CA2535403A1

CA2535403A1 - Inhibitors of semicarbazide-sensitive amine oxidase (ssao) and vap-1 mediated adhesion useful for treatment of diseases

Inhibitors of semicarbazide-sensitive amine oxidase (ssao) and vap-1 mediated adhesion useful for treatment of diseases Download PDF

Info

Publication number: CA2535403A1
Authority: CA; Canada
Prior art keywords: compounds; compound; alkyl; ssao; substituted
Prior art date: 2003-08-08
Legal status : Abandoned

Application number

CA002535403A

Other languages

English (en)

French (fr)

Inventor

Luisa Maria Salter-Cid

Eric Yanjun Wang

Keith Cockerill

Matthew D. Linnik

Edward J. Victoria

Current Assignee

La Jolla Pharmaceutical Co

Original Assignee

Individual

Priority date

2003-08-08

Filing date

2004-08-06

Publication date

2005-02-17

2004-08-06 Application filed by Individual filed Critical Individual

2005-02-17 Publication of CA2535403A1 publication Critical patent/CA2535403A1/en

Status Abandoned legal-status Critical Current

Links

102100027159 Membrane primary amine oxidase Human genes 0.000 title abstract description 141
239000003112 inhibitor Substances 0.000 title abstract description 60
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 55
108010028700 Amine Oxidase (Copper-Containing) Proteins 0.000 title abstract description 8
201000010099 disease Diseases 0.000 title description 51
230000001404 mediated effect Effects 0.000 title description 11
101000774560 Crotalus atrox Zinc metalloproteinase-disintegrin-like VAP1 Proteins 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 460
230000004054 inflammatory process Effects 0.000 claims abstract description 84
206010061218 Inflammation Diseases 0.000 claims abstract description 83
208000026278 immune system disease Diseases 0.000 claims abstract description 66
201000006417 multiple sclerosis Diseases 0.000 claims abstract description 46
208000027866 inflammatory disease Diseases 0.000 claims abstract description 32
125000001072 heteroaryl group Chemical group 0.000 claims description 107
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 67
125000003710 aryl alkyl group Chemical group 0.000 claims description 55
125000003107 substituted aryl group Chemical group 0.000 claims description 53
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 52
150000003839 salts Chemical class 0.000 claims description 50
-1 C6-C10aryl Chemical group 0.000 claims description 48
208000023275 Autoimmune disease Diseases 0.000 claims description 45
229910052739 hydrogen Inorganic materials 0.000 claims description 32
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 31
229910052740 iodine Inorganic materials 0.000 claims description 26
125000000041 C6-C10 aryl group Chemical group 0.000 claims description 21
229910052801 chlorine Inorganic materials 0.000 claims description 21
229910052731 fluorine Inorganic materials 0.000 claims description 21
150000004677 hydrates Chemical class 0.000 claims description 19
239000012453 solvate Substances 0.000 claims description 19
238000002560 therapeutic procedure Methods 0.000 claims description 13
229910052760 oxygen Inorganic materials 0.000 claims description 10
229910052717 sulfur Inorganic materials 0.000 claims description 8
229910052794 bromium Inorganic materials 0.000 claims description 6
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
101710132836 Membrane primary amine oxidase Proteins 0.000 abstract description 139
238000000034 method Methods 0.000 abstract description 131
239000000203 mixture Substances 0.000 abstract description 65
230000028709 inflammatory response Effects 0.000 abstract description 21
230000001225 therapeutic effect Effects 0.000 abstract description 12
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 abstract description 3
125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 abstract 1
208000035475 disorder Diseases 0.000 abstract 1
ZTILHLWDFSMCLZ-UHFFFAOYSA-N prop-2-enylhydrazine Chemical class NNCC=C ZTILHLWDFSMCLZ-UHFFFAOYSA-N 0.000 abstract 1
230000000694 effects Effects 0.000 description 168
230000027455 binding Effects 0.000 description 82
241000699670 Mus sp. Species 0.000 description 72
230000002401 inhibitory effect Effects 0.000 description 70
102000004190 Enzymes Human genes 0.000 description 69
108090000790 Enzymes Proteins 0.000 description 69
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
239000003814 drug Substances 0.000 description 50
238000004519 manufacturing process Methods 0.000 description 48
102000010909 Monoamine Oxidase Human genes 0.000 description 46
108010062431 Monoamine oxidase Proteins 0.000 description 46
125000000217 alkyl group Chemical group 0.000 description 45
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 44
239000000243 solution Substances 0.000 description 43
241001465754 Metazoa Species 0.000 description 41
125000003118 aryl group Chemical group 0.000 description 40
238000007912 intraperitoneal administration Methods 0.000 description 36
238000000338 in vitro Methods 0.000 description 34
239000007787 solid Substances 0.000 description 33
210000004027 cell Anatomy 0.000 description 32
230000005764 inhibitory process Effects 0.000 description 32
IHEVYQFGSZLVRV-UHFFFAOYSA-N 2-phenylprop-2-enylhydrazine Chemical compound NNCC(=C)C1=CC=CC=C1 IHEVYQFGSZLVRV-UHFFFAOYSA-N 0.000 description 30
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
238000002347 injection Methods 0.000 description 28
239000007924 injection Substances 0.000 description 28
210000004379 membrane Anatomy 0.000 description 28
239000012528 membrane Substances 0.000 description 28
229910052799 carbon Inorganic materials 0.000 description 27
208000023589 ischemic disease Diseases 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 25
230000001684 chronic effect Effects 0.000 description 25
210000002683 foot Anatomy 0.000 description 24
239000003981 vehicle Substances 0.000 description 24
241000282414 Homo sapiens Species 0.000 description 23
VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 22
229910052698 phosphorus Inorganic materials 0.000 description 22
235000019439 ethyl acetate Nutrition 0.000 description 21
238000001727 in vivo Methods 0.000 description 20
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 20
210000001519 tissue Anatomy 0.000 description 20
208000006011 Stroke Diseases 0.000 description 18
125000000753 cycloalkyl group Chemical group 0.000 description 18
238000011161 development Methods 0.000 description 18
239000002158 endotoxin Substances 0.000 description 18
229920006008 lipopolysaccharide Polymers 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
241000700159 Rattus Species 0.000 description 17
