JP2008512346A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2008512346A5 JP2008512346A5 JP2007511147A JP2007511147A JP2008512346A5 JP 2008512346 A5 JP2008512346 A5 JP 2008512346A5 JP 2007511147 A JP2007511147 A JP 2007511147A JP 2007511147 A JP2007511147 A JP 2007511147A JP 2008512346 A5 JP2008512346 A5 JP 2008512346A5
- Authority
- JP
- Japan
- Prior art keywords
- ethyl
- acetamide
- methyl
- nmr
- ppm
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 162
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 144
- 239000000243 solution Substances 0.000 description 139
- 150000001875 compounds Chemical class 0.000 description 127
- 238000005160 1H NMR spectroscopy Methods 0.000 description 118
- 238000000034 method Methods 0.000 description 117
- 238000004519 manufacturing process Methods 0.000 description 101
- 239000000203 mixture Substances 0.000 description 97
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 95
- 102100027159 Membrane primary amine oxidase Human genes 0.000 description 86
- -1 —OH Chemical group 0.000 description 85
- 101710132836 Membrane primary amine oxidase Proteins 0.000 description 84
- 230000008569 process Effects 0.000 description 74
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 71
- 239000011541 reaction mixture Substances 0.000 description 68
- 239000007787 solid Substances 0.000 description 68
- 230000002829 reductive effect Effects 0.000 description 64
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 55
- 239000003112 inhibitor Substances 0.000 description 49
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
- 238000002360 preparation method Methods 0.000 description 48
- 150000003839 salts Chemical class 0.000 description 46
- 229960001701 chloroform Drugs 0.000 description 44
- 201000010099 disease Diseases 0.000 description 44
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 44
- 125000000217 alkyl group Chemical group 0.000 description 43
- 238000003786 synthesis reaction Methods 0.000 description 41
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- 230000015572 biosynthetic process Effects 0.000 description 38
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 35
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 239000012299 nitrogen atmosphere Substances 0.000 description 33
- 239000000741 silica gel Substances 0.000 description 33
- 229910002027 silica gel Inorganic materials 0.000 description 33
- 206010012601 diabetes mellitus Diseases 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
- 238000003818 flash chromatography Methods 0.000 description 30
- 125000003118 aryl group Chemical group 0.000 description 28
- 239000002244 precipitate Substances 0.000 description 28
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
- 208000001344 Macular Edema Diseases 0.000 description 26
- 206010025415 Macular oedema Diseases 0.000 description 26
- 201000010230 macular retinal edema Diseases 0.000 description 26
- 239000000706 filtrate Substances 0.000 description 24
- 238000001914 filtration Methods 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 23
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 22
- 235000019341 magnesium sulphate Nutrition 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 229910052739 hydrogen Inorganic materials 0.000 description 20
- 239000001257 hydrogen Substances 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- 239000011734 sodium Substances 0.000 description 20
- 239000000725 suspension Substances 0.000 description 20
- 239000012267 brine Substances 0.000 description 19
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
- 208000024891 symptom Diseases 0.000 description 19
- 208000027866 inflammatory disease Diseases 0.000 description 17
- 125000004432 carbon atom Chemical group C* 0.000 description 16
- 238000001816 cooling Methods 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 description 15
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
- 208000017442 Retinal disease Diseases 0.000 description 14
- 206010038923 Retinopathy Diseases 0.000 description 14
- 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 14
- 235000019441 ethanol Nutrition 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 13
- 206010003210 Arteriosclerosis Diseases 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- 208000011775 arteriosclerosis disease Diseases 0.000 description 12
- 125000003710 aryl alkyl group Chemical group 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- 238000010898 silica gel chromatography Methods 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- 238000006467 substitution reaction Methods 0.000 description 11
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 10
- 238000011282 treatment Methods 0.000 description 10
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 9
- 206010003246 arthritis Diseases 0.000 description 9
- 201000011190 diabetic macular edema Diseases 0.000 description 9
- 150000002431 hydrogen Chemical class 0.000 description 9
- 239000003960 organic solvent Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- 229920002554 vinyl polymer Polymers 0.000 description 9
- LSBXWMQLLHVMMW-UHFFFAOYSA-N 2-[5-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]thiophen-2-yl]-n-(diaminomethylidene)acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CC(=O)NC(N)=N)=CC=2)=C1 LSBXWMQLLHVMMW-UHFFFAOYSA-N 0.000 description 8
- 206010020772 Hypertension Diseases 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 208000012322 Raynaud phenomenon Diseases 0.000 description 8
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 8
- 235000011054 acetic acid Nutrition 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 150000002367 halogens Chemical class 0.000 description 8
- 125000000623 heterocyclic group Chemical group 0.000 description 8
- 208000010125 myocardial infarction Diseases 0.000 description 8
- 201000008482 osteoarthritis Diseases 0.000 description 8
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 8
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 8
- 230000002792 vascular Effects 0.000 description 8
- ZEXMUXOCMYAHLH-UHFFFAOYSA-N 2-[4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]phenyl]acetic acid Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CC(O)=O)=CC=2)=C1 ZEXMUXOCMYAHLH-UHFFFAOYSA-N 0.000 description 7
- 201000001320 Atherosclerosis Diseases 0.000 description 7
- 208000002249 Diabetes Complications Diseases 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
- 206010047115 Vasculitis Diseases 0.000 description 7
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 7
- 125000002947 alkylene group Chemical group 0.000 description 7
- 208000019425 cirrhosis of liver Diseases 0.000 description 7
- 208000003265 stomatitis Diseases 0.000 description 7
