JP5902668B2 - ピラゾール系ｐ３８ＭＡＰキナーゼ阻害剤 - Google Patents

Info

Publication number

JP5902668B2

JP5902668B2 JP2013501951A JP2013501951A JP5902668B2 JP 5902668 B2 JP5902668 B2 JP 5902668B2 JP 2013501951 A JP2013501951 A JP 2013501951A JP 2013501951 A JP2013501951 A JP 2013501951A JP 5902668 B2 JP5902668 B2 JP 5902668B2

Authority

JP

Japan

Prior art keywords

butyl

pyrazol

ureido

pyridin

dichlorophenoxy

Prior art date

2010-04-01

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Active

Links

• Espacenet
• Global Dossier
• Discuss

• 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 title description 35
• 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 title description 35
• 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 title description 9
• 229940122696 MAP kinase inhibitor Drugs 0.000 title description 4
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims description 358
• 125000000217 alkyl group Chemical group 0.000 claims description 170
• -1 phenylene luma Chemical compound 0.000 claims description 132
• 229920006395 saturated elastomer Polymers 0.000 claims description 86
• 125000000623 heterocyclic group Chemical group 0.000 claims description 59
• 229910052757 nitrogen Inorganic materials 0.000 claims description 56
• 125000005842 heteroatom Chemical group 0.000 claims description 53
• 125000001424 substituent group Chemical group 0.000 claims description 53
• 229910052739 hydrogen Inorganic materials 0.000 claims description 46
• 229910052799 carbon Inorganic materials 0.000 claims description 43
• 229910052760 oxygen Inorganic materials 0.000 claims description 41
• 229910052717 sulfur Inorganic materials 0.000 claims description 40
• 238000011282 treatment Methods 0.000 claims description 37
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 33
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 31
• 125000003118 aryl group Chemical group 0.000 claims description 31
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 28
• 229910052736 halogen Inorganic materials 0.000 claims description 28
• 125000003545 alkoxy group Chemical group 0.000 claims description 27
• 150000002367 halogens Chemical class 0.000 claims description 27
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 25
• 125000005843 halogen group Chemical group 0.000 claims description 24
• 125000001072 heteroaryl group Chemical group 0.000 claims description 24
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 19
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
• 239000004202 carbamide Substances 0.000 claims description 17
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 16
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 15
• 239000003814 drug Substances 0.000 claims description 14
• 125000004043 oxo group Chemical group O=* 0.000 claims description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
• 150000003839 salts Chemical class 0.000 claims description 13
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
• 208000006673 asthma Diseases 0.000 claims description 9
• 125000004432 carbon atom Chemical group C* 0.000 claims description 9
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
• 239000004480 active ingredient Substances 0.000 claims description 6
• 125000002947 alkylene group Chemical group 0.000 claims description 6
• 125000004429 atom Chemical group 0.000 claims description 6
• 239000000969 carrier Substances 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000001153 fluoro group Chemical group F* 0.000 claims description 5
• 125000001188 haloalkyl group Chemical group 0.000 claims description 5
• 230000000155 isotopic effect Effects 0.000 claims description 5
• MQDVUDAZJMZQMF-UHFFFAOYSA-N pyridin-2-ylurea Chemical compound NC(=O)NC1=CC=CC=N1 MQDVUDAZJMZQMF-UHFFFAOYSA-N 0.000 claims description 5
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 4
• VLMPAMYESBASPG-UHFFFAOYSA-N 1-[2,3-dichloro-4-[2-(methylcarbamoylamino)pyridin-4-yl]oxyphenyl]-3-[5-(1-methylcyclohexyl)-2-(4-methylphenyl)pyrazol-3-yl]urea Chemical compound C1=NC(NC(=O)NC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C3(C)CCCCC3)C=3C=CC(C)=CC=3)=CC=2)Cl)=C1 VLMPAMYESBASPG-UHFFFAOYSA-N 0.000 claims description 4
• SMTVTISHQTTWIJ-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[[2-(methylcarbamoylamino)pyridin-4-yl]methoxy]phenyl]urea Chemical compound C1=NC(NC(=O)NC)=CC(COC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(OC)=CC=3)=CC=2)Cl)=C1 SMTVTISHQTTWIJ-UHFFFAOYSA-N 0.000 claims description 4
• USWDEAODPRGOFK-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[8-[[2-(methylcarbamoylamino)pyridin-4-yl]methoxy]quinolin-5-yl]urea Chemical compound C1=NC(NC(=O)NC)=CC(COC=2C3=NC=CC=C3C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)=C1 USWDEAODPRGOFK-UHFFFAOYSA-N 0.000 claims description 4
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
• 125000002837 carbocyclic group Chemical group 0.000 claims description 4
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• RKZSLFYAENDMNY-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-3-(trifluoromethyl)phenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C=C(C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)C(F)(F)F)=C1 RKZSLFYAENDMNY-UHFFFAOYSA-N 0.000 claims description 4
• WYANJWLOZNEICQ-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-3-chloro-2-cyanophenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)C#N)=C1 WYANJWLOZNEICQ-UHFFFAOYSA-N 0.000 claims description 4
• CKJSDKNLBGHJCR-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-3-methylsulfonylphenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C=C(C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)S(C)(=O)=O)=C1 CKJSDKNLBGHJCR-UHFFFAOYSA-N 0.000 claims description 4
• TXJNFPHFHSHWMX-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylsulfanylphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]pyrrolidine-1-carboxamide Chemical compound C1=CC(SC)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OC=3C=C(NC(=O)N4CCCC4)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 TXJNFPHFHSHWMX-UHFFFAOYSA-N 0.000 claims description 4
• YKLTVWLJVJBTQF-UHFFFAOYSA-N n-[4-[[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]methyl]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(COC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(OC)=CC=3)=CC=2)Cl)=C1 YKLTVWLJVJBTQF-UHFFFAOYSA-N 0.000 claims description 4
• CVKWJEKIFPWRIE-UHFFFAOYSA-N n-[4-[[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]methyl]pyridin-2-yl]pyrrolidine-1-carboxamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OCC=3C=C(NC(=O)N4CCCC4)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 CVKWJEKIFPWRIE-UHFFFAOYSA-N 0.000 claims description 4
• HCRJGKWVFQOYRB-UHFFFAOYSA-N n-[4-[[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]methyl]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(COC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)Cl)=C1 HCRJGKWVFQOYRB-UHFFFAOYSA-N 0.000 claims description 4
• JZUBZTZKPCGNRK-UHFFFAOYSA-N n-[4-[[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]methyl]pyridin-2-yl]pyrrolidine-1-carboxamide Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OCC=3C=C(NC(=O)N4CCCC4)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 JZUBZTZKPCGNRK-UHFFFAOYSA-N 0.000 claims description 4
• WMWXYOQRAMOAJE-UHFFFAOYSA-N n-[4-[[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-5,6,7,8-tetrahydronaphthalen-1-yl]oxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C=3CCCCC=3C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)=C1 WMWXYOQRAMOAJE-UHFFFAOYSA-N 0.000 claims description 4
• QZEGYHJHDSAXMB-UHFFFAOYSA-N n-[4-[[5-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]quinolin-8-yl]oxymethyl]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(COC=2C3=NC=CC=C3C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(OC)=CC=3)=CC=2)=C1 QZEGYHJHDSAXMB-UHFFFAOYSA-N 0.000 claims description 4
• MDLVXCAENWAJAD-UHFFFAOYSA-N n-[4-[[5-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]quinolin-8-yl]oxymethyl]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(COC=2C3=NC=CC=C3C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)=C1 MDLVXCAENWAJAD-UHFFFAOYSA-N 0.000 claims description 4
• IUQCOTNIPARRBG-UHFFFAOYSA-N n-[4-[[7-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-1h-indazol-4-yl]oxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C=3C=NNC=3C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)=C1 IUQCOTNIPARRBG-UHFFFAOYSA-N 0.000 claims description 4
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• CTGSLPCTBLWMRT-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-hydroxyphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[2-(methylcarbamoylamino)pyridin-4-yl]oxyphenyl]urea Chemical compound C1=NC(NC(=O)NC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(O)=CC=3)=CC=2)Cl)=C1 CTGSLPCTBLWMRT-UHFFFAOYSA-N 0.000 claims description 3
• AJHNLMKJRISUFA-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[2-(ethylcarbamoylamino)pyridin-4-yl]oxyphenyl]urea Chemical compound C1=NC(NC(=O)NCC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(OC)=CC=3)=CC=2)Cl)=C1 AJHNLMKJRISUFA-UHFFFAOYSA-N 0.000 claims description 3
• UXNCEUAZOJVHSD-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[2-[2-(dimethylamino)ethylcarbamoylamino]pyridin-4-yl]oxyphenyl]urea Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OC=3C=C(NC(=O)NCCN(C)C)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 UXNCEUAZOJVHSD-UHFFFAOYSA-N 0.000 claims description 3
• DVERJTHQZPGXQN-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[2-(methylcarbamoylamino)pyridin-4-yl]oxyphenyl]urea Chemical compound C1=NC(NC(=O)NC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)Cl)=C1 DVERJTHQZPGXQN-UHFFFAOYSA-N 0.000 claims description 3
• VVBJANIWLGGZJB-UHFFFAOYSA-N 1-[5-tert-butyl-2-[4-(hydroxymethyl)phenyl]pyrazol-3-yl]-3-[2,3-dichloro-4-[2-(methylcarbamoylamino)pyrimidin-4-yl]oxyphenyl]urea Chemical compound CNC(=O)NC1=NC=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(CO)=CC=3)=CC=2)Cl)=N1 VVBJANIWLGGZJB-UHFFFAOYSA-N 0.000 claims description 3
• XIPWBCORXDYDEH-UHFFFAOYSA-N 3-[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]-1,1-dimethylurea Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OC=3C=C(NC(=O)N(C)C)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 XIPWBCORXDYDEH-UHFFFAOYSA-N 0.000 claims description 3
• LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims description 3
• 206010006458 Bronchitis chronic Diseases 0.000 claims description 3
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
• 201000004681 Psoriasis Diseases 0.000 claims description 3
• 206010039085 Rhinitis allergic Diseases 0.000 claims description 3
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
• 125000002015 acyclic group Chemical group 0.000 claims description 3
• 125000002723 alicyclic group Chemical group 0.000 claims description 3
• 201000010105 allergic rhinitis Diseases 0.000 claims description 3
• 201000008937 atopic dermatitis Diseases 0.000 claims description 3
