ME01360B - Derives de triazolopyridinylsulfanyle en tant qu'inhibiteurs de kinase p38 map - Google Patents

Derives de triazolopyridinylsulfanyle en tant qu'inhibiteurs de kinase p38 map

Info

Publication number: ME01360B
Authority: ME; Montenegro
Prior art keywords: pyrazol; thio; pyridin; triazolo; benzyl
Prior art date: 2004-08-12

Application number

MEP-2008-934A

Other languages

English (en)

Unknown language (me)

Inventor

John Paul Mathias

David Simon Millan

Russell Andrew Lewthwaite

Christopher Phillips

Original Assignee

Pfizer

Pfizer Ltd

Priority date (The priority date 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 date listed.)

2004-08-12

Filing date

2005-08-09

Publication date

2010-06-30

2005-08-09 Application filed by Pfizer, Pfizer Ltd filed Critical Pfizer

2005-08-09 Priority claimed from EP05772546A external-priority patent/EP1778686B9/fr

2010-06-30 Publication of ME01360B publication Critical patent/ME01360B/fr

Links

102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 title description 39
108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 title description 39
239000002829 mitogen activated protein kinase inhibitor Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 583
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 156
-1 4-hydroxy-3-methylphenyl Chemical group 0.000 claims description 116
125000001424 substituent group Chemical group 0.000 claims description 112
239000004202 carbamide Substances 0.000 claims description 105
125000005843 halogen group Chemical group 0.000 claims description 82
125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 79
208000006673 asthma Diseases 0.000 claims description 76
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 75
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 74
150000003839 salts Chemical class 0.000 claims description 68
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 58
239000012453 solvate Substances 0.000 claims description 56
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 50
125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 49
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 47
125000000217 alkyl group Chemical group 0.000 claims description 42
125000003118 aryl group Chemical group 0.000 claims description 38
201000010099 disease Diseases 0.000 claims description 37
208000035475 disorder Diseases 0.000 claims description 35
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 35
206010006451 bronchitis Diseases 0.000 claims description 32
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 30
239000003814 drug Substances 0.000 claims description 30
238000011282 treatment Methods 0.000 claims description 30
125000004076 pyridyl group Chemical group 0.000 claims description 26
230000001404 mediated effect Effects 0.000 claims description 24
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
230000002757 inflammatory effect Effects 0.000 claims description 21
201000009267 bronchiectasis Diseases 0.000 claims description 19
125000004093 cyano group Chemical group *C#N 0.000 claims description 19
230000000414 obstructive effect Effects 0.000 claims description 18
208000023504 respiratory system disease Diseases 0.000 claims description 17
125000003545 alkoxy group Chemical group 0.000 claims description 16
125000001072 heteroaryl group Chemical group 0.000 claims description 16
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 14
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 14
125000000623 heterocyclic group Chemical group 0.000 claims description 14
201000010659 intrinsic asthma Diseases 0.000 claims description 14
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 13
229910052801 chlorine Inorganic materials 0.000 claims description 13
238000004519 manufacturing process Methods 0.000 claims description 13
230000008506 pathogenesis Effects 0.000 claims description 13
125000004452 carbocyclyl group Chemical group 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 12
229940079593 drug Drugs 0.000 claims description 12
229910052731 fluorine Inorganic materials 0.000 claims description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 11
208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 11
208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 11
201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 11
208000015181 infectious disease Diseases 0.000 claims description 10
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 10
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 10
229920006395 saturated elastomer Polymers 0.000 claims description 10
RJNJWHFSKNJCTB-UHFFFAOYSA-N benzylurea Chemical compound NC(=O)NCC1=CC=CC=C1 RJNJWHFSKNJCTB-UHFFFAOYSA-N 0.000 claims description 9
206010006458 Bronchitis chronic Diseases 0.000 claims description 8
206010014561 Emphysema Diseases 0.000 claims description 8
230000001154 acute effect Effects 0.000 claims description 8
125000002619 bicyclic group Chemical group 0.000 claims description 8
208000007451 chronic bronchitis Diseases 0.000 claims description 8
125000002950 monocyclic group Chemical group 0.000 claims description 8
125000001624 naphthyl group Chemical group 0.000 claims description 8
206010013975 Dyspnoeas Diseases 0.000 claims description 7
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
208000000884 Airway Obstruction Diseases 0.000 claims description 6
208000000059 Dyspnea Diseases 0.000 claims description 6
208000016300 Idiopathic chronic eosinophilic pneumonia Diseases 0.000 claims description 6
208000036142 Viral infection Diseases 0.000 claims description 6
230000001580 bacterial effect Effects 0.000 claims description 6
201000009323 chronic eosinophilic pneumonia Diseases 0.000 claims description 6
230000002458 infectious effect Effects 0.000 claims description 6
230000002427 irreversible effect Effects 0.000 claims description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
125000002757 morpholinyl group Chemical group 0.000 claims description 6
125000004193 piperazinyl group Chemical group 0.000 claims description 6
125000003386 piperidinyl group Chemical group 0.000 claims description 6
230000000750 progressive effect Effects 0.000 claims description 6
208000002815 pulmonary hypertension Diseases 0.000 claims description 6
208000011580 syndromic disease Diseases 0.000 claims description 6
208000035143 Bacterial infection Diseases 0.000 claims description 5
208000022362 bacterial infectious disease Diseases 0.000 claims description 5
125000004122 cyclic group Chemical group 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
230000005713 exacerbation Effects 0.000 claims description 5
208000024711 extrinsic asthma Diseases 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
230000001991 pathophysiological effect Effects 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
229910052717 sulfur Inorganic materials 0.000 claims description 5
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 5
238000002560 therapeutic procedure Methods 0.000 claims description 5
230000009385 viral infection Effects 0.000 claims description 5
206010003645 Atopy Diseases 0.000 claims description 4
206010006448 Bronchiolitis Diseases 0.000 claims description 4
206010006482 Bronchospasm Diseases 0.000 claims description 4
206010017533 Fungal infection Diseases 0.000 claims description 4
208000031888 Mycoses Diseases 0.000 claims description 4
230000036428 airway hyperreactivity Effects 0.000 claims description 4
239000013566 allergen Substances 0.000 claims description 4
201000009961 allergic asthma Diseases 0.000 claims description 4
230000007885 bronchoconstriction Effects 0.000 claims description 4
230000001684 chronic effect Effects 0.000 claims description 4
230000007613 environmental effect Effects 0.000 claims description 4
230000002538 fungal effect Effects 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 4
229910052757 nitrogen Inorganic materials 0.000 claims description 4
208000007892 occupational asthma Diseases 0.000 claims description 4
208000028172 protozoa infectious disease Diseases 0.000 claims description 4
MHKRCPRFEXWSKP-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-chloro-4-hydroxyphenyl)pyrazol-3-yl]-3-[[2-[[3-(2-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C=1C=C(O)C(Cl)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1Cl MHKRCPRFEXWSKP-UHFFFAOYSA-N 0.000 claims description 3
USWKEPRNTHIAES-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]-3-[[2-[[3-(2-chloro-5-hydroxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C=4C(=CC=C(O)C=4)Cl)=NN=C3C=C2)=CC(C(C)(C)C)=N1 USWKEPRNTHIAES-UHFFFAOYSA-N 0.000 claims description 3
125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 3
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
101100054666 Streptomyces halstedii sch3 gene Chemical group 0.000 claims description 3
206010069351 acute lung injury Diseases 0.000 claims description 3
125000004104 aryloxy group Chemical group 0.000 claims description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
208000027866 inflammatory disease Diseases 0.000 claims description 3
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
HGCJZTKXWWPTJY-UHFFFAOYSA-N 1-[2-(3-chloro-4-hydroxyphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound N1=C(C(C)(C)SC)C=C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)N1C1=CC=C(O)C(Cl)=C1 HGCJZTKXWWPTJY-UHFFFAOYSA-N 0.000 claims description 2
VWIZGNMFQAIFIE-UHFFFAOYSA-N 1-[5-(2-methyl-1-methylsulfanylpropan-2-yl)-2-phenylpyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound N1=C(C(C)(C)CSC)C=C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)N1C1=CC=CC=C1 VWIZGNMFQAIFIE-UHFFFAOYSA-N 0.000 claims description 2
JLIZJQPCFJINDK-UHFFFAOYSA-N 1-[5-(2-methylsulfanylpropan-2-yl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]-3-[[2-[[3-(2-phenylmethoxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C=1C=C(C(F)(F)F)C=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1OCC1=CC=CC=C1 JLIZJQPCFJINDK-UHFFFAOYSA-N 0.000 claims description 2
OSHRGQFDYBDRHX-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-chlorophenyl)pyrazol-3-yl]-3-[[2-[[3-(2-hydroxy-4-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound OC1=CC(C)=CC=C1C1=NN=C2N1C=C(SC=1C(=CC=CC=1)CNC(=O)NC=1N(N=C(C=1)C(C)(C)C)C=1C=CC(Cl)=CC=1)C=C2 OSHRGQFDYBDRHX-UHFFFAOYSA-N 0.000 claims description 2
MUOAQYPYYYJTFT-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-hydroxyphenyl)pyrazol-3-yl]-3-[[2-[[3-(2-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C=1C=C(O)C=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1Cl MUOAQYPYYYJTFT-UHFFFAOYSA-N 0.000 claims description 2
JFLUZZNSNNHZSB-UHFFFAOYSA-N 1-[[2-[[3-(2-hydroxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]-3-[5-(2-methylsulfanylpropan-2-yl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]urea Chemical compound C=1C=C(C(F)(F)F)C=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1O JFLUZZNSNNHZSB-UHFFFAOYSA-N 0.000 claims description 2
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
206010051011 Fibrinous bronchitis Diseases 0.000 claims description 2
239000002671 adjuvant Substances 0.000 claims description 2
LSGSDQGGBKSFGW-UHFFFAOYSA-N chembl1938750 Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C=4C(=CC(O)=CC=4)Cl)=NN=C3C=C2)=CC(C(C)(C)C)=N1 LSGSDQGGBKSFGW-UHFFFAOYSA-N 0.000 claims description 2
238000002651 drug therapy Methods 0.000 claims description 2
230000003325 follicular Effects 0.000 claims description 2
125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
125000005844 heterocyclyloxy group Chemical group 0.000 claims description 2
208000018916 plastic bronchitis Diseases 0.000 claims description 2
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 2
VGEXRDWWPSGZDH-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-chloro-4-hydroxyphenyl)pyrazol-3-yl]-3-[[2-[[3-[2-(2-hydroxyethylsulfanyl)phenyl]-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C=1C=C(O)C(Cl)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1SCCO VGEXRDWWPSGZDH-UHFFFAOYSA-N 0.000 claims 2
125000006413 ring segment Chemical group 0.000 claims 2
125000006529 (C3-C6) alkyl group Chemical group 0.000 claims 1
GQJUPNKTYNFBRZ-UHFFFAOYSA-N 1-(5-tert-butyl-2-phenylpyrazol-3-yl)-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound C=1N2C(C(C)C)=NN=C2C=CC=1SC1=CC=CC=C1CNC(=O)NC1=CC(C(C)(C)C)=NN1C1=CC=CC=C1 GQJUPNKTYNFBRZ-UHFFFAOYSA-N 0.000 claims 1
IRZOFSUISHPPAA-UHFFFAOYSA-N 1-[2-(3-hydroxyphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound N1=C(C(C)(C)SC)C=C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)N1C1=CC=CC(O)=C1 IRZOFSUISHPPAA-UHFFFAOYSA-N 0.000 claims 1
OTCJWOJGLBCNMX-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound N1=C(C(C)(C)SC)C=C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)N1C1=CC=C(Cl)C=C1 OTCJWOJGLBCNMX-UHFFFAOYSA-N 0.000 claims 1
BSWLHRXYSZNBKO-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[[3-(2-hydroxy-4-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C=1C=C(Cl)C=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=C(C)C=C1O BSWLHRXYSZNBKO-UHFFFAOYSA-N 0.000 claims 1
FATWFUDJNMKNJD-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[[3-(2-phenylmethoxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C=1C=C(Cl)C=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1OCC1=CC=CC=C1 FATWFUDJNMKNJD-UHFFFAOYSA-N 0.000 claims 1
SDTXXQXYKNICLQ-UHFFFAOYSA-N 1-[2-(4-hydroxyphenyl)-5-(2-methyl-1-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound N1=C(C(C)(C)CSC)C=C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)N1C1=CC=C(O)C=C1 SDTXXQXYKNICLQ-UHFFFAOYSA-N 0.000 claims 1
OJWAESHUAXJOPF-UHFFFAOYSA-N 1-[2-(4-hydroxyphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[(3-phenyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound C=1C=C(O)C=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1 OJWAESHUAXJOPF-UHFFFAOYSA-N 0.000 claims 1
