-N 0.000 claims 1
- PXQNKJOHICMOCU-UHFFFAOYSA-N n-[6-tert-butyl-2-(methanesulfonamido)-3-methoxypyridin-4-yl]-1-methyl-7-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]oxyindole-2-carboxamide Chemical compound C1=C(C(C)(C)C)N=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC2=CC=CC(OC=3C=C(N=CC=3)N3CCN(C)CC3)=C2N1C PXQNKJOHICMOCU-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 135
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
- 239000000243 solution Substances 0.000 description 99
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 68
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 61
- 235000019439 ethyl acetate Nutrition 0.000 description 51
- 239000007787 solid Substances 0.000 description 50
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 49
- 201000010099 disease Diseases 0.000 description 48
- 239000000203 mixture Substances 0.000 description 44
- 229920006395 saturated elastomer Polymers 0.000 description 44
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 39
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 39
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 38
- 229910052938 sodium sulfate Inorganic materials 0.000 description 38
- 235000011152 sodium sulphate Nutrition 0.000 description 38
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 238000000034 method Methods 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- 238000011282 treatment Methods 0.000 description 29
- 239000012044 organic layer Substances 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
- 239000010410 layer Substances 0.000 description 24
- 102000000589 Interleukin-1 Human genes 0.000 description 23
- 108010002352 Interleukin-1 Proteins 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 238000000746 purification Methods 0.000 description 21
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
- 239000000284 extract Substances 0.000 description 19
- 230000015572 biosynthetic process Effects 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 16
- 238000010898 silica gel chromatography Methods 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- 230000004054 inflammatory process Effects 0.000 description 15
- 206010028980 Neoplasm Diseases 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 206010061218 Inflammation Diseases 0.000 description 13
- 102000004889 Interleukin-6 Human genes 0.000 description 13
- 108090001005 Interleukin-6 Proteins 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 230000001404 mediated effect Effects 0.000 description 11
- 230000000770 proinflammatory effect Effects 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 239000012267 brine Substances 0.000 description 10
- 230000006378 damage Effects 0.000 description 10
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 10
- 230000002757 inflammatory effect Effects 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 9
- 239000005909 Kieselgur Substances 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 208000014674 injury Diseases 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 8
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 230000001154 acute effect Effects 0.000 description 8
- 230000014509 gene expression Effects 0.000 description 8
- 230000008506 pathogenesis Effects 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 230000008733 trauma Effects 0.000 description 8
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 8
- 108090001007 Interleukin-8 Proteins 0.000 description 7
- 102000004890 Interleukin-8 Human genes 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 102100026018 Interleukin-1 receptor antagonist protein Human genes 0.000 description 6
- 101710144554 Interleukin-1 receptor antagonist protein Proteins 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- 210000000988 bone and bone Anatomy 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000013456 study Methods 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 6
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 5
- 208000024827 Alzheimer disease Diseases 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- 239000007821 HATU Substances 0.000 description 5
- 241000725303 Human immunodeficiency virus Species 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 239000000908 ammonium hydroxide Substances 0.000 description 5
- 201000006417 multiple sclerosis Diseases 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 208000006386 Bone Resorption Diseases 0.000 description 4
- 206010006895 Cachexia Diseases 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 4
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 4
- 206010040070 Septic Shock Diseases 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 4
- 208000038016 acute inflammation Diseases 0.000 description 4
- 230000006022 acute inflammation Effects 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000024279 bone resorption Effects 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 208000037976 chronic inflammation Diseases 0.000 description 4
- 239000002158 endotoxin Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- BQSXYDIZGSJTDO-UHFFFAOYSA-N ethyl 7-(2-chloropyridin-4-yl)oxy-1-methylindole-2-carboxylate Chemical compound C=12N(C)C(C(=O)OCC)=CC2=CC=CC=1OC1=CC=NC(Cl)=C1 BQSXYDIZGSJTDO-UHFFFAOYSA-N 0.000 description 4
