ES2265596T3 - Derivados de 1,2,3-triazol-amida como inhibidores de citocinas. - Google Patents

Info

Publication number

ES2265596T3

ES2265596T3 ES03789871T ES03789871T ES2265596T3 ES 2265596 T3 ES2265596 T3 ES 2265596T3 ES 03789871 T ES03789871 T ES 03789871T ES 03789871 T ES03789871 T ES 03789871T ES 2265596 T3 ES2265596 T3 ES 2265596T3

Authority

ES

Spain

Prior art keywords

phenyl

methyl

tert

butyl

methanesulfonylamino

Prior art date

2002-11-27

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

Expired - Lifetime

Links

• Espacenet
• Global Dossier
• Discuss

• 239000003112 inhibitor Substances 0.000 title description 9
• 239000002253 acid Substances 0.000 claims abstract description 156
• 150000001875 compounds Chemical class 0.000 claims abstract description 144
• -1 carbocycle Chemical group 0.000 claims abstract description 102
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 55
• 239000001257 hydrogen Substances 0.000 claims abstract description 34
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 34
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 29
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 23
• 125000003118 aryl group Chemical group 0.000 claims abstract description 21
• 150000002431 hydrogen Chemical group 0.000 claims abstract description 20
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 19
• 150000002367 halogens Chemical class 0.000 claims abstract description 19
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 15
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 14
• 125000002252 acyl group Chemical group 0.000 claims abstract description 14
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 14
• 150000003839 salts Chemical class 0.000 claims abstract description 14
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 13
• 150000007513 acids Chemical class 0.000 claims abstract description 10
• 125000004442 acylamino group Chemical group 0.000 claims abstract description 10
• 125000004423 acyloxy group Chemical group 0.000 claims abstract description 10
• 150000002148 esters Chemical class 0.000 claims abstract description 10
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 10
• 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 9
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 8
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims abstract description 7
• 150000002825 nitriles Chemical class 0.000 claims abstract description 7
• 125000003342 alkenyl group Chemical group 0.000 claims abstract description 6
• 125000000304 alkynyl group Chemical group 0.000 claims abstract description 6
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 5
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 5
• 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 5
• 125000003435 aroyl group Chemical group 0.000 claims abstract description 4
• 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 4
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims abstract description 3
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 3
• 125000004122 cyclic group Chemical group 0.000 claims abstract description 3
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 61
• 201000010099 disease Diseases 0.000 claims description 51
• XOZZYNPAVVPHRQ-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]triazole-4-carboxylic acid Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(O)=O)=C1 XOZZYNPAVVPHRQ-UHFFFAOYSA-N 0.000 claims description 39
• 238000000034 method Methods 0.000 claims description 36
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
• 239000000460 chlorine Substances 0.000 claims description 13
• 125000004076 pyridyl group Chemical group 0.000 claims description 13
• 230000002757 inflammatory effect Effects 0.000 claims description 12
• 208000014674 injury Diseases 0.000 claims description 12
• 238000004519 manufacturing process Methods 0.000 claims description 12
• 230000001154 acute effect Effects 0.000 claims description 11
• 239000007864 aqueous solution Substances 0.000 claims description 11
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
• 230000006378 damage Effects 0.000 claims description 10
• 125000002757 morpholinyl group Chemical group 0.000 claims description 10
• 230000001575 pathological effect Effects 0.000 claims description 10
• 125000003386 piperidinyl group Chemical group 0.000 claims description 10
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 10
• 239000002904 solvent Substances 0.000 claims description 10
• 230000008569 process Effects 0.000 claims description 9
• 208000011580 syndromic disease Diseases 0.000 claims description 9
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 8
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 8
• 150000001540 azides Chemical class 0.000 claims description 8
• 208000035475 disorder Diseases 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 8
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 8
• ZNBCIZKROAZBJE-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-chlorophenyl]triazole-4-carboxylic acid Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(Cl)C(N2N=NC(=C2)C(O)=O)=C1 ZNBCIZKROAZBJE-UHFFFAOYSA-N 0.000 claims description 7
• VLHZHHLVRNKJKP-UHFFFAOYSA-N 5-amino-1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]triazole-4-carboxylic acid Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2C(=C(C(O)=O)N=N2)N)=C1 VLHZHHLVRNKJKP-UHFFFAOYSA-N 0.000 claims description 7
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 7
• 208000027418 Wounds and injury Diseases 0.000 claims description 7
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 7
• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 7
• 230000003902 lesion Effects 0.000 claims description 7
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 7
• 238000002560 therapeutic procedure Methods 0.000 claims description 7
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• 201000006417 multiple sclerosis Diseases 0.000 claims description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 6
• 208000024827 Alzheimer disease Diseases 0.000 claims description 5
• 208000006386 Bone Resorption Diseases 0.000 claims description 5
• 208000002193 Pain Diseases 0.000 claims description 5
• 239000002671 adjuvant Substances 0.000 claims description 5
• 150000001412 amines Chemical class 0.000 claims description 5
• 125000004069 aziridinyl group Chemical group 0.000 claims description 5
• 230000024279 bone resorption Effects 0.000 claims description 5
• 210000003169 central nervous system Anatomy 0.000 claims description 5
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
• 125000002883 imidazolyl group Chemical group 0.000 claims description 5
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
• 125000002971 oxazolyl group Chemical group 0.000 claims description 5
• 125000004193 piperazinyl group Chemical group 0.000 claims description 5
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
• 125000001422 pyrrolinyl group Chemical group 0.000 claims description 5
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 5
• NNLBRYQGMOYARS-UHFFFAOYSA-N thiane 1-oxide Chemical compound O=S1CCCCC1 NNLBRYQGMOYARS-UHFFFAOYSA-N 0.000 claims description 5
• 125000000335 thiazolyl group Chemical group 0.000 claims description 5
• WCNFFKHKJLERFM-UHFFFAOYSA-N thiomorpholinyl sulfone group Chemical group N1(CCSCC1)S(=O)(=O)N1CCSCC1 WCNFFKHKJLERFM-UHFFFAOYSA-N 0.000 claims description 5
• ZCAGUOCUDGWENZ-UHFFFAOYSA-N thiomorpholinyl sulfoxide group Chemical group N1(CCSCC1)S(=O)N1CCSCC1 ZCAGUOCUDGWENZ-UHFFFAOYSA-N 0.000 claims description 5
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
• VGOUIDIUWDZAMQ-UHFFFAOYSA-N 1-[5-[(5-tert-butyl-2-methoxyphenyl)carbamoyl]-2-methylphenyl]triazole-4-carboxylic acid Chemical compound COC1=CC=C(C(C)(C)C)C=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(O)=O)=C1 VGOUIDIUWDZAMQ-UHFFFAOYSA-N 0.000 claims description 4
• 201000001320 Atherosclerosis Diseases 0.000 claims description 4
• 208000011231 Crohn disease Diseases 0.000 claims description 4
• 201000009906 Meningitis Diseases 0.000 claims description 4
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
• 239000003146 anticoagulant agent Substances 0.000 claims description 4
• 208000006673 asthma Diseases 0.000 claims description 4
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 206010012601 diabetes mellitus Diseases 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 4
• 238000011065 in-situ storage Methods 0.000 claims description 4
• 125000001624 naphthyl group Chemical group 0.000 claims description 4
• 201000008482 osteoarthritis Diseases 0.000 claims description 4
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
• 235000010288 sodium nitrite Nutrition 0.000 claims description 4
• 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 4
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 4
• 150000003852 triazoles Chemical class 0.000 claims description 4
• 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 3