NGNVUYJDEYCXCJ-UHFFFAOYSA-N 1-[5-(2-methyl-1-methylsulfanylpropan-2-yl)-2-(4-methylphenyl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound N1=C(C(C)(C)CSC)C=C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)N1C1=CC=C(C)C=C1 NGNVUYJDEYCXCJ-UHFFFAOYSA-N 0.000 claims 1
GWSCCNOWJHRMON-UHFFFAOYSA-N 1-[5-(2-methylsulfanylpropan-2-yl)-2-(2-phenylmethoxyphenyl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound N1=C(C(C)(C)SC)C=C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)N1C1=CC=CC=C1OCC1=CC=CC=C1 GWSCCNOWJHRMON-UHFFFAOYSA-N 0.000 claims 1
JKZJXJKBSWHDCA-UHFFFAOYSA-N 1-[5-(2-methylsulfanylpropan-2-yl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound N1=C(C(C)(C)SC)C=C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)N1C1=CC=C(C(F)(F)F)C=C1 JKZJXJKBSWHDCA-UHFFFAOYSA-N 0.000 claims 1
VAVJPGAIFCMHQF-UHFFFAOYSA-N 1-[5-(2-methylsulfanylpropan-2-yl)-2-phenylpyrazol-3-yl]-3-[[2-[[3-(2-phenylmethoxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C=1C=CC=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1OCC1=CC=CC=C1 VAVJPGAIFCMHQF-UHFFFAOYSA-N 0.000 claims 1
MMSYODFZELFWFC-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-hydroxyphenyl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound C=1N2C(C(C)C)=NN=C2C=CC=1SC1=CC=CC=C1CNC(=O)NC1=CC(C(C)(C)C)=NN1C1=CC=CC(O)=C1 MMSYODFZELFWFC-UHFFFAOYSA-N 0.000 claims 1
RQTOPSKBWBUBCH-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-hydroxyphenyl)pyrazol-3-yl]-3-[[2-[[3-(2-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C=1C=CC(O)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1Cl RQTOPSKBWBUBCH-UHFFFAOYSA-N 0.000 claims 1
OVDYMIPFINDFKV-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-methylsulfanylphenyl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound CSC1=CC=CC(N2C(=CC(=N2)C(C)(C)C)NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)=C1 OVDYMIPFINDFKV-UHFFFAOYSA-N 0.000 claims 1
RNQGTJSGIUOXSP-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-chloro-3-hydroxyphenyl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound C=1N2C(C(C)C)=NN=C2C=CC=1SC1=CC=CC=C1CNC(=O)NC1=CC(C(C)(C)C)=NN1C1=CC=C(Cl)C(O)=C1 RNQGTJSGIUOXSP-UHFFFAOYSA-N 0.000 claims 1
QSPOVKAPDHUBSC-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-chlorophenyl)pyrazol-3-yl]-3-[[2-[[3-(2-hydroxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C=1C=C(Cl)C=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1O QSPOVKAPDHUBSC-UHFFFAOYSA-N 0.000 claims 1
CZFGSFSYQYLLPR-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-cyanophenyl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound C=1N2C(C(C)C)=NN=C2C=CC=1SC1=CC=CC=C1CNC(=O)NC1=CC(C(C)(C)C)=NN1C1=CC=C(C#N)C=C1 CZFGSFSYQYLLPR-UHFFFAOYSA-N 0.000 claims 1
AWCRHLRIVRFWLO-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxy-3-methylphenyl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound C1=C(C)C(OC)=CC=C1N1C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)=CC(C(C)(C)C)=N1 AWCRHLRIVRFWLO-UHFFFAOYSA-N 0.000 claims 1
MOWKCZWJWRZEQH-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)=CC(C(C)(C)C)=N1 MOWKCZWJWRZEQH-UHFFFAOYSA-N 0.000 claims 1
IHZRXBHSLLHTEI-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-methylsulfanylphenyl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound C1=CC(SC)=CC=C1N1C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)=CC(C(C)(C)C)=N1 IHZRXBHSLLHTEI-UHFFFAOYSA-N 0.000 claims 1
OEMZTIYNAKUKKX-UHFFFAOYSA-N 1-[[2-[[3-(2-hydroxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]-3-[5-(2-methylsulfanylpropan-2-yl)-2-phenylpyrazol-3-yl]urea Chemical compound C=1C=CC=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1O OEMZTIYNAKUKKX-UHFFFAOYSA-N 0.000 claims 1
206010003557 Asthma exercise induced Diseases 0.000 claims 1
208000004657 Exercise-Induced Asthma Diseases 0.000 claims 1
208000027771 Obstructive airways disease Diseases 0.000 claims 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
230000009429 distress Effects 0.000 claims 1
208000024695 exercise-induced bronchoconstriction Diseases 0.000 claims 1
230000035874 hyperreactivity Effects 0.000 claims 1
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 claims 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
230000000241 respiratory effect Effects 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 461
238000002360 preparation method Methods 0.000 description 260
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 234
239000000047 product Substances 0.000 description 208
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 198
238000000034 method Methods 0.000 description 183
239000000203 mixture Substances 0.000 description 163
230000002147 killing effect Effects 0.000 description 147
239000000243 solution Substances 0.000 description 141
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 136
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 89
239000007787 solid Substances 0.000 description 82
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 81
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 80
239000011541 reaction mixture Substances 0.000 description 72
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 53
238000005160 1H NMR spectroscopy Methods 0.000 description 47
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 46
238000010898 silica gel chromatography Methods 0.000 description 42
229910052943 magnesium sulfate Inorganic materials 0.000 description 40
235000019341 magnesium sulphate Nutrition 0.000 description 40
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
102100040247 Tumor necrosis factor Human genes 0.000 description 37
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 36
101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 32
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 32
238000006243 chemical reaction Methods 0.000 description 32
239000002904 solvent Substances 0.000 description 32
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
239000000741 silica gel Substances 0.000 description 26
229910002027 silica gel Inorganic materials 0.000 description 26
239000006260 foam Substances 0.000 description 25
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
239000003921 oil Substances 0.000 description 24
235000019198 oils Nutrition 0.000 description 24
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
238000004587 chromatography analysis Methods 0.000 description 22
238000010992 reflux Methods 0.000 description 22
229910052938 sodium sulfate Inorganic materials 0.000 description 22
235000011152 sodium sulphate Nutrition 0.000 description 22
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
239000002585 base Chemical class 0.000 description 21
239000000843 powder Substances 0.000 description 21
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 20
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 19
230000008569 process Effects 0.000 description 19
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
229910021529 ammonia Inorganic materials 0.000 description 18
239000012267 brine Substances 0.000 description 18
238000000746 purification Methods 0.000 description 18
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 16
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
239000007858 starting material Substances 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
239000010410 layer Substances 0.000 description 15
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 14
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 14
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
239000000460 chlorine Substances 0.000 description 14
238000009472 formulation Methods 0.000 description 14
239000000126 substance Substances 0.000 description 14
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
239000002253 acid Substances 0.000 description 13
239000002552 dosage form Substances 0.000 description 13
239000000725 suspension Substances 0.000 description 13
239000003826 tablet Substances 0.000 description 13
101100291385 Drosophila melanogaster p38a gene Proteins 0.000 description 12
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
239000000543 intermediate Substances 0.000 description 12
239000000523 sample Substances 0.000 description 12
FYWFCRHZXORPFH-UHFFFAOYSA-N (2-sulfanylphenyl)methanol Chemical compound OCC1=CC=CC=C1S FYWFCRHZXORPFH-UHFFFAOYSA-N 0.000 description 11
GCUOLJOTJRUDIZ-UHFFFAOYSA-N 2-(2-bromoethoxy)oxane Chemical compound BrCCOC1CCCCO1 GCUOLJOTJRUDIZ-UHFFFAOYSA-N 0.000 description 11
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
239000000651 prodrug Substances 0.000 description 11
229940002612 prodrug Drugs 0.000 description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 10
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 10
108010002352 Interleukin-1 Proteins 0.000 description 10
102000000589 Interleukin-1 Human genes 0.000 description 10
206010028980 Neoplasm Diseases 0.000 description 10
ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 description 10
238000004458 analytical method Methods 0.000 description 10
CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 10
210000004027 cell Anatomy 0.000 description 10
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical class ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 10
239000002244 precipitate Substances 0.000 description 10
238000001665 trituration Methods 0.000 description 10
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
239000000377 silicon dioxide Substances 0.000 description 9
238000003786 synthesis reaction Methods 0.000 description 9
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 8
108060008682 Tumor Necrosis Factor Proteins 0.000 description 8
230000000694 effects Effects 0.000 description 8
239000003112 inhibitor Substances 0.000 description 8
229910000027 potassium carbonate Inorganic materials 0.000 description 8
125000006239 protecting group Chemical group 0.000 description 8
230000002829 reductive effect Effects 0.000 description 8
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
206010061218 Inflammation Diseases 0.000 description 7
108700012920 TNF Proteins 0.000 description 7
239000000872 buffer Substances 0.000 description 7
239000003153 chemical reaction reagent Substances 0.000 description 7
239000012043 crude product Substances 0.000 description 7
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 7
238000010438 heat treatment Methods 0.000 description 7
235000011181 potassium carbonates Nutrition 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
239000011780 sodium chloride Substances 0.000 description 7
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 7
229940124597 therapeutic agent Drugs 0.000 description 7
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
125000003944 tolyl group Chemical group 0.000 description 7
102000004127 Cytokines Human genes 0.000 description 6
108090000695 Cytokines Proteins 0.000 description 6
208000010412 Glaucoma Diseases 0.000 description 6
108090001007 Interleukin-8 Proteins 0.000 description 6
208000019693 Lung disease Diseases 0.000 description 6
241000124008 Mammalia Species 0.000 description 6
206010063837 Reperfusion injury Diseases 0.000 description 6
206010040070 Septic Shock Diseases 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
201000011510 cancer Diseases 0.000 description 6
239000002299 complementary DNA Substances 0.000 description 6
239000013078 crystal Substances 0.000 description 6
125000000524 functional group Chemical group 0.000 description 6
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
230000004054 inflammatory process Effects 0.000 description 6
239000007788 liquid Substances 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
239000000546 pharmaceutical excipient Substances 0.000 description 6
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
102000004169 proteins and genes Human genes 0.000 description 6
108090000623 proteins and genes Proteins 0.000 description 6
MXZMACXOMZKYHJ-UHFFFAOYSA-N 4,4-dimethyl-3-oxopentanenitrile Chemical compound CC(C)(C)C(=O)CC#N MXZMACXOMZKYHJ-UHFFFAOYSA-N 0.000 description 5
YOELZIQOLWZLQC-UHFFFAOYSA-N 6-(4-fluorophenyl)-5-pyridin-4-yl-2,3-dihydroimidazo[2,1-b]thiazole Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)N2CCSC2=N1 YOELZIQOLWZLQC-UHFFFAOYSA-N 0.000 description 5
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 5
229920000858 Cyclodextrin Polymers 0.000 description 5
235000019502 Orange oil Nutrition 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
239000005557 antagonist Substances 0.000 description 5
238000005119 centrifugation Methods 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
239000002158 endotoxin Substances 0.000 description 5
238000005516 engineering process Methods 0.000 description 5
239000010408 film Substances 0.000 description 5
IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 5
230000009826 neoplastic cell growth Effects 0.000 description 5
150000002825 nitriles Chemical class 0.000 description 5
239000010502 orange oil Substances 0.000 description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
239000002243 precursor Substances 0.000 description 5
230000009467 reduction Effects 0.000 description 5
239000011347 resin Substances 0.000 description 5
229920005989 resin Polymers 0.000 description 5
238000007363 ring formation reaction Methods 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
239000006228 supernatant Substances 0.000 description 5
239000004094 surface-active agent Substances 0.000 description 5
201000000596 systemic lupus erythematosus Diseases 0.000 description 5
RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
108020004414 DNA Proteins 0.000 description 4