• 206010006451 bronchitis Diseases 0.000 claims description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 208000007451 chronic bronchitis Diseases 0.000 claims description 3
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
• 230000002757 inflammatory effect Effects 0.000 claims description 3
• WBTMEQBEZBHVLX-UHFFFAOYSA-N n-[4-[2,3-dichloro-4-[[5-(1-methylcyclohexyl)-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]phenoxy]pyridin-2-yl]pyrrolidine-1-carboxamide Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OC=3C=C(NC(=O)N4CCCC4)N=CC=3)=CC=2)Cl)=CC(C2(C)CCCCC2)=N1 WBTMEQBEZBHVLX-UHFFFAOYSA-N 0.000 claims description 3
• PTCQZSYEIRXAIN-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-hydroxyphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(O)=CC=3)=CC=2)Cl)=C1 PTCQZSYEIRXAIN-UHFFFAOYSA-N 0.000 claims description 3
• CZDHOGUMUFVZCC-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-hydroxyphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]pyrrolidine-1-carboxamide Chemical compound C=1C=C(O)C=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C(=C1Cl)Cl)=CC=C1OC(C=1)=CC=NC=1NC(=O)N1CCCC1 CZDHOGUMUFVZCC-UHFFFAOYSA-N 0.000 claims description 3
• URHWXOQMBIQOBQ-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(OC)=CC=3)=CC=2)Cl)=C1 URHWXOQMBIQOBQ-UHFFFAOYSA-N 0.000 claims description 3
• TZMPHXDDWVQDHH-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OC=3C=C(NC(=O)N4CC(O)CC4)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 TZMPHXDDWVQDHH-UHFFFAOYSA-N 0.000 claims description 3
• SIQMUTQLUKGUQN-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyrimidin-2-yl]-2-methoxyacetamide Chemical compound COCC(=O)NC1=NC=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(OC)=CC=3)=CC=2)Cl)=N1 SIQMUTQLUKGUQN-UHFFFAOYSA-N 0.000 claims description 3
• JSIFEAJIXNCCLD-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)Cl)=C1 JSIFEAJIXNCCLD-UHFFFAOYSA-N 0.000 claims description 3
• XQLDEOFPWWTZDI-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]pyrrolidine-1-carboxamide Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OC=3C=C(NC(=O)N4CCCC4)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 XQLDEOFPWWTZDI-UHFFFAOYSA-N 0.000 claims description 3
• VBDADDXQNNCWKR-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-2,5-dichlorophenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=CC(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=C(Cl)C=2)Cl)=C1 VBDADDXQNNCWKR-UHFFFAOYSA-N 0.000 claims description 3
• IJDGLJNPNVTWDM-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-2-(trifluoromethyl)phenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=CC(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)C(F)(F)F)=C1 IJDGLJNPNVTWDM-UHFFFAOYSA-N 0.000 claims description 3
• XCQLGETYJSGQCY-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-2-methylsulfonylphenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=CC(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)S(C)(=O)=O)=C1 XCQLGETYJSGQCY-UHFFFAOYSA-N 0.000 claims description 3
• FDHGBSRBIGBHQC-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-3-chloro-2-(trifluoromethyl)phenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)C(F)(F)F)=C1 FDHGBSRBIGBHQC-UHFFFAOYSA-N 0.000 claims description 3
• UXISBAJFIIIQHI-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-3-chloro-2-fluorophenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)F)=C1 UXISBAJFIIIQHI-UHFFFAOYSA-N 0.000 claims description 3
• ZSBGLUVHHWVFNF-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-5-chloro-2-fluorophenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=CC(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=C(Cl)C=2)F)=C1 ZSBGLUVHHWVFNF-UHFFFAOYSA-N 0.000 claims description 3
• XJDYOCRRPVKPQO-UHFFFAOYSA-N n-[4-[6-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-2,3-difluorophenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=C(F)C=CC=2NC(=O)NC=2N(N=C(C=2)C(C)(C)C)C=2C=CC(C)=CC=2)F)=C1 XJDYOCRRPVKPQO-UHFFFAOYSA-N 0.000 claims description 3
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
• 208000023504 respiratory system disease Diseases 0.000 claims description 3
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 2
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
• OIAZQNDOMLQBTC-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[2-(2-hydroxyethylcarbamoylamino)pyridin-4-yl]oxyphenyl]urea Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OC=3C=C(NC(=O)NCCO)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 OIAZQNDOMLQBTC-UHFFFAOYSA-N 0.000 claims description 2
• PRRTTXQJXYIWIX-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[2-(2-methoxyethylcarbamoylamino)pyridin-4-yl]oxyphenyl]urea Chemical compound C1=NC(NC(=O)NCCOC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(OC)=CC=3)=CC=2)Cl)=C1 PRRTTXQJXYIWIX-UHFFFAOYSA-N 0.000 claims description 2
• YBGBLFUNGGROBC-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[2-(2-morpholin-4-ylethylcarbamoylamino)pyridin-4-yl]oxyphenyl]urea Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OC=3C=C(NC(=O)NCCN4CCOCC4)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 YBGBLFUNGGROBC-UHFFFAOYSA-N 0.000 claims description 2
• NHMKKTQJKOFNIJ-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[2-(3-imidazol-1-ylpropylcarbamoylamino)pyridin-4-yl]oxyphenyl]urea Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OC=3C=C(NC(=O)NCCCN4C=NC=C4)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 NHMKKTQJKOFNIJ-UHFFFAOYSA-N 0.000 claims description 2
• QPXKCTOLMAYCEZ-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[2-(cyclopropylcarbamoylamino)pyridin-4-yl]oxyphenyl]urea Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OC=3C=C(NC(=O)NC4CC4)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 QPXKCTOLMAYCEZ-UHFFFAOYSA-N 0.000 claims description 2
• MMMMQLITLMJIGS-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[2-(methylcarbamoylamino)pyrimidin-4-yl]oxyphenyl]urea Chemical compound CNC(=O)NC1=NC=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(OC)=CC=3)=CC=2)Cl)=N1 MMMMQLITLMJIGS-UHFFFAOYSA-N 0.000 claims description 2
• AHTMBXGKCASMLK-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[6-(methylcarbamoylamino)pyrimidin-4-yl]oxyphenyl]urea Chemical compound C1=NC(NC(=O)NC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(OC)=CC=3)=CC=2)Cl)=N1 AHTMBXGKCASMLK-UHFFFAOYSA-N 0.000 claims description 2
• JWNUKWIUEVMBCP-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-[5-[2-(methylcarbamoylamino)pyridin-4-yl]oxyquinolin-8-yl]urea Chemical compound C1=NC(NC(=O)NC)=CC(OC=2C3=CC=CN=C3C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(OC)=CC=3)=CC=2)=C1 JWNUKWIUEVMBCP-UHFFFAOYSA-N 0.000 claims description 2
• MKRDTPRFOOZKLJ-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-[8-[2-(methylcarbamoylamino)pyridin-4-yl]oxyquinolin-5-yl]urea Chemical compound C1=NC(NC(=O)NC)=CC(OC=2C3=NC=CC=C3C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(OC)=CC=3)=CC=2)=C1 MKRDTPRFOOZKLJ-UHFFFAOYSA-N 0.000 claims description 2
• NKFGXRJEGVLHPA-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[2-(methylcarbamoylamino)pyrimidin-4-yl]oxyphenyl]urea Chemical compound CNC(=O)NC1=NC=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)Cl)=N1 NKFGXRJEGVLHPA-UHFFFAOYSA-N 0.000 claims description 2
• DUZLWGRPUKUKRC-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[6-(methylcarbamoylamino)pyrimidin-4-yl]oxyphenyl]urea Chemical compound C1=NC(NC(=O)NC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)Cl)=N1 DUZLWGRPUKUKRC-UHFFFAOYSA-N 0.000 claims description 2
• OVBTUBSHWNGHEB-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[[2-(methylcarbamoylamino)pyridin-4-yl]methoxy]phenyl]urea Chemical compound C1=NC(NC(=O)NC)=CC(COC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)Cl)=C1 OVBTUBSHWNGHEB-UHFFFAOYSA-N 0.000 claims description 2
• SRVVSDBSTURJMJ-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[5-[2-(methylcarbamoylamino)pyridin-4-yl]oxyquinolin-8-yl]urea Chemical compound C1=NC(NC(=O)NC)=CC(OC=2C3=CC=CN=C3C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)=C1 SRVVSDBSTURJMJ-UHFFFAOYSA-N 0.000 claims description 2
• CSEFAOSXZQCHNC-UHFFFAOYSA-N 1-[5-tert-butyl-2-[4-(hydroxymethyl)phenyl]pyrazol-3-yl]-3-[2,3-dichloro-4-[2-(2-morpholin-4-ylethylcarbamoylamino)pyridin-4-yl]oxyphenyl]urea Chemical compound C=1C=C(CO)C=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C(=C1Cl)Cl)=CC=C1OC(C=1)=CC=NC=1NC(=O)NCCN1CCOCC1 CSEFAOSXZQCHNC-UHFFFAOYSA-N 0.000 claims description 2
• BSMRUQMZPUPKCC-UHFFFAOYSA-N 1-[5-tert-butyl-2-[4-(hydroxymethyl)phenyl]pyrazol-3-yl]-3-[2,3-dichloro-4-[2-(cyclopropylcarbamoylamino)pyridin-4-yl]oxyphenyl]urea Chemical compound C=1C=C(CO)C=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C(=C1Cl)Cl)=CC=C1OC(C=1)=CC=NC=1NC(=O)NC1CC1 BSMRUQMZPUPKCC-UHFFFAOYSA-N 0.000 claims description 2
• NFEGIIQSUSSDLM-UHFFFAOYSA-N 1-[5-tert-butyl-2-[4-(hydroxymethyl)phenyl]pyrazol-3-yl]-3-[2,3-dichloro-4-[2-[2-(dimethylamino)ethylcarbamoylamino]pyridin-4-yl]oxyphenyl]urea Chemical compound C1=NC(NC(=O)NCCN(C)C)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(CO)=CC=3)=CC=2)Cl)=C1 NFEGIIQSUSSDLM-UHFFFAOYSA-N 0.000 claims description 2
• DKVWSSQEESVPSA-UHFFFAOYSA-N 1-[5-tert-butyl-2-[4-(hydroxymethyl)phenyl]pyrazol-3-yl]-3-[2,3-dichloro-4-[6-(methylcarbamoylamino)pyrimidin-4-yl]oxyphenyl]urea Chemical compound C1=NC(NC(=O)NC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(CO)=CC=3)=CC=2)Cl)=N1 DKVWSSQEESVPSA-UHFFFAOYSA-N 0.000 claims description 2
• YZZUDFVTYXDQEJ-UHFFFAOYSA-N 1-[5-tert-butyl-2-[4-(hydroxymethyl)phenyl]pyrazol-3-yl]-3-[5-[2-(methylcarbamoylamino)pyridin-4-yl]oxyquinolin-8-yl]urea Chemical compound C1=NC(NC(=O)NC)=CC(OC=2C3=CC=CN=C3C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(CO)=CC=3)=CC=2)=C1 YZZUDFVTYXDQEJ-UHFFFAOYSA-N 0.000 claims description 2
• ZLAAPNRAYFZHNK-UHFFFAOYSA-N 1-methyl-3-pyridin-2-ylurea Chemical compound CNC(=O)NC1=CC=CC=N1 ZLAAPNRAYFZHNK-UHFFFAOYSA-N 0.000 claims description 2
• MDRDQUUSTQLWDS-UHFFFAOYSA-N 4-[3-tert-butyl-5-[[2,3-dichloro-4-[2-(methylcarbamoylamino)pyridin-4-yl]oxyphenyl]carbamoylamino]pyrazol-1-yl]benzoic acid Chemical compound C1=NC(NC(=O)NC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(=CC=3)C(O)=O)=CC=2)Cl)=C1 MDRDQUUSTQLWDS-UHFFFAOYSA-N 0.000 claims description 2
• 206010006187 Breast cancer Diseases 0.000 claims description 2
• 208000026310 Breast neoplasm Diseases 0.000 claims description 2
• 206010006895 Cachexia Diseases 0.000 claims description 2
• 206010009944 Colon cancer Diseases 0.000 claims description 2
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
• 206010010741 Conjunctivitis Diseases 0.000 claims description 2
• 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 2
• 201000003883 Cystic fibrosis Diseases 0.000 claims description 2
• 206010012434 Dermatitis allergic Diseases 0.000 claims description 2
• 206010014561 Emphysema Diseases 0.000 claims description 2
• QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 2
• 206010033645 Pancreatitis Diseases 0.000 claims description 2
• 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
• 208000002205 allergic conjunctivitis Diseases 0.000 claims description 2