• AEPUKVYYZXYIJW-UHFFFAOYSA-N 1-[3-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]phenyl]triazole-4-carboxylic acid Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=CC(N2N=NC(=C2)C(O)=O)=C1 AEPUKVYYZXYIJW-UHFFFAOYSA-N 0.000 claims description 3
• CKRXHRLGSWZPKI-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2,3-dimethylphenyl]triazole-4-carboxylic acid Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC(C)=C(C)C(N2N=NC(=C2)C(O)=O)=C1 CKRXHRLGSWZPKI-UHFFFAOYSA-N 0.000 claims description 3
• SROJYDDZHUJIEF-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-3-fluoro-2-methylphenyl]triazole-4-carboxylic acid Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC(F)=C(C)C(N2N=NC(=C2)C(O)=O)=C1 SROJYDDZHUJIEF-UHFFFAOYSA-N 0.000 claims description 3
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 3
• AJHPGXZOIAYYDW-UHFFFAOYSA-N 3-(2-cyanophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=CC=C1C#N AJHPGXZOIAYYDW-UHFFFAOYSA-N 0.000 claims description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
• 206010012442 Dermatitis contact Diseases 0.000 claims description 3
• 206010048768 Dermatosis Diseases 0.000 claims description 3
• KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 claims description 3
• 206010018366 Glomerulonephritis acute Diseases 0.000 claims description 3
• 201000004681 Psoriasis Diseases 0.000 claims description 3
• 206010040047 Sepsis Diseases 0.000 claims description 3
• 208000006011 Stroke Diseases 0.000 claims description 3
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
• 150000001408 amides Chemical class 0.000 claims description 3
• 206010003246 arthritis Diseases 0.000 claims description 3
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 229910052801 chlorine Inorganic materials 0.000 claims description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• 125000004276 dioxalanyl group Chemical group 0.000 claims description 3
• 208000010227 enterocolitis Diseases 0.000 claims description 3
• 125000002541 furyl group Chemical group 0.000 claims description 3
• 210000003714 granulocyte Anatomy 0.000 claims description 3
• 238000001631 haemodialysis Methods 0.000 claims description 3
• 230000000322 hemodialysis Effects 0.000 claims description 3
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 3
• 125000001041 indolyl group Chemical group 0.000 claims description 3
• 208000010125 myocardial infarction Diseases 0.000 claims description 3
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 3
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 3
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 3
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
• 230000010410 reperfusion Effects 0.000 claims description 3
• 208000037803 restenosis Diseases 0.000 claims description 3
• 230000035939 shock Effects 0.000 claims description 3
• 208000017520 skin disease Diseases 0.000 claims description 3
• HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 3
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 3
• ISXOBTBCNRIIQO-UHFFFAOYSA-N tetrahydrothiophene 1-oxide Chemical compound O=S1CCCC1 ISXOBTBCNRIIQO-UHFFFAOYSA-N 0.000 claims description 3
• BUGOPWGPQGYYGR-UHFFFAOYSA-N thiane 1,1-dioxide Chemical compound O=S1(=O)CCCCC1 BUGOPWGPQGYYGR-UHFFFAOYSA-N 0.000 claims description 3
• 125000001544 thienyl group Chemical group 0.000 claims description 3
• 230000002537 thrombolytic effect Effects 0.000 claims description 3
• 125000001425 triazolyl group Chemical group 0.000 claims description 3
• YFHICDDUDORKJB-UHFFFAOYSA-N trimethylene carbonate Chemical compound O=C1OCCCO1 YFHICDDUDORKJB-UHFFFAOYSA-N 0.000 claims description 3
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
• FAPKMWWBUNYNKN-UHFFFAOYSA-N 1-[5-[[3-(methanesulfonamido)-2-methoxy-5-(trifluoromethyl)phenyl]carbamoyl]-2-methylphenyl]triazole-4-carboxylic acid Chemical compound C1=C(C(F)(F)F)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(O)=O)=C1 FAPKMWWBUNYNKN-UHFFFAOYSA-N 0.000 claims description 2
• SOBXUYMZUBUAOG-UHFFFAOYSA-N 4-morpholin-4-ylsulfonylmorpholine Chemical compound C1COCCN1S(=O)(=O)N1CCOCC1 SOBXUYMZUBUAOG-UHFFFAOYSA-N 0.000 claims description 2
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
• 208000000094 Chronic Pain Diseases 0.000 claims description 2
• 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 2
• 208000005298 acute pain Diseases 0.000 claims description 2
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
• 239000003054 catalyst Substances 0.000 claims description 2
• 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 claims description 2
• 239000012954 diazonium Substances 0.000 claims description 2
• 150000001989 diazonium salts Chemical class 0.000 claims description 2
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
• TYEWNBMWTXMGOC-UHFFFAOYSA-N n-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-4-methyl-3-[4-(morpholine-4-carbonyl)triazol-1-yl]benzamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)N2CCOCC2)=C1 TYEWNBMWTXMGOC-UHFFFAOYSA-N 0.000 claims description 2
• 230000000771 oncological effect Effects 0.000 claims description 2
• 210000000056 organ Anatomy 0.000 claims description 2
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 2
• RCSSHZGQHHEHPZ-MRVPVSSYSA-N (1r)-n-methyl-1-phenylethanamine Chemical compound CN[C@H](C)C1=CC=CC=C1 RCSSHZGQHHEHPZ-MRVPVSSYSA-N 0.000 claims 3
• TWMNPSJTUSFPEC-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-(2,2-dimethylpropyl)triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NCC(C)(C)C)=C1 TWMNPSJTUSFPEC-UHFFFAOYSA-N 0.000 claims 2
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 2
• MYKHBWFULXPPPE-UHFFFAOYSA-N 1-[5-[(3-amino-5-tert-butyl-2-methoxyphenyl)carbamoyl]-2-methylphenyl]-n-(2,2-dimethylpropyl)triazole-4-carboxamide Chemical compound COC1=C(N)C=C(C(C)(C)C)C=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NCC(C)(C)C)=C1 MYKHBWFULXPPPE-UHFFFAOYSA-N 0.000 claims 1
• FFDIGMODELFUPV-UHFFFAOYSA-N 1-[5-[(5-tert-butyl-2-methoxyphenyl)carbamoyl]-2-methylphenyl]-n-(2-morpholin-4-ylethyl)triazole-4-carboxamide Chemical compound COC1=CC=C(C(C)(C)C)C=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NCCN2CCOCC2)=C1 FFDIGMODELFUPV-UHFFFAOYSA-N 0.000 claims 1
• VTRVTYITLGKQKR-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-chlorophenyl]-n-(2,2-dimethylpropyl)triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(Cl)C(N2N=NC(=C2)C(=O)NCC(C)(C)C)=C1 VTRVTYITLGKQKR-UHFFFAOYSA-N 0.000 claims 1
• IEDNIQALLRPMFJ-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-chlorophenyl]-n-(pyridin-3-ylmethyl)triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(Cl)C(N2N=NC(=C2)C(=O)NCC=2C=NC=CC=2)=C1 IEDNIQALLRPMFJ-UHFFFAOYSA-N 0.000 claims 1
• WLQPPEXYIUYGHM-HSZRJFAPSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-chlorophenyl]-n-[(1r)-1-phenylpropyl]triazole-4-carboxamide Chemical compound N([C@H](CC)C=1C=CC=CC=1)C(=O)C(N=N1)=CN1C(C(=CC=1)Cl)=CC=1C(=O)NC1=CC(C(C)(C)C)=CC(NS(C)(=O)=O)=C1OC WLQPPEXYIUYGHM-HSZRJFAPSA-N 0.000 claims 1
• BSCPSIHMYYIRHZ-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-fluorophenyl]-n-(2,2-dimethylpropyl)triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(F)C(N2N=NC(=C2)C(=O)NCC(C)(C)C)=C1 BSCPSIHMYYIRHZ-UHFFFAOYSA-N 0.000 claims 1
• KNMFMVBWDXPKBO-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-(1-pyridin-3-ylethyl)triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NC(C)C=2C=NC=CC=2)=C1 KNMFMVBWDXPKBO-UHFFFAOYSA-N 0.000 claims 1
• NSNSJQAJKXHCJR-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-(2-hydroxy-2-methylpropyl)triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NCC(C)(C)O)=C1 NSNSJQAJKXHCJR-UHFFFAOYSA-N 0.000 claims 1
• MKXAJPGTSOMAFW-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-(2-morpholin-4-ylethyl)triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NCCN2CCOCC2)=C1 MKXAJPGTSOMAFW-UHFFFAOYSA-N 0.000 claims 1
• LIIRZZMKVKMXHG-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-(2-phenylpropan-2-yl)triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NC(C)(C)C=2C=CC=CC=2)=C1 LIIRZZMKVKMXHG-UHFFFAOYSA-N 0.000 claims 1
• QFXBWQVIBRTSLX-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-(piperidin-4-ylmethyl)triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NCC2CCNCC2)=C1 QFXBWQVIBRTSLX-UHFFFAOYSA-N 0.000 claims 1
• OIRLBRWAGYPJRL-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-(pyridin-3-ylmethyl)triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NCC=2C=NC=CC=2)=C1 OIRLBRWAGYPJRL-UHFFFAOYSA-N 0.000 claims 1
• UXZKSNGYAVJNHF-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-(pyridin-4-ylmethyl)triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NCC=2C=CN=CC=2)=C1 UXZKSNGYAVJNHF-UHFFFAOYSA-N 0.000 claims 1
• SZCBXPJTUSQJOC-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[(1-methylpiperidin-3-yl)methyl]triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NCC2CN(C)CCC2)=C1 SZCBXPJTUSQJOC-UHFFFAOYSA-N 0.000 claims 1
• BEUFWZFQQOTSOA-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[(1-methylpiperidin-4-yl)methyl]triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NCC2CCN(C)CC2)=C1 BEUFWZFQQOTSOA-UHFFFAOYSA-N 0.000 claims 1