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
241000700588 Human alphaherpesvirus 1 Species 0.000 description 4
241000701085 Human alphaherpesvirus 3 Species 0.000 description 4
241000701041 Human betaherpesvirus 7 Species 0.000 description 4
241001502974 Human gammaherpesvirus 8 Species 0.000 description 4
241000701027 Human herpesvirus 6 Species 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
239000012359 Methanesulfonyl chloride Substances 0.000 description 4
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
239000002202 Polyethylene glycol Substances 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
150000001540 azides Chemical class 0.000 description 4
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
229910000024 caesium carbonate Inorganic materials 0.000 description 4
238000007796 conventional method Methods 0.000 description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
239000007884 disintegrant Substances 0.000 description 4
239000006185 dispersion Substances 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000012634 fragment Substances 0.000 description 4
229910052739 hydrogen Inorganic materials 0.000 description 4
239000001257 hydrogen Substances 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
125000004464 hydroxyphenyl group Chemical group 0.000 description 4
208000014674 injury Diseases 0.000 description 4
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 4
229940043355 kinase inhibitor Drugs 0.000 description 4
239000008101 lactose Substances 0.000 description 4
239000003199 leukotriene receptor blocking agent Substances 0.000 description 4
229920006008 lipopolysaccharide Polymers 0.000 description 4
239000012280 lithium aluminium hydride Substances 0.000 description 4
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
230000001575 pathological effect Effects 0.000 description 4
239000003757 phosphotransferase inhibitor Substances 0.000 description 4
239000013612 plasmid Substances 0.000 description 4
229920001223 polyethylene glycol Polymers 0.000 description 4
238000000634 powder X-ray diffraction Methods 0.000 description 4
208000009305 pseudorabies Diseases 0.000 description 4
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
239000008107 starch Substances 0.000 description 4
238000006467 substitution reaction Methods 0.000 description 4
239000000758 substrate Substances 0.000 description 4
DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
208000030507 AIDS Diseases 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 3
206010006895 Cachexia Diseases 0.000 description 3
241000701022 Cytomegalovirus Species 0.000 description 3
241000588724 Escherichia coli Species 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
108090001005 Interleukin-6 Proteins 0.000 description 3
102000043136 MAP kinase family Human genes 0.000 description 3
108091054455 MAP kinase family Proteins 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
229920000168 Microcrystalline cellulose Polymers 0.000 description 3
229940122694 Muscarinic M3 receptor antagonist Drugs 0.000 description 3
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
206010030348 Open-Angle Glaucoma Diseases 0.000 description 3
229910019142 PO4 Inorganic materials 0.000 description 3
108091000080 Phosphotransferase Proteins 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
102000001708 Protein Isoforms Human genes 0.000 description 3
108010029485 Protein Isoforms Proteins 0.000 description 3
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
206010037660 Pyrexia Diseases 0.000 description 3
229920002684 Sepharose Polymers 0.000 description 3
208000030886 Traumatic Brain injury Diseases 0.000 description 3
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
206010064930 age-related macular degeneration Diseases 0.000 description 3
230000000172 allergic effect Effects 0.000 description 3
208000028004 allergic respiratory disease Diseases 0.000 description 3
206010003246 arthritis Diseases 0.000 description 3
238000003556 assay Methods 0.000 description 3
208000010668 atopic eczema Diseases 0.000 description 3
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
239000002775 capsule Substances 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
238000011260 co-administration Methods 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
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 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
238000009826 distribution Methods 0.000 description 3
229940112141 dry powder inhaler Drugs 0.000 description 3
UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 3
108020001507 fusion proteins Proteins 0.000 description 3
102000037865 fusion proteins Human genes 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
125000002883 imidazolyl group Chemical group 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
208000028867 ischemia Diseases 0.000 description 3
239000012669 liquid formulation Substances 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
229910052749 magnesium Inorganic materials 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
229940091250 magnesium supplement Drugs 0.000 description 3
239000002207 metabolite Substances 0.000 description 3
235000019813 microcrystalline cellulose Nutrition 0.000 description 3
239000008108 microcrystalline cellulose Substances 0.000 description 3
229940016286 microcrystalline cellulose Drugs 0.000 description 3
239000002480 mineral oil Substances 0.000 description 3
235000010446 mineral oil Nutrition 0.000 description 3
210000001616 monocyte Anatomy 0.000 description 3
150000004682 monohydrates Chemical class 0.000 description 3
239000003681 muscarinic M3 receptor antagonist Substances 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 3
235000021317 phosphate Nutrition 0.000 description 3
230000026731 phosphorylation Effects 0.000 description 3
238000006366 phosphorylation reaction Methods 0.000 description 3
102000020233 phosphotransferase Human genes 0.000 description 3
229920000642 polymer Polymers 0.000 description 3
201000006366 primary open angle glaucoma Diseases 0.000 description 3
125000003373 pyrazinyl group Chemical group 0.000 description 3
125000003226 pyrazolyl group Chemical group 0.000 description 3
125000002098 pyridazinyl group Chemical group 0.000 description 3
125000000714 pyrimidinyl group Chemical group 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
230000004044 response Effects 0.000 description 3
238000004366 reverse phase liquid chromatography Methods 0.000 description 3
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 3
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 3
239000011734 sodium Substances 0.000 description 3
239000007921 spray Substances 0.000 description 3
238000001694 spray drying Methods 0.000 description 3
238000003756 stirring Methods 0.000 description 3
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 3
238000003419 tautomerization reaction Methods 0.000 description 3
125000003831 tetrazolyl group Chemical group 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 3
239000002451 tumor necrosis factor inhibitor Substances 0.000 description 3
241001529453 unidentified herpesvirus Species 0.000 description 3
NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 2
HKDFRDIIELOLTJ-UHFFFAOYSA-N 1,4-dithianyl Chemical group [CH]1CSCCS1 HKDFRDIIELOLTJ-UHFFFAOYSA-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
HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 2
PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 2
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 2
BDDVAWDNVWLHDQ-UHFFFAOYSA-N 2-chloro-4-hydroxybenzonitrile Chemical compound OC1=CC=C(C#N)C(Cl)=C1 BDDVAWDNVWLHDQ-UHFFFAOYSA-N 0.000 description 2
UTVCLUZQPSRKMY-UHFFFAOYSA-N 2-chloro-5-hydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1Cl UTVCLUZQPSRKMY-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
206010001513 AIDS related complex Diseases 0.000 description 2
102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 description 2
108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 description 2
208000023275 Autoimmune disease Diseases 0.000 description 2
206010004146 Basal cell carcinoma Diseases 0.000 description 2
208000006386 Bone Resorption Diseases 0.000 description 2
206010048962 Brain oedema Diseases 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
206010007559 Cardiac failure congestive Diseases 0.000 description 2
208000031229 Cardiomyopathies Diseases 0.000 description 2
208000024172 Cardiovascular disease Diseases 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
108091026890 Coding region Proteins 0.000 description 2
206010009944 Colon cancer Diseases 0.000 description 2
206010011224 Cough Diseases 0.000 description 2
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 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
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 2
201000004624 Dermatitis Diseases 0.000 description 2
208000007342 Diabetic Nephropathies Diseases 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
206010014824 Endotoxic shock Diseases 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
102100022086 GRB2-related adapter protein 2 Human genes 0.000 description 2
206010017943 Gastrointestinal conditions Diseases 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
201000005569 Gout Diseases 0.000 description 2
206010018634 Gouty Arthritis Diseases 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
206010019280 Heart failures Diseases 0.000 description 2
208000032843 Hemorrhage Diseases 0.000 description 2
241000282412 Homo Species 0.000 description 2
241000701074 Human alphaherpesvirus 2 Species 0.000 description 2
241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
102100034343 Integrase Human genes 0.000 description 2
102000004890 Interleukin-8 Human genes 0.000 description 2
208000010038 Ischemic Optic Neuropathy Diseases 0.000 description 2
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
239000006137 Luria-Bertani broth Substances 0.000 description 2
206010025323 Lymphomas Diseases 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
201000009906 Meningitis Diseases 0.000 description 2
206010027476 Metastases Diseases 0.000 description 2
229920000881 Modified starch Polymers 0.000 description 2
208000003445 Mouth Neoplasms Diseases 0.000 description 2
229940121948 Muscarinic receptor antagonist Drugs 0.000 description 2
208000000112 Myalgia Diseases 0.000 description 2
206010062207 Mycobacterial infection Diseases 0.000 description 2
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
206010029113 Neovascularisation Diseases 0.000 description 2
208000036110 Neuroinflammatory disease Diseases 0.000 description 2
206010030924 Optic ischaemic neuropathy Diseases 0.000 description 2
206010031264 Osteonecrosis Diseases 0.000 description 2
239000012826 P38 inhibitor Substances 0.000 description 2
238000012408 PCR amplification Methods 0.000 description 2
208000002193 Pain Diseases 0.000 description 2
229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 2
102000001253 Protein Kinase Human genes 0.000 description 2
201000004681 Psoriasis Diseases 0.000 description 2
108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
201000007527 Retinal artery occlusion Diseases 0.000 description 2
101100545004 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YSP2 gene Proteins 0.000 description 2
206010040047 Sepsis Diseases 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
208000006011 Stroke Diseases 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
102000000551 Syk Kinase Human genes 0.000 description 2
108010016672 Syk Kinase Proteins 0.000 description 2
229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
206010044248 Toxic shock syndrome Diseases 0.000 description 2
231100000650 Toxic shock syndrome Toxicity 0.000 description 2
208000025865 Ulcer Diseases 0.000 description 2
208000027418 Wounds and injury Diseases 0.000 description 2
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
230000009471 action Effects 0.000 description 2
230000004913 activation Effects 0.000 description 2
239000000654 additive Substances 0.000 description 2
239000002465 adenosine A2a receptor agonist Substances 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
239000000556 agonist Substances 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
230000003321 amplification Effects 0.000 description 2
230000033115 angiogenesis Effects 0.000 description 2
150000001450 anions Chemical class 0.000 description 2
201000007058 anterior ischemic optic neuropathy Diseases 0.000 description 2
230000003110 anti-inflammatory effect Effects 0.000 description 2
239000003963 antioxidant agent Substances 0.000 description 2
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 description 2
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
229940124748 beta 2 agonist Drugs 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 2
230000024279 bone resorption Effects 0.000 description 2
208000006752 brain edema Diseases 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical class [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
230000000747 cardiac effect Effects 0.000 description 2
201000005849 central retinal artery occlusion Diseases 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
239000000812 cholinergic antagonist Substances 0.000 description 2
238000010367 cloning Methods 0.000 description 2
230000015271 coagulation Effects 0.000 description 2
238000005345 coagulation Methods 0.000 description 2
239000003086 colorant Substances 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
238000009833 condensation Methods 0.000 description 2
230000005494 condensation Effects 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
