JP4823218B2 - 抗−サイトカインヘテロ環式化合物 - Google Patents
抗−サイトカインヘテロ環式化合物 Download PDFInfo
- Publication number
- JP4823218B2 JP4823218B2 JP2007513213A JP2007513213A JP4823218B2 JP 4823218 B2 JP4823218 B2 JP 4823218B2 JP 2007513213 A JP2007513213 A JP 2007513213A JP 2007513213 A JP2007513213 A JP 2007513213A JP 4823218 B2 JP4823218 B2 JP 4823218B2
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- optionally
- alkoxy
- amino
- halogen
- Prior art date
- 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 - Fee Related
Links
- 230000003092 anti-cytokine Effects 0.000 title description 4
- 150000002391 heterocyclic compounds Chemical class 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims description 99
- 150000001875 compounds Chemical class 0.000 claims description 96
- -1 aminocarboxyl Chemical group 0.000 claims description 52
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 239000001257 hydrogen Substances 0.000 claims description 41
- 229910052736 halogen Inorganic materials 0.000 claims description 36
- 150000002367 halogens Chemical class 0.000 claims description 36
- 125000003545 alkoxy group Chemical group 0.000 claims description 35
- 150000002431 hydrogen Chemical class 0.000 claims description 33
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 32
- 125000003118 aryl group Chemical group 0.000 claims description 30
- 125000001072 heteroaryl group Chemical group 0.000 claims description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims description 22
- 150000002825 nitriles Chemical class 0.000 claims description 21
- 125000002252 acyl group Chemical group 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
- 125000002757 morpholinyl group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 125000003386 piperidinyl group Chemical group 0.000 claims description 13
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 12
- 125000004442 acylamino group Chemical group 0.000 claims description 12
- 125000004423 acyloxy group Chemical group 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 12
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 10
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 125000004043 oxo group Chemical group O=* 0.000 claims description 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 7
- 229910052799 carbon Inorganic materials 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
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 7
- WCNFFKHKJLERFM-UHFFFAOYSA-N thiomorpholinyl sulfone group Chemical group N1(CCSCC1)S(=O)(=O)N1CCSCC1 WCNFFKHKJLERFM-UHFFFAOYSA-N 0.000 claims description 7
- ZCAGUOCUDGWENZ-UHFFFAOYSA-N thiomorpholinyl sulfoxide group Chemical group N1(CCSCC1)S(=O)N1CCSCC1 ZCAGUOCUDGWENZ-UHFFFAOYSA-N 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 6
- 125000003435 aroyl group Chemical group 0.000 claims description 6
- 125000004069 aziridinyl group Chemical group 0.000 claims description 5
- 125000004122 cyclic group Chemical group 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
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 4
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 150000001356 alkyl thiols Chemical class 0.000 claims description 4
- 125000000000 cycloalkoxy group Chemical group 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
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 4
- 125000005940 1,4-dioxanyl group Chemical group 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
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000004276 dioxalanyl group Chemical group 0.000 claims description 3
- 125000002541 furyl group Chemical group 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
- 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
- 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
- NNLBRYQGMOYARS-UHFFFAOYSA-N thiane 1-oxide Chemical compound O=S1CCCCC1 NNLBRYQGMOYARS-UHFFFAOYSA-N 0.000 claims description 3
- 125000001544 thienyl group Chemical group 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
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 2
- JMVGHFOTIGHVGG-UHFFFAOYSA-N O1C(CCC1)C1OC(OC1)=O Chemical compound O1C(CCC1)C1OC(OC1)=O JMVGHFOTIGHVGG-UHFFFAOYSA-N 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000005605 benzo group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 150000003536 tetrazoles Chemical class 0.000 claims description 2
- 150000003852 triazoles Chemical class 0.000 claims description 2
- 230000001548 androgenic effect Effects 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 50
- 201000010099 disease Diseases 0.000 description 44
- 102000004127 Cytokines Human genes 0.000 description 42
- 108090000695 Cytokines Proteins 0.000 description 42
