CA2495518A1 - Bicyclic heteroaromatic compounds as kinase inhibitors - Google Patents

Info

Publication number

CA2495518A1

CA2495518A1 CA002495518A CA2495518A CA2495518A1 CA 2495518 A1 CA2495518 A1 CA 2495518A1 CA 002495518 A CA002495518 A CA 002495518A CA 2495518 A CA2495518 A CA 2495518A CA 2495518 A1 CA2495518 A1 CA 2495518A1

Authority

CA

Canada

Prior art keywords

group

compound

groups

formula

optionally substituted

Prior art date

2002-08-13

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• -1 Bicyclic heteroaromatic compounds Chemical class 0.000 title description 183
• 229940043355 kinase inhibitor Drugs 0.000 title description 3
• 239000003757 phosphotransferase inhibitor Substances 0.000 title description 3
• 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims abstract description 36
• 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims abstract description 36
• 239000003112 inhibitor Substances 0.000 claims abstract description 26
• 238000011282 treatment Methods 0.000 claims abstract description 20
• 239000003814 drug Substances 0.000 claims abstract description 6
• 230000002265 prevention Effects 0.000 claims abstract description 4
• 150000001875 compounds Chemical class 0.000 claims description 185
• 125000000217 alkyl group Chemical group 0.000 claims description 65
• 125000001072 heteroaryl group Chemical group 0.000 claims description 35
• 125000003118 aryl group Chemical group 0.000 claims description 32
• 125000004429 atom Chemical group 0.000 claims description 29
• 238000000034 method Methods 0.000 claims description 29
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
• 229910052757 nitrogen Inorganic materials 0.000 claims description 21
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
• 229910052799 carbon Inorganic materials 0.000 claims description 16
• 229910052739 hydrogen Inorganic materials 0.000 claims description 16
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
• 125000001931 aliphatic group Chemical group 0.000 claims description 14
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
• 125000004076 pyridyl group Chemical group 0.000 claims description 12
• 150000003839 salts Chemical class 0.000 claims description 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• 239000012453 solvate Substances 0.000 claims description 7
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 7
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
• 239000001257 hydrogen Substances 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 6
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
• 125000004432 carbon atom Chemical group C* 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 4
• 238000005304 joining Methods 0.000 claims description 4
• 150000004677 hydrates Chemical class 0.000 claims description 3
• 150000002829 nitrogen Chemical group 0.000 claims description 3
• 125000005059 halophenyl group Chemical group 0.000 claims description 2
• 150000001204 N-oxides Chemical class 0.000 claims 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
• 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 claims 1
• 208000027866 inflammatory disease Diseases 0.000 abstract description 6
• 208000026278 immune system disease Diseases 0.000 abstract description 2
• MQJNETSYXIIIKE-UHFFFAOYSA-N 7h-thieno[2,3-b]pyridin-6-one Chemical group N1C(=O)C=CC2=C1SC=C2 MQJNETSYXIIIKE-UHFFFAOYSA-N 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 114
• 238000006243 chemical reaction Methods 0.000 description 80
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 70
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 64
• 239000000543 intermediate Substances 0.000 description 60
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 59
• 125000001424 substituent group Chemical group 0.000 description 54
• 239000002904 solvent Substances 0.000 description 53
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
• 239000000203 mixture Substances 0.000 description 43
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 41
• 239000007787 solid Substances 0.000 description 41
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 40
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 38
• 125000005843 halogen group Chemical group 0.000 description 36
• 239000000243 solution Substances 0.000 description 34
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 33
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 30
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
• 235000019439 ethyl acetate Nutrition 0.000 description 27
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 26
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• 201000010099 disease Diseases 0.000 description 24
• 238000010992 reflux Methods 0.000 description 24
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
• 125000003545 alkoxy group Chemical group 0.000 description 22
• 239000002585 base Substances 0.000 description 22
• 102000018594 Tumour necrosis factor Human genes 0.000 description 21
• 108050007852 Tumour necrosis factor Proteins 0.000 description 21
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
• 239000000460 chlorine Substances 0.000 description 20
• 125000005842 heteroatom Chemical group 0.000 description 20
• 239000000377 silicon dioxide Substances 0.000 description 20
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
• 210000004027 cell Anatomy 0.000 description 19
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
• 239000002253 acid Substances 0.000 description 17
• 150000001412 amines Chemical class 0.000 description 17
• 239000011541 reaction mixture Substances 0.000 description 17
• 238000004587 chromatography analysis Methods 0.000 description 16
• 101150041968 CDC13 gene Proteins 0.000 description 14
• 230000004913 activation Effects 0.000 description 14
• 239000002158 endotoxin Substances 0.000 description 14
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
• 108091000080 Phosphotransferase Proteins 0.000 description 13
• 239000012043 crude product Substances 0.000 description 13
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
• 102000020233 phosphotransferase Human genes 0.000 description 13
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• 150000001408 amides Chemical class 0.000 description 12
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 12
• 239000003054 catalyst Substances 0.000 description 12
• 229910052801 chlorine Inorganic materials 0.000 description 12
• 125000004433 nitrogen atom Chemical group N* 0.000 description 12
• 238000002360 preparation method Methods 0.000 description 12
• 102000004127 Cytokines Human genes 0.000 description 11
• 108090000695 Cytokines Proteins 0.000 description 11
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
• 102000004890 Interleukin-8 Human genes 0.000 description 11
• 108090001007 Interleukin-8 Proteins 0.000 description 11
• 208000015181 infectious disease Diseases 0.000 description 11
• 229920006008 lipopolysaccharide Polymers 0.000 description 11
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
• 229910000104 sodium hydride Inorganic materials 0.000 description 11
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 10
• XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 10
• 101100291385 Drosophila melanogaster p38a gene Proteins 0.000 description 10
• 102000000589 Interleukin-1 Human genes 0.000 description 10
• 108010002352 Interleukin-1 Proteins 0.000 description 10
• 102000004889 Interleukin-6 Human genes 0.000 description 10