230000010250 cytokine signaling pathway Effects 0.000 description 2
230000006378 damage Effects 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
206010012601 diabetes mellitus Diseases 0.000 description 2
208000033679 diabetic kidney disease Diseases 0.000 description 2
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
238000010494 dissociation reaction Methods 0.000 description 2
230000005593 dissociations Effects 0.000 description 2
239000003995 emulsifying agent Substances 0.000 description 2
210000002919 epithelial cell Anatomy 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
230000005284 excitation Effects 0.000 description 2
239000000284 extract Substances 0.000 description 2
210000004996 female reproductive system Anatomy 0.000 description 2
238000000855 fermentation Methods 0.000 description 2
230000004151 fermentation Effects 0.000 description 2
239000000945 filler Substances 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
238000004108 freeze drying Methods 0.000 description 2
239000007789 gas Substances 0.000 description 2
239000000499 gel Substances 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
150000004677 hydrates Chemical class 0.000 description 2
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
239000001863 hydroxypropyl cellulose Substances 0.000 description 2
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
206010022000 influenza Diseases 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
239000011630 iodine Substances 0.000 description 2
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
208000032839 leukemia Diseases 0.000 description 2
VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 description 2
GWNVDXQDILPJIG-NXOLIXFESA-N leukotriene C4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O GWNVDXQDILPJIG-NXOLIXFESA-N 0.000 description 2
YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 2
OTZRAYGBFWZKMX-JUDRUQEKSA-N leukotriene E4 Chemical compound CCCCCC=CCC=C\C=C\C=C\[C@@H](SC[C@H](N)C(O)=O)[C@@H](O)CCCC(O)=O OTZRAYGBFWZKMX-JUDRUQEKSA-N 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
208000019423 liver disease Diseases 0.000 description 2
210000002540 macrophage Anatomy 0.000 description 2
208000002780 macular degeneration Diseases 0.000 description 2
201000004792 malaria Diseases 0.000 description 2
230000003211 malignant effect Effects 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
239000000463 material Substances 0.000 description 2
238000005259 measurement Methods 0.000 description 2
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
XHXXWWGGXFUMAJ-UHFFFAOYSA-N methanethiol;sodium Chemical compound [Na].SC XHXXWWGGXFUMAJ-UHFFFAOYSA-N 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 2
239000003595 mist Substances 0.000 description 2
210000005087 mononuclear cell Anatomy 0.000 description 2
201000006417 multiple sclerosis Diseases 0.000 description 2
208000027531 mycobacterial infectious disease Diseases 0.000 description 2
208000010125 myocardial infarction Diseases 0.000 description 2
239000006199 nebulizer Substances 0.000 description 2
201000008383 nephritis Diseases 0.000 description 2
208000015122 neurodegenerative disease Diseases 0.000 description 2
230000003959 neuroinflammation Effects 0.000 description 2
238000003199 nucleic acid amplification method Methods 0.000 description 2
238000005580 one pot reaction Methods 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
201000008482 osteoarthritis Diseases 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
238000007911 parenteral administration Methods 0.000 description 2
239000008188 pellet Substances 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
150000002989 phenols Chemical class 0.000 description 2
229940038531 phenylhydrazine hydrochloride Drugs 0.000 description 2
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
239000012286 potassium permanganate Substances 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
239000003380 propellant Substances 0.000 description 2
108060006633 protein kinase Proteins 0.000 description 2
150000003254 radicals Chemical class 0.000 description 2
230000002285 radioactive effect Effects 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
238000012552 review Methods 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
230000036303 septic shock Effects 0.000 description 2
230000035939 shock Effects 0.000 description 2
210000003491 skin Anatomy 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
229940083542 sodium Drugs 0.000 description 2
235000019333 sodium laurylsulphate Nutrition 0.000 description 2
235000010288 sodium nitrite Nutrition 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
239000001119 stannous chloride Substances 0.000 description 2
235000011150 stannous chloride Nutrition 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000007916 tablet composition Substances 0.000 description 2
239000006068 taste-masking agent Substances 0.000 description 2
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
HRTKQUHFGZFPPF-UHFFFAOYSA-M tetraethylazanium;fluoride;dihydrate Chemical compound O.O.[F-].CC[N+](CC)(CC)CC HRTKQUHFGZFPPF-UHFFFAOYSA-M 0.000 description 2
125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 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
208000037816 tissue injury Diseases 0.000 description 2
230000008733 trauma Effects 0.000 description 2
230000006433 tumor necrosis factor production Effects 0.000 description 2
239000000811 xylitol Substances 0.000 description 2
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
235000010447 xylitol Nutrition 0.000 description 2
229960002675 xylitol Drugs 0.000 description 2
HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
XMBSMMCPKFDGEO-ZETCQYMHSA-N (2s)-2-amino-5-[[amino-(2-methoxyethylamino)methylidene]amino]pentanoic acid Chemical compound COCCNC(=N)NCCC[C@H](N)C(O)=O XMBSMMCPKFDGEO-ZETCQYMHSA-N 0.000 description 1
PJRSUKFWFKUDTH-JWDJOUOUSA-N (2s)-6-amino-2-[[2-[[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[(2-aminoacetyl)amino]-4-methylsulfanylbutanoyl]amino]propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]propanoyl]amino]acetyl]amino]propanoyl Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(N)=O PJRSUKFWFKUDTH-JWDJOUOUSA-N 0.000 description 1
WJGGZLUXLCWVJB-UHFFFAOYSA-N (3-chloro-4-methoxyphenyl)hydrazine;hydrochloride Chemical compound Cl.COC1=CC=C(NN)C=C1Cl WJGGZLUXLCWVJB-UHFFFAOYSA-N 0.000 description 1
YRBLVJGTLXQTCJ-UHFFFAOYSA-N (3-ethyl-4-methoxyphenyl)hydrazine;hydrochloride Chemical compound Cl.CCC1=CC(NN)=CC=C1OC YRBLVJGTLXQTCJ-UHFFFAOYSA-N 0.000 description 1
JWJSWCNKBBQJMP-UHFFFAOYSA-N (3-ethylphenyl)hydrazine;hydrochloride Chemical compound Cl.CCC1=CC=CC(NN)=C1 JWJSWCNKBBQJMP-UHFFFAOYSA-N 0.000 description 1
GFZBRCMIBBSGQX-UHFFFAOYSA-N (3-methylsulfanylphenyl)hydrazine Chemical compound CSC1=CC=CC(NN)=C1 GFZBRCMIBBSGQX-UHFFFAOYSA-N 0.000 description 1
MMMGCMOISVZVKZ-UHFFFAOYSA-N (3-phenylmethoxyphenyl)hydrazine;hydrochloride Chemical compound Cl.NNC1=CC=CC(OCC=2C=CC=CC=2)=C1 MMMGCMOISVZVKZ-UHFFFAOYSA-N 0.000 description 1
RMTYJLWDVSGYDC-UHFFFAOYSA-N (4-methylsulfanylphenyl)hydrazine Chemical compound CSC1=CC=C(NN)C=C1 RMTYJLWDVSGYDC-UHFFFAOYSA-N 0.000 description 1
UFZKWTITXBRSPK-UHFFFAOYSA-N (4-phenylmethoxyphenyl)hydrazine Chemical compound C1=CC(NN)=CC=C1OCC1=CC=CC=C1 UFZKWTITXBRSPK-UHFFFAOYSA-N 0.000 description 1
QYQLEYTXFMOLEI-UHFFFAOYSA-N (5-bromopyridin-2-yl)hydrazine Chemical compound NNC1=CC=C(Br)C=N1 QYQLEYTXFMOLEI-UHFFFAOYSA-N 0.000 description 1
DAXJNUBSBFUTRP-RTQNCGMRSA-N (8r,9s,10r,13s,14s)-6-(hydroxymethyl)-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(CO)C2=C1 DAXJNUBSBFUTRP-RTQNCGMRSA-N 0.000 description 1
125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 1
LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
LQCMMXGKEGWUIM-UHFFFAOYSA-N 1-(4-bromo-2-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC=C(Br)C=C1O LQCMMXGKEGWUIM-UHFFFAOYSA-N 0.000 description 1
WZFTVIOWEJKNHR-UHFFFAOYSA-N 1-[2-(3,5-dimethylphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[[3-(2-hydroxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C=1C(C)=CC(C)=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1O WZFTVIOWEJKNHR-UHFFFAOYSA-N 0.000 description 1
FTJGUNWRYWYJDH-UHFFFAOYSA-N 1-[2-(3-cyclopropylphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound N1=C(C(C)(C)SC)C=C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)N1C(C=1)=CC=CC=1C1CC1 FTJGUNWRYWYJDH-UHFFFAOYSA-N 0.000 description 1
UDQPTSPRVWNRJS-UHFFFAOYSA-N 1-[2-(3-hydroxy-4-methylphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[[3-(2-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C=1C=C(C)C(O)=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1C UDQPTSPRVWNRJS-UHFFFAOYSA-N 0.000 description 1
LVLUDINXFCWWBT-UHFFFAOYSA-N 1-[2-(3-methylphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound N1=C(C(C)(C)SC)C=C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)N1C1=CC=CC(C)=C1 LVLUDINXFCWWBT-UHFFFAOYSA-N 0.000 description 1
OATSKNAWWGFZLA-UHFFFAOYSA-N 1-[2-(4-chloro-3-hydroxyphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[[3-(2-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C=1C=C(Cl)C(O)=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1C OATSKNAWWGFZLA-UHFFFAOYSA-N 0.000 description 1
LUEUUOUFOGCFNH-UHFFFAOYSA-N 1-[2-(4-ethyl-3-hydroxyphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[[3-(2-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C1=C(O)C(CC)=CC=C1N1C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C=4C(=CC=CC=4)C)=NN=C3C=C2)=CC(C(C)(C)SC)=N1 LUEUUOUFOGCFNH-UHFFFAOYSA-N 0.000 description 1
UYDGCJQZGJDXRK-UHFFFAOYSA-N 1-[2-(4-hydroxy-3-methylphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound N1=C(C(C)(C)SC)C=C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)N1C1=CC=C(O)C(C)=C1 UYDGCJQZGJDXRK-UHFFFAOYSA-N 0.000 description 1
MDXBQTHQEGQQQO-UHFFFAOYSA-N 1-[2-(4-hydroxy-3-methylphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[[3-(2-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C=1C=C(O)C(C)=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1C MDXBQTHQEGQQQO-UHFFFAOYSA-N 0.000 description 1
VGYRONBBDFPRLQ-UHFFFAOYSA-N 1-[2-(4-methylphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound N1=C(C(C)(C)SC)C=C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)N1C1=CC=C(C)C=C1 VGYRONBBDFPRLQ-UHFFFAOYSA-N 0.000 description 1
NXGUQRJHSXQWII-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3,5-dimethylphenyl)pyrazol-3-yl]-3-[[2-[[3-(2-hydroxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound CC1=CC(C)=CC(N2C(=CC(=N2)C(C)(C)C)NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C=4C(=CC=CC=4)O)=NN=C3C=C2)=C1 NXGUQRJHSXQWII-UHFFFAOYSA-N 0.000 description 1
APSPBSDRPIVFKO-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-ethylphenyl)pyrazol-3-yl]-3-[[2-[[3-(2-hydroxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound CCC1=CC=CC(N2C(=CC(=N2)C(C)(C)C)NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C=4C(=CC=CC=4)O)=NN=C3C=C2)=C1 APSPBSDRPIVFKO-UHFFFAOYSA-N 0.000 description 1
YMLCFJRKORVPRM-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-hydroxy-4-methylphenyl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound C=1N2C(C(C)C)=NN=C2C=CC=1SC1=CC=CC=C1CNC(=O)NC1=CC(C(C)(C)C)=NN1C1=CC=C(C)C(O)=C1 YMLCFJRKORVPRM-UHFFFAOYSA-N 0.000 description 1
ZPZQIHRNBCUXHG-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-hydroxy-4-methylphenyl)pyrazol-3-yl]-3-[[2-[[3-(2-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C1=C(O)C(C)=CC=C1N1C(NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C=4C(=CC=CC=4)Cl)=NN=C3C=C2)=CC(C(C)(C)C)=N1 ZPZQIHRNBCUXHG-UHFFFAOYSA-N 0.000 description 1
VIGPITSFZOBHNS-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-methoxyphenyl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound COC1=CC=CC(N2C(=CC(=N2)C(C)(C)C)NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C(C)C)=NN=C3C=C2)=C1 VIGPITSFZOBHNS-UHFFFAOYSA-N 0.000 description 1
BVFSVBSZZSJSJP-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-methylphenyl)pyrazol-3-yl]-3-[[2-[[3-(2-chloro-5-hydroxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound CC1=CC=CC(N2C(=CC(=N2)C(C)(C)C)NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C=4C(=CC=C(O)C=4)Cl)=NN=C3C=C2)=C1 BVFSVBSZZSJSJP-UHFFFAOYSA-N 0.000 description 1
GIRIALFSTIQROE-UHFFFAOYSA-N 1-[5-tert-butyl-2-(3-methylphenyl)pyrazol-3-yl]-3-[[2-[[3-(2-hydroxy-4-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound CC1=CC=CC(N2C(=CC(=N2)C(C)(C)C)NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C=4C(=CC(C)=CC=4)O)=NN=C3C=C2)=C1 GIRIALFSTIQROE-UHFFFAOYSA-N 0.000 description 1
WTEPBXLRGXAWES-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-chloro-3-hydroxyphenyl)pyrazol-3-yl]-3-[[2-[[3-(2-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C=1C=C(Cl)C(O)=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1Cl WTEPBXLRGXAWES-UHFFFAOYSA-N 0.000 description 1
ARAHLYDNIHOTSM-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-hydroxy-3-methylphenyl)pyrazol-3-yl]-3-[[2-[[3-(2-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound C1=C(O)C(C)=CC(N2C(=CC(=N2)C(C)(C)C)NC(=O)NCC=2C(=CC=CC=2)SC2=CN3C(C=4C(=CC=CC=4)Cl)=NN=C3C=C2)=C1 ARAHLYDNIHOTSM-UHFFFAOYSA-N 0.000 description 1
ANDIILLNPJRODX-UHFFFAOYSA-N 1-[5-tert-butyl-2-(4-hydroxyphenyl)pyrazol-3-yl]-3-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methyl]urea Chemical compound C=1N2C(C(C)C)=NN=C2C=CC=1SC1=CC=CC=C1CNC(=O)NC1=CC(C(C)(C)C)=NN1C1=CC=C(O)C=C1 ANDIILLNPJRODX-UHFFFAOYSA-N 0.000 description 1
FLFYAHLWTTYYDI-UHFFFAOYSA-N 1-[5-tert-butyl-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]-3-[[2-[[3-(2-hydroxy-4-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]urea Chemical compound OC1=CC(C)=CC=C1C1=NN=C2N1C=C(SC=1C(=CC=CC=1)CNC(=O)NC=1N(N=C(C=1)C(C)(C)C)C=1C=CC(=CC=1)C(F)(F)F)C=C2 FLFYAHLWTTYYDI-UHFFFAOYSA-N 0.000 description 1