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 38
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 38
- 238000011282 treatment Methods 0.000 description 28
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 24
- 102000000589 Interleukin-1 Human genes 0.000 description 23
- 108010002352 Interleukin-1 Proteins 0.000 description 23
- 238000000034 method Methods 0.000 description 22
- 239000007787 solid Substances 0.000 description 18
- 239000000243 solution Substances 0.000 description 17
- 230000004054 inflammatory process Effects 0.000 description 16
- 206010061218 Inflammation Diseases 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 102000004889 Interleukin-6 Human genes 0.000 description 13
- 108090001005 Interleukin-6 Proteins 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 12
- 230000006378 damage Effects 0.000 description 12
- 230000001404 mediated effect Effects 0.000 description 12
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 230000000770 proinflammatory effect Effects 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- 230000002757 inflammatory effect Effects 0.000 description 10
- 208000014674 injury Diseases 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 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
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 8
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 230000001154 acute effect Effects 0.000 description 8
- 239000008194 pharmaceutical composition Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 108090001007 Interleukin-8 Proteins 0.000 description 7
- 102000004890 Interleukin-8 Human genes 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 description 7
- 229910052717 sulfur Inorganic materials 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- 208000027418 Wounds and injury Diseases 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 230000008506 pathogenesis Effects 0.000 description 6
- 238000013456 study Methods 0.000 description 6
- 208000011580 syndromic disease Diseases 0.000 description 6
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 5
- 208000024827 Alzheimer disease Diseases 0.000 description 5
- 241000725303 Human immunodeficiency virus Species 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 208000002193 Pain Diseases 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 210000000988 bone and bone Anatomy 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- UOWOWMMJCDVLIR-UHFFFAOYSA-N ethyl 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]imidazole-4-carboxylate Chemical compound C1=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 UOWOWMMJCDVLIR-UHFFFAOYSA-N 0.000 description 5
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 201000006417 multiple sclerosis Diseases 0.000 description 5
- 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 5
- 230000008569 process Effects 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000003828 vacuum filtration Methods 0.000 description 5
- 208000006386 Bone Resorption Diseases 0.000 description 4
- 206010006895 Cachexia Diseases 0.000 description 4
- 239000007821 HATU Substances 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 4
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 4
- 206010039491 Sarcoma Diseases 0.000 description 4
- 206010040070 Septic Shock Diseases 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000024279 bone resorption Effects 0.000 description 4
- 208000037976 chronic inflammation Diseases 0.000 description 4
- 230000016396 cytokine production Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- RQPDBTNIFKTKSZ-UHFFFAOYSA-N ethyl 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]pyrazole-4-carboxylate Chemical compound C1=C(C(=O)OCC)C=NN1C1=CC(C(=O)NC=2C(=C(NS(C)(=O)=O)C=C(C=2)C(C)(C)C)OC)=CC=C1C RQPDBTNIFKTKSZ-UHFFFAOYSA-N 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 230000007302 negative regulation of cytokine production Effects 0.000 description 4
- 201000008482 osteoarthritis Diseases 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
- 210000003491 skin Anatomy 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 230000008733 trauma Effects 0.000 description 4
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- CYSWGQZFDKXUEV-UHFFFAOYSA-N 3-(4-ethoxycarbonylimidazol-1-yl)-4-methylbenzoic acid Chemical compound C1=NC(C(=O)OCC)=CN1C1=CC(C(O)=O)=CC=C1C CYSWGQZFDKXUEV-UHFFFAOYSA-N 0.000 description 3
- XKFIFYROMAAUDL-UHFFFAOYSA-N 3-amino-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1N XKFIFYROMAAUDL-UHFFFAOYSA-N 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 0 C*=*C(C(*)=O)/I(/C)=C/c1cc(C(NC)=O)cc(*)c1* Chemical compound C*=*C(C(*)=O)/I(/C)=C/c1cc(C(NC)=O)cc(*)c1* 0.000 description 3
