EA025393B1 - Пиразолилмочевины в качестве ингибиторов киназы - Google Patents

Info

Publication number

EA025393B1

EA025393B1 EA201590391A EA201590391A EA025393B1 EA 025393 B1 EA025393 B1 EA 025393B1 EA 201590391 A EA201590391 A EA 201590391A EA 201590391 A EA201590391 A EA 201590391A EA 025393 B1 EA025393 B1 EA 025393B1

Authority

EA

Eurasian Patent Office

Prior art keywords

amino

pyrazol

ureido

oxy

benzamide

Prior art date

2012-08-17

Links

• Espacenet
• Global Dossier
• Discuss

• 229940043355 kinase inhibitor Drugs 0.000 title description 4
• 239000003757 phosphotransferase inhibitor Substances 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 429
• 238000011282 treatment Methods 0.000 claims abstract description 55
• 210000001508 eye Anatomy 0.000 claims abstract description 11
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 11
• -1 C1-6 -galogenalkoksi Chemical group 0.000 claims description 370
• 238000000034 method Methods 0.000 claims description 207
• 239000000203 mixture Substances 0.000 claims description 184
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 111
• 125000000217 alkyl group Chemical group 0.000 claims description 84
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 68
• 125000000623 heterocyclic group Chemical group 0.000 claims description 65
• VFQYQYRTIQWWPE-UHFFFAOYSA-N n-(2-morpholin-4-ylethyl)benzamide Chemical compound C=1C=CC=CC=1C(=O)NCCN1CCOCC1 VFQYQYRTIQWWPE-UHFFFAOYSA-N 0.000 claims description 64
• 150000003839 salts Chemical class 0.000 claims description 60
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 57
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 56
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 49
• 125000002947 alkylene group Chemical group 0.000 claims description 47
• 238000006243 chemical reaction Methods 0.000 claims description 36
• 229910052736 halogen Inorganic materials 0.000 claims description 35
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 33
• 150000002367 halogens Chemical class 0.000 claims description 32
• 229910052739 hydrogen Inorganic materials 0.000 claims description 32
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 31
• 150000001412 amines Chemical class 0.000 claims description 31
• 125000001424 substituent group Chemical group 0.000 claims description 31
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
• 201000010099 disease Diseases 0.000 claims description 29
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 27
• 125000003545 alkoxy group Chemical group 0.000 claims description 26
• 208000006673 asthma Diseases 0.000 claims description 26
• 239000003814 drug Substances 0.000 claims description 26
• 206010046851 Uveitis Diseases 0.000 claims description 25
• 229910052700 potassium Inorganic materials 0.000 claims description 25
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 23
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 20
• 229910052799 carbon Inorganic materials 0.000 claims description 20
• 230000004054 inflammatory process Effects 0.000 claims description 20
• 206010061218 Inflammation Diseases 0.000 claims description 19
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 18
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
• 229910052757 nitrogen Inorganic materials 0.000 claims description 18
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
• 125000004432 carbon atom Chemical group C* 0.000 claims description 16
• 125000005842 heteroatom Chemical group 0.000 claims description 16
• 206010010741 Conjunctivitis Diseases 0.000 claims description 15
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 14
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 14
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
• 208000011231 Crohn disease Diseases 0.000 claims description 13
• 239000008194 pharmaceutical composition Substances 0.000 claims description 13
• 208000001344 Macular Edema Diseases 0.000 claims description 12
• 206010025415 Macular oedema Diseases 0.000 claims description 12
• 230000005713 exacerbation Effects 0.000 claims description 12
• 201000010230 macular retinal edema Diseases 0.000 claims description 12
• 208000002691 Choroiditis Diseases 0.000 claims description 11
• 206010022941 Iridocyclitis Diseases 0.000 claims description 11
• 208000003971 Posterior uveitis Diseases 0.000 claims description 11
• 201000004612 anterior uveitis Diseases 0.000 claims description 11
• 239000003085 diluting agent Substances 0.000 claims description 11
• 201000007407 panuveitis Diseases 0.000 claims description 11
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 10
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 10
• 206010006458 Bronchitis chronic Diseases 0.000 claims description 10
• 206010014561 Emphysema Diseases 0.000 claims description 10
• 206010006451 bronchitis Diseases 0.000 claims description 10
• 208000007451 chronic bronchitis Diseases 0.000 claims description 10
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 9
• 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 9
• 206010012689 Diabetic retinopathy Diseases 0.000 claims description 9
• 206010036346 Posterior capsule opacification Diseases 0.000 claims description 9
• 206010039085 Rhinitis allergic Diseases 0.000 claims description 9
• 208000036142 Viral infection Diseases 0.000 claims description 9
• 208000002205 allergic conjunctivitis Diseases 0.000 claims description 9
• 201000010105 allergic rhinitis Diseases 0.000 claims description 9
• 208000024998 atopic conjunctivitis Diseases 0.000 claims description 9
• 208000002780 macular degeneration Diseases 0.000 claims description 9
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
• 238000001356 surgical procedure Methods 0.000 claims description 9
• 230000009385 viral infection Effects 0.000 claims description 9
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
• 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 8
• 206010013774 Dry eye Diseases 0.000 claims description 8
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 8
• 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 8
• 230000000968 intestinal effect Effects 0.000 claims description 8
• 206010023332 keratitis Diseases 0.000 claims description 8
• 201000010666 keratoconjunctivitis Diseases 0.000 claims description 8
• ZZKSAVUXOUDMGW-UHFFFAOYSA-N n-(2-methoxyethyl)benzamide Chemical compound COCCNC(=O)C1=CC=CC=C1 ZZKSAVUXOUDMGW-UHFFFAOYSA-N 0.000 claims description 8
• 206010039083 rhinitis Diseases 0.000 claims description 8
• 201000000306 sarcoidosis Diseases 0.000 claims description 8
• 201000009890 sinusitis Diseases 0.000 claims description 8
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 7
• 208000015943 Coeliac disease Diseases 0.000 claims description 7
• 201000003883 Cystic fibrosis Diseases 0.000 claims description 7
• 206010012688 Diabetic retinal oedema Diseases 0.000 claims description 7
• 208000010412 Glaucoma Diseases 0.000 claims description 7
• 108010068370 Glutens Proteins 0.000 claims description 7
• 206010028980 Neoplasm Diseases 0.000 claims description 7
• 206010064930 age-related macular degeneration Diseases 0.000 claims description 7
• 230000001419 dependent effect Effects 0.000 claims description 7
• 201000011190 diabetic macular edema Diseases 0.000 claims description 7
• 208000037902 enteropathy Diseases 0.000 claims description 7
• 235000021312 gluten Nutrition 0.000 claims description 7
• 239000001257 hydrogen Substances 0.000 claims description 7
• 208000028774 intestinal disease Diseases 0.000 claims description 7
• WITGHKHDFHQKOR-UHFFFAOYSA-N n-(1-morpholin-4-ylpropan-2-yl)benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C)CN1CCOCC1 WITGHKHDFHQKOR-UHFFFAOYSA-N 0.000 claims description 7
• 201000008482 osteoarthritis Diseases 0.000 claims description 7
• 210000000496 pancreas Anatomy 0.000 claims description 7
• 125000004076 pyridyl group Chemical group 0.000 claims description 7
• 230000003612 virological effect Effects 0.000 claims description 7
• 206010064212 Eosinophilic oesophagitis Diseases 0.000 claims description 6
• 201000011510 cancer Diseases 0.000 claims description 6
• 201000000708 eosinophilic esophagitis Diseases 0.000 claims description 6
• 210000000056 organ Anatomy 0.000 claims description 6
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
• 210000001957 retinal vein Anatomy 0.000 claims description 6
• 125000001544 thienyl group Chemical group 0.000 claims description 6
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
• FRASJONUBLZVQX-UHFFFAOYSA-N 1,4-naphthoquinone Chemical compound C1=CC=C2C(=O)C=CC(=O)C2=C1 FRASJONUBLZVQX-UHFFFAOYSA-N 0.000 claims description 5
• 239000000969 carrier Substances 0.000 claims description 5
• 230000001684 chronic effect Effects 0.000 claims description 5
• 125000001188 haloalkyl group Chemical group 0.000 claims description 5
• 125000003277 amino group Chemical group 0.000 claims description 4
• 206010012601 diabetes mellitus Diseases 0.000 claims description 4
• VEPGWQJFPACQNX-UHFFFAOYSA-N n-(2-methyl-1-morpholin-4-ylpropan-2-yl)benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(C)(C)CN1CCOCC1 VEPGWQJFPACQNX-UHFFFAOYSA-N 0.000 claims description 4
• 150000003512 tertiary amines Chemical class 0.000 claims description 4
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
• YWBUMBUFDDSLCR-UHFFFAOYSA-N 1-[4-[2-[3-methoxy-5-(4-methylpiperazine-1-carbonyl)anilino]pyrimidin-4-yl]oxynaphthalen-1-yl]-3-[2-(4-methylphenyl)-5-propan-2-ylpyrazol-3-yl]urea Chemical compound C=1C(C(=O)N2CCN(C)CC2)=CC(OC)=CC=1NC(N=1)=NC=CC=1OC(C1=CC=CC=C11)=CC=C1NC(=O)NC1=CC(C(C)C)=NN1C1=CC=C(C)C=C1 YWBUMBUFDDSLCR-UHFFFAOYSA-N 0.000 claims description 3
• FGBHWWCXGQAKAZ-UHFFFAOYSA-N 1-[4-[2-[3-methoxy-5-(morpholine-4-carbonyl)anilino]pyrimidin-4-yl]oxynaphthalen-1-yl]-3-[2-(4-methylphenyl)-5-propan-2-ylpyrazol-3-yl]urea Chemical compound C=1C(C(=O)N2CCOCC2)=CC(OC)=CC=1NC(N=1)=NC=CC=1OC(C1=CC=CC=C11)=CC=C1NC(=O)NC1=CC(C(C)C)=NN1C1=CC=C(C)C=C1 FGBHWWCXGQAKAZ-UHFFFAOYSA-N 0.000 claims description 3
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
• 206010007558 Cardiac failure chronic Diseases 0.000 claims description 3
• 238000002650 immunosuppressive therapy Methods 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 150000002829 nitrogen Chemical class 0.000 claims description 3
• 238000002054 transplantation Methods 0.000 claims description 3
• BANXPZGDYGVXOC-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[4-[2-[3-(morpholine-4-carbonyl)anilino]pyrimidin-4-yl]oxynaphthalen-1-yl]urea Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=CC=4)C(=O)N4CCOCC4)N=CC=3)=CC=2)=CC(C(C)(C)C)=N1 BANXPZGDYGVXOC-UHFFFAOYSA-N 0.000 claims description 2
• IZRDLZYOQSBCNG-UHFFFAOYSA-N 2-propylbenzamide Chemical compound CCCC1=CC=CC=C1C(N)=O IZRDLZYOQSBCNG-UHFFFAOYSA-N 0.000 claims description 2
• XCGWAOXDKPENDE-UHFFFAOYSA-N 3-[[4-[2,3-dichloro-4-[[2-(4-methylphenyl)-5-propan-2-ylpyrazol-3-yl]carbamoylamino]phenoxy]pyrimidin-2-yl]amino]-5-ethynylbenzamide Chemical compound C=1C=C(C)C=CC=1N1N=C(C(C)C)C=C1NC(=O)NC(C(=C1Cl)Cl)=CC=C1OC(N=1)=CC=NC=1NC1=CC(C#C)=CC(C(N)=O)=C1 XCGWAOXDKPENDE-UHFFFAOYSA-N 0.000 claims description 2
• HHONORFVXLXKEB-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-methoxybenzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=C(OC)C=4)C(N)=O)N=CC=3)=CC=2)=CC(C(C)(C)C)=N1 HHONORFVXLXKEB-UHFFFAOYSA-N 0.000 claims description 2
