EA032315B1 - Замещенные трициклические гетероциклические соединения - Google Patents

Info

Publication number

EA032315B1

EA032315B1 EA201792034A EA201792034A EA032315B1 EA 032315 B1 EA032315 B1 EA 032315B1 EA 201792034 A EA201792034 A EA 201792034A EA 201792034 A EA201792034 A EA 201792034A EA 032315 B1 EA032315 B1 EA 032315B1

Authority

EA

Eurasian Patent Office

Prior art keywords

phenyl

dihydro

imidazo

pyridin

formula

Prior art date

2015-03-18

Links

• Espacenet
• Global Dossier
• Discuss

• 150000002391 heterocyclic compounds Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 301
• 150000003839 salts Chemical class 0.000 claims abstract description 94
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 19
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 15
• 230000002757 inflammatory effect Effects 0.000 claims abstract description 10
• -1 methylpiperazinyl Chemical group 0.000 claims description 148
• ZVWSNJQNGVRIGG-UHFFFAOYSA-N N=1C=NC2=NC=C(CC2=1)O Chemical compound N=1C=NC2=NC=C(CC2=1)O ZVWSNJQNGVRIGG-UHFFFAOYSA-N 0.000 claims description 62
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
• GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims description 28
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
• 238000011282 treatment Methods 0.000 claims description 24
• 125000001424 substituent group Chemical group 0.000 claims description 14
• 201000010099 disease Diseases 0.000 claims description 13
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 239000003937 drug carrier Substances 0.000 claims description 8
• ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 7
• 239000003085 diluting agent Substances 0.000 claims description 7
• AQHQIKSWRGMNJB-UHFFFAOYSA-N 2-[4-[5-fluoro-3-[2-(trifluoromethyl)phenyl]-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-11-yl]phenyl]propan-2-ol Chemical compound FC1CC(N2C1=NC=1C2=NC(=CC=1)C1=CC=C(C=C1)C(C)(C)O)C1=C(C=CC=C1)C(F)(F)F AQHQIKSWRGMNJB-UHFFFAOYSA-N 0.000 claims description 6
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
• 125000004076 pyridyl group Chemical group 0.000 claims description 6
• XLDXEBXBEVPCDQ-UHFFFAOYSA-N 2-[4-[3-[2-(trifluoromethyl)phenyl]-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-11-yl]phenyl]propan-2-ol Chemical compound FC(C1=C(C=CC=C1)C1CCC2=NC=3C(=NC(=CC=3)C3=CC=C(C=C3)C(C)(C)O)N21)(F)F XLDXEBXBEVPCDQ-UHFFFAOYSA-N 0.000 claims description 5
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
• FUMXWCXIKLKMMQ-UHFFFAOYSA-N 11-[4-(2-hydroxypropan-2-yl)phenyl]-3-(2-methoxyphenyl)-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-5-ol Chemical compound OC(C)(C)C1=CC=C(C=C1)C1=CC=C2C(=N1)N1C(=N2)C(CC1C1=C(C=CC=C1)OC)O FUMXWCXIKLKMMQ-UHFFFAOYSA-N 0.000 claims description 4
• UJQIXEYIQCDDAB-UHFFFAOYSA-N 2-[4-[3-(2-cyclopropylphenyl)-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-11-yl]phenyl]propan-2-ol Chemical compound C1(CC1)C1=C(C=CC=C1)C1CCC2=NC=3C(=NC(=CC=3)C3=CC=C(C=C3)C(C)(C)O)N21 UJQIXEYIQCDDAB-UHFFFAOYSA-N 0.000 claims description 4
• DCQCGNMFCGZMGL-UHFFFAOYSA-N 2-[4-[3-(2-cyclopropylphenyl)-5-fluoro-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-11-yl]phenyl]propan-2-ol Chemical compound C1(CC1)C1=C(C=CC=C1)C1CC(C2=NC=3C(=NC(=CC=3)C3=CC=C(C=C3)C(C)(C)O)N21)F DCQCGNMFCGZMGL-UHFFFAOYSA-N 0.000 claims description 4
• BVWMDSRUMHZQQY-UHFFFAOYSA-N 2-[4-[3-(2-methoxyphenyl)-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-11-yl]phenyl]propan-2-ol Chemical compound COC1=C(C=CC=C1)C1CCC2=NC=3C(=NC(=CC=3)C3=CC=C(C=C3)C(C)(C)O)N21 BVWMDSRUMHZQQY-UHFFFAOYSA-N 0.000 claims description 4
• HTWJGCUKEIUWNB-UHFFFAOYSA-N 2-[4-[3-[2-(difluoromethoxy)phenyl]-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-11-yl]phenyl]propan-2-ol Chemical compound FC(OC1=C(C=CC=C1)C1CCC2=NC=3C(=NC(=CC=3)C3=CC=C(C=C3)C(C)(C)O)N21)F HTWJGCUKEIUWNB-UHFFFAOYSA-N 0.000 claims description 4
• FXWYBCDCDHAQFS-UHFFFAOYSA-N 2-[4-[3-[2-(difluoromethoxy)phenyl]-5-fluoro-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-11-yl]phenyl]propan-2-ol Chemical compound FC(OC1=C(C=CC=C1)C1CC(C2=NC=3C(=NC(=CC=3)C3=CC=C(C=C3)C(C)(C)O)N21)F)F FXWYBCDCDHAQFS-UHFFFAOYSA-N 0.000 claims description 4
• LWOODTYOEVZSQK-UHFFFAOYSA-N 2-[4-[3-[2-fluoro-6-(trifluoromethyl)phenyl]-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-11-yl]phenyl]propan-2-ol Chemical compound FC1=C(C(=CC=C1)C(F)(F)F)C1CCC2=NC=3C(=NC(=CC=3)C3=CC=C(C=C3)C(C)(C)O)N21 LWOODTYOEVZSQK-UHFFFAOYSA-N 0.000 claims description 4
• RROYCRUUWHVBCL-UHFFFAOYSA-N 2-[4-[5-[3-(2-methoxyphenyl)-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-11-yl]pyrimidin-2-yl]piperazin-1-yl]acetic acid Chemical compound COC1=C(C=CC=C1)C1CCC2=NC=3C(=NC(=CC=3)C=3C=NC(=NC=3)N3CCN(CC3)CC(=O)O)N21 RROYCRUUWHVBCL-UHFFFAOYSA-N 0.000 claims description 4
• LMLGUPLXAVIXKY-UHFFFAOYSA-N 2-[5-[3-(2,5-dimethylphenyl)-5-fluoro-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-11-yl]pyrimidin-2-yl]propan-2-ol Chemical compound CC1=C(C=C(C=C1)C)C1CC(C2=NC=3C(=NC(=CC=3)C=3C=NC(=NC=3)C(C)(C)O)N21)F LMLGUPLXAVIXKY-UHFFFAOYSA-N 0.000 claims description 4
• XEPMXXAHTTXNFI-UHFFFAOYSA-N 2-[5-[3-[2-(difluoromethoxy)phenyl]-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-11-yl]pyrimidin-2-yl]propan-2-ol Chemical compound FC(OC1=C(C=CC=C1)C1CCC2=NC=3C(=NC(=CC=3)C=3C=NC(=NC=3)C(C)(C)O)N21)F XEPMXXAHTTXNFI-UHFFFAOYSA-N 0.000 claims description 4
• BIICWYBWGDLGDM-UHFFFAOYSA-N 2-[5-[3-[2-(difluoromethoxy)phenyl]-5-fluoro-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-11-yl]pyrimidin-2-yl]propan-2-ol Chemical compound FC(OC1=C(C=CC=C1)C1CC(C2=NC=3C(=NC(=CC=3)C=3C=NC(=NC=3)C(C)(C)O)N21)F)F BIICWYBWGDLGDM-UHFFFAOYSA-N 0.000 claims description 4
• GALYFDYKAMGDGH-UHFFFAOYSA-N 4-[5-[3-[2-(difluoromethoxy)phenyl]-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-11-yl]pyrimidin-2-yl]morpholine Chemical compound FC(OC1=C(C=CC=C1)C1CCC2=NC=3C(=NC(=CC=3)C=3C=NC(=NC=3)N3CCOCC3)N21)F GALYFDYKAMGDGH-UHFFFAOYSA-N 0.000 claims description 4
• IZIRWECBBGQVIA-UHFFFAOYSA-N 4-[5-[3-[2-(difluoromethoxy)phenyl]-5-fluoro-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-11-yl]pyrimidin-2-yl]morpholine Chemical compound FC(OC1=C(C=CC=C1)C1CC(C2=NC=3C(=NC(=CC=3)C=3C=NC(=NC=3)N3CCOCC3)N21)F)F IZIRWECBBGQVIA-UHFFFAOYSA-N 0.000 claims description 4