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- VXAPNCLMTSOGLM-UHFFFAOYSA-N n-[4-[2-[4-[(2-amino-1h-imidazol-5-yl)methyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CC=3N=C(N)NC=3)=CC=2)=C1 VXAPNCLMTSOGLM-UHFFFAOYSA-N 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
- 206010016654 Fibrosis Diseases 0.000 description 5
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 5
- 230000002411 adverse Effects 0.000 description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 5
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 5
- 239000010779 crude oil Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 5
- KBQWZCGLPJQCAU-UHFFFAOYSA-N n-(4-formyl-1,3-thiazol-2-yl)acetamide Chemical compound CC(=O)NC1=NC(C=O)=CS1 KBQWZCGLPJQCAU-UHFFFAOYSA-N 0.000 description 5
- 201000001119 neuropathy Diseases 0.000 description 5
- 230000007823 neuropathy Effects 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 208000033808 peripheral neuropathy Diseases 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 4
- 206010002383 Angina Pectoris Diseases 0.000 description 4
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 4
- 208000036487 Arthropathies Diseases 0.000 description 4
- 206010061666 Autonomic neuropathy Diseases 0.000 description 4
- 208000037157 Azotemia Diseases 0.000 description 4
- 208000027496 Behcet disease Diseases 0.000 description 4
- 208000009137 Behcet syndrome Diseases 0.000 description 4
- 201000004569 Blindness Diseases 0.000 description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 4
- 206010009900 Colitis ulcerative Diseases 0.000 description 4
- 208000011231 Crohn disease Diseases 0.000 description 4
- 206010012438 Dermatitis atopic Diseases 0.000 description 4
- 206010012442 Dermatitis contact Diseases 0.000 description 4
- 206010012655 Diabetic complications Diseases 0.000 description 4
- 208000006926 Discoid Lupus Erythematosus Diseases 0.000 description 4
- 206010014954 Eosinophilic fasciitis Diseases 0.000 description 4
- 206010015150 Erythema Diseases 0.000 description 4
- 208000003790 Foot Ulcer Diseases 0.000 description 4
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 4
- 208000032382 Ischaemic stroke Diseases 0.000 description 4
- 208000012659 Joint disease Diseases 0.000 description 4
- 208000003456 Juvenile Arthritis Diseases 0.000 description 4
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 4
- 206010054805 Macroangiopathy Diseases 0.000 description 4
- 208000003250 Mixed connective tissue disease Diseases 0.000 description 4
- 206010029164 Nephrotic syndrome Diseases 0.000 description 4
- 208000008589 Obesity Diseases 0.000 description 4
- 206010030113 Oedema Diseases 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 4
- 206010065159 Polychondritis Diseases 0.000 description 4
- 201000004681 Psoriasis Diseases 0.000 description 4
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 4
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 4
- 208000003782 Raynaud disease Diseases 0.000 description 4
- 208000033464 Reiter syndrome Diseases 0.000 description 4
- 208000001647 Renal Insufficiency Diseases 0.000 description 4
- 206010063837 Reperfusion injury Diseases 0.000 description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 4
- 208000021386 Sjogren Syndrome Diseases 0.000 description 4
- 208000006011 Stroke Diseases 0.000 description 4
- 201000009594 Systemic Scleroderma Diseases 0.000 description 4
- 206010042953 Systemic sclerosis Diseases 0.000 description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 description 4
- 230000005856 abnormality Effects 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 210000001789 adipocyte Anatomy 0.000 description 4
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 4
- 125000004450 alkenylene group Chemical group 0.000 description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 4
- 230000000172 allergic effect Effects 0.000 description 4
- 238000002266 amputation Methods 0.000 description 4
- 125000005129 aryl carbonyl group Chemical group 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 201000008937 atopic dermatitis Diseases 0.000 description 4
- 208000010668 atopic eczema Diseases 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 230000003915 cell function Effects 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 208000019069 chronic childhood arthritis Diseases 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 230000007882 cirrhosis Effects 0.000 description 4
- 210000001072 colon Anatomy 0.000 description 4
- 210000002808 connective tissue Anatomy 0.000 description 4
- 208000010247 contact dermatitis Diseases 0.000 description 4
- 230000002920 convulsive effect Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 208000004921 cutaneous lupus erythematosus Diseases 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 201000001981 dermatomyositis Diseases 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 230000003511 endothelial effect Effects 0.000 description 4
- 231100000321 erythema Toxicity 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 208000006454 hepatitis Diseases 0.000 description 4
- 231100000283 hepatitis Toxicity 0.000 description 4
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000002198 insoluble material Substances 0.000 description 4
- 208000002551 irritable bowel syndrome Diseases 0.000 description 4
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 4
- 208000017169 kidney disease Diseases 0.000 description 4
- 201000006370 kidney failure Diseases 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 201000011486 lichen planus Diseases 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 201000005518 mononeuropathy Diseases 0.000 description 4
- 201000006417 multiple sclerosis Diseases 0.000 description 4
- 208000031225 myocardial ischemia Diseases 0.000 description 4
- MVESDSWTNCLUPC-UHFFFAOYSA-N n-[4-[2-[4-(2-aminoethyl)phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CCN)=CC=2)=C1 MVESDSWTNCLUPC-UHFFFAOYSA-N 0.000 description 4
- JASURXNLEQJFTN-UHFFFAOYSA-N n-[4-[2-[4-(2-hydroxyethyl)phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CCO)=CC=2)=C1 JASURXNLEQJFTN-UHFFFAOYSA-N 0.000 description 4
- DTAMEVWADAHQQN-UHFFFAOYSA-N n-[4-[2-[5-[(diaminomethylideneamino)methyl]thiophen-2-yl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CNC(N)=N)=CC=2)=C1 DTAMEVWADAHQQN-UHFFFAOYSA-N 0.000 description 4
- 235000020824 obesity Nutrition 0.000 description 4
- 230000000414 obstructive effect Effects 0.000 description 4
- 208000005987 polymyositis Diseases 0.000 description 4
- 239000011148 porous material Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 230000002685 pulmonary effect Effects 0.000 description 4
- 208000002574 reactive arthritis Diseases 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 230000000306 recurrent effect Effects 0.000 description 4