- 206010007559 Cardiac failure congestive Diseases 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 208000011231 Crohn disease Diseases 0.000 description 3
- 206010012289 Dementia Diseases 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-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
- 206010025323 Lymphomas Diseases 0.000 description 3
- 201000009906 Meningitis Diseases 0.000 description 3
- 208000034578 Multiple myelomas Diseases 0.000 description 3
- 208000033776 Myeloid Acute Leukemia Diseases 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
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 208000038016 acute inflammation Diseases 0.000 description 3
- 230000006022 acute inflammation Effects 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 3
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 3
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 229920006008 lipopolysaccharide Polymers 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 201000001119 neuropathy Diseases 0.000 description 3
- 230000007823 neuropathy Effects 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 210000002997 osteoclast Anatomy 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 208000033808 peripheral neuropathy Diseases 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000011593 sulfur Chemical group 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000006433 tumor necrosis factor production Effects 0.000 description 3
- 210000000626 ureter Anatomy 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- NGKZNTWARWQCGU-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]imidazole-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(N=C2)C(O)=O)=C1 NGKZNTWARWQCGU-UHFFFAOYSA-N 0.000 description 2
- RLRPVJAYTQNCOX-UHFFFAOYSA-N 1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]pyrazole-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=CC(=C2)C(O)=O)=C1 RLRPVJAYTQNCOX-UHFFFAOYSA-N 0.000 description 2
- HKDJJQSDIGIFQJ-UHFFFAOYSA-N 3-(4-ethoxycarbonylpyrazol-1-yl)-4-methylbenzoic acid Chemical compound C1=C(C(=O)OCC)C=NN1C1=CC(C(O)=O)=CC=C1C HKDJJQSDIGIFQJ-UHFFFAOYSA-N 0.000 description 2
- NXQRPDUMVSUNAP-UHFFFAOYSA-N 3-(5-amino-3-ethoxycarbonylpyrazol-1-yl)-4-methylbenzoic acid Chemical compound N1=C(C(=O)OCC)C=C(N)N1C1=CC(C(O)=O)=CC=C1C NXQRPDUMVSUNAP-UHFFFAOYSA-N 0.000 description 2
- BJDSGGGWVYBYLB-UHFFFAOYSA-N 3-hydrazinyl-4-methylbenzoic acid;hydrochloride Chemical compound Cl.CC1=CC=C(C(O)=O)C=C1NN BJDSGGGWVYBYLB-UHFFFAOYSA-N 0.000 description 2
- 206010048998 Acute phase reaction Diseases 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 208000009137 Behcet syndrome Diseases 0.000 description 2
- 208000020084 Bone disease Diseases 0.000 description 2
- 208000014644 Brain disease Diseases 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- 206010009900 Colitis ulcerative Diseases 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- 206010012442 Dermatitis contact Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 206010018366 Glomerulonephritis acute Diseases 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 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
- 102000055008 Matrilin Proteins Human genes 0.000 description 2
- 108010072582 Matrilin Proteins Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 206010051606 Necrotising colitis Diseases 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 208000021161 Plasma cell disease Diseases 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 208000000453 Skin Neoplasms Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 208000006011 Stroke 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
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 231100000851 acute glomerulonephritis Toxicity 0.000 description 2
- 208000005298 acute pain Diseases 0.000 description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 230000003143 atherosclerotic effect Effects 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 206010008118 cerebral infarction Diseases 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 208000006990 cholangiocarcinoma Diseases 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 2
- 238000007887 coronary angioplasty Methods 0.000 description 2
- 229940079593 drug Drugs 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
- 239000012636 effector Substances 0.000 description 2
- 230000002124 endocrine Effects 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 210000004392 genitalia Anatomy 0.000 description 2
- 208000024908 graft versus host disease Diseases 0.000 description 2
- 210000003714 granulocyte Anatomy 0.000 description 2