• 108090001005 Interleukin-6 Proteins 0.000 description 10
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
• 239000012267 brine Substances 0.000 description 10
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 10
• 239000003153 chemical reaction reagent Substances 0.000 description 10
• 239000011737 fluorine Substances 0.000 description 10
• 229910052731 fluorine Inorganic materials 0.000 description 10
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
• 230000005764 inhibitory process Effects 0.000 description 10
• 238000006722 reduction reaction Methods 0.000 description 10
• 239000012312 sodium hydride Substances 0.000 description 10
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• 150000001721 carbon Chemical group 0.000 description 9
• 208000035475 disorder Diseases 0.000 description 9
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
• 239000002243 precursor Substances 0.000 description 9
• 239000000047 product Substances 0.000 description 9
• 230000000770 proinflammatory effect Effects 0.000 description 9
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
• 108010037462 Cyclooxygenase 2 Proteins 0.000 description 8
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 8
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
• 241000700605 Viruses Species 0.000 description 8
• 238000003556 assay Methods 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 150000008282 halocarbons Chemical class 0.000 description 8
• 235000011167 hydrochloric acid Nutrition 0.000 description 8
• 230000001404 mediated effect Effects 0.000 description 8
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
• 210000000440 neutrophil Anatomy 0.000 description 8
• SIOXPEMLGUPBBT-UHFFFAOYSA-M picolinate Chemical compound [O-]C(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-M 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• 230000008569 process Effects 0.000 description 8
• 230000009467 reduction Effects 0.000 description 8
• 238000003786 synthesis reaction Methods 0.000 description 8
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 8
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 7
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
• 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 7
• 206010040070 Septic Shock Diseases 0.000 description 7
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 7
• RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 7
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 7
• 210000004369 blood Anatomy 0.000 description 7
• 239000008280 blood Substances 0.000 description 7
• 229910052794 bromium Inorganic materials 0.000 description 7
• 125000001246 bromo group Chemical group Br* 0.000 description 7
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
• 150000004292 cyclic ethers Chemical class 0.000 description 7
• 125000001153 fluoro group Chemical group F* 0.000 description 7
• 125000000623 heterocyclic group Chemical group 0.000 description 7
• 229910052751 metal Inorganic materials 0.000 description 7
• 239000002184 metal Substances 0.000 description 7
• 229910052760 oxygen Inorganic materials 0.000 description 7
• 229910052763 palladium Inorganic materials 0.000 description 7
• 108090000623 proteins and genes Proteins 0.000 description 7
• 125000000714 pyrimidinyl group Chemical group 0.000 description 7
• 239000007858 starting material Substances 0.000 description 7
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 7
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• 208000002193 Pain Diseases 0.000 description 6
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
• 239000005864 Sulphur Chemical group 0.000 description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
• 229910000024 caesium carbonate Inorganic materials 0.000 description 6
• 125000001309 chloro group Chemical group Cl* 0.000 description 6
• QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 6
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 125000002950 monocyclic group Chemical group 0.000 description 6
• 125000002757 morpholinyl group Chemical group 0.000 description 6
• 150000007530 organic bases Chemical class 0.000 description 6
• 239000001301 oxygen Substances 0.000 description 6
• 230000036407 pain Effects 0.000 description 6
• 239000002953 phosphate buffered saline Substances 0.000 description 6
• 125000004193 piperazinyl group Chemical group 0.000 description 6
• 125000003386 piperidinyl group Chemical group 0.000 description 6
• 238000011321 prophylaxis Methods 0.000 description 6
• 102000004169 proteins and genes Human genes 0.000 description 6
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 6
• 206010039073 rheumatoid arthritis Diseases 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 150000003573 thiols Chemical class 0.000 description 6
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 6
• RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
• 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 5
• 206010006895 Cachexia Diseases 0.000 description 5
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 5
• 102000001708 Protein Isoforms Human genes 0.000 description 5
• 108010029485 Protein Isoforms Proteins 0.000 description 5
• 150000001299 aldehydes Chemical class 0.000 description 5
• 125000004414 alkyl thio group Chemical group 0.000 description 5
• 239000002168 alkylating agent Substances 0.000 description 5
• 229940100198 alkylating agent Drugs 0.000 description 5
• 125000002947 alkylene group Chemical group 0.000 description 5
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
• 206010003246 arthritis Diseases 0.000 description 5
• 230000008878 coupling Effects 0.000 description 5
• 238000005859 coupling reaction Methods 0.000 description 5
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
• 239000012039 electrophile Substances 0.000 description 5
• 229940088598 enzyme Drugs 0.000 description 5
• 150000002148 esters Chemical class 0.000 description 5
• 239000002024 ethyl acetate extract Substances 0.000 description 5
• 239000000284 extract Substances 0.000 description 5
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 5
• 230000007062 hydrolysis Effects 0.000 description 5
• 238000006460 hydrolysis reaction Methods 0.000 description 5
• 230000002757 inflammatory effect Effects 0.000 description 5
• 230000021995 interleukin-8 production Effects 0.000 description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
• 235000019341 magnesium sulphate Nutrition 0.000 description 5
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
• 239000002480 mineral oil Substances 0.000 description 5
• 235000010446 mineral oil Nutrition 0.000 description 5
• 201000008482 osteoarthritis Diseases 0.000 description 5
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 125000000168 pyrrolyl group Chemical group 0.000 description 5
• 230000004044 response Effects 0.000 description 5
• 230000011664 signaling Effects 0.000 description 5
• 239000002002 slurry Substances 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• 125000001544 thienyl group Chemical group 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• JSDBKAHWADVXFU-UHFFFAOYSA-N 1,3-dimethyluracil Chemical compound CN1C=CC(=O)N(C)C1=O JSDBKAHWADVXFU-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 208000030507 AIDS Diseases 0.000 description 4
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 4
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
• JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 4
