BR112017005266B1 - Compostos inibidores de mk2 e composição farmaceuticamente aceitável que os compreende - Google Patents

Info

Publication number

BR112017005266B1

BR112017005266B1 BR112017005266-0A BR112017005266A BR112017005266B1 BR 112017005266 B1 BR112017005266 B1 BR 112017005266B1 BR 112017005266 A BR112017005266 A BR 112017005266A BR 112017005266 B1 BR112017005266 B1 BR 112017005266B1

Authority

BR

Brazil

Prior art keywords

compound

mmol

aliphatic

int

certain embodiments

Prior art date

2014-09-17

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 499
• 239000000203 mixture Substances 0.000 title claims abstract description 138
• 229940124789 MK2 inhibitor Drugs 0.000 title abstract description 8
• 150000003839 salts Chemical class 0.000 claims description 30
• 239000003981 vehicle Substances 0.000 claims description 17
• 239000002671 adjuvant Substances 0.000 claims description 12
• 239000003937 drug carrier Substances 0.000 claims description 12
• 239000002131 composite material Substances 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 35
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 208
• 125000001931 aliphatic group Chemical group 0.000 description 196
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 192
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 169
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 166
• 229910052757 nitrogen Inorganic materials 0.000 description 164
• 239000011541 reaction mixture Substances 0.000 description 153
• 230000015572 biosynthetic process Effects 0.000 description 152
• 238000003786 synthesis reaction Methods 0.000 description 149
• 239000007787 solid Substances 0.000 description 148
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 139
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 137
• 229910052760 oxygen Inorganic materials 0.000 description 137
• 239000001301 oxygen Chemical group 0.000 description 137
• 229920006395 saturated elastomer Polymers 0.000 description 135
• 239000000243 solution Substances 0.000 description 133
• 229910052717 sulfur Chemical group 0.000 description 133
• 239000011593 sulfur Chemical group 0.000 description 133
• 229910052736 halogen Inorganic materials 0.000 description 129
• HNDGEYCCZGRMTN-UHFFFAOYSA-N thieno[3,2-f:4,5-f]bis[1]benzothiophene Chemical compound S1C2=CC=3SC=CC=3C=C2C2=C1C=C(SC=C1)C1=C2 HNDGEYCCZGRMTN-UHFFFAOYSA-N 0.000 description 126
• 125000005842 heteroatom Chemical group 0.000 description 124
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 116
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
• 238000005160 1H NMR spectroscopy Methods 0.000 description 100
• 230000002829 reductive effect Effects 0.000 description 85
• 150000002367 halogens Chemical class 0.000 description 81
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 81
• 229910052739 hydrogen Inorganic materials 0.000 description 75
• 239000001257 hydrogen Substances 0.000 description 74
• 238000006243 chemical reaction Methods 0.000 description 71
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 64
• 125000000623 heterocyclic group Chemical group 0.000 description 62
• 235000019439 ethyl acetate Nutrition 0.000 description 56
• 125000002950 monocyclic group Chemical group 0.000 description 54
• 125000005843 halogen group Chemical group 0.000 description 53
• 125000003118 aryl group Chemical group 0.000 description 51
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 47
• 239000012044 organic layer Substances 0.000 description 45
• 239000013058 crude material Substances 0.000 description 43
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 41
• -1 monocyclic hydrocarbon Chemical class 0.000 description 41
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
• 208000035475 disorder Diseases 0.000 description 35
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 32
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 32
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 30
• 125000004429 atom Chemical group 0.000 description 30
• 125000002618 bicyclic heterocycle group Chemical group 0.000 description 30
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 29
• 201000010099 disease Diseases 0.000 description 29
• 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 description 28
• 125000002619 bicyclic group Chemical group 0.000 description 27
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 27
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 25
• 235000002639 sodium chloride Nutrition 0.000 description 25
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 24
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
• 108091000080 Phosphotransferase Proteins 0.000 description 23
• 125000002947 alkylene group Chemical group 0.000 description 23
• 102000020233 phosphotransferase Human genes 0.000 description 23
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
• 239000007788 liquid Substances 0.000 description 22
• 238000010898 silica gel chromatography Methods 0.000 description 22
• 239000000725 suspension Substances 0.000 description 22
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
• 229910052799 carbon Inorganic materials 0.000 description 20
• 125000001424 substituent group Chemical group 0.000 description 20
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
• 150000002431 hydrogen Chemical group 0.000 description 18
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 17
• NFTNYEQPGPAENQ-UHFFFAOYSA-N CN(CCOC1=NC(=CC(=N1)N)F)C Chemical compound CN(CCOC1=NC(=CC(=N1)N)F)C NFTNYEQPGPAENQ-UHFFFAOYSA-N 0.000 description 17
• 239000012267 brine Substances 0.000 description 17
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
• 150000001721 carbon Chemical group 0.000 description 16
• 125000001072 heteroaryl group Chemical group 0.000 description 16
• 150000002430 hydrocarbons Chemical group 0.000 description 16
• 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
• 125000001309 chloro group Chemical group Cl* 0.000 description 15
• 238000004440 column chromatography Methods 0.000 description 15
• 230000000694 effects Effects 0.000 description 15
• 125000001153 fluoro group Chemical group F* 0.000 description 15
• 229910000027 potassium carbonate Inorganic materials 0.000 description 15
• 239000000741 silica gel Substances 0.000 description 15
• 229910002027 silica gel Inorganic materials 0.000 description 15
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
• 102000001253 Protein Kinase Human genes 0.000 description 14
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
• 230000001404 mediated effect Effects 0.000 description 14
• 108060006633 protein kinase Proteins 0.000 description 14
• 238000000746 purification Methods 0.000 description 14
• 239000000047 product Substances 0.000 description 13
• 238000003756 stirring Methods 0.000 description 13
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
• 239000000706 filtrate Substances 0.000 description 12
• 239000003112 inhibitor Substances 0.000 description 12
• 230000002401 inhibitory effect Effects 0.000 description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
• 125000004433 nitrogen atom Chemical group N* 0.000 description 12
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
• 102000004190 Enzymes Human genes 0.000 description 11
• 108090000790 Enzymes Proteins 0.000 description 11
• 239000002552 dosage form Substances 0.000 description 11
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 11
• 239000003208 petroleum Substances 0.000 description 11
• 238000012746 preparative thin layer chromatography Methods 0.000 description 11
• QDXGKRWDQCEABB-UHFFFAOYSA-N pyrimidine-5-carboxamide Chemical compound NC(=O)C1=CN=CN=C1 QDXGKRWDQCEABB-UHFFFAOYSA-N 0.000 description 11
• 229910052938 sodium sulfate Inorganic materials 0.000 description 11
• 235000011152 sodium sulphate Nutrition 0.000 description 11
• PEDMFCHWOVJDNW-UHFFFAOYSA-N 5-fluoro-2-nitroaniline Chemical compound NC1=CC(F)=CC=C1[N+]([O-])=O PEDMFCHWOVJDNW-UHFFFAOYSA-N 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
• 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 10
• UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 10
• 125000000217 alkyl group Chemical group 0.000 description 10
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 10
• 229910000024 caesium carbonate Inorganic materials 0.000 description 10
• 239000005457 ice water Substances 0.000 description 10
• 125000003566 oxetanyl group Chemical group 0.000 description 10
• 125000003386 piperidinyl group Chemical group 0.000 description 10
• 239000002904 solvent Substances 0.000 description 10
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
• 239000012472 biological sample Substances 0.000 description 9
• 239000012043 crude product Substances 0.000 description 9
• 238000009472 formulation Methods 0.000 description 9
• 229910000104 sodium hydride Inorganic materials 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 8
• 125000002837 carbocyclic group Chemical group 0.000 description 8
• OVJIHFBAXJKTRF-SSDOTTSWSA-N chembl556392 Chemical compound O=C1N[C@H](C)CNC2=C1SC1=CC=C(N=C(Cl)C=C3)C3=C21 OVJIHFBAXJKTRF-SSDOTTSWSA-N 0.000 description 8
• 239000003814 drug Substances 0.000 description 8
• 235000019441 ethanol Nutrition 0.000 description 8
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 8
• 238000004519 manufacturing process Methods 0.000 description 8
• 229920001223 polyethylene glycol Polymers 0.000 description 8
• 235000015320 potassium carbonate Nutrition 0.000 description 8
• 239000002244 precipitate Substances 0.000 description 8
• 108090000623 proteins and genes Proteins 0.000 description 8
• 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 8
• YMVNHXZFDQSCRK-UHFFFAOYSA-N 4,6-dichloro-2-iodopyrimidine Chemical compound ClC1=CC(Cl)=NC(I)=N1 YMVNHXZFDQSCRK-UHFFFAOYSA-N 0.000 description 7
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
• ZATNFORFELDNSM-GFCCVEGCSA-N C(C)(C)(C)OC(=O)N[C@@H](CNC1=C(SC=2C1=C1C=CC=NC1=CC=2)C(=O)OC)C Chemical compound C(C)(C)(C)OC(=O)N[C@@H](CNC1=C(SC=2C1=C1C=CC=NC1=CC=2)C(=O)OC)C ZATNFORFELDNSM-GFCCVEGCSA-N 0.000 description 7
• QCTQVQBBOBTFRE-UHFFFAOYSA-N ClC1=CC(=NC(=N1)OC1CN(CCC1)C)N Chemical compound ClC1=CC(=NC(=N1)OC1CN(CCC1)C)N QCTQVQBBOBTFRE-UHFFFAOYSA-N 0.000 description 7
• 206010028980 Neoplasm Diseases 0.000 description 7
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 150000001413 amino acids Chemical class 0.000 description 7
• 235000011114 ammonium hydroxide Nutrition 0.000 description 7
• 230000001363 autoimmune Effects 0.000 description 7
• 239000002775 capsule Substances 0.000 description 7
• 210000004027 cell Anatomy 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• 238000003818 flash chromatography Methods 0.000 description 7
• 238000010438 heat treatment Methods 0.000 description 7