• 201000005569 Gout Diseases 0.000 claims description 4
• 201000004681 Psoriasis Diseases 0.000 claims description 4
• 201000006417 multiple sclerosis Diseases 0.000 claims description 4
• 230000000737 periodic effect Effects 0.000 claims description 4
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 4
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
• 208000011580 syndromic disease Diseases 0.000 claims description 4
• 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 3
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
• 208000011231 Crohn disease Diseases 0.000 claims description 3
• 208000003807 Graves Disease Diseases 0.000 claims description 3
• 208000015023 Graves' disease Diseases 0.000 claims description 3
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims description 3
• 208000005777 Lupus Nephritis Diseases 0.000 claims description 3
• 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 3
• 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 3
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
• 208000006673 asthma Diseases 0.000 claims description 3
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
• 201000002215 juvenile rheumatoid arthritis Diseases 0.000 claims description 3
• 125000002757 morpholinyl group Chemical group 0.000 claims description 3
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 3
• 206010011224 Cough Diseases 0.000 claims description 2
• 206010018634 Gouty Arthritis Diseases 0.000 claims description 2
• 208000009329 Graft vs Host Disease Diseases 0.000 claims description 2
• 208000003456 Juvenile Arthritis Diseases 0.000 claims description 2
• 208000024908 graft versus host disease Diseases 0.000 claims description 2
• 206010025135 lupus erythematosus Diseases 0.000 claims description 2
• 208000004296 neuralgia Diseases 0.000 claims description 2
• 208000021722 neuropathic pain Diseases 0.000 claims description 2
• 206010016207 Familial Mediterranean fever Diseases 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 37
• 108060008682 Tumor Necrosis Factor Proteins 0.000 abstract 1
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 abstract 1
• 235000002639 sodium chloride Nutrition 0.000 description 93
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 87
• 125000003118 aryl group Chemical group 0.000 description 64
• 125000000217 alkyl group Chemical group 0.000 description 53
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 49
• 125000000623 heterocyclic group Chemical group 0.000 description 49
• 238000006243 chemical reaction Methods 0.000 description 41
• 229910052799 carbon Inorganic materials 0.000 description 40
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 38
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
• 239000000543 intermediate Substances 0.000 description 33
• 239000000047 product Substances 0.000 description 33
• 229910052739 hydrogen Inorganic materials 0.000 description 32
• 239000000243 solution Substances 0.000 description 31
• 239000000203 mixture Substances 0.000 description 29
• 239000011541 reaction mixture Substances 0.000 description 25
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
• 238000005481 NMR spectroscopy Methods 0.000 description 24
• 239000010410 layer Substances 0.000 description 24
• 206010003246 arthritis Diseases 0.000 description 21
• 125000002950 monocyclic group Chemical group 0.000 description 21
• 239000003921 oil Substances 0.000 description 21
• 235000019198 oils Nutrition 0.000 description 21
• 125000004432 carbon atom Chemical group C* 0.000 description 20
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
• 238000003756 stirring Methods 0.000 description 20
• 239000007787 solid Substances 0.000 description 19
• 150000001721 carbon Chemical group 0.000 description 18
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 16
• 239000005695 Ammonium acetate Substances 0.000 description 16
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
• 125000003545 alkoxy group Chemical group 0.000 description 16
• 235000019257 ammonium acetate Nutrition 0.000 description 16
• 229940043376 ammonium acetate Drugs 0.000 description 16
• 238000002360 preparation method Methods 0.000 description 16
• 239000000725 suspension Substances 0.000 description 16
• 125000004452 carbocyclyl group Chemical group 0.000 description 15
• 235000019441 ethanol Nutrition 0.000 description 15
• 125000003709 fluoroalkyl group Chemical group 0.000 description 15
• 239000012453 solvate Substances 0.000 description 15
• 208000035475 disorder Diseases 0.000 description 14
• 239000007789 gas Substances 0.000 description 14
• 229910052736 halogen Inorganic materials 0.000 description 14
• 150000002367 halogens Chemical class 0.000 description 14
• 125000005842 heteroatom Chemical group 0.000 description 14
• 230000015572 biosynthetic process Effects 0.000 description 13
• 125000001072 heteroaryl group Chemical group 0.000 description 13
• 229910052757 nitrogen Inorganic materials 0.000 description 13
• 239000002245 particle Substances 0.000 description 13
• 229920006395 saturated elastomer Polymers 0.000 description 13
• 238000003786 synthesis reaction Methods 0.000 description 13
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 239000007864 aqueous solution Substances 0.000 description 12
• 239000002585 base Substances 0.000 description 12
• 238000002347 injection Methods 0.000 description 12
• 239000007924 injection Substances 0.000 description 12
• 239000002904 solvent Substances 0.000 description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
• 239000012267 brine Substances 0.000 description 11
• 150000002148 esters Chemical class 0.000 description 11
• 229910052760 oxygen Inorganic materials 0.000 description 11
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 10
• 230000001363 autoimmune Effects 0.000 description 10
• 239000013256 coordination polymer Substances 0.000 description 10
• 229910052700 potassium Inorganic materials 0.000 description 10
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 10
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
• 239000002671 adjuvant Substances 0.000 description 9
• 150000001299 aldehydes Chemical class 0.000 description 9
• 239000000651 prodrug Substances 0.000 description 9
• 229940002612 prodrug Drugs 0.000 description 9