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 4
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 4
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
• 239000012826 P38 inhibitor Substances 0.000 description 4
• 102000001253 Protein Kinase Human genes 0.000 description 4
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 4
• 206010040047 Sepsis Diseases 0.000 description 4
• 238000005917 acylation reaction Methods 0.000 description 4
• 230000029936 alkylation Effects 0.000 description 4
• 238000005804 alkylation reaction Methods 0.000 description 4
• 125000000304 alkynyl group Chemical group 0.000 description 4
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 4
• 229910002092 carbon dioxide Inorganic materials 0.000 description 4
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
• 239000003638 chemical reducing agent Substances 0.000 description 4
• OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
• 230000000694 effects Effects 0.000 description 4
• 125000004494 ethyl ester group Chemical group 0.000 description 4
• 235000019253 formic acid Nutrition 0.000 description 4
• 125000002632 imidazolidinyl group Chemical group 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 150000007529 inorganic bases Chemical class 0.000 description 4
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 4
• 239000012071 phase Substances 0.000 description 4
• 230000026731 phosphorylation Effects 0.000 description 4
• 238000006366 phosphorylation reaction Methods 0.000 description 4
• 230000003389 potentiating effect Effects 0.000 description 4
• 108060006633 protein kinase Proteins 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 4
• 150000003384 small molecules Chemical class 0.000 description 4
• 239000006228 supernatant Substances 0.000 description 4
• 125000000335 thiazolyl group Chemical group 0.000 description 4
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 3
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
• 101150101604 ACVR1B gene Proteins 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
• 208000023275 Autoimmune disease Diseases 0.000 description 3
• 208000020084 Bone disease Diseases 0.000 description 3
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 3
• 206010009900 Colitis ulcerative Diseases 0.000 description 3
• 229910021590 Copper(II) bromide Inorganic materials 0.000 description 3
• 208000011231 Crohn disease Diseases 0.000 description 3
• 241000701022 Cytomegalovirus Species 0.000 description 3
• 102100023401 Dual specificity mitogen-activated protein kinase kinase 6 Human genes 0.000 description 3
• 241000588724 Escherichia coli Species 0.000 description 3
• 101000624426 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 6 Proteins 0.000 description 3
• 241000124008 Mammalia Species 0.000 description 3
• 102100033060 Mitogen-activated protein kinase kinase kinase 4 Human genes 0.000 description 3
• 206010028980 Neoplasm Diseases 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 206010037660 Pyrexia Diseases 0.000 description 3
• 206010044248 Toxic shock syndrome Diseases 0.000 description 3
• 231100000650 Toxic shock syndrome Toxicity 0.000 description 3
• 201000006704 Ulcerative Colitis Diseases 0.000 description 3
• 208000036142 Viral infection Diseases 0.000 description 3
• 230000003213 activating effect Effects 0.000 description 3
• 239000012190 activator Substances 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 230000010933 acylation Effects 0.000 description 3
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 3
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 3
• 125000005236 alkanoylamino group Chemical group 0.000 description 3
• 125000003342 alkenyl group Chemical group 0.000 description 3
• 125000003282 alkyl amino group Chemical group 0.000 description 3
• 125000004419 alkynylene group Chemical group 0.000 description 3
• 125000003277 amino group Chemical group 0.000 description 3
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
• 238000006254 arylation reaction Methods 0.000 description 3
• 208000006673 asthma Diseases 0.000 description 3
• 125000002619 bicyclic group Chemical group 0.000 description 3
• 201000011510 cancer Diseases 0.000 description 3
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
• 125000001589 carboacyl group Chemical group 0.000 description 3
• 125000002837 carbocyclic group Chemical group 0.000 description 3
• 239000001569 carbon dioxide Substances 0.000 description 3
• 125000005518 carboxamido group Chemical group 0.000 description 3
• 238000004440 column chromatography Methods 0.000 description 3
• 125000000753 cycloalkyl group Chemical group 0.000 description 3
• 206010012601 diabetes mellitus Diseases 0.000 description 3
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 3
• 239000002027 dichloromethane extract Substances 0.000 description 3
• 230000009977 dual effect Effects 0.000 description 3
• 210000002889 endothelial cell Anatomy 0.000 description 3
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
• 239000012065 filter cake Substances 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 125000002541 furyl group Chemical group 0.000 description 3
• 150000004820 halides Chemical class 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• 150000004678 hydrides Chemical class 0.000 description 3
• 238000005984 hydrogenation reaction Methods 0.000 description 3
• 125000002883 imidazolyl group Chemical group 0.000 description 3
• 239000012442 inert solvent Substances 0.000 description 3
• 230000008595 infiltration Effects 0.000 description 3
• 238000001764 infiltration Methods 0.000 description 3
• 206010022000 influenza Diseases 0.000 description 3
• 230000018276 interleukin-1 production Effects 0.000 description 3
• 229910052740 iodine Inorganic materials 0.000 description 3
• 239000006166 lysate Substances 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 239000003226 mitogen Substances 0.000 description 3
• 210000001616 monocyte Anatomy 0.000 description 3
• 208000015122 neurodegenerative disease Diseases 0.000 description 3
• 150000002825 nitriles Chemical class 0.000 description 3
• 239000012299 nitrogen atmosphere Substances 0.000 description 3
• 239000003960 organic solvent Substances 0.000 description 3
• 125000002971 oxazolyl group Chemical group 0.000 description 3
• 239000007800 oxidant agent Substances 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 150000003180 prostaglandins Chemical class 0.000 description 3
• 230000002685 pulmonary effect Effects 0.000 description 3
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 3
• 230000036303 septic shock Effects 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
• 238000010561 standard procedure Methods 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• 238000012360 testing method Methods 0.000 description 3
• 125000004306 triazinyl group Chemical group 0.000 description 3
• 239000003656 tris buffered saline Substances 0.000 description 3
• 230000009385 viral infection Effects 0.000 description 3
• NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 2
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 2
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
• SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 2
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 2
• YTQQIHUQLOZOJI-UHFFFAOYSA-N 2,3-dihydro-1,2-thiazole Chemical compound C1NSC=C1 YTQQIHUQLOZOJI-UHFFFAOYSA-N 0.000 description 2
• ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 2
• FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 2
• 239000001431 2-methylbenzaldehyde Substances 0.000 description 2
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 2
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
• 208000024827 Alzheimer disease Diseases 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
• 206010063094 Cerebral malaria Diseases 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 102000029816 Collagenase Human genes 0.000 description 2
• 108060005980 Collagenase Proteins 0.000 description 2
• 208000035473 Communicable disease Diseases 0.000 description 2
• 102100029145 DNA damage-inducible transcript 3 protein Human genes 0.000 description 2
• 101710156077 DNA damage-inducible transcript 3 protein Proteins 0.000 description 2
• 241000350052 Daniellia ogea Species 0.000 description 2
• 102100023275 Dual specificity mitogen-activated protein kinase kinase 3 Human genes 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• 208000037487 Endotoxemia Diseases 0.000 description 2
• 241000709661 Enterovirus Species 0.000 description 2
• UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• 206010018364 Glomerulonephritis Diseases 0.000 description 2
• 201000005569 Gout Diseases 0.000 description 2
• 206010018634 Gouty Arthritis Diseases 0.000 description 2
• 208000031886 HIV Infections Diseases 0.000 description 2
• 101710100504 Heat shock protein beta-1 Proteins 0.000 description 2
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
• 101001115394 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 3 Proteins 0.000 description 2
• 101000578774 Homo sapiens MAP kinase-activated protein kinase 5 Proteins 0.000 description 2
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 206010020751 Hypersensitivity Diseases 0.000 description 2
• XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 2
• 206010061218 Inflammation Diseases 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 2
• 108010075647 MAP Kinase Kinase Kinase 4 Proteins 0.000 description 2
• 102100028396 MAP kinase-activated protein kinase 5 Human genes 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 2
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
• 208000034578 Multiple myelomas Diseases 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• 206010028289 Muscle atrophy Diseases 0.000 description 2
• 208000000112 Myalgia Diseases 0.000 description 2
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
• 206010030113 Oedema Diseases 0.000 description 2
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
• KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
• 206010035226 Plasma cell myeloma Diseases 0.000 description 2
• 201000004681 Psoriasis Diseases 0.000 description 2
• 201000001263 Psoriatic Arthritis Diseases 0.000 description 2
• 208000036824 Psoriatic arthropathy Diseases 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 206010063837 Reperfusion injury Diseases 0.000 description 2
• 229940124639 Selective inhibitor Drugs 0.000 description 2
• 206010070834 Sensitisation Diseases 0.000 description 2
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 2
• 201000010001 Silicosis Diseases 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 208000006011 Stroke Diseases 0.000 description 2
• 102000008889 TNF receptor-associated factor TRAF Human genes 0.000 description 2
• 108050000808 TNF receptor-associated factor TRAF Proteins 0.000 description 2
• 206010048873 Traumatic arthritis Diseases 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 125000004450 alkenylene group Chemical group 0.000 description 2
• 150000004703 alkoxides Chemical class 0.000 description 2
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 2
• 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 2
• 230000007815 allergy Effects 0.000 description 2
• 238000005576 amination reaction Methods 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 125000006598 aminocarbonylamino group Chemical group 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 235000011114 ammonium hydroxide Nutrition 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
• 159000000032 aromatic acids Chemical class 0.000 description 2
• 150000004982 aromatic amines Chemical class 0.000 description 2
• 230000002917 arthritic effect Effects 0.000 description 2
• 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 2
• 210000003651 basophil Anatomy 0.000 description 2
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 229910052796 boron Inorganic materials 0.000 description 2
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 229960002424 collagenase Drugs 0.000 description 2
• 239000010949 copper Substances 0.000 description 2
• MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 125000000392 cycloalkenyl group Chemical group 0.000 description 2
• MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 2
• 230000016396 cytokine production Effects 0.000 description 2
• 230000001066 destructive effect Effects 0.000 description 2
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 2
• NCBFTYFOPLPRBX-UHFFFAOYSA-N dimethyl azodicarboxylate Substances COC(=O)N=NC(=O)OC NCBFTYFOPLPRBX-UHFFFAOYSA-N 0.000 description 2
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
• 238000006073 displacement reaction Methods 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 230000006353 environmental stress Effects 0.000 description 2
• 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 239000007789 gas Substances 0.000 description 2
• 239000011521 glass Substances 0.000 description 2
• 230000002140 halogenating effect Effects 0.000 description 2
• 125000004366 heterocycloalkenyl group Chemical group 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 230000004054 inflammatory process Effects 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 230000017306 interleukin-6 production Effects 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• 208000011379 keloid formation Diseases 0.000 description 2
• 239000010410 layer Substances 0.000 description 2
• 238000011694 lewis rat Methods 0.000 description 2
• 239000012280 lithium aluminium hydride Substances 0.000 description 2
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
• 239000007937 lozenge Substances 0.000 description 2
• OVWYEQOVUDKZNU-UHFFFAOYSA-N m-tolualdehyde Chemical compound CC1=CC=CC(C=O)=C1 OVWYEQOVUDKZNU-UHFFFAOYSA-N 0.000 description 2
• 210000002540 macrophage Anatomy 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 230000014759 maintenance of location Effects 0.000 description 2
• 230000036210 malignancy Effects 0.000 description 2
• 229910052987 metal hydride Inorganic materials 0.000 description 2
• 150000004681 metal hydrides Chemical class 0.000 description 2
• NCBFTYFOPLPRBX-AATRIKPKSA-N methyl (ne)-n-methoxycarbonyliminocarbamate Chemical compound COC(=O)\N=N\C(=O)OC NCBFTYFOPLPRBX-AATRIKPKSA-N 0.000 description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 201000009240 nasopharyngitis Diseases 0.000 description 2
• 230000004770 neurodegeneration Effects 0.000 description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 239000012044 organic layer Substances 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
• 150000004965 peroxy acids Chemical class 0.000 description 2
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
• 229910052698 phosphorus Inorganic materials 0.000 description 2
• 239000011574 phosphorus Substances 0.000 description 2
• 230000002062 proliferating effect Effects 0.000 description 2
