JP2007519692A - p38キナーゼ阻害剤として使用するための縮合ヘテロアリール誘導体 - Google Patents
p38キナーゼ阻害剤として使用するための縮合ヘテロアリール誘導体 Download PDFInfo
- Publication number
- JP2007519692A JP2007519692A JP2006550294A JP2006550294A JP2007519692A JP 2007519692 A JP2007519692 A JP 2007519692A JP 2006550294 A JP2006550294 A JP 2006550294A JP 2006550294 A JP2006550294 A JP 2006550294A JP 2007519692 A JP2007519692 A JP 2007519692A
- Authority
- JP
- Japan
- Prior art keywords
- fluoro
- indazol
- methyl
- phenyl
- benzamide
- 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.)
- Pending
Links
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 title claims abstract description 36
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 title claims abstract description 36
- 125000001072 heteroaryl group Chemical group 0.000 title claims description 56
- 229940043355 kinase inhibitor Drugs 0.000 title description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 330
- 208000024891 symptom Diseases 0.000 claims abstract description 26
- 230000000694 effects Effects 0.000 claims abstract description 23
- 230000001404 mediated effect Effects 0.000 claims abstract description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
- 201000010099 disease Diseases 0.000 claims abstract description 16
- 238000011282 treatment Methods 0.000 claims abstract description 14
- 102000004127 Cytokines Human genes 0.000 claims abstract description 12
- 108090000695 Cytokines Proteins 0.000 claims abstract description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 93
- 238000000034 method Methods 0.000 claims description 67
- 125000000217 alkyl group Chemical group 0.000 claims description 61
- -1 —CONHR 13 Chemical group 0.000 claims description 61
- 229910052757 nitrogen Inorganic materials 0.000 claims description 59
- 229910052736 halogen Inorganic materials 0.000 claims description 41
- 150000002367 halogens Chemical class 0.000 claims description 41
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 125000001424 substituent group Chemical group 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 22
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 22
- 125000005842 heteroatom Chemical group 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 239000001301 oxygen Substances 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 18
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 17
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 16
- 239000000654 additive Substances 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 14
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 239000011737 fluorine Chemical group 0.000 claims description 14
- 229910052731 fluorine Chemical group 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- 239000000969 carrier Substances 0.000 claims description 12
- 239000003085 diluting agent Substances 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 239000011593 sulfur Chemical group 0.000 claims description 12
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- NDSAZMGBKQEREV-UHFFFAOYSA-N 3-fluoro-5-[3-(4-fluorophenyl)-1h-indazol-6-yl]-4-methyl-n-(2-methylpyrazol-3-yl)benzamide Chemical compound CC1=C(F)C=C(C(=O)NC=2N(N=CC=2)C)C=C1C(C=C1NN=2)=CC=C1C=2C1=CC=C(F)C=C1 NDSAZMGBKQEREV-UHFFFAOYSA-N 0.000 claims description 3
- FFLVSPSGKSYFOD-UHFFFAOYSA-N N-cyclopropyl-3-fluoro-5-[3-(4-hydroxyphenyl)-1,2-benzoxazol-6-yl]-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1ON=2)=CC=C1C=2C1=CC=C(O)C=C1 FFLVSPSGKSYFOD-UHFFFAOYSA-N 0.000 claims description 3
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 150000002429 hydrazines Chemical class 0.000 claims description 3
- XXKHSBRGJGQQJN-UHFFFAOYSA-N n-(2,4-dimethylpyrazol-3-yl)-3-[3-(4-fluorophenyl)-1h-indazol-6-yl]-4-methylbenzamide Chemical compound C1=NN(C)C(NC(=O)C=2C=C(C(C)=CC=2)C=2C=C3NN=C(C3=CC=2)C=2C=CC(F)=CC=2)=C1C XXKHSBRGJGQQJN-UHFFFAOYSA-N 0.000 claims description 3
- QXTNFKQMOZXGAJ-UHFFFAOYSA-N n-(2,4-dimethylpyrazol-3-yl)-3-fluoro-5-[3-(4-fluorophenyl)-1h-indazol-6-yl]-4-methylbenzamide Chemical compound C1=NN(C)C(NC(=O)C=2C=C(C(C)=C(F)C=2)C=2C=C3NN=C(C3=CC=2)C=2C=CC(F)=CC=2)=C1C QXTNFKQMOZXGAJ-UHFFFAOYSA-N 0.000 claims description 3
- IAHWGNBUSRCASO-UHFFFAOYSA-N n-(2-ethylpyrazol-3-yl)-3-fluoro-5-[3-(4-fluorophenyl)-1h-indazol-6-yl]-4-methylbenzamide Chemical compound CCN1N=CC=C1NC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C=CC(F)=CC=2)=C1 IAHWGNBUSRCASO-UHFFFAOYSA-N 0.000 claims description 3
- UVOQFNITQPYYOI-UHFFFAOYSA-N n-cyclopropyl-3-[1-[4-(2,3-dihydroxypropylamino)phenyl]indazol-5-yl]-5-fluoro-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2C1=CC=C(NCC(O)CO)C=C1 UVOQFNITQPYYOI-UHFFFAOYSA-N 0.000 claims description 3
- BGMAADGYDIEDFZ-UHFFFAOYSA-N n-cyclopropyl-3-[3-(4-fluorophenyl)-1h-indazol-6-yl]-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1NN=2)=CC=C1C=2C1=CC=C(F)C=C1 BGMAADGYDIEDFZ-UHFFFAOYSA-N 0.000 claims description 3
- GQBCGYCOKDKXLT-UHFFFAOYSA-N n-cyclopropyl-3-[3-(4-methoxyphenyl)-1h-indazol-6-yl]-4-methylbenzamide Chemical compound C1=CC(OC)=CC=C1C1=NNC2=CC(C=3C(=CC=C(C=3)C(=O)NC3CC3)C)=CC=C12 GQBCGYCOKDKXLT-UHFFFAOYSA-N 0.000 claims description 3
- YDTSBAIFSIHQBL-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-(1-phenylindazol-5-yl)benzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2C1=CC=CC=C1 YDTSBAIFSIHQBL-UHFFFAOYSA-N 0.000 claims description 3
- XAFMUBMMTNHFMW-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[1-(4-methylsulfonylphenyl)indazol-5-yl]benzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2C1=CC=C(S(C)(=O)=O)C=C1 XAFMUBMMTNHFMW-UHFFFAOYSA-N 0.000 claims description 3
- GEURZXJNLFHMMI-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-5-[1-(4-fluoro-2-methylphenyl)indazol-5-yl]-4-methylbenzamide Chemical compound CC1=CC(F)=CC=C1N1C2=CC=C(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=C2C=N1 GEURZXJNLFHMMI-UHFFFAOYSA-N 0.000 claims description 3
- OYTNAQPOJGJNTO-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-5-[1-(4-fluorophenyl)indazol-5-yl]-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2C1=CC=C(F)C=C1 OYTNAQPOJGJNTO-UHFFFAOYSA-N 0.000 claims description 3
- LCZCYDAXLUAHIR-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-5-[3-(4-methoxyphenyl)-1,2-benzoxazol-6-yl]-4-methylbenzamide Chemical compound C1=CC(OC)=CC=C1C1=NOC2=CC(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)=CC=C12 LCZCYDAXLUAHIR-UHFFFAOYSA-N 0.000 claims description 3
- DVFVWYWKPJGSHJ-UHFFFAOYSA-N n-ethyl-3-[3-(4-fluorophenyl)-1h-indazol-6-yl]-4-methylbenzamide Chemical compound CCNC(=O)C1=CC=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C=CC(F)=CC=2)=C1 DVFVWYWKPJGSHJ-UHFFFAOYSA-N 0.000 claims description 3
- QXXQWHJTTDKUMU-UHFFFAOYSA-N n-ethyl-3-[3-(4-methoxyphenyl)-1h-indazol-6-yl]-4-methylbenzamide Chemical compound CCNC(=O)C1=CC=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C=CC(OC)=CC=2)=C1 QXXQWHJTTDKUMU-UHFFFAOYSA-N 0.000 claims description 3
- ICUDUXKKHGONMS-UHFFFAOYSA-N n-ethyl-3-fluoro-5-[3-(4-fluoro-2-methoxyphenyl)-1h-indazol-6-yl]-4-methylbenzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C(=CC(F)=CC=2)OC)=C1 ICUDUXKKHGONMS-UHFFFAOYSA-N 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- 150000001642 boronic acid derivatives Chemical class 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- JWLBNZMPMCOTIL-UHFFFAOYSA-N n-cyclopropyl-3-[1-[4-[2-(dimethylamino)ethylamino]phenyl]indazol-5-yl]-5-fluoro-4-methylbenzamide Chemical compound C1=CC(NCCN(C)C)=CC=C1N1C2=CC=C(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=C2C=N1 JWLBNZMPMCOTIL-UHFFFAOYSA-N 0.000 claims description 2
- CYKMFIZQLQHACP-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[1-[4-[2-(methylamino)-2-oxoethyl]phenyl]indazol-5-yl]benzamide Chemical compound C1=CC(CC(=O)NC)=CC=C1N1C2=CC=C(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=C2C=N1 CYKMFIZQLQHACP-UHFFFAOYSA-N 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 abstract description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 300
- 239000000543 intermediate Substances 0.000 description 189
- 239000000203 mixture Substances 0.000 description 161
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 139
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 130
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 119
- 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 117
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 99
- 239000002904 solvent Substances 0.000 description 84
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 82
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
- 239000000243 solution Substances 0.000 description 73
- 239000000377 silicon dioxide Substances 0.000 description 69
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 64
- 239000007787 solid Substances 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 58
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 58
- 235000017557 sodium bicarbonate Nutrition 0.000 description 58
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 53
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 52
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
- 239000011541 reaction mixture Substances 0.000 description 47
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 42
- 235000002639 sodium chloride Nutrition 0.000 description 42
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 42
- 150000003839 salts Chemical class 0.000 description 38
- 230000002209 hydrophobic effect Effects 0.000 description 34
- 238000007429 general method Methods 0.000 description 32
- 238000002953 preparative HPLC Methods 0.000 description 30
- 238000009472 formulation Methods 0.000 description 26
- 239000012044 organic layer Substances 0.000 description 25
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- 238000004587 chromatography analysis Methods 0.000 description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
- 239000002253 acid Substances 0.000 description 21
- 239000003446 ligand Substances 0.000 description 21
- 108091000080 Phosphotransferase Proteins 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 18
- 102000020233 phosphotransferase Human genes 0.000 description 18
- 238000010992 reflux Methods 0.000 description 18
- 239000002552 dosage form Substances 0.000 description 17
- 239000003921 oil Substances 0.000 description 17
- 235000019198 oils Nutrition 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000000843 powder Substances 0.000 description 14