• 208000024998 atopic conjunctivitis Diseases 0.000 claims description 2
• 208000010668 atopic eczema Diseases 0.000 claims description 2
• 229940125388 beta agonist Drugs 0.000 claims description 2
• 208000029771 childhood onset asthma Diseases 0.000 claims description 2
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 2
• 206010017758 gastric cancer Diseases 0.000 claims description 2
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 2
• 201000001441 melanoma Diseases 0.000 claims description 2
• 229940095102 methyl benzoate Drugs 0.000 claims description 2
• QPMSRTROJIEXKZ-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]-2,2-dimethylpyrrolidine-1-carboxamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OC=3C=C(NC(=O)N4C(CCC4)(C)C)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 QPMSRTROJIEXKZ-UHFFFAOYSA-N 0.000 claims description 2
• VEWLUNVBOUIWGE-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]-2-morpholin-4-ylacetamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OC=3C=C(NC(=O)CN4CCOCC4)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 VEWLUNVBOUIWGE-UHFFFAOYSA-N 0.000 claims description 2
• CVJOJNAYZTXXLX-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]-3-chloro-2-cyanophenoxy]pyridin-2-yl]pyrrolidine-1-carboxamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(C#N)C(OC=3C=C(NC(=O)N4CCCC4)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 CVJOJNAYZTXXLX-UHFFFAOYSA-N 0.000 claims description 2
• OXYANFFCSSZNGD-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyrimidin-2-yl]-2-methoxyacetamide Chemical compound COCC(=O)NC1=NC=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)Cl)=N1 OXYANFFCSSZNGD-UHFFFAOYSA-N 0.000 claims description 2
• IVXZQBKYEVXDCC-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-2,3-difluorophenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=C(F)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)F)=C1 IVXZQBKYEVXDCC-UHFFFAOYSA-N 0.000 claims description 2
• FGAOSVCLISNSHF-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-[4-(hydroxymethyl)phenyl]pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(CO)=CC=3)=CC=2)Cl)=C1 FGAOSVCLISNSHF-UHFFFAOYSA-N 0.000 claims description 2
• CNNQFIKMULLKJN-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-[4-(hydroxymethyl)phenyl]pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]-2-morpholin-4-ylacetamide Chemical compound C=1C=C(CO)C=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C(=C1Cl)Cl)=CC=C1OC(C=1)=CC=NC=1NC(=O)CN1CCOCC1 CNNQFIKMULLKJN-UHFFFAOYSA-N 0.000 claims description 2
• DLCRSFNRWFGILM-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-[4-(hydroxymethyl)phenyl]pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]pyrrolidine-1-carboxamide Chemical compound C=1C=C(CO)C=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NC(C(=C1Cl)Cl)=CC=C1OC(C=1)=CC=NC=1NC(=O)N1CCCC1 DLCRSFNRWFGILM-UHFFFAOYSA-N 0.000 claims description 2
• XLRYXRRLGRJESM-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-[4-(hydroxymethyl)phenyl]pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyrimidin-2-yl]-2-methoxyacetamide Chemical compound COCC(=O)NC1=NC=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(CO)=CC=3)=CC=2)Cl)=N1 XLRYXRRLGRJESM-UHFFFAOYSA-N 0.000 claims description 2
• BRVXEYILXFKRHV-UHFFFAOYSA-N n-[4-[[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenyl]sulfanylmethyl]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(CSC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(OC)=CC=3)=CC=2)Cl)=C1 BRVXEYILXFKRHV-UHFFFAOYSA-N 0.000 claims description 2
• CJDHCDKZYJEROE-UHFFFAOYSA-N n-[6-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyrimidin-4-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(OC)=CC=3)=CC=2)Cl)=N1 CJDHCDKZYJEROE-UHFFFAOYSA-N 0.000 claims description 2
• ZJGQZIMHLMTNEV-UHFFFAOYSA-N n-[6-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyrimidin-4-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)Cl)=N1 ZJGQZIMHLMTNEV-UHFFFAOYSA-N 0.000 claims description 2
• HLSACCNVCQFECH-UHFFFAOYSA-N n-[6-[4-[[5-tert-butyl-2-[3-(hydroxymethyl)phenyl]pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyrimidin-4-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=C(CO)C=CC=3)=CC=2)Cl)=N1 HLSACCNVCQFECH-UHFFFAOYSA-N 0.000 claims description 2
• NNNKDWVPDQOPGX-UHFFFAOYSA-N n-[6-[4-[[5-tert-butyl-2-[4-(hydroxymethyl)phenyl]pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyrimidin-4-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(CO)=CC=3)=CC=2)Cl)=N1 NNNKDWVPDQOPGX-UHFFFAOYSA-N 0.000 claims description 2
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 2
• 201000008482 osteoarthritis Diseases 0.000 claims description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 206010039083 rhinitis Diseases 0.000 claims description 2
• 201000000306 sarcoidosis Diseases 0.000 claims description 2
• 201000009890 sinusitis Diseases 0.000 claims description 2
• 150000003431 steroids Chemical class 0.000 claims description 2
• 201000011549 stomach cancer Diseases 0.000 claims description 2
• 125000004434 sulfur atom Chemical group 0.000 claims description 2
• 229940124597 therapeutic agent Drugs 0.000 claims description 2
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 2
• USMGBMVEIONWEF-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-[2-chloro-3-cyano-4-[2-(cyclopropylcarbamoylamino)pyridin-4-yl]oxyphenyl]urea Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(C#N)C(OC=3C=C(NC(=O)NC4CC4)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 USMGBMVEIONWEF-UHFFFAOYSA-N 0.000 claims 1
• KEUPSXIYJHLGEW-UHFFFAOYSA-N 1-[5-tert-butyl-2-[4-(hydroxymethyl)phenyl]pyrazol-3-yl]-3-[8-[2-(methylcarbamoylamino)pyridin-4-yl]oxyquinolin-5-yl]urea Chemical compound C1=NC(NC(=O)NC)=CC(OC=2C3=NC=CC=C3C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(CO)=CC=3)=CC=2)=C1 KEUPSXIYJHLGEW-UHFFFAOYSA-N 0.000 claims 1
• 206010012442 Dermatitis contact Diseases 0.000 claims 1
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims 1
• 241000023320 Luma <angiosperm> Species 0.000 claims 1
• 208000010247 contact dermatitis Diseases 0.000 claims 1
• 230000006806 disease prevention Effects 0.000 claims 1
• 208000036971 interstitial lung disease 2 Diseases 0.000 claims 1
• LCDCPQHFCOBUEF-UHFFFAOYSA-N pyrrolidine-1-carboxamide Chemical compound NC(=O)N1CCCC1 LCDCPQHFCOBUEF-UHFFFAOYSA-N 0.000 claims 1
• 229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 293
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 256
• 239000000543 intermediate Substances 0.000 description 209
• 239000000243 solution Substances 0.000 description 179
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 150
• 235000019439 ethyl acetate Nutrition 0.000 description 128
• 238000000034 method Methods 0.000 description 128
• 239000000203 mixture Substances 0.000 description 120
• 239000007787 solid Substances 0.000 description 115
• 239000011541 reaction mixture Substances 0.000 description 105
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 92
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 74
• 238000006243 chemical reaction Methods 0.000 description 66
• 238000010828 elution Methods 0.000 description 64
• 229910004298 SiO 2 Inorganic materials 0.000 description 62
• 238000003818 flash chromatography Methods 0.000 description 56
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 49
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 41
• 239000000284 extract Substances 0.000 description 40
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
• 239000010410 layer Substances 0.000 description 39
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 34
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 33
• 238000005481 NMR spectroscopy Methods 0.000 description 30
• 238000002360 preparation method Methods 0.000 description 30
• 239000000725 suspension Substances 0.000 description 30
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 26
• 239000012267 brine Substances 0.000 description 26
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
• 238000000746 purification Methods 0.000 description 25
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 24
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 24
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
• 210000004027 cell Anatomy 0.000 description 24
• 239000000463 material Substances 0.000 description 24
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
• 235000013877 carbamide Nutrition 0.000 description 20
• 238000001914 filtration Methods 0.000 description 18
• 239000001257 hydrogen Substances 0.000 description 17
• 239000003921 oil Substances 0.000 description 17
• 235000019198 oils Nutrition 0.000 description 17
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 16
• 239000002253 acid Substances 0.000 description 16
• 238000010791 quenching Methods 0.000 description 16
• 230000009467 reduction Effects 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
• 239000000706 filtrate Substances 0.000 description 14
• 239000012634 fragment Substances 0.000 description 14
• 238000006722 reduction reaction Methods 0.000 description 14
• 238000005406 washing Methods 0.000 description 14
• YCDMRUXJISDWTG-UHFFFAOYSA-N 1-nitropropa-1,2-diene Chemical compound [O-][N+](=O)C=C=C YCDMRUXJISDWTG-UHFFFAOYSA-N 0.000 description 13
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 12
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 12
• 238000009472 formulation Methods 0.000 description 12
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
• 238000004519 manufacturing process Methods 0.000 description 12
• 239000012044 organic layer Substances 0.000 description 12
• 239000000047 product Substances 0.000 description 12
• 239000002904 solvent Substances 0.000 description 12
• 102000001708 Protein Isoforms Human genes 0.000 description 11
• 108010029485 Protein Isoforms Proteins 0.000 description 11
• 238000005859 coupling reaction Methods 0.000 description 11
• 230000005764 inhibitory process Effects 0.000 description 11
• 238000012360 testing method Methods 0.000 description 11
• 241000699670 Mus sp. Species 0.000 description 10
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
• 150000001412 amines Chemical class 0.000 description 10
• 239000002585 base Substances 0.000 description 10
• 239000003054 catalyst Substances 0.000 description 10
• 239000002158 endotoxin Substances 0.000 description 10
• 238000001704 evaporation Methods 0.000 description 10
• 210000004072 lung Anatomy 0.000 description 10
• 210000000440 neutrophil Anatomy 0.000 description 10
• AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 10
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 10
• 238000009825 accumulation Methods 0.000 description 9
• 230000008878 coupling Effects 0.000 description 9
• 238000010168 coupling process Methods 0.000 description 9
• 201000010099 disease Diseases 0.000 description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
• 230000008020 evaporation Effects 0.000 description 9
• 239000000843 powder Substances 0.000 description 9
• 239000002244 precipitate Substances 0.000 description 9