• 125000006239 protecting group Chemical group 0.000 description 2
• GPTFURBXHJWNHR-UHFFFAOYSA-N protopine Chemical compound C1=C2C(=O)CC3=CC=C4OCOC4=C3CN(C)CCC2=CC2=C1OCO2 GPTFURBXHJWNHR-UHFFFAOYSA-N 0.000 description 2
• 201000003651 pulmonary sarcoidosis Diseases 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• MVILWLLYYQVYNH-UHFFFAOYSA-N pyridine-2-carboxamide Chemical compound NC(=O)C1=CC=CC=N1.NC(=O)C1=CC=CC=N1 MVILWLLYYQVYNH-UHFFFAOYSA-N 0.000 description 2
• 150000003222 pyridines Chemical class 0.000 description 2
• 150000005299 pyridinones Chemical class 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 239000011347 resin Substances 0.000 description 2
• 229920005989 resin Polymers 0.000 description 2
• 201000005404 rubella Diseases 0.000 description 2
• 238000003118 sandwich ELISA Methods 0.000 description 2
• 231100000241 scar Toxicity 0.000 description 2
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 238000013207 serial dilution Methods 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 230000000638 stimulation Effects 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
• 230000035882 stress Effects 0.000 description 2
• 108091007196 stromelysin Proteins 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
• 239000004291 sulphur dioxide Substances 0.000 description 2
• 235000010269 sulphur dioxide Nutrition 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
• 125000001984 thiazolidinyl group Chemical group 0.000 description 2
• 238000005636 thioacylation reaction Methods 0.000 description 2
• 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• 230000009772 tissue formation Effects 0.000 description 2
• 201000008827 tuberculosis Diseases 0.000 description 2
• 230000006433 tumor necrosis factor production Effects 0.000 description 2
• 241000701161 unidentified adenovirus Species 0.000 description 2
• 238000011144 upstream manufacturing Methods 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• 230000003612 virological effect Effects 0.000 description 2
• 239000003039 volatile agent Substances 0.000 description 2
• PQCUDKMMPTXMAL-UHFFFAOYSA-N (2,6-difluorophenyl)methanamine Chemical compound NCC1=C(F)C=CC=C1F PQCUDKMMPTXMAL-UHFFFAOYSA-N 0.000 description 1
• UERNRFHISLXQFU-DFWYDOINSA-N (2S)-5-oxopyrrolidine-2-carboxylic acid pyridine Chemical compound c1ccncc1.OC(=O)[C@@H]1CCC(=O)N1 UERNRFHISLXQFU-DFWYDOINSA-N 0.000 description 1
• HMHWNJGOHUYVMD-UHFFFAOYSA-N (4-methylanilino)azanium;chloride Chemical compound Cl.CC1=CC=C(NN)C=C1 HMHWNJGOHUYVMD-UHFFFAOYSA-N 0.000 description 1
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
• 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 description 1
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
• 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 description 1
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
• DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
• AUYBSFAHQLKXSW-UHFFFAOYSA-N 1,2-dichloroethane;3-(ethyliminomethylideneamino)-n,n-dimethylpropan-1-amine;hydrochloride Chemical compound Cl.ClCCCl.CCN=C=NCCCN(C)C AUYBSFAHQLKXSW-UHFFFAOYSA-N 0.000 description 1
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
• 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 1
• JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
• HKDFRDIIELOLTJ-UHFFFAOYSA-N 1,4-dithianyl Chemical group [CH]1CSCCS1 HKDFRDIIELOLTJ-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
• JZUMPNUYDJBTNO-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 JZUMPNUYDJBTNO-UHFFFAOYSA-N 0.000 description 1
• FQKFPGMGQXQHLP-UHFFFAOYSA-N 1-hydroxytriazole Chemical compound ON1C=CN=N1 FQKFPGMGQXQHLP-UHFFFAOYSA-N 0.000 description 1
• RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
• KZDCMKVLEYCGQX-UDPGNSCCSA-N 2-(diethylamino)ethyl 4-aminobenzoate;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;hydrate Chemical group O.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 KZDCMKVLEYCGQX-UDPGNSCCSA-N 0.000 description 1
• WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 1
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
• JAUPUQRPBNDMDT-UHFFFAOYSA-N 2-chloropyridine-3-carbonitrile Chemical compound ClC1=NC=CC=C1C#N JAUPUQRPBNDMDT-UHFFFAOYSA-N 0.000 description 1
• HHYZGTJSYORMHK-UHFFFAOYSA-N 2-cyano-n-phenylethanethioamide Chemical compound N#CCC(=S)NC1=CC=CC=C1 HHYZGTJSYORMHK-UHFFFAOYSA-N 0.000 description 1
• LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• SRWILAKSARHZPR-UHFFFAOYSA-N 3-chlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1 SRWILAKSARHZPR-UHFFFAOYSA-N 0.000 description 1
• ZJQWXXSZXSTKHW-UHFFFAOYSA-N 3-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1.OOC(=O)C1=CC=CC(Cl)=C1 ZJQWXXSZXSTKHW-UHFFFAOYSA-N 0.000 description 1
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
• WRXOZRLZDJAYDR-UHFFFAOYSA-N 3-methylbenzenethiol Chemical compound CC1=CC=CC(S)=C1 WRXOZRLZDJAYDR-UHFFFAOYSA-N 0.000 description 1
• 125000004364 3-pyrrolinyl group Chemical group [H]C1=C([H])C([H])([H])N(*)C1([H])[H] 0.000 description 1
• 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 description 1
• XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
• AHISYUZBWDSPQL-UHFFFAOYSA-N 6-methylpyridine-2-carbaldehyde Chemical compound CC1=CC=CC(C=O)=N1 AHISYUZBWDSPQL-UHFFFAOYSA-N 0.000 description 1
• BCLDWKPJVMPCLL-UHFFFAOYSA-N 6-oxo-2-sulfanyl-1h-pyridine-3-carbonitrile Chemical compound SC=1NC(=O)C=CC=1C#N BCLDWKPJVMPCLL-UHFFFAOYSA-N 0.000 description 1
• 108010044688 Activating Transcription Factor 2 Proteins 0.000 description 1
• 102000007481 Activating Transcription Factor 6 Human genes 0.000 description 1
• 108010085405 Activating Transcription Factor 6 Proteins 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 206010003645 Atopy Diseases 0.000 description 1
• 206010055128 Autoimmune neutropenia Diseases 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• 208000004429 Bacillary Dysentery Diseases 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 241000713704 Bovine immunodeficiency virus Species 0.000 description 1
• 201000006474 Brain Ischemia Diseases 0.000 description 1
• MUZNZUJMXBQPPF-UHFFFAOYSA-N C(=O)(Cl)Cl.N(C1=CC=CC=C1)C(=O)NC1=C(SC=2N(C(C=CC21)=O)C2=CC=CC=C2)C(=O)OCC Chemical compound C(=O)(Cl)Cl.N(C1=CC=CC=C1)C(=O)NC1=C(SC=2N(C(C=CC21)=O)C2=CC=CC=C2)C(=O)OCC MUZNZUJMXBQPPF-UHFFFAOYSA-N 0.000 description 1
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
• 101100289995 Caenorhabditis elegans mac-1 gene Proteins 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
• 208000006029 Cardiomegaly Diseases 0.000 description 1
• 102000019034 Chemokines Human genes 0.000 description 1
• 108010012236 Chemokines Proteins 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
• 206010008909 Chronic Hepatitis Diseases 0.000 description 1
• 208000000668 Chronic Pancreatitis Diseases 0.000 description 1
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
• 101150065749 Churc1 gene Proteins 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 241000711573 Coronaviridae Species 0.000 description 1
• VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
• 102100023033 Cyclic AMP-dependent transcription factor ATF-2 Human genes 0.000 description 1
• 206010048843 Cytomegalovirus chorioretinitis Diseases 0.000 description 1
• GQHTUMJGOHRCHB-UHFFFAOYSA-N DBU Substances C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 1
• 102100028559 Death domain-associated protein 6 Human genes 0.000 description 1
• 101710091772 Death domain-associated protein 6 Proteins 0.000 description 1