- 239000012453 solvate Substances 0.000 description 14
- 239000011734 sodium Substances 0.000 description 13
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 12
- 239000002480 mineral oil Substances 0.000 description 12
- 235000010446 mineral oil Nutrition 0.000 description 12
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 12
- 239000003826 tablet Substances 0.000 description 12
- 235000019270 ammonium chloride Nutrition 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 11
- 125000006317 cyclopropyl amino group Chemical group 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- GIWCBSLJBLIGKK-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-5-(1h-indazol-5-yl)-4-methylbenzamide Chemical compound C1=C(C=2C=C3C=NNC3=CC=2)C(C)=C(F)C=C1C(=O)NC1CC1 GIWCBSLJBLIGKK-UHFFFAOYSA-N 0.000 description 10
- 239000000651 prodrug Substances 0.000 description 10
- 229940002612 prodrug Drugs 0.000 description 10
- 125000006239 protecting group Chemical group 0.000 description 10
- 239000012312 sodium hydride Substances 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 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 9
- UTQNRIPCXSLLAZ-UHFFFAOYSA-N 6-bromo-3-(4-fluorophenyl)-1h-indazole Chemical compound C1=CC(F)=CC=C1C1=NNC2=CC(Br)=CC=C12 UTQNRIPCXSLLAZ-UHFFFAOYSA-N 0.000 description 9
- 229920002472 Starch Polymers 0.000 description 9
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 9
- 229910000024 caesium carbonate Inorganic materials 0.000 description 9
- 239000006260 foam Substances 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- 235000019698 starch Nutrition 0.000 description 9
- 239000008107 starch Substances 0.000 description 9
- 229940032147 starch Drugs 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 9
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 239000006071 cream Substances 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000011521 glass Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- SUZCHODXFJYVKA-UHFFFAOYSA-N 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1B1OC(C)(C)C(C)(C)O1 SUZCHODXFJYVKA-UHFFFAOYSA-N 0.000 description 7
- MMFGGDVQLQQQRX-UHFFFAOYSA-N 5-bromo-2-fluorobenzaldehyde Chemical compound FC1=CC=C(Br)C=C1C=O MMFGGDVQLQQQRX-UHFFFAOYSA-N 0.000 description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 238000007911 parenteral administration Methods 0.000 description 7
- 239000003755 preservative agent Substances 0.000 description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 description 7
- 239000012258 stirred mixture Substances 0.000 description 7
- 0 *c1cc(-c2ccc(/C=C/C=C/C=C3)c3c2)c(*)c(*)c1* Chemical compound *c1cc(-c2ccc(/C=C/C=C/C=C3)c3c2)c(*)c(*)c1* 0.000 description 6
- NCEKRDFWAZOAQO-UHFFFAOYSA-N 3-(3-bromo-2h-indazol-6-yl)-n-ethyl-5-fluoro-4-methylbenzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=C(Br)C3=CC=2)=C1 NCEKRDFWAZOAQO-UHFFFAOYSA-N 0.000 description 6
- PODTVAOVOKWNDI-UHFFFAOYSA-N 3-fluoro-5-iodo-4-methylbenzoic acid Chemical compound CC1=C(F)C=C(C(O)=O)C=C1I PODTVAOVOKWNDI-UHFFFAOYSA-N 0.000 description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- 229920000858 Cyclodextrin Polymers 0.000 description 6
- BBHLLNIOJPJRDR-UHFFFAOYSA-M FC1=CC(Br)=CC=C1[Zn]I Chemical compound FC1=CC(Br)=CC=C1[Zn]I BBHLLNIOJPJRDR-UHFFFAOYSA-M 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical class OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 241001465754 Metazoa Species 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000011230 binding agent Substances 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 239000006185 dispersion Substances 0.000 description 6
- 238000010494 dissociation reaction Methods 0.000 description 6
- 230000005593 dissociations Effects 0.000 description 6
- 239000003937 drug carrier Substances 0.000 description 6
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 6
- 239000011630 iodine Substances 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 125000000842 isoxazolyl group Chemical group 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- KUFMILFYZGSNHL-UHFFFAOYSA-N n-ethyl-3-fluoro-5-(3-iodo-2h-indazol-6-yl)-4-methylbenzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=C(I)C3=CC=2)=C1 KUFMILFYZGSNHL-UHFFFAOYSA-N 0.000 description 6
- 231100000252 nontoxic Toxicity 0.000 description 6
- 230000003000 nontoxic effect Effects 0.000 description 6
- 239000002674 ointment Substances 0.000 description 6
- 235000011056 potassium acetate Nutrition 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 235000015424 sodium Nutrition 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- 206010006895 Cachexia Diseases 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- 239000007821 HATU Substances 0.000 description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 208000002193 Pain Diseases 0.000 description 5
- 102000001708 Protein Isoforms Human genes 0.000 description 5
- 108010029485 Protein Isoforms Proteins 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 238000000576 coating method Methods 0.000 description 5
- 239000003086 colorant Substances 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000006210 lotion Substances 0.000 description 5
- 239000000314 lubricant Substances 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000000159 protein binding assay Methods 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 4
- IKPIZLINBCHNBU-UHFFFAOYSA-N 5-bromo-1-(4-fluorophenyl)indazole Chemical compound C1=CC(F)=CC=C1N1C2=CC=C(Br)C=C2C=N1 IKPIZLINBCHNBU-UHFFFAOYSA-N 0.000 description 4
- LVQMZEBELXDANN-UHFFFAOYSA-N 5-bromo-1-phenylindazole Chemical compound N1=CC2=CC(Br)=CC=C2N1C1=CC=CC=C1 LVQMZEBELXDANN-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 101150003085 Pdcl gene Proteins 0.000 description 4
- 206010035664 Pneumonia Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- ZAWITYYIKZBCGU-UHFFFAOYSA-N [5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]boronic acid Chemical compound C1=C(B(O)O)C(C)=C(F)C=C1C(=O)NC1CC1 ZAWITYYIKZBCGU-UHFFFAOYSA-N 0.000 description 4
- 230000000996 additive effect Effects 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 4
- 230000016396 cytokine production Effects 0.000 description 4
- 239000007884 disintegrant Substances 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- MDJDBOINQNIULL-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-5-(4-fluoro-3-formylphenyl)-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C1=CC=C(F)C(C=O)=C1 MDJDBOINQNIULL-UHFFFAOYSA-N 0.000 description 4
- URKFFXAJFKGGMM-UHFFFAOYSA-N n-ethyl-3-(3-iodo-2h-indazol-6-yl)-4-methylbenzamide Chemical compound CCNC(=O)C1=CC=C(C)C(C=2C=C3NN=C(I)C3=CC=2)=C1 URKFFXAJFKGGMM-UHFFFAOYSA-N 0.000 description 4
- 239000007922 nasal spray Substances 0.000 description 4
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000000375 suspending agent Substances 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- 239000002691 unilamellar liposome Substances 0.000 description 4
- 239000001993 wax Substances 0.000 description 4
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 4
- SQAMGXITIDQXGB-UHFFFAOYSA-N (4-bromo-2-fluorophenyl)-pyrimidin-5-ylmethanone Chemical compound FC1=CC(Br)=CC=C1C(=O)C1=CN=CN=C1 SQAMGXITIDQXGB-UHFFFAOYSA-N 0.000 description 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 3
- HJGITLRGVZIQKV-UHFFFAOYSA-N 3-fluoro-4-methyl-5-(1-phenylindazol-5-yl)benzoic acid Chemical compound CC1=C(F)C=C(C(O)=O)C=C1C1=CC=C(N(N=C2)C=3C=CC=CC=3)C2=C1 HJGITLRGVZIQKV-UHFFFAOYSA-N 0.000 description 3
- UOHHVCYLYIQXFG-UHFFFAOYSA-N 5-[2-[4-(aminomethyl)phenyl]-5-pyridin-4-yl-1h-imidazol-4-yl]-2-chlorophenol Chemical compound C1=CC(CN)=CC=C1C1=NC(C=2C=C(O)C(Cl)=CC=2)=C(C=2C=CN=CC=2)N1 UOHHVCYLYIQXFG-UHFFFAOYSA-N 0.000 description 3
- CUSGXVBKFRLDNA-UHFFFAOYSA-N 5-bromo-1-(3-methylphenyl)indazole Chemical compound CC1=CC=CC(N2C3=CC=C(Br)C=C3C=N2)=C1 CUSGXVBKFRLDNA-UHFFFAOYSA-N 0.000 description 3
- 244000215068 Acacia senegal Species 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 206010007558 Cardiac failure chronic Diseases 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- 208000011231 Crohn disease Diseases 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 206010018364 Glomerulonephritis Diseases 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 208000018737 Parkinson disease Diseases 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 229940097362 cyclodextrins Drugs 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 206010015037 epilepsy Diseases 0.000 description 3
- 238000000198 fluorescence anisotropy Methods 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- ADMOODHDOJVFMC-UHFFFAOYSA-N methyl 3-fluoro-5-iodo-4-methylbenzoate Chemical compound COC(=O)C1=CC(F)=C(C)C(I)=C1 ADMOODHDOJVFMC-UHFFFAOYSA-N 0.000 description 3
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- FNCQZTBZDONFIG-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[1-(pyridin-3-ylmethyl)indazol-5-yl]benzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2CC1=CC=CN=C1 FNCQZTBZDONFIG-UHFFFAOYSA-N 0.000 description 3
- LPLADBSAJQNYBD-UHFFFAOYSA-N n-ethyl-3-fluoro-5-iodo-4-methylbenzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(I)=C1 LPLADBSAJQNYBD-UHFFFAOYSA-N 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 235000019271 petrolatum Nutrition 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 125000003373 pyrazinyl group Chemical group 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 125000000168 pyrrolyl group Chemical group 0.000 description 3
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- QSBACAJBXNKUDK-UHFFFAOYSA-N tert-butyl 3-fluoro-5-(1h-indazol-6-yl)-4-methylbenzoate Chemical compound CC1=C(F)C=C(C(=O)OC(C)(C)C)C=C1C1=CC=C(C=NN2)C2=C1 QSBACAJBXNKUDK-UHFFFAOYSA-N 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 3
- HVAYIAWJHRUOBC-UHFFFAOYSA-N (2,6-dimethylpyrimidin-4-yl)hydrazine Chemical compound CC1=CC(NN)=NC(C)=N1 HVAYIAWJHRUOBC-UHFFFAOYSA-N 0.000 description 2
- KAPZJAGYFQABCJ-UHFFFAOYSA-N (4-bromo-2-fluorophenyl)-(2,5-dimethylpyrazol-3-yl)methanone Chemical compound CN1N=C(C)C=C1C(=O)C1=CC=C(Br)C=C1F KAPZJAGYFQABCJ-UHFFFAOYSA-N 0.000 description 2
- UTGJBUUPGOZHNO-UHFFFAOYSA-N (4-bromo-2-fluorophenyl)-(4-fluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)C1=CC=C(Br)C=C1F UTGJBUUPGOZHNO-UHFFFAOYSA-N 0.000 description 2