- 208000009169 relapsing polychondritis Diseases 0.000 description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 208000017520 skin disease Diseases 0.000 description 4
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 4
- 238000000638 solvent extraction Methods 0.000 description 4
- 230000001732 thrombotic effect Effects 0.000 description 4
- 201000008757 transient arthritis Diseases 0.000 description 4
- 230000007704 transition Effects 0.000 description 4
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 4
- 208000009852 uremia Diseases 0.000 description 4
- 208000019553 vascular disease Diseases 0.000 description 4
- 238000009423 ventilation Methods 0.000 description 4
- ITPGGUNSUDNGRY-UHFFFAOYSA-N (2-acetamido-1,3-thiazol-4-yl)methyl-triphenylphosphanium;chloride Chemical compound [Cl-].S1C(NC(=O)C)=NC(C[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 ITPGGUNSUDNGRY-UHFFFAOYSA-N 0.000 description 3
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 3
- MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical group CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 description 3
- YFNNZVXGMODJDU-UHFFFAOYSA-N 2-[5-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]thiophen-2-yl]acetic acid Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CC(O)=O)=CC=2)=C1 YFNNZVXGMODJDU-UHFFFAOYSA-N 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- ZGXJGFGKMZBKKB-UHFFFAOYSA-N 3-[5-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]thiophen-2-yl]propanoic acid Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CCC(O)=O)=CC=2)=C1 ZGXJGFGKMZBKKB-UHFFFAOYSA-N 0.000 description 3
- 108010028700 Amine Oxidase (Copper-Containing) Proteins 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 3
- 206010036105 Polyneuropathy Diseases 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 241000220317 Rosa Species 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000023852 carbohydrate metabolic process Effects 0.000 description 3
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 239000013058 crude material Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 235000015220 hamburgers Nutrition 0.000 description 3
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- GWPPDGBJVUYULN-UHFFFAOYSA-N n-[4-[2-[4-[2-(carbamothioylamino)ethyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CCNC(N)=S)=CC=2)=C1 GWPPDGBJVUYULN-UHFFFAOYSA-N 0.000 description 3
- RCMAXTLXGGBSJT-UHFFFAOYSA-N n-[4-[2-[5-[(diaminomethylideneamino)methyl]thiophen-2-yl]ethyl]-1,3-thiazol-2-yl]acetamide;hydrochloride Chemical compound Cl.S1C(NC(=O)C)=NC(CCC=2SC(CNC(N)=N)=CC=2)=C1 RCMAXTLXGGBSJT-UHFFFAOYSA-N 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 230000007824 polyneuropathy Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 3
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 3
- 150000003557 thiazoles Chemical class 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- KBPHJBAIARWVSC-XQIHNALSSA-N trans-lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C KBPHJBAIARWVSC-XQIHNALSSA-N 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 230000004393 visual impairment Effects 0.000 description 3
- 239000003039 volatile agent Substances 0.000 description 3
- HXYQXLFSLITFSL-UHFFFAOYSA-N (2,6-diethoxyphenyl)methanamine Chemical compound CCOC1=CC=CC(OCC)=C1CN HXYQXLFSLITFSL-UHFFFAOYSA-N 0.000 description 2
- HIXZJPWRAALXBT-UHFFFAOYSA-N (2,6-diethylphenyl)methanamine Chemical compound CCC1=CC=CC(CC)=C1CN HIXZJPWRAALXBT-UHFFFAOYSA-N 0.000 description 2
- WBJSFNLJWDAPGF-UHFFFAOYSA-N (2,6-dipropoxyphenyl)methanamine Chemical compound CCCOC1=CC=CC(OCCC)=C1CN WBJSFNLJWDAPGF-UHFFFAOYSA-N 0.000 description 2
- WUYLHICHUYNPNZ-UHFFFAOYSA-N (2-acetamido-1,3-thiazol-4-yl)methyl acetate Chemical compound CC(=O)NC1=NC(COC(C)=O)=CS1 WUYLHICHUYNPNZ-UHFFFAOYSA-N 0.000 description 2
- 150000005068 1,3,4-oxadiazines Chemical class 0.000 description 2
- SUNMBRGCANLOEG-UHFFFAOYSA-N 1,3-dichloroacetone Chemical compound ClCC(=O)CCl SUNMBRGCANLOEG-UHFFFAOYSA-N 0.000 description 2
- VYVXSFNSQXKFMI-UHFFFAOYSA-N 1-amino-4-[4-(2-amino-1,3-thiazol-4-yl)phenyl]butan-2-one;dihydrochloride Chemical compound Cl.Cl.C1=CC(CCC(=O)CN)=CC=C1C1=CSC(N)=N1 VYVXSFNSQXKFMI-UHFFFAOYSA-N 0.000 description 2
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- JDPDXEGVVCCIMH-UHFFFAOYSA-N 2-[2-(aminomethyl)-3-(2-hydroxyethoxy)phenoxy]ethanol Chemical compound NCC1=C(OCCO)C=CC=C1OCCO JDPDXEGVVCCIMH-UHFFFAOYSA-N 0.000 description 2
- JVASQHRTOWPYOU-UHFFFAOYSA-N 2-[4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]phenyl]-n-(1h-imidazol-2-yl)acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CC(=O)NC=3NC=CN=3)=CC=2)=C1 JVASQHRTOWPYOU-UHFFFAOYSA-N 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- KOHXWWQJZDCWCF-UHFFFAOYSA-N 3-(2-acetamido-1,3-thiazol-4-yl)propanoic acid Chemical compound CC(=O)NC1=NC(CCC(O)=O)=CS1 KOHXWWQJZDCWCF-UHFFFAOYSA-N 0.000 description 2
- CJHCOAWTCPYVHG-UHFFFAOYSA-N 3-[4-(2-acetamido-1,3-thiazol-4-yl)phenyl]propanoic acid Chemical compound S1C(NC(=O)C)=NC(C=2C=CC(CCC(O)=O)=CC=2)=C1 CJHCOAWTCPYVHG-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- GDHDXLLZNZUKGT-UHFFFAOYSA-N 4-[2-(1,3-dioxoisoindol-2-yl)ethyl]benzaldehyde Chemical compound C1=CC(C=O)=CC=C1CCN1C(=O)C2=CC=CC=C2C1=O GDHDXLLZNZUKGT-UHFFFAOYSA-N 0.000 description 2
- WFQKWMRPEDFZGL-UHFFFAOYSA-N 4-[2-[5-[2-(diaminomethylideneamino)-2-oxoethyl]thiophen-2-yl]ethyl]-n,n-dimethyl-1,3-thiazole-2-carboxamide Chemical compound S1C(C(=O)N(C)C)=NC(CCC=2SC(CC(=O)NC(N)=N)=CC=2)=C1 WFQKWMRPEDFZGL-UHFFFAOYSA-N 0.000 description 2
- DOCPCYDUFBHVLB-UHFFFAOYSA-N 4-[2-[5-[2-(diaminomethylideneamino)-2-oxoethyl]thiophen-2-yl]ethyl]-n-methyl-1,3-thiazole-2-carboxamide Chemical compound S1C(C(=O)NC)=NC(CCC=2SC(CC(=O)NC(N)=N)=CC=2)=C1 DOCPCYDUFBHVLB-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 208000010201 Exanthema Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 206010028116 Mucosal inflammation Diseases 0.000 description 2
- 208000000112 Myalgia Diseases 0.000 description 2
- DHAOFTIZBAHSMV-UHFFFAOYSA-N N-fluoroprop-2-en-1-amine Chemical class FNCC=C DHAOFTIZBAHSMV-UHFFFAOYSA-N 0.000 description 2
- MIGYTPGOVYBFNX-UHFFFAOYSA-N NC=1SC=C(N1)CCl.C(C)(=O)O Chemical compound NC=1SC=C(N1)CCl.C(C)(=O)O MIGYTPGOVYBFNX-UHFFFAOYSA-N 0.000 description 2
- 102000004316 Oxidoreductases Human genes 0.000 description 2
- 108090000854 Oxidoreductases Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 208000007048 Polymyalgia Rheumatica Diseases 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 208000025747 Rheumatic disease 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
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 208000024780 Urticaria Diseases 0.000 description 2
- JNGIBXKJBVBIGJ-UHFFFAOYSA-N [2,6-bis(methoxymethoxy)phenyl]methanamine Chemical compound COCOC1=CC=CC(OCOC)=C1CN JNGIBXKJBVBIGJ-UHFFFAOYSA-N 0.000 description 2