- IMKSDZLFVYKGLY-UHFFFAOYSA-N ethyl 7-phenylmethoxy-1h-indole-2-carboxylate Chemical compound C=12NC(C(=O)OCC)=CC2=CC=CC=1OCC1=CC=CC=C1 IMKSDZLFVYKGLY-UHFFFAOYSA-N 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 230000007302 negative regulation of cytokine production Effects 0.000 description 4
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 4
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- RYDADSWUZMFCHE-UHFFFAOYSA-N 2-tert-butyl-5-methoxypyridin-4-amine Chemical compound COC1=CN=C(C(C)(C)C)C=C1N RYDADSWUZMFCHE-UHFFFAOYSA-N 0.000 description 3
- UGCJAGJLFXEDPP-UHFFFAOYSA-N 7-(2-chloropyridin-4-yl)oxy-1-methylindole-2-carboxylic acid Chemical compound C=12N(C)C(C(O)=O)=CC2=CC=CC=1OC1=CC=NC(Cl)=C1 UGCJAGJLFXEDPP-UHFFFAOYSA-N 0.000 description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 206010007559 Cardiac failure congestive Diseases 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 208000011231 Crohn disease Diseases 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- 208000031886 HIV Infections Diseases 0.000 description 3
- 208000037357 HIV infectious disease Diseases 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- 201000009906 Meningitis Diseases 0.000 description 3
- 208000034578 Multiple myelomas Diseases 0.000 description 3
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 3
- BNUHAJGCKIQFGE-UHFFFAOYSA-N Nitroanisol Chemical compound COC1=CC=C([N+]([O-])=O)C=C1 BNUHAJGCKIQFGE-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 206010039491 Sarcoma Diseases 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000003092 anti-cytokine Effects 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 208000029028 brain injury Diseases 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- 208000006990 cholangiocarcinoma Diseases 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- ZDBICWIDAPIMIB-UHFFFAOYSA-N ethyl 7-hydroxy-1-methylindole-2-carboxylate Chemical compound C1=CC(O)=C2N(C)C(C(=O)OCC)=CC2=C1 ZDBICWIDAPIMIB-UHFFFAOYSA-N 0.000 description 3
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 3
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 230000009545 invasion Effects 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 229920006008 lipopolysaccharide Polymers 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 201000008482 osteoarthritis Diseases 0.000 description 3
- 210000002997 osteoclast Anatomy 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000000241 respiratory effect Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 3
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 3
- 230000006433 tumor necrosis factor production Effects 0.000 description 3
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
- OBPFDKFVBLUHMQ-UHFFFAOYSA-N 1-bromo-5-tert-butyl-2-methoxy-3-nitrobenzene Chemical compound COC1=C(Br)C=C(C(C)(C)C)C=C1[N+]([O-])=O OBPFDKFVBLUHMQ-UHFFFAOYSA-N 0.000 description 2
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 2
- VFHUJFBEFDVZPJ-UHFFFAOYSA-N 1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)N)=CC2=C1 VFHUJFBEFDVZPJ-UHFFFAOYSA-N 0.000 description 2
- CVYZVNVPQRKDLW-UHFFFAOYSA-N 2,4-dinitroanisole Chemical compound COC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O CVYZVNVPQRKDLW-UHFFFAOYSA-N 0.000 description 2
- KBJMBOZJLNXKDI-UHFFFAOYSA-N 2-bromo-4-tert-butyl-1-methoxybenzene Chemical compound COC1=CC=C(C(C)(C)C)C=C1Br KBJMBOZJLNXKDI-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- VTSFNCCQCOEPKF-UHFFFAOYSA-N 3-amino-1h-pyridin-2-one Chemical compound NC1=CC=CN=C1O VTSFNCCQCOEPKF-UHFFFAOYSA-N 0.000 description 2
- CAFLHTCAXMJHCW-UHFFFAOYSA-N 3-amino-5-tert-butyl-1h-pyridin-2-one Chemical compound CC(C)(C)C1=CNC(=O)C(N)=C1 CAFLHTCAXMJHCW-UHFFFAOYSA-N 0.000 description 2
- BFLWXPJTAKXXKT-UHFFFAOYSA-N 3-methoxybenzene-1,2-diamine Chemical compound COC1=CC=CC(N)=C1N BFLWXPJTAKXXKT-UHFFFAOYSA-N 0.000 description 2
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- CZCOOCJUCPZPSO-UHFFFAOYSA-N 4-tert-butyl-1-methylsulfanyl-2-nitrobenzene Chemical compound CSC1=CC=C(C(C)(C)C)C=C1[N+]([O-])=O CZCOOCJUCPZPSO-UHFFFAOYSA-N 0.000 description 2
- OENQUZRPYMOPNK-UHFFFAOYSA-N 5-tert-butyl-2-methylpyridin-3-amine Chemical compound CC1=NC=C(C(C)(C)C)C=C1N OENQUZRPYMOPNK-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- 206010048998 Acute phase reaction Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 208000009137 Behcet syndrome Diseases 0.000 description 2
- 206010004593 Bile duct cancer Diseases 0.000 description 2
- 208000020084 Bone disease Diseases 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- 206010009900 Colitis ulcerative Diseases 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- 206010012442 Dermatitis contact Diseases 0.000 description 2
- 238000008157 ELISA kit Methods 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
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 241000700721 Hepatitis B virus Species 0.000 description 2
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 102000055008 Matrilin Proteins Human genes 0.000 description 2
- 108010072582 Matrilin Proteins Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 206010051606 Necrotising colitis Diseases 0.000 description 2
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 2