- ASPFFJAIQHMKPO-UHFFFAOYSA-N (4-bromo-2-fluorophenyl)-(4-methoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)C1=CC=C(Br)C=C1F ASPFFJAIQHMKPO-UHFFFAOYSA-N 0.000 description 2
- QCPMOXHMCICGIE-UHFFFAOYSA-N (4-bromo-2-fluorophenyl)-(6-morpholin-4-ylpyridin-3-yl)methanone Chemical compound FC1=CC(Br)=CC=C1C(=O)C1=CC=C(N2CCOCC2)N=C1 QCPMOXHMCICGIE-UHFFFAOYSA-N 0.000 description 2
- YKNVYYABJVNKEY-UHFFFAOYSA-N (4-bromo-2-fluorophenyl)-pyrazin-2-ylmethanone Chemical compound FC1=CC(Br)=CC=C1C(=O)C1=CN=CC=N1 YKNVYYABJVNKEY-UHFFFAOYSA-N 0.000 description 2
- GWCQWHCYQDQNRC-UHFFFAOYSA-N (4-bromo-2-fluorophenyl)-pyridin-2-ylmethanone Chemical compound FC1=CC(Br)=CC=C1C(=O)C1=CC=CC=N1 GWCQWHCYQDQNRC-UHFFFAOYSA-N 0.000 description 2
- HTZONHAJTPVLLD-UHFFFAOYSA-N (4-bromo-2-fluorophenyl)-pyrimidin-2-ylmethanone Chemical compound FC1=CC(Br)=CC=C1C(=O)C1=NC=CC=N1 HTZONHAJTPVLLD-UHFFFAOYSA-N 0.000 description 2
- ZHYAENSFCNMJQQ-UHFFFAOYSA-N (4-methylsulfonylphenyl)hydrazine Chemical compound CS(=O)(=O)C1=CC=C(NN)C=C1 ZHYAENSFCNMJQQ-UHFFFAOYSA-N 0.000 description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 2
- ZFYUCIPARAFUGP-UHFFFAOYSA-N 1h-pyridazin-2-amine Chemical compound NN1NC=CC=C1 ZFYUCIPARAFUGP-UHFFFAOYSA-N 0.000 description 2
- LDGLZUCCUIXNGP-UHFFFAOYSA-N 2-(4-aminophenyl)-n-methylacetamide Chemical compound CNC(=O)CC1=CC=C(N)C=C1 LDGLZUCCUIXNGP-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- GBRZZPJGTJQZLE-UHFFFAOYSA-N 2-[4-(5-bromoindazol-1-yl)phenyl]-n-methylacetamide Chemical compound C1=CC(CC(=O)NC)=CC=C1N1C2=CC=C(Br)C=C2C=N1 GBRZZPJGTJQZLE-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- JNAKJYAPSODBSS-UHFFFAOYSA-N 3-(5-bromoindol-1-yl)benzonitrile Chemical compound C1=CC2=CC(Br)=CC=C2N1C1=CC=CC(C#N)=C1 JNAKJYAPSODBSS-UHFFFAOYSA-N 0.000 description 2
- ASGJFGPILHALRC-UHFFFAOYSA-N 3-(bromomethyl)-5-methyl-1,2-oxazole Chemical compound CC1=CC(CBr)=NO1 ASGJFGPILHALRC-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
- AGSKWMRPXWHSPF-UHFFFAOYSA-M 3-(ethyliminomethylideneamino)propyl-trimethylazanium;iodide Chemical compound [I-].CCN=C=NCCC[N+](C)(C)C AGSKWMRPXWHSPF-UHFFFAOYSA-M 0.000 description 2
- DIZMHMLCKVUVMR-UHFFFAOYSA-N 3-[1-(4-bromophenyl)indazol-5-yl]-n-cyclopropyl-5-fluoro-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2C1=CC=C(Br)C=C1 DIZMHMLCKVUVMR-UHFFFAOYSA-N 0.000 description 2
- XUQCONCMPCVUDM-UHFFFAOYSA-N 3-fluoro-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1F XUQCONCMPCVUDM-UHFFFAOYSA-N 0.000 description 2
- ZORBNKPFJRYMRH-UHFFFAOYSA-N 3-fluoro-5-[3-(4-fluorophenyl)-1h-indazol-6-yl]-4-methylbenzoic acid Chemical compound CC1=C(F)C=C(C(O)=O)C=C1C1=CC=C(C(=NN2)C=3C=CC(F)=CC=3)C2=C1 ZORBNKPFJRYMRH-UHFFFAOYSA-N 0.000 description 2
- HMZVTUMLVNCHGR-UHFFFAOYSA-N 3-fluoro-5-iodo-4-methyl-n-(1h-pyrazol-5-yl)benzamide Chemical compound C1=C(I)C(C)=C(F)C=C1C(=O)NC1=CC=NN1 HMZVTUMLVNCHGR-UHFFFAOYSA-N 0.000 description 2
- HRADVHZVMOMEPU-UHFFFAOYSA-N 3-iodopyrrolidine-2,5-dione Chemical compound IC1CC(=O)NC1=O HRADVHZVMOMEPU-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
- QLJSDHSOJRMJSL-UHFFFAOYSA-N 4-(5-bromoindol-1-yl)benzonitrile Chemical compound C1=CC2=CC(Br)=CC=C2N1C1=CC=C(C#N)C=C1 QLJSDHSOJRMJSL-UHFFFAOYSA-N 0.000 description 2
- GTKGLJCKZHJONY-UHFFFAOYSA-N 4-(6-bromo-1,2-benzoxazol-3-yl)phenol Chemical compound C1=CC(O)=CC=C1C1=NOC2=CC(Br)=CC=C12 GTKGLJCKZHJONY-UHFFFAOYSA-N 0.000 description 2
- HRUROMBXRRAYJG-UHFFFAOYSA-N 4-[5-(6-bromo-1h-indazol-3-yl)pyridin-2-yl]morpholine Chemical compound N=1NC2=CC(Br)=CC=C2C=1C(C=N1)=CC=C1N1CCOCC1 HRUROMBXRRAYJG-UHFFFAOYSA-N 0.000 description 2
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- SPQZNMYNSANFJE-UHFFFAOYSA-N 5-bromo-1-(4-methylsulfonylphenyl)indazole Chemical compound C1=CC(S(=O)(=O)C)=CC=C1N1C2=CC=C(Br)C=C2C=N1 SPQZNMYNSANFJE-UHFFFAOYSA-N 0.000 description 2
- YCEJRISUHXJIPD-UHFFFAOYSA-N 5-bromo-1-pyridin-2-ylindole Chemical compound C1=CC2=CC(Br)=CC=C2N1C1=CC=CC=N1 YCEJRISUHXJIPD-UHFFFAOYSA-N 0.000 description 2
- CSDIPVWFZZEUMT-UHFFFAOYSA-N 5-bromo-1-pyridin-3-ylindole Chemical compound C1=CC2=CC(Br)=CC=C2N1C1=CC=CN=C1 CSDIPVWFZZEUMT-UHFFFAOYSA-N 0.000 description 2
- STVHMYNPQCLUNJ-UHFFFAOYSA-N 5-bromo-1h-indazole Chemical compound BrC1=CC=C2NN=CC2=C1 STVHMYNPQCLUNJ-UHFFFAOYSA-N 0.000 description 2
- BVRAQPOJEVRTMD-UHFFFAOYSA-N 6-bromo-3-(2,5-dimethylpyrazol-3-yl)-1h-indazole Chemical compound CN1N=C(C)C=C1C1=NNC2=CC(Br)=CC=C12 BVRAQPOJEVRTMD-UHFFFAOYSA-N 0.000 description 2
- PUAJTZXLPYJHME-UHFFFAOYSA-N 6-bromo-3-(4-methoxyphenyl)-1,2-benzoxazole Chemical compound C1=CC(OC)=CC=C1C1=NOC2=CC(Br)=CC=C12 PUAJTZXLPYJHME-UHFFFAOYSA-N 0.000 description 2
- YBIGIBMLDGEKJR-UHFFFAOYSA-N 6-bromo-3-(6-methoxypyridin-3-yl)-1h-indazole Chemical compound C1=NC(OC)=CC=C1C1=NNC2=CC(Br)=CC=C12 YBIGIBMLDGEKJR-UHFFFAOYSA-N 0.000 description 2
- YQEPPWKJAMNYRH-UHFFFAOYSA-N 6-bromo-3-pyrazin-2-yl-1h-indazole Chemical compound N=1NC2=CC(Br)=CC=C2C=1C1=CN=CC=N1 YQEPPWKJAMNYRH-UHFFFAOYSA-N 0.000 description 2
- JVKLWUNCLZVPCV-UHFFFAOYSA-N 6-bromo-3-pyridin-2-yl-1h-indazole Chemical compound N=1NC2=CC(Br)=CC=C2C=1C1=CC=CC=N1 JVKLWUNCLZVPCV-UHFFFAOYSA-N 0.000 description 2
- CWTSCVRMDJKBRS-UHFFFAOYSA-N 6-bromo-3-pyrimidin-2-yl-1h-indazole Chemical compound N=1NC2=CC(Br)=CC=C2C=1C1=NC=CC=N1 CWTSCVRMDJKBRS-UHFFFAOYSA-N 0.000 description 2
- KBMAPZKINUECGB-UHFFFAOYSA-N 6-bromo-3-pyrimidin-5-yl-1h-indazole Chemical compound N=1NC2=CC(Br)=CC=C2C=1C1=CN=CN=C1 KBMAPZKINUECGB-UHFFFAOYSA-N 0.000 description 2
- SOZMLVZVUQOOND-UHFFFAOYSA-N 6-hydrazinyl-1h-pyrimidin-4-one Chemical compound NNC1=CC(=O)N=CN1 SOZMLVZVUQOOND-UHFFFAOYSA-N 0.000 description 2
- RSGAXJZKQDNFEP-UHFFFAOYSA-N 6-iodo-1h-indazole Chemical compound IC1=CC=C2C=NNC2=C1 RSGAXJZKQDNFEP-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 108091006057 GST-tagged proteins Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 206010065390 Inflammatory pain Diseases 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 2
- 239000004264 Petrolatum Substances 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 229940023476 agar Drugs 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 238000010640 amide synthesis reaction Methods 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000003435 antirheumatic agent Substances 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 235000012216 bentonite Nutrition 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 125000005997 bromomethyl group Chemical group 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 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 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 2
- 229940038472 dicalcium phosphate Drugs 0.000 description 2
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000002988 disease modifying antirheumatic drug Substances 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000010575 fractional recrystallization Methods 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 235000001727 glucose Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000007917 intracranial administration Methods 0.000 description 2
- 238000007914 intraventricular administration Methods 0.000 description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
- 229940011051 isopropyl acetate Drugs 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- WBJKEWILDLNHQF-UHFFFAOYSA-N n-(2-ethylpyrazol-3-yl)-3-fluoro-5-iodo-4-methylbenzamide Chemical compound CCN1N=CC=C1NC(=O)C1=CC(F)=C(C)C(I)=C1 WBJKEWILDLNHQF-UHFFFAOYSA-N 0.000 description 2
- CATCSZWATTUAPM-UHFFFAOYSA-N n-(4-fluorophenyl)-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide Chemical compound CC1=CC=C(C(=O)NC=2C=CC(F)=CC=2)C=C1B1OC(C)(C)C(C)(C)O1 CATCSZWATTUAPM-UHFFFAOYSA-N 0.000 description 2
- OWIUPIRUAQMTTK-UHFFFAOYSA-M n-aminocarbamate Chemical compound NNC([O-])=O OWIUPIRUAQMTTK-UHFFFAOYSA-M 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- GQXAWDLYNBTUBJ-UHFFFAOYSA-N n-cyclobutyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide Chemical compound CC1=CC=C(C(=O)NC2CCC2)C=C1B1OC(C)(C)C(C)(C)O1 GQXAWDLYNBTUBJ-UHFFFAOYSA-N 0.000 description 2
- LKALKDOQWKJYIJ-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[1-(pyridin-2-ylmethyl)indazol-5-yl]benzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2CC1=CC=CC=N1 LKALKDOQWKJYIJ-UHFFFAOYSA-N 0.000 description 2
- YIMYABYMJVFUJR-UHFFFAOYSA-N n-ethyl-3-(1h-indazol-6-yl)-4-methylbenzamide Chemical compound CCNC(=O)C1=CC=C(C)C(C=2C=C3NN=CC3=CC=2)=C1 YIMYABYMJVFUJR-UHFFFAOYSA-N 0.000 description 2
- ZJHQSALHCWABMR-UHFFFAOYSA-N n-ethyl-3-fluoro-4-methyl-5-(3-pyridin-2-yl-1h-indazol-6-yl)benzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2N=CC=CC=2)=C1 ZJHQSALHCWABMR-UHFFFAOYSA-N 0.000 description 2
- WFDYKIRBPLQUTM-UHFFFAOYSA-N n-ethyl-6-[4-[5-(ethylcarbamoyl)-2-methylphenyl]-2-fluorobenzoyl]pyridine-3-carboxamide Chemical compound N1=CC(C(=O)NCC)=CC=C1C(=O)C1=CC=C(C=2C(=CC=C(C=2)C(=O)NCC)C)C=C1F WFDYKIRBPLQUTM-UHFFFAOYSA-N 0.000 description 2
- 229940097496 nasal spray Drugs 0.000 description 2
- 208000004296 neuralgia Diseases 0.000 description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- AHVQYHFYQWKUKB-UHFFFAOYSA-N oxan-4-amine Chemical compound NC1CCOCC1 AHVQYHFYQWKUKB-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 229940066842 petrolatum Drugs 0.000 description 2
- 239000008024 pharmaceutical diluent Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 150000008105 phosphatidylcholines Chemical class 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 238000010298 pulverizing process Methods 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 238000009491 slugging Methods 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
- 229940001584 sodium metabisulfite Drugs 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 201000004595 synovitis Diseases 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- DGIUNMJCBWWUSQ-UHFFFAOYSA-N tert-butyl 3-fluoro-5-(3-iodo-2h-indazol-6-yl)-4-methylbenzoate Chemical compound CC1=C(F)C=C(C(=O)OC(C)(C)C)C=C1C1=CC=C(C(I)=NN2)C2=C1 DGIUNMJCBWWUSQ-UHFFFAOYSA-N 0.000 description 2
- JJJBIVCKSZFRAM-UHFFFAOYSA-N tert-butyl 3-fluoro-5-iodo-4-methylbenzoate Chemical compound CC1=C(F)C=C(C(=O)OC(C)(C)C)C=C1I JJJBIVCKSZFRAM-UHFFFAOYSA-N 0.000 description 2
- CAQGDWLRIQCXSP-UHFFFAOYSA-N tert-butyl 5-bromoindazole-1-carboxylate Chemical compound BrC1=CC=C2N(C(=O)OC(C)(C)C)N=CC2=C1 CAQGDWLRIQCXSP-UHFFFAOYSA-N 0.000 description 2