- IQLJYRVOZQERBH-UHFFFAOYSA-N [2,6-di(propan-2-yloxy)phenyl]methanamine Chemical compound CC(C)OC1=CC=CC(OC(C)C)=C1CN IQLJYRVOZQERBH-UHFFFAOYSA-N 0.000 description 2
- XHGOIBDHJAIWIC-UHFFFAOYSA-N [2-(acetamidomethyl)-1,3-thiazol-4-yl]methyl-triphenylphosphanium;chloride Chemical compound [Cl-].S1C(CNC(=O)C)=NC(C[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 XHGOIBDHJAIWIC-UHFFFAOYSA-N 0.000 description 2
- HPFCLDHQJUNWQD-UHFFFAOYSA-N [4-(carboxymethyl)phenyl]methyl-triphenylphosphanium;bromide Chemical compound [Br-].C1=CC(CC(=O)O)=CC=C1C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 HPFCLDHQJUNWQD-UHFFFAOYSA-N 0.000 description 2
- AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- GRMQGPVERJGWPR-UHFFFAOYSA-N ethyl 3-[2-[3-(2-acetamido-1,3-thiazol-4-yl)propanoyl]hydrazinyl]-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)NNC(=O)CCC1=CSC(NC(C)=O)=N1 GRMQGPVERJGWPR-UHFFFAOYSA-N 0.000 description 2
- DVZXWRRQCWDVOS-UHFFFAOYSA-N ethyl 3-[4-(2-bromoacetyl)phenyl]propanoate Chemical compound CCOC(=O)CCC1=CC=C(C(=O)CBr)C=C1 DVZXWRRQCWDVOS-UHFFFAOYSA-N 0.000 description 2
- 201000005884 exanthem Diseases 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- LEUJVEZIEALICS-UHFFFAOYSA-N hydrogen sulfate;1h-imidazol-2-ylazanium Chemical compound OS(O)(=O)=O.NC1=NC=CN1 LEUJVEZIEALICS-UHFFFAOYSA-N 0.000 description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- KBPHJBAIARWVSC-RGZFRNHPSA-N lutein Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\[C@H]1C(C)=C[C@H](O)CC1(C)C KBPHJBAIARWVSC-RGZFRNHPSA-N 0.000 description 2
- 229960005375 lutein Drugs 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
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- XEPLVJGUCPMHCE-UHFFFAOYSA-N methyl 2-(5-formylthiophen-2-yl)acetate Chemical compound COC(=O)CC1=CC=C(C=O)S1 XEPLVJGUCPMHCE-UHFFFAOYSA-N 0.000 description 2
- RYNMUJSOBDPDAB-UHFFFAOYSA-N methyl 2-[4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1CCC1=CSC(NC(C)=O)=N1 RYNMUJSOBDPDAB-UHFFFAOYSA-N 0.000 description 2
- NHRHDJPOTFEPLV-SNAWJCMRSA-N methyl 2-[5-[(e)-2-[2-(dimethylcarbamoyl)-1,3-thiazol-4-yl]ethenyl]thiophen-2-yl]acetate Chemical compound S1C(CC(=O)OC)=CC=C1\C=C\C1=CSC(C(=O)N(C)C)=N1 NHRHDJPOTFEPLV-SNAWJCMRSA-N 0.000 description 2
- MSWXDUDLFLNZNM-UHFFFAOYSA-N methyl 4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCC1=CSC(NC(C)=O)=N1 MSWXDUDLFLNZNM-UHFFFAOYSA-N 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 210000002200 mouth mucosa Anatomy 0.000 description 2
- WXPLRSVMGRAIGW-UHFFFAOYSA-N n-(1,3-thiazol-2-yl)acetamide Chemical compound CC(=O)NC1=NC=CS1 WXPLRSVMGRAIGW-UHFFFAOYSA-N 0.000 description 2
- CBTZUXIQRMFBMP-UHFFFAOYSA-N n-[2-[4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]phenyl]ethylcarbamothioyl]benzamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CCNC(=S)NC(=O)C=3C=CC=CC=3)=CC=2)=C1 CBTZUXIQRMFBMP-UHFFFAOYSA-N 0.000 description 2
- XRXOHGHYAPSJAV-UHFFFAOYSA-N n-[4-(hydroxymethyl)-1,3-thiazol-2-yl]acetamide Chemical compound CC(=O)NC1=NC(CO)=CS1 XRXOHGHYAPSJAV-UHFFFAOYSA-N 0.000 description 2
- DICVPQZUIVFABG-NSCUHMNNSA-N n-[4-[(e)-2-(5-nitrothiophen-2-yl)ethenyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(\C=C\C=2SC(=CC=2)[N+]([O-])=O)=C1 DICVPQZUIVFABG-NSCUHMNNSA-N 0.000 description 2
- YVYPEAZIGLTXSP-DJWKRKHSSA-N n-[4-[(z)-2-(4-nitrophenyl)ethenyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(\C=C/C=2C=CC(=CC=2)[N+]([O-])=O)=C1 YVYPEAZIGLTXSP-DJWKRKHSSA-N 0.000 description 2
- RUJGVKORXDOSBT-UHFFFAOYSA-N n-[4-[2-(4-aminophenyl)ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(N)=CC=2)=C1 RUJGVKORXDOSBT-UHFFFAOYSA-N 0.000 description 2
- PTQXBLWVKJGRAK-UHFFFAOYSA-N n-[4-[2-[4-(2-bromoethyl)phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CCBr)=CC=2)=C1 PTQXBLWVKJGRAK-UHFFFAOYSA-N 0.000 description 2
- NLHQFYLENGHOSF-UHFFFAOYSA-N n-[4-[2-[4-(2-piperazin-1-ylethyl)phenyl]ethyl]-1,3-thiazol-2-yl]acetamide;dihydrochloride Chemical compound Cl.Cl.S1C(NC(=O)C)=NC(CCC=2C=CC(CCN3CCNCC3)=CC=2)=C1 NLHQFYLENGHOSF-UHFFFAOYSA-N 0.000 description 2
- CHMIKGHIHMAZEQ-UHFFFAOYSA-N n-[4-[2-[4-(3-amino-2-oxopropyl)phenyl]ethyl]-1,3-thiazol-2-yl]acetamide;hydrochloride Chemical compound Cl.S1C(NC(=O)C)=NC(CCC=2C=CC(CC(=O)CN)=CC=2)=C1 CHMIKGHIHMAZEQ-UHFFFAOYSA-N 0.000 description 2
- SPZUGPZSNJIYIT-UHFFFAOYSA-N n-[4-[2-[4-(3-azido-2-oxopropyl)phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CC(=O)CN=[N+]=[N-])=CC=2)=C1 SPZUGPZSNJIYIT-UHFFFAOYSA-N 0.000 description 2
- CJMRHKOFFJUWAV-UHFFFAOYSA-N n-[4-[2-[4-(3-bromo-2-oxopropyl)phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CC(=O)CBr)=CC=2)=C1 CJMRHKOFFJUWAV-UHFFFAOYSA-N 0.000 description 2
- XWXQMLCMLQKVOP-UHFFFAOYSA-N n-[4-[2-[4-(bromomethyl)phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CBr)=CC=2)=C1 XWXQMLCMLQKVOP-UHFFFAOYSA-N 0.000 description 2
- APZPUVWJWAOYRV-UHFFFAOYSA-N n-[4-[2-[4-[(2-amino-1,3-thiazol-4-yl)methyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CC=3N=C(N)SC=3)=CC=2)=C1 APZPUVWJWAOYRV-UHFFFAOYSA-N 0.000 description 2
- YNCRDJRSIWTTDY-UHFFFAOYSA-N n-[4-[2-[4-[(3-aminopyrrolidin-1-yl)methyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide;dihydrochloride Chemical compound Cl.Cl.S1C(NC(=O)C)=NC(CCC=2C=CC(CN3CC(N)CC3)=CC=2)=C1 YNCRDJRSIWTTDY-UHFFFAOYSA-N 0.000 description 2
- WNGRMMAOUVLADK-UHFFFAOYSA-N n-[4-[2-[4-[(pyrrolidin-3-ylamino)methyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide;dihydrochloride Chemical compound Cl.Cl.S1C(NC(=O)C)=NC(CCC=2C=CC(CNC3CNCC3)=CC=2)=C1 WNGRMMAOUVLADK-UHFFFAOYSA-N 0.000 description 2
- GCPNVGOVCAJUSU-UHFFFAOYSA-N n-[4-[2-[4-[2-(1,3-dioxoisoindol-2-yl)ethyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CCN3C(C4=CC=CC=C4C3=O)=O)=CC=2)=C1 GCPNVGOVCAJUSU-UHFFFAOYSA-N 0.000 description 2
- CJFYWWLRQNMWRK-UHFFFAOYSA-N n-[4-[2-[4-[2-(1,3-thiazol-2-ylamino)ethyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CCNC=3SC=CN=3)=CC=2)=C1 CJFYWWLRQNMWRK-UHFFFAOYSA-N 0.000 description 2
- NDUINFXFTNPVRL-UHFFFAOYSA-N n-[4-[2-[4-[2-(2-aminoimidazol-1-yl)-2-oxoethyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CC(=O)N3C(=NC=C3)N)=CC=2)=C1 NDUINFXFTNPVRL-UHFFFAOYSA-N 0.000 description 2
- GLXKTEKDZOTYKQ-UHFFFAOYSA-N n-[4-[2-[4-[2-(2-aminoimidazol-1-yl)ethyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CCN3C(=NC=C3)N)=CC=2)=C1 GLXKTEKDZOTYKQ-UHFFFAOYSA-N 0.000 description 2
- VKEHZLMZNUESCG-UHFFFAOYSA-N n-[4-[2-[4-[2-(3-aminopyrrolidin-1-yl)ethyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide;dihydrochloride Chemical compound Cl.Cl.S1C(NC(=O)C)=NC(CCC=2C=CC(CCN3CC(N)CC3)=CC=2)=C1 VKEHZLMZNUESCG-UHFFFAOYSA-N 0.000 description 2
- AIBPZYJJLGZZAB-UHFFFAOYSA-N n-[4-[2-[4-[2-(methanesulfonamido)ethyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CCNS(C)(=O)=O)=CC=2)=C1 AIBPZYJJLGZZAB-UHFFFAOYSA-N 0.000 description 2