• 235000011181 potassium carbonates Nutrition 0.000 description 7
• 239000011734 sodium Substances 0.000 description 7
• 239000012312 sodium hydride Substances 0.000 description 7
• 208000024891 symptom Diseases 0.000 description 7
• 239000003826 tablet Substances 0.000 description 7
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 6
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
• VITWKLCJAFIUGR-UHFFFAOYSA-N C(C)(C)(C)NC1=NC(=NC(=C1)F)CI Chemical compound C(C)(C)(C)NC1=NC(=NC(=C1)F)CI VITWKLCJAFIUGR-UHFFFAOYSA-N 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• CNZPGLOLJYMTJW-SBSPUUFOSA-N OC(=O)C(F)(F)F.COC(=O)c1sc2ccc3ncccc3c2c1NC[C@@H](C)N Chemical compound OC(=O)C(F)(F)F.COC(=O)c1sc2ccc3ncccc3c2c1NC[C@@H](C)N CNZPGLOLJYMTJW-SBSPUUFOSA-N 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
• 239000002585 base Substances 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 239000000460 chlorine Substances 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 238000001914 filtration Methods 0.000 description 6
• 210000001035 gastrointestinal tract Anatomy 0.000 description 6
• 239000008101 lactose Substances 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
• 239000003921 oil Substances 0.000 description 6
• 235000019198 oils Nutrition 0.000 description 6
• 239000012074 organic phase Substances 0.000 description 6
• 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 6
• 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 6
• 239000000546 pharmaceutical excipient Substances 0.000 description 6
• 238000002953 preparative HPLC Methods 0.000 description 6
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
• 239000007858 starting material Substances 0.000 description 6
• 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 6
• PDMMBPHJODEJQV-UHFFFAOYSA-N 2,6-dichloro-n-[(4-methoxyphenyl)methyl]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1CNC1=CC(Cl)=NC(Cl)=N1 PDMMBPHJODEJQV-UHFFFAOYSA-N 0.000 description 5
• PYCIBXGKTGBHHF-UHFFFAOYSA-N 6-aminoquinoline-5-carbonitrile Chemical compound N1=CC=CC2=C(C#N)C(N)=CC=C21 PYCIBXGKTGBHHF-UHFFFAOYSA-N 0.000 description 5
• DTWHKRFZYKUTHB-UHFFFAOYSA-N 6-bromoquinoline-5-carbonitrile Chemical compound N1=CC=CC2=C(C#N)C(Br)=CC=C21 DTWHKRFZYKUTHB-UHFFFAOYSA-N 0.000 description 5
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
• 208000023275 Autoimmune disease Diseases 0.000 description 5
• JAKDAWYJWRNELA-UHFFFAOYSA-N C(C)(C)(C)NC1=NC(=NC(=C1)Cl)I Chemical compound C(C)(C)(C)NC1=NC(=NC(=C1)Cl)I JAKDAWYJWRNELA-UHFFFAOYSA-N 0.000 description 5
• QNXSIFUWJWKTTA-UHFFFAOYSA-N C(C)(C)(C)NC1=NC(=NC(=C1)Cl)OC1CN(CCC1)C Chemical compound C(C)(C)(C)NC1=NC(=NC(=C1)Cl)OC1CN(CCC1)C QNXSIFUWJWKTTA-UHFFFAOYSA-N 0.000 description 5
• VKEIGYSQABRPMW-UHFFFAOYSA-N C(C)(C)(C)NC1=NC(=NC(=C1)F)C(=O)OC Chemical compound C(C)(C)(C)NC1=NC(=NC(=C1)F)C(=O)OC VKEIGYSQABRPMW-UHFFFAOYSA-N 0.000 description 5
• JOCFQUCSEWKBKG-UHFFFAOYSA-N C(C)(C)(C)NC1=NC(=NC(=C1)F)CO Chemical compound C(C)(C)(C)NC1=NC(=NC(=C1)F)CO JOCFQUCSEWKBKG-UHFFFAOYSA-N 0.000 description 5
• ITOPAZWZNWXZGO-UHFFFAOYSA-N C(C)(C)(C)NC1=NC(=NC(=C1)F)I Chemical compound C(C)(C)(C)NC1=NC(=NC(=C1)F)I ITOPAZWZNWXZGO-UHFFFAOYSA-N 0.000 description 5
• VMCALTJFFMUSQV-UHFFFAOYSA-N C(C)(C)(C)NC1=NC(=NC(=C1)F)N Chemical compound C(C)(C)(C)NC1=NC(=NC(=C1)F)N VMCALTJFFMUSQV-UHFFFAOYSA-N 0.000 description 5
• WXGQUFSFDDYUOZ-UHFFFAOYSA-N ClC1=CC(=NC(=N1)I)NCC1=CC=C(C=C1)OC Chemical compound ClC1=CC(=NC(=N1)I)NCC1=CC=C(C=C1)OC WXGQUFSFDDYUOZ-UHFFFAOYSA-N 0.000 description 5
• BRCRRBUUZKIITM-UHFFFAOYSA-N ClC1=CC(=NC(=N1)OCCOC)N Chemical compound ClC1=CC(=NC(=N1)OCCOC)N BRCRRBUUZKIITM-UHFFFAOYSA-N 0.000 description 5
• XQFWFUOFJZOHBO-UHFFFAOYSA-N ClC1=CC(=NC(=N1)OCCOC)NCC1=CC=C(C=C1)OC Chemical compound ClC1=CC(=NC(=N1)OCCOC)NCC1=CC=C(C=C1)OC XQFWFUOFJZOHBO-UHFFFAOYSA-N 0.000 description 5
• VYJQBTBISGWCMB-UHFFFAOYSA-N ClC1=NC(=NC(=C1)NCC1=CC=C(C=C1)OC)C(=O)OC Chemical compound ClC1=NC(=NC(=C1)NCC1=CC=C(C=C1)OC)C(=O)OC VYJQBTBISGWCMB-UHFFFAOYSA-N 0.000 description 5
• OOXNZRSYNLEPIS-UHFFFAOYSA-N FC1=CC(=NC(=N1)CN1CCCCC1)N Chemical compound FC1=CC(=NC(=N1)CN1CCCCC1)N OOXNZRSYNLEPIS-UHFFFAOYSA-N 0.000 description 5
• ZAGZXJFSNYXWPH-UHFFFAOYSA-N FC1=NC(=NC(=C1)F)OCC1(COC1)C Chemical compound FC1=NC(=NC(=C1)F)OCC1(COC1)C ZAGZXJFSNYXWPH-UHFFFAOYSA-N 0.000 description 5
• 206010016654 Fibrosis Diseases 0.000 description 5
• GDCCWBXPPAQDOH-UHFFFAOYSA-N NC1=C(SC=2C1=C1C=CC=NC1=CC=2)C(=O)OC Chemical compound NC1=C(SC=2C1=C1C=CC=NC1=CC=2)C(=O)OC GDCCWBXPPAQDOH-UHFFFAOYSA-N 0.000 description 5
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 5
• NLKBUJQLMRHSKP-SSDOTTSWSA-N [(2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propyl] methanesulfonate Chemical compound CS(=O)(=O)OC[C@@H](C)NC(=O)OC(C)(C)C NLKBUJQLMRHSKP-SSDOTTSWSA-N 0.000 description 5
• 238000010521 absorption reaction Methods 0.000 description 5
• 125000002527 bicyclic carbocyclic group Chemical group 0.000 description 5
• 238000000576 coating method Methods 0.000 description 5
• MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 5
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 5
• 235000018417 cysteine Nutrition 0.000 description 5
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 5
• 125000006575 electron-withdrawing group Chemical group 0.000 description 5
• 239000003480 eluent Substances 0.000 description 5
• 239000000284 extract Substances 0.000 description 5
• 230000003176 fibrotic effect Effects 0.000 description 5
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 5
• 230000002427 irreversible effect Effects 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• SRVUVLBNPDRACT-UHFFFAOYSA-N methyl 1-bromothieno[3,2-f]quinoline-2-carboxylate Chemical compound N1=CC=CC2=C(C(=C(C(=O)OC)S3)Br)C3=CC=C21 SRVUVLBNPDRACT-UHFFFAOYSA-N 0.000 description 5
• 239000006187 pill Substances 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• 102000004169 proteins and genes Human genes 0.000 description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 5
• 239000007909 solid dosage form Substances 0.000 description 5
• 208000011580 syndromic disease Diseases 0.000 description 5
• JQXZBJAAOLPTKP-ZCFIWIBFSA-N tert-butyl n-[(2r)-1-aminopropan-2-yl]carbamate Chemical compound NC[C@@H](C)NC(=O)OC(C)(C)C JQXZBJAAOLPTKP-ZCFIWIBFSA-N 0.000 description 5
• QNBSOZHFBNUGCB-LURJTMIESA-N tert-butyl n-[(2s)-1-azidopropan-2-yl]carbamate Chemical compound [N-]=[N+]=NC[C@H](C)NC(=O)OC(C)(C)C QNBSOZHFBNUGCB-LURJTMIESA-N 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
• NLQMSBJFLQPLIJ-UHFFFAOYSA-N (3-methyloxetan-3-yl)methanol Chemical compound OCC1(C)COC1 NLQMSBJFLQPLIJ-UHFFFAOYSA-N 0.000 description 4
• ALOCUZOKRULSAA-UHFFFAOYSA-N 1-methylpiperidin-4-amine Chemical compound CN1CCC(N)CC1 ALOCUZOKRULSAA-UHFFFAOYSA-N 0.000 description 4
• NTSYSQNAPGMSIH-UHFFFAOYSA-N 2,4,6-trifluoropyrimidine Chemical compound FC1=CC(F)=NC(F)=N1 NTSYSQNAPGMSIH-UHFFFAOYSA-N 0.000 description 4
• RZVUFAWKJMGXSK-UHFFFAOYSA-N 2,4-dichloro-5-(ethoxymethyl)pyrimidine Chemical compound CCOCC1=CN=C(Cl)N=C1Cl RZVUFAWKJMGXSK-UHFFFAOYSA-N 0.000 description 4
• RSWJZQPZLNLWGF-UHFFFAOYSA-N 2H-thieno[3,2-f]quinolin-8-one Chemical compound C=1CSC=2C=1C1=CC(C=NC1=CC=2)=O RSWJZQPZLNLWGF-UHFFFAOYSA-N 0.000 description 4
• BXYZFBZFOPCYGD-UHFFFAOYSA-N 3-[[3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenoxy]methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(COC=2C=C(C=CC=2)C=2C3=CC=CC(=C3N=CC=2C(=O)C=2C=CC=CC=2)C(F)(F)F)=C1 BXYZFBZFOPCYGD-UHFFFAOYSA-N 0.000 description 4
• JPZOAVGMSDSWSW-UHFFFAOYSA-N 4,6-dichloropyrimidin-2-amine Chemical compound NC1=NC(Cl)=CC(Cl)=N1 JPZOAVGMSDSWSW-UHFFFAOYSA-N 0.000 description 4
• 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 4
• UAJOQWQMIDQIRX-UHFFFAOYSA-N C(C)(C)(C)NC1=NC(=NC(=C1)F)CN1CCCCC1 Chemical compound C(C)(C)(C)NC1=NC(=NC(=C1)F)CN1CCCCC1 UAJOQWQMIDQIRX-UHFFFAOYSA-N 0.000 description 4
• 208000024172 Cardiovascular disease Diseases 0.000 description 4
• JTVQWPUSZRNPDR-OAHLLOKOSA-N ClC1=NC=C(C(=N1)N(C1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O)C)C(=O)NCC1=CC=C(C=C1)OC Chemical compound ClC1=NC=C(C(=N1)N(C1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O)C)C(=O)NCC1=CC=C(C=C1)OC JTVQWPUSZRNPDR-OAHLLOKOSA-N 0.000 description 4
• WSPZDDYKUFPBGO-UHFFFAOYSA-N FC1=CC(=NC(=N1)OC1CN(CCC1)C)N Chemical compound FC1=CC(=NC(=N1)OC1CN(CCC1)C)N WSPZDDYKUFPBGO-UHFFFAOYSA-N 0.000 description 4
• KEZJJQMWYOAKCG-UHFFFAOYSA-N FC1=CC(=NC(=N1)OCCOC)N Chemical compound FC1=CC(=NC(=N1)OCCOC)N KEZJJQMWYOAKCG-UHFFFAOYSA-N 0.000 description 4
• WRQAPBWDQDEZIS-UHFFFAOYSA-N FC1=NC(=NC(=C1)F)OCCOC Chemical compound FC1=NC(=NC(=C1)F)OCCOC WRQAPBWDQDEZIS-UHFFFAOYSA-N 0.000 description 4
• XHFJSSYFRSWSMH-UHFFFAOYSA-N FC1=NC(=NC(=C1)OCCOC)N Chemical compound FC1=NC(=NC(=C1)OCCOC)N XHFJSSYFRSWSMH-UHFFFAOYSA-N 0.000 description 4
• OUBORTRIKPEZMG-UHFFFAOYSA-N INT-2 Chemical compound Nc1c(ncn1-c1ccc(F)cc1)C(=N)C#N OUBORTRIKPEZMG-UHFFFAOYSA-N 0.000 description 4
• 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 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• 108010041955 MAP-kinase-activated kinase 2 Proteins 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
• 241001465754 Metazoa Species 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
• 108010029485 Protein Isoforms Proteins 0.000 description 4
• 102000001708 Protein Isoforms Human genes 0.000 description 4
• 206010040070 Septic Shock Diseases 0.000 description 4
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
• 101001060278 Xenopus laevis Fibroblast growth factor 3 Proteins 0.000 description 4
• 229960000583 acetic acid Drugs 0.000 description 4
• 239000002253 acid Substances 0.000 description 4
• 230000001154 acute effect Effects 0.000 description 4
• MJBWDEQAUQTVKK-IAGOWNOFSA-N aflatoxin M1 Chemical compound C=1([C@]2(O)C=CO[C@@H]2OC=1C=C(C1=2)OC)C=2OC(=O)C2=C1CCC2=O MJBWDEQAUQTVKK-IAGOWNOFSA-N 0.000 description 4
• 229910052786 argon Inorganic materials 0.000 description 4
• 230000001908 autoinhibitory effect Effects 0.000 description 4
• 229910052801 chlorine Inorganic materials 0.000 description 4
• 239000012230 colorless oil Substances 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 4
• 125000000753 cycloalkyl group Chemical group 0.000 description 4
• 239000003085 diluting agent Substances 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 239000003995 emulsifying agent Substances 0.000 description 4
• 229910052731 fluorine Inorganic materials 0.000 description 4
• 229930195733 hydrocarbon Natural products 0.000 description 4
• 239000013038 irreversible inhibitor Substances 0.000 description 4
• 208000030159 metabolic disease Diseases 0.000 description 4
• 125000002757 morpholinyl group Chemical group 0.000 description 4
• 235000005152 nicotinamide Nutrition 0.000 description 4