- 238000001631 haemodialysis Methods 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 230000000322 hemodialysis Effects 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
- 230000001900 immune effect Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229960003130 interferon gamma Drugs 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 208000004995 necrotizing enterocolitis Diseases 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 230000000771 oncological effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000007310 pathophysiology Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 description 2
- 208000028169 periodontal disease Diseases 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 208000001685 postmenopausal osteoporosis Diseases 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 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
- 239000000126 substance Substances 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 230000002537 thrombolytic effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000000472 traumatic effect Effects 0.000 description 2
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 2
- 150000003672 ureas Chemical class 0.000 description 2
- 229910052720 vanadium Inorganic materials 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 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
- 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
- XDIAMRVROCPPBK-UHFFFAOYSA-N 2,2-dimethylpropan-1-amine Chemical compound CC(C)(C)CN XDIAMRVROCPPBK-UHFFFAOYSA-N 0.000 description 1
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
- GELMWIVBBPAMIO-UHFFFAOYSA-N 2-methylbutan-2-amine Chemical compound CCC(C)(C)N GELMWIVBBPAMIO-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 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
- 208000006468 Adrenal Cortex Neoplasms 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
- 208000000103 Anorexia Nervosa Diseases 0.000 description 1
- 206010002650 Anorexia nervosa and bulimia 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
- 206010003571 Astrocytoma 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
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 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
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- NSHAKTFJDYUTKN-UHFFFAOYSA-N C(#N)CC(O)C(=O)OCC.[Na] Chemical compound C(#N)CC(O)C(=O)OCC.[Na] NSHAKTFJDYUTKN-UHFFFAOYSA-N 0.000 description 1
- COUXIWCGPVFHKQ-UHFFFAOYSA-N CC(C(NN)=CC12)=CC1=C2C(O)=O Chemical compound CC(C(NN)=CC12)=CC1=C2C(O)=O COUXIWCGPVFHKQ-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
- 206010007275 Carcinoid tumour Diseases 0.000 description 1
- 206010051290 Central nervous system lesion Diseases 0.000 description 1
- 206010007953 Central nervous system lymphoma Diseases 0.000 description 1
- 206010008027 Cerebellar atrophy Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010063094 Cerebral malaria Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease 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
- 208000006313 Delayed Hypersensitivity Diseases 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 208000002699 Digestive System Neoplasms Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 208000006402 Ductal Carcinoma Diseases 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm 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
- 108010008165 Etanercept Proteins 0.000 description 1
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 201000004311 Gilles de la Tourette syndrome 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
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000001258 Hemangiosarcoma Diseases 0.000 description 1
- 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020365 Homocystinuria Diseases 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000033892 Hyperhomocysteinemia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 1
- 108050006617 Interleukin-1 receptor 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
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 201000003533 Leber congenital amaurosis Diseases 0.000 description 1
- 208000000265 Lobular Carcinoma Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia 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
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 206010049567 Miller Fisher syndrome 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
- 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
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 206010029240 Neuritis Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 1
- 108010021487 Nitric Oxide Synthase Proteins 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