• 125000006239 protecting group Chemical group 0.000 description 9
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 9
• 239000000010 aprotic solvent Substances 0.000 description 8
• 239000003246 corticosteroid Substances 0.000 description 8
• KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 8
• 229940079593 drug Drugs 0.000 description 8
• 230000000694 effects Effects 0.000 description 8
• 239000003112 inhibitor Substances 0.000 description 8
• 210000002540 macrophage Anatomy 0.000 description 8
• 239000002798 polar solvent Substances 0.000 description 8
• 239000000779 smoke Substances 0.000 description 8
• 238000003756 stirring Methods 0.000 description 8
• 230000000699 topical effect Effects 0.000 description 8
• 239000003981 vehicle Substances 0.000 description 8
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
• 231100000673 dose–response relationship Toxicity 0.000 description 7
• 230000002401 inhibitory effect Effects 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• 239000002953 phosphate buffered saline Substances 0.000 description 7
• 230000026731 phosphorylation Effects 0.000 description 7
• 238000006366 phosphorylation reaction Methods 0.000 description 7
• 125000004193 piperazinyl group Chemical group 0.000 description 7
• 229910052697 platinum Inorganic materials 0.000 description 7
• 239000006228 supernatant Substances 0.000 description 7
• 230000009466 transformation Effects 0.000 description 7
• 150000003672 ureas Chemical class 0.000 description 7
• JJKWHOSQTYYFAE-UHFFFAOYSA-N 2-methoxyacetyl chloride Chemical compound COCC(Cl)=O JJKWHOSQTYYFAE-UHFFFAOYSA-N 0.000 description 6
• 235000002637 Nicotiana tabacum Nutrition 0.000 description 6
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 6
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 6
• 239000000460 chlorine Substances 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 229960001334 corticosteroids Drugs 0.000 description 6
• 239000012043 crude product Substances 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 230000008569 process Effects 0.000 description 6
• 230000001225 therapeutic effect Effects 0.000 description 6
• 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 6
• APARTNVTEDZHHU-UHFFFAOYSA-N 2-methoxy-n-(4-oxo-1h-pyridin-2-yl)acetamide Chemical compound COCC(=O)NC1=CC(O)=CC=N1 APARTNVTEDZHHU-UHFFFAOYSA-N 0.000 description 5
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• 108010010803 Gelatin Proteins 0.000 description 5
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
• 241000208125 Nicotiana Species 0.000 description 5
• 229960000583 acetic acid Drugs 0.000 description 5
• 230000009471 action Effects 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 5
• 150000001721 carbon Chemical group 0.000 description 5
• 229910052801 chlorine Inorganic materials 0.000 description 5
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 5
• MVCOAUNKQVWQHZ-UHFFFAOYSA-N doramapimod Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OCCN3CCOCC3)=CC=2)=CC(C(C)(C)C)=N1 MVCOAUNKQVWQHZ-UHFFFAOYSA-N 0.000 description 5
• 238000002866 fluorescence resonance energy transfer Methods 0.000 description 5
• 229920000159 gelatin Polymers 0.000 description 5
• 239000008273 gelatin Substances 0.000 description 5
• 235000019322 gelatine Nutrition 0.000 description 5
• 235000011852 gelatine desserts Nutrition 0.000 description 5
• 238000010438 heat treatment Methods 0.000 description 5
• 125000005647 linker group Chemical group 0.000 description 5
• 229910052751 metal Inorganic materials 0.000 description 5
• 239000002184 metal Substances 0.000 description 5
• 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 5
• 150000007530 organic bases Chemical class 0.000 description 5
• 239000012074 organic phase Substances 0.000 description 5
• 125000003386 piperidinyl group Chemical group 0.000 description 5
• 229920000136 polysorbate Polymers 0.000 description 5
• 150000003222 pyridines Chemical class 0.000 description 5
• 239000000126 substance Substances 0.000 description 5
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 5
• 238000002560 therapeutic procedure Methods 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 5
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
• ZRJJXXDQIQFZBW-UHFFFAOYSA-N (2-aminopyridin-4-yl)methanol Chemical compound NC1=CC(CO)=CC=N1 ZRJJXXDQIQFZBW-UHFFFAOYSA-N 0.000 description 4
• 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 description 4
• 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 4
• 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 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
• 206010061218 Inflammation Diseases 0.000 description 4
• 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 4
• 102000015271 Intercellular Adhesion Molecule-1 Human genes 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
• 241001465754 Metazoa Species 0.000 description 4
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
• 239000000443 aerosol Substances 0.000 description 4
• 150000001408 amides Chemical class 0.000 description 4
• 238000002474 experimental method Methods 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• 238000005984 hydrogenation reaction Methods 0.000 description 4
• 125000002883 imidazolyl group Chemical group 0.000 description 4
• 230000004054 inflammatory process Effects 0.000 description 4
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical group C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 4
• 239000008101 lactose Substances 0.000 description 4
• 125000002757 morpholinyl group Chemical group 0.000 description 4
• DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 4
• LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 description 4
• 239000000546 pharmaceutical excipient Substances 0.000 description 4
• 238000001556 precipitation Methods 0.000 description 4
• 108090000765 processed proteins & peptides Proteins 0.000 description 4
• 239000003380 propellant Substances 0.000 description 4
• 230000002685 pulmonary effect Effects 0.000 description 4
• 239000000377 silicon dioxide Substances 0.000 description 4
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 4
• 239000011877 solvent mixture Substances 0.000 description 4
• 239000000600 sorbitol Substances 0.000 description 4
• 235000010356 sorbitol Nutrition 0.000 description 4
• KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• QWQJCMSWGFVURH-UHFFFAOYSA-N 2,3-dichloro-1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(Cl)=C1Cl QWQJCMSWGFVURH-UHFFFAOYSA-N 0.000 description 3
• HQNIMNQVKVPZES-UHFFFAOYSA-N 2-amino-1h-pyridin-4-one Chemical compound NC1=CC(O)=CC=N1 HQNIMNQVKVPZES-UHFFFAOYSA-N 0.000 description 3
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical group NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 3
• 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 3
• RQMWVVBHJMUJNZ-UHFFFAOYSA-N 4-chloropyridin-2-amine Chemical compound NC1=CC(Cl)=CC=N1 RQMWVVBHJMUJNZ-UHFFFAOYSA-N 0.000 description 3
• VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 3
• 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 3
• 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 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 108090001007 Interleukin-8 Proteins 0.000 description 3
• 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 3
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
• 102100034069 MAP kinase-activated protein kinase 2 Human genes 0.000 description 3
• 101710141394 MAP kinase-activated protein kinase 2 Proteins 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 3
• 230000006181 N-acylation Effects 0.000 description 3
• 238000002835 absorbance Methods 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 125000005214 aminoheteroaryl group Chemical group 0.000 description 3
• 230000003110 anti-inflammatory effect Effects 0.000 description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
• 238000004364 calculation method Methods 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
• 235000019504 cigarettes Nutrition 0.000 description 3
• 238000003776 cleavage reaction Methods 0.000 description 3
• 239000012230 colorless oil Substances 0.000 description 3
• 238000009833 condensation Methods 0.000 description 3
• 230000005494 condensation Effects 0.000 description 3
• 238000001816 cooling Methods 0.000 description 3
• 238000010908 decantation Methods 0.000 description 3
• 238000010511 deprotection reaction Methods 0.000 description 3
• 239000006196 drop Substances 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 238000011065 in-situ storage Methods 0.000 description 3
• 229910052500 inorganic mineral Inorganic materials 0.000 description 3
• 238000002955 isolation Methods 0.000 description 3
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 3
• 235000010755 mineral Nutrition 0.000 description 3
• 239000011707 mineral Substances 0.000 description 3
• 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 3
• 239000001301 oxygen Substances 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• 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 3
• 150000003230 pyrimidines Chemical class 0.000 description 3
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
• 230000000171 quenching effect Effects 0.000 description 3
• 238000004007 reversed phase HPLC Methods 0.000 description 3
• 230000007017 scission Effects 0.000 description 3
• 150000003384 small molecules Chemical class 0.000 description 3
• 239000004094 surface-active agent Substances 0.000 description 3
• 238000010189 synthetic method Methods 0.000 description 3
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 3
• 238000000825 ultraviolet detection Methods 0.000 description 3
• AVAWMINJNRAQFS-ZCFIWIBFSA-N (3r)-n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)[C@@H]1CCNC1 AVAWMINJNRAQFS-ZCFIWIBFSA-N 0.000 description 2
• HMHWNJGOHUYVMD-UHFFFAOYSA-N (4-methylanilino)azanium;chloride Chemical compound Cl.CC1=CC=C(NN)C=C1 HMHWNJGOHUYVMD-UHFFFAOYSA-N 0.000 description 2
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 2
• LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 2
• KNPRXNCNBMLIDF-UHFFFAOYSA-N 1-[4-(2,3-dichloro-4-nitrophenoxy)pyridin-2-yl]-3-methylurea Chemical compound C1=NC(NC(=O)NC)=CC(OC=2C(=C(Cl)C(=CC=2)[N+]([O-])=O)Cl)=C1 KNPRXNCNBMLIDF-UHFFFAOYSA-N 0.000 description 2
• PARGWSHOODCFOD-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[2,3-dichloro-4-[6-[2-(dimethylamino)ethylcarbamoylamino]pyrimidin-4-yl]oxyphenyl]urea Chemical compound C1=NC(NC(=O)NCCN(C)C)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)Cl)=N1 PARGWSHOODCFOD-UHFFFAOYSA-N 0.000 description 2
• IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical class [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-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
• JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 2
• SYOANZBNGDEJFH-UHFFFAOYSA-N 2,5-dihydro-1h-triazole Chemical compound C1NNN=C1 SYOANZBNGDEJFH-UHFFFAOYSA-N 0.000 description 2
• MNZQHGLKAAGSKV-UHFFFAOYSA-N 2-methoxy-n-[4-(4-nitronaphthalen-1-yl)oxypyridin-2-yl]acetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C3=CC=CC=C3C([N+]([O-])=O)=CC=2)=C1 MNZQHGLKAAGSKV-UHFFFAOYSA-N 0.000 description 2