• 239000011570 nicotinamide Substances 0.000 description 4
• 229960003966 nicotinamide Drugs 0.000 description 4
• 231100000252 nontoxic Toxicity 0.000 description 4
• 230000003000 nontoxic effect Effects 0.000 description 4
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
• 125000004193 piperazinyl group Chemical group 0.000 description 4
• 229920000642 polymer Polymers 0.000 description 4
• 125000006413 ring segment Chemical group 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 235000017557 sodium bicarbonate Nutrition 0.000 description 4
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
• 230000003381 solubilizing effect Effects 0.000 description 4
• PDAFIZPRSXHMCO-ZCFIWIBFSA-N tert-butyl n-[(2r)-1-hydroxypropan-2-yl]carbamate Chemical compound OC[C@@H](C)NC(=O)OC(C)(C)C PDAFIZPRSXHMCO-ZCFIWIBFSA-N 0.000 description 4
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 4
• 229940124597 therapeutic agent Drugs 0.000 description 4
• 230000000699 topical effect Effects 0.000 description 4
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 4
• 239000001993 wax Substances 0.000 description 4
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
• UKANCZCEGQDKGF-UHFFFAOYSA-N 1-methylpiperidin-3-ol Chemical compound CN1CCCC(O)C1 UKANCZCEGQDKGF-UHFFFAOYSA-N 0.000 description 3
• QHTUMQYGZQYEOZ-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)ethanol Chemical compound CN1CCN(CCO)CC1 QHTUMQYGZQYEOZ-UHFFFAOYSA-N 0.000 description 3
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 3
• GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 3
• UHEDQSRQDTVBPY-UHFFFAOYSA-N 4-chloro-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine Chemical compound C1CN(C)CCN1C1=NC(N)=NC(Cl)=N1 UHEDQSRQDTVBPY-UHFFFAOYSA-N 0.000 description 3
• PPUIVMHRKBEYCR-UHFFFAOYSA-N 6-fluoropyrimidin-4-amine Chemical class NC1=CC(F)=NC=N1 PPUIVMHRKBEYCR-UHFFFAOYSA-N 0.000 description 3
• CELVMQZHFSJQJV-UHFFFAOYSA-N BrCC=1C(=NC=NC=1)Cl Chemical compound BrCC=1C(=NC=NC=1)Cl CELVMQZHFSJQJV-UHFFFAOYSA-N 0.000 description 3
• XOACFSGKRSKQFZ-UHFFFAOYSA-N C(C)(C)(C)OCC=1C(=NC(=NC=1)Cl)Cl Chemical compound C(C)(C)(C)OCC=1C(=NC(=NC=1)Cl)Cl XOACFSGKRSKQFZ-UHFFFAOYSA-N 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• 239000004215 Carbon black (E152) Substances 0.000 description 3
• LBEAKINJOQNLSI-SSDOTTSWSA-N ClC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)CI)=O Chemical compound ClC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)CI)=O LBEAKINJOQNLSI-SSDOTTSWSA-N 0.000 description 3
• PXLNZVUGYJIUBK-UHFFFAOYSA-N ClC1=NC=C(C(=N1)Cl)COC(F)F Chemical compound ClC1=NC=C(C(=N1)Cl)COC(F)F PXLNZVUGYJIUBK-UHFFFAOYSA-N 0.000 description 3
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
• JWWUUHYQISHKGO-UHFFFAOYSA-N FC1=CC(=NC(=N1)OCC1(COC1)C)N Chemical compound FC1=CC(=NC(=N1)OCC1(COC1)C)N JWWUUHYQISHKGO-UHFFFAOYSA-N 0.000 description 3
• XCTOSLYYNGDVAI-GFCCVEGCSA-N FC1=CC(=NC(=N1)OCC1(COC1)C)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O Chemical compound FC1=CC(=NC(=N1)OCC1(COC1)C)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O XCTOSLYYNGDVAI-GFCCVEGCSA-N 0.000 description 3
• LVDVOJSHQJZHHJ-RXMQYKEDSA-N FC1=NC(=CC(=N1)F)O[C@H]1COCC1 Chemical compound FC1=NC(=CC(=N1)F)O[C@H]1COCC1 LVDVOJSHQJZHHJ-RXMQYKEDSA-N 0.000 description 3
• HHNVLXOWTGBYPT-RXMQYKEDSA-N FC1=NC(=NC(=C1)F)O[C@H]1COCC1 Chemical compound FC1=NC(=NC(=C1)F)O[C@H]1COCC1 HHNVLXOWTGBYPT-RXMQYKEDSA-N 0.000 description 3
• NKANYCPCMZPNTO-UHFFFAOYSA-N FC1=NC(=NC(=C1)OC1COC1)N Chemical compound FC1=NC(=NC(=C1)OC1COC1)N NKANYCPCMZPNTO-UHFFFAOYSA-N 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 206010019668 Hepatic fibrosis Diseases 0.000 description 3
• 241000124008 Mammalia Species 0.000 description 3
• 101100317378 Mus musculus Wnt3 gene Proteins 0.000 description 3
• NTOWBSWPSQHWKB-VIFPVBQESA-N N(=[N+]=[N-])C[C@H]1NC(C2=C(C=3C=4C=CC(=NC=4C=CC=3S2)NC2=NC=NC(=C2)F)NC1)=O Chemical compound N(=[N+]=[N-])C[C@H]1NC(C2=C(C=3C=4C=CC(=NC=4C=CC=3S2)NC2=NC=NC(=C2)F)NC1)=O NTOWBSWPSQHWKB-VIFPVBQESA-N 0.000 description 3
• TYQFCXKEJPCFOQ-UHFFFAOYSA-N N-(6-fluoropyrimidin-4-yl)-N',N'-dimethylethane-1,2-diamine Chemical compound CN(C)CCNC1=CC(F)=NC=N1 TYQFCXKEJPCFOQ-UHFFFAOYSA-N 0.000 description 3
• 108010066154 Nuclear Export Signals Proteins 0.000 description 3
• 108010077850 Nuclear Localization Signals Proteins 0.000 description 3
• 229910019142 PO4 Inorganic materials 0.000 description 3
• 208000002193 Pain Diseases 0.000 description 3
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
• 239000002202 Polyethylene glycol Substances 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• 229930006000 Sucrose Natural products 0.000 description 3
• 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 3
• 239000005864 Sulphur Substances 0.000 description 3
• 206010052779 Transplant rejections Diseases 0.000 description 3
• 206010047115 Vasculitis Diseases 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• 230000001476 alcoholic effect Effects 0.000 description 3
• 235000010443 alginic acid Nutrition 0.000 description 3
• 229920000615 alginic acid Polymers 0.000 description 3
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
• 125000003342 alkenyl group Chemical group 0.000 description 3
• 229910021529 ammonia Inorganic materials 0.000 description 3
• 239000012298 atmosphere Substances 0.000 description 3
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 3
• 239000001768 carboxy methyl cellulose Substances 0.000 description 3
• 230000003197 catalytic effect Effects 0.000 description 3
• 230000036755 cellular response Effects 0.000 description 3
• 208000026106 cerebrovascular disease Diseases 0.000 description 3
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
• 208000022993 cryopyrin-associated periodic syndrome Diseases 0.000 description 3
• 125000002993 cycloalkylene group Chemical group 0.000 description 3
• 210000000805 cytoplasm Anatomy 0.000 description 3
• 230000003111 delayed effect Effects 0.000 description 3
• 229910052805 deuterium Inorganic materials 0.000 description 3
• 235000014113 dietary fatty acids Nutrition 0.000 description 3
• 239000002270 dispersing agent Substances 0.000 description 3
• 239000003623 enhancer Substances 0.000 description 3
• QINRQIZOBCQKAZ-UHFFFAOYSA-N ethyl 4-amino-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(SC)N=C1N QINRQIZOBCQKAZ-UHFFFAOYSA-N 0.000 description 3
• 239000000194 fatty acid Substances 0.000 description 3
• 229930195729 fatty acid Natural products 0.000 description 3
• 230000004761 fibrosis Effects 0.000 description 3
• 239000000945 filler Substances 0.000 description 3
• 239000012065 filter cake Substances 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
• 235000013305 food Nutrition 0.000 description 3
• 239000008187 granular material Substances 0.000 description 3
• 239000003701 inert diluent Substances 0.000 description 3
• 208000027866 inflammatory disease Diseases 0.000 description 3
• 230000002757 inflammatory effect Effects 0.000 description 3
• 239000000543 intermediate Substances 0.000 description 3
• 229910052740 iodine Inorganic materials 0.000 description 3
• 150000002500 ions Chemical class 0.000 description 3
• 229940043355 kinase inhibitor Drugs 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 239000000314 lubricant Substances 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 239000002609 medium Substances 0.000 description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
• JOJUSJUMORAJNN-UHFFFAOYSA-N methyl 4-amino-6-chloropyrimidine-2-carboxylate Chemical compound NC1=NC(=NC(=C1)Cl)C(=O)OC JOJUSJUMORAJNN-UHFFFAOYSA-N 0.000 description 3
• 239000002480 mineral oil Substances 0.000 description 3
• 235000010446 mineral oil Nutrition 0.000 description 3
• 239000002674 ointment Substances 0.000 description 3
• 210000000056 organ Anatomy 0.000 description 3
• 239000008194 pharmaceutical composition Substances 0.000 description 3
• 235000021317 phosphate Nutrition 0.000 description 3
• 230000026731 phosphorylation Effects 0.000 description 3
• 238000006366 phosphorylation reaction Methods 0.000 description 3
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 3
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 125000004076 pyridyl group Chemical group 0.000 description 3
• 210000000664 rectum Anatomy 0.000 description 3
• 238000004007 reversed phase HPLC Methods 0.000 description 3
• 239000000523 sample Substances 0.000 description 3
• 230000037390 scarring Effects 0.000 description 3
• 239000000377 silicon dioxide Substances 0.000 description 3
• 210000003491 skin Anatomy 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• 235000017550 sodium carbonate Nutrition 0.000 description 3
• 239000008247 solid mixture Substances 0.000 description 3
• 241000894007 species Species 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 239000005720 sucrose Substances 0.000 description 3
• 239000000829 suppository Substances 0.000 description 3
• 239000000375 suspending agent Substances 0.000 description 3
• GKTQKQTXHNUFSP-UHFFFAOYSA-N thieno[3,4-c]pyrrole-4,6-dione Chemical compound S1C=C2C(=O)NC(=O)C2=C1 GKTQKQTXHNUFSP-UHFFFAOYSA-N 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
• 239000000080 wetting agent Substances 0.000 description 3
• YFWAJBZGZRKMJQ-UHFFFAOYSA-N (2,4-dichloropyrimidin-5-yl)methanol Chemical compound OCC1=CN=C(Cl)N=C1Cl YFWAJBZGZRKMJQ-UHFFFAOYSA-N 0.000 description 2
• FLVFPAIGVBQGET-RXMQYKEDSA-N (3r)-1-methylpyrrolidin-3-ol Chemical compound CN1CC[C@@H](O)C1 FLVFPAIGVBQGET-RXMQYKEDSA-N 0.000 description 2
• 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 2
• IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 2
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• VLOODHWTRPYFIS-UHFFFAOYSA-N 2,4-dichloro-5-(chloromethyl)pyrimidine Chemical compound ClCC1=CN=C(Cl)N=C1Cl VLOODHWTRPYFIS-UHFFFAOYSA-N 0.000 description 2
• NEIMQFSSWKAYTR-UHFFFAOYSA-N 2,4-dichloro-5-(iodomethyl)pyrimidine Chemical compound ClC1=NC=C(CI)C(Cl)=N1 NEIMQFSSWKAYTR-UHFFFAOYSA-N 0.000 description 2
• BHWWVJLPSHEQBF-UHFFFAOYSA-N 2,4-dichloro-6-pyrrolidin-1-yl-1,3,5-triazine Chemical compound ClC1=NC(Cl)=NC(N2CCCC2)=N1 BHWWVJLPSHEQBF-UHFFFAOYSA-N 0.000 description 2
• QTMPYFZNWHQZAZ-UHFFFAOYSA-N 2-(methoxymethyl)pyrrolidine;hydrochloride Chemical compound Cl.COCC1CCCN1 QTMPYFZNWHQZAZ-UHFFFAOYSA-N 0.000 description 2
• JSAKBYXSHKYFQU-UHFFFAOYSA-N 2-fluoropyridin-4-amine Chemical compound NC1=CC=NC(F)=C1 JSAKBYXSHKYFQU-UHFFFAOYSA-N 0.000 description 2
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 2
• MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 2
• DHDPUVPGALXWOL-UHFFFAOYSA-N 3-methyloxetan-3-ol Chemical compound CC1(O)COC1 DHDPUVPGALXWOL-UHFFFAOYSA-N 0.000 description 2