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 208000021161 Plasma cell disease Diseases 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 208000000453 Skin Neoplasms Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- 206010044248 Toxic shock syndrome Diseases 0.000 description 2
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 2
- 206010048873 Traumatic arthritis Diseases 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 208000005298 acute pain Diseases 0.000 description 2
- 230000004658 acute-phase response Effects 0.000 description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 208000022531 anorexia Diseases 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 208000026900 bile duct neoplasm Diseases 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000006931 brain damage Effects 0.000 description 2
- 231100000874 brain damage Toxicity 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 206010008118 cerebral infarction Diseases 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 230000016396 cytokine production Effects 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 229920001971 elastomer Polymers 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- 210000001508 eye Anatomy 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 210000004392 genitalia Anatomy 0.000 description 2
- 208000024908 graft versus host disease Diseases 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000001631 haemodialysis Methods 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 230000000322 hemodialysis Effects 0.000 description 2
- 102000057041 human TNF Human genes 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 229960003130 interferon gamma Drugs 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 208000004995 necrotizing enterocolitis Diseases 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 230000000771 oncological effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 description 2
- 208000028169 periodontal disease Diseases 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 208000001685 postmenopausal osteoporosis Diseases 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- 239000000779 smoke Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 210000001519 tissue Anatomy 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
- 238000002054 transplantation Methods 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 150000003672 ureas Chemical class 0.000 description 2
- 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 1
- RRFTZRDEDAHFIR-UHFFFAOYSA-N (4-tert-butyl-2-nitrophenyl) trifluoromethanesulfonate Chemical compound CC(C)(C)C1=CC=C(OS(=O)(=O)C(F)(F)F)C([N+]([O-])=O)=C1 RRFTZRDEDAHFIR-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- ZAORLJBUHQFZSF-UHFFFAOYSA-N 1-(3-amino-5-tert-butyl-2-methoxyphenyl)azetidin-2-one Chemical compound COC1=C(N)C=C(C(C)(C)C)C=C1N1C(=O)CC1 ZAORLJBUHQFZSF-UHFFFAOYSA-N 0.000 description 1
- CJYNXMWBGSADRG-UHFFFAOYSA-N 1-(3-amino-5-tert-butyl-2-methoxyphenyl)pyrrolidin-2-one Chemical compound COC1=C(N)C=C(C(C)(C)C)C=C1N1C(=O)CCC1 CJYNXMWBGSADRG-UHFFFAOYSA-N 0.000 description 1
- SLUIRILGOOESAP-UHFFFAOYSA-N 1-(5-tert-butyl-2-methoxy-3-nitrophenyl)pyrrolidin-2-one Chemical compound C1=C(C(C)(C)C)C=C([N+]([O-])=O)C(OC)=C1N1C(=O)CCC1 SLUIRILGOOESAP-UHFFFAOYSA-N 0.000 description 1
- ZUMJNYJMXBJJIC-UHFFFAOYSA-N 1-methyl-2-nitro-3-phenylmethoxybenzene Chemical compound CC1=CC=CC(OCC=2C=CC=CC=2)=C1[N+]([O-])=O ZUMJNYJMXBJJIC-UHFFFAOYSA-N 0.000 description 1
- OLBZCZOCFKHQNM-UHFFFAOYSA-N 1-methyl-7-phenylmethoxyindole-2-carboxylic acid Chemical compound C=12N(C)C(C(O)=O)=CC2=CC=CC=1OCC1=CC=CC=C1 OLBZCZOCFKHQNM-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- GBBSAMQTQCPOBF-UHFFFAOYSA-N 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane Chemical compound CB1OB(C)OB(C)O1 GBBSAMQTQCPOBF-UHFFFAOYSA-N 0.000 description 1
- BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
- KJKIPRQNFDUULB-UHFFFAOYSA-N 2-chloro-4-iodopyridine Chemical compound ClC1=CC(I)=CC=N1 KJKIPRQNFDUULB-UHFFFAOYSA-N 0.000 description 1
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- HLTDBMHJSBSAOM-UHFFFAOYSA-N 2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CC=N1 HLTDBMHJSBSAOM-UHFFFAOYSA-N 0.000 description 1
- GRAODNHWFLLRPC-UHFFFAOYSA-N 2-tert-butyl-5-ethoxy-1,3-oxazole Chemical compound CCOC1=CN=C(C(C)(C)C)O1 GRAODNHWFLLRPC-UHFFFAOYSA-N 0.000 description 1
- WRNQCAVPLLHVGV-UHFFFAOYSA-N 2-tert-butyl-5-hydroxypyridine-4-carbonitrile Chemical compound CC(C)(C)C1=CC(C#N)=C(O)C=N1 WRNQCAVPLLHVGV-UHFFFAOYSA-N 0.000 description 1
- BBVONLXDPCBKAJ-UHFFFAOYSA-N 2-tert-butyl-5-methoxypyridine Chemical compound COC1=CC=C(C(C)(C)C)N=C1 BBVONLXDPCBKAJ-UHFFFAOYSA-N 0.000 description 1
- MLLMSTMETJZJPU-UHFFFAOYSA-N 2-tert-butyl-5-methoxypyridine-4-carboxylic acid Chemical compound COC1=CN=C(C(C)(C)C)C=C1C(O)=O MLLMSTMETJZJPU-UHFFFAOYSA-N 0.000 description 1
- AKQAIASNJCTKGQ-UHFFFAOYSA-N 2-tert-butylpropanedial Chemical compound CC(C)(C)C(C=O)C=O AKQAIASNJCTKGQ-UHFFFAOYSA-N 0.000 description 1
- IXGGMIRNAHOBOY-UHFFFAOYSA-N 3-amino-5-tert-butyl-1-methylpyridin-2-one Chemical compound CN1C=C(C(C)(C)C)C=C(N)C1=O IXGGMIRNAHOBOY-UHFFFAOYSA-N 0.000 description 1
- BKBXULUNMQDZHV-UHFFFAOYSA-N 3-amino-5-tert-butyl-2-methoxybenzonitrile Chemical compound COC1=C(N)C=C(C(C)(C)C)C=C1C#N BKBXULUNMQDZHV-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 229940073735 4-hydroxy acetophenone Drugs 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- JULSCVANMYFIDI-UHFFFAOYSA-N 4-tert-butyl-1-methylsulfinyl-2-nitrobenzene Chemical compound CS(=O)C1=CC=C(C(C)(C)C)C=C1[N+]([O-])=O JULSCVANMYFIDI-UHFFFAOYSA-N 0.000 description 1