• CKYLZLCGQJWAKF-UHFFFAOYSA-N 2-methoxy-n-[4-(5-nitroquinolin-8-yl)oxypyridin-2-yl]acetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C3=NC=CC=C3C([N+]([O-])=O)=CC=2)=C1 CKYLZLCGQJWAKF-UHFFFAOYSA-N 0.000 description 2
• YLCOWDLPSTUUQH-UHFFFAOYSA-N 2-methoxy-n-[4-[(5-nitroquinolin-8-yl)oxymethyl]pyridin-2-yl]acetamide Chemical compound C1=NC(NC(=O)COC)=CC(COC=2C3=NC=CC=C3C([N+]([O-])=O)=CC=2)=C1 YLCOWDLPSTUUQH-UHFFFAOYSA-N 0.000 description 2
• XKXAWLQHGLJUBO-UHFFFAOYSA-N 2-methoxy-n-[4-[4-nitro-3-(trifluoromethyl)phenoxy]pyridin-2-yl]acetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C=C(C(=CC=2)[N+]([O-])=O)C(F)(F)F)=C1 XKXAWLQHGLJUBO-UHFFFAOYSA-N 0.000 description 2
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 2
• IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 2
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 2
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
• 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 2
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• 239000004322 Butylated hydroxytoluene Substances 0.000 description 2
• NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
• 102000004127 Cytokines Human genes 0.000 description 2
• 108090000695 Cytokines Proteins 0.000 description 2
• 241000588724 Escherichia coli Species 0.000 description 2
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 102000003676 Glucocorticoid Receptors Human genes 0.000 description 2
• 108090000079 Glucocorticoid Receptors Proteins 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 239000007821 HATU Substances 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
• 240000007472 Leucaena leucocephala Species 0.000 description 2
• 102000043136 MAP kinase family Human genes 0.000 description 2
• 108091054455 MAP kinase family Proteins 0.000 description 2
• 102000007399 Nuclear hormone receptor Human genes 0.000 description 2
• 108020005497 Nuclear hormone receptor Proteins 0.000 description 2
• 235000019502 Orange oil Nutrition 0.000 description 2
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
• 108091005804 Peptidases Proteins 0.000 description 2
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 108091036414 Polyinosinic:polycytidylic acid Proteins 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 238000011166 aliquoting Methods 0.000 description 2
• 125000005213 alkyl heteroaryl group Chemical group 0.000 description 2
• 150000003927 aminopyridines Chemical class 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
• 125000001246 bromo group Chemical group Br* 0.000 description 2
• JAMFGQBENKSWOF-UHFFFAOYSA-N bromo(methoxy)methane Chemical compound COCBr JAMFGQBENKSWOF-UHFFFAOYSA-N 0.000 description 2
• 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
• 229940095259 butylated hydroxytoluene Drugs 0.000 description 2
• 125000004452 carbocyclyl group Chemical group 0.000 description 2
• 238000010531 catalytic reduction reaction Methods 0.000 description 2
• 230000003833 cell viability Effects 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 239000012320 chlorinating reagent Substances 0.000 description 2
• 208000037976 chronic inflammation Diseases 0.000 description 2
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 2
• 235000015165 citric acid Nutrition 0.000 description 2
• ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 2
• 239000013058 crude material Substances 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• 235000019404 dichlorodifluoromethane Nutrition 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 239000000975 dye Substances 0.000 description 2
• 239000012039 electrophile Substances 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• 150000002170 ethers Chemical class 0.000 description 2
• WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 2
• 238000011156 evaluation Methods 0.000 description 2
• 230000001747 exhibiting effect Effects 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 239000012362 glacial acetic acid Substances 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 125000004992 haloalkylamino group Chemical group 0.000 description 2
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
• 239000012442 inert solvent Substances 0.000 description 2
• 208000027866 inflammatory disease Diseases 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 125000000468 ketone group Chemical group 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 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
• 210000000265 leukocyte Anatomy 0.000 description 2
• 238000004020 luminiscence type Methods 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 229940098779 methanesulfonic acid Drugs 0.000 description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• OLKMDXLJBGCPIS-UHFFFAOYSA-N n-[4-(2,3-dichloro-4-nitrophenoxy)pyridin-2-yl]pyrrolidine-1-carboxamide Chemical compound ClC1=C(Cl)C([N+](=O)[O-])=CC=C1OC1=CC=NC(NC(=O)N2CCCC2)=C1 OLKMDXLJBGCPIS-UHFFFAOYSA-N 0.000 description 2
• CWEDOFVUNCIXIU-UHFFFAOYSA-N n-[4-(3-chloro-2-cyano-4-nitrophenoxy)pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=C(Cl)C(=CC=2)[N+]([O-])=O)C#N)=C1 CWEDOFVUNCIXIU-UHFFFAOYSA-N 0.000 description 2
• IYZVTNJFPJFISC-UHFFFAOYSA-N n-[4-(3-fluoro-4-nitrophenoxy)pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C=C(F)C(=CC=2)[N+]([O-])=O)=C1 IYZVTNJFPJFISC-UHFFFAOYSA-N 0.000 description 2
• JDMZKIPCBAAXJU-UHFFFAOYSA-N n-[4-(4-amino-2,3-dichlorophenoxy)pyridin-2-yl]pyrrolidine-1-carboxamide Chemical compound ClC1=C(Cl)C(N)=CC=C1OC1=CC=NC(NC(=O)N2CCCC2)=C1 JDMZKIPCBAAXJU-UHFFFAOYSA-N 0.000 description 2
• NYTOWYVTYZEXCA-UHFFFAOYSA-N n-[4-(4-aminonaphthalen-1-yl)oxypyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C3=CC=CC=C3C(N)=CC=2)=C1 NYTOWYVTYZEXCA-UHFFFAOYSA-N 0.000 description 2
• SIJRGBZSVLZVKC-UHFFFAOYSA-N n-[4-[(2,3-dichloro-4-nitrophenoxy)methyl]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(COC=2C(=C(Cl)C(=CC=2)[N+]([O-])=O)Cl)=C1 SIJRGBZSVLZVKC-UHFFFAOYSA-N 0.000 description 2
• ARJJYZXGMHGPRJ-UHFFFAOYSA-N n-[4-[(2,3-dichloro-4-nitrophenoxy)methyl]pyridin-2-yl]pyrrolidine-1-carboxamide Chemical compound ClC1=C(Cl)C([N+](=O)[O-])=CC=C1OCC1=CC=NC(NC(=O)N2CCCC2)=C1 ARJJYZXGMHGPRJ-UHFFFAOYSA-N 0.000 description 2
• KIJXCHMCGNRFQQ-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]pyrrolidine-1-carboxamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OC=3C=C(NC(=O)N4CCCC4)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 KIJXCHMCGNRFQQ-UHFFFAOYSA-N 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 239000007923 nasal drop Substances 0.000 description 2
• 229940100662 nasal drops Drugs 0.000 description 2
• RJIWZDNTCBHXAL-UHFFFAOYSA-N nitroxoline Chemical compound C1=CN=C2C(O)=CC=C([N+]([O-])=O)C2=C1 RJIWZDNTCBHXAL-UHFFFAOYSA-N 0.000 description 2
• 125000006574 non-aromatic ring group Chemical group 0.000 description 2
• 239000010502 orange oil Substances 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• 230000036961 partial effect Effects 0.000 description 2
• 239000012071 phase Substances 0.000 description 2
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
• HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 2
• 229940067157 phenylhydrazine Drugs 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
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
• IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical class NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 2
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 238000012545 processing Methods 0.000 description 2
• 230000000770 proinflammatory effect Effects 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 239000000376 reactant Substances 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 230000000717 retained effect Effects 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 125000006413 ring segment Chemical group 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 238000003118 sandwich ELISA Methods 0.000 description 2
• 230000035945 sensitivity Effects 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• 238000004611 spectroscopical analysis Methods 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 229960005137 succinic acid Drugs 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 231100000419 toxicity Toxicity 0.000 description 2
• 230000001988 toxicity Effects 0.000 description 2
• 210000003437 trachea Anatomy 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 125000004784 trichloromethoxy group Chemical group ClC(O*)(Cl)Cl 0.000 description 2
• 125000004951 trihalomethoxy group Chemical group 0.000 description 2
• 230000006433 tumor necrosis factor production Effects 0.000 description 2
• 238000011144 upstream manufacturing Methods 0.000 description 2
• 235000015112 vegetable and seed oil Nutrition 0.000 description 2
• 239000008158 vegetable oil Substances 0.000 description 2
• 239000003039 volatile agent Substances 0.000 description 2
• 230000002618 waking effect Effects 0.000 description 2
• 238000010792 warming Methods 0.000 description 2
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 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
• XFQNWPYGEGCIMF-HCUGAJCMSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].[Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 XFQNWPYGEGCIMF-HCUGAJCMSA-N 0.000 description 1
• JRHPOFJADXHYBR-HTQZYQBOSA-N (1r,2r)-1-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CN[C@@H]1CCCC[C@H]1NC JRHPOFJADXHYBR-HTQZYQBOSA-N 0.000 description 1
• KZEDPVFJLQLDIZ-UHFFFAOYSA-N (5-diphenylphosphanyl-9,9-dimethylxanthen-4-yl)-diphenylphosphane Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1.C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZEDPVFJLQLDIZ-UHFFFAOYSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• 0 **CCC1(*)/C=C/C(/N)=C\*(*)/C=C1 Chemical compound **CCC1(*)/C=C/C(/N)=C\*(*)/C=C1 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
• CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-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
• CJYLPRRSAHEVAP-UHFFFAOYSA-N 1-[4-(2-aminopyridin-4-yl)oxy-2,3-dichlorophenyl]-3-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]urea Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OC=3C=C(N)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 CJYLPRRSAHEVAP-UHFFFAOYSA-N 0.000 description 1
• JPIXWCLKENSLOV-UHFFFAOYSA-N 1-[4-(4-amino-2,3-dichlorophenoxy)pyridin-2-yl]-3-(2-morpholin-4-ylethyl)urea Chemical compound ClC1=C(Cl)C(N)=CC=C1OC1=CC=NC(NC(=O)NCCN2CCOCC2)=C1 JPIXWCLKENSLOV-UHFFFAOYSA-N 0.000 description 1
• GVRXNZNMHLUHHC-UHFFFAOYSA-N 1-[4-(4-amino-2,3-dichlorophenoxy)pyridin-2-yl]-3-cyclopropylurea Chemical compound ClC1=C(Cl)C(N)=CC=C1OC1=CC=NC(NC(=O)NC2CC2)=C1 GVRXNZNMHLUHHC-UHFFFAOYSA-N 0.000 description 1
• CPLYOXRUNMOJJS-UHFFFAOYSA-N 1-[4-(4-amino-2,3-dichlorophenoxy)pyridin-2-yl]-3-methylurea Chemical compound C1=NC(NC(=O)NC)=CC(OC=2C(=C(Cl)C(N)=CC=2)Cl)=C1 CPLYOXRUNMOJJS-UHFFFAOYSA-N 0.000 description 1