• 206010016654 Fibrosis Diseases 0.000 claims description 2
• 230000004761 fibrosis Effects 0.000 claims description 2
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
• URRPWKVYUYOQBW-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-methylbenzamide Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=C(C)C=4)C(N)=O)N=CC=3)=CC=2)=CC(C(C)(C)C)=N1 URRPWKVYUYOQBW-UHFFFAOYSA-N 0.000 claims 1
• XZCLCFIAUCVNJF-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)NC=4N(N=C(C=4)C(C)(C)C)C=4C=CC(C)=CC=4)=CC=3)C=CN=2)=C1 XZCLCFIAUCVNJF-UHFFFAOYSA-N 0.000 claims 1
• 208000000208 Wet Macular Degeneration Diseases 0.000 claims 1
• 230000007850 degeneration Effects 0.000 claims 1
• 208000011325 dry age related macular degeneration Diseases 0.000 claims 1
• 230000002327 eosinophilic effect Effects 0.000 claims 1
• 125000001072 heteroaryl group Chemical group 0.000 claims 1
• YGZNOUTVUALXEX-UHFFFAOYSA-N n-(2-hydroxyethyl)-3-methoxy-4-[[4-[4-[[2-(4-methylphenyl)-5-propan-2-ylpyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzamide Chemical compound COC1=CC(C(=O)NCCO)=CC=C1NC1=NC=CC(OC=2C3=CC=CC=C3C(NC(=O)NC=3N(N=C(C=3)C(C)C)C=3C=CC(C)=CC=3)=CC=2)=N1 YGZNOUTVUALXEX-UHFFFAOYSA-N 0.000 claims 1
• ZGVCPFSIDNPESN-UHFFFAOYSA-N n-(2-hydroxyethyl)-4-methoxy-3-[[4-[4-[[2-(4-methoxyphenyl)-5-propan-2-ylpyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C(=CC=C(C=4)C(=O)NCCO)OC)N=CC=3)=CC=2)=CC(C(C)C)=N1 ZGVCPFSIDNPESN-UHFFFAOYSA-N 0.000 claims 1
• DYFJXOPTRKATQT-UHFFFAOYSA-N n-(2-hydroxyethyl)-4-methoxy-3-[[4-[4-[[2-(4-methylphenyl)-5-propan-2-ylpyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzamide Chemical compound COC1=CC=C(C(=O)NCCO)C=C1NC1=NC=CC(OC=2C3=CC=CC=C3C(NC(=O)NC=3N(N=C(C=3)C(C)C)C=3C=CC(C)=CC=3)=CC=2)=N1 DYFJXOPTRKATQT-UHFFFAOYSA-N 0.000 claims 1
• PAXVLFZEDPNTNS-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-3-methoxy-4-[[4-[4-[[2-(4-methylphenyl)-5-propan-2-ylpyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzamide Chemical compound COC1=CC(C(=O)NCCN(C)C)=CC=C1NC1=NC=CC(OC=2C3=CC=CC=C3C(NC(=O)NC=3N(N=C(C=3)C(C)C)C=3C=CC(C)=CC=3)=CC=2)=N1 PAXVLFZEDPNTNS-UHFFFAOYSA-N 0.000 claims 1
• HSXOEINUWICALJ-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-methoxy-3-[[4-[4-[[2-(4-methylphenyl)-5-propan-2-ylpyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzamide Chemical compound COC1=CC=C(C(=O)NCCN(C)C)C=C1NC1=NC=CC(OC=2C3=CC=CC=C3C(NC(=O)NC=3N(N=C(C=3)C(C)C)C=3C=CC(C)=CC=3)=CC=2)=N1 HSXOEINUWICALJ-UHFFFAOYSA-N 0.000 claims 1
• 208000004644 retinal vein occlusion Diseases 0.000 claims 1
• 210000003462 vein Anatomy 0.000 claims 1
• 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 abstract description 48
• 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 abstract description 48
• 230000005764 inhibitory process Effects 0.000 abstract description 16
• 210000004072 lung Anatomy 0.000 abstract description 12
• 238000002560 therapeutic procedure Methods 0.000 abstract description 6
• 230000003110 anti-inflammatory effect Effects 0.000 abstract description 5
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 abstract description 4
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 abstract description 4
• 210000000936 intestine Anatomy 0.000 abstract description 4
• 102000000551 Syk Kinase Human genes 0.000 abstract 1
• 108010016672 Syk Kinase Proteins 0.000 abstract 1
• 239000000543 intermediate Substances 0.000 description 387
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 351
• 239000007787 solid Substances 0.000 description 201
• 239000000243 solution Substances 0.000 description 197
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 160
• 238000005481 NMR spectroscopy Methods 0.000 description 128
• 239000011541 reaction mixture Substances 0.000 description 123
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 115
• 230000002378 acidificating effect Effects 0.000 description 83
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 60
• 235000002639 sodium chloride Nutrition 0.000 description 57
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 56
• 238000001914 filtration Methods 0.000 description 55
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 54
• 239000000725 suspension Substances 0.000 description 51
• 229920006395 saturated elastomer Polymers 0.000 description 50
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 49
• 239000012267 brine Substances 0.000 description 48
• 238000010828 elution Methods 0.000 description 45
• 239000012074 organic phase Substances 0.000 description 41
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
• 238000003818 flash chromatography Methods 0.000 description 38
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 36
• 239000012043 crude product Substances 0.000 description 35
• 239000000126 substance Substances 0.000 description 35
• 239000007864 aqueous solution Substances 0.000 description 32
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 28
• 239000002244 precipitate Substances 0.000 description 27
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 26
• 239000002253 acid Substances 0.000 description 24
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 24
• 230000002829 reductive effect Effects 0.000 description 24
• 239000003112 inhibitor Substances 0.000 description 23
• 239000000047 product Substances 0.000 description 23
• 230000015572 biosynthetic process Effects 0.000 description 22
• JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 22
• 229940011051 isopropyl acetate Drugs 0.000 description 22
• GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 22
• 108091000080 Phosphotransferase Proteins 0.000 description 21
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• 102000020233 phosphotransferase Human genes 0.000 description 21
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
• 230000000694 effects Effects 0.000 description 20
• 239000012044 organic layer Substances 0.000 description 20
• 239000013256 coordination polymer Substances 0.000 description 19
• 230000000875 corresponding effect Effects 0.000 description 19
• 239000000284 extract Substances 0.000 description 19
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
• 239000003729 cation exchange resin Substances 0.000 description 17
• 210000004027 cell Anatomy 0.000 description 17
• 239000002552 dosage form Substances 0.000 description 17
• 229940079593 drug Drugs 0.000 description 17
• 239000011777 magnesium Substances 0.000 description 17
• NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 16
• 235000019502 Orange oil Nutrition 0.000 description 16
• 125000005843 halogen group Chemical group 0.000 description 16
• 239000010502 orange oil Substances 0.000 description 16
• 238000002953 preparative HPLC Methods 0.000 description 16
• 239000002904 solvent Substances 0.000 description 16
• 239000008346 aqueous phase Substances 0.000 description 15
• 238000004587 chromatography analysis Methods 0.000 description 15
• 239000000463 material Substances 0.000 description 15
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
• 238000010898 silica gel chromatography Methods 0.000 description 15
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
• 150000004682 monohydrates Chemical class 0.000 description 13
• 230000009471 action Effects 0.000 description 12
• 239000003246 corticosteroid Substances 0.000 description 12
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
• RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 12
• 239000003921 oil Substances 0.000 description 12
• 235000019198 oils Nutrition 0.000 description 12
• 239000000546 pharmaceutical excipient Substances 0.000 description 12
• 241000709661 Enterovirus Species 0.000 description 11
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 11
• 108010029485 Protein Isoforms Proteins 0.000 description 11
• 102000001708 Protein Isoforms Human genes 0.000 description 11
• 239000002585 base Substances 0.000 description 11
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 11
• 125000006239 protecting group Chemical group 0.000 description 11
• 238000003786 synthesis reaction Methods 0.000 description 11
• 238000005406 washing Methods 0.000 description 11
• 102000004190 Enzymes Human genes 0.000 description 10
• 108090000790 Enzymes Proteins 0.000 description 10
• 239000003795 chemical substances by application Substances 0.000 description 10
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 10
• 238000005859 coupling reaction Methods 0.000 description 10
• 229940088598 enzyme Drugs 0.000 description 10
• AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 10
• 238000003756 stirring Methods 0.000 description 10
• 238000012360 testing method Methods 0.000 description 10
• 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 9
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
• 229960001334 corticosteroids Drugs 0.000 description 9
• 150000002148 esters Chemical class 0.000 description 9
• 239000000706 filtrate Substances 0.000 description 9
• 238000004128 high performance liquid chromatography Methods 0.000 description 9
• 239000010410 layer Substances 0.000 description 9
• 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 9
• 229910052760 oxygen Inorganic materials 0.000 description 9
• 238000000746 purification Methods 0.000 description 9
• 239000004094 surface-active agent Substances 0.000 description 9
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 8
• 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 8
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
• 238000001994 activation Methods 0.000 description 8
• 235000019253 formic acid Nutrition 0.000 description 8
• 230000002401 inhibitory effect Effects 0.000 description 8
• 229920000642 polymer Polymers 0.000 description 8
• 239000003755 preservative agent Substances 0.000 description 8
• 230000001225 therapeutic effect Effects 0.000 description 8
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
• 150000007513 acids Chemical class 0.000 description 7
• 230000004913 activation Effects 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 150000001408 amides Chemical class 0.000 description 7
• 230000027455 binding Effects 0.000 description 7
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 7
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 7
• 239000003880 polar aprotic solvent Substances 0.000 description 7
• 210000002345 respiratory system Anatomy 0.000 description 7
• 239000000377 silicon dioxide Substances 0.000 description 7
• 235000017557 sodium bicarbonate Nutrition 0.000 description 7
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
• 210000001519 tissue Anatomy 0.000 description 7
• 238000011200 topical administration Methods 0.000 description 7
• 230000009466 transformation Effects 0.000 description 7
• 238000000844 transformation Methods 0.000 description 7
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
• ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 6
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 6
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 6
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-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
• 206010061494 Rhinovirus infection Diseases 0.000 description 6