• 230000002829 reductive effect Effects 0.000 description 9
• 239000003826 tablet Substances 0.000 description 9
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 8
• 238000004458 analytical method Methods 0.000 description 8
• 201000011510 cancer Diseases 0.000 description 8
• 238000001514 detection method Methods 0.000 description 8
• 239000003995 emulsifying agent Substances 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• 230000014759 maintenance of location Effects 0.000 description 8
• 239000000463 material Substances 0.000 description 8
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 8
• 229910052763 palladium Inorganic materials 0.000 description 8
• 239000003755 preservative agent Substances 0.000 description 8
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 8
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 7
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 7
• 101100500565 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) ECM8 gene Proteins 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 238000003556 assay Methods 0.000 description 7
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
• 239000012043 crude product Substances 0.000 description 7
• 125000004966 cyanoalkyl group Chemical group 0.000 description 7
• 235000014113 dietary fatty acids Nutrition 0.000 description 7
• 239000000194 fatty acid Substances 0.000 description 7
• 229930195729 fatty acid Natural products 0.000 description 7
• 150000004665 fatty acids Chemical class 0.000 description 7
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 7
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
• 239000001301 oxygen Substances 0.000 description 7
• 239000000546 pharmaceutical excipient Substances 0.000 description 7
• 229910052698 phosphorus Inorganic materials 0.000 description 7
• 229910000906 Bronze Inorganic materials 0.000 description 6
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 6
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
• 208000029725 Metabolic bone disease Diseases 0.000 description 6
• 206010028980 Neoplasm Diseases 0.000 description 6
• 206010049088 Osteopenia Diseases 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-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
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 6
• 239000010974 bronze Substances 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• KUNSUQLRTQLHQQ-UHFFFAOYSA-N copper tin Chemical compound [Cu].[Sn] KUNSUQLRTQLHQQ-UHFFFAOYSA-N 0.000 description 6
• 125000000753 cycloalkyl group Chemical group 0.000 description 6
• 239000012634 fragment Substances 0.000 description 6
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 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
• 230000036961 partial effect Effects 0.000 description 6
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 5
• 206010065042 Immune reconstitution inflammatory syndrome Diseases 0.000 description 5
• 241000124008 Mammalia Species 0.000 description 5
• 239000004677 Nylon Substances 0.000 description 5
• 239000007900 aqueous suspension Substances 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 238000005119 centrifugation Methods 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 239000007859 condensation product Substances 0.000 description 5
• 238000007872 degassing Methods 0.000 description 5
• 239000000839 emulsion Substances 0.000 description 5
• 235000019197 fats Nutrition 0.000 description 5
• KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 5
• 235000003599 food sweetener Nutrition 0.000 description 5
• 238000009472 formulation Methods 0.000 description 5
• 125000001188 haloalkyl group Chemical group 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• 150000003951 lactams Chemical group 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 239000012528 membrane Substances 0.000 description 5
• 208000030159 metabolic disease Diseases 0.000 description 5
• 238000002156 mixing Methods 0.000 description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 description 5
• 231100000252 nontoxic Toxicity 0.000 description 5
• 230000003000 nontoxic effect Effects 0.000 description 5
• 229920001778 nylon Polymers 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• 239000000741 silica gel Substances 0.000 description 5
• 229910002027 silica gel Inorganic materials 0.000 description 5
• 239000003381 stabilizer Substances 0.000 description 5
• 239000003765 sweetening agent Substances 0.000 description 5
• 238000002560 therapeutic procedure Methods 0.000 description 5
• 239000000080 wetting agent Substances 0.000 description 5
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• 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 4
• ZDVRPKUWYQVVDX-UHFFFAOYSA-N 2-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC=C1C=O ZDVRPKUWYQVVDX-UHFFFAOYSA-N 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• 229920000858 Cyclodextrin Polymers 0.000 description 4
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
• 208000012902 Nervous system disease Diseases 0.000 description 4
• 208000025966 Neurological disease Diseases 0.000 description 4
• 239000002202 Polyethylene glycol Substances 0.000 description 4
• 239000002253 acid Substances 0.000 description 4
• 125000003342 alkenyl group Chemical group 0.000 description 4
• 239000003963 antioxidant agent Substances 0.000 description 4
• 235000006708 antioxidants Nutrition 0.000 description 4
• 238000013459 approach Methods 0.000 description 4
• 125000004429 atom Chemical group 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 125000002619 bicyclic group Chemical group 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 125000002837 carbocyclic group Chemical group 0.000 description 4
• 239000002270 dispersing agent Substances 0.000 description 4
• 238000010828 elution Methods 0.000 description 4
• 238000003818 flash chromatography Methods 0.000 description 4
• 239000000796 flavoring agent Substances 0.000 description 4
• 235000013355 food flavoring agent Nutrition 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• 239000008187 granular material Substances 0.000 description 4
• 235000010445 lecithin Nutrition 0.000 description 4
• 239000000787 lecithin Substances 0.000 description 4