• YQIYDFGYYSIASF-UHFFFAOYSA-N 1-[4-(4-amino-2,3-dichlorophenoxy)pyrimidin-2-yl]-3-methylurea Chemical compound CNC(=O)NC1=NC=CC(OC=2C(=C(Cl)C(N)=CC=2)Cl)=N1 YQIYDFGYYSIASF-UHFFFAOYSA-N 0.000 description 1
• ZGKWLOQTPUCFIH-UHFFFAOYSA-N 1-[4-[(5-aminoquinolin-8-yl)oxymethyl]pyridin-2-yl]-3-methylurea Chemical compound C1=NC(NC(=O)NC)=CC(COC=2C3=NC=CC=C3C(N)=CC=2)=C1 ZGKWLOQTPUCFIH-UHFFFAOYSA-N 0.000 description 1
• UJAQCIYOUMDQGW-UHFFFAOYSA-N 1-[6-(4-amino-2,3-dichlorophenoxy)pyrimidin-4-yl]-3-[2-(dimethylamino)ethyl]urea Chemical compound C1=NC(NC(=O)NCCN(C)C)=CC(OC=2C(=C(Cl)C(N)=CC=2)Cl)=N1 UJAQCIYOUMDQGW-UHFFFAOYSA-N 0.000 description 1
• WCVWRFPMUSKKAJ-UHFFFAOYSA-N 1-cyclopropyl-3-[4-(2,3-dichloro-4-nitrophenoxy)pyridin-2-yl]urea Chemical compound ClC1=C(Cl)C([N+](=O)[O-])=CC=C1OC1=CC=NC(NC(=O)NC2CC2)=C1 WCVWRFPMUSKKAJ-UHFFFAOYSA-N 0.000 description 1
• XVDSBUCGMJBTNO-UHFFFAOYSA-N 1-fluoro-4-nitronaphthalene Chemical compound C1=CC=C2C([N+](=O)[O-])=CC=C(F)C2=C1 XVDSBUCGMJBTNO-UHFFFAOYSA-N 0.000 description 1
• DFPYXQYWILNVAU-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 DFPYXQYWILNVAU-UHFFFAOYSA-N 0.000 description 1
• 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
• RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 description 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 1
• KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
• BESOQRFWCAJXLE-UHFFFAOYSA-N 2,3-bis(bromomethyl)-1,4-dimethoxybenzene Chemical compound COC1=CC=C(OC)C(CBr)=C1CBr BESOQRFWCAJXLE-UHFFFAOYSA-N 0.000 description 1
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• JBNWDYGOTHQHOZ-UHFFFAOYSA-N 2-[5-[4-[(4-fluorophenyl)methyl]piperidine-1-carbonyl]-6-methoxy-1-methylindol-3-yl]-n,n-dimethyl-2-oxoacetamide Chemical compound COC1=CC=2N(C)C=C(C(=O)C(=O)N(C)C)C=2C=C1C(=O)N(CC1)CCC1CC1=CC=C(F)C=C1 JBNWDYGOTHQHOZ-UHFFFAOYSA-N 0.000 description 1
• RQVKVJIRFKVPBF-VWLOTQADSA-N 2-[[(2s)-2-amino-3-phenylpropyl]amino]-3-methyl-5-naphthalen-2-yl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C([C@H](N)CNC=1N(C(C(C=2C=C3C=CC=CC3=CC=2)=C(C=2C=CN=CC=2)N=1)=O)C)C1=CC=CC=C1 RQVKVJIRFKVPBF-VWLOTQADSA-N 0.000 description 1
• YRXIMPFOTQVOHG-UHFFFAOYSA-N 2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetic acid Chemical compound OC(=O)CN(C)C(=O)OC(C)(C)C YRXIMPFOTQVOHG-UHFFFAOYSA-N 0.000 description 1
• XQCZBXHVTFVIFE-UHFFFAOYSA-N 2-amino-4-hydroxypyrimidine Chemical compound NC1=NC=CC(O)=N1 XQCZBXHVTFVIFE-UHFFFAOYSA-N 0.000 description 1
• XVANGCBQAQNWOS-UHFFFAOYSA-N 2-chloro-6-fluoro-3-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC=C(F)C(C#N)=C1Cl XVANGCBQAQNWOS-UHFFFAOYSA-N 0.000 description 1
• OQHQYWGUKAWEQX-UHFFFAOYSA-N 2-methoxy-n-[4-(3-methylsulfanyl-4-nitrophenoxy)pyridin-2-yl]acetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C=C(SC)C(=CC=2)[N+]([O-])=O)=C1 OQHQYWGUKAWEQX-UHFFFAOYSA-N 0.000 description 1
• MXZIYNBLDDUWLA-UHFFFAOYSA-N 2-methoxy-n-[4-(3-methylsulfonyl-4-nitrophenoxy)pyridin-2-yl]acetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C=C(C(=CC=2)[N+]([O-])=O)S(C)(=O)=O)=C1 MXZIYNBLDDUWLA-UHFFFAOYSA-N 0.000 description 1
• DYSMAVOOSSHLRE-UHFFFAOYSA-N 2-methoxy-n-[4-[(7-nitro-1h-indazol-4-yl)oxy]pyridin-2-yl]acetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C=3C=NNC=3C([N+]([O-])=O)=CC=2)=C1 DYSMAVOOSSHLRE-UHFFFAOYSA-N 0.000 description 1
• RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
• UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
• OZHRTFVZNKBMRU-UHFFFAOYSA-N 3-(1-methylcyclohexyl)-3-oxopropanenitrile Chemical compound N#CCC(=O)C1(C)CCCCC1 OZHRTFVZNKBMRU-UHFFFAOYSA-N 0.000 description 1
• FTZIQBGFCYJWKA-UHFFFAOYSA-N 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Chemical compound S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 FTZIQBGFCYJWKA-UHFFFAOYSA-N 0.000 description 1
• VYFIHEYIPLYBHE-UHFFFAOYSA-N 3-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]-1,1-dimethylurea Chemical compound C1=NC(NC(=O)N(C)C)=CC(OC=2C(=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)Cl)=C1 VYFIHEYIPLYBHE-UHFFFAOYSA-N 0.000 description 1
• VTSFNCCQCOEPKF-UHFFFAOYSA-N 3-amino-1h-pyridin-2-one Chemical compound NC1=CC=CN=C1O VTSFNCCQCOEPKF-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• CSSGKHVRDGATJL-UHFFFAOYSA-N 3-fluoro-4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C(F)=C1 CSSGKHVRDGATJL-UHFFFAOYSA-N 0.000 description 1
• MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
• MXZMACXOMZKYHJ-UHFFFAOYSA-N 4,4-dimethyl-3-oxopentanenitrile Chemical compound CC(C)(C)C(=O)CC#N MXZMACXOMZKYHJ-UHFFFAOYSA-N 0.000 description 1
• BSCYAFYSUZNOOH-UHFFFAOYSA-N 4-(2,3-dichloro-4-nitrophenoxy)pyridin-2-amine Chemical compound C1=NC(N)=CC(OC=2C(=C(Cl)C(=CC=2)[N+]([O-])=O)Cl)=C1 BSCYAFYSUZNOOH-UHFFFAOYSA-N 0.000 description 1
• PDFUCZDRWNBISJ-UHFFFAOYSA-N 4-(2,3-dichloro-4-nitrophenoxy)pyrimidin-2-amine Chemical compound NC1=NC=CC(OC=2C(=C(Cl)C(=CC=2)[N+]([O-])=O)Cl)=N1 PDFUCZDRWNBISJ-UHFFFAOYSA-N 0.000 description 1
• PQABCDBTGRKXFR-UHFFFAOYSA-N 4-(3-fluoro-4-nitrophenoxy)pyridin-2-amine Chemical compound C1=NC(N)=CC(OC=2C=C(F)C(=CC=2)[N+]([O-])=O)=C1 PQABCDBTGRKXFR-UHFFFAOYSA-N 0.000 description 1
• DDODWNHIQONPBN-UHFFFAOYSA-N 4-(4-amino-2,3-dichlorophenoxy)pyridin-2-amine Chemical compound C1=NC(N)=CC(OC=2C(=C(Cl)C(N)=CC=2)Cl)=C1 DDODWNHIQONPBN-UHFFFAOYSA-N 0.000 description 1
• ZYLBTAJGPCACPI-UHFFFAOYSA-N 4-(4-nitronaphthalen-1-yl)oxypyridin-2-amine Chemical compound C1=NC(N)=CC(OC=2C3=CC=CC=C3C([N+]([O-])=O)=CC=2)=C1 ZYLBTAJGPCACPI-UHFFFAOYSA-N 0.000 description 1
• VXJUKFKTTJFHHP-UHFFFAOYSA-N 4-(bromomethyl)pyridin-2-amine;hydrobromide Chemical compound Br.NC1=CC(CBr)=CC=N1 VXJUKFKTTJFHHP-UHFFFAOYSA-N 0.000 description 1
• RDTALXUBMCLWBB-UHFFFAOYSA-N 4-(dimethylamino)butanoic acid;hydron;chloride Chemical compound Cl.CN(C)CCCC(O)=O RDTALXUBMCLWBB-UHFFFAOYSA-N 0.000 description 1
• QJNKEJNQTOLGTB-UHFFFAOYSA-N 4-[(2,3-dichloro-4-nitrophenoxy)methyl]pyridin-2-amine Chemical compound C1=NC(N)=CC(COC=2C(=C(Cl)C(=CC=2)[N+]([O-])=O)Cl)=C1 QJNKEJNQTOLGTB-UHFFFAOYSA-N 0.000 description 1
• GMCDNQFFPFNCSR-UHFFFAOYSA-N 4-[(2,3-dichloro-4-nitrophenyl)sulfanylmethyl]pyridin-2-amine Chemical compound C1=NC(N)=CC(CSC=2C(=C(Cl)C(=CC=2)[N+]([O-])=O)Cl)=C1 GMCDNQFFPFNCSR-UHFFFAOYSA-N 0.000 description 1
• KRQVCLFOYAXMHP-UHFFFAOYSA-N 4-[(5-nitroquinolin-8-yl)oxymethyl]pyridin-2-amine Chemical compound C1=NC(N)=CC(COC=2C3=NC=CC=C3C([N+]([O-])=O)=CC=2)=C1 KRQVCLFOYAXMHP-UHFFFAOYSA-N 0.000 description 1
• MHFCCNPOKQZTIF-UHFFFAOYSA-N 4-[(7-nitro-1h-indazol-4-yl)oxy]pyridin-2-amine Chemical compound C1=NC(N)=CC(OC=2C=3C=NNC=3C([N+]([O-])=O)=CC=2)=C1 MHFCCNPOKQZTIF-UHFFFAOYSA-N 0.000 description 1
• WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
• UGEHZDRDLBACDW-UHFFFAOYSA-N 4-chloro-2-methylsulfanyl-1-nitrobenzene Chemical compound CSC1=CC(Cl)=CC=C1[N+]([O-])=O UGEHZDRDLBACDW-UHFFFAOYSA-N 0.000 description 1
• MBVFRSJFKMJRHA-UHFFFAOYSA-N 4-fluoro-1-benzofuran-7-carbaldehyde Chemical compound FC1=CC=C(C=O)C2=C1C=CO2 MBVFRSJFKMJRHA-UHFFFAOYSA-N 0.000 description 1
• WMQOSURXFLBTPC-UHFFFAOYSA-N 4-fluoro-1-nitro-2-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1C(F)(F)F WMQOSURXFLBTPC-UHFFFAOYSA-N 0.000 description 1
• CVMZDSQFDHLYSI-UHFFFAOYSA-N 4-fluoro-7-nitro-1h-indazole Chemical compound [O-][N+](=O)C1=CC=C(F)C2=C1NN=C2 CVMZDSQFDHLYSI-UHFFFAOYSA-N 0.000 description 1
• QQFBGOVNOFZJRI-UHFFFAOYSA-N 4-iodo-2-methoxy-3-methylbenzoic acid Chemical compound COC1=C(C)C(I)=CC=C1C(O)=O QQFBGOVNOFZJRI-UHFFFAOYSA-N 0.000 description 1
• 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 1
• KBIWNQVZKHSHTI-UHFFFAOYSA-N 4-n,4-n-dimethylbenzene-1,4-diamine;oxalic acid Chemical compound OC(=O)C(O)=O.CN(C)C1=CC=C(N)C=C1 KBIWNQVZKHSHTI-UHFFFAOYSA-N 0.000 description 1
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• JQIGAULVLCHDEJ-UHFFFAOYSA-N 5-(1-methylcyclohexyl)-2-(4-methylphenyl)pyrazol-3-amine Chemical compound C1=CC(C)=CC=C1N1C(N)=CC(C2(C)CCCCC2)=N1 JQIGAULVLCHDEJ-UHFFFAOYSA-N 0.000 description 1
• BUNGLKKPGWGZDC-UHFFFAOYSA-N 5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-amine Chemical compound C1=CC(OC)=CC=C1N1C(N)=CC(C(C)(C)C)=N1 BUNGLKKPGWGZDC-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
• SBNPFFZBQPGGBH-UHFFFAOYSA-N 5-tert-butyl-2-(4-methylsulfanylphenyl)pyrazol-3-amine Chemical compound C1=CC(SC)=CC=C1N1C(N)=CC(C(C)(C)C)=N1 SBNPFFZBQPGGBH-UHFFFAOYSA-N 0.000 description 1
• KTDJUMGGQMHTDC-UHFFFAOYSA-N 5-tert-butyl-2-[4-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-methoxyphenyl]pyrazol-3-amine Chemical compound C1=C(CO[Si](C)(C)C(C)(C)C)C(OC)=CC(N2C(=CC(=N2)C(C)(C)C)N)=C1 KTDJUMGGQMHTDC-UHFFFAOYSA-N 0.000 description 1
• WKYYYFIJGMOIOL-UHFFFAOYSA-N 5-tert-butyl-2-[4-[[tert-butyl(dimethyl)silyl]oxymethyl]phenyl]pyrazol-3-amine Chemical compound N1=C(C(C)(C)C)C=C(N)N1C1=CC=C(CO[Si](C)(C)C(C)(C)C)C=C1 WKYYYFIJGMOIOL-UHFFFAOYSA-N 0.000 description 1
• CHZKWWDHOLXMRZ-UHFFFAOYSA-N 5-tert-butyl-2-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]pyrazol-3-amine Chemical compound N1=C(C(C)(C)C)C=C(N)N1C1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1 CHZKWWDHOLXMRZ-UHFFFAOYSA-N 0.000 description 1
• GKJOFZNOEXAKQP-UHFFFAOYSA-N 6-(2,3-dichloro-4-nitrophenoxy)pyrimidin-4-amine Chemical compound C1=NC(N)=CC(OC=2C(=C(Cl)C(=CC=2)[N+]([O-])=O)Cl)=N1 GKJOFZNOEXAKQP-UHFFFAOYSA-N 0.000 description 1
• FYSRKRZDBHOFAY-UHFFFAOYSA-N 6-(N-carbamoyl-2,6-difluoroanilino)-2-(2,4-difluorophenyl)-3-pyridinecarboxamide Chemical compound FC=1C=CC=C(F)C=1N(C(=O)N)C(N=1)=CC=C(C(N)=O)C=1C1=CC=C(F)C=C1F FYSRKRZDBHOFAY-UHFFFAOYSA-N 0.000 description 1
• HFMLLTVIMFEQRE-UHFFFAOYSA-N 6-amino-1h-pyrimidin-4-one Chemical compound NC1=CC(O)=NC=N1 HFMLLTVIMFEQRE-UHFFFAOYSA-N 0.000 description 1
• WOSYAMNMWPZLGF-UHFFFAOYSA-N 8-fluoro-5-nitroquinoline Chemical compound C1=CC=C2C([N+](=O)[O-])=CC=C(F)C2=N1 WOSYAMNMWPZLGF-UHFFFAOYSA-N 0.000 description 1
• AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 1
• FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 1
• 235000019489 Almond oil Nutrition 0.000 description 1
• 241000416162 Astragalus gummifer Species 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
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• 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 1
• HEPIMOPHMVHJHF-UHFFFAOYSA-N COC(C(N)=O)c1cc(CSc2ccc(NC(=O)Nc3cc(nn3-c3ccc(OC)cc3)C(C)(C)C)c(Cl)c2Cl)ccn1 Chemical compound COC(C(N)=O)c1cc(CSc2ccc(NC(=O)Nc3cc(nn3-c3ccc(OC)cc3)C(C)(C)C)c(Cl)c2Cl)ccn1 HEPIMOPHMVHJHF-UHFFFAOYSA-N 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• HJEOUECVDLFDBV-UHFFFAOYSA-N ClC1=C(Cl)C([N+](=O)[O-])=CC=C1OC1=CC=NC(NC(=O)CN2CCOCC2)=C1 Chemical compound ClC1=C(Cl)C([N+](=O)[O-])=CC=C1OC1=CC=NC(NC(=O)CN2CCOCC2)=C1 HJEOUECVDLFDBV-UHFFFAOYSA-N 0.000 description 1
• SGHJTVGWDWZJAB-UHFFFAOYSA-N ClC1=C(OC2=CC(=NC=C2)NC(N)=O)C=CC(=C1Cl)[N+](=O)[O-] Chemical compound ClC1=C(OC2=CC(=NC=C2)NC(N)=O)C=CC(=C1Cl)[N+](=O)[O-] SGHJTVGWDWZJAB-UHFFFAOYSA-N 0.000 description 1
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 101100457345 Danio rerio mapk14a gene Proteins 0.000 description 1
• 101100457347 Danio rerio mapk14b gene Proteins 0.000 description 1
• 201000004624 Dermatitis Diseases 0.000 description 1