- KKMXVLXXBRHTDK-UHFFFAOYSA-N 4-tert-butyl-1-methylsulfonyl-2-nitrobenzene Chemical compound CC(C)(C)C1=CC=C(S(C)(=O)=O)C([N+]([O-])=O)=C1 KKMXVLXXBRHTDK-UHFFFAOYSA-N 0.000 description 1
- IHGNADPMUSNTJW-UHFFFAOYSA-N 4-tert-butyl-2-nitrophenol Chemical compound CC(C)(C)C1=CC=C(O)C([N+]([O-])=O)=C1 IHGNADPMUSNTJW-UHFFFAOYSA-N 0.000 description 1
- YHTWNJRXAABQAF-UHFFFAOYSA-N 5-tert-butyl-1-methyl-3-nitropyridin-2-one Chemical compound CN1C=C(C(C)(C)C)C=C([N+]([O-])=O)C1=O YHTWNJRXAABQAF-UHFFFAOYSA-N 0.000 description 1
- FYDWBUGKMKWHDN-UHFFFAOYSA-N 5-tert-butyl-2-chloro-3-nitropyridine Chemical compound CC(C)(C)C1=CN=C(Cl)C([N+]([O-])=O)=C1 FYDWBUGKMKWHDN-UHFFFAOYSA-N 0.000 description 1
- DGANIIOMQVHFAC-UHFFFAOYSA-N 5-tert-butyl-2-hydroxy-3-nitrobenzonitrile Chemical compound CC(C)(C)C1=CC(C#N)=C(O)C([N+]([O-])=O)=C1 DGANIIOMQVHFAC-UHFFFAOYSA-N 0.000 description 1
- ZVCQQLGWGRTXGC-UHFFFAOYSA-N 5-tert-butyl-2-hydroxybenzaldehyde Chemical compound CC(C)(C)C1=CC=C(O)C(C=O)=C1 ZVCQQLGWGRTXGC-UHFFFAOYSA-N 0.000 description 1
- LXFVPCYOUOUTLD-UHFFFAOYSA-N 5-tert-butyl-2-methyl-3-nitropyridine Chemical compound CC1=NC=C(C(C)(C)C)C=C1[N+]([O-])=O LXFVPCYOUOUTLD-UHFFFAOYSA-N 0.000 description 1
- SCOPDRYPQJUKKH-UHFFFAOYSA-N 5-tert-butyl-2-methylsulfinylaniline Chemical compound CS(=O)C1=CC=C(C(C)(C)C)C=C1N SCOPDRYPQJUKKH-UHFFFAOYSA-N 0.000 description 1
- MHADFNZFNWCBBB-UHFFFAOYSA-N 5-tert-butyl-2-methylsulfonylaniline Chemical compound CC(C)(C)C1=CC=C(S(C)(=O)=O)C(N)=C1 MHADFNZFNWCBBB-UHFFFAOYSA-N 0.000 description 1
- ZCNYCSXGEZHNOC-UHFFFAOYSA-N 5-tert-butyl-3-nitro-1h-pyridin-2-one Chemical compound CC(C)(C)C1=CNC(=O)C([N+]([O-])=O)=C1 ZCNYCSXGEZHNOC-UHFFFAOYSA-N 0.000 description 1
- PSKSHDLFMBFNTH-UHFFFAOYSA-N 6-tert-butyl-3-methoxypyridine-2,4-diamine Chemical compound COC1=C(N)C=C(C(C)(C)C)N=C1N PSKSHDLFMBFNTH-UHFFFAOYSA-N 0.000 description 1
- NZZPFPTTWWLJKQ-UHFFFAOYSA-N 6-tert-butyl-3-methoxypyridine-2,4-dicarboxylic acid Chemical compound COC1=C(C(O)=O)C=C(C(C)(C)C)N=C1C(O)=O NZZPFPTTWWLJKQ-UHFFFAOYSA-N 0.000 description 1
- QRMMLYQZGNBZHH-UHFFFAOYSA-N 7-hydroxy-1-methylindole-2-carboxylic acid Chemical compound C1=CC(O)=C2N(C)C(C(O)=O)=CC2=C1 QRMMLYQZGNBZHH-UHFFFAOYSA-N 0.000 description 1
- WSEMPUNMUMBGQG-UHFFFAOYSA-N 9-(2-anthracen-9-ylethynyl)anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C(C#CC=3C4=CC=CC=C4C=C4C=CC=CC4=3)=C21 WSEMPUNMUMBGQG-UHFFFAOYSA-N 0.000 description 1
- 206010065040 AIDS dementia complex Diseases 0.000 description 1
- 208000002008 AIDS-Related Lymphoma Diseases 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 208000006468 Adrenal Cortex Neoplasms Diseases 0.000 description 1
- 206010001939 Aminoaciduria Diseases 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 201000003076 Angiosarcoma Diseases 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 208000012657 Atopic disease Diseases 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- STBLFCJIGHFMAD-UHFFFAOYSA-N CC(C)(C)C1=CC(=C(C(=C1)[N+](=O)[O-])OC)N2CCC2 Chemical compound CC(C)(C)C1=CC(=C(C(=C1)[N+](=O)[O-])OC)N2CCC2 STBLFCJIGHFMAD-UHFFFAOYSA-N 0.000 description 1
- ARLSJIGFLRRRIB-UHFFFAOYSA-N CC1CCN(CC1)C2=NC=CC(=N2)OC3=CC=CC4=C3N(C(=C4)C(=O)O)C Chemical compound CC1CCN(CC1)C2=NC=CC(=N2)OC3=CC=CC4=C3N(C(=C4)C(=O)O)C ARLSJIGFLRRRIB-UHFFFAOYSA-N 0.000 description 1
- 229940124638 COX inhibitor Drugs 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 206010007275 Carcinoid tumour Diseases 0.000 description 1
- 208000005024 Castleman disease Diseases 0.000 description 1
- 206010007953 Central nervous system lymphoma Diseases 0.000 description 1
- 206010008027 Cerebellar atrophy Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010063094 Cerebral malaria Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 102000010907 Cyclooxygenase 2 Human genes 0.000 description 1
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 1
- 208000016192 Demyelinating 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
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 208000002699 Digestive System Neoplasms Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 241000709661 Enterovirus Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010014967 Ependymoma Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 206010018366 Glomerulonephritis acute Diseases 0.000 description 1
- 102100033495 Glycine dehydrogenase (decarboxylating), mitochondrial Human genes 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000001258 Hemangiosarcoma Diseases 0.000 description 1
- 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000013016 Hypoglycemia 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
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 1
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 1
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 1
- 102000010781 Interleukin-6 Receptors Human genes 0.000 description 1
- 108010038501 Interleukin-6 Receptors Proteins 0.000 description 1