• 229940067606 lecithin Drugs 0.000 description 4
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
• 208000015122 neurodegenerative disease Diseases 0.000 description 4
• 230000000926 neurological effect Effects 0.000 description 4
• 230000000771 oncological effect Effects 0.000 description 4
• 125000004193 piperazinyl group Chemical group 0.000 description 4
• 229920001223 polyethylene glycol Polymers 0.000 description 4
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
• 230000002335 preservative effect Effects 0.000 description 4
• 238000000926 separation method Methods 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 125000004434 sulfur atom Chemical group 0.000 description 4
• 239000000375 suspending agent Substances 0.000 description 4
• 238000012360 testing method Methods 0.000 description 4
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
• 229910000404 tripotassium phosphate Inorganic materials 0.000 description 4
• 235000019798 tripotassium phosphate Nutrition 0.000 description 4
• 239000003039 volatile agent Substances 0.000 description 4
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 3
• FFRFTURYWWFKIC-UHFFFAOYSA-N 2,6-dibromo-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Br)N=C1Br FFRFTURYWWFKIC-UHFFFAOYSA-N 0.000 description 3
• 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 3
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
• 239000004215 Carbon black (E152) Substances 0.000 description 3
• 208000024172 Cardiovascular disease Diseases 0.000 description 3
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 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 3
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 3
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
• WZWKXDDZPSSOMR-UHFFFAOYSA-N OC(C)(C)C1=CC=C(C=C1)OB(O)O Chemical compound OC(C)(C)C1=CC=C(C=C1)OB(O)O WZWKXDDZPSSOMR-UHFFFAOYSA-N 0.000 description 3
• 208000017442 Retinal disease Diseases 0.000 description 3
• 206010038923 Retinopathy Diseases 0.000 description 3
• 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 3
• 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 3
• 125000001931 aliphatic group Chemical group 0.000 description 3
• 125000000304 alkynyl group Chemical group 0.000 description 3
• 230000000172 allergic effect Effects 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 239000000908 ammonium hydroxide Substances 0.000 description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 3
• 238000004166 bioassay Methods 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 229920002678 cellulose Polymers 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• 229940125773 compound 10 Drugs 0.000 description 3
• 229940125797 compound 12 Drugs 0.000 description 3
• 238000007796 conventional method Methods 0.000 description 3
• 238000004132 cross linking Methods 0.000 description 3
• 125000000392 cycloalkenyl group Chemical group 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 230000000694 effects Effects 0.000 description 3
• 208000030533 eye disease Diseases 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 125000004428 fluoroalkoxy group Chemical group 0.000 description 3
• 230000005714 functional activity Effects 0.000 description 3
• 239000007903 gelatin capsule Substances 0.000 description 3
• 125000005843 halogen group Chemical group 0.000 description 3
• 229930195733 hydrocarbon Natural products 0.000 description 3
• 239000001257 hydrogen Substances 0.000 description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
• 125000001041 indolyl group Chemical group 0.000 description 3
• 238000002955 isolation Methods 0.000 description 3
• 125000000842 isoxazolyl group Chemical group 0.000 description 3
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 3
• 150000002576 ketones Chemical class 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 229940057995 liquid paraffin Drugs 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
• 239000004530 micro-emulsion Substances 0.000 description 3
• 125000006574 non-aromatic ring group Chemical group 0.000 description 3
• 239000000346 nonvolatile oil Substances 0.000 description 3
• 239000004006 olive oil Substances 0.000 description 3
• 235000008390 olive oil Nutrition 0.000 description 3
• 210000000056 organ Anatomy 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 125000003386 piperidinyl group Chemical group 0.000 description 3
• 238000012545 processing Methods 0.000 description 3
• 238000011321 prophylaxis Methods 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 230000009467 reduction Effects 0.000 description 3
• 238000006722 reduction reaction Methods 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 230000009885 systemic effect Effects 0.000 description 3
• 239000001993 wax Substances 0.000 description 3
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 2
• 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 description 2
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
• ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
• HMPLJDYRJPVIOE-UHFFFAOYSA-N 1-[2-(trifluoromethyl)phenyl]but-3-en-1-amine Chemical compound C=CCC(N)C1=CC=CC=C1C(F)(F)F HMPLJDYRJPVIOE-UHFFFAOYSA-N 0.000 description 2
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• RZWDBUXNZUWFRK-UHFFFAOYSA-N 11-bromo-3-[2-(trifluoromethyl)phenyl]-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-5-ol Chemical compound BrC1=CC=C2C(=N1)N1C(=N2)C(CC1C1=C(C=CC=C1)C(F)(F)F)O RZWDBUXNZUWFRK-UHFFFAOYSA-N 0.000 description 2
• FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical class ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 2
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 2
• DVPPBWSHROBBFJ-UHFFFAOYSA-N 2-[4-[3-[5-fluoro-2-(trifluoromethyl)phenyl]-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraen-11-yl]phenyl]propan-2-ol Chemical compound FC=1C=CC(=C(C=1)C1CCC2=NC=3C(=NC(=CC=3)C3=CC=C(C=C3)C(C)(C)O)N21)C(F)(F)F DVPPBWSHROBBFJ-UHFFFAOYSA-N 0.000 description 2
• JBKQHCAUZJBAND-UHFFFAOYSA-N 2-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl]propan-2-ol Chemical compound C1=NC(C(C)(O)C)=NC=C1B1OC(C)(C)C(C)(C)O1 JBKQHCAUZJBAND-UHFFFAOYSA-N 0.000 description 2
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