• MCLDVUCSDZGNRR-UHFFFAOYSA-N 4,6-difluoropyrimidine Chemical compound FC1=CC(F)=NC=N1 MCLDVUCSDZGNRR-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• JYXYRLZNHMIQAN-UHFFFAOYSA-N 5-(ethoxymethyl)-1h-pyrimidine-2,4-dione Chemical compound CCOCC1=CNC(=O)NC1=O JYXYRLZNHMIQAN-UHFFFAOYSA-N 0.000 description 2
• JDBGXEHEIRGOBU-UHFFFAOYSA-N 5-hydroxymethyluracil Chemical compound OCC1=CNC(=O)NC1=O JDBGXEHEIRGOBU-UHFFFAOYSA-N 0.000 description 2
• TVHRQDVVPKXZOZ-UHFFFAOYSA-N 6-chloro-4-iodopyridine-3-carbonitrile Chemical compound ClC1=CC(I)=C(C#N)C=N1 TVHRQDVVPKXZOZ-UHFFFAOYSA-N 0.000 description 2
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
• 208000024827 Alzheimer disease Diseases 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 2
• 208000033222 Biliary cirrhosis primary Diseases 0.000 description 2
• 208000020084 Bone disease Diseases 0.000 description 2
• DLDGRXKBNNQTBD-SSDOTTSWSA-N BrC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O Chemical compound BrC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O DLDGRXKBNNQTBD-SSDOTTSWSA-N 0.000 description 2
• NZIGRCNEXPKYBO-UHFFFAOYSA-N C(C)(C)(C)OC1CCN(CC1)CC=1C(=NC(=NC=1)Cl)Cl Chemical compound C(C)(C)(C)OC1CCN(CC1)CC=1C(=NC(=NC=1)Cl)Cl NZIGRCNEXPKYBO-UHFFFAOYSA-N 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
• 206010008609 Cholangitis sclerosing Diseases 0.000 description 2
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
• BOBUBXHCKDDIDY-UHFFFAOYSA-N ClC1=CC(=NC(=N1)OCCN1CCN(CC1)C)N Chemical compound ClC1=CC(=NC(=N1)OCCN1CCN(CC1)C)N BOBUBXHCKDDIDY-UHFFFAOYSA-N 0.000 description 2
• NOFJNUKFUPIGMZ-SECBINFHSA-N ClC1=CC(=NC=N1)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O Chemical compound ClC1=CC(=NC=N1)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O NOFJNUKFUPIGMZ-SECBINFHSA-N 0.000 description 2
• OUWILTNPMMHZLG-UHFFFAOYSA-N ClC1=NC=C(C(=N1)Cl)CN1CCC(CC1)OC(C)C Chemical compound ClC1=NC=C(C(=N1)Cl)CN1CCC(CC1)OC(C)C OUWILTNPMMHZLG-UHFFFAOYSA-N 0.000 description 2
• BEVGUJPCQQWNEZ-FIBGUPNXSA-N ClC1=NC=C(C(=N1)Cl)CN1CCC(CC1)OC([2H])([2H])[2H] Chemical compound ClC1=NC=C(C(=N1)Cl)CN1CCC(CC1)OC([2H])([2H])[2H] BEVGUJPCQQWNEZ-FIBGUPNXSA-N 0.000 description 2
• DDQSQZOFOWEZJS-UHFFFAOYSA-N ClC1=NC=C(C(=N1)Cl)CN1CCC(CC1)OCCO Chemical compound ClC1=NC=C(C(=N1)Cl)CN1CCC(CC1)OCCO DDQSQZOFOWEZJS-UHFFFAOYSA-N 0.000 description 2
• CTYBMGRKOQKYBU-UHFFFAOYSA-N ClC1=NC=C(C(=N1)Cl)CN1CCC(CC1)OCCOC Chemical compound ClC1=NC=C(C(=N1)Cl)CN1CCC(CC1)OCCOC CTYBMGRKOQKYBU-UHFFFAOYSA-N 0.000 description 2
• RZVUFAWKJMGXSK-ZBJDZAJPSA-N ClC1=NC=C(C(=N1)Cl)COC(C([2H])([2H])[2H])([2H])[2H] Chemical compound ClC1=NC=C(C(=N1)Cl)COC(C([2H])([2H])[2H])([2H])[2H] RZVUFAWKJMGXSK-ZBJDZAJPSA-N 0.000 description 2
• NACNPDUPSRAROD-UHFFFAOYSA-N ClC1=NC=C(C(=N1)Cl)CS(=O)(=O)C Chemical compound ClC1=NC=C(C(=N1)Cl)CS(=O)(=O)C NACNPDUPSRAROD-UHFFFAOYSA-N 0.000 description 2
• UTJXMKIBSWTBIS-SNVBAGLBSA-N ClC1=NC=CC(=C1)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O Chemical compound ClC1=NC=CC(=C1)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O UTJXMKIBSWTBIS-SNVBAGLBSA-N 0.000 description 2
• QJZDJDAKEDVGHV-SECBINFHSA-N ClC1=NC=CC(=N1)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O Chemical compound ClC1=NC=CC(=N1)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O QJZDJDAKEDVGHV-SECBINFHSA-N 0.000 description 2
• DRJYNMIMWHMTKP-UHFFFAOYSA-N ClC1=NC=NC=C1CN(C(C)(C)C)C Chemical compound ClC1=NC=NC=C1CN(C(C)(C)C)C DRJYNMIMWHMTKP-UHFFFAOYSA-N 0.000 description 2
• 229910021590 Copper(II) bromide Inorganic materials 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• FTNYJYIJPYLOHR-UHFFFAOYSA-N FC1(F)CCN(C1)C1=NC(Cl)=NC(Cl)=N1 Chemical compound FC1(F)CCN(C1)C1=NC(Cl)=NC(Cl)=N1 FTNYJYIJPYLOHR-UHFFFAOYSA-N 0.000 description 2
• SDCOHVYOCKQZPG-UHFFFAOYSA-N FC1=CC(=NC(=N1)OC1COC1)N Chemical compound FC1=CC(=NC(=N1)OC1COC1)N SDCOHVYOCKQZPG-UHFFFAOYSA-N 0.000 description 2
• ZZGDBINXVJXNRE-UHFFFAOYSA-N FC1=CC(=NC(=N1)OCCN1CCN(CC1)C)N Chemical compound FC1=CC(=NC(=N1)OCCN1CCN(CC1)C)N ZZGDBINXVJXNRE-UHFFFAOYSA-N 0.000 description 2
• KLTJZNSGAGNMIR-YFKPBYRVSA-N FC1=CC(=NC(=N1)O[C@@H]1COCC1)N Chemical compound FC1=CC(=NC(=N1)O[C@@H]1COCC1)N KLTJZNSGAGNMIR-YFKPBYRVSA-N 0.000 description 2
• BZNBGRZOZXDDPU-ZCFIWIBFSA-N FC1=CC(=NC(=N1)O[C@H]1CN(CC1)C)N Chemical compound FC1=CC(=NC(=N1)O[C@H]1CN(CC1)C)N BZNBGRZOZXDDPU-ZCFIWIBFSA-N 0.000 description 2
• KLTJZNSGAGNMIR-RXMQYKEDSA-N FC1=CC(=NC(=N1)O[C@H]1COCC1)N Chemical compound FC1=CC(=NC(=N1)O[C@H]1COCC1)N KLTJZNSGAGNMIR-RXMQYKEDSA-N 0.000 description 2
• RRCPUMPDKMAEEW-SECBINFHSA-N FC1=CC(=NC=N1)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O Chemical compound FC1=CC(=NC=N1)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O RRCPUMPDKMAEEW-SECBINFHSA-N 0.000 description 2
• CKHXGVLZMBYEJF-UHFFFAOYSA-N FC1=NC(=CC(=N1)F)OCCOC Chemical compound FC1=NC(=CC(=N1)F)OCCOC CKHXGVLZMBYEJF-UHFFFAOYSA-N 0.000 description 2
• LVDVOJSHQJZHHJ-YFKPBYRVSA-N FC1=NC(=CC(=N1)F)O[C@@H]1COCC1 Chemical compound FC1=NC(=CC(=N1)F)O[C@@H]1COCC1 LVDVOJSHQJZHHJ-YFKPBYRVSA-N 0.000 description 2
• VUBZZMPJLPVTTE-UHFFFAOYSA-N FC1=NC(=CC(=N1)OCCN(C)C)F Chemical compound FC1=NC(=CC(=N1)OCCN(C)C)F VUBZZMPJLPVTTE-UHFFFAOYSA-N 0.000 description 2
• NFTUSOXNNNJSRB-UHFFFAOYSA-N FC1=NC(=NC(=C1)F)OCCN(C)C Chemical compound FC1=NC(=NC(=C1)F)OCCN(C)C NFTUSOXNNNJSRB-UHFFFAOYSA-N 0.000 description 2
• HHNVLXOWTGBYPT-YFKPBYRVSA-N FC1=NC(=NC(=C1)F)O[C@@H]1COCC1 Chemical compound FC1=NC(=NC(=C1)F)O[C@@H]1COCC1 HHNVLXOWTGBYPT-YFKPBYRVSA-N 0.000 description 2
• UZQNKULUNUVSCZ-UHFFFAOYSA-N FC1=NC(=NC(=C1)OCC1(COC1)C)N Chemical compound FC1=NC(=NC(=C1)OCC1(COC1)C)N UZQNKULUNUVSCZ-UHFFFAOYSA-N 0.000 description 2
• JQLIRMSINVJPEJ-YFKPBYRVSA-N FC1=NC(=NC(=C1)O[C@@H]1COCC1)N Chemical compound FC1=NC(=NC(=C1)O[C@@H]1COCC1)N JQLIRMSINVJPEJ-YFKPBYRVSA-N 0.000 description 2
• JQLIRMSINVJPEJ-RXMQYKEDSA-N FC1=NC(=NC(=C1)O[C@H]1COCC1)N Chemical compound FC1=NC(=NC(=C1)O[C@H]1COCC1)N JQLIRMSINVJPEJ-RXMQYKEDSA-N 0.000 description 2
• AFIJFXDPPVNQAO-SECBINFHSA-N FC1=NC=CC(=N1)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O Chemical compound FC1=NC=CC(=N1)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O AFIJFXDPPVNQAO-SECBINFHSA-N 0.000 description 2
• 201000008808 Fibrosarcoma Diseases 0.000 description 2
• 208000032612 Glial tumor Diseases 0.000 description 2
• 206010018338 Glioma Diseases 0.000 description 2
• 206010018364 Glomerulonephritis Diseases 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 108010045100 HSP27 Heat-Shock Proteins Proteins 0.000 description 2
• 239000004705 High-molecular-weight polyethylene Substances 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 2
• 206010061218 Inflammation Diseases 0.000 description 2
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
• 102000004889 Interleukin-6 Human genes 0.000 description 2
• 108090001005 Interleukin-6 Proteins 0.000 description 2
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
• 206010025323 Lymphomas Diseases 0.000 description 2
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• YBORTKILIGMILP-UHFFFAOYSA-N NC1=NC(=NC=C1C(=O)NCC1=CC=C(C=C1)OC)Cl Chemical compound NC1=NC(=NC=C1C(=O)NCC1=CC=C(C=C1)OC)Cl YBORTKILIGMILP-UHFFFAOYSA-N 0.000 description 2
• 229910002651 NO3 Inorganic materials 0.000 description 2
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
• 206010035664 Pneumonia Diseases 0.000 description 2
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
• 208000012654 Primary biliary cholangitis Diseases 0.000 description 2
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
• 206010040047 Sepsis Diseases 0.000 description 2
• XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• 201000009594 Systemic Scleroderma Diseases 0.000 description 2
• 206010042953 Systemic sclerosis Diseases 0.000 description 2
• 206010044248 Toxic shock syndrome Diseases 0.000 description 2
• 231100000650 Toxic shock syndrome Toxicity 0.000 description 2
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 206010069351 acute lung injury Diseases 0.000 description 2
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
• 125000004450 alkenylene group Chemical group 0.000 description 2
• XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 235000001014 amino acid Nutrition 0.000 description 2
• 229940024606 amino acid Drugs 0.000 description 2
• 235000019270 ammonium chloride Nutrition 0.000 description 2
• 239000000908 ammonium hydroxide Substances 0.000 description 2
• 239000008346 aqueous phase Substances 0.000 description 2
• 239000007900 aqueous suspension Substances 0.000 description 2
• 206010003246 arthritis Diseases 0.000 description 2
• 208000006673 asthma Diseases 0.000 description 2
• 230000005784 autoimmunity Effects 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• 235000019445 benzyl alcohol Nutrition 0.000 description 2
• SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
• 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
• 238000004166 bioassay Methods 0.000 description 2
• 229920002988 biodegradable polymer Polymers 0.000 description 2
• 239000004621 biodegradable polymer Substances 0.000 description 2
• 239000012455 biphasic mixture Substances 0.000 description 2
• 239000004305 biphenyl Substances 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 239000006172 buffering agent Substances 0.000 description 2
• 235000019437 butane-1,3-diol Nutrition 0.000 description 2
• 239000006227 byproduct Substances 0.000 description 2
• 210000004899 c-terminal region Anatomy 0.000 description 2
• 125000004432 carbon atom Chemical group C* 0.000 description 2
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 239000004359 castor oil Substances 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 208000037976 chronic inflammation Diseases 0.000 description 2
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 2
• 230000007882 cirrhosis Effects 0.000 description 2
• 208000019425 cirrhosis of liver Diseases 0.000 description 2
• 230000001276 controlling effect Effects 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 229940099112 cornstarch Drugs 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 125000004122 cyclic group Chemical group 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
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• 201000001981 dermatomyositis Diseases 0.000 description 2
• 238000003745 diagnosis Methods 0.000 description 2
• NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 2
• 229940043264 dodecyl sulfate Drugs 0.000 description 2
• 239000008298 dragée Substances 0.000 description 2
• 230000002526 effect on cardiovascular system Effects 0.000 description 2
• 230000001804 emulsifying effect Effects 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 238000003821 enantio-separation Methods 0.000 description 2