• 210000001744 T-lymphocyte Anatomy 0.000 description 6
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 6
• 238000013459 approach Methods 0.000 description 6
• 125000004429 atom Chemical group 0.000 description 6
• 238000010511 deprotection reaction Methods 0.000 description 6
• 208000030533 eye disease Diseases 0.000 description 6
• 125000001153 fluoro group Chemical group F* 0.000 description 6
• 210000001035 gastrointestinal tract Anatomy 0.000 description 6
• 238000010438 heat treatment Methods 0.000 description 6
• ARRNBPCNZJXHRJ-UHFFFAOYSA-M hydron;tetrabutylazanium;phosphate Chemical compound OP(O)([O-])=O.CCCC[N+](CCCC)(CCCC)CCCC ARRNBPCNZJXHRJ-UHFFFAOYSA-M 0.000 description 6
• 208000015181 infectious disease Diseases 0.000 description 6
• 230000002757 inflammatory effect Effects 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 239000002207 metabolite Substances 0.000 description 6
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 6
• 230000026731 phosphorylation Effects 0.000 description 6
• 238000006366 phosphorylation reaction Methods 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• 230000008569 process Effects 0.000 description 6
• 238000006722 reduction reaction Methods 0.000 description 6
• 239000011347 resin Substances 0.000 description 6
• 229920005989 resin Polymers 0.000 description 6
• 239000012258 stirred mixture Substances 0.000 description 6
• 238000002604 ultrasonography Methods 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
• 102000004127 Cytokines Human genes 0.000 description 5
• 108090000695 Cytokines Proteins 0.000 description 5
• 201000008937 atopic dermatitis Diseases 0.000 description 5
• 230000033228 biological regulation Effects 0.000 description 5
• 229910052794 bromium Inorganic materials 0.000 description 5
• 229910052801 chlorine Inorganic materials 0.000 description 5
• 125000001309 chloro group Chemical group Cl* 0.000 description 5
• 238000010494 dissociation reaction Methods 0.000 description 5
• 230000005593 dissociations Effects 0.000 description 5
• 239000008241 heterogeneous mixture Substances 0.000 description 5
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
• 230000037361 pathway Effects 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• 239000002243 precursor Substances 0.000 description 5
• 108090000765 processed proteins & peptides Proteins 0.000 description 5
• 235000018102 proteins Nutrition 0.000 description 5
• 102000004169 proteins and genes Human genes 0.000 description 5
• 108090000623 proteins and genes Proteins 0.000 description 5
• 108020003175 receptors Proteins 0.000 description 5
• 102000005962 receptors Human genes 0.000 description 5
• 230000009467 reduction Effects 0.000 description 5
• 208000023504 respiratory system disease Diseases 0.000 description 5
• 235000010356 sorbitol Nutrition 0.000 description 5
• 239000000600 sorbitol Substances 0.000 description 5
• 230000000087 stabilizing effect Effects 0.000 description 5
• 238000006467 substitution reaction Methods 0.000 description 5
• 230000000699 topical effect Effects 0.000 description 5
• 238000000825 ultraviolet detection Methods 0.000 description 5
• XAMBIJWZVIZZOG-UHFFFAOYSA-N (4-methylphenyl)hydrazine Chemical compound CC1=CC=C(NN)C=C1 XAMBIJWZVIZZOG-UHFFFAOYSA-N 0.000 description 4
• RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 description 4
• RQSXRGSPGHZKFT-UHFFFAOYSA-N 3-amino-5-bromobenzoic acid Chemical compound NC1=CC(Br)=CC(C(O)=O)=C1 RQSXRGSPGHZKFT-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
• 208000014085 Chronic respiratory disease Diseases 0.000 description 4
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
• 108010010803 Gelatin Proteins 0.000 description 4
• 241000282414 Homo sapiens Species 0.000 description 4
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 102000043136 MAP kinase family Human genes 0.000 description 4
• 108091054455 MAP kinase family Proteins 0.000 description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 102000001253 Protein Kinase Human genes 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• 239000000443 aerosol Substances 0.000 description 4
• 125000003342 alkenyl group Chemical group 0.000 description 4
• 125000005275 alkylenearyl group Chemical group 0.000 description 4
• 125000005218 alkyleneheteroaryl group Chemical group 0.000 description 4
• 239000003443 antiviral agent Substances 0.000 description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
• 150000003936 benzamides Chemical class 0.000 description 4
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
• 239000000460 chlorine Substances 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• 239000010949 copper Substances 0.000 description 4
• 208000035475 disorder Diseases 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• 239000008273 gelatin Substances 0.000 description 4
• 229920000159 gelatin Polymers 0.000 description 4
• 235000019322 gelatine Nutrition 0.000 description 4
• 235000011852 gelatine desserts Nutrition 0.000 description 4
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 4
• 239000008101 lactose Substances 0.000 description 4
• 230000003902 lesion Effects 0.000 description 4
• 125000002757 morpholinyl group Chemical group 0.000 description 4
• 210000004400 mucous membrane Anatomy 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 4
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 4
• 125000004193 piperazinyl group Chemical group 0.000 description 4
• 238000002360 preparation method Methods 0.000 description 4
• 229940002612 prodrug Drugs 0.000 description 4
• 239000000651 prodrug Substances 0.000 description 4
• 239000003380 propellant Substances 0.000 description 4
• 108060006633 protein kinase Proteins 0.000 description 4
• 239000003586 protic polar solvent Substances 0.000 description 4
• 230000001105 regulatory effect Effects 0.000 description 4
• 229960002920 sorbitol Drugs 0.000 description 4
• 239000007858 starting material Substances 0.000 description 4
• 238000001308 synthesis method Methods 0.000 description 4
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 4
• 229940124597 therapeutic agent Drugs 0.000 description 4
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 3
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 description 3
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 3
• DBEMTZANGFGKMX-UHFFFAOYSA-N 3-amino-5-methoxybenzoic acid Chemical compound COC1=CC(N)=CC(C(O)=O)=C1 DBEMTZANGFGKMX-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
• 206010012438 Dermatitis atopic Diseases 0.000 description 3
• 206010061598 Immunodeficiency Diseases 0.000 description 3
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
• 206010024971 Lower respiratory tract infections Diseases 0.000 description 3
• 208000019693 Lung disease Diseases 0.000 description 3
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
• 201000004681 Psoriasis Diseases 0.000 description 3
• 241000725643 Respiratory syncytial virus Species 0.000 description 3
• 229920002125 Sokalan® Polymers 0.000 description 3
• 108091008874 T cell receptors Proteins 0.000 description 3
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 3
• 241000700605 Viruses Species 0.000 description 3
• 150000005415 aminobenzoic acids Chemical class 0.000 description 3
• 150000001448 anilines Chemical class 0.000 description 3
• 239000012298 atmosphere Substances 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• 239000012230 colorless oil Substances 0.000 description 3
• 239000013066 combination product Substances 0.000 description 3
• 229940127555 combination product Drugs 0.000 description 3
• 235000008504 concentrate Nutrition 0.000 description 3
• 239000012141 concentrate Substances 0.000 description 3
• 229910052802 copper Inorganic materials 0.000 description 3
• 238000001514 detection method Methods 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• 238000009826 distribution Methods 0.000 description 3
• 239000006196 drop Substances 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• KZGWPHUWNWRTEP-UHFFFAOYSA-N ethynyl-tri(propan-2-yl)silane Chemical compound CC(C)[Si](C#C)(C(C)C)C(C)C KZGWPHUWNWRTEP-UHFFFAOYSA-N 0.000 description 3
• 150000004675 formic acid derivatives Chemical class 0.000 description 3
• 125000004438 haloalkoxy group Chemical group 0.000 description 3
• 230000001965 increasing effect Effects 0.000 description 3
• 231100001231 less toxic Toxicity 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• 229940095102 methyl benzoate Drugs 0.000 description 3
• 238000002156 mixing Methods 0.000 description 3
• VSZGPKBBMSAYNT-RRFJBIMHSA-N oseltamivir Chemical compound CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 VSZGPKBBMSAYNT-RRFJBIMHSA-N 0.000 description 3
• 125000003566 oxetanyl group Chemical group 0.000 description 3
• 239000001301 oxygen Substances 0.000 description 3
• 229910052698 phosphorus Inorganic materials 0.000 description 3
• 229920001223 polyethylene glycol Polymers 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• 102000004196 processed proteins & peptides Human genes 0.000 description 3
• 238000011321 prophylaxis Methods 0.000 description 3
• 230000010076 replication Effects 0.000 description 3
• 238000012827 research and development Methods 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 230000019491 signal transduction Effects 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• 239000012453 solvate Substances 0.000 description 3
• 238000010561 standard procedure Methods 0.000 description 3
• 239000000829 suppository Substances 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 238000010189 synthetic method Methods 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
• 231100000419 toxicity Toxicity 0.000 description 3
• 230000001988 toxicity Effects 0.000 description 3
• 235000015112 vegetable and seed oil Nutrition 0.000 description 3
• 239000008158 vegetable oil Substances 0.000 description 3
• FQHCPFMTXFJZJS-UHFFFAOYSA-N (4-methoxyphenyl)hydrazine;hydrochloride Chemical compound Cl.COC1=CC=C(NN)C=C1 FQHCPFMTXFJZJS-UHFFFAOYSA-N 0.000 description 2
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
• CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 238000005160 1H NMR spectroscopy Methods 0.000 description 2
• BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 2
• INGRVKIBWHSBCS-UHFFFAOYSA-N 2-(2-hydroxyethyl)-3-methoxybenzamide Chemical compound OCCC1=C(C(=O)N)C=CC=C1OC INGRVKIBWHSBCS-UHFFFAOYSA-N 0.000 description 2
• ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 2
• WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
• RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 2
• XOYSLYZLEDUURQ-UHFFFAOYSA-N 3-(3-methyloxetan-3-yl)-3-oxopropanenitrile Chemical compound N#CCC(=O)C1(C)COC1 XOYSLYZLEDUURQ-UHFFFAOYSA-N 0.000 description 2
• XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 description 2
• VKZGTORDNRVMIN-UHFFFAOYSA-N 4-methyl-3-oxopentanenitrile Chemical compound CC(C)C(=O)CC#N VKZGTORDNRVMIN-UHFFFAOYSA-N 0.000 description 2
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
• 244000215068 Acacia senegal Species 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• 241000193830 Bacillus <bacterium> Species 0.000 description 2