- 206010061252 Intraocular melanoma Diseases 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 208000021342 Isolated sulfite oxidase deficiency Diseases 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 201000003533 Leber congenital amaurosis Diseases 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 206010062038 Lip neoplasm Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 206010025312 Lymphoma AIDS related Diseases 0.000 description 1
- 208000009564 MELAS Syndrome Diseases 0.000 description 1
- 201000009035 MERRF syndrome Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 208000005903 Manganese Poisoning Diseases 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 206010027202 Meningitis bacterial Diseases 0.000 description 1
- 206010027260 Meningitis viral Diseases 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 206010027439 Metal poisoning Diseases 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 206010028116 Mucosal inflammation Diseases 0.000 description 1
- 201000010927 Mucositis Diseases 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 208000010718 Multiple Organ Failure Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 206010028570 Myelopathy Diseases 0.000 description 1
- 206010069825 Myoclonic epilepsy and ragged-red fibres Diseases 0.000 description 1
- 208000018526 Narcotic-Related disease Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 208000035544 Nonketotic hyperglycinaemia Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 206010061323 Optic neuropathy Diseases 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 208000003076 Osteolysis Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 208000002471 Penile Neoplasms Diseases 0.000 description 1
- 206010034299 Penile cancer Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 201000008199 Pleuropulmonary blastoma Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 208000005374 Poisoning Diseases 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 206010038934 Retinopathy proliferative Diseases 0.000 description 1
- 208000006289 Rett Syndrome Diseases 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 1
- 206010061934 Salivary gland cancer Diseases 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 206010040844 Skin exfoliation Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 239000004280 Sodium formate Substances 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 108700036932 Sulfite oxidase deficiency Proteins 0.000 description 1
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 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
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 208000016620 Tourette disease Diseases 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
- 208000023915 Ureteral Neoplasms Diseases 0.000 description 1
- 206010046392 Ureteric cancer Diseases 0.000 description 1
- 206010046431 Urethral cancer Diseases 0.000 description 1
- 206010046458 Urethral neoplasms Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 201000005969 Uveal melanoma Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000004354 Vulvar Neoplasms Diseases 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- 208000010045 Wernicke encephalopathy Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 231100000851 acute glomerulonephritis Toxicity 0.000 description 1
- 206010069351 acute lung injury Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 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
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 208000002029 allergic contact dermatitis Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003927 aminopyridines Chemical class 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 210000001188 articular cartilage Anatomy 0.000 description 1
- 125000005418 aryl aryl group Chemical group 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 201000009904 bacterial meningitis Diseases 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- 239000003659 bee venom Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- GQBRBPWDSZJNQM-UHFFFAOYSA-N benzyl n-[6-tert-butyl-3-methoxy-2-(phenylmethoxycarbonylamino)pyridin-4-yl]carbamate Chemical compound C1=C(C(C)(C)C)N=C(NC(=O)OCC=2C=CC=CC=2)C(OC)=C1NC(=O)OCC1=CC=CC=C1 GQBRBPWDSZJNQM-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 230000010072 bone remodeling Effects 0.000 description 1
- 208000019664 bone resorption disease Diseases 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 201000002143 bronchus adenoma Diseases 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000000872 buffer Substances 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
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 201000007335 cerebellar astrocytoma Diseases 0.000 description 1
- 208000030239 cerebral astrocytoma Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 210000004720 cerebrum Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 208000029039 cyanide poisoning Diseases 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 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 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229940124698 cytokine therapeutics Drugs 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 1
- 125000005046 dihydronaphthyl group Chemical group 0.000 description 1
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- VZFRNCSOCOPNDB-AJKFJWDBSA-N domoic acid Chemical compound OC(=O)[C@@H](C)\C=C\C=C(/C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VZFRNCSOCOPNDB-AJKFJWDBSA-N 0.000 description 1