• 239000002702 enteric coating Substances 0.000 description 2
• 238000009505 enteric coating Methods 0.000 description 2
• SRJBDGLSCPDXBL-UHFFFAOYSA-N ethyl 2,4-dichloropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)N=C1Cl SRJBDGLSCPDXBL-UHFFFAOYSA-N 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 150000004665 fatty acids Chemical class 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 238000007429 general method Methods 0.000 description 2
• 239000012362 glacial acetic acid Substances 0.000 description 2
• 125000005456 glyceride group Chemical group 0.000 description 2
• 125000004475 heteroaralkyl group Chemical group 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• 238000000099 in vitro assay Methods 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 230000004054 inflammatory process Effects 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 239000007972 injectable composition Substances 0.000 description 2
• 229940100601 interleukin-6 Drugs 0.000 description 2
• 208000036971 interstitial lung disease 2 Diseases 0.000 description 2
• OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 208000017169 kidney disease Diseases 0.000 description 2
• 239000008297 liquid dosage form Substances 0.000 description 2
• 229910052744 lithium Inorganic materials 0.000 description 2
• 239000006210 lotion Substances 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 201000001441 melanoma Diseases 0.000 description 2
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• 239000004530 micro-emulsion Substances 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 150000002829 nitrogen Chemical class 0.000 description 2
• 231100000344 non-irritating Toxicity 0.000 description 2
• 239000000346 nonvolatile oil Substances 0.000 description 2
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
• 239000004006 olive oil Substances 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
• 230000000737 periodic effect Effects 0.000 description 2
• 206010034674 peritonitis Diseases 0.000 description 2
• 210000003800 pharynx Anatomy 0.000 description 2
• 239000012071 phase Substances 0.000 description 2
• 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 229910052698 phosphorus Inorganic materials 0.000 description 2
• 239000011574 phosphorus Substances 0.000 description 2
• 229920001451 polypropylene glycol Polymers 0.000 description 2
• 238000002360 preparation method Methods 0.000 description 2
• 201000000742 primary sclerosing cholangitis Diseases 0.000 description 2
• 229960004063 propylene glycol Drugs 0.000 description 2
• 210000002307 prostate Anatomy 0.000 description 2
• 235000018102 proteins Nutrition 0.000 description 2
• 125000003373 pyrazinyl group Chemical group 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 description 2
• 150000003254 radicals Chemical class 0.000 description 2
• 208000037803 restenosis Diseases 0.000 description 2
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
• 206010039073 rheumatoid arthritis Diseases 0.000 description 2
• 238000002390 rotary evaporation Methods 0.000 description 2
• 201000000306 sarcoidosis Diseases 0.000 description 2
• 208000010157 sclerosing cholangitis Diseases 0.000 description 2
• 229910052710 silicon Inorganic materials 0.000 description 2
• 239000010703 silicon Substances 0.000 description 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 235000009518 sodium iodide Nutrition 0.000 description 2
• 208000020431 spinal cord injury Diseases 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 2
• 239000012414 tert-butyl nitrite Substances 0.000 description 2
• YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 2
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 2
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• MXZROAOUCUVNHX-GSVOUGTGSA-N (1r)-1-aminopropan-1-ol Chemical compound CC[C@H](N)O MXZROAOUCUVNHX-GSVOUGTGSA-N 0.000 description 1
• AVAWMINJNRAQFS-ZCFIWIBFSA-N (3r)-n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)[C@@H]1CCNC1 AVAWMINJNRAQFS-ZCFIWIBFSA-N 0.000 description 1
• XDPCNPCKDGQBAN-SCSAIBSYSA-N (3r)-oxolan-3-ol Chemical compound O[C@@H]1CCOC1 XDPCNPCKDGQBAN-SCSAIBSYSA-N 0.000 description 1
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
• XDPCNPCKDGQBAN-BYPYZUCNSA-N (3s)-oxolan-3-ol Chemical compound O[C@H]1CCOC1 XDPCNPCKDGQBAN-BYPYZUCNSA-N 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• DQXKOHDUMJLXKH-PHEQNACWSA-N (e)-n-[2-[2-[[(e)-oct-2-enoyl]amino]ethyldisulfanyl]ethyl]oct-2-enamide Chemical compound CCCCC\C=C\C(=O)NCCSSCCNC(=O)\C=C\CCCCC DQXKOHDUMJLXKH-PHEQNACWSA-N 0.000 description 1
• 229940058015 1,3-butylene glycol Drugs 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• VYDQUABHDFWIIX-UHFFFAOYSA-N 2,2-difluoro-2-fluorosulfonylacetic acid Chemical compound OC(=O)C(F)(F)S(F)(=O)=O VYDQUABHDFWIIX-UHFFFAOYSA-N 0.000 description 1
• DPVIABCMTHHTGB-UHFFFAOYSA-N 2,4,6-trichloropyrimidine Chemical compound ClC1=CC(Cl)=NC(Cl)=N1 DPVIABCMTHHTGB-UHFFFAOYSA-N 0.000 description 1
• CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
• JKAPWXKZLYJQJJ-UHFFFAOYSA-N 2,4-dichloro-6-methoxy-1,3,5-triazine Chemical compound COC1=NC(Cl)=NC(Cl)=N1 JKAPWXKZLYJQJJ-UHFFFAOYSA-N 0.000 description 1
• MUEJUOUFUTUSED-UHFFFAOYSA-N 2,4-dichloro-6-piperidin-1-yl-1,3,5-triazine Chemical compound ClC1=NC(Cl)=NC(N2CCCCC2)=N1 MUEJUOUFUTUSED-UHFFFAOYSA-N 0.000 description 1
• CQCDGPMCNAANOQ-UHFFFAOYSA-N 2,4-dichloro-n-[(4-methoxyphenyl)methyl]pyrimidine-5-carboxamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)C1=CN=C(Cl)N=C1Cl CQCDGPMCNAANOQ-UHFFFAOYSA-N 0.000 description 1
• KMHSUNDEGHRBNV-UHFFFAOYSA-N 2,4-dichloropyrimidine-5-carbonitrile Chemical group ClC1=NC=C(C#N)C(Cl)=N1 KMHSUNDEGHRBNV-UHFFFAOYSA-N 0.000 description 1
• OWXBXLGJIFPPMS-UHFFFAOYSA-N 2,6-difluoropyridin-4-amine Chemical compound NC1=CC(F)=NC(F)=C1 OWXBXLGJIFPPMS-UHFFFAOYSA-N 0.000 description 1
• OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
• OTLLEIBWKHEHGU-UHFFFAOYSA-N 2-[5-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-4-phosphonooxyhexanedioic acid Chemical compound C1=NC=2C(N)=NC=NC=2N1C(C(C1O)O)OC1COC1C(CO)OC(OC(C(O)C(OP(O)(O)=O)C(O)C(O)=O)C(O)=O)C(O)C1O OTLLEIBWKHEHGU-UHFFFAOYSA-N 0.000 description 1
• CBXKVIFVKCNVGJ-UHFFFAOYSA-N 2-amino-4-fluorobenzonitrile Chemical group NC1=CC(F)=CC=C1C#N CBXKVIFVKCNVGJ-UHFFFAOYSA-N 0.000 description 1
• LPBDZVNGCNTELM-UHFFFAOYSA-N 2-chloropyrimidin-4-amine Chemical group NC1=CC=NC(Cl)=N1 LPBDZVNGCNTELM-UHFFFAOYSA-N 0.000 description 1
• ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
• 229940093475 2-ethoxyethanol Drugs 0.000 description 1
• SPWJNWKKNZWCPA-UHFFFAOYSA-N 2-fluoropyrimidin-4-amine Chemical compound NC1=CC=NC(F)=N1 SPWJNWKKNZWCPA-UHFFFAOYSA-N 0.000 description 1
• ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
• 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
• LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
• VAIHBHWKPBXNLR-UHFFFAOYSA-N 2-piperidin-4-yloxyethanol Chemical compound OCCOC1CCNCC1 VAIHBHWKPBXNLR-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• UOGQPXQDNUHUIB-UHFFFAOYSA-N 3,3-difluoropiperidine Chemical compound FC1(F)CCCNC1 UOGQPXQDNUHUIB-UHFFFAOYSA-N 0.000 description 1
• KVTUSMPNLUCCQO-UHFFFAOYSA-N 3,3-difluoropyrrolidine Chemical compound FC1(F)CCNC1 KVTUSMPNLUCCQO-UHFFFAOYSA-N 0.000 description 1
• YYVPZQADFREIFR-UHFFFAOYSA-N 3,3-difluoropyrrolidine;hydrochloride Chemical compound [Cl-].FC1(F)CC[NH2+]C1 YYVPZQADFREIFR-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
• MCLXKFUCPVGZEN-UHFFFAOYSA-N 4,6-dichloro-1,3,5-triazin-2-amine Chemical compound NC1=NC(Cl)=NC(Cl)=N1 MCLXKFUCPVGZEN-UHFFFAOYSA-N 0.000 description 1
• ITRGRVVBODKGCW-UHFFFAOYSA-N 4,6-dichloro-n,n-dimethyl-1,3,5-triazin-2-amine Chemical compound CN(C)C1=NC(Cl)=NC(Cl)=N1 ITRGRVVBODKGCW-UHFFFAOYSA-N 0.000 description 1
• KJFMZGRMRFLJQR-UHFFFAOYSA-N 4,6-difluoropyrimidin-2-amine Chemical compound NC1=NC(F)=CC(F)=N1 KJFMZGRMRFLJQR-UHFFFAOYSA-N 0.000 description 1
• KTXVOCUROHMWQP-UHFFFAOYSA-N 4-(2-methoxyethoxy)piperidine Chemical compound COCCOC1CCNCC1 KTXVOCUROHMWQP-UHFFFAOYSA-N 0.000 description 1
• 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 1
• UQAMDAUJTXFNAD-UHFFFAOYSA-N 4-(4,6-dichloro-1,3,5-triazin-2-yl)morpholine Chemical compound ClC1=NC(Cl)=NC(N2CCOCC2)=N1 UQAMDAUJTXFNAD-UHFFFAOYSA-N 0.000 description 1
• BLBDTBCGPHPIJK-UHFFFAOYSA-N 4-Amino-2-chloropyridine Chemical compound NC1=CC=NC(Cl)=C1 BLBDTBCGPHPIJK-UHFFFAOYSA-N 0.000 description 1
• BWVZLXTZQHILRC-UHFFFAOYSA-N 4-chloro-2-methylsulfonylpyrimidine Chemical compound CS(=O)(=O)C1=NC=CC(Cl)=N1 BWVZLXTZQHILRC-UHFFFAOYSA-N 0.000 description 1
• RPDVPWWBNQKLAS-UHFFFAOYSA-N 4-chloro-5-methylpyrimidine Chemical compound CC1=CN=CN=C1Cl RPDVPWWBNQKLAS-UHFFFAOYSA-N 0.000 description 1
• PSLFYIQTJUMHSA-UHFFFAOYSA-N 4-chloro-6-(2-methoxyethoxy)pyrimidin-2-amine Chemical compound COCCOC1=CC(Cl)=NC(N)=N1 PSLFYIQTJUMHSA-UHFFFAOYSA-N 0.000 description 1
• AMLQRNZJKHGYQI-UHFFFAOYSA-N 4-propan-2-yloxypiperidine;hydrochloride Chemical compound Cl.CC(C)OC1CCNCC1 AMLQRNZJKHGYQI-UHFFFAOYSA-N 0.000 description 1
• 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
• 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
• JEOBFTOIMFEXNK-UHFFFAOYSA-N 6-chloro-2-(methoxymethyl)pyrimidin-4-amine Chemical compound COCC1=NC(N)=CC(Cl)=N1 JEOBFTOIMFEXNK-UHFFFAOYSA-N 0.000 description 1
• DUKKRSPKJMHASP-UHFFFAOYSA-N 6-chloropyrimidin-4-amine Chemical group NC1=CC(Cl)=NC=N1 DUKKRSPKJMHASP-UHFFFAOYSA-N 0.000 description 1
• AALZEWSKCRJZID-UHFFFAOYSA-N 6-fluoro-N-(2-methoxyethyl)pyrimidin-4-amine Chemical compound FC1=CC(=NC=N1)NCCOC AALZEWSKCRJZID-UHFFFAOYSA-N 0.000 description 1
• OGIDDUSIUCSNAK-UHFFFAOYSA-N 6-fluoro-N-methylpyrimidin-4-amine Chemical compound FC1=CC(=NC=N1)NC OGIDDUSIUCSNAK-UHFFFAOYSA-N 0.000 description 1
• SMHPLBXIVNQFBA-UHFFFAOYSA-N 6-nitroquinoline Chemical compound N1=CC=CC2=CC([N+](=O)[O-])=CC=C21 SMHPLBXIVNQFBA-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
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
• 108091006112 ATPases Proteins 0.000 description 1
• 208000004476 Acute Coronary Syndrome Diseases 0.000 description 1
• 208000030090 Acute Disease Diseases 0.000 description 1
• 206010033646 Acute and chronic pancreatitis Diseases 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
• 208000026872 Addison Disease Diseases 0.000 description 1
• 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 206010002198 Anaphylactic reaction Diseases 0.000 description 1
• 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
• 235000017060 Arachis glabrata Nutrition 0.000 description 1
• 244000105624 Arachis hypogaea Species 0.000 description 1
• 235000010777 Arachis hypogaea Nutrition 0.000 description 1
• 235000018262 Arachis monticola Nutrition 0.000 description 1
• 200000000007 Arterial disease Diseases 0.000 description 1