- BCYCYOKYFUWPIE-UHFFFAOYSA-N n-[4-[2-[5-(diaminomethylideneamino)thiophen-2-yl]ethyl]-1,3-thiazol-2-yl]acetamide;hydrochloride Chemical compound Cl.S1C(NC(=O)C)=NC(CCC=2SC(NC(N)=N)=CC=2)=C1 BCYCYOKYFUWPIE-UHFFFAOYSA-N 0.000 description 2
- ZGRSVBKISYNGHR-UHFFFAOYSA-N n-[4-[2-[5-[2-(3-aminopyrrolidin-1-yl)-2-oxoethyl]thiophen-2-yl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CC(=O)N3CC(N)CC3)=CC=2)=C1 ZGRSVBKISYNGHR-UHFFFAOYSA-N 0.000 description 2
- KGTULMSYLNFBGX-UHFFFAOYSA-N n-[4-[4-(4-amino-3-oxobutyl)phenyl]-1,3-thiazol-2-yl]acetamide;hydrochloride Chemical compound Cl.S1C(NC(=O)C)=NC(C=2C=CC(CCC(=O)CN)=CC=2)=C1 KGTULMSYLNFBGX-UHFFFAOYSA-N 0.000 description 2
- HOGRWHINLHGGFG-UHFFFAOYSA-N n-[4-[4-[2-(2-amino-1h-imidazol-5-yl)ethyl]phenyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(C=2C=CC(CCC=3NC(N)=NC=3)=CC=2)=C1 HOGRWHINLHGGFG-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Chemical group 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000000552 rheumatic effect Effects 0.000 description 2
- 150000003349 semicarbazides Chemical class 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- QFNFDHNZVTWZED-UHFFFAOYSA-N tert-butyl n-[[(2-methylpropan-2-yl)oxycarbonylamino]-pyrazol-1-ylmethylidene]carbamate Chemical compound CC(C)(C)OC(=O)NC(=NC(=O)OC(C)(C)C)N1C=CC=N1 QFNFDHNZVTWZED-UHFFFAOYSA-N 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
- FJHBOVDFOQMZRV-XQIHNALSSA-N xanthophyll Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C=C(C)C(O)CC2(C)C FJHBOVDFOQMZRV-XQIHNALSSA-N 0.000 description 2
- JVDHLRACASTEFG-UHFFFAOYSA-N (2,6-dibutoxyphenyl)methanamine Chemical compound CCCCOC1=CC=CC(OCCCC)=C1CN JVDHLRACASTEFG-UHFFFAOYSA-N 0.000 description 1
- WRVDRSYYPFSEQZ-UHFFFAOYSA-N (2,6-dipropylphenyl)methanamine Chemical compound CCCC1=CC=CC(CCC)=C1CN WRVDRSYYPFSEQZ-UHFFFAOYSA-N 0.000 description 1
- MOYSTFNJSKEJDG-UHFFFAOYSA-M (3,4-dinitrophenyl)methyl-triphenylphosphanium;bromide Chemical compound [Br-].C1=C([N+]([O-])=O)C([N+](=O)[O-])=CC=C1C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 MOYSTFNJSKEJDG-UHFFFAOYSA-M 0.000 description 1
- LCMPIWIWBGHBOY-UHFFFAOYSA-N (3-chloro-2-oxopropyl) acetate Chemical compound CC(=O)OCC(=O)CCl LCMPIWIWBGHBOY-UHFFFAOYSA-N 0.000 description 1
- JKQXZKUSFCKOGQ-JLGXGRJMSA-N (3R,3'R)-beta,beta-carotene-3,3'-diol Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-JLGXGRJMSA-N 0.000 description 1
- WUWDGVKUXDZLNU-UHFFFAOYSA-M (4-methoxycarbonylphenyl)methyl-triphenylphosphanium;bromide Chemical compound [Br-].C1=CC(C(=O)OC)=CC=C1C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 WUWDGVKUXDZLNU-UHFFFAOYSA-M 0.000 description 1
- SGWNRXDQJJHFML-UHFFFAOYSA-N (5-formyl-1-methylpyrrol-2-yl)methyl acetate Chemical compound CC(=O)OCC1=CC=C(C=O)N1C SGWNRXDQJJHFML-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UUZJJNBYJDFQHL-UHFFFAOYSA-N 1,2,3-triazolidine Chemical compound C1CNNN1 UUZJJNBYJDFQHL-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-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
- QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- JJWCTKUQWXYIIU-UHFFFAOYSA-N 2-Benzimidazolylguanidine Chemical compound C1=CC=C2NC(N=C(N)N)=NC2=C1 JJWCTKUQWXYIIU-UHFFFAOYSA-N 0.000 description 1
- WCOCCXZFEJGHTC-UHFFFAOYSA-N 2-[4-(bromomethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=C(CBr)C=C1 WCOCCXZFEJGHTC-UHFFFAOYSA-N 0.000 description 1
- VOUIKXJMPKEJLI-VOTSOKGWSA-N 2-[4-[(e)-2-(2-acetamido-1,3-thiazol-4-yl)ethenyl]phenyl]acetic acid Chemical compound S1C(NC(=O)C)=NC(\C=C\C=2C=CC(CC(O)=O)=CC=2)=C1 VOUIKXJMPKEJLI-VOTSOKGWSA-N 0.000 description 1
- LILXDMFJXYAKMK-UHFFFAOYSA-N 2-bromo-1,1-diethoxyethane Chemical compound CCOC(CBr)OCC LILXDMFJXYAKMK-UHFFFAOYSA-N 0.000 description 1
- SYZRZLUNWVNNNV-UHFFFAOYSA-N 2-bromoacetyl chloride Chemical compound ClC(=O)CBr SYZRZLUNWVNNNV-UHFFFAOYSA-N 0.000 description 1
- NAFGHMDHUNHHPE-UHFFFAOYSA-N 3-[[2-[5-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]thiophen-2-yl]acetyl]amino]pyrrolidine-1-carboxylic acid Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CC(=O)NC3CN(CC3)C(O)=O)=CC=2)=C1 NAFGHMDHUNHHPE-UHFFFAOYSA-N 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- WJEZEUJKYFXNKJ-UHFFFAOYSA-N 4-(2-bromoethyl)benzaldehyde Chemical compound BrCCC1=CC=C(C=O)C=C1 WJEZEUJKYFXNKJ-UHFFFAOYSA-N 0.000 description 1
- MWWKFIPFFAXPGN-UHFFFAOYSA-N 4-(4-propylphenyl)-1,3-thiazol-2-amine Chemical compound C1=CC(CCC)=CC=C1C1=CSC(N)=N1 MWWKFIPFFAXPGN-UHFFFAOYSA-N 0.000 description 1
- QKWSLYINUYKIRF-UHFFFAOYSA-N 4-(chloromethyl)-1,3-thiazole Chemical compound ClCC1=CSC=N1 QKWSLYINUYKIRF-UHFFFAOYSA-N 0.000 description 1
- OXJRPJYPEBCFMC-UHFFFAOYSA-N 4-(chloromethyl)-1,3-thiazole-2-carboxylic acid Chemical compound OC(=O)C1=NC(CCl)=CS1 OXJRPJYPEBCFMC-UHFFFAOYSA-N 0.000 description 1
- ZHRKMVRAJVQNSO-UHFFFAOYSA-N 4-(chloromethyl)-n,n-dimethyl-1,3-thiazole-2-carboxamide Chemical compound CN(C)C(=O)C1=NC(CCl)=CS1 ZHRKMVRAJVQNSO-UHFFFAOYSA-N 0.000 description 1
- VZNCWKBEDVVOSL-UHFFFAOYSA-N 4-(chloromethyl)-n-methyl-1,3-thiazole-2-carboxamide Chemical compound CNC(=O)C1=NC(CCl)=CS1 VZNCWKBEDVVOSL-UHFFFAOYSA-N 0.000 description 1
- HBRMYBBOICKQDX-UHFFFAOYSA-N 4-[[2-[5-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]thiophen-2-yl]acetyl]amino]piperidine-1-carboxylic acid Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CC(=O)NC3CCN(CC3)C(O)=O)=CC=2)=C1 HBRMYBBOICKQDX-UHFFFAOYSA-N 0.000 description 1
- VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 description 1
- CHTSWZNXEKOLPM-UHFFFAOYSA-N 5-nitrothiophene-2-carbaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)S1 CHTSWZNXEKOLPM-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 102000016893 Amine Oxidase (Copper-Containing) Human genes 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- NXMLZFZYNLCEDF-UHFFFAOYSA-N C(C)(=O)OC=1SC(=CC1C)CCC=1N=C(SC1)C(=O)N(C)C Chemical compound C(C)(=O)OC=1SC(=CC1C)CCC=1N=C(SC1)C(=O)N(C)C NXMLZFZYNLCEDF-UHFFFAOYSA-N 0.000 description 1
- JHCDBZJCYMSVFJ-UHFFFAOYSA-N C(N)(OC(NCCC=1SC(=CC1)CCC=1N=C(SC1)NC(C)=O)OC(N)=O)=O Chemical compound C(N)(OC(NCCC=1SC(=CC1)CCC=1N=C(SC1)NC(C)=O)OC(N)=O)=O JHCDBZJCYMSVFJ-UHFFFAOYSA-N 0.000 description 1
- IKSMIGNEYNZPFO-UHFFFAOYSA-N C(N)(OC(NCCCC=1SC(=CC1)CCC=1N=C(SC1)NC(C)=O)OC(N)=O)=O Chemical compound C(N)(OC(NCCCC=1SC(=CC1)CCC=1N=C(SC1)NC(C)=O)OC(N)=O)=O IKSMIGNEYNZPFO-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 208000025985 Central nervous system inflammatory disease Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- JAGZUIGGHGTFHO-UHFFFAOYSA-N Ethyl 3-phenylpropanoate Chemical compound CCOC(=O)CCC1=CC=CC=C1 JAGZUIGGHGTFHO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010064147 Gastrointestinal inflammation Diseases 0.000 description 1
- 208000017189 Gastrointestinal inflammatory disease Diseases 0.000 description 1