• QRJUPHFHVKUAQP-UHFFFAOYSA-N 3-[(6-bromo-3-nitropyridin-2-yl)amino]-3-[2-(trifluoromethyl)phenyl]propanal Chemical compound BrC1=CC=C(C(=N1)NC(CC=O)C1=C(C=CC=C1)C(F)(F)F)[N+](=O)[O-] QRJUPHFHVKUAQP-UHFFFAOYSA-N 0.000 description 2
• WVRWGSOUMKXHBV-UHFFFAOYSA-N 4-[(3-amino-6-bromopyridin-2-yl)amino]-2-hydroxy-4-[2-(trifluoromethyl)phenyl]butanenitrile Chemical compound NC=1C(=NC(=CC=1)Br)NC(CC(C#N)O)C1=C(C=CC=C1)C(F)(F)F WVRWGSOUMKXHBV-UHFFFAOYSA-N 0.000 description 2
• RFPZXNBIDWWFSW-UHFFFAOYSA-N 4-[(6-bromo-3-nitropyridin-2-yl)amino]-2-hydroxy-4-[2-(trifluoromethyl)phenyl]butanenitrile Chemical compound BrC1=CC=C(C(=N1)NC(CC(C#N)O)C1=C(C=CC=C1)C(F)(F)F)[N+](=O)[O-] RFPZXNBIDWWFSW-UHFFFAOYSA-N 0.000 description 2
• BGJHWYHQAWSLPE-UHFFFAOYSA-N 4-[(6-bromo-3-nitropyridin-2-yl)amino]-4-[2-(trifluoromethyl)phenyl]butane-1,2-diol Chemical compound BrC1=CC=C(C(=N1)NC(CC(CO)O)C1=C(C=CC=C1)C(F)(F)F)[N+](=O)[O-] BGJHWYHQAWSLPE-UHFFFAOYSA-N 0.000 description 2
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
• 101150065749 Churc1 gene Proteins 0.000 description 2
• 229940126657 Compound 17 Drugs 0.000 description 2
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
• 101100520660 Drosophila melanogaster Poc1 gene Proteins 0.000 description 2
• 208000017701 Endocrine disease Diseases 0.000 description 2
• 206010018364 Glomerulonephritis Diseases 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 235000010469 Glycine max Nutrition 0.000 description 2
• 229920000084 Gum arabic Polymers 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
• 208000036576 Obstructive uropathy Diseases 0.000 description 2
• 239000005642 Oleic acid Substances 0.000 description 2
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
• 208000002193 Pain Diseases 0.000 description 2
• 235000019483 Peanut oil Nutrition 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 102100038239 Protein Churchill Human genes 0.000 description 2
• 206010037660 Pyrexia Diseases 0.000 description 2
• 101100520662 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PBA1 gene Proteins 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• 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 2
• 229930006000 Sucrose Natural products 0.000 description 2
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
• DPIDNFWCDMXMDY-UHFFFAOYSA-N [4-(2-hydroxypropan-2-yl)phenyl]boronic acid Chemical group CC(C)(O)C1=CC=C(B(O)O)C=C1 DPIDNFWCDMXMDY-UHFFFAOYSA-N 0.000 description 2
• 235000010489 acacia gum Nutrition 0.000 description 2
• 239000000205 acacia gum Substances 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 125000002015 acyclic group Chemical group 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 229940087168 alpha tocopherol Drugs 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 208000007502 anemia Diseases 0.000 description 2
• 230000003078 antioxidant effect Effects 0.000 description 2
• 239000000305 astragalus gummifer gum Substances 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 208000010668 atopic eczema Diseases 0.000 description 2
• 125000002393 azetidinyl group Chemical group 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
• 239000004327 boric acid Substances 0.000 description 2
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
• 229910002091 carbon monoxide Inorganic materials 0.000 description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 235000010980 cellulose Nutrition 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 229940125833 compound 23 Drugs 0.000 description 2
• 125000004093 cyano group Chemical group *C#N 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• WDUDHEOUGWAKFD-UHFFFAOYSA-N ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+) Chemical compound [Fe+2].CC(C)(C)P(C(C)(C)C)C1=CC=C[CH-]1.CC(C)(C)P(C(C)(C)C)C1=CC=C[CH-]1 WDUDHEOUGWAKFD-UHFFFAOYSA-N 0.000 description 2
• 229940079593 drug Drugs 0.000 description 2
• 239000000975 dye Substances 0.000 description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 125000004438 haloalkoxy group Chemical group 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• 230000002489 hematologic effect Effects 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• 150000004677 hydrates Chemical class 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• 239000007937 lozenge Substances 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
• 239000008108 microcrystalline cellulose Substances 0.000 description 2
• 229940016286 microcrystalline cellulose Drugs 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 230000003040 nociceptive effect Effects 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• 239000012053 oil suspension 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
• 239000012044 organic layer Substances 0.000 description 2
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 2
• 239000012285 osmium tetroxide Substances 0.000 description 2
• 238000004806 packaging method and process Methods 0.000 description 2
• 235000021400 peanut butter Nutrition 0.000 description 2
• 239000000312 peanut oil Substances 0.000 description 2
• 239000002831 pharmacologic agent Substances 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
• 229920000053 polysorbate 80 Polymers 0.000 description 2
• 239000002244 precipitate Substances 0.000 description 2
• 238000001556 precipitation Methods 0.000 description 2
• 230000002062 proliferating effect Effects 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• 238000011084 recovery Methods 0.000 description 2
• 238000007363 ring formation reaction Methods 0.000 description 2
• 239000008159 sesame oil Substances 0.000 description 2
• 235000011803 sesame oil Nutrition 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 235000010413 sodium alginate Nutrition 0.000 description 2
• 239000000661 sodium alginate Substances 0.000 description 2
• 229940005550 sodium alginate Drugs 0.000 description 2
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• 230000007928 solubilization Effects 0.000 description 2
• 238000005063 solubilization Methods 0.000 description 2
• 235000011069 sorbitan monooleate Nutrition 0.000 description 2
• 239000001593 sorbitan monooleate Substances 0.000 description 2
• 229940035049 sorbitan monooleate Drugs 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 230000000638 stimulation Effects 0.000 description 2