• 206010003267 Arthritis reactive Diseases 0.000 description 1
• 206010003571 Astrocytoma Diseases 0.000 description 1
• 208000031212 Autoimmune polyendocrinopathy Diseases 0.000 description 1
• 206010050245 Autoimmune thrombocytopenia Diseases 0.000 description 1
• 208000022715 Autoinflammatory syndrome Diseases 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 208000003950 B-cell lymphoma Diseases 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• 208000009137 Behcet syndrome Diseases 0.000 description 1
• 206010004664 Biliary fibrosis Diseases 0.000 description 1
• 206010005949 Bone cancer Diseases 0.000 description 1
• 208000018084 Bone neoplasm Diseases 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• 208000011691 Burkitt lymphomas Diseases 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• 201000003274 CINCA syndrome Diseases 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 208000000094 Chronic Pain Diseases 0.000 description 1
• 208000010833 Chronic myeloid leukaemia 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
• BOFAWQFEHDOBEY-KWCCSABGSA-N ClC1=CC(=NC(=N1)OC1CN(CCC1)C)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O Chemical compound ClC1=CC(=NC(=N1)OC1CN(CCC1)C)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O BOFAWQFEHDOBEY-KWCCSABGSA-N 0.000 description 1
• CJRFNAZXQXTXRS-ZCFIWIBFSA-N ClC1=CC(=NC(=N1)O[C@H]1CN(CC1)C)N Chemical compound ClC1=CC(=NC(=N1)O[C@H]1CN(CC1)C)N CJRFNAZXQXTXRS-ZCFIWIBFSA-N 0.000 description 1
• KRXUHTWAFIYLPJ-UHFFFAOYSA-N ClC1=NC(=NC(=C1)OCCN1CCN(CC1)C)N Chemical compound ClC1=NC(=NC(=C1)OCCN1CCN(CC1)C)N KRXUHTWAFIYLPJ-UHFFFAOYSA-N 0.000 description 1
• TZRBRFDJTHETEI-ZETCQYMHSA-N ClC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)CO)=O Chemical compound ClC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)CO)=O TZRBRFDJTHETEI-ZETCQYMHSA-N 0.000 description 1
• XQFLIKNPXOZOEM-UHFFFAOYSA-N ClC1=NC=C(C(=N1)Cl)CN1C(CCC1)COC Chemical compound ClC1=NC=C(C(=N1)Cl)CN1C(CCC1)COC XQFLIKNPXOZOEM-UHFFFAOYSA-N 0.000 description 1
• 208000015943 Coeliac disease Diseases 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• 102100034741 Cyclin-dependent kinase 20 Human genes 0.000 description 1
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 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
• 206010011878 Deafness Diseases 0.000 description 1
• 206010012438 Dermatitis atopic Diseases 0.000 description 1
• 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• 206010059866 Drug resistance Diseases 0.000 description 1
• 206010014824 Endotoxic shock Diseases 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• QLVXRVVIOFDQDX-UHFFFAOYSA-N FC1(F)CCCN(C1)C1=NC(Cl)=NC(Cl)=N1 Chemical compound FC1(F)CCCN(C1)C1=NC(Cl)=NC(Cl)=N1 QLVXRVVIOFDQDX-UHFFFAOYSA-N 0.000 description 1
• LKYDLVYHHTVZPA-UHFFFAOYSA-N FC1=CC(=NC(=N1)CN1CCN(CC1)C)N Chemical compound FC1=CC(=NC(=N1)CN1CCN(CC1)C)N LKYDLVYHHTVZPA-UHFFFAOYSA-N 0.000 description 1
• LCCRSNAYYXQSJN-KWCCSABGSA-N FC1=CC(=NC(=N1)OC1CN(CCC1)C)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O Chemical compound FC1=CC(=NC(=N1)OC1CN(CCC1)C)NC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O LCCRSNAYYXQSJN-KWCCSABGSA-N 0.000 description 1
• PWLFMHFCKGVOMR-UHFFFAOYSA-N FC1=NC(=CC(=N1)F)OCC1(COC1)C Chemical compound FC1=NC(=CC(=N1)F)OCC1(COC1)C PWLFMHFCKGVOMR-UHFFFAOYSA-N 0.000 description 1
• AUCHYEHQIYWOBU-UHFFFAOYSA-N FC1=NC=C(C#N)C(=C1)I Chemical group FC1=NC=C(C#N)C(=C1)I AUCHYEHQIYWOBU-UHFFFAOYSA-N 0.000 description 1
• 206010016207 Familial Mediterranean fever Diseases 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 208000007659 Fibroadenoma Diseases 0.000 description 1
• 208000001640 Fibromyalgia Diseases 0.000 description 1
• 239000004606 Fillers/Extenders Substances 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 206010016935 Follicular thyroid cancer Diseases 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 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
• 208000007882 Gastritis Diseases 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 241000206672 Gelidium Species 0.000 description 1
• 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
• 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 1
• 208000002705 Glucose Intolerance Diseases 0.000 description 1
• 206010018429 Glucose tolerance impaired Diseases 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
• 208000024869 Goodpasture syndrome Diseases 0.000 description 1
• 201000005569 Gout Diseases 0.000 description 1
• 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
• 208000003807 Graves Disease Diseases 0.000 description 1
• 208000015023 Graves' disease Diseases 0.000 description 1
• 239000007821 HATU Substances 0.000 description 1
• 208000001204 Hashimoto Disease Diseases 0.000 description 1
• 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 102100039165 Heat shock protein beta-1 Human genes 0.000 description 1
• 208000005176 Hepatitis C Diseases 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• 208000023105 Huntington disease Diseases 0.000 description 1
• 206010058490 Hyperoxia Diseases 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 206010020772 Hypertension Diseases 0.000 description 1
• 206010020850 Hyperthyroidism Diseases 0.000 description 1
• 206010062767 Hypophysitis Diseases 0.000 description 1
• 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
• 208000024934 IgG4-related mediastinitis Diseases 0.000 description 1
• 208000014919 IgG4-related retroperitoneal fibrosis Diseases 0.000 description 1
• 102000008070 Interferon-gamma Human genes 0.000 description 1
• 108010074328 Interferon-gamma Proteins 0.000 description 1
• 208000005615 Interstitial Cystitis Diseases 0.000 description 1
• 208000003456 Juvenile Arthritis Diseases 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• 208000002260 Keloid Diseases 0.000 description 1
• 206010023330 Keloid scar Diseases 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 201000010743 Lambert-Eaton myasthenic syndrome Diseases 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 208000004852 Lung Injury Diseases 0.000 description 1
• 208000005777 Lupus Nephritis Diseases 0.000 description 1
• 101500014379 Lymnaea stagnalis Ovulation hormone Proteins 0.000 description 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
• 102100034069 MAP kinase-activated protein kinase 2 Human genes 0.000 description 1
• 102220517763 MAP kinase-activated protein kinase 2_D207A_mutation Human genes 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 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
• 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 1
• 208000002805 Mediastinal fibrosis Diseases 0.000 description 1
• 208000027530 Meniere disease Diseases 0.000 description 1
• 201000009906 Meningitis Diseases 0.000 description 1
• 208000001145 Metabolic Syndrome Diseases 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 1
• 101710166115 Mitogen-activated protein kinase 2 Proteins 0.000 description 1
• 201000002795 Muckle-Wells syndrome Diseases 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 208000000112 Myalgia Diseases 0.000 description 1
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
• 208000009525 Myocarditis Diseases 0.000 description 1
• 201000002481 Myositis Diseases 0.000 description 1
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
• ARCDMEMPXCVFFD-UHFFFAOYSA-N NC1=CC(=NC=C1C(=O)NCC1=CC=C(C=C1)OC)Cl Chemical compound NC1=CC(=NC=C1C(=O)NCC1=CC=C(C=C1)OC)Cl ARCDMEMPXCVFFD-UHFFFAOYSA-N 0.000 description 1
• DUBGTLWCQIHABF-SSDOTTSWSA-N NC[C@H]1NC(C2=C(C=3C=4C=CC(=NC=4C=CC=3S2)Cl)NC1)=O Chemical compound NC[C@H]1NC(C2=C(C=3C=4C=CC(=NC=4C=CC=3S2)Cl)NC1)=O DUBGTLWCQIHABF-SSDOTTSWSA-N 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• 208000003510 Nephrogenic Fibrosing Dermopathy Diseases 0.000 description 1
• 206010067467 Nephrogenic systemic fibrosis Diseases 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• 108091028043 Nucleic acid sequence Proteins 0.000 description 1
• 208000008589 Obesity Diseases 0.000 description 1
• 206010030216 Oesophagitis Diseases 0.000 description 1
• 240000007817 Olea europaea Species 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 208000003435 Optic Neuritis Diseases 0.000 description 1
• 206010033165 Ovarian failure Diseases 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 229910002666 PdCl2 Inorganic materials 0.000 description 1
• 101150003085 Pdcl gene Proteins 0.000 description 1
• 241000721454 Pemphigus Species 0.000 description 1
• 208000031845 Pernicious anaemia Diseases 0.000 description 1
• 208000037581 Persistent Infection Diseases 0.000 description 1
• 239000004264 Petrolatum Substances 0.000 description 1
• 208000010067 Pituitary ACTH Hypersecretion Diseases 0.000 description 1
• 208000020627 Pituitary-dependent Cushing syndrome Diseases 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 229920002732 Polyanhydride Polymers 0.000 description 1
• 206010065159 Polychondritis Diseases 0.000 description 1
• 229920000954 Polyglycolide Polymers 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
• 206010036805 Progressive massive fibrosis Diseases 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 102000007327 Protamines Human genes 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
• 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
• 206010037549 Purpura Diseases 0.000 description 1
• 241001672981 Purpura Species 0.000 description 1
• 208000032056 Radiation Fibrosis Syndrome Diseases 0.000 description 1
• 208000012322 Raynaud phenomenon Diseases 0.000 description 1
• 208000033464 Reiter syndrome Diseases 0.000 description 1
• 206010063837 Reperfusion injury Diseases 0.000 description 1
• 206010038748 Restrictive cardiomyopathy Diseases 0.000 description 1
• 206010038979 Retroperitoneal fibrosis Diseases 0.000 description 1
• 235000004443 Ricinus communis Nutrition 0.000 description 1
• 229910019891 RuCl3 Inorganic materials 0.000 description 1
• RCEJCVWZLAYPLW-SSDOTTSWSA-N SC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O Chemical compound SC1=NC=2C=CC3=C(C=2C=C1)C1=C(S3)C(N[C@@H](CN1)C)=O RCEJCVWZLAYPLW-SSDOTTSWSA-N 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 206010048908 Seasonal allergy Diseases 0.000 description 1
• 201000010208 Seminoma Diseases 0.000 description 1
• 108091082299 Ser/Thr protein kinase family Proteins 0.000 description 1
• 208000021386 Sjogren Syndrome Diseases 0.000 description 1
• 206010041067 Small cell lung cancer Diseases 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 235000002595 Solanum tuberosum Nutrition 0.000 description 1
• 244000061456 Solanum tuberosum Species 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
• SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