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
230000037396 body weight Effects 0.000 description 17
238000002474 experimental method Methods 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 16
125000004432 carbon atom Chemical group C* 0.000 description 16
239000000679 carrageenan Substances 0.000 description 16
235000010418 carrageenan Nutrition 0.000 description 16
229920001525 carrageenan Polymers 0.000 description 16
229940113118 carrageenan Drugs 0.000 description 16
230000002757 inflammatory effect Effects 0.000 description 16
229960000485 methotrexate Drugs 0.000 description 16
125000001424 substituent group Chemical group 0.000 description 16
UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 16
SJHPCNCNNSSLPL-CSKARUKUSA-N (4e)-4-(ethoxymethylidene)-2-phenyl-1,3-oxazol-5-one Chemical compound O1C(=O)C(=C/OCC)\N=C1C1=CC=CC=C1 SJHPCNCNNSSLPL-CSKARUKUSA-N 0.000 description 15
101150041968 CDC13 gene Proteins 0.000 description 15
241000124008 Mammalia Species 0.000 description 15
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 15
239000000460 chlorine Substances 0.000 description 15
206010009887 colitis Diseases 0.000 description 15
238000004440 column chromatography Methods 0.000 description 15
210000002889 endothelial cell Anatomy 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 15
239000000741 silica gel Substances 0.000 description 15
229910002027 silica gel Inorganic materials 0.000 description 15
CCPHAMSKHBDMDS-UHFFFAOYSA-N Chetoseminudin B Natural products C=1NC2=CC=CC=C2C=1CC1(SC)NC(=O)C(CO)(SC)N(C)C1=O CCPHAMSKHBDMDS-UHFFFAOYSA-N 0.000 description 14
206010033799 Paralysis Diseases 0.000 description 14
QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical class CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 14
241000251539 Vertebrata <Metazoa> Species 0.000 description 14
229950010854 mofegiline Drugs 0.000 description 14
210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 14
238000010992 reflux Methods 0.000 description 14
239000000758 substrate Substances 0.000 description 14
VXLBSYHAEKDUSU-JXMROGBWSA-N (2e)-2-(fluoromethylidene)-4-(4-fluorophenyl)butan-1-amine Chemical compound NC\C(=C\F)CCC1=CC=C(F)C=C1 VXLBSYHAEKDUSU-JXMROGBWSA-N 0.000 description 13
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 13
238000005481 NMR spectroscopy Methods 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
239000000651 prodrug Substances 0.000 description 13
229940002612 prodrug Drugs 0.000 description 13
125000006239 protecting group Chemical group 0.000 description 13
108090000623 proteins and genes Proteins 0.000 description 13
230000004083 survival effect Effects 0.000 description 13
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 12
210000003414 extremity Anatomy 0.000 description 12
CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 12
239000003921 oil Substances 0.000 description 12
238000005160 1H NMR spectroscopy Methods 0.000 description 11
238000003556 assay Methods 0.000 description 11
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 11
239000002207 metabolite Substances 0.000 description 11
235000019198 oils Nutrition 0.000 description 11
102000004127 Cytokines Human genes 0.000 description 10
108090000695 Cytokines Proteins 0.000 description 10
206010030113 Oedema Diseases 0.000 description 10
206010003246 arthritis Diseases 0.000 description 10
238000001914 filtration Methods 0.000 description 10
230000004968 inflammatory condition Effects 0.000 description 10
210000004072 lung Anatomy 0.000 description 10
210000004698 lymphocyte Anatomy 0.000 description 10
102000004169 proteins and genes Human genes 0.000 description 10
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
125000003545 alkoxy group Chemical group 0.000 description 9
210000003169 central nervous system Anatomy 0.000 description 9
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
230000006870 function Effects 0.000 description 9
230000002829 reductive effect Effects 0.000 description 9
239000011780 sodium chloride Substances 0.000 description 9
208000024827 Alzheimer disease Diseases 0.000 description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
208000009386 Experimental Arthritis Diseases 0.000 description 8
241000699666 Mus <mouse, genus> Species 0.000 description 8
210000001744 T-lymphocyte Anatomy 0.000 description 8
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 8
229960003957 dexamethasone Drugs 0.000 description 8
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 8
150000002367 halogens Chemical group 0.000 description 8
125000005842 heteroatom Chemical group 0.000 description 8
230000009467 reduction Effects 0.000 description 8
230000008961 swelling Effects 0.000 description 8
201000001320 Atherosclerosis Diseases 0.000 description 7
125000003342 alkenyl group Chemical group 0.000 description 7
238000004458 analytical method Methods 0.000 description 7
210000000709 aorta Anatomy 0.000 description 7
229910052736 halogen Inorganic materials 0.000 description 7
125000004404 heteroalkyl group Chemical group 0.000 description 7
239000007788 liquid Substances 0.000 description 7
210000004185 liver Anatomy 0.000 description 7
210000000056 organ Anatomy 0.000 description 7
230000036961 partial effect Effects 0.000 description 7
239000000047 product Substances 0.000 description 7
206010039073 rheumatoid arthritis Diseases 0.000 description 7
208000024891 symptom Diseases 0.000 description 7
NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 6
102000016893 Amine Oxidase (Copper-Containing) Human genes 0.000 description 6
101710137189 Amyloid-beta A4 protein Proteins 0.000 description 6
101710151993 Amyloid-beta precursor protein Proteins 0.000 description 6
102100022704 Amyloid-beta precursor protein Human genes 0.000 description 6
108010062580 Concanavalin A Proteins 0.000 description 6
241000282412 Homo Species 0.000 description 6
208000022559 Inflammatory bowel disease Diseases 0.000 description 6
102000004316 Oxidoreductases Human genes 0.000 description 6
108090000854 Oxidoreductases Proteins 0.000 description 6
DPWPWRLQFGFJFI-UHFFFAOYSA-N Pargyline Chemical compound C#CCN(C)CC1=CC=CC=C1 DPWPWRLQFGFJFI-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
125000000304 alkynyl group Chemical group 0.000 description 6
DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 6
238000010171 animal model Methods 0.000 description 6
239000000427 antigen Substances 0.000 description 6
102000036639 antigens Human genes 0.000 description 6
108091007433 antigens Proteins 0.000 description 6
230000001363 autoimmune Effects 0.000 description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