• 241000894006 Bacteria Species 0.000 description 2
• 208000009137 Behcet syndrome Diseases 0.000 description 2
• 239000005711 Benzoic acid Substances 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• 206010066091 Bronchial Hyperreactivity Diseases 0.000 description 2
• VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 2
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 2
• 108010036949 Cyclosporine Proteins 0.000 description 2
• 206010012434 Dermatitis allergic Diseases 0.000 description 2
• 206010012442 Dermatitis contact Diseases 0.000 description 2
• 229920002307 Dextran Polymers 0.000 description 2
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
• 241000400611 Eucalyptus deanei Species 0.000 description 2
• 244000166102 Eucalyptus leucoxylon Species 0.000 description 2
• 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• 208000018522 Gastrointestinal disease Diseases 0.000 description 2
• 102000003676 Glucocorticoid Receptors Human genes 0.000 description 2
• 108090000079 Glucocorticoid Receptors Proteins 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• 108010001483 Glycogen Synthase Proteins 0.000 description 2
• 229920000084 Gum arabic Polymers 0.000 description 2
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 208000029462 Immunodeficiency disease Diseases 0.000 description 2
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
• QNRRHYPPQFELSF-CNYIRLTGSA-N Laninamivir Chemical compound OC[C@@H](O)[C@@H](OC)[C@@H]1OC(C(O)=O)=C[C@H](N=C(N)N)[C@H]1NC(C)=O QNRRHYPPQFELSF-CNYIRLTGSA-N 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• 229920001410 Microfiber Polymers 0.000 description 2
• 238000010934 O-alkylation reaction Methods 0.000 description 2
• 239000012826 P38 inhibitor Substances 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• 108091005804 Peptidases Proteins 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• 229940123924 Protein kinase C inhibitor Drugs 0.000 description 2
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 2
• 239000004012 Tofacitinib Substances 0.000 description 2
• 235000010489 acacia gum Nutrition 0.000 description 2
• 239000000205 acacia gum Substances 0.000 description 2
• PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 2
• 230000003213 activating effect Effects 0.000 description 2
• 229960002964 adalimumab Drugs 0.000 description 2
• 230000002411 adverse Effects 0.000 description 2
• 150000001350 alkyl halides Chemical class 0.000 description 2
• 125000000304 alkynyl group Chemical group 0.000 description 2
• 230000003281 allosteric effect Effects 0.000 description 2
• 238000007112 amidation reaction Methods 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 229940124599 anti-inflammatory drug Drugs 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• 125000004104 aryloxy group Chemical group 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 208000010668 atopic eczema Diseases 0.000 description 2
• LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 2
• 229960002170 azathioprine Drugs 0.000 description 2
• 210000003719 b-lymphocyte Anatomy 0.000 description 2
• 235000010233 benzoic acid Nutrition 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• 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
• 230000005540 biological transmission Effects 0.000 description 2
• 238000001574 biopsy Methods 0.000 description 2
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
• 125000001246 bromo group Chemical group Br* 0.000 description 2
• 229960004436 budesonide Drugs 0.000 description 2
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
• 239000008116 calcium stearate Substances 0.000 description 2
• 235000013539 calcium stearate Nutrition 0.000 description 2
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 2
• 150000001735 carboxylic acids Chemical class 0.000 description 2
• 239000004359 castor oil Substances 0.000 description 2
• 235000019438 castor oil Nutrition 0.000 description 2
• 230000032823 cell division Effects 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 229960003115 certolizumab pegol Drugs 0.000 description 2
• 208000029771 childhood onset asthma Diseases 0.000 description 2
• KYKAJFCTULSVSH-UHFFFAOYSA-N chloro(fluoro)methane Chemical compound F[C]Cl KYKAJFCTULSVSH-UHFFFAOYSA-N 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• 208000037976 chronic inflammation Diseases 0.000 description 2
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 2
• 229960001265 ciclosporin Drugs 0.000 description 2
• 229940110456 cocoa butter Drugs 0.000 description 2
• 235000019868 cocoa butter Nutrition 0.000 description 2
• 230000005494 condensation Effects 0.000 description 2
• 208000010247 contact dermatitis Diseases 0.000 description 2
• OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
• 239000006184 cosolvent Substances 0.000 description 2
• 239000007822 coupling agent Substances 0.000 description 2
• 229930182912 cyclosporin Natural products 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 2
• 235000019404 dichlorodifluoromethane Nutrition 0.000 description 2
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
• 239000003480 eluent Substances 0.000 description 2
• 230000007613 environmental effect Effects 0.000 description 2
• 239000012065 filter cake Substances 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 239000006260 foam Substances 0.000 description 2
• GKDRMWXFWHEQQT-UHFFFAOYSA-N fostamatinib Chemical compound COC1=C(OC)C(OC)=CC(NC=2N=C(NC=3N=C4N(COP(O)(O)=O)C(=O)C(C)(C)OC4=CC=3)C(F)=CN=2)=C1 GKDRMWXFWHEQQT-UHFFFAOYSA-N 0.000 description 2
• 229950005309 fostamatinib Drugs 0.000 description 2
• 239000012634 fragment Substances 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 238000007306 functionalization reaction Methods 0.000 description 2
• 206010017758 gastric cancer Diseases 0.000 description 2
• 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 2
• 229960001743 golimumab Drugs 0.000 description 2
• 230000012010 growth Effects 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• 150000002431 hydrogen Chemical class 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 230000007813 immunodeficiency Effects 0.000 description 2
• 229960003444 immunosuppressant agent Drugs 0.000 description 2
• 239000003018 immunosuppressive agent Substances 0.000 description 2
• 230000001771 impaired effect Effects 0.000 description 2
• 230000001976 improved effect Effects 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• 210000004969 inflammatory cell Anatomy 0.000 description 2
• 229960000598 infliximab Drugs 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 229940125369 inhaled corticosteroids Drugs 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 229950004244 laninamivir Drugs 0.000 description 2
• 239000000787 lecithin Substances 0.000 description 2
• 235000010445 lecithin Nutrition 0.000 description 2
• 229940067606 lecithin Drugs 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 210000002540 macrophage Anatomy 0.000 description 2
• 238000012423 maintenance Methods 0.000 description 2
• 239000000594 mannitol Substances 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• 229960000485 methotrexate Drugs 0.000 description 2
• DJLFOMMCQBAMAA-UHFFFAOYSA-N methyl 4-amino-3-methoxybenzoate Chemical compound COC(=O)C1=CC=C(N)C(OC)=C1 DJLFOMMCQBAMAA-UHFFFAOYSA-N 0.000 description 2
• 150000004702 methyl esters Chemical class 0.000 description 2
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
• 239000003658 microfiber Substances 0.000 description 2
• 230000000394 mitotic effect Effects 0.000 description 2
• 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 2
• AQWZQWQZVKBOHA-UHFFFAOYSA-N n-(1-methoxypropan-2-yl)benzamide Chemical compound COCC(C)NC(=O)C1=CC=CC=C1 AQWZQWQZVKBOHA-UHFFFAOYSA-N 0.000 description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 239000007923 nasal drop Substances 0.000 description 2
• 229940100662 nasal drops Drugs 0.000 description 2
• 210000000440 neutrophil Anatomy 0.000 description 2
• 125000006574 non-aromatic ring group Chemical group 0.000 description 2
• 229960003752 oseltamivir Drugs 0.000 description 2
• 125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 2
• PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 229920000867 polyelectrolyte Polymers 0.000 description 2
• 229920005862 polyol Polymers 0.000 description 2
• 150000003077 polyols Chemical class 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• 230000000770 proinflammatory effect Effects 0.000 description 2
• 235000013772 propylene glycol Nutrition 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
• 239000003881 protein kinase C inhibitor Substances 0.000 description 2
• USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 2
• DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 2
• ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 2
• 230000007115 recruitment Effects 0.000 description 2
• 210000000664 rectum Anatomy 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 230000000717 retained effect Effects 0.000 description 2
• 238000004007 reversed phase HPLC Methods 0.000 description 2
• 238000007363 ring formation reaction Methods 0.000 description 2
• 238000007127 saponification reaction Methods 0.000 description 2
• 230000035945 sensitivity Effects 0.000 description 2
• 230000000405 serological effect Effects 0.000 description 2
• 230000011664 signaling Effects 0.000 description 2
• 235000021309 simple sugar Nutrition 0.000 description 2
• 208000017520 skin disease Diseases 0.000 description 2
• 239000010802 sludge Substances 0.000 description 2
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
• 238000005059 solid analysis Methods 0.000 description 2
• OAVGBZOFDPFGPJ-UHFFFAOYSA-N sotrastaurin Chemical compound C1CN(C)CCN1C1=NC(C=2C(NC(=O)C=2C=2C3=CC=CC=C3NC=2)=O)=C(C=CC=C2)C2=N1 OAVGBZOFDPFGPJ-UHFFFAOYSA-N 0.000 description 2
• 150000005846 sugar alcohols Chemical class 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 229960001967 tacrolimus Drugs 0.000 description 2
• QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 2
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 2
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 2
• LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical compound O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 description 2
• 229940110309 tiotropium Drugs 0.000 description 2
• UJLAWZDWDVHWOW-YPMHNXCESA-N tofacitinib Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=NC=NC2=C1C=CN2 UJLAWZDWDVHWOW-YPMHNXCESA-N 0.000 description 2
• 229960001350 tofacitinib Drugs 0.000 description 2
• 238000012546 transfer Methods 0.000 description 2
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 2
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 2
• 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 2
• MDYZKJNTKZIUSK-UHFFFAOYSA-N tyloxapol Chemical compound O=C.C1CO1.CC(C)(C)CC(C)(C)C1=CC=C(O)C=C1 MDYZKJNTKZIUSK-UHFFFAOYSA-N 0.000 description 2
• 229920001664 tyloxapol Polymers 0.000 description 2
• 229960004224 tyloxapol Drugs 0.000 description 2
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
• 241000712461 unidentified influenza virus Species 0.000 description 2