- 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 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 208000010159 IgA glomerulonephritis Diseases 0.000 description 1
- 206010021263 IgA nephropathy Diseases 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
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- GUPWHNYVUSEODT-UHFFFAOYSA-N NC(=N)NCCC1=CC=C(S1)CCC=1N=CSC1 Chemical compound NC(=N)NCCC1=CC=C(S1)CCC=1N=CSC1 GUPWHNYVUSEODT-UHFFFAOYSA-N 0.000 description 1
- JBRSGDCCUGHLLT-UHFFFAOYSA-N NC(=N)NCCCC1=CC=C(S1)CCC=1N=CSC1 Chemical compound NC(=N)NCCCC1=CC=C(S1)CCC=1N=CSC1 JBRSGDCCUGHLLT-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- WLHBRQYVZLNQFE-UHFFFAOYSA-N O[S+]1C2=CC=CC=C2N=C1 Chemical compound O[S+]1C2=CC=CC=C2N=C1 WLHBRQYVZLNQFE-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 206010036030 Polyarthritis Diseases 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101100438134 Rattus norvegicus Cabs1 gene Proteins 0.000 description 1
- 241001303601 Rosacea Species 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282887 Suidae Species 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
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 101150012983 VAP-1 gene Proteins 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- JKQXZKUSFCKOGQ-LQFQNGICSA-N Z-zeaxanthin Natural products C([C@H](O)CC=1C)C(C)(C)C=1C=CC(C)=CC=CC(C)=CC=CC=C(C)C=CC=C(C)C=CC1=C(C)C[C@@H](O)CC1(C)C JKQXZKUSFCKOGQ-LQFQNGICSA-N 0.000 description 1
- QOPRSMDTRDMBNK-RNUUUQFGSA-N Zeaxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCC(O)C1(C)C)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C QOPRSMDTRDMBNK-RNUUUQFGSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- SHSMPHBXSMDTRH-UHFFFAOYSA-N [2,6-bis(methoxymethyl)phenyl]methanamine Chemical compound COCC1=CC=CC(COC)=C1CN SHSMPHBXSMDTRH-UHFFFAOYSA-N 0.000 description 1
- VWKXVJUGKHXXFX-UHFFFAOYSA-M [2-(dimethylcarbamoyl)-1,3-thiazol-4-yl]methyl-triphenylphosphanium;chloride Chemical compound [Cl-].S1C(C(=O)N(C)C)=NC(C[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 VWKXVJUGKHXXFX-UHFFFAOYSA-M 0.000 description 1
- DQOUHLJQKVKWGN-UHFFFAOYSA-N [2-(methylcarbamoyl)-1,3-thiazol-4-yl]methyl-triphenylphosphanium;chloride Chemical compound [Cl-].S1C(C(=O)NC)=NC(C[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 DQOUHLJQKVKWGN-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000001118 alkylidene group Chemical group 0.000 description 1
- JKQXZKUSFCKOGQ-LOFNIBRQSA-N all-trans-Zeaxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C JKQXZKUSFCKOGQ-LOFNIBRQSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 208000002399 aphthous stomatitis Diseases 0.000 description 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-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
- CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 210000004155 blood-retinal barrier Anatomy 0.000 description 1
- 230000004378 blood-retinal barrier Effects 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 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
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- QNEFNFIKZWUAEQ-UHFFFAOYSA-N carbonic acid;potassium Chemical compound [K].OC(O)=O QNEFNFIKZWUAEQ-UHFFFAOYSA-N 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 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 1
- XXTZHYXQVWRADW-UHFFFAOYSA-N diazomethanone Chemical class [N]N=C=O XXTZHYXQVWRADW-UHFFFAOYSA-N 0.000 description 1
- GRTGGSXWHGKRSB-UHFFFAOYSA-N dichloromethyl methyl ether Chemical compound COC(Cl)Cl GRTGGSXWHGKRSB-UHFFFAOYSA-N 0.000 description 1
- QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical compound NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- FPULFENIJDPZBX-UHFFFAOYSA-N ethyl 2-isocyanoacetate Chemical compound CCOC(=O)C[N+]#[C-] FPULFENIJDPZBX-UHFFFAOYSA-N 0.000 description 1
- XXFFFMAOWGKEAA-UHFFFAOYSA-N ethyl 3-[4-(2-amino-1,3-thiazol-4-yl)phenyl]propanoate Chemical compound C1=CC(CCC(=O)OCC)=CC=C1C1=CSC(N)=N1 XXFFFMAOWGKEAA-UHFFFAOYSA-N 0.000 description 1
- HCPOCMMGKBZWSJ-UHFFFAOYSA-N ethyl 3-hydrazinyl-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)NN HCPOCMMGKBZWSJ-UHFFFAOYSA-N 0.000 description 1
- JSYOQGQNLKDSGQ-UHFFFAOYSA-N ethyl 4-(chloromethyl)-1,3-thiazole-2-carboxylate Chemical compound CCOC(=O)C1=NC(CCl)=CS1 JSYOQGQNLKDSGQ-UHFFFAOYSA-N 0.000 description 1
- FOGLNGQYERMUQC-UHFFFAOYSA-N ethyl 5-[2-[4-(2-acetamido-1,3-thiazol-4-yl)phenyl]ethyl]-1,3-oxazole-4-carboxylate Chemical compound N1=COC(CCC=2C=CC(=CC=2)C=2N=C(NC(C)=O)SC=2)=C1C(=O)OCC FOGLNGQYERMUQC-UHFFFAOYSA-N 0.000 description 1
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 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
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960000789 guanidine hydrochloride Drugs 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 125000000268 heptanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])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
- 125000005935 hexyloxycarbonyl group Chemical group 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 230000002427 irreversible effect Effects 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
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
- NIZHERJWXFHGGU-UHFFFAOYSA-N isocyanato(trimethyl)silane Chemical compound C[Si](C)(C)N=C=O NIZHERJWXFHGGU-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000013532 laser treatment Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 235000012680 lutein Nutrition 0.000 description 1
- 239000001656 lutein Substances 0.000 description 1
- ORAKUVXRZWMARG-WZLJTJAWSA-N lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C ORAKUVXRZWMARG-WZLJTJAWSA-N 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- DPPTUKDXXGYNGD-ONEGZZNKSA-N methyl (E)-3-(2-acetamido-1,3-thiazol-4-yl)prop-2-enoate Chemical compound COC(=O)\C=C\C1=CSC(NC(C)=O)=N1 DPPTUKDXXGYNGD-ONEGZZNKSA-N 0.000 description 1
- AYXWQIOKNMILQX-SNAWJCMRSA-N methyl (e)-3-(5-formylthiophen-2-yl)prop-2-enoate Chemical compound COC(=O)\C=C\C1=CC=C(C=O)S1 AYXWQIOKNMILQX-SNAWJCMRSA-N 0.000 description 1
- XUNOBCAUDRRJCP-DYWGDJMRSA-N methyl (e)-3-[5-[(e)-2-(2-acetamido-1,3-thiazol-4-yl)ethenyl]thiophen-2-yl]prop-2-enoate Chemical compound S1C(/C=C/C(=O)OC)=CC=C1\C=C\C1=CSC(NC(C)=O)=N1 XUNOBCAUDRRJCP-DYWGDJMRSA-N 0.000 description 1
- CGYVDYLHQYNGFC-UHFFFAOYSA-N methyl 2-(1-methylpyrrol-2-yl)acetate Chemical compound COC(=O)CC1=CC=CN1C CGYVDYLHQYNGFC-UHFFFAOYSA-N 0.000 description 1
- NTNUDYROPUKXNA-UHFFFAOYSA-N methyl 2-(triphenyl-$l^{5}-phosphanylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC)C1=CC=CC=C1 NTNUDYROPUKXNA-UHFFFAOYSA-N 0.000 description 1
- ARHHUSSVAXYZAE-ONEGZZNKSA-N methyl 2-[5-[(e)-2-[2-(acetamidomethyl)-1,3-thiazol-4-yl]ethenyl]thiophen-2-yl]acetate Chemical compound S1C(CC(=O)OC)=CC=C1\C=C\C1=CSC(CNC(C)=O)=N1 ARHHUSSVAXYZAE-ONEGZZNKSA-N 0.000 description 1