239000000872 buffer Substances 0.000 description 6
210000001072 colon Anatomy 0.000 description 6
230000000875 corresponding effect Effects 0.000 description 6
125000004093 cyano group Chemical group *C#N 0.000 description 6
206010012601 diabetes mellitus Diseases 0.000 description 6
XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 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
230000002255 enzymatic effect Effects 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
229960000905 indomethacin Drugs 0.000 description 6
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
229960001779 pargyline Drugs 0.000 description 6
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 6
239000002953 phosphate buffered saline Substances 0.000 description 6
239000008057 potassium phosphate buffer Substances 0.000 description 6
238000003757 reverse transcription PCR Methods 0.000 description 6
DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 6
239000000126 substance Substances 0.000 description 6
230000009885 systemic effect Effects 0.000 description 6
108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
206010009900 Colitis ulcerative Diseases 0.000 description 5
238000001061 Dunnett's test Methods 0.000 description 5
238000002965 ELISA Methods 0.000 description 5
206010017577 Gait disturbance Diseases 0.000 description 5
101000694615 Homo sapiens Membrane primary amine oxidase Proteins 0.000 description 5
206010040047 Sepsis Diseases 0.000 description 5
108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
102100040247 Tumor necrosis factor Human genes 0.000 description 5
201000006704 Ulcerative Colitis Diseases 0.000 description 5
239000002671 adjuvant Substances 0.000 description 5
238000000540 analysis of variance Methods 0.000 description 5
210000003423 ankle Anatomy 0.000 description 5
239000002585 base Substances 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
230000000903 blocking effect Effects 0.000 description 5
210000004369 blood Anatomy 0.000 description 5
239000008280 blood Substances 0.000 description 5
BTFHLQRNAMSNLC-UHFFFAOYSA-N clorgyline Chemical compound C#CCN(C)CCCOC1=CC=C(Cl)C=C1Cl BTFHLQRNAMSNLC-UHFFFAOYSA-N 0.000 description 5
125000004122 cyclic group Chemical group 0.000 description 5
230000034994 death Effects 0.000 description 5
231100000517 death Toxicity 0.000 description 5
229960002986 dinoprostone Drugs 0.000 description 5
102000056133 human AOC3 Human genes 0.000 description 5
150000002430 hydrocarbons Chemical group 0.000 description 5
230000003053 immunization Effects 0.000 description 5
238000002649 immunization Methods 0.000 description 5
230000006698 induction Effects 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 description 5
230000005012 migration Effects 0.000 description 5
238000013508 migration Methods 0.000 description 5
238000010172 mouse model Methods 0.000 description 5
239000012044 organic layer Substances 0.000 description 5
XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 5
108020004418 ribosomal RNA Proteins 0.000 description 5
238000005096 rolling process Methods 0.000 description 5
210000002966 serum Anatomy 0.000 description 5
ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
MBVFRSJFKMJRHA-UHFFFAOYSA-N 4-fluoro-1-benzofuran-7-carbaldehyde Chemical compound FC1=CC=C(C=O)C2=C1C=CO2 MBVFRSJFKMJRHA-UHFFFAOYSA-N 0.000 description 4
206010003591 Ataxia Diseases 0.000 description 4
208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 4
208000017667 Chronic Disease Diseases 0.000 description 4
208000011231 Crohn disease Diseases 0.000 description 4
208000016192 Demyelinating disease Diseases 0.000 description 4
206010012305 Demyelination Diseases 0.000 description 4
206010061818 Disease progression Diseases 0.000 description 4
101001112162 Homo sapiens Kinetochore protein NDC80 homolog Proteins 0.000 description 4
229920000663 Hydroxyethyl cellulose Polymers 0.000 description 4
206010067125 Liver injury Diseases 0.000 description 4
108010083674 Myelin Proteins Proteins 0.000 description 4
102000006386 Myelin Proteins Human genes 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
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
108010081690 Pertussis Toxin Proteins 0.000 description 4
201000004681 Psoriasis Diseases 0.000 description 4
238000011803 SJL/J (JAX™ mice strain) Methods 0.000 description 4
ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 4
108700012920 TNF Proteins 0.000 description 4
230000002159 abnormal effect Effects 0.000 description 4
238000002835 absorbance Methods 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
125000004423 acyloxy group Chemical group 0.000 description 4
230000003321 amplification Effects 0.000 description 4
208000006673 asthma Diseases 0.000 description 4
150000003857 carboxamides Chemical class 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
AUQDITHEDVOTCU-UHFFFAOYSA-N cyclopropyl cyanide Chemical compound N#CC1CC1 AUQDITHEDVOTCU-UHFFFAOYSA-N 0.000 description 4
229920003045 dextran sodium sulfate Polymers 0.000 description 4
230000005750 disease progression Effects 0.000 description 4
229940079593 drug Drugs 0.000 description 4
208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 4
231100000753 hepatic injury Toxicity 0.000 description 4
238000001990 intravenous administration Methods 0.000 description 4
210000000265 leukocyte Anatomy 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
238000005259 measurement Methods 0.000 description 4
238000012544 monitoring process Methods 0.000 description 4
210000005012 myelin Anatomy 0.000 description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
238000003199 nucleic acid amplification method Methods 0.000 description 4
238000003305 oral gavage Methods 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
239000007858 starting material Substances 0.000 description 4
239000012258 stirred mixture Substances 0.000 description 4
229960001052 streptozocin Drugs 0.000 description 4
239000006228 supernatant Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
201000004595 synovitis Diseases 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
239000003826 tablet Substances 0.000 description 4
DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 4
238000012360 testing method Methods 0.000 description 4
125000005309 thioalkoxy group Chemical group 0.000 description 4
238000011830 transgenic mouse model Methods 0.000 description 4
208000001072 type 2 diabetes mellitus Diseases 0.000 description 4
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical group BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
108020004463 18S ribosomal RNA Proteins 0.000 description 3