- 208000011623 Obstructive Lung disease Diseases 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- 206010031096 Oropharyngeal cancer Diseases 0.000 description 1
- 206010057444 Oropharyngeal neoplasm 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
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 208000000821 Parathyroid Neoplasms Diseases 0.000 description 1
- 208000018737 Parkinson disease 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
- 208000002471 Penile Neoplasms Diseases 0.000 description 1
- 206010034299 Penile cancer Diseases 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
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 208000007641 Pinealoma Diseases 0.000 description 1
- 201000008199 Pleuropulmonary blastoma Diseases 0.000 description 1
- 206010035664 Pneumonia 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
- 241000700159 Rattus Species 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 206010038923 Retinopathy 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
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 108700036932 Sulfite oxidase deficiency Proteins 0.000 description 1
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 208000016620 Tourette disease Diseases 0.000 description 1
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
- 208000023915 Ureteral Neoplasms Diseases 0.000 description 1
- 206010046392 Ureteric cancer Diseases 0.000 description 1
- 206010046431 Urethral cancer Diseases 0.000 description 1
- 206010046458 Urethral neoplasms Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 201000005969 Uveal melanoma Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 241000256838 Vespula Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000004354 Vulvar Neoplasms Diseases 0.000 description 1
- 208000016025 Waldenstroem macroglobulinemia Diseases 0.000 description 1
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- FXAGBTBXSJBNMD-UHFFFAOYSA-N acetic acid;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound CC(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O FXAGBTBXSJBNMD-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 206010069351 acute lung injury Diseases 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 238000004458 analytical method Methods 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
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 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
- 210000001367 artery Anatomy 0.000 description 1
- 210000001188 articular cartilage Anatomy 0.000 description 1
- 125000005418 aryl aryl group Chemical group 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
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 230000010072 bone remodeling Effects 0.000 description 1
- 208000019664 bone resorption disease Diseases 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 201000003714 breast lobular carcinoma 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
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 201000007335 cerebellar astrocytoma Diseases 0.000 description 1
- 208000030239 cerebral astrocytoma Diseases 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- BJDCWCLMFKKGEE-CMDXXVQNSA-N chembl252518 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-CMDXXVQNSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 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
- 208000029742 colonic neoplasm Diseases 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
- 208000010247 contact dermatitis Diseases 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
- 239000000498 cooling water Substances 0.000 description 1
- 230000002596 correlated effect Effects 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
- 208000029039 cyanide poisoning Diseases 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 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
- 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
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 125000005046 dihydronaphthyl group Chemical group 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
- 239000003792 electrolyte Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229940073621 enbrel Drugs 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- HMFLBGNCDZYITR-UHFFFAOYSA-N ethyl 2-formyl-3-oxopropanoate Chemical compound CCOC(=O)C(C=O)C=O HMFLBGNCDZYITR-UHFFFAOYSA-N 0.000 description 1
- FTKASJMIPSSXBP-UHFFFAOYSA-N ethyl 2-nitroacetate Chemical compound CCOC(=O)C[N+]([O-])=O FTKASJMIPSSXBP-UHFFFAOYSA-N 0.000 description 1