• ARAIBEBZBOPLMB-UFGQHTETSA-N zanamivir Chemical compound CC(=O)N[C@@H]1[C@@H](N=C(N)N)C=C(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO ARAIBEBZBOPLMB-UFGQHTETSA-N 0.000 description 2
• 229960001028 zanamivir Drugs 0.000 description 2
• XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 1
• YUHZIUAREWNXJT-UHFFFAOYSA-N (2-fluoropyridin-3-yl)boronic acid Chemical class OB(O)C1=CC=CN=C1F YUHZIUAREWNXJT-UHFFFAOYSA-N 0.000 description 1
• KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
• YYMIOVAEQIEPET-UHFFFAOYSA-N (3,4-dimethylanilino)azanium;chloride Chemical compound Cl.CC1=CC=C(NN)C=C1C YYMIOVAEQIEPET-UHFFFAOYSA-N 0.000 description 1
• FDBQTRARWCKEJY-UHFFFAOYSA-N (4-hydroxynaphthalen-1-yl)azanium;chloride Chemical compound [Cl-].C1=CC=C2C([NH3+])=CC=C(O)C2=C1 FDBQTRARWCKEJY-UHFFFAOYSA-N 0.000 description 1
• PVRSIFAEUCUJPK-UHFFFAOYSA-N (4-methoxyphenyl)hydrazine Chemical compound COC1=CC=C(NN)C=C1 PVRSIFAEUCUJPK-UHFFFAOYSA-N 0.000 description 1
• SRQWKLIXHJRVSG-UHFFFAOYSA-N (6-methoxypyridin-3-yl)hydrazine Chemical compound COC1=CC=C(NN)C=N1 SRQWKLIXHJRVSG-UHFFFAOYSA-N 0.000 description 1
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 1
• LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
• KOFLVDBWRHFSAB-UHFFFAOYSA-N 1,2,4,5-tetrahydro-1-(phenylmethyl)-5,9b(1',2')-benzeno-9bh-benz(g)indol-3(3ah)-one Chemical compound C1C(C=2C3=CC=CC=2)C2=CC=CC=C2C23C1C(=O)CN2CC1=CC=CC=C1 KOFLVDBWRHFSAB-UHFFFAOYSA-N 0.000 description 1
• OPCJOXGBLDJWRM-UHFFFAOYSA-N 1,2-diamino-2-methylpropane Chemical compound CC(C)(N)CN OPCJOXGBLDJWRM-UHFFFAOYSA-N 0.000 description 1
• DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
• VEKWVLWWZITZTK-UHFFFAOYSA-N 1,2-dimethylcyclohexane-1,2-diamine Chemical compound CC1(N)CCCCC1(C)N VEKWVLWWZITZTK-UHFFFAOYSA-N 0.000 description 1
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
• SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 description 1
• SIMIJFMLPBQPEH-UHFFFAOYSA-N 1-[2,3-dichloro-4-(2-chloropyrimidin-4-yl)oxyphenyl]-3-[2-(4-methylphenyl)-5-propan-2-ylpyrazol-3-yl]urea Chemical compound C=1C=C(C)C=CC=1N1N=C(C(C)C)C=C1NC(=O)NC(C(=C1Cl)Cl)=CC=C1OC1=CC=NC(Cl)=N1 SIMIJFMLPBQPEH-UHFFFAOYSA-N 0.000 description 1
• QBYNDSJKFSEANN-UHFFFAOYSA-N 1-[4-(2-chloropyrimidin-4-yl)oxy-2,3-difluorophenyl]-3-[2-(4-methylphenyl)-5-propan-2-ylpyrazol-3-yl]urea Chemical compound C=1C=C(C)C=CC=1N1N=C(C(C)C)C=C1NC(=O)NC(C(=C1F)F)=CC=C1OC1=CC=NC(Cl)=N1 QBYNDSJKFSEANN-UHFFFAOYSA-N 0.000 description 1
• WXHZLPWYECEASQ-UHFFFAOYSA-N 1-[4-(2-chloropyrimidin-4-yl)oxynaphthalen-1-yl]-3-[2-(4-methylphenyl)-5-propan-2-ylpyrazol-3-yl]urea Chemical compound C=1C=C(C)C=CC=1N1N=C(C(C)C)C=C1NC(=O)NC(C1=CC=CC=C11)=CC=C1OC1=CC=NC(Cl)=N1 WXHZLPWYECEASQ-UHFFFAOYSA-N 0.000 description 1
• REQNABLJIFPJSM-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-[4-(2-chloropyrimidin-4-yl)oxynaphthalen-1-yl]urea Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(Cl)N=CC=3)=CC=2)=CC(C(C)(C)C)=N1 REQNABLJIFPJSM-UHFFFAOYSA-N 0.000 description 1
• DLFLHNWVIWRKLC-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[4-(2-chloropyrimidin-4-yl)oxynaphthalen-1-yl]urea Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(Cl)N=CC=3)=CC=2)=CC(C(C)(C)C)=N1 DLFLHNWVIWRKLC-UHFFFAOYSA-N 0.000 description 1
• TWTFETDTUZVJND-UHFFFAOYSA-N 1-iodo-3-(2-methoxyethoxy)benzene Chemical compound COCCOC1=CC=CC(I)=C1 TWTFETDTUZVJND-UHFFFAOYSA-N 0.000 description 1
• JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 1
• KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 description 1
• YKGZFLFDDRRNNQ-UHFFFAOYSA-N 2,2-dimethyl-3-oxopentanedinitrile Chemical compound N#CC(C)(C)C(=O)CC#N YKGZFLFDDRRNNQ-UHFFFAOYSA-N 0.000 description 1
• MGLQOPDFRIBFME-UHFFFAOYSA-N 2,3-dichloro-4-(2-chloropyrimidin-4-yl)oxyaniline Chemical compound ClC1=C(Cl)C(N)=CC=C1OC1=CC=NC(Cl)=N1 MGLQOPDFRIBFME-UHFFFAOYSA-N 0.000 description 1
• NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 1
• FIOZTIGMJAQWQH-UHFFFAOYSA-N 2-(2-hydroxyethyl)-4-methoxybenzamide Chemical compound OCCC1=C(C(=O)N)C=CC(=C1)OC FIOZTIGMJAQWQH-UHFFFAOYSA-N 0.000 description 1
• WFHMZVGXSMJRKD-UHFFFAOYSA-N 2-(3,4-dimethylphenyl)-5-propan-2-ylpyrazol-3-amine Chemical compound N1=C(C(C)C)C=C(N)N1C1=CC=C(C)C(C)=C1 WFHMZVGXSMJRKD-UHFFFAOYSA-N 0.000 description 1
• FCAZTZCJGRZOJY-UHFFFAOYSA-N 2-(4-methoxyphenyl)-5-(3-methyloxetan-3-yl)pyrazol-3-amine Chemical compound C1=CC(OC)=CC=C1N1C(N)=CC(C2(C)COC2)=N1 FCAZTZCJGRZOJY-UHFFFAOYSA-N 0.000 description 1
• WXPAFXABBVDCCF-UHFFFAOYSA-N 2-(4-methoxyphenyl)-5-(oxolan-2-yl)pyrazol-3-amine Chemical compound C1=CC(OC)=CC=C1N1C(N)=CC(C2OCCC2)=N1 WXPAFXABBVDCCF-UHFFFAOYSA-N 0.000 description 1
• PANHIXHKJNFABR-UHFFFAOYSA-N 2-(4-methoxyphenyl)-5-(oxolan-3-yl)pyrazol-3-amine Chemical compound C1=CC(OC)=CC=C1N1C(N)=CC(C2COCC2)=N1 PANHIXHKJNFABR-UHFFFAOYSA-N 0.000 description 1
• MBSNWKYWASMZRU-UHFFFAOYSA-N 2-(4-methylphenyl)-5-(1,1,1-trifluoro-2-methylpropan-2-yl)pyrazol-3-amine Chemical compound C1=CC(C)=CC=C1N1C(N)=CC(C(C)(C)C(F)(F)F)=N1 MBSNWKYWASMZRU-UHFFFAOYSA-N 0.000 description 1
• LVWWWVCVJOTNMC-UHFFFAOYSA-N 2-(4-methylphenyl)-5-(1,1,2,2,2-pentafluoroethyl)pyrazol-3-amine Chemical compound C1=CC(C)=CC=C1N1C(N)=CC(C(F)(F)C(F)(F)F)=N1 LVWWWVCVJOTNMC-UHFFFAOYSA-N 0.000 description 1
• BNPYSFKALZUZSA-UHFFFAOYSA-N 2-(4-methylphenyl)-5-prop-1-en-2-ylpyrazol-3-amine Chemical compound N1=C(C(=C)C)C=C(N)N1C1=CC=C(C)C=C1 BNPYSFKALZUZSA-UHFFFAOYSA-N 0.000 description 1
• POVNIOLRQWADGS-UHFFFAOYSA-N 2-(4-methylphenyl)-5-propan-2-ylpyrazol-3-amine Chemical compound N1=C(C(C)C)C=C(N)N1C1=CC=C(C)C=C1 POVNIOLRQWADGS-UHFFFAOYSA-N 0.000 description 1
• FBUFXKHEPHHMSR-UHFFFAOYSA-N 2-(6-methoxypyridin-3-yl)-5-propan-2-ylpyrazol-3-amine Chemical compound C1=NC(OC)=CC=C1N1C(N)=CC(C(C)C)=N1 FBUFXKHEPHHMSR-UHFFFAOYSA-N 0.000 description 1
• WIHWMDOXEBATJG-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-3-methoxybenzamide Chemical compound CN(CCC1=C(C(=O)N)C=CC=C1OC)C WIHWMDOXEBATJG-UHFFFAOYSA-N 0.000 description 1
• AAHBMULJAJVVBJ-UHFFFAOYSA-N 2-[5-amino-1-(4-methylphenyl)pyrazol-3-yl]-2-methylpropanenitrile Chemical compound C1=CC(C)=CC=C1N1C(N)=CC(C(C)(C)C#N)=N1 AAHBMULJAJVVBJ-UHFFFAOYSA-N 0.000 description 1
• VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 1
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
• JCXYZQUYVNLCTG-UHFFFAOYSA-N 2-methyl-1-morpholin-4-ylpropan-2-amine Chemical compound CC(C)(N)CN1CCOCC1 JCXYZQUYVNLCTG-UHFFFAOYSA-N 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
• GSWYUZQBLVUEPH-UHFFFAOYSA-N 3-(azaniumylmethyl)benzoate Chemical compound NCC1=CC=CC(C(O)=O)=C1 GSWYUZQBLVUEPH-UHFFFAOYSA-N 0.000 description 1
• NEWRACMECZXMLE-UHFFFAOYSA-N 3-[[4-(4-aminonaphthalen-1-yl)oxypyrimidin-2-yl]amino]benzoic acid Chemical compound C12=CC=CC=C2C(N)=CC=C1OC(N=1)=CC=NC=1NC1=CC=CC(C(O)=O)=C1 NEWRACMECZXMLE-UHFFFAOYSA-N 0.000 description 1
• HBKWMWJALRWCIZ-UHFFFAOYSA-N 3-[[4-[4-[(2-methylpropan-2-yl)oxycarbonylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-(trifluoromethyl)benzoic acid Chemical compound C12=CC=CC=C2C(NC(=O)OC(C)(C)C)=CC=C1OC(N=1)=CC=NC=1NC1=CC(C(O)=O)=CC(C(F)(F)F)=C1 HBKWMWJALRWCIZ-UHFFFAOYSA-N 0.000 description 1
• WBTHOSZMTIPJLR-UHFFFAOYSA-N 3-amino-5-(trifluoromethyl)benzoic acid Chemical compound NC1=CC(C(O)=O)=CC(C(F)(F)F)=C1 WBTHOSZMTIPJLR-UHFFFAOYSA-N 0.000 description 1
• LNSUAHOQXPBKCI-UHFFFAOYSA-N 3-amino-5-[2-tri(propan-2-yl)silylethynyl]benzamide Chemical compound CC(C)[Si](C(C)C)(C(C)C)C#CC1=CC(N)=CC(C(N)=O)=C1 LNSUAHOQXPBKCI-UHFFFAOYSA-N 0.000 description 1
• YTHIROYGANGIDH-UHFFFAOYSA-N 3-amino-5-bromobenzamide Chemical compound NC(=O)C1=CC(N)=CC(Br)=C1 YTHIROYGANGIDH-UHFFFAOYSA-N 0.000 description 1
• ATFAXWNNFCBZNY-UHFFFAOYSA-N 3-amino-5-chlorobenzoic acid Chemical compound NC1=CC(Cl)=CC(C(O)=O)=C1 ATFAXWNNFCBZNY-UHFFFAOYSA-N 0.000 description 1
• VVOMCYCHTRIFEK-UHFFFAOYSA-N 3-amino-5-ethynylbenzamide Chemical compound NC(=O)C1=CC(N)=CC(C#C)=C1 VVOMCYCHTRIFEK-UHFFFAOYSA-N 0.000 description 1
• CWBYBPGSAFKSEJ-UHFFFAOYSA-N 3-amino-5-methylbenzoic acid Chemical compound CC1=CC(N)=CC(C(O)=O)=C1 CWBYBPGSAFKSEJ-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
• BLVFEGLTCWYFJV-UHFFFAOYSA-N 3-bromo-5-[[4-[4-[(2-methylpropan-2-yl)oxycarbonylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzoic acid Chemical compound C12=CC=CC=C2C(NC(=O)OC(C)(C)C)=CC=C1OC(N=1)=CC=NC=1NC1=CC(Br)=CC(C(O)=O)=C1 BLVFEGLTCWYFJV-UHFFFAOYSA-N 0.000 description 1
• SKUGRGWTSCMXBV-UHFFFAOYSA-N 3-chloro-5-[[4-[4-[(2-methylpropan-2-yl)oxycarbonylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzoic acid Chemical compound C12=CC=CC=C2C(NC(=O)OC(C)(C)C)=CC=C1OC(N=1)=CC=NC=1NC1=CC(Cl)=CC(C(O)=O)=C1 SKUGRGWTSCMXBV-UHFFFAOYSA-N 0.000 description 1
• XDQFNRKBERZMKN-UHFFFAOYSA-N 3-ethynyl-5-[[4-[4-[(2-methylpropan-2-yl)oxycarbonylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzoic acid Chemical compound C12=CC=CC=C2C(NC(=O)OC(C)(C)C)=CC=C1OC(N=1)=CC=NC=1NC1=CC(C#C)=CC(C(O)=O)=C1 XDQFNRKBERZMKN-UHFFFAOYSA-N 0.000 description 1
• UUOIRFKDVRMTSA-UHFFFAOYSA-N 3-methoxy-4-[[4-[4-[(2-methylpropan-2-yl)oxycarbonylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1NC1=NC=CC(OC=2C3=CC=CC=C3C(NC(=O)OC(C)(C)C)=CC=2)=N1 UUOIRFKDVRMTSA-UHFFFAOYSA-N 0.000 description 1
• MEPIALPCYOPYLL-UHFFFAOYSA-N 3-methoxy-5-[[4-[4-[(2-methylpropan-2-yl)oxycarbonylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)OC(C)(C)C)=CC=3)C=CN=2)=C1 MEPIALPCYOPYLL-UHFFFAOYSA-N 0.000 description 1
• URALCCPDSSHACS-UHFFFAOYSA-N 3-methoxy-5-[[6-[4-[(2-methylpropan-2-yl)oxycarbonylamino]naphthalen-1-yl]oxypyrimidin-4-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC(NC=2N=CN=C(OC=3C4=CC=CC=C4C(NC(=O)OC(C)(C)C)=CC=3)C=2)=C1 URALCCPDSSHACS-UHFFFAOYSA-N 0.000 description 1
• OLRXEPJYASCSRS-UHFFFAOYSA-N 3-methyl-5-[[4-[4-[(2-methylpropan-2-yl)oxycarbonylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(C)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)OC(C)(C)C)=CC=3)C=CN=2)=C1 OLRXEPJYASCSRS-UHFFFAOYSA-N 0.000 description 1
• IQIMAWJRPYKXBL-UHFFFAOYSA-N 3-oxo-3-(oxolan-2-yl)propanenitrile Chemical compound N#CCC(=O)C1CCCO1 IQIMAWJRPYKXBL-UHFFFAOYSA-N 0.000 description 1
• FUXCNUVQVSLRSP-UHFFFAOYSA-N 3-oxo-3-(oxolan-3-yl)propanenitrile Chemical compound N#CCC(=O)C1CCOC1 FUXCNUVQVSLRSP-UHFFFAOYSA-N 0.000 description 1
• NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 1
• MHEGVPMXHHPCDX-UHFFFAOYSA-N 4-(2-chloropyrimidin-4-yl)oxynaphthalen-1-amine Chemical compound C12=CC=CC=C2C(N)=CC=C1OC1=CC=NC(Cl)=N1 MHEGVPMXHHPCDX-UHFFFAOYSA-N 0.000 description 1
• RVSCPXYYENHSBV-UHFFFAOYSA-N 4-(6-chloropyrimidin-4-yl)oxynaphthalen-1-amine Chemical compound C12=CC=CC=C2C(N)=CC=C1OC1=CC(Cl)=NC=N1 RVSCPXYYENHSBV-UHFFFAOYSA-N 0.000 description 1
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
• OQHWFUQNSLMSBG-UHFFFAOYSA-N 4-amino-2,3-dichlorophenol Chemical compound NC1=CC=C(O)C(Cl)=C1Cl OQHWFUQNSLMSBG-UHFFFAOYSA-N 0.000 description 1
• LYFMJLYBTMEYDV-UHFFFAOYSA-N 4-amino-2,3-difluorophenol Chemical compound NC1=CC=C(O)C(F)=C1F LYFMJLYBTMEYDV-UHFFFAOYSA-N 0.000 description 1
• ABJQKDJOYSQVFX-UHFFFAOYSA-N 4-aminonaphthalen-1-ol Chemical compound C1=CC=C2C(N)=CC=C(O)C2=C1 ABJQKDJOYSQVFX-UHFFFAOYSA-N 0.000 description 1
• CGEPRVBWGCYTOV-UHFFFAOYSA-N 4-fluoro-4-methyl-3-oxopentanenitrile Chemical compound CC(C)(F)C(=O)CC#N CGEPRVBWGCYTOV-UHFFFAOYSA-N 0.000 description 1