XBDBSCIBEHFLGZ-UHFFFAOYSA-N 1-[[2-[[3-(2-chloro-4-hydroxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]-3-[2-(4-methylphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]urea Chemical compound C=1C=C(C)C=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=C(O)C=C1Cl XBDBSCIBEHFLGZ-UHFFFAOYSA-N 0.000 description 1
ABQFOAZVBZLKDL-UHFFFAOYSA-N 1-[[2-[[3-(2-chloro-5-hydroxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]-3-[2-(3-methylphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]urea Chemical compound C=1C=CC(C)=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC(O)=CC=C1Cl ABQFOAZVBZLKDL-UHFFFAOYSA-N 0.000 description 1
YOZBWSKMNBMYAU-UHFFFAOYSA-N 1-[[2-[[3-(2-chloro-5-hydroxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]-3-[2-(4-methylphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]urea Chemical compound C=1C=C(C)C=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC(O)=CC=C1Cl YOZBWSKMNBMYAU-UHFFFAOYSA-N 0.000 description 1
XCSBEHOXIZGMDD-UHFFFAOYSA-N 1-[[2-[[3-(2-hydroxy-4-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]-3-[2-(3-methylphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]urea Chemical compound C=1C=CC(C)=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=C(C)C=C1O XCSBEHOXIZGMDD-UHFFFAOYSA-N 0.000 description 1
VSZWLLCZDHANMQ-UHFFFAOYSA-N 1-[[2-[[3-(2-hydroxy-4-methylphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]-3-[2-(4-methylphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]urea Chemical compound C=1C=C(C)C=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=C(C)C=C1O VSZWLLCZDHANMQ-UHFFFAOYSA-N 0.000 description 1
MCAZXNVMMJKCCB-UHFFFAOYSA-N 1-[[2-[[3-(2-hydroxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]-3-[2-(3-methylphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]urea Chemical compound C=1C=CC(C)=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1O MCAZXNVMMJKCCB-UHFFFAOYSA-N 0.000 description 1
JOPQAFFNQTXZTA-UHFFFAOYSA-N 1-[[2-[[3-(2-hydroxyphenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl]sulfanyl]phenyl]methyl]-3-[2-(4-methylphenyl)-5-(2-methylsulfanylpropan-2-yl)pyrazol-3-yl]urea Chemical compound C=1C=C(C)C=CC=1N1N=C(C(C)(C)SC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1O JOPQAFFNQTXZTA-UHFFFAOYSA-N 0.000 description 1
GYWCJBXKTAFVMH-UHFFFAOYSA-N 1-[phenyl(2h-triazolo[4,5-b]pyridin-5-ylsulfanyl)methyl]-1-(1h-pyrazol-5-yl)urea Chemical class C1=CNN=C1N(C(=O)N)C(SC=1N=C2N=NNC2=CC=1)C1=CC=CC=C1 GYWCJBXKTAFVMH-UHFFFAOYSA-N 0.000 description 1
QWFHNVJNLZJNBU-UHFFFAOYSA-N 1-bromo-3-methyl-5-phenylmethoxybenzene Chemical compound CC1=CC(Br)=CC(OCC=2C=CC=CC=2)=C1 QWFHNVJNLZJNBU-UHFFFAOYSA-N 0.000 description 1
SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 1
VSWPGAIWKHPTKX-UHFFFAOYSA-N 1-methyl-10-[2-(4-methyl-1-piperazinyl)-1-oxoethyl]-5H-thieno[3,4-b][1,5]benzodiazepin-4-one Chemical compound C1CN(C)CCN1CC(=O)N1C2=CC=CC=C2NC(=O)C2=CSC(C)=C21 VSWPGAIWKHPTKX-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
IQFIWJDBZRZLNO-UHFFFAOYSA-N 1h-pyrazole;urea Chemical class NC(N)=O.C=1C=NNC=1 IQFIWJDBZRZLNO-UHFFFAOYSA-N 0.000 description 1
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
XKLMLKSXPIITAL-UHFFFAOYSA-N 2-chloro-3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1Cl XKLMLKSXPIITAL-UHFFFAOYSA-N 0.000 description 1
ZMOMCILMBYEGLD-UHFFFAOYSA-N 2-chloro-4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C(Cl)=C1 ZMOMCILMBYEGLD-UHFFFAOYSA-N 0.000 description 1
NYDXXBPGGPYUDR-UHFFFAOYSA-N 2-chloro-4-phenylmethoxybenzaldehyde Chemical compound C1=C(C=O)C(Cl)=CC(OCC=2C=CC=CC=2)=C1 NYDXXBPGGPYUDR-UHFFFAOYSA-N 0.000 description 1
BAYTZPDBXASXLK-UHFFFAOYSA-N 2-chloro-5-hydroxybenzaldehyde Chemical compound OC1=CC=C(Cl)C(C=O)=C1 BAYTZPDBXASXLK-UHFFFAOYSA-N 0.000 description 1
VEIWWFBTDZYPQN-UHFFFAOYSA-N 2-chloro-5-phenylmethoxybenzaldehyde Chemical compound C1=C(C=O)C(Cl)=CC=C1OCC1=CC=CC=C1 VEIWWFBTDZYPQN-UHFFFAOYSA-N 0.000 description 1
ZWDVQMVZZYIAHO-UHFFFAOYSA-N 2-fluorobenzaldehyde Chemical compound FC1=CC=CC=C1C=O ZWDVQMVZZYIAHO-UHFFFAOYSA-N 0.000 description 1
DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
PBEJTRAJWCNHRS-UHFFFAOYSA-N 2-phenylmethoxybenzaldehyde Chemical compound O=CC1=CC=CC=C1OCC1=CC=CC=C1 PBEJTRAJWCNHRS-UHFFFAOYSA-N 0.000 description 1
DTALCVXXATYTQJ-UHFFFAOYSA-N 2-propan-2-ylbenzaldehyde Chemical compound CC(C)C1=CC=CC=C1C=O DTALCVXXATYTQJ-UHFFFAOYSA-N 0.000 description 1
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
125000001698 2H-pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
KAABRGOOVGMZFB-UHFFFAOYSA-N 3-(5-amino-3-tert-butylpyrazol-1-yl)phenol Chemical compound N1=C(C(C)(C)C)C=C(N)N1C1=CC=CC(O)=C1 KAABRGOOVGMZFB-UHFFFAOYSA-N 0.000 description 1
AAXTYMPBRBJBMN-UHFFFAOYSA-N 3-[3-tert-butyl-5-[[2-[(3-propan-2-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)sulfanyl]phenyl]methylcarbamoylamino]pyrazol-1-yl]benzoic acid Chemical compound C=1N2C(C(C)C)=NN=C2C=CC=1SC1=CC=CC=C1CNC(=O)NC1=CC(C(C)(C)C)=NN1C1=CC=CC(C(O)=O)=C1 AAXTYMPBRBJBMN-UHFFFAOYSA-N 0.000 description 1
OTUYBYTUBWJBLO-UHFFFAOYSA-N 3-bromo-5-methylphenol Chemical compound CC1=CC(O)=CC(Br)=C1 OTUYBYTUBWJBLO-UHFFFAOYSA-N 0.000 description 1
LNKBDFVSILQKSI-UHFFFAOYSA-N 4-Chloro-3-methoxyaniline Chemical compound COC1=CC(N)=CC=C1Cl LNKBDFVSILQKSI-UHFFFAOYSA-N 0.000 description 1
BIDHQMJRQFWEDT-UHFFFAOYSA-N 4-bromo-1-ethyl-2-methoxybenzene Chemical compound CCC1=CC=C(Br)C=C1OC BIDHQMJRQFWEDT-UHFFFAOYSA-N 0.000 description 1
UDLRGQOHGYWLCS-UHFFFAOYSA-N 4-bromo-1-methoxy-2-methylbenzene Chemical compound COC1=CC=C(Br)C=C1C UDLRGQOHGYWLCS-UHFFFAOYSA-N 0.000 description 1
FPIQNBOUYZLESW-UHFFFAOYSA-N 4-bromo-2-chloro-1-methoxybenzene Chemical compound COC1=CC=C(Br)C=C1Cl FPIQNBOUYZLESW-UHFFFAOYSA-N 0.000 description 1
IRITUNGQFQNGKP-UHFFFAOYSA-N 4-bromo-2-ethyl-1-methoxybenzene Chemical compound CCC1=CC(Br)=CC=C1OC IRITUNGQFQNGKP-UHFFFAOYSA-N 0.000 description 1
ZPNJDGLWSCMYIJ-UHFFFAOYSA-N 4-chloro-3-(hydroxymethyl)phenol Chemical compound OCC1=CC(O)=CC=C1Cl ZPNJDGLWSCMYIJ-UHFFFAOYSA-N 0.000 description 1
LKZASOMCICKMLK-UHFFFAOYSA-N 4-methyl-4-methylsulfanyl-3-oxopentanenitrile Chemical compound CSC(C)(C)C(=O)CC#N LKZASOMCICKMLK-UHFFFAOYSA-N 0.000 description 1
QRVYABWJVXXOTN-UHFFFAOYSA-N 4-methylsulfanylbenzaldehyde Chemical compound CSC1=CC=C(C=O)C=C1 QRVYABWJVXXOTN-UHFFFAOYSA-N 0.000 description 1
KRMXBOYTFUYEJZ-UHFFFAOYSA-N 5-(5-amino-3-tert-butylpyrazol-1-yl)-2-methylphenol;hydrochloride Chemical compound Cl.C1=C(O)C(C)=CC=C1N1C(N)=CC(C(C)(C)C)=N1 KRMXBOYTFUYEJZ-UHFFFAOYSA-N 0.000 description 1
102000004023 5-Lipoxygenase-Activating Proteins Human genes 0.000 description 1
108090000411 5-Lipoxygenase-Activating Proteins Proteins 0.000 description 1
IHOXNOQMRZISPV-YJYMSZOUSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-methoxyphenyl)propan-2-yl]azaniumyl]ethyl]-2-oxo-1h-quinolin-8-olate Chemical compound C1=CC(OC)=CC=C1C[C@@H](C)NC[C@H](O)C1=CC=C(O)C2=C1C=CC(=O)N2 IHOXNOQMRZISPV-YJYMSZOUSA-N 0.000 description 1
PEAOEIWYQVXZMB-UHFFFAOYSA-N 5-bromo-2-chloropyridine Chemical compound ClC1=CC=C(Br)C=N1 PEAOEIWYQVXZMB-UHFFFAOYSA-N 0.000 description 1
NEQRQRAHVANUAZ-UHFFFAOYSA-N 5-bromo-n-[(2-phenylmethoxyphenyl)methylideneamino]pyridin-2-amine Chemical compound N1=CC(Br)=CC=C1NN=CC1=CC=CC=C1OCC1=CC=CC=C1 NEQRQRAHVANUAZ-UHFFFAOYSA-N 0.000 description 1
CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 1
ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical class OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
GFWSTBBSSBVVQP-UHFFFAOYSA-N 5-tert-butyl-2-phenylpyrazol-3-amine Chemical compound N1=C(C(C)(C)C)C=C(N)N1C1=CC=CC=C1 GFWSTBBSSBVVQP-UHFFFAOYSA-N 0.000 description 1
GUULKYKPJKFSFK-UHFFFAOYSA-N 5-tert-butyl-2-pyridin-2-ylpyrazol-3-amine Chemical compound N1=C(C(C)(C)C)C=C(N)N1C1=CC=CC=N1 GUULKYKPJKFSFK-UHFFFAOYSA-N 0.000 description 1
PKZOPZWDEDXAED-UHFFFAOYSA-N 5-tert-butyl-2-pyridin-3-ylpyrazol-3-amine Chemical compound N1=C(C(C)(C)C)C=C(N)N1C1=CC=CN=C1 PKZOPZWDEDXAED-UHFFFAOYSA-N 0.000 description 1
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
OIRDTQYFTABQOQ-CRKDRTNXSA-N 9-α-D-ribofuranosyl-9H-Purin-6-amine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-CRKDRTNXSA-N 0.000 description 1
206010048998 Acute phase reaction Diseases 0.000 description 1
229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
201000002862 Angle-Closure Glaucoma Diseases 0.000 description 1
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
208000003950 B-cell lymphoma Diseases 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
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
206010005003 Bladder cancer Diseases 0.000 description 1
206010005949 Bone cancer Diseases 0.000 description 1
208000018084 Bone neoplasm Diseases 0.000 description 1
201000006474 Brain Ischemia Diseases 0.000 description 1
208000003174 Brain Neoplasms Diseases 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
208000026310 Breast neoplasm Diseases 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
QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 1
108091008038 CHOP Proteins 0.000 description 1
229940124638 COX inhibitor Drugs 0.000 description 1
LERNTVKEWCAPOY-VOGVJGKGSA-N C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 Chemical compound C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 LERNTVKEWCAPOY-VOGVJGKGSA-N 0.000 description 1
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
201000009030 Carcinoma Diseases 0.000 description 1
PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
206010008120 Cerebral ischaemia Diseases 0.000 description 1
206010008342 Cervix carcinoma Diseases 0.000 description 1
229920001661 Chitosan Polymers 0.000 description 1
LUKZNWIVRBCLON-GXOBDPJESA-N Ciclesonide Chemical compound C1([C@H]2O[C@@]3([C@H](O2)C[C@@H]2[C@@]3(C[C@H](O)[C@@H]3[C@@]4(C)C=CC(=O)C=C4CC[C@H]32)C)C(=O)COC(=O)C(C)C)CCCCC1 LUKZNWIVRBCLON-GXOBDPJESA-N 0.000 description 1
208000018652 Closed Head injury Diseases 0.000 description 1
206010009900 Colitis ulcerative Diseases 0.000 description 1
208000001333 Colorectal Neoplasms Diseases 0.000 description 1
208000035473 Communicable disease Diseases 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 1
206010011017 Corneal graft rejection Diseases 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
229920002785 Croscarmellose sodium Polymers 0.000 description 1
229910002483 Cu Ka Inorganic materials 0.000 description 1
102100023033 Cyclic AMP-dependent transcription factor ATF-2 Human genes 0.000 description 1
JVTAAEKCZFNVCJ-UWTATZPHSA-N D-lactic acid Chemical compound C[C@@H](O)C(O)=O JVTAAEKCZFNVCJ-UWTATZPHSA-N 0.000 description 1
102100021246 DDIT3 upstream open reading frame protein Human genes 0.000 description 1
NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
102000012410 DNA Ligases Human genes 0.000 description 1
108010061982 DNA Ligases Proteins 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
206010012689 Diabetic retinopathy Diseases 0.000 description 1
101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 description 1
101100135868 Dictyostelium discoideum pde3 gene Proteins 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
102000015554 Dopamine receptor Human genes 0.000 description 1
108050004812 Dopamine receptor Proteins 0.000 description 1
238000002965 ELISA Methods 0.000 description 1
201000009273 Endometriosis Diseases 0.000 description 1
241000792859 Enema Species 0.000 description 1
241001302160 Escherichia coli str. K-12 substr. DH10B Species 0.000 description 1
208000000461 Esophageal Neoplasms Diseases 0.000 description 1
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
241000400611 Eucalyptus deanei Species 0.000 description 1
229920001917 Ficoll Polymers 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
208000007882 Gastritis Diseases 0.000 description 1
206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
108010024636 Glutathione Proteins 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
208000010496 Heart Arrest Diseases 0.000 description 1
208000016988 Hemorrhagic Stroke Diseases 0.000 description 1
229940122236 Histamine receptor antagonist Drugs 0.000 description 1
108010033040 Histones Proteins 0.000 description 1
101000974934 Homo sapiens Cyclic AMP-dependent transcription factor ATF-2 Proteins 0.000 description 1
101000997829 Homo sapiens Glial cell line-derived neurotrophic factor Proteins 0.000 description 1
101001125071 Homo sapiens Neuromedin-K receptor Proteins 0.000 description 1
101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
208000023105 Huntington disease Diseases 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
239000003458 I kappa b kinase inhibitor Substances 0.000 description 1
208000022559 Inflammatory bowel disease Diseases 0.000 description 1
108010008212 Integrin alpha4beta1 Proteins 0.000 description 1
102000004889 Interleukin-6 Human genes 0.000 description 1
102000042838 JAK family Human genes 0.000 description 1
208000003456 Juvenile Arthritis Diseases 0.000 description 1
206010073678 Juvenile angiofibroma Diseases 0.000 description 1
206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
229930194542 Keto Natural products 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
206010061523 Lip and/or oral cavity cancer Diseases 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
102000055120 MEF2 Transcription Factors Human genes 0.000 description 1
108010018650 MEF2 Transcription Factors Proteins 0.000 description 1
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
102100029409 Neuromedin-K receptor Human genes 0.000 description 1
206010061876 Obstruction Diseases 0.000 description 1