• MPTIBCHEZCLPEU-HXUWFJFHSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[(1r)-1-phenylethyl]triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)N[C@H](C)C=2C=CC=CC=2)=C1 MPTIBCHEZCLPEU-HXUWFJFHSA-N 0.000 claims 1
• DBGHYGSALMWLLM-XMMPIXPASA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[(1r)-1-phenylpropyl]triazole-4-carboxamide Chemical compound N([C@H](CC)C=1C=CC=CC=1)C(=O)C(N=N1)=CN1C(C(=CC=1)C)=CC=1C(=O)NC1=CC(C(C)(C)C)=CC(NS(C)(=O)=O)=C1OC DBGHYGSALMWLLM-XMMPIXPASA-N 0.000 claims 1
• XMEBCDMICYXMPN-AREMUKBSSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[(1r)-3-(dimethylamino)-1-phenylpropyl]triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)N[C@H](CCN(C)C)C=2C=CC=CC=2)=C1 XMEBCDMICYXMPN-AREMUKBSSA-N 0.000 claims 1
• GQEQCKCNBUCAMO-FQEVSTJZSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[(1s)-1-cyclohexylethyl]triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)N[C@@H](C)C2CCCCC2)=C1 GQEQCKCNBUCAMO-FQEVSTJZSA-N 0.000 claims 1
• MPTIBCHEZCLPEU-FQEVSTJZSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[(1s)-1-phenylethyl]triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)N[C@@H](C)C=2C=CC=CC=2)=C1 MPTIBCHEZCLPEU-FQEVSTJZSA-N 0.000 claims 1
• RZLBVMIOOFAEBX-HHHXNRCGSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[(1s)-2-(dimethylamino)-1-phenylethyl]triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)N[C@H](CN(C)C)C=2C=CC=CC=2)=C1 RZLBVMIOOFAEBX-HHHXNRCGSA-N 0.000 claims 1
• MOYBVQRLCMRPHZ-HHHXNRCGSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[(1s)-2-methoxy-1-phenylethyl]triazole-4-carboxamide Chemical compound N([C@H](COC)C=1C=CC=CC=1)C(=O)C(N=N1)=CN1C(C(=CC=1)C)=CC=1C(=O)NC1=CC(C(C)(C)C)=CC(NS(C)(=O)=O)=C1OC MOYBVQRLCMRPHZ-HHHXNRCGSA-N 0.000 claims 1
• BCZVTYMHNFUTNX-SFHVURJKSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[(2s)-3,3-dimethylbutan-2-yl]triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)N[C@@H](C)C(C)(C)C)=C1 BCZVTYMHNFUTNX-SFHVURJKSA-N 0.000 claims 1
• DLJBAWIPWXUPHU-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[(3-methylphenyl)methyl]triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NCC=2C=C(C)C=CC=2)=C1 DLJBAWIPWXUPHU-UHFFFAOYSA-N 0.000 claims 1
• FXKFUQGISSNGPZ-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[2-(dimethylamino)-2-methylpropyl]triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NCC(C)(C)N(C)C)=C1 FXKFUQGISSNGPZ-UHFFFAOYSA-N 0.000 claims 1
• UGWSSKXHAHYOAM-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[3-(dimethylamino)-2,2-dimethylpropyl]triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NCC(C)(C)CN(C)C)=C1 UGWSSKXHAHYOAM-UHFFFAOYSA-N 0.000 claims 1
• UYAPGVFFEFPITJ-JOCHJYFZSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[[(2r)-1-ethylpyrrolidin-2-yl]methyl]triazole-4-carboxamide Chemical compound CCN1CCC[C@@H]1CNC(=O)C1=CN(C=2C(=CC=C(C=2)C(=O)NC=2C(=C(NS(C)(=O)=O)C=C(C=2)C(C)(C)C)OC)C)N=N1 UYAPGVFFEFPITJ-JOCHJYFZSA-N 0.000 claims 1
• UYAPGVFFEFPITJ-QFIPXVFZSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]triazole-4-carboxamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=CN(C=2C(=CC=C(C=2)C(=O)NC=2C(=C(NS(C)(=O)=O)C=C(C=2)C(C)(C)C)OC)C)N=N1 UYAPGVFFEFPITJ-QFIPXVFZSA-N 0.000 claims 1
• OPAOMYVCXCLDME-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-pyridin-4-yltriazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NC=2C=CN=CC=2)=C1 OPAOMYVCXCLDME-UHFFFAOYSA-N 0.000 claims 1
• QSDPAWDWCPJGAE-UHFFFAOYSA-N 2-methyl-n-(pyridin-3-ylmethyl)propan-2-amine Chemical compound CC(C)(C)NCC1=CC=CN=C1 QSDPAWDWCPJGAE-UHFFFAOYSA-N 0.000 claims 1
• CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical compound NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 claims 1
• PANOUFIWMXHNES-UHFFFAOYSA-N 5-amino-1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-(2,2-dimethylpropyl)triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2C(=C(C(=O)NCC(C)(C)C)N=N2)N)=C1 PANOUFIWMXHNES-UHFFFAOYSA-N 0.000 claims 1
• GLZIQUGSLFRMPD-KRWDZBQOSA-N 5-amino-1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]-n-[(2s)-3,3-dimethylbutan-2-yl]triazole-4-carboxamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2C(=C(C(=O)N[C@@H](C)C(C)(C)C)N=N2)N)=C1 GLZIQUGSLFRMPD-KRWDZBQOSA-N 0.000 claims 1
• AZQHRFIZPVTYNX-UHFFFAOYSA-N CC(C)(C)C(C=C1NS(C)(=O)=O)=CC(NC(C2=CC=C(C)C(N3N=NC(C(O)=O)=C3)=C2)=O)=C1OC.CNCC1=CC=CC=C1 Chemical compound CC(C)(C)C(C=C1NS(C)(=O)=O)=CC(NC(C2=CC=C(C)C(N3N=NC(C(O)=O)=C3)=C2)=O)=C1OC.CNCC1=CC=CC=C1 AZQHRFIZPVTYNX-UHFFFAOYSA-N 0.000 claims 1
• 208000000860 Compassion Fatigue Diseases 0.000 claims 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims 1
• 206010065390 Inflammatory pain Diseases 0.000 claims 1
• 206010049567 Miller Fisher syndrome Diseases 0.000 claims 1
• 230000002378 acidificating effect Effects 0.000 claims 1
• JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 claims 1
• 208000010247 contact dermatitis Diseases 0.000 claims 1
• 229910052802 copper Inorganic materials 0.000 claims 1
• 239000010949 copper Substances 0.000 claims 1
• MKSRIAPRXGGSJY-UHFFFAOYSA-N ethyl 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-chlorophenyl]triazole-4-carboxylate Chemical compound N1=NC(C(=O)OCC)=CN1C1=CC(C(=O)NC=2C(=C(NS(C)(=O)=O)C=C(C=2)C(C)(C)C)OC)=CC=C1Cl MKSRIAPRXGGSJY-UHFFFAOYSA-N 0.000 claims 1
• SSTIHKVVJKBUKR-UHFFFAOYSA-N ethyl 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]triazole-4-carboxylate Chemical compound N1=NC(C(=O)OCC)=CN1C1=CC(C(=O)NC=2C(=C(NS(C)(=O)=O)C=C(C=2)C(C)(C)C)OC)=CC=C1C SSTIHKVVJKBUKR-UHFFFAOYSA-N 0.000 claims 1
• 210000004165 myocardium Anatomy 0.000 claims 1
• DNLSFPVYJMSODF-UHFFFAOYSA-N n-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-3-[4-(2,6-dichlorobenzoyl)triazol-1-yl]-4-methylbenzamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)C=2C(=CC=CC=2Cl)Cl)=C1 DNLSFPVYJMSODF-UHFFFAOYSA-N 0.000 claims 1
• UEBKINPAGUSUBV-UHFFFAOYSA-N n-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-3-[4-(2,6-dimethylbenzoyl)triazol-1-yl]-4-methylbenzamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)C=2C(=CC=CC=2C)C)=C1 UEBKINPAGUSUBV-UHFFFAOYSA-N 0.000 claims 1
• WUGPWNUTZZUASG-UHFFFAOYSA-N n-benzyl-1-[5-[(5-tert-butyl-2-methoxyphenyl)carbamoyl]-2-methylphenyl]triazole-4-carboxamide Chemical compound COC1=CC=C(C(C)(C)C)C=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)NCC=2C=CC=CC=2)=C1 WUGPWNUTZZUASG-UHFFFAOYSA-N 0.000 claims 1
• 201000004193 respiratory failure Diseases 0.000 claims 1
• 231100000331 toxic Toxicity 0.000 claims 1
• 230000002588 toxic effect Effects 0.000 claims 1
• 230000000472 traumatic effect Effects 0.000 claims 1
• 229910052760 oxygen Inorganic materials 0.000 abstract description 6
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 abstract 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 90
• 239000000243 solution Substances 0.000 description 51
• 239000000203 mixture Substances 0.000 description 49
• 102000004127 Cytokines Human genes 0.000 description 43
• 108090000695 Cytokines Proteins 0.000 description 43
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 41
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 37
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 37
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 34
• MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 26
• 102000000589 Interleukin-1 Human genes 0.000 description 25
• 108010002352 Interleukin-1 Proteins 0.000 description 25
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
• 239000007787 solid Substances 0.000 description 24
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
• 239000002244 precipitate Substances 0.000 description 18
• 238000011282 treatment Methods 0.000 description 17
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
• 235000019439 ethyl acetate Nutrition 0.000 description 16
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• 230000015572 biosynthetic process Effects 0.000 description 15
• 210000004027 cell Anatomy 0.000 description 15
• 230000004054 inflammatory process Effects 0.000 description 15
• 206010061218 Inflammation Diseases 0.000 description 14
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
• 229910052938 sodium sulfate Inorganic materials 0.000 description 14
• 235000011152 sodium sulphate Nutrition 0.000 description 14
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 13
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
• 238000006243 chemical reaction Methods 0.000 description 13
• 239000012074 organic phase Substances 0.000 description 13
• 238000003786 synthesis reaction Methods 0.000 description 13
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
• 102000004889 Interleukin-6 Human genes 0.000 description 11
• 108090001005 Interleukin-6 Proteins 0.000 description 11
• 239000008346 aqueous phase Substances 0.000 description 11
• 239000012141 concentrate Substances 0.000 description 11
• 235000008504 concentrate Nutrition 0.000 description 11
• 230000001404 mediated effect Effects 0.000 description 11