- KLJYFDIFYHULKB-UHFFFAOYSA-N tert-butyl n-[[(4-bromo-2-fluorophenyl)-(6-morpholin-4-ylpyridin-3-yl)methylidene]amino]carbamate Chemical compound C=1C=C(Br)C=C(F)C=1C(=NNC(=O)OC(C)(C)C)C(C=N1)=CC=C1N1CCOCC1 KLJYFDIFYHULKB-UHFFFAOYSA-N 0.000 description 2
- AYDYGCMPSHUUIP-UHFFFAOYSA-N tert-butyl n-[[(4-bromo-2-fluorophenyl)-pyrazin-2-ylmethylidene]amino]carbamate Chemical compound C=1C=C(Br)C=C(F)C=1C(=NNC(=O)OC(C)(C)C)C1=CN=CC=N1 AYDYGCMPSHUUIP-UHFFFAOYSA-N 0.000 description 2
- MIHYVOUSMGCHBY-UHFFFAOYSA-N tert-butyl n-[[(4-bromo-2-fluorophenyl)-pyrimidin-2-ylmethylidene]amino]carbamate Chemical compound C=1C=C(Br)C=C(F)C=1C(=NNC(=O)OC(C)(C)C)C1=NC=CC=N1 MIHYVOUSMGCHBY-UHFFFAOYSA-N 0.000 description 2
- AXRPYCGMNHTBFE-UHFFFAOYSA-N tert-butyl n-[[(4-bromo-2-fluorophenyl)-pyrimidin-5-ylmethylidene]amino]carbamate Chemical compound C=1C=C(Br)C=C(F)C=1C(=NNC(=O)OC(C)(C)C)C1=CN=CN=C1 AXRPYCGMNHTBFE-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000003944 tolyl group Chemical group 0.000 description 2
- 238000011200 topical administration Methods 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
- 238000012546 transfer Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 2
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 2
- GNZHZNSHJWDVSO-UHFFFAOYSA-M zinc;1-bromo-3-fluorobenzene-4-ide;iodide Chemical compound I[Zn+].FC1=CC(Br)=CC=[C-]1 GNZHZNSHJWDVSO-UHFFFAOYSA-M 0.000 description 2
- 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 1
- RJNRORZRFGUAKL-ADMBVFOFSA-N (1r)-1-[(3ar,5r,6s,6ar)-6-[3-(dimethylamino)propoxy]-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]ethane-1,2-diol;hydrochloride Chemical compound Cl.O1C(C)(C)O[C@@H]2[C@@H](OCCCN(C)C)[C@@H]([C@H](O)CO)O[C@@H]21 RJNRORZRFGUAKL-ADMBVFOFSA-N 0.000 description 1
- HXOYWCSTHVTLOW-UHFFFAOYSA-N (2,2-dimethyl-1,3-dioxolan-4-yl)methanamine Chemical compound CC1(C)OCC(CN)O1 HXOYWCSTHVTLOW-UHFFFAOYSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- RGHNJXZEOKUKBD-NRXMZTRTSA-N (2r,3r,4r,5s)-2,3,4,5,6-pentahydroxyhexanoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-NRXMZTRTSA-N 0.000 description 1
- CRYXXTXWUCPIMU-WNQIDUERSA-N (2s)-2-aminobutanediamide;phenol Chemical compound OC1=CC=CC=C1.NC(=O)[C@@H](N)CC(N)=O CRYXXTXWUCPIMU-WNQIDUERSA-N 0.000 description 1
- GPTOGZLZMLJZCV-UHFFFAOYSA-N (3-methylphenyl)hydrazine Chemical compound CC1=CC=CC(NN)=C1 GPTOGZLZMLJZCV-UHFFFAOYSA-N 0.000 description 1
- CMBWCZRPKJGFSK-UHFFFAOYSA-N (4-bromo-2-fluorophenyl)-(6-methoxypyridin-3-yl)methanone Chemical compound C1=NC(OC)=CC=C1C(=O)C1=CC=C(Br)C=C1F CMBWCZRPKJGFSK-UHFFFAOYSA-N 0.000 description 1
- NRESDXFFSNBDGP-UHFFFAOYSA-N (4-bromophenyl)hydrazine Chemical compound NNC1=CC=C(Br)C=C1 NRESDXFFSNBDGP-UHFFFAOYSA-N 0.000 description 1
- WRQNDLDUNQMTCL-UHFFFAOYSA-N (4-ethoxyphenyl)boronic acid Chemical compound CCOC1=CC=C(B(O)O)C=C1 WRQNDLDUNQMTCL-UHFFFAOYSA-N 0.000 description 1
- BIIIMFCIGWHVMX-UHFFFAOYSA-N (4-fluoro-2-methylphenyl)boron Chemical compound [B]C1=CC=C(F)C=C1C BIIIMFCIGWHVMX-UHFFFAOYSA-N 0.000 description 1
- IQMLIVUHMSIOQP-UHFFFAOYSA-N (4-fluoro-2-methylphenyl)boronic acid Chemical compound CC1=CC(F)=CC=C1B(O)O IQMLIVUHMSIOQP-UHFFFAOYSA-N 0.000 description 1
- FEKUXLUOKFSMRO-UHFFFAOYSA-N (4-fluorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=C(F)C=C1 FEKUXLUOKFSMRO-UHFFFAOYSA-N 0.000 description 1
- BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 description 1
- VDUKDQTYMWUSAC-UHFFFAOYSA-N (4-methylsulfonylphenyl)boronic acid Chemical compound CS(=O)(=O)C1=CC=C(B(O)O)C=C1 VDUKDQTYMWUSAC-UHFFFAOYSA-N 0.000 description 1
- YBQSUBNCWMCREW-UHFFFAOYSA-N (4-morpholin-4-ylphenyl)boron Chemical compound C1=CC([B])=CC=C1N1CCOCC1 YBQSUBNCWMCREW-UHFFFAOYSA-N 0.000 description 1
- WHDIUBHAKZDSJL-UHFFFAOYSA-N (4-morpholin-4-ylphenyl)boronic acid Chemical compound C1=CC(B(O)O)=CC=C1N1CCOCC1 WHDIUBHAKZDSJL-UHFFFAOYSA-N 0.000 description 1
- OJBYZWHAPXIJID-UHFFFAOYSA-N (6-fluoropyridin-3-yl)boronic acid Chemical compound OB(O)C1=CC=C(F)N=C1 OJBYZWHAPXIJID-UHFFFAOYSA-N 0.000 description 1
- HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
- NVNPLEPBDPJYRZ-UHFFFAOYSA-N 1-(bromomethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CBr)C=C1 NVNPLEPBDPJYRZ-UHFFFAOYSA-N 0.000 description 1
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
- MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
- AHTVCDZZGBELIK-UHFFFAOYSA-N 2,4-dimethylpyrazol-3-amine Chemical compound CC=1C=NN(C)C=1N AHTVCDZZGBELIK-UHFFFAOYSA-N 0.000 description 1
- ZIAPGUFDEJWQHC-UHFFFAOYSA-N 2,5-dimethylpyrazole-3-carbonyl chloride Chemical compound CC=1C=C(C(Cl)=O)N(C)N=1 ZIAPGUFDEJWQHC-UHFFFAOYSA-N 0.000 description 1
- NJZFLGLVTILGPJ-UHFFFAOYSA-N 2-(4-hydrazinylphenyl)-n-methylacetamide Chemical compound CNC(=O)CC1=CC=C(NN)C=C1 NJZFLGLVTILGPJ-UHFFFAOYSA-N 0.000 description 1
- QQQJVBPYBFFPRU-UHFFFAOYSA-N 2-(4-hydrazinylphenyl)-n-methylacetamide;hydrochloride Chemical compound Cl.CNC(=O)CC1=CC=C(NN)C=C1 QQQJVBPYBFFPRU-UHFFFAOYSA-N 0.000 description 1
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 1
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 1
- FSJOLBAFVKSQQJ-UHFFFAOYSA-N 2-ethylpyrazol-3-amine Chemical compound CCN1N=CC=C1N FSJOLBAFVKSQQJ-UHFFFAOYSA-N 0.000 description 1
- PLKJXPACQBBJDC-UHFFFAOYSA-N 2-fluoro-4-methylbenzamide Chemical compound CC1=CC=C(C(N)=O)C(F)=C1 PLKJXPACQBBJDC-UHFFFAOYSA-N 0.000 description 1
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- OPJKGTJXHVPYIM-UHFFFAOYSA-N 2-methylprop-2-enamide;phenol Chemical compound CC(=C)C(N)=O.OC1=CC=CC=C1 OPJKGTJXHVPYIM-UHFFFAOYSA-N 0.000 description 1
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
- JESRNIJXVIFVOV-UHFFFAOYSA-N 2-methylpyrazol-3-amine Chemical compound CN1N=CC=C1N JESRNIJXVIFVOV-UHFFFAOYSA-N 0.000 description 1
- LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- INSUSOZBMWJGDG-UHFFFAOYSA-N 3,5-dimethyl-1,2-oxazol-4-amine Chemical compound CC1=NOC(C)=C1N INSUSOZBMWJGDG-UHFFFAOYSA-N 0.000 description 1
- XAABNUVFOMOJTR-UHFFFAOYSA-N 3-(1-benzylindazol-5-yl)-n-cyclopropyl-5-fluoro-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 XAABNUVFOMOJTR-UHFFFAOYSA-N 0.000 description 1
- BDBDIEBGSNUAGZ-UHFFFAOYSA-N 3-[1-(3-cyanophenyl)indol-5-yl]-n-cyclopropyl-5-fluoro-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=C2)=CC=C1N2C1=CC=CC(C#N)=C1 BDBDIEBGSNUAGZ-UHFFFAOYSA-N 0.000 description 1
- BPGCKVRRMDSUKE-UHFFFAOYSA-N 3-[1-(4-cyanophenyl)indol-5-yl]-n-cyclopropyl-5-fluoro-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=C2)=CC=C1N2C1=CC=C(C#N)C=C1 BPGCKVRRMDSUKE-UHFFFAOYSA-N 0.000 description 1
- HAYCFSVBCPIYPB-UHFFFAOYSA-N 3-[1-[4-(cyclohexylmethylamino)phenyl]indazol-5-yl]-n-cyclopropyl-5-fluoro-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2C(C=C1)=CC=C1NCC1CCCCC1 HAYCFSVBCPIYPB-UHFFFAOYSA-N 0.000 description 1
- XLPWDCDRNPGIQC-UHFFFAOYSA-N 3-[3-(2,3-dimethylimidazol-4-yl)-1h-indazol-6-yl]-n-ethyl-5-fluoro-4-methylbenzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2N(C(C)=NC=2)C)=C1 XLPWDCDRNPGIQC-UHFFFAOYSA-N 0.000 description 1
- HCMIUTZNWFKZAE-UHFFFAOYSA-N 3-[3-(2,5-dimethylpyrazol-3-yl)-1h-indazol-6-yl]-n-ethyl-4-methylbenzamide Chemical compound CCNC(=O)C1=CC=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2N(N=C(C)C=2)C)=C1 HCMIUTZNWFKZAE-UHFFFAOYSA-N 0.000 description 1
- QZUOJRFIRHIVTO-UHFFFAOYSA-N 3-[3-(3,5-dimethyl-1,2-oxazol-4-yl)-1h-indazol-6-yl]-n-ethyl-5-fluoro-4-methylbenzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=C(C3=CC=2)C2=C(ON=C2C)C)=C1 QZUOJRFIRHIVTO-UHFFFAOYSA-N 0.000 description 1
- STAXMSTYOSCIDV-UHFFFAOYSA-N 3-[3-(4-chlorophenyl)-1h-indazol-6-yl]-n-ethyl-5-fluoro-4-methylbenzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C=CC(Cl)=CC=2)=C1 STAXMSTYOSCIDV-UHFFFAOYSA-N 0.000 description 1
- CNZIGMODVMOJQJ-UHFFFAOYSA-N 3-[3-(4-ethoxyphenyl)-1h-indazol-6-yl]-n,4-diethylbenzamide Chemical compound CCNC(=O)C1=CC=C(CC)C(C=2C=C3NN=C(C3=CC=2)C=2C=CC(OCC)=CC=2)=C1 CNZIGMODVMOJQJ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
- LEUKFTOPDOPBDS-UHFFFAOYSA-N 3-fluoro-4-methyl-5-(1-phenylindazol-5-yl)-n-propylbenzamide Chemical compound CCCNC(=O)C1=CC(F)=C(C)C(C=2C=C3C=NN(C3=CC=2)C=2C=CC=CC=2)=C1 LEUKFTOPDOPBDS-UHFFFAOYSA-N 0.000 description 1
- NAUZJZJTQWXHIP-UHFFFAOYSA-N 3-fluoro-4-methyl-5-(1-phenylindazol-5-yl)-n-pyridazin-3-ylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC=2N=NC=CC=2)C=C1C(C=C1C=N2)=CC=C1N2C1=CC=CC=C1 NAUZJZJTQWXHIP-UHFFFAOYSA-N 0.000 description 1
- OZSWFLRDVNDEBZ-UHFFFAOYSA-N 3-fluoro-4-methyl-5-(1-phenylindazol-5-yl)-n-pyrimidin-2-ylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC=2N=CC=CN=2)C=C1C(C=C1C=N2)=CC=C1N2C1=CC=CC=C1 OZSWFLRDVNDEBZ-UHFFFAOYSA-N 0.000 description 1
- IMWAJHGCHZNRHF-UHFFFAOYSA-N 3-fluoro-4-methyl-n-(1h-pyrazol-5-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide Chemical compound CC1=C(F)C=C(C(=O)NC=2NN=CC=2)C=C1B1OC(C)(C)C(C)(C)O1 IMWAJHGCHZNRHF-UHFFFAOYSA-N 0.000 description 1
- LWLJCPQBFXTRMF-UHFFFAOYSA-N 3-fluoro-5-[3-(4-fluorophenyl)-1h-indazol-6-yl]-4-methyl-n-(1h-pyrazol-5-yl)benzamide Chemical compound CC1=C(F)C=C(C(=O)NC2=NNC=C2)C=C1C(C=C1NN=2)=CC=C1C=2C1=CC=C(F)C=C1 LWLJCPQBFXTRMF-UHFFFAOYSA-N 0.000 description 1
- TYNLGDBUJLVSMA-UHFFFAOYSA-N 4,5-diacetyloxy-9,10-dioxo-2-anthracenecarboxylic acid Chemical compound O=C1C2=CC(C(O)=O)=CC(OC(C)=O)=C2C(=O)C2=C1C=CC=C2OC(=O)C TYNLGDBUJLVSMA-UHFFFAOYSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- PWATUXGJXJPDET-UHFFFAOYSA-N 5,5-dimethyl-1,3,2-dioxaborinane Chemical compound CC1(C)COBOC1 PWATUXGJXJPDET-UHFFFAOYSA-N 0.000 description 1
- IQUCLICJOGHSGP-UHFFFAOYSA-N 5-bromo-1-[4-(trifluoromethyl)phenyl]indazole Chemical compound C1=CC(C(F)(F)F)=CC=C1N1C2=CC=C(Br)C=C2C=N1 IQUCLICJOGHSGP-UHFFFAOYSA-N 0.000 description 1
- VXWVFZFZYXOBTA-UHFFFAOYSA-N 5-bromo-1h-indole Chemical compound BrC1=CC=C2NC=CC2=C1 VXWVFZFZYXOBTA-UHFFFAOYSA-N 0.000 description 1
- NTCKZTBRFXTYBD-UHFFFAOYSA-N 5-methoxycarbonylpyridine-2-carboxylic acid Chemical compound COC(=O)C1=CC=C(C(O)=O)N=C1 NTCKZTBRFXTYBD-UHFFFAOYSA-N 0.000 description 1
- FSASCYKUNNXGPV-UHFFFAOYSA-N 6-(4-bromo-2-fluorobenzoyl)pyridine-3-carboxylic acid Chemical compound N1=CC(C(=O)O)=CC=C1C(=O)C1=CC=C(Br)C=C1F FSASCYKUNNXGPV-UHFFFAOYSA-N 0.000 description 1
- HQKMAMPORASMRV-UHFFFAOYSA-N 6-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1h-indazole Chemical compound O1CC(C)(C)COB1C1=CC=C(C=NN2)C2=C1 HQKMAMPORASMRV-UHFFFAOYSA-N 0.000 description 1