• 208000007107 Stomach Ulcer Diseases 0.000 description 1
• 206010042971 T-cell lymphoma Diseases 0.000 description 1
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 206010043276 Teratoma Diseases 0.000 description 1
• DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 description 1
• 241000534944 Thia Species 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
• 208000030886 Traumatic Brain injury Diseases 0.000 description 1
• 206010069363 Traumatic lung injury Diseases 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• 206010046798 Uterine leiomyoma Diseases 0.000 description 1
• 206010046851 Uveitis Diseases 0.000 description 1
• 206010047642 Vitiligo Diseases 0.000 description 1
• 108010046377 Whey Proteins Proteins 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
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• ZEYSHALLPAKUHG-FIBGUPNXSA-N [2H]C([2H])([2H])OC1CCNCC1 Chemical compound [2H]C([2H])([2H])OC1CCNCC1 ZEYSHALLPAKUHG-FIBGUPNXSA-N 0.000 description 1
• NEDPBMIBOQZRIS-UHFFFAOYSA-N [Na].S=S Chemical class [Na].S=S NEDPBMIBOQZRIS-UHFFFAOYSA-N 0.000 description 1
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 239000003655 absorption accelerator Substances 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
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 208000005298 acute pain Diseases 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 230000001919 adrenal effect Effects 0.000 description 1
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 150000008055 alkyl aryl sulfonates Chemical class 0.000 description 1
• 150000008052 alkyl sulfonates Chemical class 0.000 description 1
• 125000000304 alkynyl group Chemical group 0.000 description 1
• 125000004419 alkynylene group Chemical group 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 230000007815 allergy Effects 0.000 description 1
• 125000005336 allyloxy group Chemical group 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 229940063655 aluminum stearate Drugs 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 230000036783 anaphylactic response Effects 0.000 description 1
• 208000003455 anaphylaxis Diseases 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
• 230000001640 apoptogenic effect Effects 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 125000005160 aryl oxy alkyl group Chemical group 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 230000003143 atherosclerotic effect Effects 0.000 description 1
• 201000008937 atopic dermatitis Diseases 0.000 description 1
• 230000001746 atrial effect Effects 0.000 description 1
• 201000004339 autoimmune neuropathy Diseases 0.000 description 1
• 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
• 238000010533 azeotropic distillation Methods 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 239000000440 bentonite Substances 0.000 description 1
• 229910000278 bentonite Inorganic materials 0.000 description 1
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 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
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 229940050390 benzoate Drugs 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 229960002903 benzyl benzoate Drugs 0.000 description 1
• 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 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 230000008512 biological response Effects 0.000 description 1
• 238000001574 biopsy Methods 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 210000001124 body fluid Anatomy 0.000 description 1
• 239000010839 body fluid Substances 0.000 description 1
• 230000036760 body temperature Effects 0.000 description 1
• 238000006664 bond formation reaction Methods 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 208000029028 brain injury Diseases 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 206010006451 bronchitis Diseases 0.000 description 1
• 235000014121 butter Nutrition 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
• 239000001506 calcium phosphate Substances 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
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 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
• 201000011510 cancer Diseases 0.000 description 1
• 208000035269 cancer or benign tumor Diseases 0.000 description 1
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 230000009787 cardiac fibrosis Effects 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000033077 cellular process Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 208000015114 central nervous system disease Diseases 0.000 description 1
• 210000003679 cervix uteri Anatomy 0.000 description 1
• UJNKPILYEWVUNG-UHFFFAOYSA-L cesium;sodium;carbonate Chemical compound [Na+].[Cs+].[O-]C([O-])=O UJNKPILYEWVUNG-UHFFFAOYSA-L 0.000 description 1
• 229940081733 cetearyl alcohol Drugs 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 239000003610 charcoal Substances 0.000 description 1
• 229910052729 chemical element Inorganic materials 0.000 description 1
• 125000003636 chemical group Chemical group 0.000 description 1
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
• 208000020832 chronic kidney disease Diseases 0.000 description 1
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
• 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
• 239000004927 clay Substances 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000010835 comparative analysis Methods 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 208000018631 connective tissue disease Diseases 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 210000004351 coronary vessel Anatomy 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 108010011222 cyclo(Arg-Pro) Proteins 0.000 description 1
• 125000000392 cycloalkenyl group Chemical group 0.000 description 1
• USVZFSNDGFNNJT-UHFFFAOYSA-N cyclopenta-1,4-dien-1-yl(diphenyl)phosphane (2,3-dichlorocyclopenta-1,4-dien-1-yl)-diphenylphosphane iron(2+) Chemical compound [Fe++].c1cc[c-](c1)P(c1ccccc1)c1ccccc1.Clc1c(cc[c-]1Cl)P(c1ccccc1)c1ccccc1 USVZFSNDGFNNJT-UHFFFAOYSA-N 0.000 description 1
• 125000004980 cyclopropylene group Chemical group 0.000 description 1
• 230000016396 cytokine production Effects 0.000 description 1
• 231100000895 deafness Toxicity 0.000 description 1
• 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
• 230000001934 delay Effects 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 238000012217 deletion Methods 0.000 description 1
• 230000037430 deletion Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 125000004431 deuterium atom Chemical group 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 208000033679 diabetic kidney disease Diseases 0.000 description 1
• 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• BSHICDXRSZQYBP-UHFFFAOYSA-N dichloromethane;palladium(2+) Chemical compound [Pd+2].ClCCl BSHICDXRSZQYBP-UHFFFAOYSA-N 0.000 description 1
• LCSNDSFWVKMJCT-UHFFFAOYSA-N dicyclohexyl-(2-phenylphenyl)phosphane Chemical group C1CCCCC1P(C=1C(=CC=CC=1)C=1C=CC=CC=1)C1CCCCC1 LCSNDSFWVKMJCT-UHFFFAOYSA-N 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 1
• 230000001079 digestive effect Effects 0.000 description 1
• GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
• 125000000532 dioxanyl group Chemical group 0.000 description 1
• 125000005879 dioxolanyl group Chemical group 0.000 description 1
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
• 235000019797 dipotassium phosphate Nutrition 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 239000003596 drug target Substances 0.000 description 1
• 239000003221 ear drop Substances 0.000 description 1
• 229940047652 ear drops Drugs 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 239000008387 emulsifying waxe Substances 0.000 description 1
• 239000012060 enantioenriched intermediate Substances 0.000 description 1
• 206010014599 encephalitis Diseases 0.000 description 1
• 201000010048 endomyocardial fibrosis Diseases 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940095399 enema Drugs 0.000 description 1
• 208000010227 enterocolitis Diseases 0.000 description 1
• 208000006881 esophagitis Diseases 0.000 description 1
• 210000003238 esophagus Anatomy 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
• 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
• QQXMRTNJTHNBJF-UHFFFAOYSA-N ethyl 2-amino-4-chloropyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(N)N=C1Cl QQXMRTNJTHNBJF-UHFFFAOYSA-N 0.000 description 1
• ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
• SNNHLSHDDGJVDM-UHFFFAOYSA-N ethyl 4-chloro-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(SC)N=C1Cl SNNHLSHDDGJVDM-UHFFFAOYSA-N 0.000 description 1
• 229940093499 ethyl acetate Drugs 0.000 description 1
• DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 239000002095 exotoxin Substances 0.000 description 1
• 231100000776 exotoxin Toxicity 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 235000019197 fats Nutrition 0.000 description 1
• 208000010706 fatty liver disease Diseases 0.000 description 1
• 210000003608 fece Anatomy 0.000 description 1
• 206010016629 fibroma Diseases 0.000 description 1
• 230000004907 flux Effects 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 210000000232 gallbladder Anatomy 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 208000007565 gingivitis Diseases 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 150000002315 glycerophosphates Chemical class 0.000 description 1
• 229960002449 glycine Drugs 0.000 description 1
• 208000024908 graft versus host disease Diseases 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 125000001188 haloalkyl group Chemical group 0.000 description 1
• 210000003128 head Anatomy 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 208000016354 hearing loss disease Diseases 0.000 description 1
• 230000002489 hematologic effect Effects 0.000 description 1
• 230000002949 hemolytic effect Effects 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004415 heterocyclylalkyl group Chemical group 0.000 description 1
• 239000008241 heterogeneous mixture Substances 0.000 description 1
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 230000000222 hyperoxic effect Effects 0.000 description 1
• 150000002460 imidazoles Chemical class 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 229960003130 interferon gamma Drugs 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 230000031146 intracellular signal transduction Effects 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 238000007919 intrasynovial administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 238000005342 ion exchange Methods 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• 230000000302 ischemic effect Effects 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