208000022309 Alcoholic Liver disease Diseases 0.000 description 3
206010003827 Autoimmune hepatitis Diseases 0.000 description 3
208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 3
208000033222 Biliary cirrhosis primary Diseases 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
102000019034 Chemokines Human genes 0.000 description 3
108010012236 Chemokines Proteins 0.000 description 3
206010008609 Cholangitis sclerosing Diseases 0.000 description 3
206010012442 Dermatitis contact Diseases 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
206010013975 Dyspnoeas Diseases 0.000 description 3
208000003456 Juvenile Arthritis Diseases 0.000 description 3
206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 3
241000699660 Mus musculus Species 0.000 description 3
108010058846 Ovalbumin Proteins 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
208000012654 Primary biliary cholangitis Diseases 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
241000283984 Rodentia Species 0.000 description 3
238000011579 SCID mouse model Methods 0.000 description 3
108090000184 Selectins Proteins 0.000 description 3
102000003800 Selectins Human genes 0.000 description 3
206010044565 Tremor Diseases 0.000 description 3
208000027418 Wounds and injury Diseases 0.000 description 3
RROKVPAOLJHHES-BORNJIKYSA-N [(e)-3-fluoro-2-phenylprop-2-enyl]hydrazine;hydrochloride Chemical compound Cl.NNC\C(=C\F)C1=CC=CC=C1 RROKVPAOLJHHES-BORNJIKYSA-N 0.000 description 3
125000001931 aliphatic group Chemical group 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
208000018093 autoimmune cholangitis Diseases 0.000 description 3
239000011575 calcium Substances 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000000969 carrier Substances 0.000 description 3
208000019069 chronic childhood arthritis Diseases 0.000 description 3
208000010247 contact dermatitis Diseases 0.000 description 3
230000006378 damage Effects 0.000 description 3
238000009472 formulation Methods 0.000 description 3
239000000499 gel Substances 0.000 description 3
208000014674 injury Diseases 0.000 description 3
201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 3
239000000463 material Substances 0.000 description 3
230000007246 mechanism Effects 0.000 description 3
DQQJYBYIABSMFM-UHFFFAOYSA-N methyl 2-benzylprop-2-enoate Chemical compound COC(=O)C(=C)CC1=CC=CC=C1 DQQJYBYIABSMFM-UHFFFAOYSA-N 0.000 description 3
RNECFOCWMJDAMM-UHFFFAOYSA-N methyl 2-methylidene-4-phenylbutanoate Chemical compound COC(=O)C(=C)CCC1=CC=CC=C1 RNECFOCWMJDAMM-UHFFFAOYSA-N 0.000 description 3
208000010125 myocardial infarction Diseases 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
229940092253 ovalbumin Drugs 0.000 description 3
229960003424 phenylacetic acid Drugs 0.000 description 3
SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 3
229960005205 prednisolone Drugs 0.000 description 3
OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 3
230000008569 process Effects 0.000 description 3
230000002685 pulmonary effect Effects 0.000 description 3
208000010157 sclerosing cholangitis Diseases 0.000 description 3
210000000278 spinal cord Anatomy 0.000 description 3
238000013223 sprague-dawley female rat Methods 0.000 description 3
238000007920 subcutaneous administration Methods 0.000 description 3
125000000547 substituted alkyl group Chemical group 0.000 description 3
SQBKTZZBVJZXDF-UHFFFAOYSA-N tert-butyl n-[2-(4-chlorophenyl)prop-2-enylamino]carbamate Chemical compound CC(C)(C)OC(=O)NNCC(=C)C1=CC=C(Cl)C=C1 SQBKTZZBVJZXDF-UHFFFAOYSA-N 0.000 description 3
DRDVJQOGFWAVLH-UHFFFAOYSA-N tert-butyl n-hydroxycarbamate Chemical compound CC(C)(C)OC(=O)NO DRDVJQOGFWAVLH-UHFFFAOYSA-N 0.000 description 3
230000003827 upregulation Effects 0.000 description 3
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
ZHFURHRJUWYDKG-UHFFFAOYSA-N 1-phenylcyclopropane-1-carbonitrile Chemical compound C=1C=CC=CC=1C1(C#N)CC1 ZHFURHRJUWYDKG-UHFFFAOYSA-N 0.000 description 2
OLWRRBNHIYEGMR-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)oxirane Chemical compound C1=C(OC)C(OC)=CC=C1C1OC1 OLWRRBNHIYEGMR-UHFFFAOYSA-N 0.000 description 2
MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 2
YJFNTOKQVRSFQZ-UHFFFAOYSA-N 2-cyclopropyl-2-phenylethanamine Chemical compound C=1C=CC=CC=1C(CN)C1CC1 YJFNTOKQVRSFQZ-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
RLFWWDJHLFCNIJ-UHFFFAOYSA-N 4-aminoantipyrine Chemical compound CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 2
238000011740 C57BL/6 mouse Methods 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
239000004215 Carbon black (E152) Substances 0.000 description 2
206010007559 Cardiac failure congestive Diseases 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
206010010904 Convulsion Diseases 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
201000004624 Dermatitis Diseases 0.000 description 2
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
208000037487 Endotoxemia Diseases 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
102000020897 Formins Human genes 0.000 description 2
108091022623 Formins Proteins 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
206010019280 Heart failures Diseases 0.000 description 2
108090001005 Interleukin-6 Proteins 0.000 description 2
206010023232 Joint swelling Diseases 0.000 description 2
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 2
235000019759 Maize starch Nutrition 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
102100023302 Myelin-oligodendrocyte glycoprotein Human genes 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
206010070834 Sensitisation Diseases 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
208000025865 Ulcer Diseases 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
239000013543 active substance Substances 0.000 description 2
231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 2
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
208000037883 airway inflammation Diseases 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
229940024606 amino acid Drugs 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
230000003110 anti-inflammatory effect Effects 0.000 description 2
230000003376 axonal effect Effects 0.000 description 2
150000007514 bases Chemical class 0.000 description 2
230000008901 benefit Effects 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 2
125000002837 carbocyclic group Chemical group 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
239000003086 colorant Substances 0.000 description 2
238000007398 colorimetric assay Methods 0.000 description 2
239000002299 complementary DNA Substances 0.000 description 2
230000036461 convulsion Effects 0.000 description 2