- RCISJVBIWAENTA-UHFFFAOYSA-N ethyl 5-amino-1-[5-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoyl]-2-methylphenyl]pyrazole-3-carboxylate Chemical compound N1=C(C(=O)OCC)C=C(N)N1C1=CC(C(=O)NC=2C(=C(NS(C)(=O)=O)C=C(C=2)C(C)(C)C)OC)=CC=C1C RCISJVBIWAENTA-UHFFFAOYSA-N 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 208000024519 eye neoplasm Diseases 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 210000001654 germ layer Anatomy 0.000 description 1
- 201000011205 glycine encephalopathy Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 201000009277 hairy cell leukemia Diseases 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
- 231100000869 headache Toxicity 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000007386 hepatic encephalopathy Diseases 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 208000006359 hepatoblastoma Diseases 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 230000002157 hypercatabolic effect Effects 0.000 description 1
- 230000003225 hyperhomocysteinemia Effects 0.000 description 1
- 208000023399 hyperprolinemia Diseases 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 238000001727 in vivo Methods 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
- 229960000598 infliximab Drugs 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003407 interleukin 1 receptor blocking agent Substances 0.000 description 1
- 230000021995 interleukin-8 production Effects 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 230000007154 intracellular accumulation Effects 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
- 206010073095 invasive ductal breast carcinoma Diseases 0.000 description 1
- 201000010985 invasive ductal carcinoma Diseases 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
- 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
- 201000010982 kidney cancer Diseases 0.000 description 1
- 210000000244 kidney pelvis Anatomy 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 238000012332 laboratory investigation Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 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
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 208000025036 lymphosarcoma Diseases 0.000 description 1
- 208000029791 lytic metastatic bone lesion Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 208000014432 malignant adrenal gland pheochromocytoma Diseases 0.000 description 1
- 208000030883 malignant astrocytoma Diseases 0.000 description 1
- 208000020984 malignant renal pelvis neoplasm Diseases 0.000 description 1
- 208000026045 malignant tumor of parathyroid gland 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
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 201000001441 melanoma Diseases 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
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000002829 mitogen activated protein kinase inhibitor Substances 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
- 238000010172 mouse model Methods 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 210000003739 neck Anatomy 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
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- JCZMXVGQBBATMY-UHFFFAOYSA-N nitro acetate Chemical compound CC(=O)O[N+]([O-])=O JCZMXVGQBBATMY-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 201000002575 ocular melanoma Diseases 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 201000006958 oropharynx cancer Diseases 0.000 description 1
- 210000000963 osteoblast Anatomy 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
- 210000000496 pancreas Anatomy 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 210000003899 penis Anatomy 0.000 description 1
- 201000005528 peripheral nervous system neoplasm Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000026749 regulation of bone remodeling Effects 0.000 description 1
- 201000007444 renal pelvis carcinoma Diseases 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 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
- 201000000849 skin cancer Diseases 0.000 description 1
- 201000008261 skin carcinoma Diseases 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 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
- 230000005062 synaptic transmission Effects 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 210000005222 synovial tissue Anatomy 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 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
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic 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
- 238000001665 trituration Methods 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 208000013139 vaginal neoplasm Diseases 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
- 239000002435 venom Substances 0.000 description 1
- 210000001048 venom Anatomy 0.000 description 1