• 230000000770 proinflammatory effect Effects 0.000 description 11
• 238000003756 stirring Methods 0.000 description 11
• XDIAMRVROCPPBK-UHFFFAOYSA-N 2,2-dimethylpropan-1-amine Chemical compound CC(C)(C)CN XDIAMRVROCPPBK-UHFFFAOYSA-N 0.000 description 10
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• 206010028980 Neoplasm Diseases 0.000 description 10
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 10
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
• 239000000725 suspension Substances 0.000 description 10
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 9
• 239000000543 intermediate Substances 0.000 description 9
• 230000014509 gene expression Effects 0.000 description 8
• 239000007788 liquid Substances 0.000 description 8
• 239000011541 reaction mixture Substances 0.000 description 8
• 235000017557 sodium bicarbonate Nutrition 0.000 description 8
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 7
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 7
• 108090001007 Interleukin-8 Proteins 0.000 description 7
• 102000004890 Interleukin-8 Human genes 0.000 description 7
• 206010039491 Sarcoma Diseases 0.000 description 7
• 230000000694 effects Effects 0.000 description 7
• 239000000284 extract Substances 0.000 description 7
• 229910052757 nitrogen Inorganic materials 0.000 description 7
• 239000000047 product Substances 0.000 description 7
• 239000011734 sodium Substances 0.000 description 7
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
• 102100026018 Interleukin-1 receptor antagonist protein Human genes 0.000 description 6
• 101710144554 Interleukin-1 receptor antagonist protein Proteins 0.000 description 6
• 201000011510 cancer Diseases 0.000 description 6
• 238000004587 chromatography analysis Methods 0.000 description 6
• 230000008506 pathogenesis Effects 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• 229920006395 saturated elastomer Polymers 0.000 description 6
• 239000012047 saturated solution Substances 0.000 description 6
• 238000012360 testing method Methods 0.000 description 6
• 230000008733 trauma Effects 0.000 description 6
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
• 241000725303 Human immunodeficiency virus Species 0.000 description 5
• 206010020772 Hypertension Diseases 0.000 description 5
• 206010025323 Lymphomas Diseases 0.000 description 5
• 239000007832 Na2SO4 Substances 0.000 description 5
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
• 235000011114 ammonium hydroxide Nutrition 0.000 description 5
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
• 210000000988 bone and bone Anatomy 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 230000001684 chronic effect Effects 0.000 description 5
• 238000011161 development Methods 0.000 description 5
• 239000002552 dosage form Substances 0.000 description 5
• 239000007789 gas Substances 0.000 description 5
• 125000005842 heteroatom Chemical group 0.000 description 5
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
• 238000013456 study Methods 0.000 description 5
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
• 206010006895 Cachexia Diseases 0.000 description 4
• 229910004373 HOAc Inorganic materials 0.000 description 4
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
• 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 4
• 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 4
• 206010040070 Septic Shock Diseases 0.000 description 4
• 239000000908 ammonium hydroxide Substances 0.000 description 4
• 239000012298 atmosphere Substances 0.000 description 4
• 125000004429 atom Chemical group 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• 239000012267 brine Substances 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 229940125782 compound 2 Drugs 0.000 description 4
• 239000002158 endotoxin Substances 0.000 description 4
• 230000005764 inhibitory process Effects 0.000 description 4
• 230000004048 modification Effects 0.000 description 4
• 238000012986 modification Methods 0.000 description 4
• RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 4
• 230000007302 negative regulation of cytokine production Effects 0.000 description 4
• 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 4
• 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 4
• 239000012071 phase Substances 0.000 description 4
• 239000000651 prodrug Substances 0.000 description 4
• 229940002612 prodrug Drugs 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• 239000003981 vehicle Substances 0.000 description 4
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• LMOXPGJOBXPJOX-UHFFFAOYSA-N 1-(5-carboxy-2-methylphenyl)triazole-4-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)C=C1N1N=NC(C(O)=O)=C1 LMOXPGJOBXPJOX-UHFFFAOYSA-N 0.000 description 3
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
• XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
• 206010007559 Cardiac failure congestive Diseases 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 208000031886 HIV Infections Diseases 0.000 description 3
• 208000037357 HIV infectious disease Diseases 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• 208000034578 Multiple myelomas Diseases 0.000 description 3
• 241000699670 Mus sp. Species 0.000 description 3
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 3
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 206010035226 Plasma cell myeloma Diseases 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• 210000001744 T-lymphocyte Anatomy 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• 238000013019 agitation Methods 0.000 description 3
• 150000001345 alkine derivatives Chemical class 0.000 description 3
• 239000005557 antagonist Substances 0.000 description 3
• 230000003092 anti-cytokine Effects 0.000 description 3
• 210000004556 brain Anatomy 0.000 description 3
• 210000000845 cartilage Anatomy 0.000 description 3
• 208000037976 chronic inflammation Diseases 0.000 description 3
• 230000016396 cytokine production Effects 0.000 description 3
• 239000012065 filter cake Substances 0.000 description 3
• 238000005755 formation reaction Methods 0.000 description 3
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 208000015181 infectious disease Diseases 0.000 description 3
• 210000003734 kidney Anatomy 0.000 description 3
• 208000032839 leukemia Diseases 0.000 description 3
• 229920006008 lipopolysaccharide Polymers 0.000 description 3
• 210000000440 neutrophil Anatomy 0.000 description 3
• 210000005259 peripheral blood Anatomy 0.000 description 3
• 239000011886 peripheral blood Substances 0.000 description 3
• 230000002093 peripheral effect Effects 0.000 description 3
• 230000001105 regulatory effect Effects 0.000 description 3
• 239000000741 silica gel Substances 0.000 description 3
• 229910002027 silica gel Inorganic materials 0.000 description 3
• 239000000377 silicon dioxide Substances 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 239000011593 sulfur Substances 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 230000006433 tumor necrosis factor production Effects 0.000 description 3
• 238000003828 vacuum filtration Methods 0.000 description 3
• GPJCOEQTQFSCML-UHFFFAOYSA-N 1-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]ethanone Chemical compound CC(=O)C1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1 GPJCOEQTQFSCML-UHFFFAOYSA-N 0.000 description 2
• YMAQHAVEPHTWAZ-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-fluorophenyl]triazole-4-carboxylic acid Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(F)C(N2N=NC(=C2)C(O)=O)=C1 YMAQHAVEPHTWAZ-UHFFFAOYSA-N 0.000 description 2
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
• USNMEXZFIQEGFX-UHFFFAOYSA-N 2-methoxy-5-(1-methylcyclopropyl)-1,3-dinitrobenzene Chemical compound C1=C([N+]([O-])=O)C(OC)=C([N+]([O-])=O)C=C1C1(C)CC1 USNMEXZFIQEGFX-UHFFFAOYSA-N 0.000 description 2
• HNIKMYLSIUXTME-UHFFFAOYSA-N 2-methoxy-5-(1-methylcyclopropyl)benzene-1,3-diamine Chemical compound C1=C(N)C(OC)=C(N)C=C1C1(C)CC1 HNIKMYLSIUXTME-UHFFFAOYSA-N 0.000 description 2
• ABGXUDXGHZBNOW-UHFFFAOYSA-N 3-(4-benzoyltriazol-1-yl)-4,5-dimethylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC(N2N=NC(=C2)C(=O)C=2C=CC=CC=2)=C1C ABGXUDXGHZBNOW-UHFFFAOYSA-N 0.000 description 2
• YAEMLESXRFYIPI-UHFFFAOYSA-N 3-azido-n-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-4,5-dimethylbenzamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC(C)=C(C)C(N=[N+]=[N-])=C1 YAEMLESXRFYIPI-UHFFFAOYSA-N 0.000 description 2
• TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 2
• URBFAECGYIAXDC-UHFFFAOYSA-N 4-(1-methylcyclopropyl)phenol Chemical compound C=1C=C(O)C=CC=1C1(C)CC1 URBFAECGYIAXDC-UHFFFAOYSA-N 0.000 description 2
• 206010065040 AIDS dementia complex Diseases 0.000 description 2
• 206010048998 Acute phase reaction Diseases 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• 208000000103 Anorexia Nervosa Diseases 0.000 description 2
• 208000023275 Autoimmune disease Diseases 0.000 description 2
• 208000009137 Behcet syndrome Diseases 0.000 description 2