230000001186 cumulative effect Effects 0.000 description 2
230000016396 cytokine production Effects 0.000 description 2
238000000326 densiometry Methods 0.000 description 2
238000000151 deposition Methods 0.000 description 2
230000008021 deposition Effects 0.000 description 2
239000010432 diamond Substances 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
230000001712 encephalitogenic effect Effects 0.000 description 2
230000003511 endothelial effect Effects 0.000 description 2
210000003038 endothelium Anatomy 0.000 description 2
230000009088 enzymatic function Effects 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
210000000416 exudates and transudate Anatomy 0.000 description 2
239000012530 fluid Substances 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
125000001207 fluorophenyl group Chemical group 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
239000008187 granular material Substances 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
125000001183 hydrocarbyl group Chemical group 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N hydroxylamine hydrochloride Substances Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
230000036039 immunity Effects 0.000 description 2
102000006495 integrins Human genes 0.000 description 2
108010044426 integrins Proteins 0.000 description 2
230000003993 interaction Effects 0.000 description 2
239000007928 intraperitoneal injection Substances 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
239000008101 lactose Substances 0.000 description 2
230000023404 leukocyte cell-cell adhesion Effects 0.000 description 2
239000003446 ligand Substances 0.000 description 2
239000012280 lithium aluminium hydride Substances 0.000 description 2
208000019423 liver disease Diseases 0.000 description 2
210000005228 liver tissue Anatomy 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
108020004999 messenger RNA Proteins 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 2
230000010807 negative regulation of binding Effects 0.000 description 2
230000008506 pathogenesis Effects 0.000 description 2
231100000915 pathological change Toxicity 0.000 description 2
230000036285 pathological change Effects 0.000 description 2
239000003208 petroleum Substances 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
239000008363 phosphate buffer Substances 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
239000013641 positive control Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
229920001592 potato starch Polymers 0.000 description 2
239000000843 powder Substances 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
108090000765 processed proteins & peptides Proteins 0.000 description 2
238000012545 processing Methods 0.000 description 2
230000006337 proteolytic cleavage Effects 0.000 description 2
238000000746 purification Methods 0.000 description 2
230000007115 recruitment Effects 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
239000000523 sample Substances 0.000 description 2
230000008313 sensitization Effects 0.000 description 2
230000035939 shock Effects 0.000 description 2
150000003384 small molecules Chemical class 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
241000894007 species Species 0.000 description 2
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
235000012222 talc Nutrition 0.000 description 2
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
TUJFXQRIPWTJHL-UHFFFAOYSA-N tert-butyl n-(2-hydroxy-2-phenylethoxy)carbamate Chemical compound CC(C)(C)OC(=O)NOCC(O)C1=CC=CC=C1 TUJFXQRIPWTJHL-UHFFFAOYSA-N 0.000 description 2
KHDPYDFAFPXHMO-UHFFFAOYSA-N tert-butyl n-(2-phenylprop-2-enylamino)carbamate Chemical compound CC(C)(C)OC(=O)NNCC(=C)C1=CC=CC=C1 KHDPYDFAFPXHMO-UHFFFAOYSA-N 0.000 description 2
UVRKINUFAZWHJG-UHFFFAOYSA-N tert-butyl n-[2-(4-chlorophenyl)prop-2-enyl-methylamino]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)N(C)CC(=C)C1=CC=C(Cl)C=C1 UVRKINUFAZWHJG-UHFFFAOYSA-N 0.000 description 2
FZJMYBYRSVECNR-UHFFFAOYSA-N tert-butyl n-[2-(4-chlorophenyl)prop-2-enyl-methylamino]carbamate Chemical compound CC(C)(C)OC(=O)NN(C)CC(=C)C1=CC=C(Cl)C=C1 FZJMYBYRSVECNR-UHFFFAOYSA-N 0.000 description 2
ZKRINGVIBXZSNR-UHFFFAOYSA-N tert-butyl n-[2-(4-fluorophenyl)prop-2-enyl]-n-[(2-methylpropan-2-yl)oxycarbonylamino]carbamate Chemical compound CC(C)(C)OC(=O)NN(C(=O)OC(C)(C)C)CC(=C)C1=CC=C(F)C=C1 ZKRINGVIBXZSNR-UHFFFAOYSA-N 0.000 description 2
229940124597 therapeutic agent Drugs 0.000 description 2
231100000027 toxicology Toxicity 0.000 description 2
230000009466 transformation Effects 0.000 description 2
238000002054 transplantation Methods 0.000 description 2
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 2
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 2
230000036269 ulceration Effects 0.000 description 2
238000011870 unpaired t-test Methods 0.000 description 2
235000015112 vegetable and seed oil Nutrition 0.000 description 2
239000008158 vegetable oil Substances 0.000 description 2
210000000264 venule Anatomy 0.000 description 2
WJUFSDZVCOTFON-UHFFFAOYSA-N veratraldehyde Chemical compound COC1=CC=C(C=O)C=C1OC WJUFSDZVCOTFON-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
239000000080 wetting agent Substances 0.000 description 2
210000000707 wrist Anatomy 0.000 description 2
MIVHNNWMFIPWIF-UHFFFAOYSA-N (1-benzylcyclopropyl)methanamine Chemical compound C=1C=CC=CC=1CC1(CN)CC1 MIVHNNWMFIPWIF-UHFFFAOYSA-N 0.000 description 1
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
ANRRZBDRZFSLOU-UHFFFAOYSA-N 1-(1-phenylethyl)cyclopropane-1-carbonitrile Chemical compound C1CC1(C#N)C(C)C1=CC=CC=C1 ANRRZBDRZFSLOU-UHFFFAOYSA-N 0.000 description 1
RVLXQVFSQVDAJR-UHFFFAOYSA-N 1-benzylcyclopropane-1-carbonitrile Chemical compound C=1C=CC=CC=1CC1(C#N)CC1 RVLXQVFSQVDAJR-UHFFFAOYSA-N 0.000 description 1
VIXHMBLBLJSGIB-UHFFFAOYSA-N 1-fluoro-4-prop-1-en-2-ylbenzene Chemical compound CC(=C)C1=CC=C(F)C=C1 VIXHMBLBLJSGIB-UHFFFAOYSA-N 0.000 description 1
HCKNRHBSGZMOOF-UHFFFAOYSA-N 1-methoxy-2-methylperoxyethane Chemical compound COCCOOC HCKNRHBSGZMOOF-UHFFFAOYSA-N 0.000 description 1
UYHBBRNZXFPZDY-UHFFFAOYSA-N 2-(4-chlorophenyl)prop-2-enylhydrazine;hydrochloride Chemical compound Cl.NNCC(=C)C1=CC=C(Cl)C=C1 UYHBBRNZXFPZDY-UHFFFAOYSA-N 0.000 description 1
MZTVYRBWPUOPQJ-UHFFFAOYSA-N 2-aminooxy-1-(3,4-dimethoxyphenyl)ethanol Chemical compound COC1=CC=C(C(O)CON)C=C1OC MZTVYRBWPUOPQJ-UHFFFAOYSA-N 0.000 description 1
ZLBWPYIKHLGYQC-UHFFFAOYSA-N 2-aminooxy-1-phenylethanol Chemical compound NOCC(O)C1=CC=CC=C1 ZLBWPYIKHLGYQC-UHFFFAOYSA-N 0.000 description 1
CXJMDHNSLHEFGD-UHFFFAOYSA-N 2-aminooxy-1-phenylethanol;hydrochloride Chemical compound Cl.NOCC(O)C1=CC=CC=C1 CXJMDHNSLHEFGD-UHFFFAOYSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