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 201000002215 juvenile rheumatoid arthritis Diseases 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
• 210000001117 keloid Anatomy 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 238000012933 kinetic analysis Methods 0.000 description 1
• 238000002372 labelling Methods 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
• 210000000867 larynx Anatomy 0.000 description 1
• 229940070765 laurate Drugs 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 201000010260 leiomyoma Diseases 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 231100000515 lung injury Toxicity 0.000 description 1
• 208000002780 macular degeneration Diseases 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000000391 magnesium silicate Substances 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
• 235000019793 magnesium trisilicate Nutrition 0.000 description 1
• 229940099273 magnesium trisilicate Drugs 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• 239000011976 maleic acid Substances 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
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 201000006512 mast cell neoplasm Diseases 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• DQNQNLWKAGZNIT-UHFFFAOYSA-N methyl 2,6-dichloropyrimidine-4-carboxylate Chemical compound COC(=O)C1=CC(Cl)=NC(Cl)=N1 DQNQNLWKAGZNIT-UHFFFAOYSA-N 0.000 description 1
• MKIJJIMOAABWGF-UHFFFAOYSA-N methyl 2-sulfanylacetate Chemical compound COC(=O)CS MKIJJIMOAABWGF-UHFFFAOYSA-N 0.000 description 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 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
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 229940042472 mineral oil Drugs 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000000116 mitigating effect Effects 0.000 description 1
• 108091005573 modified proteins Proteins 0.000 description 1
• 102000035118 modified proteins Human genes 0.000 description 1
• CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
• 108091005763 multidomain proteins Proteins 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• 206010028417 myasthenia gravis Diseases 0.000 description 1
• 206010028537 myelofibrosis Diseases 0.000 description 1
• 208000010125 myocardial infarction 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
• ZQGJEUVBUVKZKS-UHFFFAOYSA-N n,2-dimethylpropan-2-amine Chemical compound CNC(C)(C)C ZQGJEUVBUVKZKS-UHFFFAOYSA-N 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 229940097496 nasal spray Drugs 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 210000003739 neck Anatomy 0.000 description 1
• 230000027405 negative regulation of phosphorylation Effects 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 208000004296 neuralgia Diseases 0.000 description 1
• 208000007538 neurilemmoma Diseases 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 208000021722 neuropathic pain Diseases 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 1
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 1
• 125000006574 non-aromatic ring group Chemical group 0.000 description 1
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
• 230000030147 nuclear export Effects 0.000 description 1
• 150000007523 nucleic acids Chemical group 0.000 description 1
• 235000020824 obesity Nutrition 0.000 description 1
• GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 201000005737 orchitis Diseases 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 201000008968 osteosarcoma Diseases 0.000 description 1
• 201000004535 ovarian dysfunction Diseases 0.000 description 1
• 231100000539 ovarian failure Toxicity 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• OJEOJUQOECNDND-UHFFFAOYSA-N oxetan-3-amine Chemical compound NC1COC1 OJEOJUQOECNDND-UHFFFAOYSA-N 0.000 description 1
• QMLWSAXEQSBAAQ-UHFFFAOYSA-N oxetan-3-ol Chemical compound OC1COC1 QMLWSAXEQSBAAQ-UHFFFAOYSA-N 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 235000020232 peanut Nutrition 0.000 description 1
• 239000002304 perfume Substances 0.000 description 1
• 201000001245 periodontitis Diseases 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
• 229940066842 petrolatum Drugs 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
• 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 125000005545 phthalimidyl group Chemical group 0.000 description 1
• 229950010765 pivalate Drugs 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 201000006292 polyarteritis nodosa Diseases 0.000 description 1
• 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
• 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 229940113124 polysorbate 60 Drugs 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000004302 potassium sorbate Substances 0.000 description 1
• 235000010241 potassium sorbate Nutrition 0.000 description 1
• 229940069338 potassium sorbate Drugs 0.000 description 1
• 239000012041 precatalyst Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 238000011165 process development Methods 0.000 description 1
• 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229950008679 protamine sulfate Drugs 0.000 description 1
• 239000003909 protein kinase inhibitor Substances 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• HAMAGKWXRRTWCJ-UHFFFAOYSA-N pyrido[2,3-b][1,4]oxazin-3-one Chemical compound C1=CN=C2OC(=O)C=NC2=C1 HAMAGKWXRRTWCJ-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
• YPOXGDJGKBXRFP-UHFFFAOYSA-M pyrimidine-4-carboxylate Chemical compound [O-]C(=O)C1=CC=NC=N1 YPOXGDJGKBXRFP-UHFFFAOYSA-M 0.000 description 1
• AHRQYOSAXZQCIG-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=C=NC=N[CH]1 AHRQYOSAXZQCIG-UHFFFAOYSA-N 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• 125000001453 quaternary ammonium group Chemical group 0.000 description 1
• LOAUVZALPPNFOQ-UHFFFAOYSA-M quinaldate Chemical compound C1=CC=CC2=NC(C(=O)[O-])=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-M 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
• 238000000163 radioactive labelling Methods 0.000 description 1
• 239000002287 radioligand Substances 0.000 description 1
• 239000002994 raw material Substances 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 208000002574 reactive arthritis Diseases 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 229940100618 rectal suppository Drugs 0.000 description 1
• 239000006215 rectal suppository Substances 0.000 description 1
• 230000025053 regulation of cell proliferation Effects 0.000 description 1
• 230000014493 regulation of gene expression Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 208000009169 relapsing polychondritis Diseases 0.000 description 1
• 201000002793 renal fibrosis Diseases 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 239000013557 residual solvent Substances 0.000 description 1
• 230000003938 response to stress Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 239000013037 reversible inhibitor Substances 0.000 description 1
• YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 1
• 210000003296 saliva Anatomy 0.000 description 1
• 210000000582 semen Anatomy 0.000 description 1
• 230000036303 septic shock Effects 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 201000009890 sinusitis Diseases 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• QDRKDTQENPPHOJ-LUIAAVAXSA-N sodium 1,1,2,2,2-pentadeuterioethanolate Chemical compound C(C([2H])([2H])[2H])([O-])([2H])[2H].[Na+] QDRKDTQENPPHOJ-LUIAAVAXSA-N 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 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
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 1
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
• LYPGDCWPTHTUDO-UHFFFAOYSA-M sodium;methanesulfinate Chemical compound [Na+].CS([O-])=O LYPGDCWPTHTUDO-UHFFFAOYSA-M 0.000 description 1
• 238000000935 solvent evaporation Methods 0.000 description 1
• 238000000527 sonication Methods 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
• 239000001587 sorbitan monostearate Substances 0.000 description 1
• 235000011076 sorbitan monostearate Nutrition 0.000 description 1
• 229940035048 sorbitan monostearate Drugs 0.000 description 1
• 230000003595 spectral effect Effects 0.000 description 1
• 230000007863 steatosis Effects 0.000 description 1
• 231100000240 steatosis hepatitis Toxicity 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 239000003206 sterilizing agent Substances 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 230000035882 stress Effects 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection 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
• 239000001384 succinic acid Substances 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 210000001138 tear Anatomy 0.000 description 1
• 230000002123 temporal effect Effects 0.000 description 1
• 208000001608 teratocarcinoma Diseases 0.000 description 1
• PCVMBAOWKUKBRU-QMMMGPOBSA-N tert-butyl (4s)-4-(aminomethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate Chemical compound CC(C)(C)OC(=O)N1[C@@H](CN)COC1(C)C PCVMBAOWKUKBRU-QMMMGPOBSA-N 0.000 description 1
• 210000001550 testis Anatomy 0.000 description 1
• MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• DBAKEZYZWPGPHH-UHFFFAOYSA-N thieno[3,2-f]quinoline Chemical compound C1=CC=C2C(C=CS3)=C3C=CC2=N1 DBAKEZYZWPGPHH-UHFFFAOYSA-N 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 230000002446 thrombocytic effect Effects 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• 208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
• 206010043778 thyroiditis Diseases 0.000 description 1
• 208000005057 thyrotoxicosis Diseases 0.000 description 1
• 208000037816 tissue injury Diseases 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
• 238000011200 topical administration Methods 0.000 description 1
• 239000012049 topical pharmaceutical composition Substances 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 230000002103 transcriptional effect Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 230000009529 traumatic brain injury Effects 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 230000006433 tumor necrosis factor production Effects 0.000 description 1
• 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
• ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
• 210000003932 urinary bladder Anatomy 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 210000004291 uterus Anatomy 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
• 235000013311 vegetables Nutrition 0.000 description 1
• 239000003039 volatile agent Substances 0.000 description 1
• 238000010792 warming Methods 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 235000021119 whey protein Nutrition 0.000 description 1
• 210000002268 wool Anatomy 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 235000016804 zinc Nutrition 0.000 description 1