• 239000005711 Benzoic acid Substances 0.000 description 2
• 206010006187 Breast cancer Diseases 0.000 description 2
• 208000026310 Breast neoplasm Diseases 0.000 description 2
• 201000009030 Carcinoma Diseases 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 208000035473 Communicable disease Diseases 0.000 description 2
• 206010010904 Convulsion Diseases 0.000 description 2
• 102100029133 DNA damage-induced apoptosis suppressor protein Human genes 0.000 description 2
• 206010012438 Dermatitis atopic Diseases 0.000 description 2
• 238000008157 ELISA kit Methods 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
• 206010019280 Heart failures Diseases 0.000 description 2
• 241000700721 Hepatitis B virus Species 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 241000282414 Homo sapiens Species 0.000 description 2
• 101000918646 Homo sapiens DNA damage-induced apoptosis suppressor protein Proteins 0.000 description 2
• 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 2
• 206010021143 Hypoxia Diseases 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
• 108010002350 Interleukin-2 Proteins 0.000 description 2
• 102000000588 Interleukin-2 Human genes 0.000 description 2
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
• 229930182816 L-glutamine Natural products 0.000 description 2
• 102000003960 Ligases Human genes 0.000 description 2
• 108090000364 Ligases Proteins 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
• 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 2
• 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 2
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
• 208000002774 Paraproteinemias Diseases 0.000 description 2
• 206010035664 Pneumonia Diseases 0.000 description 2
• 206010037660 Pyrexia Diseases 0.000 description 2
• 239000012980 RPMI-1640 medium Substances 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 208000000453 Skin Neoplasms Diseases 0.000 description 2
• 206010044248 Toxic shock syndrome Diseases 0.000 description 2
• 231100000650 Toxic shock syndrome Toxicity 0.000 description 2
• 206010048873 Traumatic arthritis Diseases 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 231100000851 acute glomerulonephritis Toxicity 0.000 description 2
• 208000038016 acute inflammation Diseases 0.000 description 2
• 230000006022 acute inflammation Effects 0.000 description 2
• 230000000172 allergic effect Effects 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 229940072107 ascorbate Drugs 0.000 description 2
• 235000010323 ascorbic acid Nutrition 0.000 description 2
• 239000011668 ascorbic acid Substances 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 230000003143 atherosclerotic effect Effects 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 201000008937 atopic dermatitis Diseases 0.000 description 2
• 208000010668 atopic eczema Diseases 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 235000010233 benzoic acid Nutrition 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• 125000002619 bicyclic group Chemical group 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• 230000010072 bone remodeling Effects 0.000 description 2
• 235000013877 carbamide Nutrition 0.000 description 2
• 230000015556 catabolic process Effects 0.000 description 2
• 206010008118 cerebral infarction Diseases 0.000 description 2
• 208000006990 cholangiocarcinoma Diseases 0.000 description 2
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 2
• 208000024207 chronic leukemia Diseases 0.000 description 2
• 238000006731 degradation reaction Methods 0.000 description 2
• 206010013663 drug dependence Diseases 0.000 description 2
• 230000004064 dysfunction Effects 0.000 description 2
• 230000002526 effect on cardiovascular system Effects 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 2
• 239000012091 fetal bovine serum Substances 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 238000007429 general method Methods 0.000 description 2
• 210000003128 head Anatomy 0.000 description 2
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
• 239000012456 homogeneous solution Substances 0.000 description 2
• 102000057041 human TNF Human genes 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 208000030603 inherited susceptibility to asthma Diseases 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
• 210000004185 liver Anatomy 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• 210000002540 macrophage Anatomy 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 201000001441 melanoma Diseases 0.000 description 2
• 239000002207 metabolite Substances 0.000 description 2
• 208000037890 multiple organ injury Diseases 0.000 description 2
• XNPVTUDLRVNVLW-UHFFFAOYSA-N n-(3-amino-5-tert-butyl-2-methoxyphenyl)methanesulfonamide Chemical compound COC1=C(N)C=C(C(C)(C)C)C=C1NS(C)(=O)=O XNPVTUDLRVNVLW-UHFFFAOYSA-N 0.000 description 2
• MHCJTTVYNIBTAB-UHFFFAOYSA-N n-(3-amino-5-tert-butyl-2-methoxyphenyl)methanesulfonamide;hydrochloride Chemical compound Cl.COC1=C(N)C=C(C(C)(C)C)C=C1NS(C)(=O)=O MHCJTTVYNIBTAB-UHFFFAOYSA-N 0.000 description 2
• HRSAVGBBYYPWNX-UHFFFAOYSA-N n-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-3,4-dimethyl-5-nitrobenzamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC(C)=C(C)C([N+]([O-])=O)=C1 HRSAVGBBYYPWNX-UHFFFAOYSA-N 0.000 description 2
• 125000006574 non-aromatic ring group Chemical group 0.000 description 2
• 239000003921 oil Substances 0.000 description 2
• 210000002997 osteoclast Anatomy 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• 210000000496 pancreas Anatomy 0.000 description 2
• 230000001717 pathogenic effect Effects 0.000 description 2
• 230000007170 pathology Effects 0.000 description 2
• 230000007310 pathophysiology Effects 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 238000009522 phase III clinical trial Methods 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• IPOVLZSJBYKHHU-UHFFFAOYSA-N piperidin-3-ylmethanamine Chemical compound NCC1CCCNC1 IPOVLZSJBYKHHU-UHFFFAOYSA-N 0.000 description 2
• 208000001685 postmenopausal osteoporosis Diseases 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 230000035755 proliferation Effects 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 238000001953 recrystallisation Methods 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000006722 reduction reaction Methods 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 230000010076 replication Effects 0.000 description 2
• 230000000241 respiratory effect Effects 0.000 description 2
• 210000002345 respiratory system Anatomy 0.000 description 2
• 206010039083 rhinitis Diseases 0.000 description 2
• 230000036303 septic shock Effects 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 239000000779 smoke Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 2
• 229910000342 sodium bisulfate Inorganic materials 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 208000011117 substance-related disease Diseases 0.000 description 2
• GANAAUIATAGRLR-UHFFFAOYSA-N tert-butyl-dimethyl-(4-prop-1-en-2-ylphenoxy)silane Chemical compound CC(=C)C1=CC=C(O[Si](C)(C)C(C)(C)C)C=C1 GANAAUIATAGRLR-UHFFFAOYSA-N 0.000 description 2
• 210000001685 thyroid gland Anatomy 0.000 description 2
• ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
• 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 2
• 150000003672 ureas Chemical class 0.000 description 2
• KEDTYNCWGSIWBK-UHFFFAOYSA-N (1-methylpiperidin-3-yl)methanamine Chemical compound CN1CCCC(CN)C1 KEDTYNCWGSIWBK-UHFFFAOYSA-N 0.000 description 1
• AGTPSAZJSOQXHJ-UHFFFAOYSA-N (1-methylpiperidin-4-yl)methanamine Chemical compound CN1CCC(CN)CC1 AGTPSAZJSOQXHJ-UHFFFAOYSA-N 0.000 description 1
• RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 1
• RGXUCUWVGKLACF-UHFFFAOYSA-N (3-methylphenyl)methanamine Chemical compound CC1=CC=CC(CN)=C1 RGXUCUWVGKLACF-UHFFFAOYSA-N 0.000 description 1
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
• SKWYLBYYJCZUEY-UHFFFAOYSA-N 1-[5-[[3-(methanesulfonamido)-2-methoxy-5-(1-methylcyclopropyl)phenyl]carbamoyl]-2-methylphenyl]triazole-4-carboxylic acid Chemical compound C1=C(C2(C)CC2)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C(C=1)=CC=C(C)C=1N1C=C(C(O)=O)N=N1 SKWYLBYYJCZUEY-UHFFFAOYSA-N 0.000 description 1
• LXQMHOKEXZETKB-UHFFFAOYSA-N 1-amino-2-methylpropan-2-ol Chemical compound CC(C)(O)CN LXQMHOKEXZETKB-UHFFFAOYSA-N 0.000 description 1
• PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• IQVQNBXPYJGNEA-UHFFFAOYSA-N 1-pyridin-3-ylethanamine Chemical compound CC(N)C1=CC=CN=C1 IQVQNBXPYJGNEA-UHFFFAOYSA-N 0.000 description 1
• XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
• PKZCRWFNSBIBEW-UHFFFAOYSA-N 2-n,2-n,2-trimethylpropane-1,2-diamine Chemical compound CN(C)C(C)(C)CN PKZCRWFNSBIBEW-UHFFFAOYSA-N 0.000 description 1
• KDFDOINBXBEOLZ-UHFFFAOYSA-N 2-phenylpropan-2-amine Chemical compound CC(C)(N)C1=CC=CC=C1 KDFDOINBXBEOLZ-UHFFFAOYSA-N 0.000 description 1
• OSKSVLBJJXQUPI-UHFFFAOYSA-N 2h-triazole-4-carboxamide Chemical compound NC(=O)C1=CNN=N1 OSKSVLBJJXQUPI-UHFFFAOYSA-N 0.000 description 1