- 231100000611 venom Toxicity 0.000 description 1
- 230000006648 viral gene expression Effects 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 201000010044 viral meningitis Diseases 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 210000003905 vulva Anatomy 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US57028404P | 2004-05-12 | 2004-05-12 | |
| US60/570,284 | 2004-05-12 | ||
| PCT/US2005/015601 WO2005115991A1 (en) | 2004-05-12 | 2005-05-05 | Anti-cytokine heterocyclic compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2007537255A JP2007537255A (ja) | 2007-12-20 |
| JP2007537255A5 JP2007537255A5 (enExample) | 2008-06-26 |
| JP4823218B2 true JP4823218B2 (ja) | 2011-11-24 |
Family
ID=34968384
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007513213A Expired - Fee Related JP4823218B2 (ja) | 2004-05-12 | 2005-05-05 | 抗−サイトカインヘテロ環式化合物 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US7485657B2 (enExample) |
| EP (1) | EP1756065A1 (enExample) |
| JP (1) | JP4823218B2 (enExample) |
| CA (1) | CA2563466A1 (enExample) |
| WO (1) | WO2005115991A1 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4926402B2 (ja) * | 2002-11-27 | 2012-05-09 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | サイトカインインヒビターとしての１，２，３−トリアゾールアミド誘導体 |
| US7485657B2 (en) | 2004-05-12 | 2009-02-03 | Boehringer Ingelheim Pharmaceuticals, Inc. | Anti-cytokine heterocyclic compounds |
| US7531560B2 (en) * | 2004-11-10 | 2009-05-12 | Boehringer Ingelheim Pharmaceuticals, Inc. | Anti-cytokine heterocyclic compounds |
| EP1991274A4 (en) * | 2006-01-20 | 2009-06-10 | Women S And Children S Health | METHOD OF TREATMENT, PROPHYLAXIS AND DIAGNOSIS OF BONE PATHOLOGIES |
| EP2041116A1 (de) * | 2006-07-07 | 2009-04-01 | Boehringer Ingelheim International GmbH | Phenyl substituierte heteroaryl-derivate und deren verwendung als antitumormittel |
| CL2008001943A1 (es) * | 2007-07-02 | 2009-09-11 | Boehringer Ingelheim Int | Compuestos derivados de fenil-triazol, inhibidores de enzimas de señales especificas que participan del control de la proliferacion celular; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar cancer, infecciones, enfermedades inflamatorias y autoinmunes. |
| US20100240657A1 (en) * | 2007-07-02 | 2010-09-23 | Boehringer Ingelheim International Gmbh | Chemical compounds |
| AR073501A1 (es) | 2008-09-08 | 2010-11-10 | Boehringer Ingelheim Int | Derivados de pirimido[5,4-d]pirimidina inhibidores de la tirosinoquinasa |
| US8778929B2 (en) | 2008-09-29 | 2014-07-15 | Boehringer Ingelheim International Gmbh | Substituted heteroaryl inhibitors of B-RAF |
| US8569316B2 (en) | 2009-02-17 | 2013-10-29 | Boehringer Ingelheim International Gmbh | Pyrimido [5,4-D] pyrimidine derivatives for the inhibition of tyrosine kinases |
| JP2011057661A (ja) * | 2009-08-14 | 2011-03-24 | Bayer Cropscience Ag | 殺虫性カルボキサミド類 |
| EP2552905B1 (en) | 2010-03-26 | 2016-10-05 | Boehringer Ingelheim International GmbH | B-Raf kinase inhibitors |
| JP5871897B2 (ja) | 2010-03-26 | 2016-03-01 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ピリジルトリアゾール |
| US8710055B2 (en) | 2010-12-21 | 2014-04-29 | Boehringer Ingelheim International Gmbh | Triazolylphenyl sulfonamides as serine/threonine kinase inhibitors |
| US8889684B2 (en) | 2011-02-02 | 2014-11-18 | Boehringer Ingelheim International Gmbh | Azaindolylphenyl sulfonamides as serine/threonine kinase inhibitors |
| TW201822637A (zh) | 2016-11-07 | 2018-07-01 | 德商拜耳廠股份有限公司 | 用於控制動物害蟲的經取代磺醯胺類 |
| GB201815696D0 (en) * | 2018-09-26 | 2018-11-07 | Mereo Biopharma 1 Ltd | Synthetic method |
| GB201815695D0 (en) | 2018-09-26 | 2018-11-07 | Mereo Biopharma 1 Ltd | Synthetic method |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992009279A1 (fr) * | 1990-11-30 | 1992-06-11 | Teijin Limited | Derive de 2-arylthiazole et composition pharmaceutique contenant ce derive |
| WO2001072740A1 (en) * | 2000-03-23 | 2001-10-04 | Boehringer Ingelheim Pharmaceuticals, Inc. | Substituted 1-(4-aminophenyl) triazoles and their use as anti-inflammatory agents |
| JP2001521934A (ja) * | 1997-11-03 | 2001-11-13 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | 抗炎症薬としての芳香族ヘテロ環式化合物 |
| JP2002516909A (ja) * | 1998-06-05 | 2002-06-11 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | 置換１−（４−アミノフェニル）ピラゾール及び抗炎症剤としてのそれらの使用 |
| JP2003509495A (ja) * | 1999-09-22 | 2003-03-11 | エフ．ホフマン−ラ ロシュ アーゲー | ピラゾール誘導体 |
| JP2003518110A (ja) * | 1999-12-23 | 2003-06-03 | アイコス コーポレイション | ピラゾール環状ａｍｐ特異的ｐｄｅインヒビター |
| JP2003176273A (ja) * | 1999-02-10 | 2003-06-24 | Mitsubishi Pharma Corp | アミド化合物およびその医薬としての用途 |