• FJWMASRRHPBXCT-UHFFFAOYSA-N 4-methoxy-3-[[4-[4-[(2-methylpropan-2-yl)oxycarbonylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1NC1=NC=CC(OC=2C3=CC=CC=C3C(NC(=O)OC(C)(C)C)=CC=2)=N1 FJWMASRRHPBXCT-UHFFFAOYSA-N 0.000 description 1
• WVMCMPAYDPFEJF-UHFFFAOYSA-N 5-(2-methoxypropan-2-yl)-2-(4-methylphenyl)pyrazol-3-amine Chemical compound N1=C(C(C)(C)OC)C=C(N)N1C1=CC=C(C)C=C1 WVMCMPAYDPFEJF-UHFFFAOYSA-N 0.000 description 1
• SSNYCARMICROKY-UHFFFAOYSA-N 5-(3-methyloxetan-3-yl)-2-(4-methylphenyl)pyrazol-3-amine Chemical compound C1=CC(C)=CC=C1N1C(N)=CC(C2(C)COC2)=N1 SSNYCARMICROKY-UHFFFAOYSA-N 0.000 description 1
• SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
• GVNREOVPXNVVCZ-UHFFFAOYSA-N 5-cyclopropyl-2-(4-methylphenyl)pyrazol-3-amine Chemical compound C1=CC(C)=CC=C1N1C(N)=CC(C2CC2)=N1 GVNREOVPXNVVCZ-UHFFFAOYSA-N 0.000 description 1
• QKWZSJOAFPNOAR-UHFFFAOYSA-N 5-ethyl-2-(4-methylphenyl)pyrazol-3-amine Chemical compound N1=C(CC)C=C(N)N1C1=CC=C(C)C=C1 QKWZSJOAFPNOAR-UHFFFAOYSA-N 0.000 description 1
• ZHBXGHWSVIBUCQ-UHFFFAOYSA-N 5-tert-butyl-1h-pyrazol-3-amine Chemical compound CC(C)(C)C1=CC(N)=NN1 ZHBXGHWSVIBUCQ-UHFFFAOYSA-N 0.000 description 1
• ITHNHEWXIBNEDG-UHFFFAOYSA-N 5-tert-butyl-2-(4-methylphenyl)pyrazol-3-amine Chemical compound C1=CC(C)=CC=C1N1C(N)=CC(C(C)(C)C)=N1 ITHNHEWXIBNEDG-UHFFFAOYSA-N 0.000 description 1
• RHMYSCXFRDIJCV-UHFFFAOYSA-N 5-tert-butyl-2-[3-(2-methoxyethoxy)phenyl]pyrazol-3-amine Chemical compound COCCOC1=CC=CC(N2C(=CC(=N2)C(C)(C)C)N)=C1 RHMYSCXFRDIJCV-UHFFFAOYSA-N 0.000 description 1
• AFVIFKSHHHFWHT-UHFFFAOYSA-N 5-tert-butyl-2-[4-(dimethylamino)phenyl]pyrazole-3-carboxylic acid Chemical compound C1=CC(N(C)C)=CC=C1N1C(C(O)=O)=CC(C(C)(C)C)=N1 AFVIFKSHHHFWHT-UHFFFAOYSA-N 0.000 description 1
• MJZJYWCQPMNPRM-UHFFFAOYSA-N 6,6-dimethyl-1-[3-(2,4,5-trichlorophenoxy)propoxy]-1,6-dihydro-1,3,5-triazine-2,4-diamine Chemical compound CC1(C)N=C(N)N=C(N)N1OCCCOC1=CC(Cl)=C(Cl)C=C1Cl MJZJYWCQPMNPRM-UHFFFAOYSA-N 0.000 description 1
• XDBHURGONHZNJF-UHFFFAOYSA-N 6-[2-(3,4-diethoxyphenyl)-1,3-thiazol-4-yl]pyridine-2-carboxylic acid Chemical compound C1=C(OCC)C(OCC)=CC=C1C1=NC(C=2N=C(C=CC=2)C(O)=O)=CS1 XDBHURGONHZNJF-UHFFFAOYSA-N 0.000 description 1
• XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 101150072179 ATP1 gene Proteins 0.000 description 1
• 235000019489 Almond oil Nutrition 0.000 description 1
• 101100003366 Arabidopsis thaliana ATPA gene Proteins 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• IVRMZWNICZWHMI-UHFFFAOYSA-N Azide Chemical class [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
• KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 description 1
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
• 102000015735 Beta-catenin Human genes 0.000 description 1
• 108060000903 Beta-catenin Proteins 0.000 description 1
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• 206010006440 Bronchial obstruction Diseases 0.000 description 1
• 108010074051 C-Reactive Protein Proteins 0.000 description 1
• 102100032752 C-reactive protein Human genes 0.000 description 1
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
• 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
• 238000006964 Chan-Lam coupling reaction Methods 0.000 description 1
• 229920001287 Chondroitin sulfate Polymers 0.000 description 1
• 208000017667 Chronic Disease Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
• 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• 101100457345 Danio rerio mapk14a gene Proteins 0.000 description 1
• 101100457347 Danio rerio mapk14b gene Proteins 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
• QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
• 101100291385 Drosophila melanogaster p38a gene Proteins 0.000 description 1
• 206010013710 Drug interaction Diseases 0.000 description 1
• 102100023274 Dual specificity mitogen-activated protein kinase kinase 4 Human genes 0.000 description 1
• 102100023401 Dual specificity mitogen-activated protein kinase kinase 6 Human genes 0.000 description 1
• 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
• 102100021649 Elongator complex protein 6 Human genes 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• 241000402754 Erythranthe moschata Species 0.000 description 1
• 229930091371 Fructose Natural products 0.000 description 1
• 239000005715 Fructose Substances 0.000 description 1
• RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
• 206010064571 Gene mutation Diseases 0.000 description 1
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
• 241000152447 Hades Species 0.000 description 1
• 101000725401 Homo sapiens Cytochrome c oxidase subunit 2 Proteins 0.000 description 1
• 101001115395 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 4 Proteins 0.000 description 1
• 101000624426 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 6 Proteins 0.000 description 1
• 101100065219 Homo sapiens ELP6 gene Proteins 0.000 description 1
• 101000628954 Homo sapiens Mitogen-activated protein kinase 12 Proteins 0.000 description 1
• 101000605127 Homo sapiens Prostaglandin G/H synthase 2 Proteins 0.000 description 1
• 229920001908 Hydrogenated starch hydrolysate Polymers 0.000 description 1
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
• 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 1
• 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
• 102000004890 Interleukin-8 Human genes 0.000 description 1
• 108090001007 Interleukin-8 Proteins 0.000 description 1
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
• 108010044467 Isoenzymes Proteins 0.000 description 1
• UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
• 240000000759 Lepidium meyenii Species 0.000 description 1
• 235000000421 Lepidium meyenii Nutrition 0.000 description 1
• 229940122696 MAP kinase inhibitor Drugs 0.000 description 1
• 108700012928 MAPK14 Proteins 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 101150003941 Mapk14 gene Proteins 0.000 description 1
• 239000004430 Mapka Substances 0.000 description 1
• 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
• 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
• 229910017976 MgO 4 Inorganic materials 0.000 description 1
• 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 1
• 102100026932 Mitogen-activated protein kinase 12 Human genes 0.000 description 1
• 102000054819 Mitogen-activated protein kinase 14 Human genes 0.000 description 1
• 101710166115 Mitogen-activated protein kinase 2 Proteins 0.000 description 1
• 238000006751 Mitsunobu reaction Methods 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
• 102000003896 Myeloperoxidases Human genes 0.000 description 1
• 108090000235 Myeloperoxidases Proteins 0.000 description 1
• LWLSVNFEVKJDBZ-UHFFFAOYSA-N N-[4-(trifluoromethoxy)phenyl]-4-[[3-[5-(trifluoromethyl)pyridin-2-yl]oxyphenyl]methyl]piperidine-1-carboxamide Chemical compound FC(OC1=CC=C(C=C1)NC(=O)N1CCC(CC1)CC1=CC(=CC=C1)OC1=NC=C(C=C1)C(F)(F)F)(F)F LWLSVNFEVKJDBZ-UHFFFAOYSA-N 0.000 description 1
• NSGDYZCDUPSTQT-UHFFFAOYSA-N N-[5-bromo-1-[(4-fluorophenyl)methyl]-4-methyl-2-oxopyridin-3-yl]cycloheptanecarboxamide Chemical compound Cc1c(Br)cn(Cc2ccc(F)cc2)c(=O)c1NC(=O)C1CCCCCC1 NSGDYZCDUPSTQT-UHFFFAOYSA-N 0.000 description 1
• 206010030113 Oedema Diseases 0.000 description 1
• 206010051741 Pancreas infection Diseases 0.000 description 1
• 208000009608 Papillomavirus Infections Diseases 0.000 description 1
• 229920001774 Perfluoroether Polymers 0.000 description 1
• 201000007100 Pharyngitis Diseases 0.000 description 1
• 241000709664 Picornaviridae Species 0.000 description 1
• 208000005155 Picornaviridae Infections Diseases 0.000 description 1
• RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 1
• 206010037660 Pyrexia Diseases 0.000 description 1
• 206010061603 Respiratory syncytial virus infection Diseases 0.000 description 1
• 206010062106 Respiratory tract infection viral Diseases 0.000 description 1
• 206010057190 Respiratory tract infections Diseases 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• 239000004147 Sorbitan trioleate Substances 0.000 description 1
• PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
• 241000191967 Staphylococcus aureus Species 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 208000005718 Stomach Neoplasms Diseases 0.000 description 1
• 102100030416 Stromelysin-1 Human genes 0.000 description 1
• 101710108790 Stromelysin-1 Proteins 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 230000006044 T cell activation Effects 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
• DQHNAVOVODVIMG-UHFFFAOYSA-M Tiotropium bromide Chemical compound [Br-].C1C(C2C3O2)[N+](C)(C)C3CC1OC(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 DQHNAVOVODVIMG-UHFFFAOYSA-M 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
• 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
• 241000289690 Xenarthra Species 0.000 description 1
• TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
• RIIPFHVHLXPMHQ-UHFFFAOYSA-N [4-(dimethylamino)phenyl]boronic acid Chemical compound CN(C)C1=CC=C(B(O)O)C=C1 RIIPFHVHLXPMHQ-UHFFFAOYSA-N 0.000 description 1
• SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
• 150000001241 acetals Chemical class 0.000 description 1
• 229960000583 acetic acid Drugs 0.000 description 1
• 239000003377 acid catalyst Substances 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 229960001456 adenosine triphosphate Drugs 0.000 description 1
• 239000003732 agents acting on the eye Substances 0.000 description 1
• NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 1
• 150000001347 alkyl bromides Chemical class 0.000 description 1
• 150000005215 alkyl ethers Chemical class 0.000 description 1
• 239000008168 almond oil Substances 0.000 description 1
• WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
• 210000001132 alveolar macrophage Anatomy 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 230000001078 anti-cholinergic effect Effects 0.000 description 1
• 230000000840 anti-viral effect Effects 0.000 description 1
• 239000000010 aprotic solvent Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
• 101150105046 atpI gene Proteins 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 229960004669 basiliximab Drugs 0.000 description 1
• 229950000210 beclometasone dipropionate Drugs 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 229960000686 benzalkonium chloride Drugs 0.000 description 1
• KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 description 1
• 229940073464 benzododecinium bromide Drugs 0.000 description 1
• 229960004217 benzyl alcohol Drugs 0.000 description 1
• CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
• 229940125388 beta agonist Drugs 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 239000012455 biphasic mixture Substances 0.000 description 1
• 229910021538 borax Inorganic materials 0.000 description 1
• KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
• 239000004327 boric acid Substances 0.000 description 1
• 235000010338 boric acid Nutrition 0.000 description 1
• 229910052796 boron Inorganic materials 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 239000007853 buffer solution Substances 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
• 239000001110 calcium chloride Substances 0.000 description 1
• 229910001628 calcium chloride Inorganic materials 0.000 description 1