• 229940014800 succinic anhydride Drugs 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 229960000984 tocofersolan Drugs 0.000 description 2
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• 201000002327 urinary tract obstruction Diseases 0.000 description 2
• 235000015112 vegetable and seed oil Nutrition 0.000 description 2
• 239000008158 vegetable oil Substances 0.000 description 2
• UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 2
• 239000002076 α-tocopherol Substances 0.000 description 2
• UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 description 1
• 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 1
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
• GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
• CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 description 1
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
• PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical class [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 description 1
• XAVBIIPDPUWJMY-UHFFFAOYSA-N 11-bromo-3-[2-(trifluoromethyl)phenyl]-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraene Chemical compound BrC1=CC=C2C(=N1)N1C(=N2)CCC1C1=C(C=CC=C1)C(F)(F)F XAVBIIPDPUWJMY-UHFFFAOYSA-N 0.000 description 1
• NBWQGAKWPHRHSF-UHFFFAOYSA-N 11-bromo-5-chloro-3-[2-(trifluoromethyl)phenyl]-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraene Chemical compound BrC1=CC=C2C(=N1)N1C(=N2)C(CC1C1=C(C=CC=C1)C(F)(F)F)Cl NBWQGAKWPHRHSF-UHFFFAOYSA-N 0.000 description 1
• MCTCNRSXMFNTDK-UHFFFAOYSA-N 11-bromo-5-fluoro-3-[2-(trifluoromethyl)phenyl]-2,7,12-triazatricyclo[6.4.0.02,6]dodeca-1(8),6,9,11-tetraene Chemical compound BrC1=CC=C2C(=N1)N1C(=N2)C(CC1C1=C(C=CC=C1)C(F)(F)F)F MCTCNRSXMFNTDK-UHFFFAOYSA-N 0.000 description 1
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• 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
• MKHGVMIXRPGHOO-UHFFFAOYSA-N 2-(benzenesulfonyl)-3-phenyloxaziridine Chemical compound C=1C=CC=CC=1S(=O)(=O)N1OC1C1=CC=CC=C1 MKHGVMIXRPGHOO-UHFFFAOYSA-N 0.000 description 1
• 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
• MWFMGBPGAXYFAR-UHFFFAOYSA-N 2-hydroxy-2-methylpropanenitrile Chemical compound CC(C)(O)C#N MWFMGBPGAXYFAR-UHFFFAOYSA-N 0.000 description 1
• 125000005916 2-methylpentyl group Chemical group 0.000 description 1
• 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
• 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
• 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• CRMACCRNCSJWTO-UHFFFAOYSA-N 2h-pyridine-1,2-diamine Chemical compound NC1C=CC=CN1N CRMACCRNCSJWTO-UHFFFAOYSA-N 0.000 description 1
• QOJPAVNWONGHAR-UHFFFAOYSA-N 3,4-dibromo-2-nitropyridine Chemical class [O-][N+](=O)C1=NC=CC(Br)=C1Br QOJPAVNWONGHAR-UHFFFAOYSA-N 0.000 description 1
• 125000005917 3-methylpentyl group Chemical group 0.000 description 1
• 125000005986 4-piperidonyl group Chemical group 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
• 208000026872 Addison Disease Diseases 0.000 description 1
• 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• 208000036487 Arthropathies Diseases 0.000 description 1
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
• 108010011485 Aspartame Proteins 0.000 description 1
• 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
• 238000006822 Barton-McCombie deoxygenation reaction Methods 0.000 description 1
• 238000006237 Beckmann rearrangement reaction Methods 0.000 description 1
• 208000009137 Behcet syndrome Diseases 0.000 description 1
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
• 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
• 238000006443 Buchwald-Hartwig cross coupling reaction Methods 0.000 description 1
• 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
• 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 description 1
• 206010006895 Cachexia Diseases 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
• 208000006029 Cardiomegaly Diseases 0.000 description 1
• 206010062746 Carditis Diseases 0.000 description 1
• 206010008685 Chondritis Diseases 0.000 description 1
• 208000017667 Chronic Disease Diseases 0.000 description 1
• 206010010904 Convulsion Diseases 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 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
• 206010012438 Dermatitis atopic Diseases 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
• 206010012688 Diabetic retinal oedema Diseases 0.000 description 1
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 1
• 206010013911 Dysgeusia Diseases 0.000 description 1
• 208000032928 Dyslipidaemia Diseases 0.000 description 1
• 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 206010018374 Glomerulonephritis minimal lesion Diseases 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
• 238000003747 Grignard reaction Methods 0.000 description 1
• 239000007818 Grignard reagent Substances 0.000 description 1
• 206010019196 Head injury Diseases 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 206010019668 Hepatic fibrosis Diseases 0.000 description 1
• 101000965660 Homo sapiens U6 snRNA-associated Sm-like protein LSm8 Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• 208000023105 Huntington disease Diseases 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 206010020772 Hypertension Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• 208000012659 Joint disease Diseases 0.000 description 1
• 208000017170 Lipid metabolism disease Diseases 0.000 description 1
• 208000004883 Lipoid Nephrosis Diseases 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• 208000001344 Macular Edema Diseases 0.000 description 1
• 206010025415 Macular oedema Diseases 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 208000001145 Metabolic Syndrome Diseases 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 208000009525 Myocarditis Diseases 0.000 description 1
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 208000022873 Ocular disease Diseases 0.000 description 1
• 108091034117 Oligonucleotide Proteins 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 241000721454 Pemphigus Species 0.000 description 1
• 208000031845 Pernicious anaemia Diseases 0.000 description 1
• 206010035664 Pneumonia Diseases 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 239000004372 Polyvinyl alcohol Substances 0.000 description 1