• GGONDCZAKSGASR-UHFFFAOYSA-N 3-(4-benzoyltriazol-1-yl)-n-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-4-methylbenzamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)C=2C=CC=CC=2)=C1 GGONDCZAKSGASR-UHFFFAOYSA-N 0.000 description 1
• SPSIIMCLQHSNAT-UHFFFAOYSA-N 3-(4-methoxycarbonyltriazol-1-yl)-4-methylbenzoic acid Chemical compound N1=NC(C(=O)OC)=CN1C1=CC(C(O)=O)=CC=C1C SPSIIMCLQHSNAT-UHFFFAOYSA-N 0.000 description 1
• BVLBDHMTBYUDFH-UHFFFAOYSA-N 3-azido-n-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-4-fluorobenzamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(F)C(N=[N+]=[N-])=C1 BVLBDHMTBYUDFH-UHFFFAOYSA-N 0.000 description 1
• MWOAEGADPJFAKP-UHFFFAOYSA-N 3-azido-n-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-4-methylbenzamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N=[N+]=[N-])=C1 MWOAEGADPJFAKP-UHFFFAOYSA-N 0.000 description 1
• JMECOYXOIATLJA-UHFFFAOYSA-N 3-azido-n-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-5-fluoro-4-methylbenzamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC(F)=C(C)C(N=[N+]=[N-])=C1 JMECOYXOIATLJA-UHFFFAOYSA-N 0.000 description 1
• NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
• 229940073735 4-hydroxy acetophenone Drugs 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• 208000002008 AIDS-Related Lymphoma Diseases 0.000 description 1
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
• 206010001939 Aminoaciduria Diseases 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
• 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
• 206010002198 Anaphylactic reaction Diseases 0.000 description 1
• 201000003076 Angiosarcoma Diseases 0.000 description 1
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
• 206010002660 Anoxia Diseases 0.000 description 1
• 241000976983 Anoxia Species 0.000 description 1
• 208000019901 Anxiety disease Diseases 0.000 description 1
• 200000000007 Arterial disease Diseases 0.000 description 1
• 206010060971 Astrocytoma malignant Diseases 0.000 description 1
• 208000012657 Atopic disease Diseases 0.000 description 1
• 206010003645 Atopy Diseases 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• 208000020084 Bone disease Diseases 0.000 description 1
• 241000589969 Borreliella burgdorferi Species 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• 201000006474 Brain Ischemia Diseases 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• 208000014644 Brain disease Diseases 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• 206010006550 Bulimia nervosa Diseases 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• 229940124638 COX inhibitor Drugs 0.000 description 1
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
• 208000005024 Castleman disease Diseases 0.000 description 1
• 206010008120 Cerebral ischaemia Diseases 0.000 description 1
• 206010063094 Cerebral malaria Diseases 0.000 description 1
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 102000010907 Cyclooxygenase 2 Human genes 0.000 description 1
• 108010037462 Cyclooxygenase 2 Proteins 0.000 description 1
• 206010012289 Dementia Diseases 0.000 description 1
• 208000016192 Demyelinating disease Diseases 0.000 description 1
• 206010012305 Demyelination Diseases 0.000 description 1
• 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
• 206010052804 Drug tolerance Diseases 0.000 description 1
• 208000006402 Ductal Carcinoma Diseases 0.000 description 1
• 208000032274 Encephalopathy Diseases 0.000 description 1
• 208000001976 Endocrine Gland Neoplasms Diseases 0.000 description 1
• 201000009273 Endometriosis Diseases 0.000 description 1
• 241000709661 Enterovirus Species 0.000 description 1
• 206010014967 Ependymoma Diseases 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
• 108010008165 Etanercept Proteins 0.000 description 1
• JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
• 208000006168 Ewing Sarcoma Diseases 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• 206010017708 Ganglioneuroblastoma Diseases 0.000 description 1
• 208000010412 Glaucoma Diseases 0.000 description 1
• 208000032612 Glial tumor Diseases 0.000 description 1
• 206010018338 Glioma Diseases 0.000 description 1
• 206010018364 Glomerulonephritis Diseases 0.000 description 1
• 102100033495 Glycine dehydrogenase (decarboxylating), mitochondrial Human genes 0.000 description 1
• 239000007821 HATU Substances 0.000 description 1
• 208000001258 Hemangiosarcoma Diseases 0.000 description 1
• 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 description 1
• 208000035150 Hypercholesterolemia Diseases 0.000 description 1
• 206010020674 Hypermetabolism Diseases 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 208000013016 Hypoglycemia Diseases 0.000 description 1
• 101150074243 Il1rn gene Proteins 0.000 description 1
• 102000006992 Interferon-alpha Human genes 0.000 description 1
• 108010047761 Interferon-alpha Proteins 0.000 description 1
• 102000014150 Interferons Human genes 0.000 description 1
• 108010050904 Interferons Proteins 0.000 description 1
• 102000003777 Interleukin-1 beta Human genes 0.000 description 1
• 108090000193 Interleukin-1 beta Proteins 0.000 description 1
• 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
• 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 1
• 102000010781 Interleukin-6 Receptors Human genes 0.000 description 1
• 108010038501 Interleukin-6 Receptors Proteins 0.000 description 1
• 206010061252 Intraocular melanoma Diseases 0.000 description 1
• 208000021342 Isolated sulfite oxidase deficiency Diseases 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• 239000005909 Kieselgur Substances 0.000 description 1
• 201000003533 Leber congenital amaurosis Diseases 0.000 description 1
• 208000016604 Lyme disease Diseases 0.000 description 1
• 206010025312 Lymphoma AIDS related Diseases 0.000 description 1
• 208000009564 MELAS Syndrome Diseases 0.000 description 1
• 201000009035 MERRF syndrome Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
• 208000005903 Manganese Poisoning Diseases 0.000 description 1
• 208000000172 Medulloblastoma Diseases 0.000 description 1
• 206010027202 Meningitis bacterial Diseases 0.000 description 1
• 206010027260 Meningitis viral Diseases 0.000 description 1
• 206010027406 Mesothelioma Diseases 0.000 description 1
• 206010027439 Metal poisoning Diseases 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 208000019695 Migraine disease Diseases 0.000 description 1
• 206010027761 Mixed hepatocellular cholangiocarcinoma Diseases 0.000 description 1
• 206010028116 Mucosal inflammation Diseases 0.000 description 1
• 201000010927 Mucositis Diseases 0.000 description 1
• 208000034486 Multi-organ failure Diseases 0.000 description 1
• 208000010718 Multiple Organ Failure Diseases 0.000 description 1
• 208000001089 Multiple system atrophy Diseases 0.000 description 1
• 241000699660 Mus musculus Species 0.000 description 1
• 208000000112 Myalgia Diseases 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• 206010069825 Myoclonic epilepsy and ragged-red fibres Diseases 0.000 description 1
• 229910017917 NH4 Cl Inorganic materials 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 208000009277 Neuroectodermal Tumors Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 208000035544 Nonketotic hyperglycinaemia Diseases 0.000 description 1
• 208000008589 Obesity Diseases 0.000 description 1
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
• 208000003435 Optic Neuritis Diseases 0.000 description 1
• 206010061323 Optic neuropathy Diseases 0.000 description 1
• 208000010191 Osteitis Deformans Diseases 0.000 description 1
• 208000003076 Osteolysis Diseases 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 208000027868 Paget disease Diseases 0.000 description 1
• 206010033645 Pancreatitis Diseases 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 208000037273 Pathologic Processes Diseases 0.000 description 1
• 206010061336 Pelvic neoplasm Diseases 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 208000037581 Persistent Infection Diseases 0.000 description 1
• BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
• 208000007641 Pinealoma Diseases 0.000 description 1
• 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
• 201000008199 Pleuropulmonary blastoma Diseases 0.000 description 1
• 208000005374 Poisoning Diseases 0.000 description 1
• 239000004743 Polypropylene Substances 0.000 description 1
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
• 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 206010063837 Reperfusion injury Diseases 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• 206010038934 Retinopathy proliferative Diseases 0.000 description 1
• 208000006289 Rett Syndrome Diseases 0.000 description 1
• 241000219061 Rheum Species 0.000 description 1
• 206010070834 Sensitisation Diseases 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
• 108700036932 Sulfite oxidase deficiency Proteins 0.000 description 1
• 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
• YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