206010030043 Ocular hypertension Diseases 0.000 description 1
206010030155 Oesophageal carcinoma Diseases 0.000 description 1
239000005642 Oleic acid Substances 0.000 description 1
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
208000001388 Opportunistic Infections Diseases 0.000 description 1
208000030768 Optic nerve injury Diseases 0.000 description 1
208000001132 Osteoporosis Diseases 0.000 description 1
206010033128 Ovarian cancer Diseases 0.000 description 1
206010061535 Ovarian neoplasm Diseases 0.000 description 1
239000012661 PARP inhibitor Substances 0.000 description 1
206010061902 Pancreatic neoplasm Diseases 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
229910002666 PdCl2 Inorganic materials 0.000 description 1
208000008469 Peptic Ulcer Diseases 0.000 description 1
229940123263 Phosphodiesterase 3 inhibitor Drugs 0.000 description 1
229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 description 1
206010034960 Photophobia Diseases 0.000 description 1
101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 description 1
206010035664 Pneumonia Diseases 0.000 description 1
229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
241000677647 Proba Species 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 1
108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 description 1
206010060862 Prostate cancer Diseases 0.000 description 1
208000000236 Prostatic Neoplasms Diseases 0.000 description 1
208000019155 Radiation injury Diseases 0.000 description 1
208000006265 Renal cell carcinoma Diseases 0.000 description 1
208000007135 Retinal Neovascularization Diseases 0.000 description 1
206010038910 Retinitis Diseases 0.000 description 1
206010038923 Retinopathy Diseases 0.000 description 1
206010038933 Retinopathy of prematurity Diseases 0.000 description 1
206010051497 Rhinotracheitis Diseases 0.000 description 1
206010061494 Rhinovirus infection Diseases 0.000 description 1
125000000066 S-methyl group Chemical group [H]C([H])([H])S* 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
102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
201000010001 Silicosis Diseases 0.000 description 1
241000580858 Simian-Human immunodeficiency virus Species 0.000 description 1
208000000453 Skin Neoplasms Diseases 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-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
208000006045 Spondylarthropathies Diseases 0.000 description 1
208000005718 Stomach Neoplasms Diseases 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
239000000150 Sympathomimetic Substances 0.000 description 1
229920002253 Tannate Polymers 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
108090000190 Thrombin Proteins 0.000 description 1
208000007536 Thrombosis Diseases 0.000 description 1
108091023040 Transcription factor Proteins 0.000 description 1
102000040945 Transcription factor Human genes 0.000 description 1
206010052779 Transplant rejections Diseases 0.000 description 1
HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
239000013504 Triton X-100 Substances 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
201000006704 Ulcerative Colitis Diseases 0.000 description 1
208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
206010046851 Uveitis Diseases 0.000 description 1
241000700605 Viruses Species 0.000 description 1
238000002441 X-ray diffraction Methods 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
239000003377 acid catalyst Substances 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000004658 acute-phase response Effects 0.000 description 1
125000005042 acyloxymethyl group Chemical group 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
208000009956 adenocarcinoma Diseases 0.000 description 1
WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical class OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 1
239000003470 adrenal cortex hormone Substances 0.000 description 1
239000000048 adrenergic agonist Substances 0.000 description 1
239000003463 adsorbent Substances 0.000 description 1
208000037883 airway inflammation Diseases 0.000 description 1
125000003158 alcohol group Chemical group 0.000 description 1
238000011166 aliquoting Methods 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
150000001348 alkyl chlorides Chemical class 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
230000007815 allergy Effects 0.000 description 1
HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
125000003368 amide group Chemical group 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 1
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
229960000723 ampicillin Drugs 0.000 description 1
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
239000002269 analeptic agent Substances 0.000 description 1
230000000202 analgesic effect Effects 0.000 description 1
230000002491 angiogenic effect Effects 0.000 description 1
150000001448 anilines Chemical class 0.000 description 1
238000005349 anion exchange Methods 0.000 description 1
238000005571 anion exchange chromatography Methods 0.000 description 1
230000000954 anitussive effect Effects 0.000 description 1
208000022531 anorexia Diseases 0.000 description 1
230000001754 anti-pyretic effect Effects 0.000 description 1
239000002518 antifoaming agent Substances 0.000 description 1
239000002221 antipyretic Substances 0.000 description 1
239000003434 antitussive agent Substances 0.000 description 1
229940124584 antitussives Drugs 0.000 description 1
230000001640 apoptogenic effect Effects 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
229960003121 arginine Drugs 0.000 description 1
235000019568 aromas Nutrition 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical class N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
HKVFISRIUUGTIB-UHFFFAOYSA-O azanium;cerium;nitrate Chemical compound [NH4+].[Ce].[O-][N+]([O-])=O HKVFISRIUUGTIB-UHFFFAOYSA-O 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
229950000210 beclometasone dipropionate Drugs 0.000 description 1
230000008901 benefit Effects 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
150000001558 benzoic acid derivatives Chemical class 0.000 description 1
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
HMSXMDJIPWYWCD-UHFFFAOYSA-N benzyl 2-chloro-5-phenylmethoxybenzoate Chemical compound C1=C(C(=O)OCC=2C=CC=CC=2)C(Cl)=CC=C1OCC1=CC=CC=C1 HMSXMDJIPWYWCD-UHFFFAOYSA-N 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
239000000227 bioadhesive Substances 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
230000008512 biological response Effects 0.000 description 1
230000002051 biphasic effect Effects 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
208000019664 bone resorption disease Diseases 0.000 description 1
150000001642 boronic acid derivatives Chemical class 0.000 description 1
150000001649 bromium compounds Chemical class 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
229960004436 budesonide Drugs 0.000 description 1
XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
235000013539 calcium stearate Nutrition 0.000 description 1
125000001589 carboacyl group Chemical group 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 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
239000000969 carrier Substances 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
208000015114 central nervous system disease Diseases 0.000 description 1
206010008118 cerebral infarction Diseases 0.000 description 1
XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 1
201000010881 cervical cancer Diseases 0.000 description 1
230000008859 change Effects 0.000 description 1
DTHLCVJWGVEPFM-UHFFFAOYSA-N chembl1938747 Chemical compound C=1C=CC=CC=1N1N=C(C(C)(C)CSC)C=C1NC(=O)NCC1=CC=CC=C1SC(=CN12)C=CC1=NN=C2C1=CC=CC=C1O DTHLCVJWGVEPFM-UHFFFAOYSA-N 0.000 description 1
239000007910 chewable tablet Substances 0.000 description 1
229940112822 chewing gum Drugs 0.000 description 1
235000015218 chewing gum Nutrition 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
229960003728 ciclesonide Drugs 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
208000029742 colonic neoplasm Diseases 0.000 description 1
238000010668 complexation reaction Methods 0.000 description 1
239000012468 concentrated sample Substances 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
239000002826 coolant Substances 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
RKHQGWMMUURILY-UHRZLXHJSA-N cortivazol Chemical compound C([C@H]1[C@@H]2C[C@H]([C@]([C@@]2(C)C[C@H](O)[C@@H]1[C@@]1(C)C2)(O)C(=O)COC(C)=O)C)=C(C)C1=CC1=C2C=NN1C1=CC=CC=C1 RKHQGWMMUURILY-UHRZLXHJSA-N 0.000 description 1
238000003869 coulometry Methods 0.000 description 1
229940111134 coxibs Drugs 0.000 description 1
229960000265 cromoglicic acid Drugs 0.000 description 1
229960001681 croscarmellose sodium Drugs 0.000 description 1
229960000913 crospovidone Drugs 0.000 description 1
238000006880 cross-coupling reaction Methods 0.000 description 1
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
239000002178 crystalline material Substances 0.000 description 1
238000009109 curative therapy Methods 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical class OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
239000003260 cyclooxygenase 1 inhibitor Substances 0.000 description 1
239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
239000000850 decongestant Substances 0.000 description 1
229940124581 decongestants Drugs 0.000 description 1
206010061428 decreased appetite Diseases 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000018044 dehydration Effects 0.000 description 1
238000006297 dehydration reaction Methods 0.000 description 1
230000008021 deposition Effects 0.000 description 1
238000000151 deposition Methods 0.000 description 1
238000013461 design Methods 0.000 description 1
238000001514 detection method Methods 0.000 description 1
229910052805 deuterium Inorganic materials 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
238000006193 diazotization reaction Methods 0.000 description 1
FHHZOYXKOICLGH-UHFFFAOYSA-N dichloromethane;ethanol Chemical compound CCO.ClCCl FHHZOYXKOICLGH-UHFFFAOYSA-N 0.000 description 1
WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
239000006047 digesta Substances 0.000 description 1
125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
229950010286 diolamine Drugs 0.000 description 1
VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
229940110377 dl- arginine Drugs 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
229940000406 drug candidate Drugs 0.000 description 1
238000009510 drug design Methods 0.000 description 1
229940126534 drug product Drugs 0.000 description 1
238000007908 dry granulation Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000009977 dual effect Effects 0.000 description 1
239000003602 elastase inhibitor Substances 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000003974 emollient agent Substances 0.000 description 1
210000002889 endothelial cell Anatomy 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940079360 enema for constipation Drugs 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
208000037828 epithelial carcinoma Diseases 0.000 description 1
201000004101 esophageal cancer Diseases 0.000 description 1
YKDCATRNPVJHMY-UHFFFAOYSA-N ethyl 2,2-dimethylbutanoate Chemical compound CCOC(=O)C(C)(C)CC YKDCATRNPVJHMY-UHFFFAOYSA-N 0.000 description 1
JLURSSXMQSLZQL-UHFFFAOYSA-N ethyl 2-methyl-2-methylsulfanylpropanoate Chemical compound CCOC(=O)C(C)(C)SC JLURSSXMQSLZQL-UHFFFAOYSA-N 0.000 description 1
MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
239000003172 expectorant agent Substances 0.000 description 1
239000013613 expression plasmid Substances 0.000 description 1
210000002950 fibroblast Anatomy 0.000 description 1
230000003176 fibrotic effect Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000013020 final formulation Substances 0.000 description 1
239000012530 fluid Substances 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
229960000289 fluticasone propionate Drugs 0.000 description 1
239000011888 foil Substances 0.000 description 1
230000037406 food intake Effects 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
150000004675 formic acid derivatives Chemical class 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
238000001640 fractional crystallisation Methods 0.000 description 1
238000004508 fractional distillation Methods 0.000 description 1
230000008014 freezing Effects 0.000 description 1
238000007710 freezing Methods 0.000 description 1
230000006870 function Effects 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
206010017758 gastric cancer Diseases 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
238000001641 gel filtration chromatography Methods 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229960003180 glutathione Drugs 0.000 description 1
150000004676 glycans Chemical class 0.000 description 1
229960002449 glycine Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
239000007902 hard capsule Substances 0.000 description 1
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
230000000004 hemodynamic effect Effects 0.000 description 1
150000002391 heterocyclic compounds Chemical class 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
239000003395 histamine H3 receptor antagonist Substances 0.000 description 1
238000000265 homogenisation Methods 0.000 description 1
239000003906 humectant Substances 0.000 description 1
150000002429 hydrazines Chemical class 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
239000000416 hydrocolloid Substances 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
OVNUPJXMCMTQCN-UHFFFAOYSA-N hydron;(4-phenylmethoxyphenyl)hydrazine;chloride Chemical compound Cl.C1=CC(NN)=CC=C1OCC1=CC=CC=C1 OVNUPJXMCMTQCN-UHFFFAOYSA-N 0.000 description 1