• 206010012438 Dermatitis atopic Diseases 0.000 description 1
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• 238000002965 ELISA Methods 0.000 description 1
• 239000004150 EU approved colour Substances 0.000 description 1
• 206010014824 Endotoxic shock Diseases 0.000 description 1
• 241000713730 Equine infectious anemia virus Species 0.000 description 1
• 108090000371 Esterases Proteins 0.000 description 1
• 229910052693 Europium Inorganic materials 0.000 description 1
• 108700024394 Exon Proteins 0.000 description 1
• 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 1
• 241000713800 Feline immunodeficiency virus Species 0.000 description 1
• 108010070675 Glutathione transferase Proteins 0.000 description 1
• 241000126965 Gonytrichum caesium Species 0.000 description 1
• 208000009329 Graft vs Host Disease Diseases 0.000 description 1
• 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
• 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
• 208000003807 Graves Disease Diseases 0.000 description 1
• 208000015023 Graves' disease Diseases 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 206010020164 HIV infection CDC Group III Diseases 0.000 description 1
• 208000037357 HIV infectious disease Diseases 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 102100039165 Heat shock protein beta-1 Human genes 0.000 description 1
• 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
• 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
• 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 1
• 208000005176 Hepatitis C Diseases 0.000 description 1
• 206010019755 Hepatitis chronic active Diseases 0.000 description 1
• 208000009889 Herpes Simplex Diseases 0.000 description 1
• 208000007514 Herpes zoster Diseases 0.000 description 1
• 108010093488 His-His-His-His-His-His Proteins 0.000 description 1
• 102100022893 Histone acetyltransferase KAT5 Human genes 0.000 description 1
• 101001018147 Homo sapiens Mitogen-activated protein kinase kinase kinase 4 Proteins 0.000 description 1
• 101001112229 Homo sapiens Neutrophil cytosol factor 1 Proteins 0.000 description 1
• 101000945096 Homo sapiens Ribosomal protein S6 kinase alpha-5 Proteins 0.000 description 1
• 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 1
• 241000725303 Human immunodeficiency virus Species 0.000 description 1
• 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
• 241000430519 Human rhinovirus sp. Species 0.000 description 1
• LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• 206010061598 Immunodeficiency Diseases 0.000 description 1
• 208000029462 Immunodeficiency disease Diseases 0.000 description 1
• 101000668058 Infectious salmon anemia virus (isolate Atlantic salmon/Norway/810/9/99) RNA-directed RNA polymerase catalytic subunit Proteins 0.000 description 1
• 229930194542 Keto Natural products 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 108020002496 Lysophospholipase Proteins 0.000 description 1
• 102100034069 MAP kinase-activated protein kinase 2 Human genes 0.000 description 1
• 101710141394 MAP kinase-activated protein kinase 2 Proteins 0.000 description 1
• 102100028397 MAP kinase-activated protein kinase 3 Human genes 0.000 description 1
• 101710141393 MAP kinase-activated protein kinase 3 Proteins 0.000 description 1
• 108700012928 MAPK14 Proteins 0.000 description 1
• 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
• 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 235000019759 Maize starch Nutrition 0.000 description 1
• 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
• NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
• UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 1
• 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 1
• 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 1
• 108700015929 Mitogen-activated protein kinase 12 Proteins 0.000 description 1
• 102000056243 Mitogen-activated protein kinase 12 Human genes 0.000 description 1
• 102000054819 Mitogen-activated protein kinase 14 Human genes 0.000 description 1
• 102000047918 Myelin Basic Human genes 0.000 description 1
• 108700028031 Myelin Basic Proteins 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• 102100023620 Neutrophil cytosol factor 1 Human genes 0.000 description 1
• IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 206010033645 Pancreatitis Diseases 0.000 description 1
• 206010033647 Pancreatitis acute Diseases 0.000 description 1
• 206010033649 Pancreatitis chronic Diseases 0.000 description 1
• 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 239000004264 Petrolatum Substances 0.000 description 1
• YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
• 102100026918 Phospholipase A2 Human genes 0.000 description 1
• 101710096328 Phospholipase A2 Proteins 0.000 description 1
• 108010064785 Phospholipases Proteins 0.000 description 1
• 102000015439 Phospholipases Human genes 0.000 description 1
• 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
• 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
• ATTZFSUZZUNHBP-UHFFFAOYSA-N Piperonyl sulfoxide Chemical compound CCCCCCCCS(=O)C(C)CC1=CC=C2OCOC2=C1 ATTZFSUZZUNHBP-UHFFFAOYSA-N 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 206010036030 Polyarthritis Diseases 0.000 description 1
• 229920001214 Polysorbate 60 Polymers 0.000 description 1
• 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
• 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
• 102100038239 Protein Churchill Human genes 0.000 description 1
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 239000012980 RPMI-1640 medium Substances 0.000 description 1
• 208000033464 Reiter syndrome Diseases 0.000 description 1
• 241000725643 Respiratory syncytial virus Species 0.000 description 1
• 206010062106 Respiratory tract infection viral Diseases 0.000 description 1
• 208000005074 Retroviridae Infections Diseases 0.000 description 1
• 206010061494 Rhinovirus infection Diseases 0.000 description 1
• 102100033645 Ribosomal protein S6 kinase alpha-5 Human genes 0.000 description 1
• 238000000297 Sandmeyer reaction Methods 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 206010040550 Shigella infections Diseases 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 239000004141 Sodium laurylsulphate Substances 0.000 description 1
• HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• QYTDEUPAUMOIOP-UHFFFAOYSA-N TEMPO Chemical group CC1(C)CCCC(C)(C)N1[O] QYTDEUPAUMOIOP-UHFFFAOYSA-N 0.000 description 1
• JQAWYCUUFIMTHE-WLTAIBSBSA-N Thr-Gly-Tyr Chemical group [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O JQAWYCUUFIMTHE-WLTAIBSBSA-N 0.000 description 1
• 108090000190 Thrombin Proteins 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• 206010043781 Thyroiditis chronic Diseases 0.000 description 1
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• 102100023132 Transcription factor Jun Human genes 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• 102100040247 Tumor necrosis factor Human genes 0.000 description 1
• 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 1
• 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 1
• 241000713325 Visna/maedi virus Species 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical class [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
• MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 1
• MNLVCBKWEVXHGE-UHFFFAOYSA-N [CH]1[CH]CC[CH]1 Chemical group [CH]1[CH]CC[CH]1 MNLVCBKWEVXHGE-UHFFFAOYSA-N 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 231100000354 acute hepatitis Toxicity 0.000 description 1