• 206010012438 Dermatitis atopic Diseases 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical class COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 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
• 238000002965 ELISA Methods 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
• 208000018522 Gastrointestinal disease Diseases 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 239000007995 HEPES buffer Substances 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
• 101000599852 Homo sapiens Intercellular adhesion molecule 1 Proteins 0.000 description 1
• 101000628954 Homo sapiens Mitogen-activated protein kinase 12 Proteins 0.000 description 1
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
• 102100037877 Intercellular adhesion molecule 1 Human genes 0.000 description 1
• 239000002841 Lewis acid Substances 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 208000019693 Lung disease Diseases 0.000 description 1
• 108700012928 MAPK14 Proteins 0.000 description 1
• 238000000134 MTT assay Methods 0.000 description 1
• 231100000002 MTT assay Toxicity 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
• 101150003941 Mapk14 gene Proteins 0.000 description 1
• 239000004430 Mapka Substances 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 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
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-methylmorpholine Substances CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 1
• XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methylthiourea Natural products CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 description 1
• IKEUKNFIGWZUDB-UHFFFAOYSA-N NC(NC(C=CC(OC1=CC(NC(NC2CC2)=O)=NC=C1)=C1C#N)=C1Cl)=O Chemical compound NC(NC(C=CC(OC1=CC(NC(NC2CC2)=O)=NC=C1)=C1C#N)=C1Cl)=O IKEUKNFIGWZUDB-UHFFFAOYSA-N 0.000 description 1
• 244000061176 Nicotiana tabacum Species 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 208000030880 Nose disease Diseases 0.000 description 1
• 239000012425 OXONE® Substances 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 208000021063 Respiratory fume inhalation disease Diseases 0.000 description 1
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 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
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-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
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 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
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 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
• 208000025865 Ulcer Diseases 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• OTHOKCUOYUULCR-UHFFFAOYSA-N [4-(5-amino-3-tert-butylpyrazol-1-yl)-2-methoxyphenyl]methanol Chemical compound C1=C(CO)C(OC)=CC(N2C(=CC(=N2)C(C)(C)C)N)=C1 OTHOKCUOYUULCR-UHFFFAOYSA-N 0.000 description 1
• FYJKEHKQUPSJDH-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;potassium Chemical compound [K].C[Si](C)(C)N[Si](C)(C)C FYJKEHKQUPSJDH-UHFFFAOYSA-N 0.000 description 1
• 150000007960 acetonitrile Chemical class 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 229960001456 adenosine triphosphate Drugs 0.000 description 1
• 230000002411 adverse Effects 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
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 125000003282 alkyl amino group Chemical group 0.000 description 1
• 125000005037 alkyl phenyl group Chemical group 0.000 description 1
• 239000008168 almond oil Substances 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 210000001132 alveolar macrophage Anatomy 0.000 description 1
• 238000007112 amidation reaction Methods 0.000 description 1
• 125000006242 amine protecting group Chemical group 0.000 description 1
• 150000001414 amino alcohols Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 150000005005 aminopyrimidines Chemical class 0.000 description 1
• 229960004909 aminosalicylic acid Drugs 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
• 239000003443 antiviral agent Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 150000004982 aromatic amines Chemical class 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 125000005604 azodicarboxylate group Chemical group 0.000 description 1
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 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
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 238000004820 blood count Methods 0.000 description 1
• 229910000085 borane Inorganic materials 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 210000000424 bronchial epithelial cell Anatomy 0.000 description 1
• 229960004436 budesonide Drugs 0.000 description 1
• 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 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
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 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
• 229940105329 carboxymethylcellulose Drugs 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 238000005341 cation exchange Methods 0.000 description 1
• 238000003570 cell viability assay Methods 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 238000011944 chemoselective reduction Methods 0.000 description 1
• 238000005660 chlorination reaction Methods 0.000 description 1
• KYKAJFCTULSVSH-UHFFFAOYSA-N chloro(fluoro)methane Chemical compound F[C]Cl KYKAJFCTULSVSH-UHFFFAOYSA-N 0.000 description 1
• LUULLKSXBMRSPR-UHFFFAOYSA-N chloro(trimethyl)silane Chemical compound C[Si](C)(C)Cl.C[Si](C)(C)Cl LUULLKSXBMRSPR-UHFFFAOYSA-N 0.000 description 1
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
• 239000000812 cholinergic antagonist Substances 0.000 description 1
• 230000001684 chronic effect Effects 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
• 238000004440 column chromatography Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 235000001671 coumarin Nutrition 0.000 description 1
• 229960000956 coumarin Drugs 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 238000003235 crystal violet staining Methods 0.000 description 1
• 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
• OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical group NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000017858 demethylation Effects 0.000 description 1
• 238000010520 demethylation reaction Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 239000011903 deuterated solvents‎ Substances 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
• 238000007865 diluting Methods 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 230000009266 disease activity Effects 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 239000000890 drug combination Substances 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 239000008157 edible vegetable oil Substances 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• FDLDWKIEWAWOSL-UHFFFAOYSA-N ethyl acetate;2-methylpentane Chemical compound CCCC(C)C.CCOC(C)=O FDLDWKIEWAWOSL-UHFFFAOYSA-N 0.000 description 1
• UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
• 239000012894 fetal calf serum Substances 0.000 description 1
• 239000000945 filler Substances 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
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
• 238000001917 fluorescence detection Methods 0.000 description 1
• 239000007850 fluorescent dye Substances 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
• 229960001469 fluticasone furoate Drugs 0.000 description 1
• XTULMSXFIHGYFS-VLSRWLAYSA-N fluticasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(F)[C@@]4(C)C=CC(=O)C=C4[C@@H](F)C[C@H]3[C@@H]2C[C@H]1C)C(=O)SCF)C(=O)C1=CC=CO1 XTULMSXFIHGYFS-VLSRWLAYSA-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
• 239000012458 free base Substances 0.000 description 1
• 239000012737 fresh medium Substances 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical class NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 description 1
• 229960004275 glycolic acid Drugs 0.000 description 1
• 239000010439 graphite Substances 0.000 description 1
• 229910002804 graphite Inorganic materials 0.000 description 1
• 150000005748 halopyridines Chemical class 0.000 description 1
• 239000007887 hard shell capsule Substances 0.000 description 1
• 210000002216 heart 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
• 150000004677 hydrates Chemical class 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
• 238000007654 immersion Methods 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 206010022000 influenza Diseases 0.000 description 1
• 230000004941 influx Effects 0.000 description 1
• 229940125369 inhaled corticosteroids Drugs 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 230000021995 interleukin-8 production Effects 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 238000010829 isocratic elution Methods 0.000 description 1
• 239000012948 isocyanate Substances 0.000 description 1
• 150000002513 isocyanates Chemical class 0.000 description 1
• DBBRJAWSDTYYBM-UHFFFAOYSA-N isocyanatocyclopropane Chemical compound O=C=NC1CC1 DBBRJAWSDTYYBM-UHFFFAOYSA-N 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 229960000448 lactic acid Drugs 0.000 description 1
• 150000007517 lewis acids Chemical class 0.000 description 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
• 239000006193 liquid solution Substances 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 210000004185 liver Anatomy 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
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• RMIODHQZRUFFFF-UHFFFAOYSA-N methoxyacetic acid Chemical compound COCC(O)=O RMIODHQZRUFFFF-UHFFFAOYSA-N 0.000 description 1
• NKZISBBWNQEPAH-UHFFFAOYSA-N methyl 1-methylcyclohexane-1-carboxylate Chemical compound COC(=O)C1(C)CCCCC1 NKZISBBWNQEPAH-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
• 235000013336 milk Nutrition 0.000 description 1
• 239000008267 milk Substances 0.000 description 1
• 210000004080 milk Anatomy 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 239000003226 mitogen Substances 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 238000003032 molecular docking Methods 0.000 description 1
• 229910052750 molybdenum Inorganic materials 0.000 description 1
• 229960002744 mometasone furoate Drugs 0.000 description 1
• WOFMFGQZHJDGCX-ZULDAHANSA-N mometasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(Cl)[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@H]1C)C(=O)CCl)C(=O)C1=CC=CO1 WOFMFGQZHJDGCX-ZULDAHANSA-N 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
• 210000004877 mucosa Anatomy 0.000 description 1
• GKUCGVQIDDQHIP-UHFFFAOYSA-N n-[4-(4-amino-2,3-dichlorophenoxy)pyrimidin-2-yl]-2-methoxyacetamide Chemical compound COCC(=O)NC1=NC=CC(OC=2C(=C(Cl)C(N)=CC=2)Cl)=N1 GKUCGVQIDDQHIP-UHFFFAOYSA-N 0.000 description 1
• ZUTBYPMKCZJAFB-UHFFFAOYSA-N n-[4-(4-amino-3-chloro-2-cyanophenoxy)pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=C(Cl)C(N)=CC=2)C#N)=C1 ZUTBYPMKCZJAFB-UHFFFAOYSA-N 0.000 description 1
• AWMKBRJOTXQXTK-UHFFFAOYSA-N n-[4-(4-amino-3-fluorophenoxy)pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C=C(F)C(N)=CC=2)=C1 AWMKBRJOTXQXTK-UHFFFAOYSA-N 0.000 description 1