• 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
• 102000007327 Protamines Human genes 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• 239000007868 Raney catalyst Substances 0.000 description 1
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
• 229910000564 Raney nickel Inorganic materials 0.000 description 1
• 208000006265 Renal cell carcinoma Diseases 0.000 description 1
• 108700008625 Reporter Genes Proteins 0.000 description 1
• 206010038687 Respiratory distress Diseases 0.000 description 1
• 206010038934 Retinopathy proliferative Diseases 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 238000006923 Schmidt rearrangement reaction Methods 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 206010040047 Sepsis Diseases 0.000 description 1
• 208000021386 Sjogren Syndrome Diseases 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 208000005718 Stomach Neoplasms Diseases 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 201000009594 Systemic Scleroderma Diseases 0.000 description 1
• 206010042953 Systemic sclerosis Diseases 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
• 206010052779 Transplant rejections Diseases 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 102100040948 U6 snRNA-associated Sm-like protein LSm8 Human genes 0.000 description 1
• 206010047115 Vasculitis Diseases 0.000 description 1
• 108010046377 Whey Proteins Proteins 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 206010064930 age-related macular degeneration Diseases 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 125000002947 alkylene group Chemical group 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 208000030961 allergic reaction Diseases 0.000 description 1
• HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
• 229940043377 alpha-cyclodextrin Drugs 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
• 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
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 150000001499 aryl bromides Chemical class 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 239000000605 aspartame Substances 0.000 description 1
• IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
• 235000010357 aspartame Nutrition 0.000 description 1
• 229960003438 aspartame Drugs 0.000 description 1
• 201000008937 atopic dermatitis Diseases 0.000 description 1
• 125000002785 azepinyl group Chemical group 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
• 229960004853 betadex Drugs 0.000 description 1
• 125000002527 bicyclic carbocyclic group Chemical group 0.000 description 1
• IISBACLAFKSPIT-UHFFFAOYSA-N bisphenol A Chemical compound C=1C=C(O)C=CC=1C(C)(C)C1=CC=C(O)C=C1 IISBACLAFKSPIT-UHFFFAOYSA-N 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
• 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
• CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
• 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 125000002843 carboxylic acid group Chemical group 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 210000000845 cartilage Anatomy 0.000 description 1
• 238000006555 catalytic reaction Methods 0.000 description 1
• 229920006217 cellulose acetate butyrate Polymers 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 208000024207 chronic leukemia Diseases 0.000 description 1
• 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
• 229960004316 cisplatin Drugs 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 230000036461 convulsion Effects 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 210000004087 cornea Anatomy 0.000 description 1
• 229940099112 cornstarch Drugs 0.000 description 1
• 238000012937 correction Methods 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 239000007822 coupling agent Substances 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 229960001681 croscarmellose sodium Drugs 0.000 description 1
• 229960000913 crospovidone Drugs 0.000 description 1
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 229940097362 cyclodextrins Drugs 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000005508 decahydronaphthalenyl group Chemical group 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 238000006392 deoxygenation reaction Methods 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 208000033679 diabetic kidney disease Diseases 0.000 description 1
• 201000011190 diabetic macular edema Diseases 0.000 description 1
• 238000010586 diagram Methods 0.000 description 1
• 125000004611 dihydroisoindolyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 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
• 239000006185 dispersion Substances 0.000 description 1
• LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 239000008387 emulsifying waxe Substances 0.000 description 1
• 238000003821 enantio-separation Methods 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 206010015037 epilepsy Diseases 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• ZCSFFBZXCQGHRG-UHFFFAOYSA-N ethyl 2-cyano-3-(9-ethylcarbazol-3-yl)iminopropanoate Chemical compound CCN1C2=C(C=C(C=C2)N=CC(C#N)C(=O)OCC)C3=CC=CC=C31 ZCSFFBZXCQGHRG-UHFFFAOYSA-N 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• FPVGTPBMTFTMRT-NSKUCRDLSA-L fast yellow Chemical class [Na+].[Na+].C1=C(S([O-])(=O)=O)C(N)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 FPVGTPBMTFTMRT-NSKUCRDLSA-L 0.000 description 1
• 230000003176 fibrotic effect Effects 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 239000011888 foil Substances 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 238000007306 functionalization reaction Methods 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 1
• 229940080345 gamma-cyclodextrin Drugs 0.000 description 1
• 206010017758 gastric cancer Diseases 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• UHUSDOQQWJGJQS-UHFFFAOYSA-N glycerol 1,2-dioctadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCCCC UHUSDOQQWJGJQS-UHFFFAOYSA-N 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 229960002449 glycine Drugs 0.000 description 1
• 150000004795 grignard reagents Chemical class 0.000 description 1
• 229920000591 gum Polymers 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 208000007475 hemolytic anemia Diseases 0.000 description 1