• 208000033781 Thyroid carcinoma Diseases 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
• 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
• 201000005969 Uveal melanoma Diseases 0.000 description 1
• 206010046851 Uveitis Diseases 0.000 description 1
• 108700005077 Viral Genes Proteins 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
• 208000010045 Wernicke encephalopathy Diseases 0.000 description 1
• 108010046377 Whey Proteins Proteins 0.000 description 1
• 206010052428 Wound Diseases 0.000 description 1
• YQKFJYBRZVNXKQ-UHFFFAOYSA-N [Na].BC#N Chemical compound [Na].BC#N YQKFJYBRZVNXKQ-UHFFFAOYSA-N 0.000 description 1
• WXIONIWNXBAHRU-UHFFFAOYSA-N [dimethylamino(triazolo[4,5-b]pyridin-3-yloxy)methylidene]-dimethylazanium Chemical compound C1=CN=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 WXIONIWNXBAHRU-UHFFFAOYSA-N 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 206010069351 acute lung injury Diseases 0.000 description 1
• 230000004658 acute-phase response Effects 0.000 description 1
• 238000011360 adjunctive therapy Methods 0.000 description 1
• 208000020990 adrenal cortex carcinoma Diseases 0.000 description 1
• 208000007128 adrenocortical carcinoma Diseases 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
• 239000013566 allergen Substances 0.000 description 1
• 208000002029 allergic contact dermatitis Diseases 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 230000007815 allergy Effects 0.000 description 1
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 238000010976 amide bond formation reaction Methods 0.000 description 1
• 125000003368 amide group Chemical group 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 230000036783 anaphylactic response Effects 0.000 description 1
• 208000003455 anaphylaxis Diseases 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 230000007953 anoxia Effects 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 229940127219 anticoagulant drug Drugs 0.000 description 1
• 230000036506 anxiety Effects 0.000 description 1
• 238000003782 apoptosis assay Methods 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 239000011260 aqueous acid Substances 0.000 description 1
• 238000010936 aqueous wash Methods 0.000 description 1
• 210000001367 artery Anatomy 0.000 description 1
• 210000001188 articular cartilage Anatomy 0.000 description 1
• 201000009904 bacterial meningitis Diseases 0.000 description 1
• 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• 208000019664 bone resorption disease Diseases 0.000 description 1
• 208000030224 brain astrocytoma Diseases 0.000 description 1
• 208000029028 brain injury Diseases 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 201000002143 bronchus adenoma Diseases 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 208000002458 carcinoid tumor Diseases 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 230000002612 cardiopulmonary effect Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 208000015114 central nervous system disease Diseases 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 201000007335 cerebellar astrocytoma Diseases 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• 208000026106 cerebrovascular disease Diseases 0.000 description 1
• 230000001713 cholinergic effect Effects 0.000 description 1
• 210000001612 chondrocyte Anatomy 0.000 description 1
• 230000006020 chronic inflammation Effects 0.000 description 1
• 235000019504 cigarettes Nutrition 0.000 description 1
• 230000007882 cirrhosis Effects 0.000 description 1
• 208000019425 cirrhosis of liver Diseases 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 208000011588 combined hepatocellular carcinoma and cholangiocarcinoma Diseases 0.000 description 1
• 230000000052 comparative effect Effects 0.000 description 1
• 229940125904 compound 1 Drugs 0.000 description 1
• 229940126214 compound 3 Drugs 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 238000011443 conventional therapy Methods 0.000 description 1
• 150000001879 copper Chemical class 0.000 description 1
• ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
• 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
• 208000030381 cutaneous melanoma Diseases 0.000 description 1
• 208000029039 cyanide poisoning Diseases 0.000 description 1
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 239000000824 cytostatic agent Substances 0.000 description 1
• 230000001085 cytostatic effect Effects 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
• 230000007123 defense Effects 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 230000008021 deposition Effects 0.000 description 1
• 230000003831 deregulation Effects 0.000 description 1
• 230000001066 destructive effect Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 230000001079 digestive effect Effects 0.000 description 1
• 125000005046 dihydronaphthyl group Chemical group 0.000 description 1
• NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• VZFRNCSOCOPNDB-AJKFJWDBSA-N domoic acid Chemical compound OC(=O)[C@@H](C)\C=C\C=C(/C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VZFRNCSOCOPNDB-AJKFJWDBSA-N 0.000 description 1
• VZFRNCSOCOPNDB-UHFFFAOYSA-N domoic acid Natural products OC(=O)C(C)C=CC=C(C)C1CNC(C(O)=O)C1CC(O)=O VZFRNCSOCOPNDB-UHFFFAOYSA-N 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 229940073621 enbrel Drugs 0.000 description 1
• 230000003826 endocrine responses Effects 0.000 description 1
• 230000002357 endometrial effect Effects 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 201000004101 esophageal cancer Diseases 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 210000001508 eye Anatomy 0.000 description 1
• 208000024519 eye neoplasm Diseases 0.000 description 1
• 208000028149 female reproductive system neoplasm Diseases 0.000 description 1
• 239000003527 fibrinolytic agent Substances 0.000 description 1
• 230000003480 fibrinolytic effect Effects 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 210000000232 gallbladder Anatomy 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 238000005227 gel permeation chromatography Methods 0.000 description 1
• 210000004602 germ cell Anatomy 0.000 description 1
• 201000011205 glycine encephalopathy Diseases 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 210000002768 hair cell Anatomy 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 201000010536 head and neck cancer Diseases 0.000 description 1
• 208000014829 head and neck neoplasm Diseases 0.000 description 1
• 230000035876 healing Effects 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 208000007386 hepatic encephalopathy Diseases 0.000 description 1
• 208000006359 hepatoblastoma Diseases 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 210000001320 hippocampus Anatomy 0.000 description 1
• 230000013632 homeostatic process Effects 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• 208000023399 hyperprolinemia Diseases 0.000 description 1
• 230000001631 hypertensive effect Effects 0.000 description 1
• 230000002218 hypoglycaemic effect Effects 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 210000002865 immune cell Anatomy 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 239000012642 immune effector Substances 0.000 description 1
• 230000036737 immune function Effects 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 229940121354 immunomodulator Drugs 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 239000012678 infectious agent Substances 0.000 description 1
• 210000004969 inflammatory cell Anatomy 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 229960000598 infliximab Drugs 0.000 description 1
• 206010022000 influenza Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 238000011081 inoculation Methods 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 229940079322 interferon Drugs 0.000 description 1
• 239000003407 interleukin 1 receptor blocking agent Substances 0.000 description 1
• 230000021995 interleukin-8 production Effects 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 201000007450 intrahepatic cholangiocarcinoma Diseases 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 201000008893 intraocular retinoblastoma Diseases 0.000 description 1
• 238000007919 intrasynovial administration Methods 0.000 description 1
• 230000009545 invasion Effects 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 239000002085 irritant Substances 0.000 description 1
• 231100000021 irritant Toxicity 0.000 description 1
• 208000001875 irritant dermatitis Diseases 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• VZFRNCSOCOPNDB-OXYNIABMSA-N isodomoic acid D Natural products CC(C=C/C=C(/C)C1CNC(C1CC(=O)O)C(=O)O)C(=O)O VZFRNCSOCOPNDB-OXYNIABMSA-N 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 238000012332 laboratory investigation Methods 0.000 description 1
• 210000000867 larynx Anatomy 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• 201000007270 liver cancer Diseases 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 210000005265 lung cell Anatomy 0.000 description 1