OEWJOARNIZVJLM-UHFFFAOYSA-N 2-phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1.N#CCC1=CC=CC=C1 OEWJOARNIZVJLM-UHFFFAOYSA-N 0.000 description 1
WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
UKVQBONVSSLJBB-UHFFFAOYSA-N 2-pyridin-2-ylacetonitrile Chemical compound N#CCC1=CC=CC=N1 UKVQBONVSSLJBB-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
USEGQJLHQSTGHW-UHFFFAOYSA-N 3-bromo-2-methylprop-1-ene Chemical compound CC(=C)CBr USEGQJLHQSTGHW-UHFFFAOYSA-N 0.000 description 1
NFERCJTWCQRBMG-UHFFFAOYSA-N 3-phenylprop-2-enylhydrazine;hydrochloride Chemical compound Cl.NNCC=CC1=CC=CC=C1 NFERCJTWCQRBMG-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
229960000549 4-dimethylaminophenol Drugs 0.000 description 1
HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
102000002260 Alkaline Phosphatase Human genes 0.000 description 1
108020004774 Alkaline Phosphatase Proteins 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
208000037259 Amyloid Plaque Diseases 0.000 description 1
241000486679 Antitype Species 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
208000030767 Autoimmune encephalitis Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
101000694614 Bos taurus Primary amine oxidase, liver isozyme Proteins 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
ACPQBYSKUWZMQZ-UHFFFAOYSA-N CC=1C(=C(C=CC1OC)C(=O)C(=O)C1=CC=C(C=C1)OC)C Chemical compound CC=1C(=C(C=CC1OC)C(=O)C(=O)C1=CC=C(C=C1)OC)C ACPQBYSKUWZMQZ-UHFFFAOYSA-N 0.000 description 1
101100193977 Caenorhabditis elegans rcan-1 gene Proteins 0.000 description 1
206010007558 Cardiac failure chronic Diseases 0.000 description 1
108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
206010053398 Clonic convulsion Diseases 0.000 description 1
102000008186 Collagen Human genes 0.000 description 1
108010035532 Collagen Proteins 0.000 description 1
102000000503 Collagen Type II Human genes 0.000 description 1
108010041390 Collagen Type II Proteins 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
206010012289 Dementia Diseases 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
208000002249 Diabetes Complications Diseases 0.000 description 1
BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Chemical group CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
102100038591 Endothelial cell-selective adhesion molecule Human genes 0.000 description 1
239000001856 Ethyl cellulose Substances 0.000 description 1
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
206010016654 Fibrosis Diseases 0.000 description 1
238000002738 Giemsa staining Methods 0.000 description 1
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
208000032843 Hemorrhage Diseases 0.000 description 1
101000694718 Homo sapiens Amine oxidase [flavin-containing] A Proteins 0.000 description 1
101000768078 Homo sapiens Amine oxidase [flavin-containing] B Proteins 0.000 description 1
101000882622 Homo sapiens Endothelial cell-selective adhesion molecule Proteins 0.000 description 1
101001115699 Homo sapiens Myelin-oligodendrocyte glycoprotein Proteins 0.000 description 1
101000622137 Homo sapiens P-selectin Proteins 0.000 description 1
108010001336 Horseradish Peroxidase Proteins 0.000 description 1
108090000144 Human Proteins Proteins 0.000 description 1
102000003839 Human Proteins Human genes 0.000 description 1
108060003951 Immunoglobulin Proteins 0.000 description 1
108010002352 Interleukin-1 Proteins 0.000 description 1
YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical class OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
208000026139 Memory disease Diseases 0.000 description 1
102000009664 Microtubule-Associated Proteins Human genes 0.000 description 1
108010020004 Microtubule-Associated Proteins Proteins 0.000 description 1
238000006751 Mitsunobu reaction Methods 0.000 description 1
101001135737 Mus musculus Parathyroid hormone-related protein Proteins 0.000 description 1
101100046526 Mus musculus Tnf gene Proteins 0.000 description 1
108010000123 Myelin-Oligodendrocyte Glycoprotein Proteins 0.000 description 1
HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
102000005348 Neuraminidase Human genes 0.000 description 1
108010006232 Neuraminidase Proteins 0.000 description 1
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
102100023472 P-selectin Human genes 0.000 description 1
101150044441 PECAM1 gene Proteins 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
108010033276 Peptide Fragments Proteins 0.000 description 1
102000007079 Peptide Fragments Human genes 0.000 description 1
102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 1
229920005372 Plexiglas® Polymers 0.000 description 1
206010035664 Pneumonia Diseases 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
239000004743 Polypropylene Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
241000282849 Ruminantia Species 0.000 description 1
108010032838 Sialoglycoproteins Proteins 0.000 description 1
102000007365 Sialoglycoproteins Human genes 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
AWMVMTVKBNGEAK-UHFFFAOYSA-N Styrene oxide Chemical compound C1OC1C1=CC=CC=C1 AWMVMTVKBNGEAK-UHFFFAOYSA-N 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
102000003929 Transaminases Human genes 0.000 description 1
108090000340 Transaminases Proteins 0.000 description 1
GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
201000004810 Vascular dementia Diseases 0.000 description 1
YOKWWIFIZYCEGO-UHFFFAOYSA-N [1-(1-phenylethyl)cyclopropyl]methanamine Chemical compound C1CC1(CN)C(C)C1=CC=CC=C1 YOKWWIFIZYCEGO-UHFFFAOYSA-N 0.000 description 1
206010000269 abscess Diseases 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
235000011054 acetic acid Nutrition 0.000 description 1
230000004913 activation Effects 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
208000038016 acute inflammation Diseases 0.000 description 1
230000006022 acute inflammation Effects 0.000 description 1
230000010398 acute inflammatory response Effects 0.000 description 1
231100000403 acute toxicity Toxicity 0.000 description 1
230000007059 acute toxicity Effects 0.000 description 1
150000003855 acyl compounds Chemical class 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000001464 adherent effect Effects 0.000 description 1
108010013985 adhesion receptor Proteins 0.000 description 1
102000019997 adhesion receptor Human genes 0.000 description 1
239000000853 adhesive Substances 0.000 description 1
230000001070 adhesive effect Effects 0.000 description 1
210000001789 adipocyte Anatomy 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
230000008369 airway response Effects 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