• 230000002949 hemolytic effect Effects 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• CBCIHIVRDWLAME-UHFFFAOYSA-N hexanitrodiphenylamine Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1NC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O CBCIHIVRDWLAME-UHFFFAOYSA-N 0.000 description 1
• JUINSXZKUKVTMD-UHFFFAOYSA-N hydrogen azide Chemical compound N=[N+]=[N-] JUINSXZKUKVTMD-UHFFFAOYSA-N 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 208000033065 inborn errors of immunity Diseases 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 229910052738 indium Inorganic materials 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 208000000509 infertility Diseases 0.000 description 1
• 230000036512 infertility Effects 0.000 description 1
• 231100000535 infertility Toxicity 0.000 description 1
• 208000021646 inflammation of heart layer Diseases 0.000 description 1
• 206010022000 influenza Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 230000001788 irregular Effects 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 208000028867 ischemia Diseases 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
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000003971 isoxazolinyl group Chemical group 0.000 description 1
• 230000000366 juvenile effect Effects 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
• 150000004715 keto acids Chemical class 0.000 description 1
• TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
• 208000002780 macular degeneration Diseases 0.000 description 1
• 201000010230 macular retinal edema Diseases 0.000 description 1
• 239000000395 magnesium oxide Substances 0.000 description 1
• CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
• 235000012245 magnesium oxide Nutrition 0.000 description 1
• 239000000391 magnesium silicate Substances 0.000 description 1
• 229940099273 magnesium trisilicate Drugs 0.000 description 1
• 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
• 235000019793 magnesium trisilicate Nutrition 0.000 description 1
• AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 230000000873 masking effect Effects 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 206010027191 meningioma Diseases 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 239000000693 micelle Substances 0.000 description 1
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
• 201000006938 muscular dystrophy Diseases 0.000 description 1
• 206010028417 myasthenia gravis Diseases 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• 229940043348 myristyl alcohol Drugs 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 229910052754 neon Inorganic materials 0.000 description 1
• GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
• GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
• 239000007764 o/w emulsion Substances 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 150000002923 oximes Chemical class 0.000 description 1
• 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 238000005949 ozonolysis reaction Methods 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 230000000144 pharmacologic effect Effects 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
• 235000021317 phosphate Nutrition 0.000 description 1
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 239000008389 polyethoxylated castor oil Substances 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229940113116 polyethylene glycol 1000 Drugs 0.000 description 1
• 208000005987 polymyositis Diseases 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
• 229920000523 polyvinylpolypyrrolidone Polymers 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
• 230000002028 premature Effects 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 208000028529 primary immunodeficiency disease Diseases 0.000 description 1
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000013772 propylene glycol Nutrition 0.000 description 1
• 229950008679 protamine sulfate Drugs 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 239000012264 purified product Substances 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000002755 pyrazolinyl group Chemical group 0.000 description 1
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 239000002287 radioligand Substances 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 238000006476 reductive cyclization reaction Methods 0.000 description 1
• 206010039083 rhinitis Diseases 0.000 description 1
• YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 201000000306 sarcoidosis Diseases 0.000 description 1
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 208000013223 septicemia Diseases 0.000 description 1
• 238000010898 silica gel chromatography Methods 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000015424 sodium Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 238000007614 solvation 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
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 208000020431 spinal cord injury Diseases 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 235000011150 stannous chloride Nutrition 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 201000011549 stomach cancer Diseases 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 229960004793 sucrose Drugs 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000006092 tetrahydro-1,1-dioxothienyl group Chemical group 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• 150000003536 tetrazoles Chemical class 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000006090 thiamorpholinyl sulfone group Chemical group 0.000 description 1
• 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 230000003582 thrombocytopenic effect Effects 0.000 description 1
• 206010043778 thyroiditis Diseases 0.000 description 1
• AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
• 208000025086 undetermined colitis Diseases 0.000 description 1
• 229910052720 vanadium Inorganic materials 0.000 description 1
• 208000019553 vascular disease Diseases 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 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
• 150000003751 zinc Chemical class 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 235000004835 α-tocopherol Nutrition 0.000 description 1