• 235000011148 calcium chloride Nutrition 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 238000005341 cation exchange Methods 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 230000005754 cellular signaling Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 150000001793 charged compounds Chemical class 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 239000000812 cholinergic antagonist Substances 0.000 description 1
• 229940059329 chondroitin sulfate Drugs 0.000 description 1
• VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
• 230000007012 clinical effect Effects 0.000 description 1
• 238000010549 co-Evaporation Methods 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 239000003026 cod liver oil Substances 0.000 description 1
• 235000012716 cod liver oil Nutrition 0.000 description 1
• 206010009887 colitis Diseases 0.000 description 1
• 238000001246 colloidal dispersion Methods 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 230000009137 competitive binding Effects 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 238000006482 condensation reaction Methods 0.000 description 1
• 238000011109 contamination Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• CEEVJKFQOOTIBO-UHFFFAOYSA-L copper;diiodocopper Chemical compound [Cu].I[Cu]I CEEVJKFQOOTIBO-UHFFFAOYSA-L 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
• 229960002806 daclizumab Drugs 0.000 description 1
• 238000006900 dealkylation reaction Methods 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 210000004443 dendritic cell Anatomy 0.000 description 1
• 239000011903 deuterated solvents‎ Substances 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 229960003957 dexamethasone Drugs 0.000 description 1
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
• 229920003045 dextran sodium sulfate Polymers 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• RUHCATDGSSLXPZ-UHFFFAOYSA-N dicarboxyazaniumylideneazanide Chemical compound OC(=O)[N+](=[N-])C(O)=O RUHCATDGSSLXPZ-UHFFFAOYSA-N 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000003974 emollient agent Substances 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940079360 enema for constipation Drugs 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 210000002919 epithelial cell Anatomy 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• MYIRARNXCGWFHI-UHFFFAOYSA-N ethoxyethane;2-methylpentane Chemical compound CCOCC.CCCC(C)C MYIRARNXCGWFHI-UHFFFAOYSA-N 0.000 description 1
• RCXMILPYEKVQLB-UHFFFAOYSA-N ethyl 5-tert-butyl-1h-pyrazole-3-carboxylate Chemical compound CCOC(=O)C=1C=C(C(C)(C)C)NN=1 RCXMILPYEKVQLB-UHFFFAOYSA-N 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 239000003885 eye ointment Substances 0.000 description 1
• 239000003925 fat Substances 0.000 description 1
• 235000019197 fats Nutrition 0.000 description 1
• 239000012091 fetal bovine serum Substances 0.000 description 1
• 239000000835 fiber Substances 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 229960001347 fluocinolone acetonide Drugs 0.000 description 1
• FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 238000002866 fluorescence resonance energy transfer Methods 0.000 description 1
• 125000003709 fluoroalkyl group Chemical group 0.000 description 1
• 229960002714 fluticasone Drugs 0.000 description 1
• MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 description 1
• 229960000289 fluticasone propionate Drugs 0.000 description 1
• WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 1
• 229960002848 formoterol Drugs 0.000 description 1
• BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 229930182830 galactose Natural products 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 208000010749 gastric carcinoma Diseases 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 230000030279 gene silencing Effects 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 208000007565 gingivitis Diseases 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 150000004676 glycans Chemical class 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 229930182470 glycoside Natural products 0.000 description 1
• 150000002338 glycosides Chemical class 0.000 description 1
• 229910052737 gold Inorganic materials 0.000 description 1
• LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 239000007887 hard shell capsule Substances 0.000 description 1
• 210000002216 heart Anatomy 0.000 description 1
• 210000000777 hematopoietic system Anatomy 0.000 description 1
• UKACHOXRXFQJFN-UHFFFAOYSA-N heptafluoropropane Chemical compound FC(F)C(F)(F)C(F)(F)F UKACHOXRXFQJFN-UHFFFAOYSA-N 0.000 description 1
• 150000002390 heteroarenes Chemical class 0.000 description 1
• 125000005553 heteroaryloxy group Chemical group 0.000 description 1
• 229960001340 histamine Drugs 0.000 description 1
• 229920002674 hyaluronan Polymers 0.000 description 1
• 229960003160 hyaluronic acid Drugs 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 230000036039 immunity Effects 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 206010022000 influenza Diseases 0.000 description 1
• 230000015788 innate immune response Effects 0.000 description 1
• XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 1
• 229940096397 interleukin-8 Drugs 0.000 description 1
• QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 1
• 230000031146 intracellular signal transduction Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 1
• 229960001888 ipratropium Drugs 0.000 description 1
• 239000002085 irritant Substances 0.000 description 1
• 231100000021 irritant Toxicity 0.000 description 1
• 239000012948 isocyanate Substances 0.000 description 1
• PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical compound C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 description 1
• 235000010439 isomalt Nutrition 0.000 description 1
• 239000000905 isomalt Substances 0.000 description 1
• HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 239000000832 lactitol Substances 0.000 description 1
• 235000010448 lactitol Nutrition 0.000 description 1
• VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[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 VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 1
• 229960003451 lactitol Drugs 0.000 description 1
• 235000012902 lepidium meyenii Nutrition 0.000 description 1
• 239000006193 liquid solution Substances 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 229940125389 long-acting beta agonist Drugs 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• 235000011147 magnesium chloride Nutrition 0.000 description 1
• 239000000845 maltitol Substances 0.000 description 1
• 235000010449 maltitol Nutrition 0.000 description 1
• VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[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 VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
• 229940035436 maltitol Drugs 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 229960001855 mannitol Drugs 0.000 description 1
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
• 229960004961 mechlorethamine Drugs 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 229960001428 mercaptopurine Drugs 0.000 description 1
• JABGXPCRNXUENL-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1N=CNC2=NC=N[C]12 JABGXPCRNXUENL-UHFFFAOYSA-N 0.000 description 1
• KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 1
• 229960004963 mesalazine Drugs 0.000 description 1
• HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• XBFPKZGFUYJRPK-UHFFFAOYSA-N methanol;propanenitrile Chemical compound OC.CCC#N XBFPKZGFUYJRPK-UHFFFAOYSA-N 0.000 description 1
• DRHCDXVRPQZGFZ-UHFFFAOYSA-N methyl 3-[[4-(4-aminonaphthalen-1-yl)oxypyrimidin-2-yl]amino]-5-bromobenzoate Chemical compound COC(=O)C1=CC(Br)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(N)=CC=3)C=CN=2)=C1 DRHCDXVRPQZGFZ-UHFFFAOYSA-N 0.000 description 1
• VEYKEABTQXWYLY-UHFFFAOYSA-N methyl 3-[[4-(4-aminonaphthalen-1-yl)oxypyrimidin-2-yl]amino]-5-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(N)=CC=3)C=CN=2)=C1 VEYKEABTQXWYLY-UHFFFAOYSA-N 0.000 description 1
• KCORJSKXSBAUMP-UHFFFAOYSA-N methyl 3-[[4-(4-aminonaphthalen-1-yl)oxypyrimidin-2-yl]amino]-5-methylbenzoate Chemical compound COC(=O)C1=CC(C)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(N)=CC=3)C=CN=2)=C1 KCORJSKXSBAUMP-UHFFFAOYSA-N 0.000 description 1
• LZPWWGJUZCUTBD-UHFFFAOYSA-N methyl 3-[[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)NC=4N(N=C(C=4)C(C)(C)C)C=4C=CC(OC)=CC=4)=CC=3)C=CN=2)=C1 LZPWWGJUZCUTBD-UHFFFAOYSA-N 0.000 description 1
• ISWRKQIBSABUIK-UHFFFAOYSA-N methyl 3-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-methylbenzoate Chemical compound COC(=O)C1=CC(C)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)NC=4N(N=C(C=4)C(C)(C)C)C=4C=CC(C)=CC=4)=CC=3)C=CN=2)=C1 ISWRKQIBSABUIK-UHFFFAOYSA-N 0.000 description 1
• QVDWKLDUBSJEOG-UHFFFAOYSA-N methyl 3-amino-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(N)=C1 QVDWKLDUBSJEOG-UHFFFAOYSA-N 0.000 description 1
• MNXLJDUZJCMJCI-UHFFFAOYSA-N methyl 3-amino-5-bromobenzoate Chemical compound COC(=O)C1=CC(N)=CC(Br)=C1 MNXLJDUZJCMJCI-UHFFFAOYSA-N 0.000 description 1
• WZZCERUOCYQGRP-UHFFFAOYSA-N methyl 3-amino-5-ethynylbenzoate Chemical compound COC(=O)C1=CC(N)=CC(C#C)=C1 WZZCERUOCYQGRP-UHFFFAOYSA-N 0.000 description 1
• OWMZQNZFHGAVCN-UHFFFAOYSA-N methyl 3-amino-5-methoxybenzoate Chemical compound COC(=O)C1=CC(N)=CC(OC)=C1 OWMZQNZFHGAVCN-UHFFFAOYSA-N 0.000 description 1
• SWHJGAJWQLQEKD-UHFFFAOYSA-N methyl 3-ethynyl-5-[[4-[4-[(2-methylpropan-2-yl)oxycarbonylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzoate Chemical compound C#CC1=CC(C(=O)OC)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)OC(C)(C)C)=CC=3)C=CN=2)=C1 SWHJGAJWQLQEKD-UHFFFAOYSA-N 0.000 description 1
• IBVLMZMFILBEGC-UHFFFAOYSA-N methyl 3-ethynyl-5-nitrobenzoate Chemical compound COC(=O)C1=CC(C#C)=CC([N+]([O-])=O)=C1 IBVLMZMFILBEGC-UHFFFAOYSA-N 0.000 description 1
• WSVTVZRHDGBNSX-UHFFFAOYSA-N methyl 3-methoxy-4-[[4-[4-[(2-methylpropan-2-yl)oxycarbonylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1NC1=NC=CC(OC=2C3=CC=CC=C3C(NC(=O)OC(C)(C)C)=CC=2)=N1 WSVTVZRHDGBNSX-UHFFFAOYSA-N 0.000 description 1
• URZJGQPLAUSDBK-UHFFFAOYSA-N methyl 3-methoxy-5-[[4-[4-[(2-methylpropan-2-yl)oxycarbonylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzoate Chemical compound COC1=CC(C(=O)OC)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)OC(C)(C)C)=CC=3)C=CN=2)=C1 URZJGQPLAUSDBK-UHFFFAOYSA-N 0.000 description 1
• YWUUASOOYILSPM-UHFFFAOYSA-N methyl 4-[[4-(4-aminonaphthalen-1-yl)oxypyrimidin-2-yl]amino]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1NC1=NC=CC(OC=2C3=CC=CC=C3C(N)=CC=2)=N1 YWUUASOOYILSPM-UHFFFAOYSA-N 0.000 description 1
• BKSLXSQBHXCWDY-UHFFFAOYSA-N methyl 4-methoxy-3-[[4-[4-[(2-methylpropan-2-yl)oxycarbonylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzoate Chemical compound COC(=O)C1=CC=C(OC)C(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)OC(C)(C)C)=CC=3)C=CN=2)=C1 BKSLXSQBHXCWDY-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• 229960004584 methylprednisolone Drugs 0.000 description 1
• 239000004530 micro-emulsion Substances 0.000 description 1
• 230000000813 microbial effect Effects 0.000 description 1