| WO2003076405A1 (en) * | 2002-03-14 | 2003-09-18 | Bayer Healthcare Ag | Monocyclic aroylpyridinones as antiinflammatory agents |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4302051A1 (de) | 1993-01-26 | 1994-07-28 | Thomae Gmbh Dr K | 5-gliedrige Heterocyclen, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel |
| FR2732967B1 (fr) | 1995-04-11 | 1997-07-04 | Sanofi Sa | 1-phenylpyrazole-3-carboxamides substitues, actifs sur la neurotensine, leur preparation, les compositions pharmaceutiques en contenant |
| AU3387999A (en) | 1998-04-08 | 1999-10-25 | Abbott Laboratories | Pyrazole inhibitors of cytokine production |
| ES2200566T3 (es) | 1998-10-23 | 2004-03-01 | Dow Agrosciences Llc | 3-(piridilo sustituido)-1,2,4-triazoles insecticidas. |
| US6498423B1 (en) | 2001-06-27 | 2002-12-24 | Welch Allyn, Inc. | Lamp thermal control by directed air flow |
| US7297708B2 (en) | 2001-09-06 | 2007-11-20 | Bristol-Myers Squibb Company | Heteroaromatic substituted cyclopropane as corticotropin releasing hormone ligands |
| WO2003030902A1 (en) | 2001-10-09 | 2003-04-17 | Tularik Inc. | Imidazole derivates as anti-inflammatory agents |
| AU2003209388A1 (en) | 2002-01-29 | 2003-09-02 | Merck And Co., Inc. | Substituted imidazoles as cannabinoid receptor modulators |
| JP4926402B2 (ja) | 2002-11-27 | 2012-05-09 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | サイトカインインヒビターとしての１，２，３−トリアゾールアミド誘導体 |
| DE602004029242D1 (en) | 2003-05-01 | 2010-11-04 | Bristol Myers Squibb Co | Pyrazolamidverbindungen |
| BRPI0411825B8 (pt) | 2003-06-26 | 2021-05-25 | Novartis Ag | inibidores de p38 quinase a base de heterociclo de 5 elementos, seus processos de preparação e seus usos, bem como composição farmacêutica |
| US7511042B2 (en) | 2003-12-03 | 2009-03-31 | Boehringer Ingelheim Pharmaceuticals, Inc. | Triazole compounds |
| US7485657B2 (en) | 2004-05-12 | 2009-02-03 | Boehringer Ingelheim Pharmaceuticals, Inc. | Anti-cytokine heterocyclic compounds |
-
2005
- 2005-05-03 US US11/120,735 patent/US7485657B2/en active Active
- 2005-05-05 JP JP2007513213A patent/JP4823218B2/ja not_active Expired - Fee Related
- 2005-05-05 CA CA002563466A patent/CA2563466A1/en not_active Abandoned
- 2005-05-05 WO PCT/US2005/015601 patent/WO2005115991A1/en not_active Ceased
- 2005-05-05 EP EP05744331A patent/EP1756065A1/en not_active Withdrawn
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992009279A1 (fr) * | 1990-11-30 | 1992-06-11 | Teijin Limited | Derive de 2-arylthiazole et composition pharmaceutique contenant ce derive |
| JP2001521934A (ja) * | 1997-11-03 | 2001-11-13 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | 抗炎症薬としての芳香族ヘテロ環式化合物 |
| JP2002516909A (ja) * | 1998-06-05 | 2002-06-11 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | 置換１−（４−アミノフェニル）ピラゾール及び抗炎症剤としてのそれらの使用 |
| JP2003176273A (ja) * | 1999-02-10 | 2003-06-24 | Mitsubishi Pharma Corp | アミド化合物およびその医薬としての用途 |
| JP2003509495A (ja) * | 1999-09-22 | 2003-03-11 | エフ．ホフマン−ラ ロシュ アーゲー | ピラゾール誘導体 |
| JP2003518110A (ja) * | 1999-12-23 | 2003-06-03 | アイコス コーポレイション | ピラゾール環状ａｍｐ特異的ｐｄｅインヒビター |
| WO2001072740A1 (en) * | 2000-03-23 | 2001-10-04 | Boehringer Ingelheim Pharmaceuticals, Inc. | Substituted 1-(4-aminophenyl) triazoles and their use as anti-inflammatory agents |
| WO2003076405A1 (en) * | 2002-03-14 | 2003-09-18 | Bayer Healthcare Ag | Monocyclic aroylpyridinones as antiinflammatory agents |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2007537255A (ja) | 2007-12-20 |
| EP1756065A1 (en) | 2007-02-28 |
| WO2005115991A8 (en) | 2007-04-26 |
| US7485657B2 (en) | 2009-02-03 |
| US20050256113A1 (en) | 2005-11-17 |
| CA2563466A1 (en) | 2005-12-08 |
| WO2005115991A1 (en) | 2005-12-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4865702B2 (ja) | サイトカイン阻害剤 | |
| JP4954701B2 (ja) | サイトカインインヒビター | |
| JP4823218B2 (ja) | 抗−サイトカインヘテロ環式化合物 | |
| US7531560B2 (en) | Anti-cytokine heterocyclic compounds | |
| JP2005506350A (ja) | サイトカイン阻害薬としての１，４−二置換ベンゾ−縮合尿素化合物 | |
| KR20010094748A (ko) | 소염제로서의 방향족 헤테로사이클릭 화합물 | |
| JP4824576B2 (ja) | サイトカイン生成のインヒビターとしての１，２，３−トリアゾールアミド誘導体 | |
| JP4926402B2 (ja) | サイトカインインヒビターとしての１，２，３−トリアゾールアミド誘導体 | |
| JP4551765B2 (ja) | ベンズイミダゾロン及びサイトカイン抑制剤としてのそれらの使用 | |
| JP5038139B2 (ja) | サイトカインインヒビター | |
| EP1867646A1 (en) | Cytokine inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080507 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080507 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110427 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20110427 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110726 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20110822 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20110906 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140916 Year of fee payment: 3 |
|
| LAPS | Cancellation because of no payment of annual fees |