150000001347 alkyl bromides Chemical class 0.000 description 1
239000013566 allergen Substances 0.000 description 1
230000000172 allergic effect Effects 0.000 description 1
XYLMUPLGERFSHI-UHFFFAOYSA-N alpha-Methylstyrene Chemical compound CC(=C)C1=CC=CC=C1 XYLMUPLGERFSHI-UHFFFAOYSA-N 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
NHKJDYJCQARWDK-UHFFFAOYSA-N amino(tert-butyl)carbamic acid tert-butyl N-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN.CC(C)(C)N(N)C(O)=O NHKJDYJCQARWDK-UHFFFAOYSA-N 0.000 description 1
BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
239000010775 animal oil Substances 0.000 description 1
238000000137 annealing Methods 0.000 description 1
125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
230000003367 anti-collagen effect Effects 0.000 description 1
210000000436 anus Anatomy 0.000 description 1
230000006907 apoptotic process Effects 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000008365 aqueous carrier Substances 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
230000005784 autoimmunity Effects 0.000 description 1
210000001142 back Anatomy 0.000 description 1
239000002199 base oil Substances 0.000 description 1
230000006399 behavior Effects 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
229960002903 benzyl benzoate Drugs 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
XGIUDIMNNMKGDE-UHFFFAOYSA-N bis(trimethylsilyl)azanide Chemical compound C[Si](C)(C)[N-][Si](C)(C)C XGIUDIMNNMKGDE-UHFFFAOYSA-N 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
239000012888 bovine serum Substances 0.000 description 1
239000012267 brine Substances 0.000 description 1
230000031709 bromination Effects 0.000 description 1
238000005893 bromination reaction Methods 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000010804 cDNA synthesis Methods 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
230000004663 cell proliferation Effects 0.000 description 1
230000003833 cell viability Effects 0.000 description 1
210000003710 cerebral cortex Anatomy 0.000 description 1
230000008859 change Effects 0.000 description 1
125000003636 chemical group Chemical group 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
235000013985 cinnamic acid Nutrition 0.000 description 1
229930016911 cinnamic acid Natural products 0.000 description 1
239000007979 citrate buffer Substances 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
238000010367 cloning Methods 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
238000004737 colorimetric analysis Methods 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
229940125782 compound 2 Drugs 0.000 description 1
230000002596 correlated effect Effects 0.000 description 1
239000006071 cream Substances 0.000 description 1
125000006165 cyclic alkyl group Chemical group 0.000 description 1
230000001351 cycling effect Effects 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
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 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
230000007423 decrease Effects 0.000 description 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000007547 defect Effects 0.000 description 1
238000004925 denaturation Methods 0.000 description 1
230000036425 denaturation Effects 0.000 description 1
210000004443 dendritic cell Anatomy 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000001212 derivatisation Methods 0.000 description 1
239000002274 desiccant Substances 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
229910003460 diamond Inorganic materials 0.000 description 1
GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
238000009826 distribution Methods 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
238000006911 enzymatic reaction Methods 0.000 description 1
YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
210000003979 eosinophil Anatomy 0.000 description 1
210000002919 epithelial cell Anatomy 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
229960005542 ethidium bromide Drugs 0.000 description 1
235000019325 ethyl cellulose Nutrition 0.000 description 1
229920001249 ethyl cellulose Polymers 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
230000005284 excitation Effects 0.000 description 1
210000002950 fibroblast Anatomy 0.000 description 1
230000004761 fibrosis Effects 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000007850 fluorescent dye Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000013305 food Nutrition 0.000 description 1
230000037406 food intake Effects 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000003205 fragrance Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
210000001280 germinal center Anatomy 0.000 description 1
230000000762 glandular Effects 0.000 description 1
239000011521 glass Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
150000002306 glutamic acid derivatives Chemical class 0.000 description 1
210000004013 groin Anatomy 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
230000035876 healing Effects 0.000 description 1
230000036541 health Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
208000035861 hematochezia Diseases 0.000 description 1
238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
231100000234 hepatic damage Toxicity 0.000 description 1
230000002440 hepatic effect Effects 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000012188 high-throughput screening assay Methods 0.000 description 1
210000000548 hind-foot Anatomy 0.000 description 1
210000001320 hippocampus Anatomy 0.000 description 1
238000010231 histologic analysis Methods 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
OUUQCZGPVNCOIJ-UHFFFAOYSA-N hydroperoxyl Chemical compound O[O] OUUQCZGPVNCOIJ-UHFFFAOYSA-N 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
239000005457 ice water Substances 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
210000002865 immune cell Anatomy 0.000 description 1
238000003365 immunocytochemistry Methods 0.000 description 1
102000018358 immunoglobulin Human genes 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
230000037456 inflammatory mechanism Effects 0.000 description 1
230000003914 insulin secretion Effects 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
210000004153 islets of langerhan Anatomy 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
229960003299 ketamine Drugs 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
239000010410 layer Substances 0.000 description 1
230000003902 lesion Effects 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
231100000225 lethality Toxicity 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
239000002502 liposome Substances 0.000 description 1