- VZFRNCSOCOPNDB-UHFFFAOYSA-N domoic acid Natural products OC(=O)C(C)C=CC=C(C)C1CNC(C(O)=O)C1CC(O)=O VZFRNCSOCOPNDB-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000003372 endocrine gland Anatomy 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- YXVKELWZRXDQTH-UHFFFAOYSA-N ethyl 1-methyl-7-phenylmethoxyindole-2-carboxylate Chemical compound C=12N(C)C(C(=O)OCC)=CC2=CC=CC=1OCC1=CC=CC=C1 YXVKELWZRXDQTH-UHFFFAOYSA-N 0.000 description 1
- DHQMUWAZUBPECM-UHFFFAOYSA-N ethyl 2-cyano-3-methoxypyridine-4-carboxylate Chemical compound CCOC(=O)c1ccnc(C#N)c1OC DHQMUWAZUBPECM-UHFFFAOYSA-N 0.000 description 1
- YWILMOPMGCUWIS-UHFFFAOYSA-N ethyl 2-hydroxy-3-(2-nitro-3-phenylmethoxyphenyl)prop-2-enoate;potassium Chemical compound [K].CCOC(=O)C(O)=CC1=CC=CC(OCC=2C=CC=CC=2)=C1[N+]([O-])=O YWILMOPMGCUWIS-UHFFFAOYSA-N 0.000 description 1
- FTKASJMIPSSXBP-UHFFFAOYSA-N ethyl 2-nitroacetate Chemical compound CCOC(=O)C[N+]([O-])=O FTKASJMIPSSXBP-UHFFFAOYSA-N 0.000 description 1
- BWGRPWRFPZTZPJ-UHFFFAOYSA-N ethyl 2-tert-butyl-5-hydroxypyridine-4-carboxylate Chemical compound CCOC(=O)C1=CC(C(C)(C)C)=NC=C1O BWGRPWRFPZTZPJ-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- MCRPKBUFXAKDKI-UHFFFAOYSA-N ethyl pyridine-4-carboxylate Chemical compound CCOC(=O)C1=CC=NC=C1 MCRPKBUFXAKDKI-UHFFFAOYSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 210000003499 exocrine gland Anatomy 0.000 description 1
- 231100000040 eye damage Toxicity 0.000 description 1
- 208000024519 eye neoplasm Diseases 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000001752 female genitalia Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 201000010175 gallbladder cancer Diseases 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 201000011205 glycine encephalopathy Diseases 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000020169 heat generation Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 208000006359 hepatoblastoma Diseases 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 239000003407 interleukin 1 receptor blocking agent Substances 0.000 description 1
- 230000021995 interleukin-8 production Effects 0.000 description 1
- 208000014899 intrahepatic bile duct cancer Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 201000008893 intraocular retinoblastoma Diseases 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 208000001875 irritant dermatitis Diseases 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- VZFRNCSOCOPNDB-OXYNIABMSA-N isodomoic acid D Natural products CC(C=C/C=C(/C)C1CNC(C1CC(=O)O)C(=O)O)C(=O)O VZFRNCSOCOPNDB-OXYNIABMSA-N 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 210000000244 kidney pelvis Anatomy 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 238000012332 laboratory investigation Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 201000011061 large intestine cancer Diseases 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 201000006721 lip cancer Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 208000025036 lymphosarcoma Diseases 0.000 description 1
- 208000029791 lytic metastatic bone lesion Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 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
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 208000020984 malignant renal pelvis neoplasm Diseases 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000000716 merkel cell Anatomy 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 1
- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- CWUDCNRJQJLSKL-UHFFFAOYSA-N n-(5-tert-butyl-1-methyl-2-oxopyridin-3-yl)-1-methyl-7-pyridin-4-yloxyindole-2-carboxamide Chemical compound C=12N(C)C(C(=O)NC=3C(N(C)C=C(C=3)C(C)(C)C)=O)=CC2=CC=CC=1OC1=CC=NC=C1 CWUDCNRJQJLSKL-UHFFFAOYSA-N 0.000 description 1
- MXRPOIGVONJRCS-UHFFFAOYSA-N n-[3-amino-2-methoxy-5-(1-methylcyclopropyl)phenyl]methanesulfonamide Chemical compound C1=C(NS(C)(=O)=O)C(OC)=C(N)C=C1C1(C)CC1 MXRPOIGVONJRCS-UHFFFAOYSA-N 0.000 description 1
- RXGDLJRIJKYANC-UHFFFAOYSA-N n-methyl-2-nitroacetamide Chemical compound CNC(=O)C[N+]([O-])=O RXGDLJRIJKYANC-UHFFFAOYSA-N 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 208000029140 neonatal diabetes Diseases 0.000 description 1
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 201000002575 ocular melanoma Diseases 0.000 description 1
- 201000005040 opiate dependence Diseases 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003349 osteoarthritic effect Effects 0.000 description 1
- 210000000963 osteoblast Anatomy 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 210000003899 penis Anatomy 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 201000005528 peripheral nervous system neoplasm Diseases 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 208000028591 pheochromocytoma Diseases 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000026749 regulation of bone remodeling Effects 0.000 description 1
- 201000007444 renal pelvis carcinoma Diseases 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000032253 retinal ischemia Diseases 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 238000011894 semi-preparative HPLC Methods 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 201000008261 skin carcinoma Diseases 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 201000002314 small intestine cancer Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
- 235000019254 sodium formate Nutrition 0.000 description 1