• 201000003229 acute pancreatitis Diseases 0.000 description 1
• 125000004423 acyloxy group Chemical group 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 102000035181 adaptor proteins Human genes 0.000 description 1
• 108091005764 adaptor proteins Proteins 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 125000003158 alcohol group Chemical group 0.000 description 1
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 1
• 125000004949 alkyl amino carbonyl amino group Chemical group 0.000 description 1
• 125000004670 alkyl amino thio carbonyl group Chemical group 0.000 description 1
• 150000005215 alkyl ethers Chemical group 0.000 description 1
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 1
• 125000005530 alkylenedioxy group Chemical group 0.000 description 1
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 230000036592 analgesia Effects 0.000 description 1
• 230000002491 angiogenic effect Effects 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 210000003423 ankle Anatomy 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 229940124599 anti-inflammatory drug Drugs 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000000010 aprotic solvent Substances 0.000 description 1
• 239000008135 aqueous vehicle Substances 0.000 description 1
• 229940114079 arachidonic acid Drugs 0.000 description 1
• 235000021342 arachidonic acid Nutrition 0.000 description 1
• 125000005333 aroyloxy group Chemical group 0.000 description 1
• 125000004104 aryloxy group Chemical group 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 201000008937 atopic dermatitis Diseases 0.000 description 1
• 201000005000 autoimmune gastritis Diseases 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
• 239000012964 benzotriazole Substances 0.000 description 1
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 238000004166 bioassay Methods 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 230000036983 biotransformation Effects 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 208000019664 bone resorption disease Diseases 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 239000000337 buffer salt Substances 0.000 description 1
• FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 229940081733 cetearyl alcohol Drugs 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 238000012822 chemical development Methods 0.000 description 1
• 239000002975 chemoattractant Substances 0.000 description 1
• 239000005482 chemotactic factor Substances 0.000 description 1
• 230000035605 chemotaxis Effects 0.000 description 1
• 229960002152 chlorhexidine acetate Drugs 0.000 description 1
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
• 125000000068 chlorophenyl group Chemical group 0.000 description 1
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 239000013068 control sample Substances 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 150000001879 copper Chemical class 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 125000000000 cycloalkoxy group Chemical group 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 1
• 208000001763 cytomegalovirus retinitis Diseases 0.000 description 1
• 230000003436 cytoskeletal effect Effects 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 239000012024 dehydrating agents‎ Substances 0.000 description 1
• 230000018044 dehydration Effects 0.000 description 1
• 238000006297 dehydration reaction Methods 0.000 description 1
• 239000003405 delayed action preparation Substances 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 125000004663 dialkyl amino group Chemical group 0.000 description 1
• RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 1
• 229910000071 diazene Inorganic materials 0.000 description 1
• 235000019700 dicalcium phosphate Nutrition 0.000 description 1
• 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
• 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
• 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 125000004212 difluorophenyl group Chemical group 0.000 description 1
• 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
• 125000005051 dihydropyrazinyl group Chemical group N1(CC=NC=C1)* 0.000 description 1
• 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• WQOXQRCZOLPYPM-UHFFFAOYSA-N dimethyl disulfide Chemical compound CSSC WQOXQRCZOLPYPM-UHFFFAOYSA-N 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• 125000005879 dioxolanyl group Chemical group 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 210000001671 embryonic stem cell Anatomy 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000008387 emulsifying waxe Substances 0.000 description 1
• 230000002124 endocrine Effects 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 210000002919 epithelial cell Anatomy 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• 238000010931 ester hydrolysis Methods 0.000 description 1
• PVBRSNZAOAJRKO-UHFFFAOYSA-N ethyl 2-sulfanylacetate Chemical compound CCOC(=O)CS PVBRSNZAOAJRKO-UHFFFAOYSA-N 0.000 description 1
• PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
• FQYYIPZPELSLDK-UHFFFAOYSA-N ethyl pyridine-2-carboxylate Chemical compound CCOC(=O)C1=CC=CC=N1 FQYYIPZPELSLDK-UHFFFAOYSA-N 0.000 description 1
• 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
• 230000007717 exclusion Effects 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 239000012997 ficoll-paque Substances 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 210000002683 foot Anatomy 0.000 description 1
• 230000022244 formylation Effects 0.000 description 1
• 238000006170 formylation reaction Methods 0.000 description 1
• 239000003517 fume Substances 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 239000000417 fungicide Substances 0.000 description 1
• 230000008570 general process Effects 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• AWUCVROLDVIAJX-UHFFFAOYSA-N glycerol 1-phosphate Chemical compound OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
• RJHLTVSLYWWTEF-UHFFFAOYSA-K gold trichloride Chemical compound Cl[Au](Cl)Cl RJHLTVSLYWWTEF-UHFFFAOYSA-K 0.000 description 1
• 208000024908 graft versus host disease Diseases 0.000 description 1
• 210000003714 granulocyte Anatomy 0.000 description 1
• 150000004795 grignard reagents Chemical class 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 125000004438 haloalkoxy group Chemical group 0.000 description 1
• 125000001188 haloalkyl group Chemical group 0.000 description 1
• 125000004969 haloethyl group Chemical group 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 230000026030 halogenation Effects 0.000 description 1
• 238000005658 halogenation reaction Methods 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 125000004970 halomethyl group Chemical group 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 208000007475 hemolytic anemia Diseases 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 208000005252 hepatitis A Diseases 0.000 description 1
• 208000002672 hepatitis B Diseases 0.000 description 1
• 150000002390 heteroarenes Chemical class 0.000 description 1
• 229960001340 histamine Drugs 0.000 description 1
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• 150000002440 hydroxy compounds Chemical class 0.000 description 1
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 206010020718 hyperplasia Diseases 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• 125000004283 imidazolin-2-yl group Chemical group [H]N1C(*)=NC([H])([H])C1([H])[H] 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 150000003949 imides Chemical class 0.000 description 1