- NVDJVEQITUWZDT-UHFFFAOYSA-N 6-Methoxy-pyridine-3-carboxylic acid Chemical compound COC1=CC=C(C(O)=O)C=N1 NVDJVEQITUWZDT-UHFFFAOYSA-N 0.000 description 1
- ABMCJKWEGUUQBB-UHFFFAOYSA-N 6-[4-[5-(ethylcarbamoyl)-2-methylphenyl]-2-fluorobenzoyl]pyridine-3-carboxylic acid Chemical compound CCNC(=O)C1=CC=C(C)C(C=2C=C(F)C(C(=O)C=3N=CC(=CC=3)C(O)=O)=CC=2)=C1 ABMCJKWEGUUQBB-UHFFFAOYSA-N 0.000 description 1
- WMKDUJVLNZANRN-UHFFFAOYSA-N 6-bromo-1h-indazole Chemical compound BrC1=CC=C2C=NNC2=C1 WMKDUJVLNZANRN-UHFFFAOYSA-N 0.000 description 1
- RIGKWDWZQYCGMD-UHFFFAOYSA-N 6-bromo-3-(4-methoxyphenyl)-1h-indazole Chemical compound C1=CC(OC)=CC=C1C1=NNC2=CC(Br)=CC=C12 RIGKWDWZQYCGMD-UHFFFAOYSA-N 0.000 description 1
- CUYODHVYKUWKCO-UHFFFAOYSA-N 6-morpholin-4-ylpyridine-3-carbonyl chloride Chemical compound N1=CC(C(=O)Cl)=CC=C1N1CCOCC1 CUYODHVYKUWKCO-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002329 Aneurysm Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- XHVAWZZCDCWGBK-WYRLRVFGSA-M Aurothioglucose Chemical compound OC[C@H]1O[C@H](S[Au])[C@H](O)[C@@H](O)[C@@H]1O XHVAWZZCDCWGBK-WYRLRVFGSA-M 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- QHGICOPLNDPABO-UHFFFAOYSA-N CC(C(C=C1)c2cc(C(NC3CC3)=O)cc(F)c2C)c2c1[n](Cc1ccccn1)nc2 Chemical compound CC(C(C=C1)c2cc(C(NC3CC3)=O)cc(F)c2C)c2c1[n](Cc1ccccn1)nc2 QHGICOPLNDPABO-UHFFFAOYSA-N 0.000 description 1
- CQLAQHRVIBPRRO-MDAYZVFASA-N CCNC(c1cc(-c2ccc(/C(/c(nc3)ccc3C(NCC)=O)=N\NC(OC(C)(C)C)=O)c(F)c2)c(C)cc1)=O Chemical compound CCNC(c1cc(-c2ccc(/C(/c(nc3)ccc3C(NCC)=O)=N\NC(OC(C)(C)C)=O)c(F)c2)c(C)cc1)=O CQLAQHRVIBPRRO-MDAYZVFASA-N 0.000 description 1
- VTIVPCLKMSJQDE-UHFFFAOYSA-N CCNC(c1cc(C2OC(C)(C)C(C)(C)C2)c(C)cc1)=O Chemical compound CCNC(c1cc(C2OC(C)(C)C(C)(C)C2)c(C)cc1)=O VTIVPCLKMSJQDE-UHFFFAOYSA-N 0.000 description 1
- ZSUOMKRLCNWKFM-UHFFFAOYSA-N CS(c(cc1)ccc1N(CC=Cc1c2)c1ccc2Br)(=O)=O Chemical compound CS(c(cc1)ccc1N(CC=Cc1c2)c1ccc2Br)(=O)=O ZSUOMKRLCNWKFM-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- HMMPHXCOTBASBC-UHFFFAOYSA-N Cc1ccc(cn[nH]2)c2c1 Chemical compound Cc1ccc(cn[nH]2)c2c1 HMMPHXCOTBASBC-UHFFFAOYSA-N 0.000 description 1
- DCUNRLLJHAWKRZ-UHFFFAOYSA-N Cc1ccc2[nH]ncc2c1 Chemical compound Cc1ccc2[nH]ncc2c1 DCUNRLLJHAWKRZ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 206010011668 Cutaneous leishmaniasis Diseases 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 201000004624 Dermatitis 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
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 101100224482 Drosophila melanogaster PolE1 gene Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000037487 Endotoxemia Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 102100022086 GRB2-related adapter protein 2 Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000282575 Gorilla Species 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010018634 Gouty Arthritis Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010019909 Hernia Diseases 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 101000628954 Homo sapiens Mitogen-activated protein kinase 12 Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 208000004575 Infectious Arthritis Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 229940119178 Interleukin 1 receptor antagonist Drugs 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
- 102000003815 Interleukin-11 Human genes 0.000 description 1
- 108090000177 Interleukin-11 Proteins 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- 206010024453 Ligament sprain Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 102100026932 Mitogen-activated protein kinase 12 Human genes 0.000 description 1
- 102000056248 Mitogen-activated protein kinase 13 Human genes 0.000 description 1
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 1
- HZQDCMWJEBCWBR-UUOKFMHZSA-N Mizoribine Chemical compound OC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 HZQDCMWJEBCWBR-UUOKFMHZSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- BKBXKPQAZUUQHA-UHFFFAOYSA-N N-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide Chemical compound C(C1=CC=CC=C1)(=O)NB1OC(C(O1)(C)C)(C)C BKBXKPQAZUUQHA-UHFFFAOYSA-N 0.000 description 1
- XTUVJUMINZSXGF-UHFFFAOYSA-N N-methylcyclohexylamine Chemical compound CNC1CCCCC1 XTUVJUMINZSXGF-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- XPUJQEGMNQWMJI-UHFFFAOYSA-N OCC(=O)O.[Na] Chemical compound OCC(=O)O.[Na] XPUJQEGMNQWMJI-UHFFFAOYSA-N 0.000 description 1
- 102100027069 Odontogenic ameloblast-associated protein Human genes 0.000 description 1
- 101710091533 Odontogenic ameloblast-associated protein Proteins 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 239000012826 P38 inhibitor Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229920002230 Pectic acid Chemical class 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 208000012287 Prolapse Diseases 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical class CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 201000010001 Silicosis Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 201000002661 Spondylitis Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- 208000000491 Tendinopathy Diseases 0.000 description 1
- 206010043255 Tendonitis Diseases 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 206010048873 Traumatic arthritis Diseases 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- CDWOEORWPZQVNL-UHFFFAOYSA-N [4-(4-bromo-2-fluorophenyl)-2-fluorophenyl]-(6-methoxypyridin-3-yl)methanone Chemical compound C1=NC(OC)=CC=C1C(=O)C1=CC=C(C=2C(=CC(Br)=CC=2)F)C=C1F CDWOEORWPZQVNL-UHFFFAOYSA-N 0.000 description 1
- ALMFIOZYDASRRC-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(C(F)(F)F)C=C1 ALMFIOZYDASRRC-UHFFFAOYSA-N 0.000 description 1
- DBNLGTYGKCMLLR-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]hydrazine Chemical compound NNC1=CC=C(C(F)(F)F)C=C1 DBNLGTYGKCMLLR-UHFFFAOYSA-N 0.000 description 1
- BIBGVBYNIWLCFH-UHFFFAOYSA-N [5-(ethylcarbamoyl)-3-fluoro-2-methylphenyl]boronic acid Chemical compound CCNC(=O)C1=CC(F)=C(C)C(B(O)O)=C1 BIBGVBYNIWLCFH-UHFFFAOYSA-N 0.000 description 1
- LYMIRAMTHDJMGF-UHFFFAOYSA-H [B+3].[B+3].C(CO)(=O)[O-].C(CO)(=O)[O-].C(CO)(=O)[O-].C(CO)(=O)[O-].C(CO)(=O)[O-].C(CO)(=O)[O-] Chemical compound [B+3].[B+3].C(CO)(=O)[O-].C(CO)(=O)[O-].C(CO)(=O)[O-].C(CO)(=O)[O-].C(CO)(=O)[O-].C(CO)(=O)[O-] LYMIRAMTHDJMGF-UHFFFAOYSA-H 0.000 description 1
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000000061 acid fraction Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000005103 alkyl silyl group Chemical group 0.000 description 1
- 208000002205 allergic conjunctivitis Diseases 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 229920000469 amphiphilic block copolymer Polymers 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 229960004238 anakinra Drugs 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical group 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 208000024998 atopic conjunctivitis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- AUJRCFUBUPVWSZ-XTZHGVARSA-M auranofin Chemical compound CCP(CC)(CC)=[Au]S[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O AUJRCFUBUPVWSZ-XTZHGVARSA-M 0.000 description 1
- 229960005207 auranofin Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940092782 bentonite Drugs 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 208000019664 bone resorption disease Diseases 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229940081733 cetearyl alcohol Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229940090805 clavulanate Drugs 0.000 description 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 238000013267 controlled drug release Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 229940076286 cupric acetate Drugs 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
- IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 229920006237 degradable polymer Polymers 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229960004590 diacerein Drugs 0.000 description 1
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical class [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- UZZWBUYVTBPQIV-UHFFFAOYSA-N dme dimethoxyethane Chemical compound COCCOC.COCCOC UZZWBUYVTBPQIV-UHFFFAOYSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 239000003221 ear drop Substances 0.000 description 1
- 229940047652 ear drops Drugs 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000008387 emulsifying waxe Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- VYSYZMNJHYOXGN-UHFFFAOYSA-N ethyl n-aminocarbamate Chemical compound CCOC(=O)NN VYSYZMNJHYOXGN-UHFFFAOYSA-N 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000005454 flavour additive Substances 0.000 description 1
- 230000009969 flowable effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049654 glyceryl behenate Drugs 0.000 description 1
- 229940015045 gold sodium thiomalate Drugs 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000009499 grossing Methods 0.000 description 1
- 235000015220 hamburgers Nutrition 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- UKACHOXRXFQJFN-UHFFFAOYSA-N heptafluoropropane Chemical compound FC(F)C(F)(F)C(F)(F)F UKACHOXRXFQJFN-UHFFFAOYSA-N 0.000 description 1
- UBHWBODXJBSFLH-UHFFFAOYSA-N hexadecan-1-ol;octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO.CCCCCCCCCCCCCCCCCCO UBHWBODXJBSFLH-UHFFFAOYSA-N 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 150000005828 hydrofluoroalkanes Chemical class 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- VIPHVHVAGBKHGR-UHFFFAOYSA-N hydron;pyridine-2-carbonyl chloride;chloride Chemical compound Cl.ClC(=O)C1=CC=CC=N1 VIPHVHVAGBKHGR-UHFFFAOYSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 229940041682 inhalant solution Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940074383 interleukin-11 Drugs 0.000 description 1
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 239000006204 intramuscular dosage form Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007916 intrasternal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007915 intraurethral administration Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
- 229960000681 leflunomide Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- 229940049920 malate Drugs 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