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 210000005222 synovial tissue Anatomy 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 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
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 150000003595 thromboxanes Chemical class 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- QQJLHRRUATVHED-UHFFFAOYSA-N tramazoline Chemical compound N1CCN=C1NC1=CC=CC2=C1CCCC2 QQJLHRRUATVHED-UHFFFAOYSA-N 0.000 description 1
- 229960001262 tramazoline Drugs 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 208000024722 urethra neoplasm Diseases 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 208000037965 uterine sarcoma Diseases 0.000 description 1
- 208000013139 vaginal neoplasm Diseases 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 230000006648 viral gene expression Effects 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 201000010044 viral meningitis Diseases 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- 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
-
- 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
- A61P35/00—Antineoplastic agents
-
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US56769304P | 2004-05-03 | 2004-05-03 | |
| US60/567,693 | 2004-05-03 | ||
| PCT/US2005/014947 WO2005108387A2 (en) | 2004-05-03 | 2005-04-29 | Cytokine inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2007536231A JP2007536231A (ja) | 2007-12-13 |
| JP2007536231A5 JP2007536231A5 (enExample) | 2008-06-19 |
| JP4865702B2 true JP4865702B2 (ja) | 2012-02-01 |
Family
ID=35229785
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007511450A Expired - Fee Related JP4865702B2 (ja) | 2004-05-03 | 2005-04-29 | サイトカイン阻害剤 |
Country Status (5)
| Country | Link |
|---|---|
| US (3) | US7285545B2 (enExample) |
| EP (1) | EP1745036A2 (enExample) |
| JP (1) | JP4865702B2 (enExample) |
| CA (1) | CA2560387C (enExample) |
| WO (1) | WO2005108387A2 (enExample) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PE20060664A1 (es) | 2004-09-15 | 2006-08-04 | Novartis Ag | Amidas biciclicas como inhibidores de cinasa |
| US7531560B2 (en) * | 2004-11-10 | 2009-05-12 | Boehringer Ingelheim Pharmaceuticals, Inc. | Anti-cytokine heterocyclic compounds |
| WO2007056016A2 (en) * | 2005-11-02 | 2007-05-18 | Kemia, Inc. | Bisamide cytokine inhibitors |
| CN101365682A (zh) * | 2005-12-08 | 2009-02-11 | 千禧药品公司 | 具有激酶抑制活性的双环化合物 |
| JP5587914B2 (ja) | 2009-01-30 | 2014-09-10 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | キマーゼ阻害剤として有用なアザキナゾリンジオン |
| US9630896B2 (en) | 2013-11-22 | 2017-04-25 | Tansna Therapeutics, Inc. | 2,5-dialkyl-4-H/halo/ether-phenol compounds |
| SG11201700777VA (en) | 2014-08-04 | 2017-02-27 | Nuevolution As | Optionally fused heterocyclyl-substituted derivatives of pyrimidine useful for the treatment of inflammatory, metabolic, oncologic and autoimmune diseases |
| MA52119A (fr) | 2015-10-19 | 2018-08-29 | Ncyte Corp | Composés hétérocycliques utilisés comme immunomodulateurs |
| PT3377488T (pt) | 2015-11-19 | 2022-11-21 | Incyte Corp | Compostos heterocíclicos como imunomoduladores |
| SI3394033T1 (sl) | 2015-12-22 | 2021-03-31 | Incyte Corporation | Heterociklične spojine kot imunomodulatorji |
| WO2017192961A1 (en) | 2016-05-06 | 2017-11-09 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| EP3464279B1 (en) | 2016-05-26 | 2021-11-24 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| CN109311848B (zh) | 2016-06-07 | 2022-02-01 | 北京加科思新药研发有限公司 | 可用作shp2抑制剂的新型杂环衍生物 |
| PL3472167T3 (pl) | 2016-06-20 | 2022-12-19 | Incyte Corporation | Związki heterocykliczne jako immunomodulatory |
| EP3484866B1 (en) | 2016-07-14 | 2022-09-07 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| ES2941716T3 (es) | 2016-08-29 | 2023-05-25 | Incyte Corp | Compuestos heterocíclicos como inmunomoduladores |
| CA3035308A1 (en) * | 2016-08-31 | 2018-03-08 | Taro Pharmaceutical Industries, Ltd. | Fenoldopam topical formulations for treating skin disorders |
| KR102696516B1 (ko) | 2016-12-22 | 2024-08-22 | 인사이트 코포레이션 | 면역조절제로서의 벤조옥사졸 유도체 |
| US20180179201A1 (en) | 2016-12-22 | 2018-06-28 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| EP3558973B1 (en) | 2016-12-22 | 2021-09-15 | Incyte Corporation | Pyridine derivatives as immunomodulators |
| MY197501A (en) | 2016-12-22 | 2023-06-19 | Incyte Corp | Tetrahydro imidazo[4,5-c]pyridine derivatives as pd-l1 internalization inducers |
| WO2018119286A1 (en) | 2016-12-22 | 2018-06-28 | Incyte Corporation | Bicyclic heteroaromatic compounds as immunomodulators |
| SMT202400385T1 (it) | 2017-03-23 | 2024-11-15 | Jacobio Pharmaceuticals Co Ltd | Nuovi derivati eterociclici utili come inibitori di shp2 |
| US10364245B2 (en) | 2017-06-07 | 2019-07-30 | Chiesi Farmaceutici S.P.A. | Kinase inhibitors |
| EP4212529B1 (en) | 2018-03-30 | 2025-01-29 | Incyte Corporation | Heterocyclic compounds as immunomodulators |
| FI4219492T3 (fi) | 2018-05-11 | 2025-02-17 | Incyte Corp | Heterosyklisiä yhdisteitä immunomodulaattoreina |
| US20210393623A1 (en) | 2018-09-26 | 2021-12-23 | Jacobio Pharmaceuticals Co., Ltd. | Novel Heterocyclic Derivatives Useful as SHP2 Inhibitors |
| WO2020183322A1 (en) | 2019-03-08 | 2020-09-17 | Taro Pharmaceutical Industries Ltd. | Stable topical compositions of fenoldopam |