125000005113 hydroxyalkoxy group Chemical group 0.000 description 1
230000000222 hyperoxic effect Effects 0.000 description 1
125000001841 imino group Chemical group [H]N=* 0.000 description 1
239000003018 immunosuppressive agent Substances 0.000 description 1
229940125721 immunosuppressive agent Drugs 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
229960004078 indacaterol Drugs 0.000 description 1
QZZUEBNBZAPZLX-QFIPXVFZSA-N indacaterol Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)CNC1CC(C=C(C(=C2)CC)CC)=C2C1 QZZUEBNBZAPZLX-QFIPXVFZSA-N 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
230000028709 inflammatory response Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
102000014909 interleukin-1 receptor activity proteins Human genes 0.000 description 1
108040006732 interleukin-1 receptor activity proteins Proteins 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
208000020658 intracerebral hemorrhage Diseases 0.000 description 1
238000007917 intracranial administration Methods 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000007916 intrasternal administration Methods 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
238000007915 intraurethral administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000007914 intraventricular administration Methods 0.000 description 1
150000004694 iodide salts Chemical class 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical class O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 1
229960001361 ipratropium bromide Drugs 0.000 description 1
KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 description 1
230000001678 irradiating effect Effects 0.000 description 1
208000002551 irritable bowel syndrome Diseases 0.000 description 1
230000000302 ischemic effect Effects 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
230000000155 isotopic effect Effects 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
238000010902 jet-milling Methods 0.000 description 1
230000000366 juvenile effect Effects 0.000 description 1
208000012496 juvenile nasopharyngeal angiofibroma Diseases 0.000 description 1
208000011379 keloid formation Diseases 0.000 description 1
210000002510 keratinocyte Anatomy 0.000 description 1
125000000468 ketone group Chemical group 0.000 description 1
150000003951 lactams Chemical class 0.000 description 1
150000003893 lactate salts Chemical class 0.000 description 1
150000002596 lactones Chemical class 0.000 description 1
231100000518 lethal Toxicity 0.000 description 1
230000001665 lethal effect Effects 0.000 description 1
229960004873 levomenthol Drugs 0.000 description 1
208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
239000002502 liposome Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
201000007270 liver cancer Diseases 0.000 description 1
208000014018 liver neoplasm Diseases 0.000 description 1
230000033001 locomotion Effects 0.000 description 1
229940127212 long-acting beta 2 agonist Drugs 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
229960003646 lysine Drugs 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
150000004701 malic acid derivatives Chemical class 0.000 description 1
230000036210 malignancy Effects 0.000 description 1
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
150000002690 malonic acid derivatives Chemical class 0.000 description 1
230000000873 masking effect Effects 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
229960003194 meglumine Drugs 0.000 description 1
238000007909 melt granulation Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
229940041616 menthol Drugs 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
239000003475 metalloproteinase inhibitor Substances 0.000 description 1
229940071648 metered dose inhaler Drugs 0.000 description 1
KJRFTNVYOAGTHK-UHFFFAOYSA-N methyl 3-hydroxy-2,2-dimethylpropanoate Chemical compound COC(=O)C(C)(C)CO KJRFTNVYOAGTHK-UHFFFAOYSA-N 0.000 description 1
LJDLEEKULCGTLS-UHFFFAOYSA-N methyl 4-(5-amino-3-tert-butylpyrazol-1-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1N1C(N)=CC(C(C)(C)C)=N1 LJDLEEKULCGTLS-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
150000005451 methyl sulfates Chemical class 0.000 description 1
125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
238000003801 milling Methods 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000003607 modifier Substances 0.000 description 1
238000010369 molecular cloning Methods 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
229960004123 mometasone furoate monohydrate Drugs 0.000 description 1
230000003232 mucoadhesive effect Effects 0.000 description 1
230000000510 mucolytic effect Effects 0.000 description 1
229940066491 mucolytics Drugs 0.000 description 1
210000004877 mucosa Anatomy 0.000 description 1
210000003097 mucus Anatomy 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
FTNFEHXDETWERN-UHFFFAOYSA-N n-[bis(aziridin-1-yl)phosphoryl]-2,6-dimethyl-5-[(4-propan-2-yloxyphenyl)methyl]pyrimidin-4-amine Chemical compound C1=CC(OC(C)C)=CC=C1CC1=C(C)N=C(C)N=C1NP(=O)(N1CC1)N1CC1 FTNFEHXDETWERN-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000002105 nanoparticle Substances 0.000 description 1
125000005487 naphthalate group Chemical group 0.000 description 1
201000003142 neovascular glaucoma Diseases 0.000 description 1
208000004296 neuralgia Diseases 0.000 description 1
208000021722 neuropathic pain Diseases 0.000 description 1
150000002814 niacins Chemical class 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
208000037915 non-allergic respiratory disease Diseases 0.000 description 1
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
235000016709 nutrition Nutrition 0.000 description 1
229950004864 olamine Drugs 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
210000001328 optic nerve Anatomy 0.000 description 1
230000008816 organ damage Effects 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
125000002524 organometallic group Chemical group 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
230000008723 osmotic stress Effects 0.000 description 1
238000012261 overproduction Methods 0.000 description 1
150000003891 oxalate salts Chemical class 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
125000003544 oxime group Chemical group 0.000 description 1
NVOYVOBDTVTBDX-PMEUIYRNSA-N oxitropium Chemical class CC[N+]1(C)[C@H]2C[C@@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)[C@H](CO)C1=CC=CC=C1 NVOYVOBDTVTBDX-PMEUIYRNSA-N 0.000 description 1
LCELQERNWLBPSY-KHSTUMNDSA-M oxitropium bromide Chemical compound [Br-].C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)CC)=CC=CC=C1 LCELQERNWLBPSY-KHSTUMNDSA-M 0.000 description 1
229960001609 oxitropium bromide Drugs 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
238000012856 packing Methods 0.000 description 1
238000002638 palliative care Methods 0.000 description 1
150000002942 palmitic acid derivatives Chemical class 0.000 description 1
201000002528 pancreatic cancer Diseases 0.000 description 1
208000008443 pancreatic carcinoma Diseases 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000037361 pathway Effects 0.000 description 1
235000019371 penicillin G benzathine Nutrition 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
208000011906 peptic ulcer disease Diseases 0.000 description 1
108010021753 peptide-Gly-Leu-amide Proteins 0.000 description 1
210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
208000033808 peripheral neuropathy Diseases 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
JOVOSQBPPZZESK-UHFFFAOYSA-N phenylhydrazine hydrochloride Chemical compound Cl.NNC1=CC=CC=C1 JOVOSQBPPZZESK-UHFFFAOYSA-N 0.000 description 1
QJFMCHRSDOLMHA-UHFFFAOYSA-N phenylmethanamine;hydrobromide Chemical compound Br.NCC1=CC=CC=C1 QJFMCHRSDOLMHA-UHFFFAOYSA-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
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
239000002570 phosphodiesterase III inhibitor Substances 0.000 description 1
239000002590 phosphodiesterase V inhibitor Substances 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
229920001282 polysaccharide Polymers 0.000 description 1
239000005017 polysaccharide Substances 0.000 description 1
229940068968 polysorbate 80 Drugs 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
238000012877 positron emission topography Methods 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229960003975 potassium Drugs 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
OVLYOKPGZAOTSN-UHFFFAOYSA-N potassium;tri(propan-2-yl)-tri(propan-2-yl)silylsulfanylsilane Chemical compound [K].CC(C)[Si](C(C)C)(C(C)C)S[Si](C(C)C)(C(C)C)C(C)C OVLYOKPGZAOTSN-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000001144 powder X-ray diffraction data Methods 0.000 description 1
229960005205 prednisolone Drugs 0.000 description 1
OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
229960004618 prednisone Drugs 0.000 description 1
XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
238000001742 protein purification Methods 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
238000010298 pulverizing process Methods 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
NWELCUKYUCBVKK-UHFFFAOYSA-N pyridin-2-ylhydrazine Chemical compound NNC1=CC=CC=N1 NWELCUKYUCBVKK-UHFFFAOYSA-N 0.000 description 1
KFUSANSHCADHNJ-UHFFFAOYSA-N pyridine-3-carbohydrazide Chemical compound NNC(=O)C1=CC=CN=C1 KFUSANSHCADHNJ-UHFFFAOYSA-N 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
230000005855 radiation Effects 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
229940044601 receptor agonist Drugs 0.000 description 1
239000000018 receptor agonist Substances 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000007142 ring opening reaction Methods 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
210000003296 saliva Anatomy 0.000 description 1
229960004017 salmeterol Drugs 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
238000009738 saturating Methods 0.000 description 1
230000037390 scarring Effects 0.000 description 1
230000007017 scission Effects 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
239000011863 silicon-based powder Substances 0.000 description 1
125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
230000022379 skeletal muscle tissue development Effects 0.000 description 1
201000000849 skin cancer Diseases 0.000 description 1
208000017520 skin disease Diseases 0.000 description 1
201000002314 small intestine cancer Diseases 0.000 description 1
230000000391 smoking effect Effects 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000017550 sodium carbonate Nutrition 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
229940023144 sodium glycolate Drugs 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
229940045902 sodium stearyl fumarate Drugs 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000006104 solid solution Substances 0.000 description 1
235000019337 sorbitan trioleate Nutrition 0.000 description 1
229960000391 sorbitan trioleate Drugs 0.000 description 1
241000894007 species Species 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
208000020431 spinal cord injury Diseases 0.000 description 1
201000005671 spondyloarthropathy Diseases 0.000 description 1
206010041823 squamous cell carcinoma Diseases 0.000 description 1
208000017572 squamous cell neoplasm Diseases 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
201000005428 steroid-induced glaucoma Diseases 0.000 description 1
201000011549 stomach cancer Diseases 0.000 description 1
238000003860 storage Methods 0.000 description 1
230000035882 stress Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
229940127230 sympathomimetic drug Drugs 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
229950004351 telenzepine Drugs 0.000 description 1
GGCIPOJRYPYRKF-UHFFFAOYSA-N tert-butyl n-(4-methoxy-3-methylphenyl)-n-[(2-methylpropan-2-yl)oxycarbonylamino]carbamate Chemical compound COC1=CC=C(N(NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C=C1C GGCIPOJRYPYRKF-UHFFFAOYSA-N 0.000 description 1
125000001302 tertiary amino group Chemical group 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
229960000278 theophylline Drugs 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
239000010409 thin film Substances 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical class 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
229960000257 tiotropium bromide Drugs 0.000 description 1
238000004448 titration Methods 0.000 description 1
125000005490 tosylate group Chemical group 0.000 description 1
230000009466 transformation Effects 0.000 description 1
201000006397 traumatic glaucoma Diseases 0.000 description 1
CPKHFNMJTBLKLK-UHFFFAOYSA-N tri(propan-2-yl)-sulfanylsilane Chemical compound CC(C)[Si](S)(C(C)C)C(C)C CPKHFNMJTBLKLK-UHFFFAOYSA-N 0.000 description 1
OVCXRBARSPBVMC-UHFFFAOYSA-N triazolopyridine Chemical compound C=1N2C(C(C)C)=NN=C2C=CC=1C=1OC=NC=1C1=CC=C(F)C=C1 OVCXRBARSPBVMC-UHFFFAOYSA-N 0.000 description 1
150000008523 triazolopyridines Chemical class 0.000 description 1
UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical class ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
229910052722 tritium Inorganic materials 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
241000712461 unidentified influenza virus Species 0.000 description 1
201000005112 urinary bladder cancer Diseases 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
230000002792 vascular Effects 0.000 description 1
239000005526 vasoconstrictor agent Substances 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
210000001835 viscera Anatomy 0.000 description 1
238000005303 weighing Methods 0.000 description 1
238000005550 wet granulation Methods 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1
XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