• 244000005706 microflora Species 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000011278 mitosis Effects 0.000 description 1
• 239000011259 mixed solution Substances 0.000 description 1
• 238000003032 molecular docking Methods 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 229960001664 mometasone Drugs 0.000 description 1
• QLIIKPVHVRXHRI-CXSFZGCWSA-N mometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CCl)(O)[C@@]1(C)C[C@@H]2O QLIIKPVHVRXHRI-CXSFZGCWSA-N 0.000 description 1
• 125000005322 morpholin-1-yl group Chemical group 0.000 description 1
• 210000000214 mouth Anatomy 0.000 description 1
• RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
• 229960004866 mycophenolate mofetil Drugs 0.000 description 1
• PWDYHMBTPGXCSN-VCBMUGGBSA-N n,n'-bis[3,5-bis[(e)-n-(diaminomethylideneamino)-c-methylcarbonimidoyl]phenyl]decanediamide Chemical compound NC(N)=N/N=C(\C)C1=CC(C(=N/N=C(N)N)/C)=CC(NC(=O)CCCCCCCCC(=O)NC=2C=C(C=C(C=2)C(\C)=N\N=C(N)N)C(\C)=N\N=C(N)N)=C1 PWDYHMBTPGXCSN-VCBMUGGBSA-N 0.000 description 1
• IMNDHOCGZLYMRO-UHFFFAOYSA-N n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC=C1 IMNDHOCGZLYMRO-UHFFFAOYSA-N 0.000 description 1
• PAMCRRDMORMCSM-UHFFFAOYSA-N n-(trifluoromethyl)benzamide Chemical compound FC(F)(F)NC(=O)C1=CC=CC=C1 PAMCRRDMORMCSM-UHFFFAOYSA-N 0.000 description 1
• LBZUJSQLLVDWDQ-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]benzamide Chemical compound CN(C)CCNC(=O)C1=CC=CC=C1 LBZUJSQLLVDWDQ-UHFFFAOYSA-N 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
• 150000002790 naphthalenes Chemical class 0.000 description 1
• 150000005002 naphthylamines Chemical class 0.000 description 1
• 210000003928 nasal cavity Anatomy 0.000 description 1
• 229960005027 natalizumab Drugs 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 230000027498 negative regulation of mitosis Effects 0.000 description 1
• 239000002547 new drug Substances 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• 150000005338 nitrobenzoic acids Chemical class 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 239000012454 non-polar solvent Substances 0.000 description 1
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
• 230000000269 nucleophilic effect Effects 0.000 description 1
• 230000000414 obstructive effect Effects 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• QQBDLJCYGRGAKP-FOCLMDBBSA-N olsalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=C(C(O)=CC=2)C(O)=O)=C1 QQBDLJCYGRGAKP-FOCLMDBBSA-N 0.000 description 1
• 229960004110 olsalazine Drugs 0.000 description 1
• 239000003605 opacifier Substances 0.000 description 1
• 229940125702 ophthalmic agent Drugs 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 229960002194 oseltamivir phosphate Drugs 0.000 description 1
• IVMHDOBGNQOUHO-UHFFFAOYSA-N oxathiane Chemical compound C1CCSOC1 IVMHDOBGNQOUHO-UHFFFAOYSA-N 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 235000021400 peanut butter Nutrition 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 229960001084 peramivir Drugs 0.000 description 1
• UGTYTOKVOXBJBZ-LINPMSLLSA-N peramivir hydrate Chemical compound O.O.O.O.CCC(CC)[C@H](NC(C)=O)[C@@H]1[C@H](O)[C@@H](C(O)=O)C[C@H]1NC(N)=N UGTYTOKVOXBJBZ-LINPMSLLSA-N 0.000 description 1
• 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
• 201000001245 periodontitis Diseases 0.000 description 1
• 210000005259 peripheral blood Anatomy 0.000 description 1
• 239000011886 peripheral blood Substances 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 238000005191 phase separation Methods 0.000 description 1
• YLRIAWQVHWQGNH-UHFFFAOYSA-N phenyl N-[2-(4-methylphenyl)-5-(1,1,2,2,2-pentafluoroethyl)pyrazol-3-yl]carbamate Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)OC=2C=CC=CC=2)=CC(C(F)(F)C(F)(F)F)=N1 YLRIAWQVHWQGNH-UHFFFAOYSA-N 0.000 description 1
• BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 1
• PBMYQHAFFITFBQ-UHFFFAOYSA-N phenyl n-[2-(4-methylphenyl)-5-propan-2-ylpyrazol-3-yl]carbamate Chemical compound C=1C=C(C)C=CC=1N1N=C(C(C)C)C=C1NC(=O)OC1=CC=CC=C1 PBMYQHAFFITFBQ-UHFFFAOYSA-N 0.000 description 1
• UFAXUYGXKVGYJP-UHFFFAOYSA-N phenyl n-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamate Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)OC=2C=CC=CC=2)=CC(C(C)(C)C)=N1 UFAXUYGXKVGYJP-UHFFFAOYSA-N 0.000 description 1
• XRDLXGAZQMXZFG-UHFFFAOYSA-N phenyl n-[5-tert-butyl-2-(6-methoxypyridin-3-yl)pyrazol-3-yl]carbamate Chemical compound C1=NC(OC)=CC=C1N1C(NC(=O)OC=2C=CC=CC=2)=CC(C(C)(C)C)=N1 XRDLXGAZQMXZFG-UHFFFAOYSA-N 0.000 description 1
• 229940067107 phenylethyl alcohol Drugs 0.000 description 1
• 239000002953 phosphate buffered saline Substances 0.000 description 1
• 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
• 235000011007 phosphoric acid Nutrition 0.000 description 1
• 150000003016 phosphoric acids Chemical class 0.000 description 1
• SFLGSKRGOWRGBR-UHFFFAOYSA-N phthalane Chemical compound C1=CC=C2COCC2=C1 SFLGSKRGOWRGBR-UHFFFAOYSA-N 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 239000004014 plasticizer Substances 0.000 description 1
• 229960000502 poloxamer Drugs 0.000 description 1
• 229920001983 poloxamer Polymers 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 239000004584 polyacrylic acid Substances 0.000 description 1
• 229920001515 polyalkylene glycol Polymers 0.000 description 1
• 229940057838 polyethylene glycol 4000 Drugs 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 229950008882 polysorbate Drugs 0.000 description 1
• 229920000136 polysorbate Polymers 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
• 230000008092 positive effect Effects 0.000 description 1
• 231100000683 possible toxicity Toxicity 0.000 description 1
• 239000001103 potassium chloride Substances 0.000 description 1
• 235000011164 potassium chloride Nutrition 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• 229960005205 prednisolone Drugs 0.000 description 1
• OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
• 229960004618 prednisone Drugs 0.000 description 1
• XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
• 238000004321 preservation Methods 0.000 description 1
• 230000004647 pro-inflammatory pathway Effects 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• GLVAUDGFNGKCSF-UHFFFAOYSA-N purine-6-thione Natural products S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
• 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 description 1
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 210000001533 respiratory mucosa Anatomy 0.000 description 1
• 208000030925 respiratory syncytial virus infectious disease Diseases 0.000 description 1
• 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 235000002020 sage Nutrition 0.000 description 1
• 229960002052 salbutamol Drugs 0.000 description 1
• 229960004017 salmeterol Drugs 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 229960004540 secukinumab Drugs 0.000 description 1
• 229950011005 semapimod Drugs 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 235000020374 simple syrup Nutrition 0.000 description 1
• 229960002930 sirolimus Drugs 0.000 description 1
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
• 210000002027 skeletal muscle Anatomy 0.000 description 1
• 206010040882 skin lesion Diseases 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 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
• 235000011083 sodium citrates Nutrition 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 229910000162 sodium phosphate Inorganic materials 0.000 description 1
• 235000011008 sodium phosphates Nutrition 0.000 description 1
• 235000010339 sodium tetraborate Nutrition 0.000 description 1
• 239000007905 soft elastic gelatin capsule Substances 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 229940035044 sorbitan monolaurate Drugs 0.000 description 1
• 235000019337 sorbitan trioleate Nutrition 0.000 description 1
• 229960000391 sorbitan trioleate Drugs 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 229940046810 spiriva Drugs 0.000 description 1
• 210000004989 spleen cell Anatomy 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 201000011549 stomach cancer Diseases 0.000 description 1
• 201000000498 stomach carcinoma Diseases 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
• 229960001940 sulfasalazine Drugs 0.000 description 1
• NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
• 239000002511 suppository base Substances 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 231100000057 systemic toxicity Toxicity 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• URLYINUFLXOMHP-HTVVRFAVSA-N tcn-p Chemical compound C=12C3=NC=NC=1N(C)N=C(N)C2=CN3[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O URLYINUFLXOMHP-HTVVRFAVSA-N 0.000 description 1
• 229960000195 terbutaline Drugs 0.000 description 1
• JYMAMQZSAFVUOT-UHFFFAOYSA-N tert-butyl N-[4-[2-[3-methoxy-5-(2-morpholin-4-ylethylcarbamoyl)anilino]pyrimidin-4-yl]oxynaphthalen-1-yl]carbamate Chemical compound C=1C(OC)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)OC(C)(C)C)=CC=3)C=CN=2)=CC=1C(=O)NCCN1CCOCC1 JYMAMQZSAFVUOT-UHFFFAOYSA-N 0.000 description 1
• GDVXBLGVBZJTCC-UHFFFAOYSA-N tert-butyl n-(4-hydroxynaphthalen-1-yl)carbamate Chemical compound C1=CC=C2C(NC(=O)OC(C)(C)C)=CC=C(O)C2=C1 GDVXBLGVBZJTCC-UHFFFAOYSA-N 0.000 description 1
• WQETVWOFBYIXGK-UHFFFAOYSA-N tert-butyl n-[4-(2-chloropyrimidin-4-yl)oxynaphthalen-1-yl]carbamate Chemical compound C12=CC=CC=C2C(NC(=O)OC(C)(C)C)=CC=C1OC1=CC=NC(Cl)=N1 WQETVWOFBYIXGK-UHFFFAOYSA-N 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 210000001550 testis Anatomy 0.000 description 1
• 229950002896 tetomilast Drugs 0.000 description 1
• 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 238000011287 therapeutic dose Methods 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 239000002562 thickening agent Substances 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
• 239000012929 tonicity agent Substances 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 229910052723 transition metal Inorganic materials 0.000 description 1
• 150000003624 transition metals Chemical class 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• 229960002117 triamcinolone acetonide Drugs 0.000 description 1
• YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 1
• 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 1
• 229940029284 trichlorofluoromethane Drugs 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
• BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-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
• GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
• 238000011144 upstream manufacturing Methods 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• 150000003673 urethanes Chemical class 0.000 description 1
• 229960003824 ustekinumab Drugs 0.000 description 1
• 210000001215 vagina Anatomy 0.000 description 1
• 229960004914 vedolizumab Drugs 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 244000052613 viral pathogen Species 0.000 description 1
• 210000004127 vitreous body Anatomy 0.000 description 1
• 239000011534 wash buffer Substances 0.000 description 1
• 235000010447 xylitol Nutrition 0.000 description 1
• 239000000811 xylitol Substances 0.000 description 1
• HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
• 229960002675 xylitol Drugs 0.000 description 1