• MUZTWBREHAZJEP-UHFFFAOYSA-N n-[4-(4-amino-3-methylsulfonylphenoxy)pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C=C(C(N)=CC=2)S(C)(=O)=O)=C1 MUZTWBREHAZJEP-UHFFFAOYSA-N 0.000 description 1
• INBIZRCOHZGVNV-UHFFFAOYSA-N n-[4-(5-aminoquinolin-8-yl)oxypyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C3=NC=CC=C3C(N)=CC=2)=C1 INBIZRCOHZGVNV-UHFFFAOYSA-N 0.000 description 1
• YZFOZVXPKUWDPE-UHFFFAOYSA-N n-[4-[(2,3-dichloro-4-nitrophenyl)sulfanylmethyl]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(CSC=2C(=C(Cl)C(=CC=2)[N+]([O-])=O)Cl)=C1 YZFOZVXPKUWDPE-UHFFFAOYSA-N 0.000 description 1
• MMWMXCVVEVFWJS-UHFFFAOYSA-N n-[4-[(4-amino-2,3-dichlorophenoxy)methyl]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(COC=2C(=C(Cl)C(N)=CC=2)Cl)=C1 MMWMXCVVEVFWJS-UHFFFAOYSA-N 0.000 description 1
• PJQBDJJWHAXGJH-UHFFFAOYSA-N n-[4-[(4-amino-2,3-dichlorophenoxy)methyl]pyridin-2-yl]pyrrolidine-1-carboxamide Chemical compound ClC1=C(Cl)C(N)=CC=C1OCC1=CC=NC(NC(=O)N2CCCC2)=C1 PJQBDJJWHAXGJH-UHFFFAOYSA-N 0.000 description 1
• FONWDIZRGNLQAW-UHFFFAOYSA-N n-[4-[(4-amino-2,3-dichlorophenyl)sulfanylmethyl]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(CSC=2C(=C(Cl)C(N)=CC=2)Cl)=C1 FONWDIZRGNLQAW-UHFFFAOYSA-N 0.000 description 1
• QIWOVRRUUPFEIB-UHFFFAOYSA-N n-[4-[(5-aminoquinolin-8-yl)oxymethyl]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(COC=2C3=NC=CC=C3C(N)=CC=2)=C1 QIWOVRRUUPFEIB-UHFFFAOYSA-N 0.000 description 1
• KDDMPLYVXHJXBX-UHFFFAOYSA-N n-[4-[(5-aminoquinolin-8-yl)oxymethyl]pyridin-2-yl]pyrrolidine-1-carboxamide Chemical compound C12=NC=CC=C2C(N)=CC=C1OCC(C=1)=CC=NC=1NC(=O)N1CCCC1 KDDMPLYVXHJXBX-UHFFFAOYSA-N 0.000 description 1
• WZTODJSVSXVLSQ-UHFFFAOYSA-N n-[4-[(7-amino-1h-indazol-4-yl)oxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C=3C=NNC=3C(N)=CC=2)=C1 WZTODJSVSXVLSQ-UHFFFAOYSA-N 0.000 description 1
• IRACFNPOYFDTAE-UHFFFAOYSA-N n-[4-[2-bromo-4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]phenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=CC(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)Br)=C1 IRACFNPOYFDTAE-UHFFFAOYSA-N 0.000 description 1
• WWDLBEFLCLNAIH-UHFFFAOYSA-N n-[4-[3-bromo-4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]phenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C=C(Br)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)=C1 WWDLBEFLCLNAIH-UHFFFAOYSA-N 0.000 description 1
• TWDRTUOIZCNWSB-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dichlorophenoxy]pyridin-2-yl]-1,3-dihydroisoindole-2-carboxamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(Cl)C(OC=3C=C(NC(=O)N4CC5=CC=CC=C5C4)N=CC=3)=CC=2)Cl)=CC(C(C)(C)C)=N1 TWDRTUOIZCNWSB-UHFFFAOYSA-N 0.000 description 1
• JANPGMQDVZLNRS-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-2-chlorophenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C(=CC(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)Cl)=C1 JANPGMQDVZLNRS-UHFFFAOYSA-N 0.000 description 1
• OZKWRAYSJOTLAP-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]-3-chlorophenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C=C(Cl)C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)=C1 OZKWRAYSJOTLAP-UHFFFAOYSA-N 0.000 description 1
• AVUUHIYJPTWYNX-UHFFFAOYSA-N n-[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C3=CC=CC=C3C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)=C1 AVUUHIYJPTWYNX-UHFFFAOYSA-N 0.000 description 1
• GJAYSUGFBVVQKM-UHFFFAOYSA-N n-[4-[4-amino-3-(trifluoromethyl)phenoxy]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C=C(C(N)=CC=2)C(F)(F)F)=C1 GJAYSUGFBVVQKM-UHFFFAOYSA-N 0.000 description 1
• VXRQDEQIKFKWIV-UHFFFAOYSA-N n-[4-[8-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]quinolin-5-yl]oxypyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(OC=2C3=CC=CN=C3C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)=C1 VXRQDEQIKFKWIV-UHFFFAOYSA-N 0.000 description 1
• UUDYZFKBRVQSSX-UHFFFAOYSA-N n-[6-(2,3-dichloro-4-nitrophenoxy)pyrimidin-4-yl]-4-(dimethylamino)butanamide Chemical compound C1=NC(NC(=O)CCCN(C)C)=CC(OC=2C(=C(Cl)C(=CC=2)[N+]([O-])=O)Cl)=N1 UUDYZFKBRVQSSX-UHFFFAOYSA-N 0.000 description 1
• OVWSLMBKKLDENQ-UHFFFAOYSA-N n-[6-(4-amino-2,3-dichlorophenoxy)pyrimidin-4-yl]-4-(dimethylamino)butanamide Chemical compound C1=NC(NC(=O)CCCN(C)C)=CC(OC=2C(=C(Cl)C(N)=CC=2)Cl)=N1 OVWSLMBKKLDENQ-UHFFFAOYSA-N 0.000 description 1
• RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 1
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
• 150000002790 naphthalenes Chemical class 0.000 description 1
• 125000004957 naphthylene group Chemical group 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 238000006386 neutralization reaction Methods 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• PSACHCMMPFMFAJ-UHFFFAOYSA-N nmm n-methylmorpholine Chemical compound CN1CCOCC1.CN1CCOCC1 PSACHCMMPFMFAJ-UHFFFAOYSA-N 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 1
• 239000012038 nucleophile Substances 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 235000014593 oils and fats Nutrition 0.000 description 1
• 239000003605 opacifier Substances 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• IVMHDOBGNQOUHO-UHFFFAOYSA-N oxathiane Chemical compound C1CCSOC1 IVMHDOBGNQOUHO-UHFFFAOYSA-N 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
• 102000013415 peroxidase activity proteins Human genes 0.000 description 1
• 108040007629 peroxidase activity proteins Proteins 0.000 description 1
• 230000002688 persistence Effects 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 1
• RDNFUEALAUVXBO-UHFFFAOYSA-N phenyl N-[6-(4-amino-2,3-dichlorophenoxy)pyrimidin-4-yl]-N-phenoxycarbonylcarbamate Chemical compound Nc1ccc(Oc2cc(ncn2)N(C(=O)Oc2ccccc2)C(=O)Oc2ccccc2)c(Cl)c1Cl RDNFUEALAUVXBO-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
• QIIPQYDSKRYMFG-UHFFFAOYSA-N phenyl hydrogen carbonate Chemical compound OC(=O)OC1=CC=CC=C1 QIIPQYDSKRYMFG-UHFFFAOYSA-N 0.000 description 1
• ULAILTQVTCEUMP-UHFFFAOYSA-N phenyl n-[4-(4-amino-2,3-dichlorophenoxy)pyridin-2-yl]-n-phenoxycarbonylcarbamate Chemical compound ClC1=C(Cl)C(N)=CC=C1OC1=CC=NC(N(C(=O)OC=2C=CC=CC=2)C(=O)OC=2C=CC=CC=2)=C1 ULAILTQVTCEUMP-UHFFFAOYSA-N 0.000 description 1
• FOXXAQRNEIMDEC-UHFFFAOYSA-N phenyl n-phenoxycarbonylcarbamate Chemical compound C=1C=CC=CC=1OC(=O)NC(=O)OC1=CC=CC=C1 FOXXAQRNEIMDEC-UHFFFAOYSA-N 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
• 239000004014 plasticizer Substances 0.000 description 1
• 229920001515 polyalkylene glycol Polymers 0.000 description 1
• 125000003367 polycyclic group Chemical group 0.000 description 1
• 229920000728 polyester Polymers 0.000 description 1
• 229940057838 polyethylene glycol 4000 Drugs 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• AVTYONGGKAJVTE-OLXYHTOASA-L potassium L-tartrate Chemical compound [K+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O AVTYONGGKAJVTE-OLXYHTOASA-L 0.000 description 1
• IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
• OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 1
• 239000001472 potassium tartrate Substances 0.000 description 1
• 229940111695 potassium tartrate Drugs 0.000 description 1
• 235000011005 potassium tartrates Nutrition 0.000 description 1
• ZRLVQFQTCMUIRM-UHFFFAOYSA-N potassium;2-methylbutan-2-olate Chemical compound [K+].CCC(C)(C)[O-] ZRLVQFQTCMUIRM-UHFFFAOYSA-N 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 229940095574 propionic acid Drugs 0.000 description 1
• 235000013772 propylene glycol Nutrition 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 239000003586 protic polar solvent Substances 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 230000005588 protonation Effects 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
• DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
• LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
• DNENQQPLJPZMGZ-UHFFFAOYSA-N pyrimidin-2-ylurea Chemical class NC(=O)NC1=NC=CC=N1 DNENQQPLJPZMGZ-UHFFFAOYSA-N 0.000 description 1
• FUXJMHXHGDAHPD-UHFFFAOYSA-N pyrimidine-2-carboxamide Chemical compound NC(=O)C1=NC=CC=N1 FUXJMHXHGDAHPD-UHFFFAOYSA-N 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 239000012048 reactive intermediate Substances 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 230000007115 recruitment Effects 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• DPZNOMCNRMUKPS-UHFFFAOYSA-N resorcinol dimethyl ether Natural products COC1=CC=CC(OC)=C1 DPZNOMCNRMUKPS-UHFFFAOYSA-N 0.000 description 1
• 229960002052 salbutamol Drugs 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 229960004017 salmeterol Drugs 0.000 description 1
• 150000003333 secondary alcohols Chemical class 0.000 description 1
• 230000001235 sensitizing effect Effects 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 235000020374 simple syrup Nutrition 0.000 description 1
• 210000002027 skeletal muscle Anatomy 0.000 description 1
• 208000017520 skin disease Diseases 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• PNGLEYLFMHGIQO-UHFFFAOYSA-M sodium;3-(n-ethyl-3-methoxyanilino)-2-hydroxypropane-1-sulfonate;dihydrate Chemical compound O.O.[Na+].[O-]S(=O)(=O)CC(O)CN(CC)C1=CC=CC(OC)=C1 PNGLEYLFMHGIQO-UHFFFAOYSA-M 0.000 description 1
• 235000019337 sorbitan trioleate Nutrition 0.000 description 1
• 229960000391 sorbitan trioleate Drugs 0.000 description 1
• 229940046810 spiriva Drugs 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 239000001384 succinic acid Substances 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
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000006188 syrup Substances 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
• ZMELOYOKMZBMRB-DLBZAZTESA-N talmapimod Chemical compound C([C@@H](C)N(C[C@@H]1C)C(=O)C=2C(=CC=3N(C)C=C(C=3C=2)C(=O)C(=O)N(C)C)Cl)N1CC1=CC=C(F)C=C1 ZMELOYOKMZBMRB-DLBZAZTESA-N 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229960000195 terbutaline Drugs 0.000 description 1
• 210000001550 testis Anatomy 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000006173 tetrahydropyranylmethyl group Chemical group 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 229960000278 theophylline Drugs 0.000 description 1
• 150000003568 thioethers Chemical class 0.000 description 1
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical group 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 1
• 229940110309 tiotropium Drugs 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 238000001890 transfection Methods 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 238000011269 treatment regimen Methods 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
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
• MHNHYTDAOYJUEZ-UHFFFAOYSA-N triphenylphosphane Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 MHNHYTDAOYJUEZ-UHFFFAOYSA-N 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 231100000397 ulcer Toxicity 0.000 description 1
• 229910052720 vanadium Inorganic materials 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 239000011534 wash buffer Substances 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• 229940075420 xanthine Drugs 0.000 description 1