• 125000001841 imino group Chemical group [H]N=* 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 230000007813 immunodeficiency Effects 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 229910001502 inorganic halide Inorganic materials 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 102000006495 integrins Human genes 0.000 description 1
• 108010044426 integrins Proteins 0.000 description 1
• 230000004068 intracellular signaling Effects 0.000 description 1
• 230000007728 intracellular signaling mechanism Effects 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 210000002510 keratinocyte Anatomy 0.000 description 1
• 125000000468 ketone group Chemical group 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
• 208000021601 lentivirus infection Diseases 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 238000003760 magnetic stirring Methods 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• 208000021039 metastatic melanoma Diseases 0.000 description 1
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
• HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
• 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 229940042472 mineral oil Drugs 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 108010085212 mitogen and stress-activated protein kinase 1 Proteins 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 210000005087 mononuclear cell Anatomy 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 206010028417 myasthenia gravis Diseases 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
• ZDZVWJQUOACMTH-UHFFFAOYSA-N n-(phenylsulfamoyl)aniline Chemical compound C=1C=CC=CC=1NS(=O)(=O)NC1=CC=CC=C1 ZDZVWJQUOACMTH-UHFFFAOYSA-N 0.000 description 1
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
• RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000005893 naphthalimidyl group Chemical group 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 230000027405 negative regulation of phosphorylation Effects 0.000 description 1
• 230000002232 neuromuscular Effects 0.000 description 1
• 230000011242 neutrophil chemotaxis Effects 0.000 description 1
• 229910052759 nickel Inorganic materials 0.000 description 1
• 238000006396 nitration reaction Methods 0.000 description 1
• 150000002826 nitrites Chemical class 0.000 description 1
• 210000000929 nociceptor Anatomy 0.000 description 1
• 239000002687 nonaqueous vehicle Substances 0.000 description 1
• 125000003518 norbornenyl group Chemical group C12(C=CC(CC1)C2)* 0.000 description 1
• GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
• 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
• 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 229940066842 petrolatum Drugs 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
• 125000004344 phenylpropyl group Chemical group 0.000 description 1
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
• FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 125000005544 phthalimido group Chemical group 0.000 description 1
• 125000005545 phthalimidyl group Chemical group 0.000 description 1
• 208000030428 polyarticular arthritis Diseases 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
• 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 229940113124 polysorbate 60 Drugs 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• MCSINKKTEDDPNK-UHFFFAOYSA-N propyl propionate Chemical compound CCCOC(=O)CC MCSINKKTEDDPNK-UHFFFAOYSA-N 0.000 description 1
• 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 238000001243 protein synthesis Methods 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000002755 pyrazolinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• 230000000171 quenching effect Effects 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 208000002574 reactive arthritis Diseases 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 230000007115 recruitment Effects 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 238000005932 reductive alkylation reaction Methods 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 230000008521 reorganization Effects 0.000 description 1
• 230000010410 reperfusion Effects 0.000 description 1
• 230000010076 replication Effects 0.000 description 1
• 230000019254 respiratory burst Effects 0.000 description 1
• 230000003938 response to stress Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 210000003705 ribosome Anatomy 0.000 description 1
• 102200035859 rs6138 Human genes 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 230000008313 sensitization Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 150000003355 serines Chemical class 0.000 description 1
• 201000005113 shigellosis Diseases 0.000 description 1
• 230000035939 shock Effects 0.000 description 1
• 210000002027 skeletal muscle Anatomy 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• VILMUCRZVVVJCA-UHFFFAOYSA-M sodium glycolate Chemical compound [Na+].OCC([O-])=O VILMUCRZVVVJCA-UHFFFAOYSA-M 0.000 description 1
• 235000009518 sodium iodide Nutrition 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• HCRQDHWQFLNEGE-UHFFFAOYSA-M sodium;3-cyano-6-oxo-1-phenylpyridine-2-thiolate Chemical compound [Na+].[S-]C1=C(C#N)C=CC(=O)N1C1=CC=CC=C1 HCRQDHWQFLNEGE-UHFFFAOYSA-M 0.000 description 1
• LFQULJPVXNYWAG-UHFFFAOYSA-N sodium;phenylmethanolate Chemical compound [Na]OCC1=CC=CC=C1 LFQULJPVXNYWAG-UHFFFAOYSA-N 0.000 description 1
• 239000011343 solid material Substances 0.000 description 1
• 238000000527 sonication Methods 0.000 description 1
• 239000001587 sorbitan monostearate Substances 0.000 description 1
• 235000011076 sorbitan monostearate Nutrition 0.000 description 1
• 229940035048 sorbitan monostearate Drugs 0.000 description 1
• 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 230000003019 stabilising effect Effects 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
• 125000001174 sulfone group Chemical group 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 201000004595 synovitis Diseases 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
• 239000012414 tert-butyl nitrite Substances 0.000 description 1
• 210000001550 testis Anatomy 0.000 description 1
• MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000002769 thiazolinyl group Chemical group 0.000 description 1
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
• 125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• 229960004072 thrombin Drugs 0.000 description 1
• 206010043554 thrombocytopenia Diseases 0.000 description 1
• 239000003104 tissue culture media Substances 0.000 description 1
• 125000003944 tolyl group Chemical group 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 230000001131 transforming effect Effects 0.000 description 1
• 229910052723 transition metal Inorganic materials 0.000 description 1
• 150000003624 transition metals Chemical class 0.000 description 1
• 230000014616 translation Effects 0.000 description 1
• 230000008736 traumatic injury Effects 0.000 description 1
• 125000005270 trialkylamine group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
• 241000712461 unidentified influenza virus Species 0.000 description 1
• 230000003827 upregulation Effects 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 210000003556 vascular endothelial cell Anatomy 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 238000013389 whole blood assay Methods 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1