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- 239000002032 methanolic fraction Substances 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- JMCOYJWUCDGIPI-UHFFFAOYSA-N methyl 3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate Chemical compound COC(=O)C1=CC(F)=C(C)C(B2OC(C)(C)C(C)(C)O2)=C1 JMCOYJWUCDGIPI-UHFFFAOYSA-N 0.000 description 1
- PWGDZDWFDKJBDO-UHFFFAOYSA-N methyl 6-(4-bromo-2-fluorobenzoyl)pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1C(=O)C1=CC=C(Br)C=C1F PWGDZDWFDKJBDO-UHFFFAOYSA-N 0.000 description 1
- FUGOPLLTIUPDDN-UHFFFAOYSA-N methyl 6-carbonochloridoylpyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(C(Cl)=O)N=C1 FUGOPLLTIUPDDN-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 229950000844 mizoribine Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- CJAHDFUKLBIQBM-UHFFFAOYSA-N n-(3,5-dimethyl-1,2-oxazol-4-yl)-3-[3-(4-fluorophenyl)-1h-indazol-6-yl]-4-methylbenzamide Chemical compound CC1=NOC(C)=C1NC(=O)C1=CC=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C=CC(F)=CC=2)=C1 CJAHDFUKLBIQBM-UHFFFAOYSA-N 0.000 description 1
- GAKMFCZHJOFLMT-UHFFFAOYSA-N n-(3,5-dimethyl-1,2-oxazol-4-yl)-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide Chemical compound CC1=NOC(C)=C1NC(=O)C1=CC=C(C)C(B2OC(C)(C)C(C)(C)O2)=C1 GAKMFCZHJOFLMT-UHFFFAOYSA-N 0.000 description 1
- UTBQXALOUHZIDB-UHFFFAOYSA-N n-azaniumyl-n-tert-butylcarbamate Chemical compound CC(C)(C)N(N)C(O)=O UTBQXALOUHZIDB-UHFFFAOYSA-N 0.000 description 1
- ULASBDREKKAFLK-UHFFFAOYSA-N n-cyclobutyl-3-[1-(4-fluorophenyl)indazol-5-yl]-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CCC2)C=C1C(C=C1C=N2)=CC=C1N2C1=CC=C(F)C=C1 ULASBDREKKAFLK-UHFFFAOYSA-N 0.000 description 1
- GFGJJRCORGVYJX-UHFFFAOYSA-N n-cyclopropyl-3-[1-(2,6-dimethylpyrimidin-4-yl)indazol-5-yl]-5-fluoro-4-methylbenzamide Chemical compound CC1=NC(C)=CC(N2C3=CC=C(C=C3C=N2)C=2C(=C(F)C=C(C=2)C(=O)NC2CC2)C)=N1 GFGJJRCORGVYJX-UHFFFAOYSA-N 0.000 description 1
- WJFYVPJVVFJQCH-UHFFFAOYSA-N n-cyclopropyl-3-[1-(4-fluorophenyl)indazol-5-yl]-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2C1=CC=C(F)C=C1 WJFYVPJVVFJQCH-UHFFFAOYSA-N 0.000 description 1
- NNTJZTNFDLRKQB-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-(1-pyridin-2-ylindol-5-yl)benzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=C2)=CC=C1N2C1=CC=CC=N1 NNTJZTNFDLRKQB-UHFFFAOYSA-N 0.000 description 1
- YTOSCRNOYWHUJA-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-(1-pyridin-3-ylindol-5-yl)benzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=C2)=CC=C1N2C1=CC=CN=C1 YTOSCRNOYWHUJA-UHFFFAOYSA-N 0.000 description 1
- KTKXKAUXBKMPFU-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[1-(3-methylphenyl)indazol-5-yl]benzamide Chemical compound CC1=CC=CC(N2C3=CC=C(C=C3C=N2)C=2C(=C(F)C=C(C=2)C(=O)NC2CC2)C)=C1 KTKXKAUXBKMPFU-UHFFFAOYSA-N 0.000 description 1
- HUXZHQWROUSXCW-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[1-(4-oxo-1h-pyrimidin-6-yl)indazol-5-yl]benzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2C1=CC(=O)NC=N1 HUXZHQWROUSXCW-UHFFFAOYSA-N 0.000 description 1
- NZTBUDPFRREBAK-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[1-(pyridin-4-ylmethyl)indazol-5-yl]benzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2CC1=CC=NC=C1 NZTBUDPFRREBAK-UHFFFAOYSA-N 0.000 description 1
- HVGDUOYATMQBDE-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[1-[(5-methyl-1,2-oxazol-3-yl)methyl]indazol-5-yl]benzamide Chemical compound O1C(C)=CC(CN2C3=CC=C(C=C3C=N2)C=2C(=C(F)C=C(C=2)C(=O)NC2CC2)C)=N1 HVGDUOYATMQBDE-UHFFFAOYSA-N 0.000 description 1
- QJIKUFLACUBXHW-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[1-[4-(trifluoromethyl)phenyl]indazol-5-yl]benzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2C1=CC=C(C(F)(F)F)C=C1 QJIKUFLACUBXHW-UHFFFAOYSA-N 0.000 description 1
- WXNCMOUYVVGHME-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[1-[[4-(trifluoromethyl)phenyl]methyl]indazol-5-yl]benzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2CC1=CC=C(C(F)(F)F)C=C1 WXNCMOUYVVGHME-UHFFFAOYSA-N 0.000 description 1
- JDQVRNQCEDPRIO-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-5-[1-[(4-fluorophenyl)methyl]indazol-5-yl]-4-methylbenzamide Chemical compound CC1=C(F)C=C(C(=O)NC2CC2)C=C1C(C=C1C=N2)=CC=C1N2CC1=CC=C(F)C=C1 JDQVRNQCEDPRIO-UHFFFAOYSA-N 0.000 description 1
- GLSSVRGOTTUQNM-UHFFFAOYSA-N n-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1B1OC(C)(C)C(C)(C)O1 GLSSVRGOTTUQNM-UHFFFAOYSA-N 0.000 description 1
- ANJCTCHWVMSSJR-UHFFFAOYSA-N n-ethyl-3-[3-(6-fluoropyridin-3-yl)-1h-indazol-6-yl]-4-methylbenzamide Chemical compound CCNC(=O)C1=CC=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C=NC(F)=CC=2)=C1 ANJCTCHWVMSSJR-UHFFFAOYSA-N 0.000 description 1
- XJCZDKOVAOLSPG-UHFFFAOYSA-N n-ethyl-3-fluoro-4-methyl-5-(3-pyridin-3-yl-1h-indazol-6-yl)benzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C=NC=CC=2)=C1 XJCZDKOVAOLSPG-UHFFFAOYSA-N 0.000 description 1
- ORKSYKPAICYYSK-UHFFFAOYSA-N n-ethyl-3-fluoro-4-methyl-5-(3-pyrimidin-2-yl-1h-indazol-6-yl)benzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2N=CC=CN=2)=C1 ORKSYKPAICYYSK-UHFFFAOYSA-N 0.000 description 1
- JRYVQTRFUPGUJD-UHFFFAOYSA-N n-ethyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(B2OC(C)(C)C(C)(C)O2)=C1 JRYVQTRFUPGUJD-UHFFFAOYSA-N 0.000 description 1
- QETLCPMBMMDBEM-UHFFFAOYSA-N n-ethyl-3-fluoro-4-methyl-5-[3-(4-methylphenyl)-1h-indazol-6-yl]benzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C=CC(C)=CC=2)=C1 QETLCPMBMMDBEM-UHFFFAOYSA-N 0.000 description 1
- WRHFWHMEXRDEFO-UHFFFAOYSA-N n-ethyl-3-fluoro-4-methyl-5-[3-[4-(trifluoromethyl)phenyl]-1h-indazol-6-yl]benzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C=CC(=CC=2)C(F)(F)F)=C1 WRHFWHMEXRDEFO-UHFFFAOYSA-N 0.000 description 1
- AUIINSOCKDQPRK-UHFFFAOYSA-N n-ethyl-3-fluoro-5-(1h-indazol-6-yl)-4-methylbenzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=CC3=CC=2)=C1 AUIINSOCKDQPRK-UHFFFAOYSA-N 0.000 description 1
- HCOCFQKLKQSGLE-UHFFFAOYSA-N n-ethyl-3-fluoro-5-[3-(2-methoxypyridin-3-yl)-1h-indazol-6-yl]-4-methylbenzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C(=NC=CC=2)OC)=C1 HCOCFQKLKQSGLE-UHFFFAOYSA-N 0.000 description 1
- QESYLBXKGNKJHG-UHFFFAOYSA-N n-ethyl-3-fluoro-5-[3-(4-fluoro-2-methylphenyl)-1h-indazol-6-yl]-4-methylbenzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C(=CC(F)=CC=2)C)=C1 QESYLBXKGNKJHG-UHFFFAOYSA-N 0.000 description 1
- JECACOKCQKOBQV-UHFFFAOYSA-N n-ethyl-3-fluoro-5-[3-(6-methoxypyridin-3-yl)-1h-indazol-6-yl]-4-methylbenzamide Chemical compound CCNC(=O)C1=CC(F)=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C=NC(OC)=CC=2)=C1 JECACOKCQKOBQV-UHFFFAOYSA-N 0.000 description 1
- LJLSNJGQMLUIJV-UHFFFAOYSA-N n-ethyl-4-methyl-3-(3-pyrazin-2-yl-1h-indazol-6-yl)benzamide Chemical compound CCNC(=O)C1=CC=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2N=CC=NC=2)=C1 LJLSNJGQMLUIJV-UHFFFAOYSA-N 0.000 description 1
- AQWZNSTXHKOOCJ-UHFFFAOYSA-N n-ethyl-4-methyl-3-(3-pyrimidin-5-yl-1h-indazol-6-yl)benzamide Chemical compound CCNC(=O)C1=CC=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C=NC=NC=2)=C1 AQWZNSTXHKOOCJ-UHFFFAOYSA-N 0.000 description 1
- UBSOWCULIXVZGE-UHFFFAOYSA-N n-ethyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide Chemical compound CCNC(=O)C1=CC=C(C)C(B2OC(C)(C)C(C)(C)O2)=C1 UBSOWCULIXVZGE-UHFFFAOYSA-N 0.000 description 1
- ZVCRLZXNJDOQAH-UHFFFAOYSA-N n-ethyl-4-methyl-3-[3-(4-methylsulfonylphenyl)-1h-indazol-6-yl]benzamide Chemical compound CCNC(=O)C1=CC=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C=CC(=CC=2)S(C)(=O)=O)=C1 ZVCRLZXNJDOQAH-UHFFFAOYSA-N 0.000 description 1
- ZLILSJXAOMVVIF-UHFFFAOYSA-N n-ethyl-4-methyl-3-[3-(6-morpholin-4-ylpyridin-3-yl)-1h-indazol-6-yl]benzamide Chemical compound CCNC(=O)C1=CC=C(C)C(C=2C=C3NN=C(C3=CC=2)C=2C=NC(=CC=2)N2CCOCC2)=C1 ZLILSJXAOMVVIF-UHFFFAOYSA-N 0.000 description 1
- GXMBMSWZFYNJRR-UHFFFAOYSA-N n-ethyl-6-[6-[5-(ethylcarbamoyl)-2-methylphenyl]-1h-indazol-3-yl]pyridine-3-carboxamide Chemical compound N1=CC(C(=O)NCC)=CC=C1C1=NNC2=CC(C=3C(=CC=C(C=3)C(=O)NCC)C)=CC=C12 GXMBMSWZFYNJRR-UHFFFAOYSA-N 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000002232 neuromuscular Effects 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
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 208000002865 osteopetrosis Diseases 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- YNOGYQAEJGADFJ-UHFFFAOYSA-N oxolan-2-ylmethanamine Chemical compound NCC1CCCO1 YNOGYQAEJGADFJ-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000002948 pantothenic acids Chemical class 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920002721 polycyanoacrylate Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Chemical class 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- QPMDWIOUHQWKHV-ODZAUARKSA-M potassium;(z)-4-hydroxy-4-oxobut-2-enoate Chemical compound [K+].OC(=O)\C=C/C([O-])=O QPMDWIOUHQWKHV-ODZAUARKSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 239000011253 protective coating Substances 0.000 description 1
- 229940076372 protein antagonist Drugs 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- TXJKATOSKLUITR-UHFFFAOYSA-N pyrazine-2-carbonyl chloride Chemical compound ClC(=O)C1=CN=CC=N1 TXJKATOSKLUITR-UHFFFAOYSA-N 0.000 description 1
- NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
- FOVRZAGACROHCK-UHFFFAOYSA-N pyrimidine-2-carbonyl chloride Chemical compound ClC(=O)C1=NC=CC=N1 FOVRZAGACROHCK-UHFFFAOYSA-N 0.000 description 1
- ZFCHNZDUMIOWFV-UHFFFAOYSA-N pyrimidine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CC=N1 ZFCHNZDUMIOWFV-UHFFFAOYSA-N 0.000 description 1
- NFKXXURQUMEXDJ-UHFFFAOYSA-N pyrimidine-5-carbonyl chloride Chemical compound ClC(=O)C1=CN=CN=C1 NFKXXURQUMEXDJ-UHFFFAOYSA-N 0.000 description 1
- IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 230000015227 regulation of liquid surface tension Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- QTTRZHGPGKRAFB-OOKHYKNYSA-N rimexolone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CC)(C)[C@@]1(C)C[C@@H]2O QTTRZHGPGKRAFB-OOKHYKNYSA-N 0.000 description 1