• 206010025135 lupus erythematosus Diseases 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 230000000527 lymphocytic effect Effects 0.000 description 1
• 208000025036 lymphosarcoma Diseases 0.000 description 1
• 208000029791 lytic metastatic bone lesion Diseases 0.000 description 1
• 201000000564 macroglobulinemia Diseases 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• 206010025482 malaise Diseases 0.000 description 1
• 208000012166 male reproductive system neoplasm Diseases 0.000 description 1
• 208000027202 mammary Paget disease Diseases 0.000 description 1
• 229910052748 manganese Inorganic materials 0.000 description 1
• 239000011572 manganese Substances 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 210000000716 merkel cell Anatomy 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• ANGDWNBGPBMQHW-UHFFFAOYSA-N methyl cyanoacetate Chemical compound COC(=O)CC#N ANGDWNBGPBMQHW-UHFFFAOYSA-N 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• AZFQCTBZOPUVOW-UHFFFAOYSA-N methyl(triphenyl)phosphanium Chemical compound C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 AZFQCTBZOPUVOW-UHFFFAOYSA-N 0.000 description 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
• 206010027599 migraine Diseases 0.000 description 1
• ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 238000010172 mouse model Methods 0.000 description 1
• 210000000214 mouth Anatomy 0.000 description 1
• 210000004877 mucosa Anatomy 0.000 description 1
• 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
• 210000003205 muscle Anatomy 0.000 description 1
• 201000005962 mycosis fungoides Diseases 0.000 description 1
• 208000031225 myocardial ischemia Diseases 0.000 description 1
• ULDIVZQLPBUHAG-UHFFFAOYSA-N n',n',2,2-tetramethylpropane-1,3-diamine Chemical compound CN(C)CC(C)(C)CN ULDIVZQLPBUHAG-UHFFFAOYSA-N 0.000 description 1
• DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
• MXRPOIGVONJRCS-UHFFFAOYSA-N n-[3-amino-2-methoxy-5-(1-methylcyclopropyl)phenyl]methanesulfonamide Chemical compound C1=C(NS(C)(=O)=O)C(OC)=C(N)C=C1C1(C)CC1 MXRPOIGVONJRCS-UHFFFAOYSA-N 0.000 description 1
• LERLXXIEBXXATD-UHFFFAOYSA-N n-[3-amino-2-methoxy-5-(trifluoromethyl)phenyl]methanesulfonamide Chemical compound COC1=C(N)C=C(C(F)(F)F)C=C1NS(C)(=O)=O LERLXXIEBXXATD-UHFFFAOYSA-N 0.000 description 1
• HOPHKMATGGUWCH-HSZRJFAPSA-N n-[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]-3-[4-[(2s)-3-hydroxy-2-phenylpropanoyl]triazol-1-yl]-4-methylbenzamide Chemical compound C1=C(C(C)(C)C)C=C(NS(C)(=O)=O)C(OC)=C1NC(=O)C1=CC=C(C)C(N2N=NC(=C2)C(=O)[C@H](CO)C=2C=CC=CC=2)=C1 HOPHKMATGGUWCH-HSZRJFAPSA-N 0.000 description 1
• OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 1
• RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
• 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
• 201000009240 nasopharyngitis Diseases 0.000 description 1
• 210000003739 neck Anatomy 0.000 description 1
• 230000001338 necrotic effect Effects 0.000 description 1
• 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 1
• 208000023833 nerve sheath neoplasm Diseases 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 206010061311 nervous system neoplasm Diseases 0.000 description 1
• 208000004296 neuralgia Diseases 0.000 description 1
• 208000021722 neuropathic pain Diseases 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 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
• 235000016709 nutrition Nutrition 0.000 description 1
• 230000035764 nutrition Effects 0.000 description 1
• 235000020824 obesity Nutrition 0.000 description 1
• 230000000414 obstructive effect Effects 0.000 description 1
• 201000002575 ocular melanoma Diseases 0.000 description 1
• 208000031237 olivopontocerebellar atrophy Diseases 0.000 description 1
• 208000020911 optic nerve disease Diseases 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 230000003349 osteoarthritic effect Effects 0.000 description 1
• 210000000963 osteoblast Anatomy 0.000 description 1
• 230000001599 osteoclastic effect Effects 0.000 description 1
• 201000008968 osteosarcoma Diseases 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
• 244000045947 parasite Species 0.000 description 1
• 230000009054 pathological process Effects 0.000 description 1
• 230000001991 pathophysiological effect Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
• 208000028169 periodontal disease Diseases 0.000 description 1
• 201000005528 peripheral nervous system neoplasm Diseases 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
• 208000028591 pheochromocytoma Diseases 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 208000024724 pineal body neoplasm Diseases 0.000 description 1
• LTEKQAPRXFBRNN-UHFFFAOYSA-N piperidin-4-ylmethanamine Chemical compound NCC1CCNCC1 LTEKQAPRXFBRNN-UHFFFAOYSA-N 0.000 description 1
• 125000004928 piperidonyl group Chemical group 0.000 description 1
• 230000001817 pituitary effect Effects 0.000 description 1
• 208000010916 pituitary tumor Diseases 0.000 description 1
• 231100000572 poisoning Toxicity 0.000 description 1
• 230000000607 poisoning effect Effects 0.000 description 1
• 229920001155 polypropylene Polymers 0.000 description 1
• 231100000683 possible toxicity Toxicity 0.000 description 1
• 230000001124 posttranscriptional effect Effects 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 238000002360 preparation method Methods 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 208000029340 primitive neuroectodermal tumor Diseases 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 230000005522 programmed cell death Effects 0.000 description 1
• 230000006785 proliferative vitreoretinopathy Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 150000003180 prostaglandins Chemical class 0.000 description 1
• 235000018102 proteins Nutrition 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• TXQWFIVRZNOPCK-UHFFFAOYSA-N pyridin-4-ylmethanamine Chemical compound NCC1=CC=NC=C1 TXQWFIVRZNOPCK-UHFFFAOYSA-N 0.000 description 1
• 238000003127 radioimmunoassay Methods 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 230000001850 reproductive effect Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 208000032253 retinal ischemia Diseases 0.000 description 1
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
• 210000003079 salivary gland Anatomy 0.000 description 1
• 201000000980 schizophrenia Diseases 0.000 description 1
• 230000008313 sensitization Effects 0.000 description 1
• 238000010898 silica gel chromatography Methods 0.000 description 1
• 238000009097 single-agent therapy Methods 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 201000000849 skin cancer Diseases 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 235000010378 sodium ascorbate Nutrition 0.000 description 1
• PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
• 229960005055 sodium ascorbate Drugs 0.000 description 1
• PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 239000012086 standard solution Substances 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 210000001179 synovial fluid Anatomy 0.000 description 1
• 210000005222 synovial tissue Anatomy 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
• 239000003826 tablet Substances 0.000 description 1
• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 210000001550 testis Anatomy 0.000 description 1
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 125000000464 thioxo group Chemical group S=* 0.000 description 1
• 150000003595 thromboxanes Chemical class 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 208000013077 thyroid gland carcinoma Diseases 0.000 description 1
• GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
• FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 208000037816 tissue injury Diseases 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• QQJLHRRUATVHED-UHFFFAOYSA-N tramazoline Chemical compound N1CCN=C1NC1=CC=CC2=C1CCCC2 QQJLHRRUATVHED-UHFFFAOYSA-N 0.000 description 1
• 229960001262 tramazoline Drugs 0.000 description 1
• 238000011830 transgenic mouse model Methods 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• 230000005951 type IV hypersensitivity Effects 0.000 description 1
• 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
• 210000000626 ureter Anatomy 0.000 description 1
• 208000029584 urinary system neoplasm Diseases 0.000 description 1
• 210000001635 urinary tract Anatomy 0.000 description 1
• 210000004291 uterus Anatomy 0.000 description 1
• 210000001215 vagina Anatomy 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
• 229940124549 vasodilator Drugs 0.000 description 1
• 239000003071 vasodilator agent Substances 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 201000010044 viral meningitis Diseases 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 210000003905 vulva Anatomy 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000002578 wasp venom Substances 0.000 description 1
• 208000016261 weight loss Diseases 0.000 description 1
• 230000004580 weight loss Effects 0.000 description 1
• 235000021119 whey protein Nutrition 0.000 description 1