- ARHHUSSVAXYZAE-ARJAWSKDSA-N methyl 2-[5-[(z)-2-[2-(acetamidomethyl)-1,3-thiazol-4-yl]ethenyl]thiophen-2-yl]acetate Chemical compound S1C(CC(=O)OC)=CC=C1\C=C/C1=CSC(CNC(C)=O)=N1 ARHHUSSVAXYZAE-ARJAWSKDSA-N 0.000 description 1
- KNKIXYMOHMYZJR-UHFFFAOYSA-N methyl 2-thiophen-2-ylacetate Chemical compound COC(=O)CC1=CC=CS1 KNKIXYMOHMYZJR-UHFFFAOYSA-N 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 239000011785 micronutrient Substances 0.000 description 1
- 235000013369 micronutrients Nutrition 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- BOSZVWXMCNBHPJ-UHFFFAOYSA-N n-(2-amino-2-sulfanylideneethyl)acetamide Chemical compound CC(=O)NCC(S)=N BOSZVWXMCNBHPJ-UHFFFAOYSA-N 0.000 description 1
- NBUKMHXINQOFDI-UHFFFAOYSA-N n-[4-(chloromethyl)-1,3-thiazol-2-yl]acetamide Chemical compound CC(=O)NC1=NC(CCl)=CS1 NBUKMHXINQOFDI-UHFFFAOYSA-N 0.000 description 1
- AXYITKGCXWAYOP-DUXPYHPUSA-N n-[4-[(e)-2-(3,4-dinitrophenyl)ethenyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(\C=C\C=2C=C(C(=CC=2)[N+]([O-])=O)[N+]([O-])=O)=C1 AXYITKGCXWAYOP-DUXPYHPUSA-N 0.000 description 1
- ZGGANLACNJIJRQ-NSCUHMNNSA-N n-[4-[(e)-2-(5-aminothiophen-2-yl)ethenyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(\C=C\C=2SC(N)=CC=2)=C1 ZGGANLACNJIJRQ-NSCUHMNNSA-N 0.000 description 1
- KYOSASCFIRFBQS-NSCUHMNNSA-N n-[4-[(e)-2-(5-formylthiophen-2-yl)ethenyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(\C=C\C=2SC(C=O)=CC=2)=C1 KYOSASCFIRFBQS-NSCUHMNNSA-N 0.000 description 1
- LLHXRSQFZYVMSN-ZHACJKMWSA-N n-[4-[(e)-2-[4-[2-(1,3-dioxoisoindol-2-yl)ethyl]phenyl]ethenyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(\C=C\C=2C=CC(CCN3C(C4=CC=CC=C4C3=O)=O)=CC=2)=C1 LLHXRSQFZYVMSN-ZHACJKMWSA-N 0.000 description 1
- AXYITKGCXWAYOP-RQOWECAXSA-N n-[4-[(z)-2-(3,4-dinitrophenyl)ethenyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(\C=C/C=2C=C(C(=CC=2)[N+]([O-])=O)[N+]([O-])=O)=C1 AXYITKGCXWAYOP-RQOWECAXSA-N 0.000 description 1
- VRAUKJDMIXOYDR-UHFFFAOYSA-N n-[4-[2-(3,4-diaminophenyl)ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=C(N)C(N)=CC=2)=C1 VRAUKJDMIXOYDR-UHFFFAOYSA-N 0.000 description 1
- KEVKADBDQBRUCP-UHFFFAOYSA-N n-[4-[2-[2-(diaminomethylideneamino)-3h-benzimidazol-5-yl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=C3NC(NC(N)=N)=NC3=CC=2)=C1 KEVKADBDQBRUCP-UHFFFAOYSA-N 0.000 description 1
- LMDXCMJWFMSUAI-UHFFFAOYSA-N n-[4-[2-[4-(diaminomethylideneamino)phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(NC(N)=N)=CC=2)=C1 LMDXCMJWFMSUAI-UHFFFAOYSA-N 0.000 description 1
- XGMNNTAXCHMDMV-UHFFFAOYSA-N n-[4-[2-[4-(hydroxymethyl)phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CO)=CC=2)=C1 XGMNNTAXCHMDMV-UHFFFAOYSA-N 0.000 description 1
- ZFVMCDFKFYUOKU-UHFFFAOYSA-N n-[4-[2-[4-(piperazin-1-ylmethyl)phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CN3CCNCC3)=CC=2)=C1 ZFVMCDFKFYUOKU-UHFFFAOYSA-N 0.000 description 1
- VTYVTTDVOUKLLT-UHFFFAOYSA-N n-[4-[2-[4-[2-(carbamoylamino)ethyl]phenyl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CCNC(N)=O)=CC=2)=C1 VTYVTTDVOUKLLT-UHFFFAOYSA-N 0.000 description 1
- OLYHPXQMHGHVRW-UHFFFAOYSA-N n-[4-[2-[5-(2-oxo-2-piperazin-1-ylethyl)thiophen-2-yl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CC(=O)N3CCNCC3)=CC=2)=C1 OLYHPXQMHGHVRW-UHFFFAOYSA-N 0.000 description 1
- REWMMQHKKRBBGR-UHFFFAOYSA-N n-[4-[2-[5-(3-aminopropyl)thiophen-2-yl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CCCN)=CC=2)=C1 REWMMQHKKRBBGR-UHFFFAOYSA-N 0.000 description 1
- RONSEEFVHOVKMI-UHFFFAOYSA-N n-[4-[2-[5-(3-hydroxypropyl)thiophen-2-yl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CCCO)=CC=2)=C1 RONSEEFVHOVKMI-UHFFFAOYSA-N 0.000 description 1
- SESXMZAWFXWTQO-UHFFFAOYSA-N n-[4-[2-[5-(aminomethyl)thiophen-2-yl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CN)=CC=2)=C1 SESXMZAWFXWTQO-UHFFFAOYSA-N 0.000 description 1
- ZVWLISVVWKTZRF-UHFFFAOYSA-N n-[4-[2-[5-(hydroxymethyl)thiophen-2-yl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CO)=CC=2)=C1 ZVWLISVVWKTZRF-UHFFFAOYSA-N 0.000 description 1
- ZWTRSEPVRKESHI-UHFFFAOYSA-N n-[4-[2-[5-[(1,3-dioxoisoindol-2-yl)methyl]thiophen-2-yl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CN3C(C4=CC=CC=C4C3=O)=O)=CC=2)=C1 ZWTRSEPVRKESHI-UHFFFAOYSA-N 0.000 description 1
- XFJYGXGKTOJPHP-UHFFFAOYSA-N n-[4-[2-[5-[2-(diaminomethylideneamino)ethyl]thiophen-2-yl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CCNC(N)=N)=CC=2)=C1 XFJYGXGKTOJPHP-UHFFFAOYSA-N 0.000 description 1
- NMQGWVDOKHFVJW-UHFFFAOYSA-N n-[4-[2-[5-[3-(1,3-dioxoisoindol-2-yl)propyl]thiophen-2-yl]ethyl]-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CCCN3C(C4=CC=CC=C4C3=O)=O)=CC=2)=C1 NMQGWVDOKHFVJW-UHFFFAOYSA-N 0.000 description 1
- CRPDUTQJSUZDJJ-UHFFFAOYSA-N n-[4-[2-[5-[3-(diaminomethylideneamino)propyl]thiophen-2-yl]ethyl]-1,3-thiazol-2-yl]acetamide;hydrochloride Chemical compound Cl.S1C(NC(=O)C)=NC(CCC=2SC(CCCNC(N)=N)=CC=2)=C1 CRPDUTQJSUZDJJ-UHFFFAOYSA-N 0.000 description 1
- IZELWSRWUAZIGZ-UHFFFAOYSA-N n-butoxy-1-phenylmethanamine Chemical compound CCCCONCC1=CC=CC=C1 IZELWSRWUAZIGZ-UHFFFAOYSA-N 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical class CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 208000020470 nervous system symptom Diseases 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
- 238000001050 pharmacotherapy Methods 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
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- 230000000649 photocoagulation Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 208000030428 polyarticular arthritis Diseases 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- OSFBJERFMQCEQY-UHFFFAOYSA-N propylidene Chemical group [CH]CC OSFBJERFMQCEQY-UHFFFAOYSA-N 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 201000004700 rosacea Diseases 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
- 125000005930 sec-butyloxycarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 1
- CJPBYGBWNWZARG-UHFFFAOYSA-N tert-butyl 4-[2-[4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]phenyl]ethyl]piperazine-1-carboxylate Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CCN3CCN(CC3)C(=O)OC(C)(C)C)=CC=2)=C1 CJPBYGBWNWZARG-UHFFFAOYSA-N 0.000 description 1
- IQUKCLPQPXJWPE-UHFFFAOYSA-N tert-butyl 4-[[4-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]phenyl]methyl]piperazine-1-carboxylate Chemical compound S1C(NC(=O)C)=NC(CCC=2C=CC(CN3CCN(CC3)C(=O)OC(C)(C)C)=CC=2)=C1 IQUKCLPQPXJWPE-UHFFFAOYSA-N 0.000 description 1
- NRZYYKACXDZFRF-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O.CC(C)(C)OC(N)=O NRZYYKACXDZFRF-UHFFFAOYSA-N 0.000 description 1