- 229960001487 rimexolone Drugs 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 201000001223 septic arthritis Diseases 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- AGHLUVOCTHWMJV-UHFFFAOYSA-J sodium;gold(3+);2-sulfanylbutanedioate Chemical compound [Na+].[Au+3].[O-]C(=O)CC(S)C([O-])=O.[O-]C(=O)CC(S)C([O-])=O AGHLUVOCTHWMJV-UHFFFAOYSA-J 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 239000006203 subcutaneous dosage form Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 201000004415 tendinitis Diseases 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- YDTJDBMLMMWJJX-UHFFFAOYSA-N tert-butyl 3-[3-(2,3-dimethylimidazol-4-yl)-1-(2-trimethylsilylethoxymethyl)indazol-6-yl]-5-fluoro-4-methylbenzoate Chemical compound CN1C(C)=NC=C1C1=NN(COCC[Si](C)(C)C)C2=CC(C=3C(=C(F)C=C(C=3)C(=O)OC(C)(C)C)C)=CC=C12 YDTJDBMLMMWJJX-UHFFFAOYSA-N 0.000 description 1
- RFDWLOJJQVQVCF-UHFFFAOYSA-N tert-butyl 3-fluoro-5-[3-iodo-1-(2-trimethylsilylethoxymethyl)indazol-6-yl]-4-methylbenzoate Chemical compound CC1=C(F)C=C(C(=O)OC(C)(C)C)C=C1C1=CC=C(C(I)=NN2COCC[Si](C)(C)C)C2=C1 RFDWLOJJQVQVCF-UHFFFAOYSA-N 0.000 description 1
- QWKJDWLDKQAOSJ-UHFFFAOYSA-N tert-butyl 5-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]indazole-1-carboxylate Chemical compound C1=C(C=2C=C3C=NN(C3=CC=2)C(=O)OC(C)(C)C)C(C)=C(F)C=C1C(=O)NC1CC1 QWKJDWLDKQAOSJ-UHFFFAOYSA-N 0.000 description 1
- VYLRFCJIOMUBPO-UHFFFAOYSA-N tert-butyl n-[[(4-bromo-2-fluorophenyl)-(4-methoxyphenyl)methylidene]amino]carbamate Chemical compound C1=CC(OC)=CC=C1C(=NNC(=O)OC(C)(C)C)C1=CC=C(Br)C=C1F VYLRFCJIOMUBPO-UHFFFAOYSA-N 0.000 description 1
- CQLAQHRVIBPRRO-UHFFFAOYSA-N tert-butyl n-[[[4-[5-(ethylcarbamoyl)-2-methylphenyl]-2-fluorophenyl]-[5-(ethylcarbamoyl)pyridin-2-yl]methylidene]amino]carbamate Chemical compound N1=CC(C(=O)NCC)=CC=C1C(=NNC(=O)OC(C)(C)C)C1=CC=C(C=2C(=CC=C(C=2)C(=O)NCC)C)C=C1F CQLAQHRVIBPRRO-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- MUQNAPSBHXFMHT-UHFFFAOYSA-N tert-butylhydrazine Chemical compound CC(C)(C)NN MUQNAPSBHXFMHT-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000005505 thiomorpholino group Chemical group 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 238000004454 trace mineral analysis Methods 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- CWAPIHCLJCNFTN-UHFFFAOYSA-N tributyl-(2,3-dimethylimidazol-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CN=C(C)N1C CWAPIHCLJCNFTN-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
- 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/08—Antibacterial agents for leprosy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an alkyl or cycloalkyl radical attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Cardiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Vascular Medicine (AREA)
- Transplantation (AREA)
- Obesity (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0402143.2A GB0402143D0 (en) | 2004-01-30 | 2004-01-30 | Novel compounds |
| PCT/GB2005/000265 WO2005073189A1 (en) | 2004-01-30 | 2005-01-27 | Fused heteroyral derivatives for use as p38 kinase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007519692A true JP2007519692A (ja) | 2007-07-19 |
| JP2007519692A5 JP2007519692A5 (enExample) | 2008-03-13 |
Family
ID=31971803
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006550294A Pending JP2007519692A (ja) | 2004-01-30 | 2005-01-27 | p38キナーゼ阻害剤として使用するための縮合ヘテロアリール誘導体 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20090023725A1 (enExample) |
| EP (1) | EP1708996B1 (enExample) |
| JP (1) | JP2007519692A (enExample) |
| AT (1) | ATE406351T1 (enExample) |
| DE (1) | DE602005009318D1 (enExample) |
| ES (1) | ES2313283T3 (enExample) |
| GB (1) | GB0402143D0 (enExample) |
| WO (1) | WO2005073189A1 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007519695A (ja) * | 2004-01-30 | 2007-07-19 | スミスクライン ビーチャム コーポレーション | I.A.関節リウマチの治療においてp38キナーゼ阻害剤として使用するための縮合ヘテロアリール誘導体 |
| JP2023179378A (ja) * | 2022-06-02 | 2023-12-19 | イーライ リリー アンド カンパニー | cGAS阻害剤 |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0124934D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124933D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124939D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124938D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124941D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| ES2295553T3 (es) * | 2002-02-12 | 2008-04-16 | Smithkline Beecham Corporation | Derivados de nicotinamida utiles como inhibidores de p38. |
| GB0402138D0 (en) | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| CA2655999A1 (en) * | 2006-06-28 | 2008-01-03 | Aska Pharmaceutical Co., Ltd. | Treating agent of inflammatory bowel disease |
| JP2010509265A (ja) | 2006-11-09 | 2010-03-25 | エフ.ホフマン−ラ ロシュ アーゲー | キナーゼ阻害剤としての置換6−フェニル−ピリド[2,3−d]ピリミジン−7−オン誘導体及びそれの使用方法 |
| WO2008099615A1 (ja) | 2007-02-16 | 2008-08-21 | Aska Pharmaceutical Co., Ltd. | 微粒子油性懸濁液を含む医薬組成物 |
| CA2685597C (en) | 2007-05-07 | 2012-10-02 | Amgen Inc. | Pyrazolo-pyridinone and pyrazolo-pyrazinone compounds as p38 modulators, process for their preparation, and their pharmaceutical use |
| EP2152704A1 (en) * | 2007-05-07 | 2010-02-17 | Amgen, Inc | Pyrazolo-pyridinone compounds, process for their preparation, and their pharmaceutical use |
| EP1992344A1 (en) | 2007-05-18 | 2008-11-19 | Institut Curie | P38 alpha as a therapeutic target in pathologies linked to FGFR3 mutation |
| WO2009079797A1 (en) | 2007-12-26 | 2009-07-02 | Critical Outcome Technologies, Inc. | Compounds and method for treatment of cancer |
| US8367671B2 (en) | 2008-03-21 | 2013-02-05 | Amgen Inc. | Pyrazolo[3.4-B]pyrazine compounds as p38 modulators and methods of use as anti-inflamatory agents |
| EP3023426A1 (en) | 2008-07-17 | 2016-05-25 | Critical Outcome Technologies, Inc. | Thiosemicarbazone inhibitor compounds and cancer treatment methods |
| CN102209721A (zh) | 2008-09-11 | 2011-10-05 | 安姆根有限公司 | 作为β-分泌酶调节剂的螺四环化合物及其使用方法 |
| US8969350B2 (en) * | 2008-12-18 | 2015-03-03 | Astrazeneca Ab | Pharmaceutical product comprising a p38 kinase inhibitor and a second active ingredient |
| US8822485B2 (en) | 2009-11-23 | 2014-09-02 | Amgen Inc. | Amino heteroaryl compounds as beta-secretase modulators and methods of use |
| WO2011063233A1 (en) | 2009-11-23 | 2011-05-26 | Amgen Inc. | Amino heteroaryl compounds as beta-secretase modulators and methods of use |
| WO2011090911A1 (en) | 2010-01-19 | 2011-07-28 | Amgen Inc. | Amino heteroaryl compounds as beta-secretase modulators and methods of use |
| EP2547686B1 (en) | 2010-03-15 | 2014-01-22 | Amgen Inc. | Amino-dihydrooxazine and amino-dihydrothiazine spiro compounds as beta-secretase modulators and their medical use |
| US8883782B2 (en) | 2010-03-15 | 2014-11-11 | Amgen Inc. | Spiro-tetracyclic ring compounds as beta-secretase modulators and methods of use |
| WO2011120153A1 (en) | 2010-04-01 | 2011-10-06 | Critical Outcome Technologies Inc. | Compounds and method for treatment of hiv |
| US8293738B2 (en) | 2010-05-12 | 2012-10-23 | Abbott Laboratories | Indazole inhibitors of kinase |
| US8921363B2 (en) | 2010-08-05 | 2014-12-30 | Amgen Inc. | Derivatives of 1 H-isoindol-3-amine, 1 H-iso-aza-indol-3amine, 3,4-dihydroisoquinolin-1-amine, and 1,4-dihydroisoquinolin-3-amine as beta-secretase inhibitors |
| EP2643325A1 (en) | 2010-11-23 | 2013-10-02 | Amgen Inc. | Spiro-amino-imidazolone and spiro-amino-dihydro-pyrimidinone compounds as beta-secretase modulators and methods of use |
| EP2673279A1 (en) | 2011-02-07 | 2013-12-18 | Amgen Inc. | 5-amino-oxazepine and 5-amino-thiazepane compounds as beta-secretase antagonists and methods of use |
| EP2675810A1 (en) | 2011-02-15 | 2013-12-25 | Amgen Inc. | Spiro-amino-imidazo-fused heterocyclic compounds as beta-secretase modulators and methods of use |
| JP2014526560A (ja) | 2011-09-21 | 2014-10-06 | アムジエン・インコーポレーテツド | β‐セクレターゼ調節因子としてのアミノオキサジン化合物およびアミノジヒドロチアジン化合物および使用方法 |
| US9725469B2 (en) | 2012-11-15 | 2017-08-08 | Amgen, Inc. | Amino-oxazine and amino-dihydrothiazine compounds as beta-secretase modulators and methods of use |
| CN105017256A (zh) | 2014-04-29 | 2015-11-04 | 浙江导明医药科技有限公司 | 多氟化合物作为布鲁顿酪氨酸激酶抑制剂 |
| US9717745B2 (en) | 2015-03-19 | 2017-08-01 | Zhejiang DTRM Biopharma Co. Ltd. | Pharmaceutical compositions and their use for treatment of cancer and autoimmune diseases |
| US10342786B2 (en) | 2017-10-05 | 2019-07-09 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD |
| PT3691620T (pt) | 2017-10-05 | 2022-10-06 | Fulcrum Therapeutics Inc | Os inibidores da quinase p38 reduzem a expressão de dux4 e genes a jusante para o tratamento de fshd |
| TW201922256A (zh) | 2017-10-27 | 2019-06-16 | 中國大陸商浙江導明醫藥科技有限公司 | 治療淋巴樣惡性疾病之方法 |
| WO2021038419A1 (en) * | 2019-08-23 | 2021-03-04 | Insilico Medicine Ip Limited | Kinase inhibitors and methods of synthesis and treatment |
| US12293809B2 (en) | 2019-08-23 | 2025-05-06 | Insilico Medicine Ip Limited | Workflow for generating compounds with biological activity against a specific biological target |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002055517A2 (en) * | 2000-12-20 | 2002-07-18 | Jingrong Cui | 4-(hetero)aryl substituted indolinones |
| WO2003093248A1 (en) * | 2002-04-30 | 2003-11-13 | Smithkline Beecham Corporation | Heteroaryl substituted biphenyl derivatives as p38 kinase inhibitors |
| WO2004010995A1 (en) * | 2002-07-31 | 2004-02-05 | Smithkline Beecham Corporation | Fused heteroaryl derivatives for use as p38 kinase inhibitors in the treatment of i.a. rheumatoid arthristis |
Family Cites Families (70)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4200750A (en) * | 1977-01-07 | 1980-04-29 | Westwood Pharmaceuticals Inc. | 4-Substituted imidazo [1,2-a]quinoxalines |
| MX16687A (es) * | 1988-07-07 | 1994-01-31 | Ciba Geigy Ag | Compuestos de biarilo y procedimiento para su preparacion. |
| GB9816837D0 (en) * | 1998-08-04 | 1998-09-30 | Zeneca Ltd | Amide derivatives |
| US5246943A (en) * | 1992-05-19 | 1993-09-21 | Warner-Lambert Company | Substituted 1,2,3,4-tetahydroisoquinolines with angiotensin II receptor antagonist properties |
| US5236934A (en) * | 1992-08-26 | 1993-08-17 | E. I. Du Pont De Nemours And Company | 1,2,3,4-tetrahydroisoquinolines useful in the treatment of CNS disorders |
| IL108630A0 (en) * | 1993-02-18 | 1994-05-30 | Fmc Corp | Insecticidal substituted 2,4-diaminoquinazolines |
| GB9408577D0 (en) * | 1994-04-29 | 1994-06-22 | Fujisawa Pharmaceutical Co | New compound |
| US5521213A (en) * | 1994-08-29 | 1996-05-28 | Merck Frosst Canada, Inc. | Diaryl bicyclic heterocycles as inhibitors of cyclooxygenase-2 |
| IL118544A (en) * | 1995-06-07 | 2001-08-08 | Smithkline Beecham Corp | History of imidazole, the process for their preparation and the pharmaceutical preparations containing them |