MEP-2008-934A 2004-08-12 2005-08-09 Derives de triazolopyridinylsulfanyle en tant qu'inhibiteurs de kinase p38 map ME01360B (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GB0418015A GB0418015D0 (en)	2004-08-12	2004-08-12	New compounds
US69155905P	2005-06-17	2005-06-17
EP05772546A EP1778686B9 (fr)	2004-08-12	2005-08-09	Derives de triazolopyridinylsulfanyle en tant qu'inhibiteurs de kinase p38 map
PCT/IB2005/002574 WO2006018718A2 (fr)	2004-08-12	2005-08-09	Derives de triazolopyridinylsulfanyle en tant qu'inhibiteurs de kinase p38 map

Publications (1)

Publication Number	Publication Date
ME01360B true ME01360B (fr)	2010-06-30

Family

ID=33017410

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
MEP-2008-934A ME01360B (fr)	2004-08-12	2005-08-09	Derives de triazolopyridinylsulfanyle en tant qu'inhibiteurs de kinase p38 map

Country Status (9)

Country	Link
CN (1)	CN101006087B (fr)
GB (1)	GB0418015D0 (fr)
ME (1)	ME01360B (fr)
NI (1)	NI200700039A (fr)
PE (1)	PE20060618A1 (fr)
RS (1)	RS50642B (fr)
TW (1)	TWI295926B (fr)
UA (1)	UA93032C2 (fr)
ZA (1)	ZA200700923B (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PL2303267T3 (pl) *	2008-02-04	2013-11-29	Pfizer Ltd	Polimorficzna postać pochodnej [1,2,4]triazolo[4,3-a]pirydyny do leczenia chorób zapalnych
AU2010215261A1 (en) *	2009-02-17	2011-09-08	Chiesi Farmaceutici S.P.A.	Triazolopyridine derivatives as p38 MAP kinase inhibitors
GB201009731D0 (en) *	2010-06-10	2010-07-21	Pulmagen Therapeutics Inflamma	Kinase inhibitors
PE20141370A1 (es) *	2011-12-09	2014-10-17	Chiesi Farma Spa	Inhibidores de quinasa
CN105693716A (zh) *	2016-03-01	2016-06-22	孙霖	晶型a及制备方法
CN105646484A (zh) *	2016-03-01	2016-06-08	孙霖	晶型b及制备方法

2004
- 2004-08-12 GB GB0418015A patent/GB0418015D0/en not_active Ceased
2005
- 2005-08-09 TW TW94126968A patent/TWI295926B/zh not_active IP Right Cessation
- 2005-08-09 PE PE2005000916A patent/PE20060618A1/es not_active Application Discontinuation
- 2005-08-09 CN CN2005800274566A patent/CN101006087B/zh not_active Expired - Fee Related
- 2005-08-09 UA UAA200701488A patent/UA93032C2/uk unknown
- 2005-08-09 RS RSP-2008/0599A patent/RS50642B/sr unknown
- 2005-08-09 ME MEP-2008-934A patent/ME01360B/fr unknown
2007
- 2007-01-31 ZA ZA200700923A patent/ZA200700923B/xx unknown
- 2007-02-09 NI NI200700039A patent/NI200700039A/es unknown

Also Published As

Publication number	Publication date
ZA200700923B (en)	2008-09-25
TWI295926B (en)	2008-04-21
UA93032C2 (uk)	2011-01-10
CN101006087A (zh)	2007-07-25
GB0418015D0 (en)	2004-09-15
PE20060618A1 (es)	2006-07-14
TW200610529A (en)	2006-04-01
CN101006087B (zh)	2010-09-29
RS50642B (sr)	2010-06-30
NI200700039A (es)	2008-03-07

Publication	Publication Date	Title
CA2576297C (fr)	2011-01-25	Derives de triazolopyridinylsulfanyle en tant qu'inhibiteurs de kinase p38 map
US20090012079A1 (en)	2009-01-08	Triazolopyridine Compounds
ES2737696T3 (es)	2020-01-15	Pirazolopiridinas y pirazolopirimidinas
CN113365631B (zh)	2024-08-30	布鲁顿酪氨酸激酶抑制剂
EP1595881A1 (fr)	2005-11-16	Dérivés de tetrahydronaphthyridine en tant que ligands de récepteur H3 d'histamine
WO2009153720A1 (fr)	2009-12-23	Dérivés de nicotinamide
CN103930424A (zh)	2014-07-16	作为c-Kit激酶抑制剂的化合物和组合物
CN107810185A (zh)	2018-03-16	作为溴结构域抑制剂的二环杂环衍生物
CN119451959A (zh)	2025-02-14	咪唑并[4,5-c]吡啶衍生物作为sik调节剂用于类风湿性关节炎的治疗
ME01360B (fr)	2010-06-30	Derives de triazolopyridinylsulfanyle en tant qu'inhibiteurs de kinase p38 map
EP1846409A1 (fr)	2007-10-24	Dérivés d' octahydropyrrolo[3,4-c]pyrrole
KR100871535B1 (ko)	2008-12-05	Ｐ38 ｍａｐ 키나아제 억제제로서의트리아졸로피리딘일설판일 유도체
HK1105536B (en)	2011-05-06	Triazolopyridinylsulfanyl derivatives as p38 map kinase inhibitors
CN120957978A (zh)	2025-11-14	作为pkmyt1激酶抑制剂的吲唑化合物
HK40053093A (en)	2022-01-28	2,3-dihydro-1h-pyrrolo[3,4-c]pyridin-1-one derivatives as hpk1 inhibitors for the treatment of cancer
HK1234392A1 (en)	2018-02-15	Pyrazolopyridines and pyrazolopyrimidines