239000012669 liquid formulation Substances 0.000 description 1
238000005567 liquid scintillation counting Methods 0.000 description 1
230000008818 liver damage Effects 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
210000001165 lymph node Anatomy 0.000 description 1
230000001926 lymphatic effect Effects 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
125000005394 methallyl group Chemical group 0.000 description 1
NSPJNIDYTSSIIY-UHFFFAOYSA-N methoxy(methoxymethoxy)methane Chemical compound COCOCOC NSPJNIDYTSSIIY-UHFFFAOYSA-N 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
239000003068 molecular probe Substances 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
210000004877 mucosa Anatomy 0.000 description 1
210000004400 mucous membrane Anatomy 0.000 description 1
230000003387 muscular Effects 0.000 description 1
230000035772 mutation Effects 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
210000002850 nasal mucosa Anatomy 0.000 description 1
239000006199 nebulizer Substances 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
210000002682 neurofibrillary tangle Anatomy 0.000 description 1
210000000440 neutrophil Anatomy 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000002560 nitrile group Chemical group 0.000 description 1
125000006502 nitrobenzyl group Chemical group 0.000 description 1
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
238000007833 oxidative deamination reaction Methods 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000001717 pathogenic effect Effects 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
230000007170 pathology Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
210000003668 pericyte Anatomy 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
210000001986 peyer's patch Anatomy 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
239000006187 pill Substances 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
229920001515 polyalkylene glycol Polymers 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
239000004926 polymethyl methacrylate Substances 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
238000011886 postmortem examination Methods 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
238000011533 pre-incubation Methods 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
229960004618 prednisone Drugs 0.000 description 1
230000002265 prevention Effects 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000000770 proinflammatory effect Effects 0.000 description 1
AAEVYOVXGOFMJO-UHFFFAOYSA-N prometryn Chemical compound CSC1=NC(NC(C)C)=NC(NC(C)C)=N1 AAEVYOVXGOFMJO-UHFFFAOYSA-N 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
YQUVCSBJEUQKSH-UHFFFAOYSA-N protochatechuic acid Natural products OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
238000007420 radioactive assay Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
201000010727 rectal prolapse Diseases 0.000 description 1
230000026304 regulation of glucose transport Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
238000011808 rodent model Methods 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
238000007423 screening assay Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000012163 sequencing technique Methods 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000017550 sodium carbonate Nutrition 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000002904 solvent Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
210000000952 spleen Anatomy 0.000 description 1
210000004988 splenocyte Anatomy 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000003068 static effect Effects 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
230000004960 subcellular localization Effects 0.000 description 1
125000005017 substituted alkenyl group Chemical group 0.000 description 1
125000004426 substituted alkynyl group Chemical group 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
102000013498 tau Proteins Human genes 0.000 description 1
108010026424 tau Proteins Proteins 0.000 description 1
210000004876 tela submucosa Anatomy 0.000 description 1
FEBHPIMSAATNQM-UHFFFAOYSA-N tert-butyl N-hydroxycarbamate tert-butyl(hydroxy)carbamic acid Chemical compound CC(C)(C)OC(=O)NO.CC(C)(C)N(O)C(O)=O FEBHPIMSAATNQM-UHFFFAOYSA-N 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
IOPZBVFVFPPDSC-UHFFFAOYSA-N tert-butyl n-(1,3-dioxoisoindol-2-yl)carbamate Chemical compound C1=CC=C2C(=O)N(NC(=O)OC(C)(C)C)C(=O)C2=C1 IOPZBVFVFPPDSC-UHFFFAOYSA-N 0.000 description 1
OUXKAMDZULXKAV-UHFFFAOYSA-N tert-butyl n-(2-methylprop-2-enylamino)carbamate Chemical compound CC(=C)CNNC(=O)OC(C)(C)C OUXKAMDZULXKAV-UHFFFAOYSA-N 0.000 description 1
TYSZETYVESRFNT-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylamino]carbamate Chemical compound CC(C)(C)OC(=O)NNC(=O)OC(C)(C)C TYSZETYVESRFNT-UHFFFAOYSA-N 0.000 description 1
ZSNAHFNVIGEOCK-UHFFFAOYSA-N tert-butyl n-[2-(3,4-dimethoxyphenyl)-2-hydroxyethoxy]carbamate Chemical compound COC1=CC=C(C(O)CONC(=O)OC(C)(C)C)C=C1OC ZSNAHFNVIGEOCK-UHFFFAOYSA-N 0.000 description 1
QFVIVIIQEGBIGC-UHFFFAOYSA-N tert-butyl n-[2-(4-chlorophenyl)prop-2-enyl-ethylamino]carbamate Chemical compound CC(C)(C)OC(=O)NN(CC)CC(=C)C1=CC=C(Cl)C=C1 QFVIVIIQEGBIGC-UHFFFAOYSA-N 0.000 description 1
RSMHENSUKPNMRB-UHFFFAOYSA-N tert-butyl n-[2-(4-fluorophenyl)prop-2-enyl]-n-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]carbamate Chemical compound CC(C)(C)OC(=O)N(C)N(C(=O)OC(C)(C)C)CC(=C)C1=CC=C(F)C=C1 RSMHENSUKPNMRB-UHFFFAOYSA-N 0.000 description 1
KUEMQQBUBQYBRK-UHFFFAOYSA-N tert-butyl n-[2-(4-fluorophenyl)prop-2-enylamino]carbamate Chemical compound CC(C)(C)OC(=O)NNCC(=C)C1=CC=C(F)C=C1 KUEMQQBUBQYBRK-UHFFFAOYSA-N 0.000 description 1
HWZWAXUFYVFIKP-XFXZXTDPSA-N tert-butyl n-amino-n-[(e)-3-fluoro-2-phenylprop-2-enyl]carbamate Chemical compound CC(C)(C)OC(=O)N(N)C\C(=C\F)C1=CC=CC=C1 HWZWAXUFYVFIKP-XFXZXTDPSA-N 0.000 description 1
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
230000001550 time effect Effects 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000032258 transport Effects 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
VFJYIHQDILEQNR-UHFFFAOYSA-M trimethylsulfanium;iodide Chemical compound [I-].C[S+](C)C VFJYIHQDILEQNR-UHFFFAOYSA-M 0.000 description 1
229960003732 tyramine Drugs 0.000 description 1
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 description 1
TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 0.000 description 1
210000005166 vasculature Anatomy 0.000 description 1
239000004034 viscosity adjusting agent Substances 0.000 description 1
BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
229960001600 xylazine Drugs 0.000 description 1