| WO1997008133A1 (fr) * | 1995-08-22 | 1997-03-06 | Japan Tobacco Inc. | Composes amide et leur utilisation |
| US6323227B1 (en) * | 1996-01-02 | 2001-11-27 | Aventis Pharmaceuticals Products Inc. | Substituted N-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides |
| US6080767A (en) * | 1996-01-02 | 2000-06-27 | Aventis Pharmaceuticals Products Inc. | Substituted n-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides |
| TR199801361T2 (xx) * | 1996-01-11 | 1998-10-21 | Smithkline Beecham Corporation | Yeni ikameli imidazol bile�imleri. |
| FR2754260B1 (fr) * | 1996-10-04 | 1998-10-30 | Adir | Nouveaux derives substitues de biphenyle ou de phenylpyridine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US6147080A (en) * | 1996-12-18 | 2000-11-14 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| US5945418A (en) * | 1996-12-18 | 1999-08-31 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| US6087496A (en) * | 1998-05-22 | 2000-07-11 | G. D. Searle & Co. | Substituted pyrazoles suitable as p38 kinase inhibitors |
| CA2288741A1 (en) * | 1997-05-22 | 1998-11-26 | G.D. Searle And Co. | 4-aryl-3(5)-heteroaryl substituted pyrazoles as p38 kinase inhibitors |
| EP1023066A4 (en) * | 1997-06-13 | 2001-05-23 | Smithkline Beecham Corp | NEW PYRAZOLE AND PYRAZOLINE SUBSTITUTED COMPOUND |
| US6060491A (en) * | 1997-06-19 | 2000-05-09 | Dupont Pharmaceuticals | 6-membered aromatics as factor Xa inhibitors |
| CA2295762A1 (en) * | 1997-07-02 | 1999-01-14 | Ravi Shanker Garigipati | Novel cycloalkyl substituted imidazoles |
| DE69816651T2 (de) * | 1997-09-05 | 2004-04-01 | Glaxo Group Ltd., Greenford | 2,3-diaryl-pyrazolo[1,5-b]pyridazin derivate, deren herstellung und deren verwendung als cyclooxygenase 2 (cox-2) inhibitoren |
| KR100340273B1 (ko) * | 1997-10-14 | 2002-06-14 | 야마모토 카즈모토 | 비페닐-5-알칸산 유도체 및 이의 용도 |
| DE19817461A1 (de) * | 1998-04-20 | 1999-10-21 | Basf Ag | Neue substituierte Benzamide, deren Herstellung und Anwendung |
| JP2002515476A (ja) * | 1998-05-15 | 2002-05-28 | アストラゼネカ アクチボラグ | サイトカインにより仲介される疾病の処置のためのベンズアミド誘導体 |
| US6448257B1 (en) * | 1998-05-22 | 2002-09-10 | Scios, Inc. | Compounds and methods to treat cardiac failure and other disorders |
| US6130235A (en) * | 1998-05-22 | 2000-10-10 | Scios Inc. | Compounds and methods to treat cardiac failure and other disorders |
| US6867209B1 (en) * | 1998-05-22 | 2005-03-15 | Scios, Inc. | Indole-type derivatives as inhibitors of p38 kinase |
| US6184226B1 (en) * | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
| AU762245B2 (en) * | 1998-09-18 | 2003-06-19 | Vertex Pharmaceuticals Incorporated | Inhibitors of p38 |
| EP1140840B1 (en) * | 1999-01-13 | 2006-03-22 | Bayer Pharmaceuticals Corp. | -g(v)-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| WO2000047554A2 (en) * | 1999-02-11 | 2000-08-17 | Cor Therapeutics Inc. | INHIBITORS OF FACTOR Xa |
| ES2216631T3 (es) * | 1999-02-27 | 2004-10-16 | Glaxo Group Limited | Pirazolpiridinas. |
| US6509361B1 (en) * | 1999-05-12 | 2003-01-21 | Pharmacia Corporation | 1,5-Diaryl substituted pyrazoles as p38 kinase inhibitors |
| CA2374793A1 (en) * | 1999-05-24 | 2000-11-30 | Penglie Zhang | Inhibitors of factor xa |
| DE19932571A1 (de) * | 1999-07-13 | 2001-01-18 | Clariant Gmbh | Verfahren zur Herstellung von Biarylen unter Palladophosphacyclobutan-Katalyse |
| GB9919778D0 (en) * | 1999-08-21 | 1999-10-27 | Zeneca Ltd | Chemical compounds |
| US6576632B1 (en) * | 1999-08-27 | 2003-06-10 | Pfizer Inc | Biaryl compounds useful as anticancer agents |
| PE20020506A1 (es) * | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
| DE10059418A1 (de) * | 2000-11-30 | 2002-06-20 | Aventis Pharma Gmbh | Ortho, meta-substituierte Bisarylverbindungen, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| DE10060807A1 (de) * | 2000-12-07 | 2002-06-20 | Aventis Pharma Gmbh | Ortho, ortho-substituierte stickstoffhaltige Bisarylverbindungen, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| DE10063008A1 (de) * | 2000-12-16 | 2002-06-20 | Merck Patent Gmbh | Carbonsäureamidderivate |
| DE10110749A1 (de) * | 2001-03-07 | 2002-09-12 | Bayer Ag | Substituierte Aminodicarbonsäurederivate |
| OA12552A (en) * | 2001-03-09 | 2006-06-06 | Pfizer Prod Inc | Triazolopyridines as anti-inflammatory agents. |
| EP1383731B1 (en) * | 2001-04-06 | 2009-08-05 | Biocryst Pharmaceuticals, Inc. | Biaryl compounds as serine protease inhibitors |
| FR2824827B1 (fr) * | 2001-05-17 | 2004-02-13 | Fournier Lab Sa | Nouveaux derives de 5-phenyl-1h-indole antagoniste des recepteurs de l'interleukine-8 |
| AR037233A1 (es) * | 2001-09-07 | 2004-11-03 | Euro Celtique Sa | Piridinas aril sustituidas, composiciones farmaceuticas y el uso de dichos compuestos para la elaboracion de un medicamento |
| GB0124848D0 (en) * | 2001-10-16 | 2001-12-05 | Celltech R&D Ltd | Chemical compounds |
| GB0124931D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124941D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124936D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124932D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124938D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124934D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124939D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| GB0124933D0 (en) * | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| ES2295553T3 (es) * | 2002-02-12 | 2008-04-16 | Smithkline Beecham Corporation | Derivados de nicotinamida utiles como inhibidores de p38. |
| US20030225089A1 (en) * | 2002-04-10 | 2003-12-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and p38 kinase inhibitors |
| US20040116479A1 (en) * | 2002-10-04 | 2004-06-17 | Fortuna Haviv | Method of inhibiting angiogenesis |
| US7136850B2 (en) * | 2002-12-20 | 2006-11-14 | International Business Machines Corporation | Self tuning database retrieval optimization using regression functions |
| ATE406360T1 (de) * | 2003-03-07 | 2008-09-15 | Lilly Co Eli | Antagonisten der opioidrezeptoren |
| GB0308186D0 (en) * | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
| GB0308201D0 (en) * | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
| GB0308185D0 (en) * | 2003-04-09 | 2003-05-14 | Smithkline Beecham Corp | Novel compounds |
| DE602004029293D1 (de) * | 2003-07-25 | 2010-11-04 | Novartis Ag | p-38-Kinasehemmer |
| GB0318814D0 (en) * | 2003-08-11 | 2003-09-10 | Smithkline Beecham Corp | Novel compounds |
| GB0402140D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| GB0402137D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| GB0402138D0 (en) * | 2004-01-30 | 2004-03-03 | Smithkline Beecham Corp | Novel compounds |
| US20080051416A1 (en) * | 2004-10-05 | 2008-02-28 | Smithkline Beecham Corporation | Novel Compounds |
-
2004
- 2004-01-30 GB GBGB0402143.2A patent/GB0402143D0/en not_active Ceased
-
2005
- 2005-01-27 JP JP2006550294A patent/JP2007519692A/ja active Pending
- 2005-01-27 DE DE602005009318T patent/DE602005009318D1/de not_active Expired - Lifetime
- 2005-01-27 EP EP05702022A patent/EP1708996B1/en not_active Expired - Lifetime
- 2005-01-27 WO PCT/GB2005/000265 patent/WO2005073189A1/en not_active Ceased
- 2005-01-27 US US10/587,790 patent/US20090023725A1/en not_active Abandoned
- 2005-01-27 ES ES05702022T patent/ES2313283T3/es not_active Expired - Lifetime
- 2005-01-27 AT AT05702022T patent/ATE406351T1/de not_active IP Right Cessation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002055517A2 (en) * | 2000-12-20 | 2002-07-18 | Jingrong Cui | 4-(hetero)aryl substituted indolinones |
| WO2003093248A1 (en) * | 2002-04-30 | 2003-11-13 | Smithkline Beecham Corporation | Heteroaryl substituted biphenyl derivatives as p38 kinase inhibitors |
| WO2004010995A1 (en) * | 2002-07-31 | 2004-02-05 | Smithkline Beecham Corporation | Fused heteroaryl derivatives for use as p38 kinase inhibitors in the treatment of i.a. rheumatoid arthristis |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007519695A (ja) * | 2004-01-30 | 2007-07-19 | スミスクライン ビーチャム コーポレーション | I.A.関節リウマチの治療においてp38キナーゼ阻害剤として使用するための縮合ヘテロアリール誘導体 |
| JP2023179378A (ja) * | 2022-06-02 | 2023-12-19 | イーライ リリー アンド カンパニー | cGAS阻害剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2313283T3 (es) | 2009-03-01 |
| US20090023725A1 (en) | 2009-01-22 |
| ATE406351T1 (de) | 2008-09-15 |
| EP1708996A1 (en) | 2006-10-11 |
| DE602005009318D1 (de) | 2008-10-09 |
| EP1708996B1 (en) | 2008-08-27 |
| WO2005073189A1 (en) | 2005-08-11 |
| GB0402143D0 (en) | 2004-03-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2007519692A (ja) | p38キナーゼ阻害剤として使用するための縮合ヘテロアリール誘導体 | |
| JP4901102B2 (ja) | プロテインキナーゼモジュレーターおよびその使用方法 | |
| EP1709046B1 (en) | P38 kinase inhibitors | |
| JP4630662B2 (ja) | I.A.慢性関節リウマチの治療においてp38キナーゼ阻害剤として使用される縮合ヘテロアリール誘導体 | |
| CN1832928B (zh) | 以5元杂环为基础的p38激酶抑制剂 | |
| US7687532B2 (en) | Fused heteroaryl derivatives for use as p38 kinase inhibitors in the treatment of I.A. rheumatoid arthritis | |
| JP5425057B2 (ja) | Hsp90阻害剤としてのキナゾリン−オキシム誘導体 | |
| JP4679509B2 (ja) | 2,3,6−置換−4−ピリミドン誘導体 | |
| CN102066353B (zh) | 二取代的酞嗪Hedgehog通路拮抗剂 | |
| US20060211709A1 (en) | Protein kinase modulators and methods of use | |
| US20010039286A1 (en) | 2-aryl indole derivatives and their use as therapeutic agents | |
| US7750026B2 (en) | Fused heteroaryl derivatives and their use as p38 kinase inhibitors | |
| CN114269755A (zh) | 作为magl抑制剂的4,4a,5,7,8,8a-六吡啶并[4,3-b][1,4]噁嗪-3-酮化合物 | |
| CN103917525A (zh) | Lrrk2激酶活性的抑制剂 | |
| CN101547916A (zh) | mGluR5调节剂 | |
| JP2005508967A (ja) | p38キナーゼ阻害剤としてのビフェニルカルボン酸アミド誘導体 | |
| EP1730114A1 (en) | Benzazepine derivatives for the treatment of neurological and psychiatric disorders | |
| CN101965338B (zh) | 杂环 | |
| US20250154147A1 (en) | Novel amine-substituted phthalazines and derivatives as sos1 inhibitors | |
| TWI472514B (zh) | 吡唑類化合物 | |
| TWI434686B (zh) | 咪唑-4-酮及咪唑-4-硫酮化合物 | |
| WO2025215121A1 (en) | Hedgehog acyltransferase inhibitors | |
| HK40062310A (en) | 4,4a,5,7,8,8a-hexapyrido[4,3-b][1,4]oxazin-3-one compounds as magl inhibitors | |
| MXPA06008080A (en) | Indole derivatives and use thereof as kinase inhibitors in particular ikk2 inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080122 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080122 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110405 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110624 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110701 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20111213 |