- OSQDXDIWTIIHML-UHFFFAOYSA-N tert-butyl n-[2-[5-[2-(2-acetamido-1,3-thiazol-4-yl)ethyl]thiophen-2-yl]ethyl]carbamate Chemical compound S1C(NC(=O)C)=NC(CCC=2SC(CCNC(=O)OC(C)(C)C)=CC=2)=C1 OSQDXDIWTIIHML-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005934 tert-pentyloxycarbonyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- OTMRXENQDSQACG-UHFFFAOYSA-N thiophene-2,5-dicarbaldehyde Chemical compound O=CC1=CC=C(C=O)S1 OTMRXENQDSQACG-UHFFFAOYSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000011200 topical administration Methods 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
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 230000004304 visual acuity Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000008210 xanthophylls Nutrition 0.000 description 1
- 235000010930 zeaxanthin Nutrition 0.000 description 1
- 229940043269 zeaxanthin Drugs 0.000 description 1
- 239000001775 zeaxanthin Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2004905183A AU2004905183A0 (en) | 2004-09-09 | Thiazole Derivatives Having VAP-1 Inhibitory Activity | |
| PCT/JP2005/016984 WO2006028269A2 (en) | 2004-09-09 | 2005-09-08 | Thiazole derivatives having vap-1 ihibitory activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008512346A JP2008512346A (ja) | 2008-04-24 |
| JP2008512346A5 true JP2008512346A5 (enExample) | 2008-09-18 |
Family
ID=35395819
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007511147A Abandoned JP2008512346A (ja) | 2004-09-09 | 2005-09-08 | Ｖａｐ−１阻害活性を有するチアゾール誘導体 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20080015202A1 (enExample) |
| EP (1) | EP1791835A2 (enExample) |
| JP (1) | JP2008512346A (enExample) |
| CA (1) | CA2579889A1 (enExample) |
| WO (1) | WO2006028269A2 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2008011791A (es) * | 2006-03-15 | 2008-09-25 | Wyeth Corp | Azaciclilaminas-n-sustituidas como antagonistas de histamina-3. |
| CA2691520A1 (en) | 2007-06-25 | 2008-12-31 | R-Tech Ueno, Ltd. | Composition for ophthalmic disease associated with hypoxia or ischemia |
| CN101903045B (zh) | 2007-10-19 | 2013-03-13 | 株式会社·R-技术上野 | 用于治疗白内障的药物组合物 |
| TWI437986B (zh) | 2008-01-31 | 2014-05-21 | R Tech Ueno Ltd | 噻唑衍生物及使用該衍生物作為ｖａｐ－１抑制劑之用途 |
| TWI490214B (zh) | 2008-05-30 | 2015-07-01 | 艾德克 上野股份有限公司 | 苯或噻吩衍生物及該等作為ｖａｐ－１抑制劑之用途 |
| UA112154C2 (uk) | 2009-09-08 | 2016-08-10 | Біоті Терапіс Корп. | Застосування повністю людського анти-vap-1-антитіла для лікування фіброзних станів |
| FI20115234A0 (fi) | 2011-03-08 | 2011-03-08 | Biotie Therapies Corp | Uusia pyridatsinoni- ja pyridoniyhdisteitä |
| US20160113893A1 (en) | 2013-06-12 | 2016-04-28 | Proximagen Limited | New therapeutic uses of enzyme inhibitors |
| HUE042625T2 (hu) | 2014-04-15 | 2019-07-29 | Pecsi Tudomanyegyetem | Szemikarbazid-szenzitiv amin-oxidáz gátlók fájdalomcsillapítóként való alkalmazásra traumás neuropátiában és neurogén gyulladásban |
| MX2016014143A (es) | 2014-04-30 | 2017-02-15 | Pfizer | Derivados de diheterociclo enlazado a cicloalquilo. |
| WO2015189534A1 (en) | 2014-06-12 | 2015-12-17 | Proximagen Limited | Vap-1 inhibitors for treating muscular dystrophy |
| GB201506660D0 (en) | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| GB201506658D0 (en) | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| GB201507048D0 (en) * | 2015-04-24 | 2015-06-10 | Proximagen Ltd | Treatment of pain |
| JP2018076236A (ja) | 2015-06-05 | 2018-05-17 | 株式会社アールテック・ウエノ | がんを処置するための医薬組成物 |
| JP2019502672A (ja) | 2015-12-07 | 2019-01-31 | ベネボレンタイ ケンブリッジ リミティド | 疼痛の治療のためのｖａｐ−１阻害剤 |
| EP3423436B1 (en) * | 2016-03-03 | 2020-09-16 | Boehringer Ingelheim International GmbH | Pyridinylmethyl carbamimidoylcarbamate derivatives and their use as aoc3 inhibitors |
| JP6695441B2 (ja) * | 2016-03-03 | 2020-05-20 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ４−シアノ−ベンジルカルバミミドイルカルバメート誘導体およびａｏｃ３阻害剤としてのそれらの使用 |
| FI3873600T3 (fi) | 2018-10-29 | 2023-12-07 | Boehringer Ingelheim Int | Pyridinyylisulfonamidijohdannaisia, farmaseuttisia koostumuksia ja niiden käytöt |
| CN112955214B (zh) | 2018-10-29 | 2024-05-07 | 勃林格殷格翰国际有限公司 | 吡啶基磺酰胺衍生物、药物组合物及其用途 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4699928A (en) * | 1984-07-13 | 1987-10-13 | Merrell Dow Pharmaceuticals Inc. | Fluoroallylamine derivatives |
| WO1986003203A1 (fr) * | 1984-11-22 | 1986-06-05 | Yoshitomi Pharmaceutical Industries, Ltd. | Derives de thienylthiazole |
| IT1181871B (it) * | 1985-04-01 | 1987-09-30 | Consiglio Nazionale Ricerche | Inibitori selettivi delle benzilamminossidasi rispetto ad altre amminossidasi |
| US4650907A (en) * | 1985-12-05 | 1987-03-17 | Merrell Dow Pharmaceuticals Inc. | Nonaromatic fluoroallylamine MAO inhibitors |
| US4916151A (en) * | 1985-12-05 | 1990-04-10 | Merrell Dow Pharmaceuticals Inc. | Method of treating parkinson's syndrome |
| DD261153A1 (de) * | 1987-03-19 | 1988-10-19 | Bitterfeld Chemie | Verfahren zur herstellung von neuen 2-heteroaryl-5-acylamino-thiazolen |
| US4965288A (en) * | 1988-02-25 | 1990-10-23 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
| US5021456A (en) * | 1988-02-25 | 1991-06-04 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
| US5059714A (en) * | 1988-02-25 | 1991-10-22 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
| US4943593A (en) * | 1988-02-25 | 1990-07-24 | Merrell Dow Pharmaceuticals Inc. | Inhibitors of lysyl oxidase |
| AU2001282162A1 (en) * | 2000-07-05 | 2002-01-14 | Biotie Therapies Corp. | Inhibitors of copper-containing amine oxidases |
| CA2514573A1 (en) * | 2003-01-27 | 2004-08-12 | Astellas Pharma Inc. | Thiazole derivatives and their use as vap-1 inhibitors |
| TW200524575A (en) * | 2003-10-27 | 2005-08-01 | S Bio Pte Ltd | Biaryl linked hydroxamates: preparation and pharmaceutical applications |
-
2005
- 2005-09-08 CA CA002579889A patent/CA2579889A1/en not_active Abandoned
- 2005-09-08 EP EP05783547A patent/EP1791835A2/en not_active Withdrawn
- 2005-09-08 US US11/574,946 patent/US20080015202A1/en not_active Abandoned
- 2005-09-08 WO PCT/JP2005/016984 patent/WO2006028269A2/en not_active Ceased
- 2005-09-08 JP JP2007511147A patent/JP2008512346A/ja not_active Abandoned
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2008512346A5 (enExample) | ||
| JP4650412B2 (ja) | チアゾール誘導体およびｖａｐ−１阻害剤としてのその使用 | |
| JP2008512346A (ja) | Ｖａｐ−１阻害活性を有するチアゾール誘導体 | |
| CN101827832B (zh) | 作为葡糖激酶活化剂的乙酰胺衍生物、其制备方法及医药应用 | |
| AU2011312203B2 (en) | Compositions and methods for treating ocular edema, neovascularization and related diseases | |
| US9675596B2 (en) | 1,2,4-thiazolidin-3-one derivatives and their use in the treatment of cancer | |
| JP4978464B2 (ja) | Ｖａｐ−１阻害剤活性を有するチアゾール誘導体 | |
| JP4758337B2 (ja) | 血管透過性亢進疾患を治療する方法 | |
| US8507690B2 (en) | Thiazole derivative and use thereof as VAP-1 inhibitor | |
| AU2015229188A1 (en) | Compounds, compositions, and methods for increasing CFTR activity | |
| CN102762101B (zh) | 取代的稠合咪唑衍生物、药物组合物及其使用方法 | |
| JP2008508188A5 (enExample) | ||
| KR20040095339A (ko) | 히드록시모르폴리논 유도체 및 이의 의약 용도 |