| CA3150434A1 (en) | 2019-08-09 | 2021-02-18 | Incyte Corporation | Salts of a pd-1/pd-l1 inhibitor |
| AR120109A1 (es) | 2019-09-30 | 2022-02-02 | Incyte Corp | Compuestos de pirido[3,2-d]pirimidina como inmunomoduladores |
| IL292524A (en) | 2019-11-11 | 2022-06-01 | Incyte Corp | Salts and crystalline forms of a pd-1/pd-l1 inhibitor |
| TWI872177B (zh) | 2019-12-20 | 2025-02-11 | 丹麥商紐韋盧森公司 | 對核受體具有活性之化合物 |
| US11447479B2 (en) | 2019-12-20 | 2022-09-20 | Nuevolution A/S | Compounds active towards nuclear receptors |
| JP7713953B2 (ja) | 2020-03-31 | 2025-07-28 | ヌエヴォリューション・アクティーゼルスカブ | 核内受容体に対して活性な化合物 |
| CA3174176A1 (en) | 2020-03-31 | 2021-10-07 | Sanne Schroder Glad | Compounds active towards nuclear receptors |
| WO2022099075A1 (en) | 2020-11-06 | 2022-05-12 | Incyte Corporation | Crystalline form of a pd-1/pd-l1 inhibitor |
| PE20231438A1 (es) | 2020-11-06 | 2023-09-14 | Incyte Corp | Proceso para hacer un inhibidor de pd-1/pd-l1 y sales y formas cristalinas del mismo |
| US11780836B2 (en) | 2020-11-06 | 2023-10-10 | Incyte Corporation | Process of preparing a PD-1/PD-L1 inhibitor |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003511442A (ja) * | 1999-10-13 | 2003-03-25 | アストラゼネカ アクチボラグ | ピリミジン誘導体 |
| WO2003087085A1 (en) * | 2002-04-11 | 2003-10-23 | Boehringer Ingelheim Pharmaceuticals, Inc. | Heterocyclic amide derivatives as cytokine inhibitors |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5744776A (en) * | 1989-07-14 | 1998-04-28 | Tip Engineering Group, Inc. | Apparatus and for laser preweakening an automotive trim cover for an air bag deployment opening |
| DE4302051A1 (de) | 1993-01-26 | 1994-07-28 | Thomae Gmbh Dr K | 5-gliedrige Heterocyclen, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel |
| FR2732967B1 (fr) | 1995-04-11 | 1997-07-04 | Sanofi Sa | 1-phenylpyrazole-3-carboxamides substitues, actifs sur la neurotensine, leur preparation, les compositions pharmaceutiques en contenant |
| DE19546585A1 (de) * | 1995-12-13 | 1997-06-19 | Trw Repa Gmbh | Gassack-Abdeckung für ein Fahrzeuginsassen-Rückhaltesystem sowie Verfahren zu deren Herstellung |
| JP3430841B2 (ja) * | 1997-03-05 | 2003-07-28 | 豊田合成株式会社 | エアバッグカバー |
| EP1068187A1 (en) | 1998-04-08 | 2001-01-17 | Abbott Laboratories | Pyrazole inhibitors of cytokine production |
| EP1123287B1 (en) | 1998-10-23 | 2003-07-30 | Dow AgroSciences LLC | Insecticidal 3- (substituted pyridyl) -1, 2, 4-triazoles |
| US6498423B1 (en) | 2001-06-27 | 2002-12-24 | Welch Allyn, Inc. | Lamp thermal control by directed air flow |
| WO2003022820A1 (en) | 2001-09-06 | 2003-03-20 | Bristol-Myers Squibb Pharma Company. | Heteroaromatic substituted cyclopropane as corticotropin releasing hormone |
| WO2003030902A1 (en) | 2001-10-09 | 2003-04-17 | Tularik Inc. | Imidazole derivates as anti-inflammatory agents |
| AU2003209388A1 (en) | 2002-01-29 | 2003-09-02 | Merck And Co., Inc. | Substituted imidazoles as cannabinoid receptor modulators |
| US7078419B2 (en) * | 2003-03-10 | 2006-07-18 | Boehringer Ingelheim Pharmaceuticals, Inc. | Cytokine inhibitors |
| ATE522525T1 (de) | 2003-05-01 | 2011-09-15 | Bristol Myers Squibb Co | Arylsubstituierte pyrazolamidverbindungen, die als kinase-inhibitoren von nutzen sind |
-
2005
- 2005-04-29 WO PCT/US2005/014947 patent/WO2005108387A2/en not_active Ceased
- 2005-04-29 CA CA2560387A patent/CA2560387C/en not_active Expired - Fee Related
- 2005-04-29 EP EP05745042A patent/EP1745036A2/en not_active Withdrawn
- 2005-04-29 US US11/119,524 patent/US7285545B2/en not_active Expired - Lifetime
- 2005-04-29 JP JP2007511450A patent/JP4865702B2/ja not_active Expired - Fee Related
-
2007
- 2007-08-15 US US11/839,136 patent/US20070275946A1/en not_active Abandoned
-
2008
- 2008-08-29 US US12/201,766 patent/US7592332B2/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003511442A (ja) * | 1999-10-13 | 2003-03-25 | アストラゼネカ アクチボラグ | ピリミジン誘導体 |
| WO2003087085A1 (en) * | 2002-04-11 | 2003-10-23 | Boehringer Ingelheim Pharmaceuticals, Inc. | Heterocyclic amide derivatives as cytokine inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| US7592332B2 (en) | 2009-09-22 |
| WO2005108387A2 (en) | 2005-11-17 |
| US7285545B2 (en) | 2007-10-23 |
| US20050245536A1 (en) | 2005-11-03 |
| US20090023701A1 (en) | 2009-01-22 |
| CA2560387A1 (en) | 2005-11-17 |
| US20070275946A1 (en) | 2007-11-29 |
| JP2007536231A (ja) | 2007-12-13 |
| CA2560387C (en) | 2013-09-24 |
| WO2005108387A3 (en) | 2006-02-16 |
| EP1745036A2 (en) | 2007-01-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4865702B2 (ja) | サイトカイン阻害剤 | |
| AU2004264409B2 (en) | Heterocyclic N-aryl carboxamides as cytokine inhibitors | |
| JP4824576B2 (ja) | サイトカイン生成のインヒビターとしての１，２，３−トリアゾールアミド誘導体 | |
| JP4578106B2 (ja) | サイトカインインヒビターとしてのヘテロ環式アミド誘導体 | |
| JP4823218B2 (ja) | 抗−サイトカインヘテロ環式化合物 | |
| JP4926402B2 (ja) | サイトカインインヒビターとしての１，２，３−トリアゾールアミド誘導体 | |
| JP5038139B2 (ja) | サイトカインインヒビター | |
| EP1867646A1 (en) | Cytokine inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080428 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080428 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110627 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110927 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20111024 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20111110 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20141118 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |