JP5419466B2 - 抗炎症剤としてのホウ素含有小分子 - Google Patents
抗炎症剤としてのホウ素含有小分子 Download PDFInfo
- Publication number
- JP5419466B2 JP5419466B2 JP2008555528A JP2008555528A JP5419466B2 JP 5419466 B2 JP5419466 B2 JP 5419466B2 JP 2008555528 A JP2008555528 A JP 2008555528A JP 2008555528 A JP2008555528 A JP 2008555528A JP 5419466 B2 JP5419466 B2 JP 5419466B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- pharmaceutically acceptable
- solvate
- acceptable salt
- hydroxy
- 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.)
- Active
Links
- 229910052796 boron Inorganic materials 0.000 title description 10
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 title description 7
- 150000003384 small molecules Chemical class 0.000 title description 5
- 229940121363 anti-inflammatory agent Drugs 0.000 title description 3
- 239000002260 anti-inflammatory agent Substances 0.000 title description 3
- -1 phenyloxy Chemical group 0.000 claims description 317
- 150000001875 compounds Chemical class 0.000 claims description 244
- 102000004127 Cytokines Human genes 0.000 claims description 121
- 108090000695 Cytokines Proteins 0.000 claims description 121
- 239000000203 mixture Substances 0.000 claims description 105
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 94
- 201000010099 disease Diseases 0.000 claims description 87
- 150000003839 salts Chemical class 0.000 claims description 74
- 239000003814 drug Substances 0.000 claims description 57
- 230000004054 inflammatory process Effects 0.000 claims description 53
- 206010061218 Inflammation Diseases 0.000 claims description 52
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 47
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 47
- 241001465754 Metazoa Species 0.000 claims description 46
- 239000012453 solvate Substances 0.000 claims description 46
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 44
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 40
- 150000008064 anhydrides Chemical class 0.000 claims description 39
- 230000014509 gene expression Effects 0.000 claims description 39
- 238000011282 treatment Methods 0.000 claims description 39
- 230000000770 proinflammatory effect Effects 0.000 claims description 36
- 201000004681 Psoriasis Diseases 0.000 claims description 32
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 32
- 238000009472 formulation Methods 0.000 claims description 31
- 230000002757 inflammatory effect Effects 0.000 claims description 29
- 239000008194 pharmaceutical composition Substances 0.000 claims description 29
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 22
- 108090001005 Interleukin-6 Proteins 0.000 claims description 20
- 102000004889 Interleukin-6 Human genes 0.000 claims description 20
- 230000001225 therapeutic effect Effects 0.000 claims description 20
- 201000004624 Dermatitis Diseases 0.000 claims description 19
- 208000011231 Crohn disease Diseases 0.000 claims description 18
- 241000282412 Homo Species 0.000 claims description 16
- 206010003246 arthritis Diseases 0.000 claims description 16
- 102000003814 Interleukin-10 Human genes 0.000 claims description 15
- 108090000174 Interleukin-10 Proteins 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 14
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 14
- 230000002401 inhibitory effect Effects 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- 108090000978 Interleukin-4 Proteins 0.000 claims description 10
- 208000006673 asthma Diseases 0.000 claims description 10
- 108010002350 Interleukin-2 Proteins 0.000 claims description 9
- 102000000588 Interleukin-2 Human genes 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 102000013462 Interleukin-12 Human genes 0.000 claims description 7
- 108010065805 Interleukin-12 Proteins 0.000 claims description 7
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 6
- 201000008937 atopic dermatitis Diseases 0.000 claims description 6
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 5
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 5
- 108050003558 Interleukin-17 Proteins 0.000 claims description 5
- 102000013691 Interleukin-17 Human genes 0.000 claims description 5
- 108010002386 Interleukin-3 Proteins 0.000 claims description 5
- 108010002586 Interleukin-7 Proteins 0.000 claims description 5
- 108010002335 Interleukin-9 Proteins 0.000 claims description 5
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 5
- 206010046851 Uveitis Diseases 0.000 claims description 5
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 5
- 201000010105 allergic rhinitis Diseases 0.000 claims description 5
- 208000024998 atopic conjunctivitis Diseases 0.000 claims description 5
- 230000028709 inflammatory response Effects 0.000 claims description 5
- 230000004936 stimulating effect Effects 0.000 claims description 5
- UBMGTTRDNUKZMT-UHFFFAOYSA-N 4-[(1-hydroxy-3h-2,1-benzoxaborol-5-yl)oxy]benzene-1,2-dicarbonitrile Chemical compound C=1C=C2B(O)OCC2=CC=1OC1=CC=C(C#N)C(C#N)=C1 UBMGTTRDNUKZMT-UHFFFAOYSA-N 0.000 claims description 4
- SOSLTXWXZNBJIP-UHFFFAOYSA-N 6-[(1-hydroxy-3h-2,1-benzoxaborol-5-yl)oxy]pyridine-3-carbonitrile Chemical compound C=1C=C2B(O)OCC2=CC=1OC1=CC=C(C#N)C=N1 SOSLTXWXZNBJIP-UHFFFAOYSA-N 0.000 claims description 4
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 4
- 108091007914 CDKs Proteins 0.000 claims description 4
- 102000003903 Cyclin-dependent kinases Human genes 0.000 claims description 4
- 108090000266 Cyclin-dependent kinases Proteins 0.000 claims description 4
- 206010012442 Dermatitis contact Diseases 0.000 claims description 4
- 108090000177 Interleukin-11 Proteins 0.000 claims description 4
- 102000003815 Interleukin-11 Human genes 0.000 claims description 4
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 4
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 4
- 208000010668 atopic eczema Diseases 0.000 claims description 4
- 208000010247 contact dermatitis Diseases 0.000 claims description 4
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 201000000306 sarcoidosis Diseases 0.000 claims description 4
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims description 4
- GWZBDMXSRRGGLN-UHFFFAOYSA-N 2-[(1-hydroxy-3h-2,1-benzoxaborol-5-yl)oxy]benzonitrile Chemical group C=1C=C2B(O)OCC2=CC=1OC1=CC=CC=C1C#N GWZBDMXSRRGGLN-UHFFFAOYSA-N 0.000 claims description 3
- 208000009137 Behcet syndrome Diseases 0.000 claims description 3
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims description 3
- 108090000171 Interleukin-18 Proteins 0.000 claims description 3
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 2
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 2
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 2
- RUQIPEQILCQEGE-UHFFFAOYSA-N 3-[(1-hydroxy-3h-2,1-benzoxaborol-5-yl)oxy]benzonitrile Chemical group C=1C=C2B(O)OCC2=CC=1OC1=CC=CC(C#N)=C1 RUQIPEQILCQEGE-UHFFFAOYSA-N 0.000 claims 1
- AUGXOBNKGYGYFA-UHFFFAOYSA-N 4-[(1-hydroxy-3H-2,1-benzoxaborol-5-yl)sulfanyl]benzonitrile Chemical group OB1OCc2cc(Sc3ccc(cc3)C#N)ccc12 AUGXOBNKGYGYFA-UHFFFAOYSA-N 0.000 claims 1
- 230000007794 irritation Effects 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 70
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 61
- 239000007858 starting material Substances 0.000 description 61
- 238000000034 method Methods 0.000 description 54
- XOQABDOICLHPIS-UHFFFAOYSA-N 1-hydroxy-2,1-benzoxaborole Chemical compound C1=CC=C2B(O)OCC2=C1 XOQABDOICLHPIS-UHFFFAOYSA-N 0.000 description 52
- 229940079593 drug Drugs 0.000 description 50
- 201000006417 multiple sclerosis Diseases 0.000 description 50
- 239000002904 solvent Substances 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
- 125000003118 aryl group Chemical group 0.000 description 40
- 125000000217 alkyl group Chemical group 0.000 description 39
- 238000005481 NMR spectroscopy Methods 0.000 description 35
- 125000001072 heteroaryl group Chemical group 0.000 description 34
- 230000008018 melting Effects 0.000 description 33
- 238000002844 melting Methods 0.000 description 33
- 235000019441 ethanol Nutrition 0.000 description 32
- 239000000243 solution Substances 0.000 description 32
- 238000005160 1H NMR spectroscopy Methods 0.000 description 31
- 125000004404 heteroalkyl group Chemical group 0.000 description 31
- 210000003491 skin Anatomy 0.000 description 31
- 239000000126 substance Substances 0.000 description 29
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 28
- 125000004429 atom Chemical group 0.000 description 28
- 125000000753 cycloalkyl group Chemical group 0.000 description 28
- 210000000282 nail Anatomy 0.000 description 28
- 125000001424 substituent group Chemical group 0.000 description 28
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 26
- 210000004209 hair Anatomy 0.000 description 25
- 210000000003 hoof Anatomy 0.000 description 25
- 210000000078 claw Anatomy 0.000 description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 23
- 239000012049 topical pharmaceutical composition Substances 0.000 description 23
- 229910052757 nitrogen Inorganic materials 0.000 description 22
- 102000000589 Interleukin-1 Human genes 0.000 description 21
- 108010002352 Interleukin-1 Proteins 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 21
- 239000003795 chemical substances by application Substances 0.000 description 21
- 235000019439 ethyl acetate Nutrition 0.000 description 21
- 230000002829 reductive effect Effects 0.000 description 21
- 125000004093 cyano group Chemical group *C#N 0.000 description 20
- 238000004128 high performance liquid chromatography Methods 0.000 description 20
- 208000024827 Alzheimer disease Diseases 0.000 description 19
- 239000013543 active substance Substances 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 229910052736 halogen Inorganic materials 0.000 description 18
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 17
- 238000002360 preparation method Methods 0.000 description 17
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 17
- 230000000694 effects Effects 0.000 description 16
- 150000002367 halogens Chemical class 0.000 description 16
- 239000003755 preservative agent Substances 0.000 description 16
- 230000000699 topical effect Effects 0.000 description 16
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
- 238000003556 assay Methods 0.000 description 15
- 239000012267 brine Substances 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000003995 emulsifying agent Substances 0.000 description 14
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 14
- 239000002609 medium Substances 0.000 description 14
- 239000004480 active ingredient Substances 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- 239000003974 emollient agent Substances 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 206010022489 Insulin Resistance Diseases 0.000 description 12
- 208000018737 Parkinson disease Diseases 0.000 description 12
- 230000006378 damage Effects 0.000 description 12
- 125000005842 heteroatom Chemical group 0.000 description 12
- 208000024891 symptom Diseases 0.000 description 12
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 11
- 238000010171 animal model Methods 0.000 description 11
- 230000001684 chronic effect Effects 0.000 description 11
- 239000006071 cream Substances 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- 230000001404 mediated effect Effects 0.000 description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 11
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 11
- 229920001451 polypropylene glycol Polymers 0.000 description 11
- 230000001154 acute effect Effects 0.000 description 10
- 239000003963 antioxidant agent Substances 0.000 description 10
- 235000006708 antioxidants Nutrition 0.000 description 10
- 239000000839 emulsion Substances 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 208000015122 neurodegenerative disease Diseases 0.000 description 10
- 231100000252 nontoxic Toxicity 0.000 description 10
- 230000003000 nontoxic effect Effects 0.000 description 10
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 239000003981 vehicle Substances 0.000 description 10
- USCKQKQTFCBECF-UHFFFAOYSA-N 1-hydroxy-3h-2,1-benzoxaborol-6-amine Chemical compound NC1=CC=C2COB(O)C2=C1 USCKQKQTFCBECF-UHFFFAOYSA-N 0.000 description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 9
- 206010019280 Heart failures Diseases 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 206010012601 diabetes mellitus Diseases 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 208000015181 infectious disease Diseases 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 239000003883 ointment base Substances 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- 150000003254 radicals Chemical class 0.000 description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 108010008165 Etanercept Proteins 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 208000037976 chronic inflammation Diseases 0.000 description 8
- 230000006020 chronic inflammation Effects 0.000 description 8
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 8
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 8
- 239000003623 enhancer Substances 0.000 description 8
- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
- 230000002335 preservative effect Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 8
- 238000012384 transportation and delivery Methods 0.000 description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 8
- 206010007559 Cardiac failure congestive Diseases 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 7
- PHEDXBVPIONUQT-UHFFFAOYSA-N Cocarcinogen A1 Natural products CCCCCCCCCCCCCC(=O)OC1C(C)C2(O)C3C=C(C)C(=O)C3(O)CC(CO)=CC2C2C1(OC(C)=O)C2(C)C PHEDXBVPIONUQT-UHFFFAOYSA-N 0.000 description 7
- 206010017912 Gastroenteritis radiation Diseases 0.000 description 7
- 206010020751 Hypersensitivity Diseases 0.000 description 7
- 208000002193 Pain Diseases 0.000 description 7
- 125000002947 alkylene group Chemical group 0.000 description 7
- 230000007815 allergy Effects 0.000 description 7
- 239000003435 antirheumatic agent Substances 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 229960000541 cetyl alcohol Drugs 0.000 description 7
- 239000002988 disease modifying antirheumatic drug Substances 0.000 description 7
- 125000001153 fluoro group Chemical group F* 0.000 description 7
- 235000021588 free fatty acids Nutrition 0.000 description 7
- 230000010534 mechanism of action Effects 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 208000020624 radiation proctitis Diseases 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 6
- 201000001320 Atherosclerosis Diseases 0.000 description 6
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- 101710144554 Interleukin-1 receptor antagonist protein Proteins 0.000 description 6
- 102100026018 Interleukin-1 receptor antagonist protein Human genes 0.000 description 6
- 108090001007 Interleukin-8 Proteins 0.000 description 6
- 102000004890 Interleukin-8 Human genes 0.000 description 6
- 208000006011 Stroke Diseases 0.000 description 6
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 6
- 210000000577 adipose tissue Anatomy 0.000 description 6
- 230000003078 antioxidant effect Effects 0.000 description 6
- 230000001580 bacterial effect Effects 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 239000002738 chelating agent Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000002537 cosmetic Substances 0.000 description 6
- USZAGAREISWJDP-UHFFFAOYSA-N crisaborole Chemical compound C=1C=C2B(O)OCC2=CC=1OC1=CC=C(C#N)C=C1 USZAGAREISWJDP-UHFFFAOYSA-N 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 238000009792 diffusion process Methods 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 210000001035 gastrointestinal tract Anatomy 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 230000007774 longterm Effects 0.000 description 6
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 230000003472 neutralizing effect Effects 0.000 description 6
- 230000008506 pathogenesis Effects 0.000 description 6
- 230000035515 penetration Effects 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- 229960003742 phenol Drugs 0.000 description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 239000004094 surface-active agent Substances 0.000 description 6
- 239000000375 suspending agent Substances 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- 230000009885 systemic effect Effects 0.000 description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 5
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 5
- AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 5
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 5
- 206010006895 Cachexia Diseases 0.000 description 5
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 5
- 208000001640 Fibromyalgia Diseases 0.000 description 5
- 206010016654 Fibrosis Diseases 0.000 description 5
- 208000018522 Gastrointestinal disease Diseases 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 208000008589 Obesity Diseases 0.000 description 5
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 5
- 241000219061 Rheum Species 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- WVDBMCNGKCSQFN-UHFFFAOYSA-N [4-(4-cyanophenoxy)phenyl]boronic acid Chemical compound C1=CC(B(O)O)=CC=C1OC1=CC=C(C#N)C=C1 WVDBMCNGKCSQFN-UHFFFAOYSA-N 0.000 description 5
- 206010000496 acne Diseases 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 210000001789 adipocyte Anatomy 0.000 description 5
- 208000026935 allergic disease Diseases 0.000 description 5
- 208000007502 anemia Diseases 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 229960002537 betamethasone Drugs 0.000 description 5
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone 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-DVTGEIKXSA-N 0.000 description 5
- 210000000988 bone and bone Anatomy 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
- 239000003086 colorant Substances 0.000 description 5
- 239000007859 condensation product Substances 0.000 description 5
- 229960003957 dexamethasone Drugs 0.000 description 5
- 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 5
- 235000005911 diet Nutrition 0.000 description 5
- 230000037213 diet Effects 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 229940073621 enbrel Drugs 0.000 description 5
- 201000002491 encephalomyelitis Diseases 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 239000003102 growth factor Substances 0.000 description 5
- 125000004474 heteroalkylene group Chemical group 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 239000006210 lotion Substances 0.000 description 5
- 229960000485 methotrexate Drugs 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 5
- 235000020824 obesity Nutrition 0.000 description 5
- OHENQANLQNOMAO-UHFFFAOYSA-N oxaborole Chemical compound O1B=CC=C1 OHENQANLQNOMAO-UHFFFAOYSA-N 0.000 description 5
- 230000036961 partial effect Effects 0.000 description 5
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 238000001959 radiotherapy Methods 0.000 description 5
- 210000000664 rectum Anatomy 0.000 description 5
- 229940116176 remicade Drugs 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- 239000002562 thickening agent Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 238000011200 topical administration Methods 0.000 description 5
- 239000008158 vegetable oil Substances 0.000 description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- HBXWUCXDUUJDRB-UHFFFAOYSA-N 1-octadecoxyoctadecane Chemical compound CCCCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCCCC HBXWUCXDUUJDRB-UHFFFAOYSA-N 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 4
- 208000002874 Acne Vulgaris Diseases 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 102000004506 Blood Proteins Human genes 0.000 description 4
- 108010017384 Blood Proteins Proteins 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 4
- 102000019034 Chemokines Human genes 0.000 description 4
- 108010012236 Chemokines Proteins 0.000 description 4
- 206010012735 Diarrhoea Diseases 0.000 description 4
- 206010014025 Ear swelling Diseases 0.000 description 4
- 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 4
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 4
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 4
- 208000019693 Lung disease Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 208000001132 Osteoporosis Diseases 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 108010047620 Phytohemagglutinins Proteins 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 239000007900 aqueous suspension Substances 0.000 description 4
- 235000010323 ascorbic acid Nutrition 0.000 description 4
- 239000011668 ascorbic acid Substances 0.000 description 4
- 229960005070 ascorbic acid Drugs 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 235000019445 benzyl alcohol Nutrition 0.000 description 4
- 229960004217 benzyl alcohol Drugs 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 239000013553 cell monolayer Substances 0.000 description 4
- 229940126214 compound 3 Drugs 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 4
- 239000000539 dimer Substances 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000003596 drug target Substances 0.000 description 4
- 230000004761 fibrosis Effects 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- 238000005755 formation reaction Methods 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 239000003018 immunosuppressive agent Substances 0.000 description 4
- 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 229940125396 insulin Drugs 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 208000017169 kidney disease Diseases 0.000 description 4
- 208000019423 liver disease Diseases 0.000 description 4
- 208000030159 metabolic disease Diseases 0.000 description 4
- 239000002480 mineral oil Substances 0.000 description 4
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 4
- 125000002757 morpholinyl group Chemical group 0.000 description 4
- 210000004877 mucosa Anatomy 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 239000003961 penetration enhancing agent Substances 0.000 description 4
- 230000035699 permeability Effects 0.000 description 4
- 230000001885 phytohemagglutinin Effects 0.000 description 4
- 239000002798 polar solvent Substances 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 208000037803 restenosis Diseases 0.000 description 4
- 238000002390 rotary evaporation Methods 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 239000000516 sunscreening agent Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000037317 transdermal delivery Effects 0.000 description 4
- 239000013638 trimer Substances 0.000 description 4
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 4
- 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 4
- 235000015112 vegetable and seed oil Nutrition 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 3
- GFFKBQCIGADRSN-UHFFFAOYSA-N 1-hydroxy-6-nitro-3h-2,1-benzoxaborole Chemical compound C1=C([N+]([O-])=O)C=C2B(O)OCC2=C1 GFFKBQCIGADRSN-UHFFFAOYSA-N 0.000 description 3
- ILCOCZBHMDEIAI-UHFFFAOYSA-N 2-(2-octadecoxyethoxy)ethanol Chemical compound CCCCCCCCCCCCCCCCCCOCCOCCO ILCOCZBHMDEIAI-UHFFFAOYSA-N 0.000 description 3
- RXRIGCPVWWYVQV-UHFFFAOYSA-N 4-(4-bromophenoxy)benzonitrile Chemical compound C1=CC(Br)=CC=C1OC1=CC=C(C#N)C=C1 RXRIGCPVWWYVQV-UHFFFAOYSA-N 0.000 description 3
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 3
- OTNUPHBMWRIGJT-UHFFFAOYSA-N 5-fluoro-1-hydroxy-3h-2,1-benzoxaborol-6-amine Chemical compound C1=C(F)C(N)=CC2=C1COB2O OTNUPHBMWRIGJT-UHFFFAOYSA-N 0.000 description 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 3
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 3
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 206010018364 Glomerulonephritis Diseases 0.000 description 3
- 102100023541 Glutathione S-transferase omega-1 Human genes 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 3
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 3
- 206010024229 Leprosy Diseases 0.000 description 3
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 3
- 102000006386 Myelin Proteins Human genes 0.000 description 3
- 108010083674 Myelin Proteins Proteins 0.000 description 3
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 3
- 206010033645 Pancreatitis Diseases 0.000 description 3
- 239000004264 Petrolatum Substances 0.000 description 3
- 239000004721 Polyphenylene oxide Substances 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 208000001647 Renal Insufficiency Diseases 0.000 description 3
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 3
- 206010047115 Vasculitis Diseases 0.000 description 3
- 206010047249 Venous thrombosis Diseases 0.000 description 3
- OGQICQVSFDPSEI-UHFFFAOYSA-N Zorac Chemical compound N1=CC(C(=O)OCC)=CC=C1C#CC1=CC=C(SCCC2(C)C)C2=C1 OGQICQVSFDPSEI-UHFFFAOYSA-N 0.000 description 3
- 229960002916 adapalene Drugs 0.000 description 3
- LZCDAPDGXCYOEH-UHFFFAOYSA-N adapalene Chemical compound C1=C(C(O)=O)C=CC2=CC(C3=CC=C(C(=C3)C34CC5CC(CC(C5)C3)C4)OC)=CC=C21 LZCDAPDGXCYOEH-UHFFFAOYSA-N 0.000 description 3
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 3
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 3
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 3
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 3
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 3
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 3
- 125000000129 anionic group Chemical group 0.000 description 3
- 206010002906 aortic stenosis Diseases 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 238000001815 biotherapy Methods 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 3
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 206010009887 colitis Diseases 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 239000003246 corticosteroid Substances 0.000 description 3
- 229960001334 corticosteroids Drugs 0.000 description 3
- 239000006184 cosolvent Substances 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 230000003831 deregulation Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000003651 drinking water Substances 0.000 description 3
- 235000020188 drinking water Nutrition 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000001804 emulsifying effect Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 229960000403 etanercept Drugs 0.000 description 3
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 229940075507 glyceryl monostearate Drugs 0.000 description 3
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 3
- 229940048921 humira Drugs 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
- 201000001421 hyperglycemia Diseases 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 229960003444 immunosuppressant agent Drugs 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 125000001041 indolyl group Chemical group 0.000 description 3
- 239000000411 inducer Substances 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 229960000598 infliximab Drugs 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 201000006370 kidney failure Diseases 0.000 description 3
- 229940054136 kineret Drugs 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 238000002483 medication Methods 0.000 description 3
- 125000005358 mercaptoalkyl group Chemical group 0.000 description 3
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 3
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 3
- 229960002216 methylparaben Drugs 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 3
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 description 3
- 210000004400 mucous membrane Anatomy 0.000 description 3
- 210000005012 myelin Anatomy 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 239000002736 nonionic surfactant Substances 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 231100000915 pathological change Toxicity 0.000 description 3
- 230000036285 pathological change Effects 0.000 description 3
- 229940066842 petrolatum Drugs 0.000 description 3
- 235000019271 petrolatum Nutrition 0.000 description 3
- 150000002989 phenols Chemical class 0.000 description 3
- 239000002644 phorbol ester Substances 0.000 description 3
- 230000000704 physical effect Effects 0.000 description 3
- 229920000570 polyether Polymers 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000003380 propellant Substances 0.000 description 3
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 3
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 3
- 229960003415 propylparaben Drugs 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 208000017520 skin disease Diseases 0.000 description 3
- 235000011069 sorbitan monooleate Nutrition 0.000 description 3
- 239000001593 sorbitan monooleate Substances 0.000 description 3
- 229940035049 sorbitan monooleate Drugs 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 229960000565 tazarotene Drugs 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- 230000000472 traumatic effect Effects 0.000 description 3
- 229960001727 tretinoin Drugs 0.000 description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 3
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- MPDQGMVOZYTKKO-UHFFFAOYSA-N (1-hydroxy-3h-2,1-benzoxaborol-7-yl)methanol Chemical compound OCC1=CC=CC2=C1B(O)OC2 MPDQGMVOZYTKKO-UHFFFAOYSA-N 0.000 description 2
- UJBWTRGCFGARTH-UHFFFAOYSA-N 1-[3-[(1-hydroxy-3h-2,1-benzoxaborol-5-yl)oxymethyl]phenyl]pentan-1-one Chemical compound CCCCC(=O)C1=CC=CC(COC=2C=C3COB(O)C3=CC=2)=C1 UJBWTRGCFGARTH-UHFFFAOYSA-N 0.000 description 2
- UNGCWOQNUSRHBE-UHFFFAOYSA-N 1-hydroxy-6-(4-methoxyphenoxy)-3h-2,1-benzoxaborole Chemical compound C1=CC(OC)=CC=C1OC1=CC=C(COB2O)C2=C1 UNGCWOQNUSRHBE-UHFFFAOYSA-N 0.000 description 2
- JEILWIPPHXIUER-UHFFFAOYSA-N 1-hydroxy-6-(4-methoxyphenyl)sulfanyl-3h-2,1-benzoxaborole Chemical compound C1=CC(OC)=CC=C1SC1=CC=C(COB2O)C2=C1 JEILWIPPHXIUER-UHFFFAOYSA-N 0.000 description 2
- FTLQVRSKWJJVIV-UHFFFAOYSA-N 1-hydroxy-6-(4-methoxyphenyl)sulfinyl-3h-2,1-benzoxaborole Chemical compound C1=CC(OC)=CC=C1S(=O)C1=CC=C(COB2O)C2=C1 FTLQVRSKWJJVIV-UHFFFAOYSA-N 0.000 description 2
- GPFWKPNFJFFFET-UHFFFAOYSA-N 1-hydroxy-6-(4-methoxyphenyl)sulfonyl-3h-2,1-benzoxaborole Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1=CC=C(COB2O)C2=C1 GPFWKPNFJFFFET-UHFFFAOYSA-N 0.000 description 2
- WGGPBPHYAGICNK-UHFFFAOYSA-N 1-hydroxy-6-[4-(trifluoromethoxy)phenoxy]-3h-2,1-benzoxaborole Chemical compound C1=C2B(O)OCC2=CC=C1OC1=CC=C(OC(F)(F)F)C=C1 WGGPBPHYAGICNK-UHFFFAOYSA-N 0.000 description 2
- ZMFMGJUEAIXARG-UHFFFAOYSA-N 1-hydroxy-6-phenylsulfanyl-3h-2,1-benzoxaborole Chemical compound C1=C2B(O)OCC2=CC=C1SC1=CC=CC=C1 ZMFMGJUEAIXARG-UHFFFAOYSA-N 0.000 description 2
- BKTIWUOBYOQTHE-UHFFFAOYSA-N 1-hydroxy-7-methyl-3h-2,1-benzoxaborole Chemical compound CC1=CC=CC2=C1B(O)OC2 BKTIWUOBYOQTHE-UHFFFAOYSA-N 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 2
- HNURKXXMYARGAY-UHFFFAOYSA-N 2,6-Di-tert-butyl-4-hydroxymethylphenol Chemical compound CC(C)(C)C1=CC(CO)=CC(C(C)(C)C)=C1O HNURKXXMYARGAY-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- BDLAKAMWILIVFM-UHFFFAOYSA-N 3-[(1-hydroxy-3h-2,1-benzoxaborol-5-yl)oxymethyl]benzonitrile Chemical compound C=1C=C2B(O)OCC2=CC=1OCC1=CC=CC(C#N)=C1 BDLAKAMWILIVFM-UHFFFAOYSA-N 0.000 description 2
- KNAQQPUJSZIUGO-UHFFFAOYSA-N 3-[(1-hydroxy-3h-2,1-benzoxaborol-6-yl)oxy]benzonitrile Chemical compound C1=C2B(O)OCC2=CC=C1OC1=CC=CC(C#N)=C1 KNAQQPUJSZIUGO-UHFFFAOYSA-N 0.000 description 2
- MFLIWWLDMLFNPM-UHFFFAOYSA-N 3-[5-chloro-1-(1-hydroxy-3h-2,1-benzoxaborol-6-yl)indol-3-yl]sulfanylpropanenitrile Chemical compound C1=C(SCCC#N)C2=CC(Cl)=CC=C2N1C1=CC=C2COB(O)C2=C1 MFLIWWLDMLFNPM-UHFFFAOYSA-N 0.000 description 2
- BFJMHTOBRRZELQ-UHFFFAOYSA-N 3-iodo-2h-pyrazolo[3,4-c]pyridine Chemical compound N1=CC=C2C(I)=NNC2=C1 BFJMHTOBRRZELQ-UHFFFAOYSA-N 0.000 description 2
- JHCANABFXFFJEV-UHFFFAOYSA-N 4-[(1-hydroxy-3h-2,1-benzoxaborol-4-yl)oxy]benzonitrile Chemical compound OB1OCC2=C1C=CC=C2OC1=CC=C(C#N)C=C1 JHCANABFXFFJEV-UHFFFAOYSA-N 0.000 description 2
- HMBNNGONNFTMDW-UHFFFAOYSA-N 4-[(1-hydroxy-3h-2,1-benzoxaborol-5-yl)oxymethyl]benzonitrile Chemical compound C=1C=C2B(O)OCC2=CC=1OCC1=CC=C(C#N)C=C1 HMBNNGONNFTMDW-UHFFFAOYSA-N 0.000 description 2
- IQBSCLXAECVABP-UHFFFAOYSA-N 4-[(1-hydroxy-3h-2,1-benzoxaborol-6-yl)oxy]benzonitrile Chemical compound C1=C2B(O)OCC2=CC=C1OC1=CC=C(C#N)C=C1 IQBSCLXAECVABP-UHFFFAOYSA-N 0.000 description 2
- DAMOSKSUIVLOJT-UHFFFAOYSA-N 4-[4-bromo-3-(hydroxymethyl)phenoxy]benzonitrile Chemical compound C1=C(Br)C(CO)=CC(OC=2C=CC(=CC=2)C#N)=C1 DAMOSKSUIVLOJT-UHFFFAOYSA-N 0.000 description 2
- GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 2
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- HMAFTPZYFJFEHK-UHFFFAOYSA-N 5-chloro-1-hydroxy-3h-2,1-benzoxaborole Chemical compound ClC1=CC=C2B(O)OCC2=C1 HMAFTPZYFJFEHK-UHFFFAOYSA-N 0.000 description 2
- QOQMJYSGCZLJFD-UHFFFAOYSA-N 5-fluoro-1-hydroxy-6-nitro-3h-2,1-benzoxaborole Chemical compound FC1=C([N+]([O-])=O)C=C2B(O)OCC2=C1 QOQMJYSGCZLJFD-UHFFFAOYSA-N 0.000 description 2
- MFBJMYHUTVPLKW-UHFFFAOYSA-N 6-(4-chlorophenoxy)-1-hydroxy-3h-2,1-benzoxaborole Chemical compound C1=C2B(O)OCC2=CC=C1OC1=CC=C(Cl)C=C1 MFBJMYHUTVPLKW-UHFFFAOYSA-N 0.000 description 2
- MNAFJMBSTDIAKH-UHFFFAOYSA-N 6-(4-chlorophenyl)sulfinyl-1-hydroxy-3h-2,1-benzoxaborole Chemical compound C1=C2B(O)OCC2=CC=C1S(=O)C1=CC=C(Cl)C=C1 MNAFJMBSTDIAKH-UHFFFAOYSA-N 0.000 description 2
- OBHRHSYGQBYLNH-UHFFFAOYSA-N 6-fluoro-1-hydroxy-3,4-dihydro-2,1-benzoxaborinine Chemical compound FC1=CC=C2B(O)OCCC2=C1 OBHRHSYGQBYLNH-UHFFFAOYSA-N 0.000 description 2
- QNCOVKFUYLBCNG-UHFFFAOYSA-N 6-fluoro-1-hydroxy-3h-2,1-benzoxaborole Chemical compound C1=C(F)C=C2B(O)OCC2=C1 QNCOVKFUYLBCNG-UHFFFAOYSA-N 0.000 description 2
- LIGKOZHDSGAHME-UHFFFAOYSA-N 7-fluoro-1-hydroxy-3h-2,1-benzoxaborole Chemical compound C1=CC(F)=C2B(O)OCC2=C1 LIGKOZHDSGAHME-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 208000007788 Acute Liver Failure Diseases 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 241001116389 Aloe Species 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 208000037259 Amyloid Plaque Diseases 0.000 description 2
- 235000003911 Arachis Nutrition 0.000 description 2
- 244000105624 Arachis hypogaea Species 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 2
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 2
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 2
- 208000020084 Bone disease Diseases 0.000 description 2
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 2
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 2
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 2
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 2
- ONAIRGOTKJCYEY-XXDXYRHBSA-N CCCCCCCCCCCCCCCCCC(O)=O.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 Chemical compound CCCCCCCCCCCCCCCCCC(O)=O.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 ONAIRGOTKJCYEY-XXDXYRHBSA-N 0.000 description 2
- 206010063094 Cerebral malaria Diseases 0.000 description 2
- 108010055166 Chemokine CCL5 Proteins 0.000 description 2
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 2
- 208000015943 Coeliac disease Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- 201000003883 Cystic fibrosis Diseases 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 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
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 102100030948 Glutathione S-transferase omega-2 Human genes 0.000 description 2
- 201000005569 Gout Diseases 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 208000005176 Hepatitis C Diseases 0.000 description 2
- 101000906386 Homo sapiens Glutathione S-transferase omega-1 Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 108010034219 Insulin Receptor Substrate Proteins Proteins 0.000 description 2
- 102100025087 Insulin receptor substrate 1 Human genes 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
- 208000001145 Metabolic Syndrome Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 108010057466 NF-kappa B Proteins 0.000 description 2
- 102000003945 NF-kappa B Human genes 0.000 description 2
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 2
- 108010016731 PPAR gamma Proteins 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 206010036105 Polyneuropathy Diseases 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- 208000010378 Pulmonary Embolism Diseases 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 101000935814 Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720) Periplasmic beta-glucosidase Proteins 0.000 description 2
- 206010040070 Septic Shock 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
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229940123155 T cell inhibitor Drugs 0.000 description 2
- WPMWEFXCIYCJSA-UHFFFAOYSA-N Tetraethylene glycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCO WPMWEFXCIYCJSA-UHFFFAOYSA-N 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 description 2
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- KYFAMGIFGMGPHC-UHFFFAOYSA-N [3-(4-cyanophenoxy)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(OC=2C=CC(=CC=2)C#N)=C1 KYFAMGIFGMGPHC-UHFFFAOYSA-N 0.000 description 2
- ZVRUWHKEIJYTPW-UHFFFAOYSA-N [4-(4-cyanophenoxy)-2-methylphenyl]boronic acid Chemical compound C1=C(B(O)O)C(C)=CC(OC=2C=CC(=CC=2)C#N)=C1 ZVRUWHKEIJYTPW-UHFFFAOYSA-N 0.000 description 2
- LDKHXGIHIBYPGK-UHFFFAOYSA-N [4-[(1-hydroxy-3h-2,1-benzoxaborol-5-yl)oxy]phenyl]-morpholin-4-ylmethanone Chemical compound C=1C=C2B(O)OCC2=CC=1OC(C=C1)=CC=C1C(=O)N1CCOCC1 LDKHXGIHIBYPGK-UHFFFAOYSA-N 0.000 description 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 208000009621 actinic keratosis Diseases 0.000 description 2
- 229960002964 adalimumab Drugs 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 235000011399 aloe vera Nutrition 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000002280 amphoteric surfactant Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 239000003945 anionic surfactant Substances 0.000 description 2
- 230000003712 anti-aging effect Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000002917 arthritic effect Effects 0.000 description 2
- 230000003305 autocrine Effects 0.000 description 2
- 229960002170 azathioprine Drugs 0.000 description 2
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 2
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- 125000005620 boronic acid group Chemical class 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 2
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
- LWQQLNNNIPYSNX-UROSTWAQSA-N calcipotriol Chemical compound C1([C@H](O)/C=C/[C@@H](C)[C@@H]2[C@]3(CCCC(/[C@@H]3CC2)=C\C=C\2C([C@@H](O)C[C@H](O)C/2)=C)C)CC1 LWQQLNNNIPYSNX-UROSTWAQSA-N 0.000 description 2
- 229960002882 calcipotriol Drugs 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 239000003093 cationic surfactant Substances 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 229940120503 dihydroxyacetone Drugs 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 208000016097 disease of metabolism Diseases 0.000 description 2
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 206010013663 drug dependence Diseases 0.000 description 2
- 230000036267 drug metabolism Effects 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 230000008482 dysregulation Effects 0.000 description 2
- 229950007919 egtazic acid Drugs 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- OODKNBSXBVWRAB-UHFFFAOYSA-N ethyl 2-[4-bromo-3-(hydroxymethyl)phenoxy]acetate Chemical compound CCOC(=O)COC1=CC=C(Br)C(CO)=C1 OODKNBSXBVWRAB-UHFFFAOYSA-N 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 208000030533 eye disease Diseases 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 206010016256 fatigue Diseases 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 208000010758 granulomatous inflammation Diseases 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 210000001503 joint Anatomy 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 210000002429 large intestine Anatomy 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 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
- 238000007726 management method Methods 0.000 description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- ZXYACEYBZNPPLS-UHFFFAOYSA-N n,n-diethyl-4-[(1-hydroxy-3h-2,1-benzoxaborol-5-yl)oxy]benzamide Chemical compound C1=CC(C(=O)N(CC)CC)=CC=C1OC1=CC=C(B(O)OC2)C2=C1 ZXYACEYBZNPPLS-UHFFFAOYSA-N 0.000 description 2
- XFOBIUGYWIONIM-UHFFFAOYSA-N n-(1-hydroxy-3h-2,1-benzoxaborol-5-yl)-n-methylbenzenesulfonamide Chemical compound C=1C=C2B(O)OCC2=CC=1N(C)S(=O)(=O)C1=CC=CC=C1 XFOBIUGYWIONIM-UHFFFAOYSA-N 0.000 description 2
- MLTONBYGSGVNMI-UHFFFAOYSA-N n-(1-hydroxy-3h-2,1-benzoxaborol-6-yl)acetamide Chemical compound CC(=O)NC1=CC=C2COB(O)C2=C1 MLTONBYGSGVNMI-UHFFFAOYSA-N 0.000 description 2
- HJXKOPMRKLRHPC-UHFFFAOYSA-N n-(1-hydroxy-3h-2,1-benzoxaborol-6-yl)benzamide Chemical compound C1=C2B(O)OCC2=CC=C1NC(=O)C1=CC=CC=C1 HJXKOPMRKLRHPC-UHFFFAOYSA-N 0.000 description 2
- 208000004296 neuralgia Diseases 0.000 description 2
- 230000003959 neuroinflammation Effects 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 231100000344 non-irritating Toxicity 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 238000005580 one pot reaction Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 238000012261 overproduction Methods 0.000 description 2
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 230000003076 paracrine Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 230000007824 polyneuropathy Effects 0.000 description 2
- 229920000259 polyoxyethylene lauryl ether Polymers 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 239000000473 propyl gallate Substances 0.000 description 2
- 235000010388 propyl gallate Nutrition 0.000 description 2
- 229940075579 propyl gallate Drugs 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 208000010157 sclerosing cholangitis Diseases 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 210000000434 stratum corneum Anatomy 0.000 description 2
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical compound OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000000475 sunscreen effect Effects 0.000 description 2
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 210000001258 synovial membrane Anatomy 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 125000004523 tetrazol-1-yl group Chemical group N1(N=NN=C1)* 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 125000005309 thioalkoxy group Chemical group 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 2
- 230000008728 vascular permeability Effects 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- WTVHAMTYZJGJLJ-UHFFFAOYSA-N (+)-(4S,8R)-8-epi-beta-bisabolol Natural products CC(C)=CCCC(C)C1(O)CCC(C)=CC1 WTVHAMTYZJGJLJ-UHFFFAOYSA-N 0.000 description 1
- RGZSQWQPBWRIAQ-CABCVRRESA-N (-)-alpha-Bisabolol Chemical compound CC(C)=CCC[C@](C)(O)[C@H]1CCC(C)=CC1 RGZSQWQPBWRIAQ-CABCVRRESA-N 0.000 description 1
- AOMOMZHKVMHEAM-UHFFFAOYSA-N (1-bromonaphthalen-2-yl)methanol Chemical compound C1=CC=CC2=C(Br)C(CO)=CC=C21 AOMOMZHKVMHEAM-UHFFFAOYSA-N 0.000 description 1
- WGBLBANWTOEASN-UHFFFAOYSA-N (2-bromo-3-fluorophenyl)methanol Chemical compound OCC1=CC=CC(F)=C1Br WGBLBANWTOEASN-UHFFFAOYSA-N 0.000 description 1
- KOMJECHMWYAILT-UHFFFAOYSA-N (2-bromo-3-methylphenyl)methanol Chemical compound CC1=CC=CC(CO)=C1Br KOMJECHMWYAILT-UHFFFAOYSA-N 0.000 description 1
- CUYVKVMYMVIBDZ-UHFFFAOYSA-N (2-bromo-3-phenylmethoxyphenyl)methanol Chemical compound OCC1=CC=CC(OCC=2C=CC=CC=2)=C1Br CUYVKVMYMVIBDZ-UHFFFAOYSA-N 0.000 description 1
- RCUJMOALRDOYBM-UHFFFAOYSA-N (2-bromo-4-indol-1-ylphenyl)methanol Chemical compound C1=C(Br)C(CO)=CC=C1N1C2=CC=CC=C2C=C1 RCUJMOALRDOYBM-UHFFFAOYSA-N 0.000 description 1
- FNYBKAHWKJZLET-UHFFFAOYSA-N (2-bromo-4-morpholin-4-ylphenyl)methanol Chemical compound C1=C(Br)C(CO)=CC=C1N1CCOCC1 FNYBKAHWKJZLET-UHFFFAOYSA-N 0.000 description 1
- YREHUJOPVDVQHE-UHFFFAOYSA-N (2-bromo-4-pyridin-2-ylsulfanylphenyl)methanol Chemical compound C1=C(Br)C(CO)=CC=C1SC1=CC=CC=N1 YREHUJOPVDVQHE-UHFFFAOYSA-N 0.000 description 1
- YAEMSWXBKWTPDP-UHFFFAOYSA-N (2-bromo-4-pyridin-4-ylsulfanylphenyl)methanol Chemical compound C1=C(Br)C(CO)=CC=C1SC1=CC=NC=C1 YAEMSWXBKWTPDP-UHFFFAOYSA-N 0.000 description 1
- XBYSVESIBILXQL-UHFFFAOYSA-N (2-bromo-4-thiophen-2-ylsulfanylphenyl)methanol Chemical compound C1=C(Br)C(CO)=CC=C1SC1=CC=CS1 XBYSVESIBILXQL-UHFFFAOYSA-N 0.000 description 1
- YOLUSOFTODTRQV-UHFFFAOYSA-N (2-bromo-5-chlorophenyl)methanol Chemical compound OCC1=CC(Cl)=CC=C1Br YOLUSOFTODTRQV-UHFFFAOYSA-N 0.000 description 1
- HXGZPMHPSBJMKB-UHFFFAOYSA-N (2-bromo-5-fluorophenyl)methanol Chemical compound OCC1=CC(F)=CC=C1Br HXGZPMHPSBJMKB-UHFFFAOYSA-N 0.000 description 1
- NRDAKNCVXNJCGB-UHFFFAOYSA-N (2-bromo-5-methoxyphenyl)methanol Chemical compound COC1=CC=C(Br)C(CO)=C1 NRDAKNCVXNJCGB-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 1
- UXUFTKZYJYGMGO-CMCWBKRRSA-N (2s,3s,4r,5r)-5-[6-amino-2-[2-[4-[3-(2-aminoethylamino)-3-oxopropyl]phenyl]ethylamino]purin-9-yl]-n-ethyl-3,4-dihydroxyoxolane-2-carboxamide Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(NCCC=3C=CC(CCC(=O)NCCN)=CC=3)=NC(N)=C2N=C1 UXUFTKZYJYGMGO-CMCWBKRRSA-N 0.000 description 1
- RGEMJCLUPGZKTQ-WAUHAFJUSA-N (3s,8r,9s,10r,13s,14s)-3-[2-(dimethylamino)ethoxy]-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one Chemical compound C([C@@H]12)C[C@]3(C)C(=O)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OCCN(C)C)C1 RGEMJCLUPGZKTQ-WAUHAFJUSA-N 0.000 description 1
- XYYBAJXSNPIXTC-UHFFFAOYSA-N (6-bromo-1,3-benzodioxol-5-yl)methanol Chemical compound C1=C(Br)C(CO)=CC2=C1OCO2 XYYBAJXSNPIXTC-UHFFFAOYSA-N 0.000 description 1
- HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000000196 1,4-pentadienyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])=C([H])[H] 0.000 description 1
- SRUQARLMFOLRDN-UHFFFAOYSA-N 1-(2,4,5-Trihydroxyphenyl)-1-butanone Chemical compound CCCC(=O)C1=CC(O)=C(O)C=C1O SRUQARLMFOLRDN-UHFFFAOYSA-N 0.000 description 1
- VOEQIMWZXAUWFJ-UHFFFAOYSA-N 1-[3-[[4-bromo-3-(hydroxymethyl)phenoxy]methyl]phenyl]pentan-1-one Chemical compound CCCCC(=O)C1=CC=CC(COC=2C=C(CO)C(Br)=CC=2)=C1 VOEQIMWZXAUWFJ-UHFFFAOYSA-N 0.000 description 1
- MICXSWCQEMESAN-UHFFFAOYSA-N 1-bromo-2-(methoxymethoxymethyl)-4-methylbenzene Chemical compound COCOCC1=CC(C)=CC=C1Br MICXSWCQEMESAN-UHFFFAOYSA-N 0.000 description 1
- MOLXAVNVHPKEID-UHFFFAOYSA-N 1-bromo-2-(methoxymethoxymethyl)-4-phenoxybenzene Chemical compound C1=C(Br)C(COCOC)=CC(OC=2C=CC=CC=2)=C1 MOLXAVNVHPKEID-UHFFFAOYSA-N 0.000 description 1
- DIZPEZNNOODNQE-UHFFFAOYSA-N 1-bromo-2-(methoxymethoxymethyl)benzene Chemical compound COCOCC1=CC=CC=C1Br DIZPEZNNOODNQE-UHFFFAOYSA-N 0.000 description 1
- YIHFZZAUSZFESU-UHFFFAOYSA-N 1-bromo-2-(methoxymethoxymethyl)naphthalene Chemical compound C1=CC=CC2=C(Br)C(COCOC)=CC=C21 YIHFZZAUSZFESU-UHFFFAOYSA-N 0.000 description 1
- GFKOSSVFTZTCCG-UHFFFAOYSA-N 1-bromo-2-[1-(methoxymethoxy)-2-phenylethyl]benzene Chemical compound C=1C=CC=C(Br)C=1C(OCOC)CC1=CC=CC=C1 GFKOSSVFTZTCCG-UHFFFAOYSA-N 0.000 description 1
- WGUMLDWTJJLTES-UHFFFAOYSA-N 1-bromo-2-[2-(methoxymethoxy)-1-phenylpropan-2-yl]benzene Chemical compound C=1C=CC=C(Br)C=1C(C)(OCOC)CC1=CC=CC=C1 WGUMLDWTJJLTES-UHFFFAOYSA-N 0.000 description 1
- QQBYSVGVCORKNY-UHFFFAOYSA-N 1-bromo-3-fluoro-2-(methoxymethoxymethyl)benzene Chemical compound COCOCC1=C(F)C=CC=C1Br QQBYSVGVCORKNY-UHFFFAOYSA-N 0.000 description 1
- VHGIRMPYUVXOAR-UHFFFAOYSA-N 1-bromo-4,5-difluoro-2-(methoxymethoxymethyl)benzene Chemical compound COCOCC1=CC(F)=C(F)C=C1Br VHGIRMPYUVXOAR-UHFFFAOYSA-N 0.000 description 1
- WWEZFHIIGHABQR-UHFFFAOYSA-N 1-bromo-4-chloro-2-(methoxymethoxymethyl)benzene Chemical compound COCOCC1=CC(Cl)=CC=C1Br WWEZFHIIGHABQR-UHFFFAOYSA-N 0.000 description 1
- DWRMHMOLSZZYDZ-UHFFFAOYSA-N 1-bromo-4-fluoro-2-(methoxymethoxymethyl)benzene Chemical compound COCOCC1=CC(F)=CC=C1Br DWRMHMOLSZZYDZ-UHFFFAOYSA-N 0.000 description 1
- VYHPSVZCABRZFI-UHFFFAOYSA-N 1-bromo-4-fluoro-2-[1-(methoxymethoxy)ethyl]benzene Chemical compound COCOC(C)C1=CC(F)=CC=C1Br VYHPSVZCABRZFI-UHFFFAOYSA-N 0.000 description 1
- ATWHLVHDDXTKFJ-UHFFFAOYSA-N 1-bromo-4-fluoro-2-[2-(methoxymethoxy)ethyl]benzene Chemical compound COCOCCC1=CC(F)=CC=C1Br ATWHLVHDDXTKFJ-UHFFFAOYSA-N 0.000 description 1
- KVDNNBDHBSSKNZ-UHFFFAOYSA-N 1-bromo-4-methoxy-2-(methoxymethoxymethyl)benzene Chemical compound COCOCC1=CC(OC)=CC=C1Br KVDNNBDHBSSKNZ-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000005978 1-naphthyloxy group Chemical group 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- UGDAWAQEKLURQI-UHFFFAOYSA-N 2-(2-hydroxyethoxy)ethanol;hydrate Chemical compound O.OCCOCCO UGDAWAQEKLURQI-UHFFFAOYSA-N 0.000 description 1
- WGIMXKDCVCTHGW-UHFFFAOYSA-N 2-(2-hydroxyethoxy)ethyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCOCCO WGIMXKDCVCTHGW-UHFFFAOYSA-N 0.000 description 1
- FKOKUHFZNIUSLW-UHFFFAOYSA-N 2-Hydroxypropyl stearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(C)O FKOKUHFZNIUSLW-UHFFFAOYSA-N 0.000 description 1
- KETFSMJIUTVHFQ-UHFFFAOYSA-N 2-[4-bromo-3-(hydroxymethyl)phenoxy]-1-(4-pyrimidin-2-ylpiperazin-1-yl)ethanone Chemical compound C1=C(Br)C(CO)=CC(OCC(=O)N2CCN(CC2)C=2N=CC=CN=2)=C1 KETFSMJIUTVHFQ-UHFFFAOYSA-N 0.000 description 1
- LKBANZVZCWENOA-UHFFFAOYSA-N 2-[4-bromo-3-(hydroxymethyl)phenoxy]-1-piperidin-1-ylethanone Chemical compound C1=C(Br)C(CO)=CC(OCC(=O)N2CCCCC2)=C1 LKBANZVZCWENOA-UHFFFAOYSA-N 0.000 description 1
- FGXQXFQVGYAFLP-UHFFFAOYSA-N 2-[4-bromo-3-(methoxymethoxymethyl)phenoxy]benzonitrile Chemical compound C1=C(Br)C(COCOC)=CC(OC=2C(=CC=CC=2)C#N)=C1 FGXQXFQVGYAFLP-UHFFFAOYSA-N 0.000 description 1
- NBGAYCYFNGPNPV-UHFFFAOYSA-N 2-aminooxybenzoic acid Chemical class NOC1=CC=CC=C1C(O)=O NBGAYCYFNGPNPV-UHFFFAOYSA-N 0.000 description 1
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- MLRBNIXMTWSDJU-UHFFFAOYSA-N 2-benzylfuran Chemical class C=1C=CC=CC=1CC1=CC=CO1 MLRBNIXMTWSDJU-UHFFFAOYSA-N 0.000 description 1
- VCYJEELJKYYVKI-UHFFFAOYSA-N 2-bromo-1-(methoxymethoxymethyl)-4-phenoxybenzene Chemical compound C1=C(Br)C(COCOC)=CC=C1OC1=CC=CC=C1 VCYJEELJKYYVKI-UHFFFAOYSA-N 0.000 description 1
- ZLJRCGBPPIFXHC-UHFFFAOYSA-N 2-bromo-4-(4-chlorophenoxy)-1-(methoxymethoxymethyl)benzene Chemical compound C1=C(Br)C(COCOC)=CC=C1OC1=CC=C(Cl)C=C1 ZLJRCGBPPIFXHC-UHFFFAOYSA-N 0.000 description 1
- ALJWIUYVYZYOBZ-UHFFFAOYSA-N 2-bromo-4-fluoro-1-(methoxymethoxymethyl)benzene Chemical compound COCOCC1=CC=C(F)C=C1Br ALJWIUYVYZYOBZ-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- ICIDSZQHPUZUHC-UHFFFAOYSA-N 2-octadecoxyethanol Chemical compound CCCCCCCCCCCCCCCCCCOCCO ICIDSZQHPUZUHC-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- ODJQKYXPKWQWNK-UHFFFAOYSA-N 3,3'-Thiobispropanoic acid Chemical compound OC(=O)CCSCCC(O)=O ODJQKYXPKWQWNK-UHFFFAOYSA-N 0.000 description 1
- BTBCAIREAHNNSA-UHFFFAOYSA-N 3-[1-[3-bromo-4-(hydroxymethyl)phenyl]-5-chloroindol-3-yl]sulfanylpropanenitrile Chemical compound C1=C(Br)C(CO)=CC=C1N1C2=CC=C(Cl)C=C2C(SCCC#N)=C1 BTBCAIREAHNNSA-UHFFFAOYSA-N 0.000 description 1
- YGTHNCUXEPAWFD-UHFFFAOYSA-N 3-[1-[3-bromo-4-(hydroxymethyl)phenyl]-5-methoxyindol-3-yl]sulfanylpropanenitrile Chemical compound C1=C(SCCC#N)C2=CC(OC)=CC=C2N1C1=CC=C(CO)C(Br)=C1 YGTHNCUXEPAWFD-UHFFFAOYSA-N 0.000 description 1
- QRSNVSPHRSETBM-UHFFFAOYSA-N 3-[1-[3-bromo-4-(hydroxymethyl)phenyl]indol-3-yl]sulfanylpropanenitrile Chemical compound C1=C(Br)C(CO)=CC=C1N1C2=CC=CC=C2C(SCCC#N)=C1 QRSNVSPHRSETBM-UHFFFAOYSA-N 0.000 description 1
- ZWUASDNUBOMNPA-UHFFFAOYSA-N 3-[[4-bromo-3-(hydroxymethyl)phenoxy]methyl]benzonitrile Chemical compound C1=C(Br)C(CO)=CC(OCC=2C=C(C=CC=2)C#N)=C1 ZWUASDNUBOMNPA-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- MNOJRWOWILAHAV-UHFFFAOYSA-N 3-bromophenol Chemical compound OC1=CC=CC(Br)=C1 MNOJRWOWILAHAV-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- JZTPKAROPNTQQV-UHFFFAOYSA-N 3-fluorobenzonitrile Chemical compound FC1=CC=CC(C#N)=C1 JZTPKAROPNTQQV-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- MWKJPIMAYNGEFN-UHFFFAOYSA-N 4-(3-bromophenoxy)benzonitrile Chemical compound BrC1=CC=CC(OC=2C=CC(=CC=2)C#N)=C1 MWKJPIMAYNGEFN-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- APXBXIUYTIHSJQ-UHFFFAOYSA-N 4-[(1-hydroxy-2,3-dihydro-1h-inden-5-yl)oxy]benzonitrile Chemical compound C=1C=C2C(O)CCC2=CC=1OC1=CC=C(C#N)C=C1 APXBXIUYTIHSJQ-UHFFFAOYSA-N 0.000 description 1
- HYXMTRJYRKGOAJ-UHFFFAOYSA-N 4-[(1-hydroxy-3h-2,1-benzoxaborol-7-yl)oxy]benzonitrile Chemical compound C=12B(O)OCC2=CC=CC=1OC1=CC=C(C#N)C=C1 HYXMTRJYRKGOAJ-UHFFFAOYSA-N 0.000 description 1
- RIWSPEIIJLBVBK-UHFFFAOYSA-N 4-[2-bromo-3-(hydroxymethyl)phenoxy]benzonitrile Chemical compound OCC1=CC=CC(OC=2C=CC(=CC=2)C#N)=C1Br RIWSPEIIJLBVBK-UHFFFAOYSA-N 0.000 description 1
- UTSZBZGSKRWEBL-UHFFFAOYSA-N 4-[3-bromo-4-(methoxymethoxymethyl)phenoxy]benzonitrile Chemical compound C1=C(Br)C(COCOC)=CC=C1OC1=CC=C(C#N)C=C1 UTSZBZGSKRWEBL-UHFFFAOYSA-N 0.000 description 1
- LJTVCOFOOMAXKA-UHFFFAOYSA-N 4-[4-bromo-3-(methoxymethoxymethyl)phenoxy]benzene-1,2-dicarbonitrile Chemical compound C1=C(Br)C(COCOC)=CC(OC=2C=C(C(C#N)=CC=2)C#N)=C1 LJTVCOFOOMAXKA-UHFFFAOYSA-N 0.000 description 1
- QAAOKUXSTGHCIQ-UHFFFAOYSA-N 4-[4-bromo-3-(methoxymethoxymethyl)phenoxy]benzonitrile Chemical compound C1=C(Br)C(COCOC)=CC(OC=2C=CC(=CC=2)C#N)=C1 QAAOKUXSTGHCIQ-UHFFFAOYSA-N 0.000 description 1
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- MKEWOMLQLUYQPK-UHFFFAOYSA-N 4-bromo-3-(hydroxymethyl)benzonitrile Chemical compound OCC1=CC(C#N)=CC=C1Br MKEWOMLQLUYQPK-UHFFFAOYSA-N 0.000 description 1
- OJZIIAHGEBFDRF-UHFFFAOYSA-N 4-bromo-3-(methoxymethoxymethyl)benzonitrile Chemical compound COCOCC1=CC(C#N)=CC=C1Br OJZIIAHGEBFDRF-UHFFFAOYSA-N 0.000 description 1
- GPOQODYGMUTOQL-UHFFFAOYSA-N 4-bromo-3-methylphenol Chemical compound CC1=CC(O)=CC=C1Br GPOQODYGMUTOQL-UHFFFAOYSA-N 0.000 description 1
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- MLMPLBPSIHKMAU-UHFFFAOYSA-N 6-[4-bromo-3-(hydroxymethyl)phenoxy]pyridine-3-carbonitrile Chemical compound C1=C(Br)C(CO)=CC(OC=2N=CC(=CC=2)C#N)=C1 MLMPLBPSIHKMAU-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 206010065040 AIDS dementia complex Diseases 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 1
- 206010000804 Acute hepatic failure Diseases 0.000 description 1
- 206010048998 Acute phase reaction Diseases 0.000 description 1
- 102000011690 Adiponectin Human genes 0.000 description 1
- 108010076365 Adiponectin Proteins 0.000 description 1
- 229920001817 Agar Polymers 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
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 206010001939 Aminoaciduria Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 206010002329 Aneurysm Diseases 0.000 description 1
- 208000000103 Anorexia Nervosa Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 206010003880 Axillary vein thrombosis Diseases 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 241000195940 Bryophyta Species 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 1
- 102100036150 C-X-C motif chemokine 5 Human genes 0.000 description 1
- 108010084313 CD58 Antigens Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 206010007558 Cardiac failure chronic Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 208000005024 Castleman disease Diseases 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 206010008027 Cerebellar atrophy Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 108010014419 Chemokine CXCL1 Proteins 0.000 description 1
- 102000016950 Chemokine CXCL1 Human genes 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 208000006561 Cluster Headache Diseases 0.000 description 1
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 1
- 206010057669 Colon injury Diseases 0.000 description 1
- 208000002330 Congenital Heart Defects Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 208000001778 Coronary Occlusion Diseases 0.000 description 1
- 206010011086 Coronary artery occlusion Diseases 0.000 description 1
- 208000028399 Critical Illness Diseases 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- 102000016736 Cyclin Human genes 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- CIWBSHSKHKDKBQ-DUZGATOHSA-N D-araboascorbic acid Natural products OC[C@@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-DUZGATOHSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- MQJKPEGWNLWLTK-UHFFFAOYSA-N Dapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 MQJKPEGWNLWLTK-UHFFFAOYSA-N 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 206010012455 Dermatitis exfoliative Diseases 0.000 description 1
- 206010048768 Dermatosis Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- GHKOFFNLGXMVNJ-UHFFFAOYSA-N Didodecyl thiobispropanoate Chemical compound CCCCCCCCCCCCOC(=O)CCSCCC(=O)OCCCCCCCCCCCC GHKOFFNLGXMVNJ-UHFFFAOYSA-N 0.000 description 1
- 239000003508 Dilauryl thiodipropionate Substances 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 208000002087 Endarteritis Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 208000037487 Endotoxemia Diseases 0.000 description 1
- 206010014824 Endotoxic shock Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- FPVVYTCTZKCSOJ-UHFFFAOYSA-N Ethylene glycol distearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCOC(=O)CCCCCCCCCCCCCCCCC FPVVYTCTZKCSOJ-UHFFFAOYSA-N 0.000 description 1
- 208000020564 Eye injury Diseases 0.000 description 1
- 206010016717 Fistula Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010017076 Fracture Diseases 0.000 description 1
- 241001427367 Gardena Species 0.000 description 1
- 208000007465 Giant cell arteritis Diseases 0.000 description 1
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 206010018366 Glomerulonephritis acute Diseases 0.000 description 1
- 101710145248 Glutathione S-transferase omega-1 Proteins 0.000 description 1
- 101710145255 Glutathione S-transferase omega-2 Proteins 0.000 description 1
- 102100033495 Glycine dehydrogenase (decarboxylating), mitochondrial Human genes 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 241000147041 Guaiacum officinale Species 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 description 1
- 206010019909 Hernia Diseases 0.000 description 1
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 101000947186 Homo sapiens C-X-C motif chemokine 5 Proteins 0.000 description 1
- 101001010149 Homo sapiens Glutathione S-transferase omega-2 Proteins 0.000 description 1
- 206010020365 Homocystinuria Diseases 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical class [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000033892 Hyperhomocysteinemia Diseases 0.000 description 1
- 208000004044 Hypesthesia Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 108060006678 I-kappa-B kinase Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 241000692870 Inachis io Species 0.000 description 1
- 208000004575 Infectious Arthritis Diseases 0.000 description 1
- 102100021854 Inhibitor of nuclear factor kappa-B kinase subunit beta Human genes 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 208000021342 Isolated sulfite oxidase deficiency Diseases 0.000 description 1
- 101150008942 J gene Proteins 0.000 description 1
- 206010023203 Joint destruction Diseases 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 201000003533 Leber congenital amaurosis Diseases 0.000 description 1
- 208000004554 Leishmaniasis Diseases 0.000 description 1
- 108010092277 Leptin Proteins 0.000 description 1
- 102000016267 Leptin Human genes 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 208000035172 MERRF Diseases 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 206010058858 Meningococcal bacteraemia Diseases 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical class SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 101710151805 Mitochondrial intermediate peptidase 1 Proteins 0.000 description 1
- 208000034819 Mobility Limitation Diseases 0.000 description 1
- 241000907681 Morpho Species 0.000 description 1
- 206010067994 Mucosal atrophy Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 206010028391 Musculoskeletal Pain Diseases 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- 206010028570 Myelopathy Diseases 0.000 description 1
- 208000021908 Myocardial disease Diseases 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- 240000001307 Myosotis scorpioides Species 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 206010051606 Necrotising colitis Diseases 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 239000006057 Non-nutritive feed additive Substances 0.000 description 1
- 208000035544 Nonketotic hyperglycinaemia Diseases 0.000 description 1
- YBGZDTIWKVFICR-JLHYYAGUSA-N Octyl 4-methoxycinnamic acid Chemical compound CCCCC(CC)COC(=O)\C=C\C1=CC=C(OC)C=C1 YBGZDTIWKVFICR-JLHYYAGUSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 206010034464 Periarthritis Diseases 0.000 description 1
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 208000004983 Phantom Limb Diseases 0.000 description 1
- 206010056238 Phantom pain Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- 206010036772 Proctalgia Diseases 0.000 description 1
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 1
- 206010037575 Pustular psoriasis Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 208000019155 Radiation injury Diseases 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 206010057071 Rectal tenesmus Diseases 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 102000007156 Resistin Human genes 0.000 description 1
- 108010047909 Resistin Proteins 0.000 description 1
- 206010038934 Retinopathy proliferative Diseases 0.000 description 1
- 208000006289 Rett Syndrome Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010039509 Scab Diseases 0.000 description 1
- 208000008765 Sciatica Diseases 0.000 description 1
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 201000010001 Silicosis Diseases 0.000 description 1
- 244000044822 Simmondsia californica Species 0.000 description 1
- 235000004433 Simmondsia californica Nutrition 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 206010040893 Skin necrosis Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 description 1
- 206010072005 Spinal pain Diseases 0.000 description 1
- 201000002661 Spondylitis Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 108700036932 Sulfite oxidase deficiency Proteins 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 108700012920 TNF Proteins 0.000 description 1
- 208000001106 Takayasu Arteritis Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010043189 Telangiectasia Diseases 0.000 description 1
- 208000000491 Tendinopathy Diseases 0.000 description 1
- 206010043255 Tendonitis Diseases 0.000 description 1
- 208000004760 Tenosynovitis Diseases 0.000 description 1
- 206010043269 Tension headache Diseases 0.000 description 1
- 208000008548 Tension-Type Headache Diseases 0.000 description 1
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- 239000003490 Thiodipropionic acid Substances 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 208000016620 Tourette disease Diseases 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- 206010048873 Traumatic arthritis Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 208000000558 Varicose Ulcer Diseases 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 206010047095 Vascular pain Diseases 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 208000010045 Wernicke encephalopathy Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- IJCWFDPJFXGQBN-RYNSOKOISA-N [(2R)-2-[(2R,3R,4S)-4-hydroxy-3-octadecanoyloxyoxolan-2-yl]-2-octadecanoyloxyethyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCCCCCCCCCCCC IJCWFDPJFXGQBN-RYNSOKOISA-N 0.000 description 1
- WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
- OCRUMFQGIMSFJR-FSAWCSQFSA-N [(2s,3s,4r,5r)-4-hydroxy-5-(hydroxymethyl)-3-[(z)-octadec-9-enoyl]oxy-2-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxolan-2-yl]methyl (z)-octadec-9-enoate Chemical compound O([C@@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@]1(COC(=O)CCCCCCC\C=C/CCCCCCCC)O[C@H](CO)[C@@H](O)[C@@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC OCRUMFQGIMSFJR-FSAWCSQFSA-N 0.000 description 1
- ALNZHGZKERXBKV-UHFFFAOYSA-N [2,5-dibromo-4-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC(Br)=C(CO)C=C1Br ALNZHGZKERXBKV-UHFFFAOYSA-N 0.000 description 1
- NTQJRWICDDWUOR-UHFFFAOYSA-N [2,5-dibromo-4-(methoxymethyl)phenyl]methanol Chemical compound COCC1=CC(Br)=C(CO)C=C1Br NTQJRWICDDWUOR-UHFFFAOYSA-N 0.000 description 1
- HVUMOYIDDBPOLL-XGKPLOKHSA-N [2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XGKPLOKHSA-N 0.000 description 1
- HMWUDZNSYLWLBM-UHFFFAOYSA-N [2-bromo-3-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=CC(CO)=C1Br HMWUDZNSYLWLBM-UHFFFAOYSA-N 0.000 description 1
- XJNNFZUOOPIFQC-UHFFFAOYSA-N [2-bromo-4-(3-phenylsulfanylindol-1-yl)phenyl]methanol Chemical compound C1=C(Br)C(CO)=CC=C1N1C2=CC=CC=C2C(SC=2C=CC=CC=2)=C1 XJNNFZUOOPIFQC-UHFFFAOYSA-N 0.000 description 1
- DOWLWLAADKJVCL-UHFFFAOYSA-N [2-bromo-4-(4-chlorophenyl)sulfanylphenyl]methanol Chemical compound C1=C(Br)C(CO)=CC=C1SC1=CC=C(Cl)C=C1 DOWLWLAADKJVCL-UHFFFAOYSA-N 0.000 description 1
- NSDBPRKMESEIJM-UHFFFAOYSA-N [2-bromo-4-(4-fluorophenyl)sulfanylphenyl]methanol Chemical compound C1=C(Br)C(CO)=CC=C1SC1=CC=C(F)C=C1 NSDBPRKMESEIJM-UHFFFAOYSA-N 0.000 description 1
- VGLJQNOKRSDBRW-UHFFFAOYSA-N [2-bromo-4-(4-methylphenyl)sulfanylphenyl]methanol Chemical compound C1=CC(C)=CC=C1SC1=CC=C(CO)C(Br)=C1 VGLJQNOKRSDBRW-UHFFFAOYSA-N 0.000 description 1
- BWWJHACUQVIUHX-UHFFFAOYSA-N [2-bromo-4-(4-methylsulfanylphenyl)sulfanylphenyl]methanol Chemical compound C1=CC(SC)=CC=C1SC1=CC=C(CO)C(Br)=C1 BWWJHACUQVIUHX-UHFFFAOYSA-N 0.000 description 1
- MAYUQGAVEZAZSK-UHFFFAOYSA-N [2-bromo-4-(4-phenylpiperazin-1-yl)phenyl]methanol Chemical compound C1=C(Br)C(CO)=CC=C1N1CCN(C=2C=CC=CC=2)CC1 MAYUQGAVEZAZSK-UHFFFAOYSA-N 0.000 description 1
- ANSJYXSNYFEYJQ-UHFFFAOYSA-N [2-bromo-4-(4-pyridin-2-ylpiperazin-1-yl)phenyl]methanol Chemical compound C1=C(Br)C(CO)=CC=C1N1CCN(C=2N=CC=CC=2)CC1 ANSJYXSNYFEYJQ-UHFFFAOYSA-N 0.000 description 1
- BQBHJJHJGMXEJI-UHFFFAOYSA-N [2-bromo-4-(4-pyrimidin-2-ylpiperazin-1-yl)phenyl]methanol Chemical compound C1=C(Br)C(CO)=CC=C1N1CCN(C=2N=CC=CN=2)CC1 BQBHJJHJGMXEJI-UHFFFAOYSA-N 0.000 description 1
- ALRHCSZLGXZSJA-UHFFFAOYSA-N [2-bromo-4-(5-chloro-3-phenylsulfanylindol-1-yl)phenyl]methanol Chemical compound C1=C(Br)C(CO)=CC=C1N1C2=CC=C(Cl)C=C2C(SC=2C=CC=CC=2)=C1 ALRHCSZLGXZSJA-UHFFFAOYSA-N 0.000 description 1
- CBOUIWUIMNKAEX-UHFFFAOYSA-N [2-bromo-4-(5-chloroindol-1-yl)phenyl]methanol Chemical compound C1=C(Br)C(CO)=CC=C1N1C2=CC=C(Cl)C=C2C=C1 CBOUIWUIMNKAEX-UHFFFAOYSA-N 0.000 description 1
- MWMRHQRVHHRJKG-UHFFFAOYSA-N [2-bromo-4-(5-methoxy-3-phenylsulfanylindol-1-yl)phenyl]methanol Chemical compound C12=CC(OC)=CC=C2N(C=2C=C(Br)C(CO)=CC=2)C=C1SC1=CC=CC=C1 MWMRHQRVHHRJKG-UHFFFAOYSA-N 0.000 description 1
- HNCGBLXBGUUGKE-UHFFFAOYSA-N [2-bromo-4-(5-methoxyindol-1-yl)phenyl]methanol Chemical compound C1=CC2=CC(OC)=CC=C2N1C1=CC=C(CO)C(Br)=C1 HNCGBLXBGUUGKE-UHFFFAOYSA-N 0.000 description 1
- BUMQWIASFCFLOW-UHFFFAOYSA-N [2-bromo-4-[4-(trifluoromethyl)phenoxy]phenyl]methanol Chemical compound C1=C(Br)C(CO)=CC=C1OC1=CC=C(C(F)(F)F)C=C1 BUMQWIASFCFLOW-UHFFFAOYSA-N 0.000 description 1
- YTGIXKGZVHSXLX-UHFFFAOYSA-N [2-bromo-4-[4-(trifluoromethyl)phenyl]sulfanylphenyl]methanol Chemical compound C1=C(Br)C(CO)=CC=C1SC1=CC=C(C(F)(F)F)C=C1 YTGIXKGZVHSXLX-UHFFFAOYSA-N 0.000 description 1
- OHXPYFUSSYWSAB-UHFFFAOYSA-N [2-bromo-5-[tert-butyl(dimethyl)silyl]oxyphenyl]methanol Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=C(Br)C(CO)=C1 OHXPYFUSSYWSAB-UHFFFAOYSA-N 0.000 description 1
- ISIUBPFNBPWXMF-UHFFFAOYSA-N [4-(4-cyanophenyl)sulfanylphenyl]boronic acid Chemical compound C1=CC(B(O)O)=CC=C1SC1=CC=C(C#N)C=C1 ISIUBPFNBPWXMF-UHFFFAOYSA-N 0.000 description 1
- KEDPCRXYKBYTOV-UHFFFAOYSA-N [4-bromo-3-(methoxymethoxymethyl)phenoxy]-tert-butyl-dimethylsilane Chemical compound COCOCC1=CC(O[Si](C)(C)C(C)(C)C)=CC=C1Br KEDPCRXYKBYTOV-UHFFFAOYSA-N 0.000 description 1
- KOHUATWNGBDXMV-UHFFFAOYSA-N [Mg]N Chemical class [Mg]N KOHUATWNGBDXMV-UHFFFAOYSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- RRUDCFGSUDOHDG-UHFFFAOYSA-N acetohydroxamic acid Chemical compound CC(O)=NO RRUDCFGSUDOHDG-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 231100000851 acute glomerulonephritis Toxicity 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 230000004658 acute-phase response Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000003919 adipocyte function Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229940040563 agaric acid Drugs 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 208000037883 airway inflammation Diseases 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 229960002459 alefacept Drugs 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000005237 alkyleneamino group Chemical group 0.000 description 1
- 125000005238 alkylenediamino group Chemical group 0.000 description 1
- 125000005530 alkylenedioxy group Chemical group 0.000 description 1
- 125000005529 alkyleneoxy group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 239000002160 alpha blocker Substances 0.000 description 1
- RGZSQWQPBWRIAQ-LSDHHAIUSA-N alpha-Bisabolol Natural products CC(C)=CCC[C@@](C)(O)[C@@H]1CCC(C)=CC1 RGZSQWQPBWRIAQ-LSDHHAIUSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229940124308 alpha-adrenoreceptor antagonist Drugs 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 229940113720 aminosalicylate Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 229960004238 anakinra Drugs 0.000 description 1
- 229940031955 anhydrous lanolin Drugs 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000003975 animal breeding Methods 0.000 description 1
- 239000012296 anti-solvent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 210000001188 articular cartilage Anatomy 0.000 description 1
- 125000005165 aryl thioxy group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 208000037979 autoimmune inflammatory disease Diseases 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 229960003872 benzethonium Drugs 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 150000001277 beta hydroxy acids Chemical class 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
- 229940036350 bisabolol Drugs 0.000 description 1
- HHGZABIIYIWLGA-UHFFFAOYSA-N bisabolol Natural products CC1CCC(C(C)(O)CCC=C(C)C)CC1 HHGZABIIYIWLGA-UHFFFAOYSA-N 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 208000019664 bone resorption disease Diseases 0.000 description 1
- 150000001638 boron Chemical class 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 235000010376 calcium ascorbate Nutrition 0.000 description 1
- 239000011692 calcium ascorbate Substances 0.000 description 1
- 229940047036 calcium ascorbate Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- BLORRZQTHNGFTI-ZZMNMWMASA-L calcium-L-ascorbate Chemical compound [Ca+2].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] BLORRZQTHNGFTI-ZZMNMWMASA-L 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 239000001913 cellulose Chemical class 0.000 description 1
- 229920002678 cellulose Chemical class 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 229940081733 cetearyl alcohol Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229960002242 chlorocresol Drugs 0.000 description 1
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 208000018912 cluster headache syndrome Diseases 0.000 description 1
- 239000011280 coal tar Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 235000017471 coenzyme Q10 Nutrition 0.000 description 1
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 1
- 229940110767 coenzyme Q10 Drugs 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 229940124301 concurrent medication Drugs 0.000 description 1
- 208000028831 congenital heart disease Diseases 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 229960000860 dapsone Drugs 0.000 description 1
- DIOQZVSQGTUSAI-NJFSPNSNSA-N decane Chemical compound CCCCCCCCC[14CH3] DIOQZVSQGTUSAI-NJFSPNSNSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000002074 deregulated effect Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 235000019304 dilauryl thiodipropionate Nutrition 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- SIYLLGKDQZGJHK-UHFFFAOYSA-N dimethyl-(phenylmethyl)-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethyl]ammonium Chemical compound C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 SIYLLGKDQZGJHK-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 229960000284 efalizumab Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000008387 emulsifying waxe Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 235000010350 erythorbic acid Nutrition 0.000 description 1
- 239000004318 erythorbic acid Substances 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 230000003890 fistula Effects 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 201000003444 follicular lymphoma Diseases 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000012254 genetic linkage analysis Methods 0.000 description 1
- 229910052732 germanium Inorganic materials 0.000 description 1
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
- 230000009229 glucose formation Effects 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 201000011205 glycine encephalopathy Diseases 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 229940091561 guaiac Drugs 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 208000007386 hepatic encephalopathy Diseases 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 230000003118 histopathologic effect Effects 0.000 description 1
- 238000011577 humanized mouse model Methods 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000003225 hyperhomocysteinemia Effects 0.000 description 1
- 208000023399 hyperprolinemia Diseases 0.000 description 1
- 208000034783 hypoesthesia Diseases 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000017306 interleukin-6 production Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- ZCYVEMRRCGMTRW-YPZZEJLDSA-N iodine-125 Chemical compound [125I] ZCYVEMRRCGMTRW-YPZZEJLDSA-N 0.000 description 1
- 229940044173 iodine-125 Drugs 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 229940026239 isoascorbic acid Drugs 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
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 230000003780 keratinization Effects 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 239000003410 keratolytic agent Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000037805 labour Diseases 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 235000019136 lipoic acid Nutrition 0.000 description 1
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 1
- 230000004130 lipolysis Effects 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000006742 locomotor activity Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- 229940067190 mentholatum Drugs 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000006263 metalation reaction Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- SJFNDMHZXCUXSA-UHFFFAOYSA-M methoxymethyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(COC)C1=CC=CC=C1 SJFNDMHZXCUXSA-UHFFFAOYSA-M 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 1
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
- 235000011929 mousse Nutrition 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 208000025113 myeloid leukemia Diseases 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 210000004457 myocytus nodalis Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- DIOQZVSQGTUSAI-UHFFFAOYSA-N n-butylhexane Natural products CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 208000004995 necrotizing enterocolitis Diseases 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000019079 negative regulation of cytokine secretion Effects 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 1
- 210000000885 nephron Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000009251 neurologic dysfunction Effects 0.000 description 1
- 208000015015 neurological dysfunction Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000012875 nonionic emulsifier Substances 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 1
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
- 229960001679 octinoxate Drugs 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 208000002865 osteopetrosis Diseases 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 210000004197 pelvis Anatomy 0.000 description 1
- 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000003209 petroleum derivative Substances 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 238000001126 phototherapy Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 229940093625 propylene glycol monostearate Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- FGVVTMRZYROCTH-UHFFFAOYSA-N pyridine-2-thiol N-oxide Chemical compound [O-][N+]1=CC=CC=C1S FGVVTMRZYROCTH-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 229960002026 pyrithione Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 201000002793 renal fibrosis Diseases 0.000 description 1
- 208000032253 retinal ischemia Diseases 0.000 description 1
- 150000004492 retinoid derivatives Chemical class 0.000 description 1
- 229960003471 retinol Drugs 0.000 description 1
- 235000020944 retinol Nutrition 0.000 description 1
- 239000011607 retinol Substances 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 201000000980 schizophrenia 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
- 230000003248 secreting effect Effects 0.000 description 1
- VIDTVPHHDGRGAF-UHFFFAOYSA-N selenium sulfide Chemical compound [Se]=S VIDTVPHHDGRGAF-UHFFFAOYSA-N 0.000 description 1
- 229960005265 selenium sulfide Drugs 0.000 description 1
- 201000001223 septic arthritis Diseases 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 210000001599 sigmoid colon Anatomy 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- CBXWGGFGZDVPNV-UHFFFAOYSA-N so4-so4 Chemical compound OS(O)(=O)=O.OS(O)(=O)=O CBXWGGFGZDVPNV-UHFFFAOYSA-N 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 235000011071 sorbitan monopalmitate Nutrition 0.000 description 1
- 239000001570 sorbitan monopalmitate Substances 0.000 description 1
- 229940031953 sorbitan monopalmitate Drugs 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 235000011078 sorbitan tristearate Nutrition 0.000 description 1
- 239000001589 sorbitan tristearate Substances 0.000 description 1
- 229960004129 sorbitan tristearate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 201000005671 spondyloarthropathy Diseases 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940098760 steareth-2 Drugs 0.000 description 1
- 229940100458 steareth-21 Drugs 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 229940012831 stearyl alcohol Drugs 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 125000005864 sulfonamidyl group Chemical group 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LFQDNHWZDQTITF-UHFFFAOYSA-N tavaborole Chemical compound FC1=CC=C2B(O)OCC2=C1 LFQDNHWZDQTITF-UHFFFAOYSA-N 0.000 description 1
- 208000009056 telangiectasis Diseases 0.000 description 1
- 206010043207 temporal arteritis Diseases 0.000 description 1
- 201000004415 tendinitis Diseases 0.000 description 1
- 208000012271 tenesmus Diseases 0.000 description 1
- 239000004250 tert-Butylhydroquinone Substances 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 235000019281 tert-butylhydroquinone Nutrition 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- XAGUNWDMROKIFJ-UHFFFAOYSA-J tetrapotassium;2-[2-[[8-[bis(carboxylatomethyl)amino]-6-methoxyquinolin-2-yl]methoxy]-n-(carboxylatomethyl)-4-methylanilino]acetate Chemical compound [K+].[K+].[K+].[K+].C1=CC2=CC(OC)=CC(N(CC([O-])=O)CC([O-])=O)=C2N=C1COC1=CC(C)=CC=C1N(CC([O-])=O)CC([O-])=O XAGUNWDMROKIFJ-UHFFFAOYSA-J 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 229960002663 thioctic acid Drugs 0.000 description 1
- 235000019303 thiodipropionic acid Nutrition 0.000 description 1
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical class SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 230000009723 vascular congestion Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 208000009935 visceral pain Diseases 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- 229960001296 zinc oxide Drugs 0.000 description 1
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/69—Boron compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/08—Antibacterial agents for leprosy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/027—Organoboranes and organoborohydrides
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Virology (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Pulmonology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Communicable Diseases (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Ophthalmology & Optometry (AREA)
- Obesity (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
Description
本出願は、2006年8月29日出願の米国仮特許出願第60/823,888号明細書、及び2006年2月16日出願の同第60/774,532号明細書に対する優先権を主張するものであり、これらはあらゆる目的のために全体として参照により本明細書に援用される。
不規則な炎症は、広範なヒト疾患における主要素である。変性障害の罹患者は、その血液中に過剰なレベルの炎症誘発性調節因子をしばしば呈する。そのような炎症誘発性調節因子の1つのタイプは、IL−1α、β、IL−2、IL−3、IL−6、IL−7、IL−9、IL−12、IL−17、IL−18、IL−23、TNF−α、LT、LIF、オンコスタチン、及びIFNc1α、β、γを含むサイトカインである。
, Int J Clin Pract, Suppl 10-17,(2003);Haugeberg, G., Curr Opin Rheumatol, 15: 469-475,(2003);Tanaka, Y., J Bone Miner Metab, 21: 61-66,(2003);Williams, J. D., Clin Exp Dermatol, 27: 585-590,(2002))。かなり進行した段階の疾患のなかには、生命にかかわるものもあり得る。いくつかの方法論がそのような炎症性疾患の治療に利用できるが、効力が不足していること及び付随する薬物関連副作用から明らかな通り、結果は概して不十分なものである。
炎症性腸疾患(IBD)には、クローン病(CD)及び潰瘍性大腸炎(UC)が含まれ、これらは両者とも、世界各地で発生頻度が高まっている特発性慢性疾患である。米国内では、毎年600,000人超が罹患している。IBDは、小腸、大腸、又はその両方に関与することができる。CDは胃腸管の任意の部分を冒し得るが、遠位の小腸及び結腸を冒す頻度が最も高い。CDでは、直腸は免れるか、あるいは直腸周囲でドレナージを伴って炎症又は感染症が引き起こされるかのいずれかである。UCは通常、しばしば直腸を始端とする大腸下部に潰瘍を引き起こす。症状は様々だが、下痢、発熱、及び疼痛を含むことができる。持続性UC患者は結腸癌に罹るリスクが高い。感染及び免疫の作用機序は提言されているがIBDの原因はいまだ分かっていないため、現在のところ満足のいく治療はない。IBD治療は、従来ではコルチコステロイド、アミノサリチル酸塩、及び標準的な免疫抑制剤、例えばアザチオプリン(6−メルカプトプリン)、メトトレキサート、及びシクロスポリンなどを用いて炎症症状を調節することを目的とする。これらのなかで、唯一の疾患を軽減させる治療薬は、免疫抑制剤のアザチオプリン及びメトトレキサートであるが、これらは両方とも作用の発現が遅く、中等度の効力しかない。長期の治療により、肝障害(線維症又は硬変)及び骨髄抑制が引き起こされ得る。患者はしばしば、そのような治療に不応性となる。他の治療法は単に症状に対処するに過ぎない(Rutgeerts, P. A, J Gastroenterol Hepatol, 17 Suppl: S176-185(2002);Rutgeerts, P., Aliment Pharmacol Ther, 17: 185-192(2003))。
乾癬は、最も一般的な免疫仲介慢性皮膚疾患の1つであり、異なる状態及び様々な重症度レベルで生じ、米国では人口の約2%すなわち450万人超が罹患しており、そのうち150万人がこの疾患の中程度から重度の状態であると見られる。10〜30%の乾癬患者は、関節周囲の骨及び結合組織に損傷を与える関節炎−乾癬性関節炎の状態にも罹る。乾癬は、鱗状の白色形成物で覆われた斑状の盛り上がった赤い皮膚として現れる。乾癬は、吹き出物のような(膿疱性乾癬)、又は真っ赤になった(紅皮症)外見も有し得る。乾癬は、激しいかゆみ及び灼熱感も引き起こし得る。患者は、身体的に加え精神的にも苦しむ。現在、局所治療、光線療法、及び全身的な適用を含むいくつかの手法が、乾癬の治療に利用できる。しかしながら、これらは概して疾患の抑制及び疾患の軽減に過ぎないと考えられ、いずれも治癒的ではない。さらに、多くの治療は、美容的に望ましくないか、長期使用に不都合であるか、あるいは重大な毒性が付随するかのいずれかである。
関節リウマチ(RA)は、別の厄介な炎症性障害の例を示している。これは、関節及び/又は他の内臓器官の内膜(滑膜)における慢性的な炎症を特徴とする典型的な慢性炎症関連疾患である。炎症細胞は浸潤して、骨及び軟骨に損傷をも与え得る。冒された関節はその形状及び配列を喪失し、結果として動きを失う。RA患者は、関節における疼痛、こわばり感、温熱感、発赤及び腫脹、並びに発熱、疲労感、及び貧血といった他の全身症状を有する。米国では現在、人口の約1%すなわち210万人が罹患しており、そのうち女性(150万人)が男性(60万人)より多い。RAの病理は完全には解明されていないが、作用機序としては不適切な免疫反応の連鎖が想定されている。従来の治療は残念なことに、RAに対し効果がない(Bessis, N., J Gene Med, 4: 581-591,(2002))(29)。この疾患は、1950年代から使用されるコルチコステロイド及び非ステロイド性抗炎症薬(NSAID)を含む対症薬物療法には完全には応答しない。また、これらの薬物療法は、重篤な有害作用のリスクを伴う。メトトレキサート(MTX)などの疾患修飾性抗リウマチ薬(DMARD)の治療効果はしばしば一貫性がなく、一時的なものである。
多発性硬化症(MS)は、米国で350,000〜500,000人が診断を受けている自己免疫疾患である。複数の領域にわたる炎症並びに脳及び脊髄におけるミエリンの喪失が、この疾患を示す。MS患者は、ミエリン喪失の部位及び範囲に応じて様々な程度の神経機能障害を呈する。MSの一般的な症状には、疲労感、脱力感、痙縮、平衡障害、膀胱及び腸の問題、しびれ感、視力喪失、振戦及び鬱が含まれる。現行のMSの治療は症状を緩和するか、あるいは障害の進行を遅延させるのみであり、いくつかの新しいMS治療は、幹細胞移植及び遺伝子治療を含め現状維持的なものである(Fassas, A., Blood Rev, 17: 233-240,(2003);Furlan, R., Curr Pharm Des, 9: 2002-2008,(2003))。抗TNF抗体は実験的な自己免疫性脳脊髄炎(EAE)では保護効果を示すが、MS患者においては疾患を緩和し、これはTNF−α単独での阻害が十分ではないことを示唆する(Ghezzi, P., Neuroimmunomodulation, 9: 178-182,(2001))。
アルツハイマー病(AD)及びパーキンソン病(PK)は、最も一般的な2つの神経変性障害である。ADは、人の日常的な活動を行う能力に深刻な影響を及ぼす。ADは、思考、記憶、及び言語を司る脳の各部を冒す。通常は60歳を過ぎた4百万人のアメリカ人がADに罹患していると推定される。
第1の態様において、本発明は、治療上有効量の本明細書に記載される化合物をヒト又は動物に投与することを含む、ヒト又は動物における炎症関連疾患を治療又は予防する方法を提供する。例示的実施形態において、本化合物はC1〜C100から選択されるメンバーである。例示的実施形態において、本化合物は、式Iによる構造を有する:
I.定義及び略称
本明細書で使用される略称は、概してその化学及び生物学分野内での慣用的な意味を有する。
本発明は、炎症誘発性サイトカイン発現及び/又は抗炎症発現の低減に関連する炎症関連疾患の治療方法に関する。本発明の方法は、そのような治療を必要とするヒト又は動物に1種以上の本発明の化合物を単独であるいは医薬製剤の一部として投与することを伴う。好ましい実施形態において、投与される化合物は、炎症誘発性サイトカイン発現を阻害するか、及び/又は抗炎症性サイトカインを刺激することにより炎症関連疾患を治療するのに十分であるが、サイクリン依存性キナーゼ(CDK)を実質的に阻害するには不十分な量である。
第1の態様において、本発明は、ここに記載される化合物を提供する。例示的実施形態において、本化合物は、式Iによる構造を有する:
H、メチル、
本発明は、対象の新規組成物も提供する。例示的実施形態において、対象の組成物は本明細書に記載される。別の例示的実施形態において、対象の組成物は、式IIによる構造を有する:
本方法は、限定するものではないが、本発明の化合物で炎症関連疾患を治療することを含むことが理解されなければならない。
本発明の医薬製剤は、選択された投与経路に適合する様々な形態をとることができる。当業者は、本明細書に記載される化合物を組み込む非毒性医薬製剤を調製するために用いることができる様々な合成方法を認識している。当業者は、本発明の化合物の溶媒和物を調製するために使用することができる多種多様な非毒性の薬学的に許容可能な溶媒、例えば、水、エタノール、プロピレングリコール、鉱油、植物油、及びジメチルスルホキシド(DMSO)などを認識している。
好ましい実施形態において、本発明の方法は、本明細書に記載される化合物の局所適用を通じて用いられることで使用することができる。
以下は、本発明の局所医薬製剤に添加することができる化粧品及び医薬品の例である。以下の薬剤は既知の化合物であり、市販品として容易に入手できる。
本局所製剤における使用に好ましい化合物は、一定の薬理学的特性を有する。そのような特性には、限定するものではないが、低毒性、低い血清タンパク質結合性、及び所望のインビトロ及びインビボ半減期が含まれる。アッセイを使用してこれらの所望の薬理学的特性を予測することができる。バイオアベイラビリティを予測するために使用されるアッセイは、Caco−2細胞単層を含むヒト腸の細胞単層を横断する輸送を伴う。血清タンパク質結合性は、アルブミン結合アッセイから予測することができる。そのようなアッセイは、Oravcovaら(1996, J. Chromat. B677: 1-27)によるレビューに記載されている。化合物の半減期は、化合物の投薬頻度に反比例する。化合物のインビトロ半減期は、Kuhnz及びGleschen(Drug Metabolism and Disposition, (1998) 第26巻, 1120-1127頁)により記載されるようなクロソーム半減期のアッセイから予測することができる。
本発明の方法で使用される任意の化合物について、治療上有効な用量は、本明細書に記載されるとおり、最初は細胞培養物アッセイから推定できる。例えば、動物モデルにおいて、細胞培養物中で測定されるときのEC50(50%の上昇に有効な用量)を含む血中濃度範囲、すなわち、細菌細胞成長の最高値の半分の阻害を達成する試験化合物濃度を実現するような用量が処方することができる。そのような情報を使用して、ヒトにおいて有用な用量をより正確に決定することができる。
プロトンNMRをVarian AS 300分光計で記録し、化学シフトをテトラメチルシランから低磁場側へのδ(ppm)として報告する。質量スペクトルはMicromass Quattro IIで測定される。
1からの3の調製
1.1 カルボン酸の還元
窒素下の無水THF(70mL)中の1(23.3mmol)の溶液にBH3THF溶液(1.0M、55mL、55mmol)を0℃で滴下しながら添加し、反応混合物を一晩室温で攪拌した。次に混合物を氷浴で再冷却し、MeOH(20mL)を滴下しながら添加して過剰なBH3を分解した。得られた混合物を気泡が放出されなくなるまで攪拌し、次に10%のNaOH(10mL)を添加した。混合物を濃縮して残渣を水(200mL)と混合し、EtOAcで抽出した。回転蒸発の残渣をシリカゲルによるフラッシュカラムクロマトグラフィーで精製すると、20.7mmolの3が得られた。
上記の方法により調製された例示的構造化合物3を以下に提供する。
1H NMR(300MHz,DMSO−d6):δ7.57(d,J=8.7Hz,1H),7.50〜7.49(m,1H),7.28〜7.24(m,1H),5.59(t,J=6.0Hz,1H)及び4.46(d,J=6.0Hz,2H)ppm。
1H NMR(300MHz,DMSO−d6):δ7.42(d,J=8.7Hz,1H),7.09(d,J=2.4Hz,1H),6.77(dd,J1=3Hz,J2=3Hz,1H),5.43(t,J=5.7Hz,1H),4.44(d,J=5.1Hz,2H),3.76(s,3H)。
2からの3の調製
2.1.アルデヒドの還元
メタノール(30mL)中の2(Z=H、10.7mmol)の溶液に水素化ホウ素ナトリウム(5.40mol)を添加し、混合物を室温で1時間攪拌した。水を添加し、混合物を酢酸エチルで抽出した。有機層を塩水で洗浄し、無水硫酸ナトリウムで乾燥させた。減圧下で溶媒を除去すると、9.9mmolの3が得られた。
上記の方法により調製された例示的構造化合物3を以下に提供する。
1H−NMR(300MHz,CDCl3)δ(ppm)2.00(br s,1H),4.75(s,2H),6.88(dd,J=8.5,2.9Hz,1H),7.02(d,J=8.8Hz,1H),7.26(d,J=2.6Hz,1H),7.56(d,J=8.5Hz,1H),7.62(d,J=8.8Hz,2H)。
1H NMR(300MHz,DMSO−d6):δ7.83(d,2H),7.58(d,1H),7.39(d,1H),7.18(dd,1H),7.11(d,2H),5.48(t,1H)及び4.50(d,2H)ppm。
融点50〜53℃。MS(ESI+):m/z=252(M+1)。HPLC:254nmで99.7%純度及び220nmで99.0%。1H NMR(300MHz,DMSO−d6):δ7.80(d,2H),7.37(d,1H),7.04(d,2H),6.98〜6.93(m,2H),5.27(d,1H),5.03(q,1H),2.95〜2.85(m,1H),2.75〜2.64(m,1H),2.39〜2.29(m,1H)及び1.85〜1.74(m,1H)ppm。
1H−NMR(300MHz,CDCl3)δ(ppm)0.20(s,6H),0.98(s,9H),4.67(br s,1H),6.65(dd,J=8.2,2.6Hz,1H),6.98(d,J=2.9Hz,1H),7.36(d,J=8.8Hz,1H)。
3からの4の調製
3.1 保護アルキル化
化合物3(20.7mmol)をCH2Cl2(150mL)中に溶解し、氷浴で0℃に冷却した。窒素下のこの溶液にN,N−ジ−イソプロピルエチルアミン(5.4mL、31.02mmol、1.5当量)及びクロロメチルメチルエーテル(2mL、25.85mmol、1.25当量)を順に添加した。反応混合物を一晩室温で攪拌し、NaHCO3飽和水、次にNaCl飽和水で洗浄した。回転蒸発後の残渣をシリカゲルによるフラッシュカラムクロマトグラフィーで精製すると、17.6mmolの4が得られた。
上記の方法により調製された例示的構造化合物4を以下に提供する。
1H NMR(300MHz,DMSO−d6):δ7.63(d,J=8.7Hz,1H),7.50(dd,J=2.4&0.6Hz,1H),7.32(dd,J=8.4&2.4Hz,1H),4.71(s,2H),4.53(s,2H)及び3.30(s,3H)ppm。
1H−NMR(300.058MHz,CDCl3)δppm 1.43(d,J=6.5Hz,3H),3.38(s,3H),4.55(d,J=6.5Hz,1H),4.63(d,J=6.5Hz,1H),5.07(q,J=6.5Hz,1H),6.85(m,1H),7.25(dd,J=9.7,2.6Hz,1H),7.46(dd,J=8.8,5.3Hz,1H)。
1H−NMR(300.058MHz,CDCl3)δppm 3.04(t,J=6.7Hz,2H),3.31(s,3H),3.77(t,J=6.7Hz,2H),4.62(s,2H),6.82(td,J=8.2,3.2Hz,1H),7.04(dd,J=9.4,2.9Hz,1H),7.48(dd,J=8.8,5.3Hz,1H)。
1H−NMR(300.058MHz,CDCl3)δppm 3.42(s,3H),4.57(d,J=1.2Hz,2H),4.76(s,2H),7.3〜7.5(m,2H)。
1H−NMR(300.058MHz,CDCl3)δppm 3.43(s,3H),4.65(s,2H),4.80(s,2H),7.43(dd,J=8.2,4.1Hz,1H),7.66(d,J=8.2Hz,1H),7.82(d,J=4.1Hz,1H)。
1H NMR(300MHz,DMSO−d6):δ7.48(dd,J1=1.2Hz,J2=1.2Hz,1H),7.05(d,J=2.7Hz,1H),6.83(dd,J1=3Hz,J2=3Hz,1H),4.69(d,J=1.2Hz,2H),4.5(s,2H),3.74(d,J=1.5Hz,3H),3.32(d,J=2.1Hz,3H)ppm。
1H NMR(300MHz,DMSO−d6):δ7.70〜7.67(m,1H),7.25〜7.09(m,6H),6.96〜6.93(m,2H),4.61(d,1H),4.48(d,1H),3.36〜3.26(m,2H),3.22(s,3H)及び1.63(s,3H)ppm。
1H−NMR(300MHz,CDCl3)δ(ppm)3.43(s,3H),4.74(s,2H),4.76(d,J=2.1Hz,2H),7.05(t,J=9.1Hz,1H),7.18(td,J=8.2,5.9Hz,1H),7.40(d,J=8.2Hz,1H)。
1H NMR(300MHz,DMSO−d6):δ7.84(d,2H),7.56(d,1H),7.44(d,1H),7.19〜7.12(m,3H),4.69(s,2H),4.56(s,2H)及び3.31(s,3H)ppm。
1H−NMR(300MHz,CDCl3)δ(ppm)0.19(s,6H),0.98(s,9H),3.43(s,3H),4.59(s,2H),4.75(s,2H),6.64(dd,J=8.5,2.9Hz,1H),6.98(d,J=2.9Hz,1H),7.36(d,J=8.5Hz,1H)。
1H−NMR(300MHz,CDCl3)δ(ppm)3.41(s,3H),4.64(s,2H),4.76(s,2H),6.8〜6.9(m,2H),7.16(td,J=7.6,0.9Hz,1H),7.28(d,J=2.9Hz,1H),7.49(ddd,J=8.8,7.6,1.8Hz,1H),7.56(d,J=8.5Hz,1H),7.67(dd,J=7.9,1.8Hz,1H)。
1H−NMR(300MHz,CDCl3)δ(ppm)3.40(s,3H),4.62(s,2H),4.74(s,2H),6.80(dd,J=8.8,2.9hz,1H),7.01(d,J=8.5Hz,2H),7.12(t,J=7.9Hz,1H),7.19(d,J=2.9hz,1H),7.35(t,J=7.6Hz,2H),7.48(d,J=8.5Hz,1H)。
5を介した4からのIの調製
4.1 メタル化及びボロニル化(boronylation)
−78℃、窒素下で無水THF(80mL)中の4(17.3mmol)の溶液にtert−BuLi又はn−BuLi(11.7mL)を滴下しながら添加すると、溶液は褐色となった。次に、B(OMe)3(1.93mL、17.3mmol)を一度に注入し、冷浴を取り外した。混合物は30分間攪拌しながら徐々に温めた後、水浴中で2時間攪拌した。6NのHCl(6mL)の添加後、混合物を一晩室温で攪拌したところ、約50%の加水分解が生じたことがTLC分析により示された。溶液を回転蒸発させ、残渣をMeOH(50mL)及び6NのHCl(4mL)中に溶解させた。この溶液を1時間還流すると、加水分解の完了がTLC分析により示された。回転蒸発により生じた残渣をEtOAc中に溶解させ、水で洗浄して乾燥させた後、蒸発させた。粗生成物をシリカゲルによるフラッシュカラムクロマトグラフィーで精製すると、80%純度の固形物が得られた。固形物をヘキサンで洗浄してさらに精製すると、7.2mmolのIが得られた。
例示的構造化合物Iについての分析データを以下に提供する。
融点142〜150℃。MS(ESI):m/z=169(M+1,ポジティブ)及び167(M−1,ネガティブ)。HPLC(220nm):99%純度。1H NMR(300MHz,DMSO−d6):δ9.30(s,1H),7.71(d,J=7.8Hz,1H),7.49(s,1H),7.38(d,J=7.8Hz,1H)及び4.96(s,2H)ppm。
融点83〜86℃。MS(ESI):m/z=135(M+1,ポジティブ)及び133(M−1,ネガティブ)。HPLC(220nm):95.4%純度。1H NMR(300MHz,DMSO−d6):δ9.14(s,1H),7.71(d,J=7.2Hz,1H),7.45(t,J=7.5Hz,1H),7.38(d,J=7.5Hz,1H),7.32(t,J=7.1Hz,1H)及び4.97(s,2H)ppm。
1H−NMR(300MHz,DMSO−d6)δppm 1.37(d,J=6.4Hz,3H),5.17(q,J=6.4Hz,1H),7.14(m,1H),7.25(dd,J=9.7,2.3Hz,1H),7.70(dd,J=8.2,5.9Hz,1H),9.14(s,1H)。
1H−NMR(300MHz,DMSO−d6)δppm 2.86(t,J=5.9Hz,2H),4.04(t,J=5.9Hz,2H),7.0〜7.1(m,2H),7.69(dd,J=8.2,7.2Hz,1H),8.47(s,1H)。
1H−NMR(300MHz,DMSO−d6)δppm 4.94(s,2H),7.50(dd,J=10.7,6.8Hz,1H),7.62(dd,J=9.7,8.2Hz,1H),9.34(s,1H)。
1H−NMR(300MHz,DMSO−d6)δppm 5.03(s,2H),7.76(d,J=8.2Hz,1H),7.89(d,J=8.2Hz,1H),7.90(s,1H),9.53(s,1H)。
融点102〜104℃。MS ESI:m/z=165.3(M+1)及び162.9(M−1)。1H NMR(300MHz,DMSO−d6):δ8.95(s,1H),7.60(d,J=8.1Hz,1H),6.94(s,1H),6.88(d,J=8.1Hz,1H),4.91(s,2H),3.77(s,3H)ppm。
融点124〜128℃。MS ESI:m/z=148.9(M+1)及び146.9(M−1)。1H NMR(300MHz,DMSO−d6):δ9.05(s,1H),7.58(d,J=7.2Hz,1H),7.18(s,1H),7.13(d,J=7.2Hz,2H),4.91(s,2H),2.33(s,3H)ppm。
MS:m/z=163(M−1、ESI−)。1H NMR(300MHz,DMSO−d6):δ9.08(s,1H),7.64(d,1H),7.33(s,1H),7.27(d,1H),5.23(t,1H),4.96(s,2H),4.53(d,2H)ppm。
融点110〜114℃。MS ESI:m/z=150.9(M−1)。1H NMR(300MHz,DMSO−d6):δ9.20(s,1H),7.73(dd,J1=6Hz,J2=6Hz,1H),7.21(m,1H),7.14(m,1H),4.95(s,2H)ppm。
融点139〜143℃。MS ESI:m/z=184.9(M+1)。1H NMR(300MHz,DMSO−d6):δ9.21(s,1H),8.28(dd,J1=6.9Hz,J2=0.6Hz,1H),7.99(d,J=8.1Hz,1H),7.95(d,J=7.5Hz,1H),7.59〜7.47(m,3H),5.09(s,2H)ppm。
1H−NMR(300MHz,DMSO−d6):δppm 5.00(s,2H),7.45(d,J=5.0Hz,1H),8.57(d,J=5.3Hz,1H),8.91(s,1H),9.57(s,1H)。ESI−MS m/z 134(M−H)−,C6H6BNO2=135。
融点110〜117.5℃。MS(ESI):m/z=151(M−1,ネガティブ)。HPLC(220nm):100%純度。1H NMR(300MHz,DMSO−d6):δ9.29(s,1H),7.46〜7.41(m,2H),7.29(td,1H)及び4.95(s,2H)ppm。
MS(ESI):m/z=239(M+1,ポジティブ)。HPLC:220nmで99.5%純度及び254nmで95.9%。1H NMR(300MHz,DMSO−d6):δ8.89(s,1H),7.49〜7.40(m,3H),7.25〜7.19(m,1H),7.09〜7.05(m,3H),6.96〜6.94(m,2H),3.10(d,1H),3.00(d,1H)及び1.44(s,3H)ppm。
MS(ESI+):m/z=225(M+1)。HPLC:220nmで93.4%純度。1H NMR(300MHz,DMSO−d6):δ9.08(s,1H),7.63(dd,1H),7.43(t,1H),7.35〜7.14(m,7H),5.38(dd,1H),3.21(dd,1H)及び2.77(dd,1H)ppm。
1H−NMR(300MHz,DMSO−d6)δ(ppm)5.06(s,2H),7.26(ddd,J=9.7,7.9,0.6Hz,1H),7.40(td,J=8.2,4.7Hz,1H),7.55(d,J=7.0Hz,1H),9.41(s,1H)。
1H−NMR(300MHz,DMSO−d6)δppm 4.95(s,2H),7.08(dd,J=7.9,2.1Hz,1H),7.14(d,J=8.8Hz,1H),7.15(d,J=2.1Hz,1H),7.78(d,J=7.9Hz,1H),7.85(d,J=9.1Hz,2H),9.22(s,1H)。
融点148〜151℃。MS:m/z=252(M+1)(ESI+)及びm/z=250(M−1)(ESI−)。HPLC:254nmで100%純度及び220nmで98.7%。1H NMR(300MHz,DMSO−d6):δ9.26(s,1H),7.82(d,2H),7.50(d,1H),7.39(d,1H),7.26(dd,1H),7.08(d,2H)及び4.99(s,2H)ppm。
融点146〜149℃。MS:m/z=252(M+1)(ESI+)及びm/z=250(M−1)(ESI−)。HPLC:254nmで100%純度及び220nmで97.9%。1H NMR(300MHz,DMSO−d6):δ9.21(s,1H),7.60〜7.54(m,2H),7.50〜7.45(m,2H),7.34〜7.30(m,2H),7.23(dd,1H)及び4.98(s,2H)ppm。
融点119〜130℃。MS:m/z=261(M+1)(ESI+)及びm/z=259(M−1)(ESI−)。HPLC:254nmで100%純度及び220nmで98.9%。1H NMR(300MHz,DMSO−d6):δ9.18(s,1H),7.45〜7.41(m,3H),7.29(d,1H),7.19(dd,1H),7.01(d,2H)及び4.96(s,2H)ppm。
融点95〜99℃。MS:m/z=227(M+1)(ESI+)及びm/z=225(M−1)(ESI−)。HPLC:254nmで100%純度及び220nmで98.4%。1H NMR(300MHz,DMSO−d6):δ9.17(s,1H),7.43〜7.35(m,3H),7.28(s,1H),7.19〜7.09(m,2H),6.99(d,2H)及び4.96(s,2H)ppm。
1H−NMR(300MHz,DMSO−d6)δ(ppm)4.90(s,2H),5.25(s,2H),6.98(dd,J=7.9,2.1Hz,1H),7.03(d,J=1.8Hz,1H),7.62(d,J=7.9Hz,1H),7.64(d,J=8.5Hz,2H),7.86(d,J=8.5Hz,1H),9.01(s,1H)。
1H−NMR(300MHz,DMSO−d6)δ(ppm)4.95(s,2H),7.0〜7.2(m,3H),7.32(td,J=7.6,1.2Hz,1H),7.68(ddd,J=9.1,7.6,1.8Hz,1H),7.77(d,J=7.9Hz,1H),7.91(dd,J=7.9,1.8Hz,1H)。
1H−NMR(300MHz,DMSO−d6)δ(ppm)4.91(s,2H),6.94(s,1H),6.96(d,J=8.8Hz,1H),7.05(d,J=7.6Hz,2H),7.17(t,J=7.3Hz,1H),7.41(t,J=7.3Hz,2H),7.70(d,J=8.5Hz,1H),9.11(s,1H)。
1H−NMR(300MHz,DMSO−d6)δ(ppm)1.08(br s,6H),3.1〜3.5(m,4H),4.93(s,2H),7.0〜7.1(m,4H),7.37(d,J=8.5Hz,2H),7.73(d,J=7.9Hz,1H),9.15(s,1H)。
1H−NMR(300MHz,DMSO−d6)δ(ppm)3.3〜3.7(m,8H),4.93(s,2H),7.0〜7.1(m,4H),7.44(d,J=8.8Hz,2H),7.73(d,J=7.9Hz,1H),9.16(s,1H)。
1H−NMR(300MHz,DMSO−d6)δ(ppm)4.97(s,2H),7.13(dd,J=7.9,2.1Hz,1H),7.21(d,J=1.5Hz,1H),7.43(dd,J=8.8,2.6Hz,1H),7.81(d,J=7.9Hz,1H),7.82(d,J=2.6Hz,1H),8.11(d,J=8.5Hz,1H),9.26(s,1H)。
出発物質2を得るための4−フルオロベンゾニトリルと置換フェノールとの間のカップリング反応については、Igarashi, S.; et al. Chemical & Pharmaceutical Bulletin (2000), 48(11), 1689-1697を参照のこと。
出発物質2を得るための4−フルオロベンゾニトリルと置換フェノールとの間のカップリング反応については、Igarashi, S.; et al. Chemical & Pharmaceutical Bulletin (2000), 48(11), 1689-1697を参照のこと。
出発物質2を得るための3−フルオロベンゾニトリルと置換フェノールとの間のカップリングについては、Li, F. et al., Organic Letters (2003), 5(12), 2169-2171にある。
エタノール(10mL)中のC17(430mg、1.71mmol)で得られた5−(4−シアノフェノキシ)−1−ヒドロキシ−2,1−ベンゾオキサボロールの溶液に6mol/Lの水酸化ナトリウム(2mL)を添加し、混合物を3時間還流した。塩酸(6mol/L、3mL)を添加し、混合物を酢酸エチルで抽出した。有機層を塩水で洗浄して無水硫酸ナトリウムで乾燥させた。溶媒を減圧下で除去し、残渣をシリカゲルカラムクロマトグラフィー(酢酸エチル)による精製後にジイソプロピルエーテルを用いて粉砕すると、標的化合物(37mg、8%)が得られた。
N,N−ジメチルホルムアミド(5mL)中の5−(4−シアノフェノキシ)−1−ヒドロキシ−2,1−ベンゾオキサボロール(200mg、0.797mmol)、ナトリウムアジド(103mg、1.59mmol)、及び塩化アンモニウム(85mg、1.6mmol)の混合物を80℃で2日間攪拌した。水を添加し、混合物を酢酸エチルで抽出した。有機層を水及び塩水で洗浄し、無水硫酸ナトリウムで乾燥させた。溶媒を減圧下で除去し、残渣をシリカゲルカラムクロマトグラフィー(酢酸エチル)による精製後に酢酸エチルを用いて粉砕すると、標的化合物(55mg、23%)が得られた。
6を介した2からのIの調製
5.1 触媒的ボロニル化、還元、及び環化
1,4−ジオキサン(40mL)中の2(10.0mmol)、ビス(ピナコラート)ジボロン(2.79g、11.0mmol)、PdCl2(dppf)(250mg、3 mol%)、及び酢酸カリウム(2.94g、30.0mmol)の混合物を80℃で一晩攪拌した。水を添加し、混合物を酢酸エチルで抽出した。有機層を塩水で洗浄し、無水硫酸ナトリウムで乾燥させた。溶媒を減圧下で除去した。粗生成物をテトラヒドロフラン(80mL)中に溶解させた後、過ヨウ素酸ナトリウム(5.56g、26.0mmol)を添加した。室温で30分間攪拌後、2NのHCl(10mL)を添加し、混合物を室温で一晩攪拌した。水を添加し、混合物を酢酸エチルで抽出した。有機層を塩水で洗浄して無水硫酸ナトリウムで乾燥させた。溶媒を減圧下で除去し、残渣をエーテルで処理すると6.3mmolの対応するボロン酸が得られた。メタノール(5mL)中の得られたボロン酸(0.595mmol)の溶液に水素化ホウ素ナトリウム(11mg、0.30mmol)を添加し、混合物を室温で1時間攪拌した。水を添加し、混合物を酢酸エチルで抽出した。有機層を塩水で洗浄して無水硫酸ナトリウムで乾燥させた。溶媒を減圧下で除去し、残渣をシリカゲルカラムクロマトグラフィーにより精製すると、0.217mmolのIが得られた。
例示的構造化合物Iについての分析データを以下に提供する。
この化合物についての分析データは、4.2.jに含まれる。
3からのIの調製
6.1 ワンポットボロニル化及び環化
テトラヒドロフラン(10mL)中の3(4.88mmol)及びホウ酸トリイソプロピル(1.35mL、5.86mmol)の溶液にn−ブチルリチウム(ヘキサン(6.7mL、10.7mmol)中1.6mol/L)を−78℃での窒素雰囲気下で15分間にわたり滴下しながら添加し、混合物を室温に暖めながら2時間攪拌した。反応物を2NのHClでクエンチし、酢酸エチルで抽出した。有機層を塩水で洗浄して無水硫酸ナトリウムで乾燥させた。溶媒を減圧下で除去し、残渣をシリカゲルカラムクロマトグラフィーにより精製してペンタンで処理すると、0.41mmolのIが得られた。
例示的構造化合物Iの分析データを以下に提供する。
この化合物についての分析データは、4.2.jに含まれる。
3からのIの調製
7.1 蒸留を伴うワンポットボロニル化及び環化
トルエン(20mL)中の3(4.88mmol)の溶液にホウ酸トリイソプロピル(2.2mL、9.8mmol)を添加し、混合物を1時間、還流加熱した。溶媒、得られたイソプロピルアルコール、及び過剰なホウ酸トリイソプロピルを減圧下で除去した。残渣をテトラヒドロフラン(10mL)中に溶解させ、−78℃に冷却した。n−ブチルリチウム(3.2mL、5.1mmol)を10分間にわたり滴下しながら添加し、混合物を室温に暖めながら1時間攪拌した。反応物を2NのHClでクエンチし、酢酸エチルで抽出した。有機層を塩水で洗浄して無水硫酸ナトリウムで乾燥させた。溶媒を減圧下で除去し、残渣をシリカゲルカラムクロマトグラフィーにより精製すると、1.54mmolのIが得られた。
例示的構造化合物Iの分析データを以下に提供する。
この化合物についての分析データは、4.2.jに含まれる。
7からの8の調製
8.1 臭素化
四塩化炭素(200mL)中の7(49.5mmol)の溶液にN−ブロモコハク酸イミド(8.81g、49.5mmol)及びN,N−アゾイソブチロニトリル(414mg、5mol%)を添加し、混合物を3時間、還流加熱した。水を添加し、混合物をクロロホルムで抽出した。有機層を塩水で洗浄して無水硫酸ナトリウムで乾燥させた。溶媒を減圧下で除去すると、粗生成のメチル基臭素化中間体8が得られた。
8からの3の調製
9.1 ヒドロキシル化
粗生成の8(49.5mmol)に対し、ジメチルホルムアミド(150mL)及び酢酸ナトリウム(20.5g、250mmol)を添加し、混合物を80℃で一晩攪拌した。水を添加し、混合物をエーテルで抽出した。有機層を水及び塩水で洗浄して無水硫酸ナトリウムで乾燥させた。溶媒を減圧下で除去した。残渣にメタノール(150mL)及び1Nの水酸化ナトリウム(50mL)を添加し、混合物を室温で1時間攪拌した。反応混合物を減圧下でおよそ3分の1の体積になるまで濃縮した。水及び塩酸を添加し、混合物を酢酸エチルで抽出した。有機層を水及び塩水で洗浄して無水硫酸ナトリウムで乾燥させた。溶媒を減圧下で除去し、残渣をシリカゲルカラムクロマトグラフィーによる精製後にジクロロメタンを用いて粉砕すると、21.8mmolの3が得られた。
上記の方法により調製された例示的構造化合物3を以下に提供する。
1H−NMR(300MHz,DMSO−d6)δppm 4.51(d,J=5.9Hz,2H),5.67(t,J=5.6Hz,1H),7.67(dd,J=8.2,2.0Hz,1H),7.80(s,J=8.2Hz,1H),7.83(d,J=2.0Hz,1H)。
2からの9の調製
10.1 反応
N,N−ジメチルホルムアミド(50mL)中の2(20.0mmol)、(メトキシメチル)塩化トリフェニルホスホニウム(8.49g、24.0mmol)、及びカリウムtert−ブトキシド(2.83g、24.0mol)の混合物を室温で一晩攪拌した。反応物を6NのHClでクエンチし、混合物を酢酸エチルで抽出した。有機層を水(×2)及び塩水で洗浄して無水硫酸ナトリウムで乾燥させた。溶媒を減圧下で除去した。残渣にテトラヒドロフラン(60mL)及び6NのHClを添加し、混合物を8時間、還流加熱した。水を添加し、混合物をエーテルで抽出した。有機層を塩水で洗浄して無水硫酸ナトリウムで乾燥させた。溶媒を減圧下で除去すると、16.6mmolの9が得られた。
工程13の調製方法
11.1 反応
適切なアルコール溶媒(R1−OH)中のIの溶液を窒素雰囲気下で還流した後、蒸留によりアルコールを除去すると、対応するエステルが得られた。
IaからのIbの調製
12.1 反応
トルエン中のIaの溶液にアミノアルコールを添加して関連固形物を回収すると、Ibが得られた。
(500mg、3.3mmol)をトルエン(37mL)中に80℃で溶解し、エタノールアミン(0.20mL、3.3mmol)を添加した。混合物を室温に冷却後、氷浴してろ過すると、C38が白色粉末として得られた(600.5mg、94%)。
1H−NMR(300MHz,DMSO−d6)δ(ppm)2.88(t,J=6.2Hz,2H),3.75(t,J=6.3Hz,2H),4.66(s,2H),5.77(br,2H),6.85〜6.91(m,2H),7.31(td,J=7.2,1.2Hz,1H)。
5−(4−カルボキシフェノキシ)−1−ヒドロキシ−2,1−ベンゾオキサボロール
1−ヒドロキシ−5−[4−(テトラゾール−1−イル)フェノキシ]−2,1−ベンゾオキサボロール
4−(4−シアノフェノキシ)フェニルボロン酸(C97)
3−(4−シアノフェノキシ)フェニルボロン酸(C98)
4−(4−シアノフェノキシ)−2−メチルフェニルボロン酸(C99)
抗炎症試験
本発明の化合物について炎症誘発性サイトカインの阻害能力を試験した。凍結したヒト末梢血単核球(PBMC)中のIL−1β、IL−4、TNFα、及びIFNγサイトカイン放出プロファイルに対する本化合物の影響を調べた。PBMC細胞を10μM濃度の各試料に曝露させた後、20μg/mLのフィトヘマグルチニン(PHA)で刺激した。サイトカイン放出プロファイルをLuminex 4-plexアッセイを使用して分析した。(IL−1β、IFNγ、IL−4、TNF−α)。試験の結果を図1に提供する。
試験物質及び投薬パターン
凍結ヒトPBMCを解凍及び遠心する。凍結した保存培地を細胞ペレットから吸引し、この細胞を新鮮な培地に再懸濁した。PBMC用の培地(CM)は、RPMI1640、10%FBS、1%P/S、2mMのL−グルタミンとした。細胞を37℃、5%CO2でインキュベートした。式(I)又は式(II)によるものなどの本明細書に記載される化合物の乾燥固体をDMSOに溶解させて、20mMの試料(DMSO、100%)を形成した。20mM試料を200μM(10×)までCM(DMSO、1%)中に希釈した。10μLの希釈試料を190μLのCM+細胞(n=3)に添加し、最終試料濃度を10μMとした(最終DMSOは0.05%)。試料は細胞とともに37℃で15〜30分間インキュベートした後、誘導剤(PHA、20μg/mL)を添加した。誘導剤と媒体(PHA+0.05%DMSO)を本実験の対照として使用した。誘導剤を含まない媒体を陰性対照として使用した。デキサメタゾン(50nM、n=3)を陽性対照に使用した。上清を24時間及び48時間で抽出し、−80℃で保存した。上清を解凍し、試料の細胞毒性についてAlamar Blueで分析した。次に、Luminex 4-plexアッセイを使用してIL−1β、IL−4、TNF−α及びIFNγについて上清を分析した。
サイトカイン分泌のデキサメタゾン阻害は予測された範囲内であったことから、アッセイは妥当であったと確認された。本発明の様々な化合物についてのIL−1β、IL−4、TNF−α及びIFNγ阻害%を図1に提供する。
局所・ホルボールエステルマウス耳アッセイ
方法:
試験物質及び投薬パターン
5−(4−シアノフェノキシ)−1−ヒドロキシ−2,1−ジヒドロベンゾオキサボロール及びベタメタゾンはAnacor Pharmaceuticals, Inc.から提供された。ベタメタゾンは、そう痒、発赤、乾燥、痂皮、鱗屑、炎症、及び様々な皮膚病態の不快感の治療に使用される。
体重24±2gのCD−1(Crl.)系雄性マウスは、BioLasco Taiwan(Charles River Laboratoriesの技術許諾下)から提供された。10匹の動物に対する空間割当ては、29×18×13cmであった。マウスはAPEC(商標登録)ケージに入れられた。全ての動物は使用に先立ち、制御された温度(22℃〜23℃)及び湿度(70%〜80%)の環境において12時間の明暗サイクルで少なくとも1週間、MDS Pharma Services-Taiwan Laboratoryで管理された。標準的なマウス実験用餌(Lab Diet, Rodent Diet, PMI Nutrition International, USA)及び水道水は自由に摂取できるよう与えられた。動物の飼育、実験、及び処分を含め、この作業はあらゆる側面において、概してGuide for the Care and Use of Laboratory Animals(National Academy Press, Washington, D. C., 1996)に従って実施された。
アセトン(Wako、日本国)、エタノールアブソリュート(Merck、独国)、デキサメタゾン(Sigma、米国)、及びホルボール12−ミリステート13−アセテート(Sigma、米国)。
動物ケージ(Allentown、米国)、Dyerモデルマイクロメータゲージ(Peacock、日本国)及びPipetman(Gilson、仏国)。
体重24±2gの5匹のCD−1(Crl.)系雄性マウス群が使用された。PMA(20μlのアセトン中4pg)を各動物の右耳の前表面及び後表面に対し局所的に適用した。媒体(エタノール:アセトン/1:1、20μL/耳、又はクリーム、20mg/耳)及び5−(4−シアノフェノキシ)−1−ヒドロキシ−2,1−ジヒドロベンゾオキサボロール及びベタメタゾンを含む試験物質を、各々、PMA適用の30分前及び15分後に適用した。陽性対照としてのデキサメタゾン(アセトン:エタノール/1:1の20μL/耳中3mg、3mg/耳)も同様に同じタイミングで適用した。次に、耳の腫脹を炎症の指標としてPMA適用後6時間においてDyerモデルマイクロメータゲージにより計測した。阻害パーセントを式([Ic−It]/Ic)×100%(式中、Ic及びItは、それぞれ対照マウス及び治療マウスにおける耳の厚さの増加分(mm)を指す)に従い計算した。30パーセント以上(≧30%)の阻害を有意な抗炎症活性と見なす。
それぞれの媒体(エタノール:アセトン/1:1)又はクリーム状プラセボ対照群と比較すると、5−(4−シアノフェノキシ)−1−ヒドロキシ−2,1−ベンゾオキサボロール(1mg/耳×2)、ベタメタゾン(0.2mg/耳×2)は、PMA誘発性耳腫脹の有意な阻害をもたらした。
環状ボロン酸エステル
本明細書に記載される方法によりさらなる化合物が生成することができる。1又は3などの適切な出発物質を選択することにより、本明細書に記載される方法を使用して以下の化合物を調製できる。入手可能な場合、これらの化合物について融点特性を提供する。
例示的構造化合物Iの分析データを以下に提供する。
Claims (43)
- 下記式による構造を有する化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩を含む、ヒト又は動物における炎症関連疾患を治療又は予防するための医薬製剤であって、炎症関連疾患が、乾癬、関節炎、皮膚炎、アレルギー性鼻炎、強直性脊椎炎、クローン病、潰瘍性大腸炎、慢性閉塞性肺疾患、ブドウ膜炎、サルコイドーシス、ベーチェット病、アレルギー性結膜炎、ドライアイ疾患、及び喘息から選択されるメンバーである、医薬製剤:
R1は、Hであり、
R4aは、Hであり、
R10aは、置換又は非置換フェニルオキシ、置換又は非置換フェニルチオ、置換又は非置換ピリジニルオキシ、及び置換又は非置換ピリジニルチオから選択されるメンバーである)。 - 薬学的に許容可能な賦形剤をさらに含む、請求項1に記載の医薬製剤。
- R10aが、
式中、
R15は、CN、COOH、及び
pは、1〜5から選択される整数であり、
Xは、S及びOから選択されるメンバーである、請求項1に記載の医薬製剤。 - 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、炎症誘発性サイトカイン発現を阻害するか、あるいは抗炎症性サイトカイン発現を刺激することにより炎症関連疾患を治療するのに十分な量であるが、該量はサイクリン依存性キナーゼを実質的に阻害するには不十分である、請求項1に記載の医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、5−(4−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロール又はその無水物、溶媒和物若しくは薬学的に許容可能な塩である、請求項4に記載の医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、IL−1α、β、IL−2、IL−3、IL−6、IL−7、IL−9、IL−12、IL−17、IL−18、IL−23、TNF−α、LT、LIF、オンコスタチン、及びIFNc1α、β、γから選択されるメンバーであるサイトカインを阻害するのに十分な濃度で投与される、請求項1に記載の医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、5−(4−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロール又はその無水物、溶媒和物若しくは薬学的に許容可能な塩である、請求項6に記載の医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、IL−4、IL−10、IL−11、W−13、及びTGF−βから選択されるメンバーであるサイトカインの発現を刺激するのに十分な濃度で投与される、請求項1に記載の医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、5−(4−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロール又はその無水物、溶媒和物若しくは薬学的に許容可能な塩である、請求項8に記載の医薬製剤。
- サイトカイン発現レベルに関連する炎症関連疾患の医薬製剤であって、炎症関連疾患が、乾癬、関節炎、皮膚炎、アレルギー性鼻炎、強直性脊椎炎、クローン病、潰瘍性大腸炎、慢性閉塞性肺疾患、ブドウ膜炎、サルコイドーシス、ベーチェット病、アレルギー性結膜炎、ドライアイ疾患、及び喘息から選択されるメンバーであり、そのような治療を必要とするヒト又は動物に請求項1に記載の化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩を投与することを含む、医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、5−(4−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロール又はその無水物、溶媒和物若しくは薬学的に許容可能な塩である、請求項10に記載の医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、炎症誘発性サイトカイン発現を阻害するか、あるいは抗炎症性サイトカイン発現を刺激することにより炎症関連疾患を治療するのに十分な量であるが、該量はサイクリン依存性キナーゼを実質的に阻害するには不十分である、請求項1に記載の医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、5−(4−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロール又はその無水物、溶媒和物若しくは薬学的に許容可能な塩である、請求項12に記載の医薬製剤。
- 前記動物がヒトである、請求項1に記載の医薬製剤。
- 炎症性サイトカインタンパク質を産生することができる細胞による炎症性サイトカインタンパク質の産生を阻害するための医薬製剤であって、前記細胞を治療量の請求項1に記載の化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩と合わせることを含み、それにより前記細胞による前記炎症性サイトカインの産生が阻害される、医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、5−(4−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロール又はその無水物、溶媒和物若しくは薬学的に許容可能な塩である、請求項15に記載の医薬製剤。
- 前記治療量が前記炎症性サイトカインタンパク質の産生を50%〜99%阻害するのに十分である、請求項15に記載の医薬製剤。
- ヒト又は動物の炎症反応を阻害するための医薬製剤であって、前記ヒト又は動物を治療量の請求項1に記載の化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩と接触させることを含み、それにより前記炎症反応が阻害される、医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、5−(4−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロール又はその無水物、溶媒和物若しくは薬学的に許容可能な塩である、請求項18に記載の医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、4−((1−ヒドロキシ−1,3−ジヒドロベンゾ[c][1,2]オキサボロール−5−イル)チオ)ベンゾニトリル、3−((1−ヒドロキシ−1,3−ジヒドロベンゾ[c][1,2]オキサボロール−5−イル)チオ)ベンゾニトリル、2−((1−ヒドロキシ−1,3−ジヒドロベンゾ[c][1,2]オキサボロール−5−イル)チオ)ベンゾニトリル、5−(3,4−ジシアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロール、6−(1−ヒドロキシ−1,3−ジヒドロベンゾ[c][1,2]オキサボロール−5−イルオキシ)ニコチノニトリル、5−(4−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロール、5−(3−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロール、及び5−(2−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロールからなる群から選択される化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩である、請求項1に記載の医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、6−(1−ヒドロキシ−1,3−ジヒドロベンゾ[c][1,2]オキサボロール−5−イルオキシ)ニコチノニトリル又はその無水物、溶媒和物若しくは薬学的に許容可能な塩である、請求項1に記載の医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、5−(4−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロール又はその無水物、溶媒和物若しくは薬学的に許容可能な塩である、請求項1に記載の医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、5−(3−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロール又はその無水物、溶媒和物若しくは薬学的に許容可能な塩である、請求項1に記載の医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、5−(2−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロール又はその無水物、溶媒和物若しくは薬学的に許容可能な塩である、請求項1に記載の医薬製剤。
- 前記化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩が、5−(3,4−ジシアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロール又はその無水物、溶媒和物若しくは薬学的に許容可能な塩である、請求項1に記載の医薬製剤。
- 炎症関連疾患が、皮膚炎である、請求項1に記載の医薬製剤。
- 炎症関連疾患が、皮膚炎であり、前記皮膚炎が、接触性皮膚炎である、請求項1に記載の医薬製剤。
- 炎症関連疾患が、皮膚炎であり、前記皮膚炎が、アトピー性皮膚炎である、請求項1に記載の医薬製剤。
- 炎症関連疾患が、皮膚炎であり、前記皮膚炎が、湿疹である、請求項1に記載の医薬製剤。
- 炎症関連疾患が、乾癬である、請求項1に記載の医薬製剤。
- 炎症関連疾患が、関節炎であり、関節炎が関節リウマチである、請求項1に記載の医薬製剤。
- 炎症関連疾患が、関節炎であり、関節炎が乾癬性関節炎である、請求項1に記載の医薬製剤。
- 炎症関連疾患が、喘息であり、喘息が気管支喘息である、請求項1に記載の医薬製剤。
- ヒト又は動物における皮膚炎を治療又は予防するための医薬製剤であって、5−(4−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロールである化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩を含む、医薬製剤。
- ヒト又は動物における皮膚炎を治療又は予防するための医薬製剤であって、5−(3,4−ジシアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロールである化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩を含む、医薬製剤。
- ヒト又は動物における接触性皮膚炎を治療又は予防するための医薬製剤であって、5−(4−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロールである化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩を含む、医薬製剤。
- ヒト又は動物における接触性皮膚炎を治療又は予防するための医薬製剤であって、5−(3,4−ジシアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロールである化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩を含む、医薬製剤。
- ヒト又は動物におけるアトピー性皮膚炎を治療又は予防するための医薬製剤であって、5−(4−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロールである化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩を含む、医薬製剤。
- ヒト又は動物におけるアトピー性皮膚炎を治療又は予防するための医薬製剤であって、5−(3,4−ジシアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロールである化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩を含む、医薬製剤。
- ヒト又は動物における湿疹を治療又は予防するための医薬製剤であって、5−(4−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロールである化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩を含む、医薬製剤。
- ヒト又は動物における湿疹を治療又は予防するための医薬製剤であって、5−(3,4−ジシアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロールである化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩を含む、医薬製剤。
- ヒト又は動物における乾癬を治療又は予防するための医薬製剤であって、5−(4−シアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロールである化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩を含む、医薬製剤。
- ヒト又は動物における乾癬を治療又は予防するための医薬製剤であって、5−(3,4−ジシアノフェノキシ)−1,3−ジヒドロ−1−ヒドロキシ−2,1−ベンゾオキサボロールである化合物又はその無水物、溶媒和物若しくは薬学的に許容可能な塩を含む、医薬製剤。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US77453206P | 2006-02-16 | 2006-02-16 | |
US60/774,532 | 2006-02-16 | ||
US82388806P | 2006-08-29 | 2006-08-29 | |
US60/823,888 | 2006-08-29 | ||
PCT/US2007/062350 WO2007095638A2 (en) | 2006-02-16 | 2007-02-16 | Boron-containing small molecules as anti-inflammatory agents |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013173486A Division JP2013253097A (ja) | 2006-02-16 | 2013-08-23 | 抗炎症剤としてのホウ素含有小分子 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2009531292A JP2009531292A (ja) | 2009-09-03 |
JP2009531292A5 JP2009531292A5 (ja) | 2010-04-08 |
JP5419466B2 true JP5419466B2 (ja) | 2014-02-19 |
Family
ID=38372267
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008555528A Active JP5419466B2 (ja) | 2006-02-16 | 2007-02-16 | 抗炎症剤としてのホウ素含有小分子 |
JP2013173486A Pending JP2013253097A (ja) | 2006-02-16 | 2013-08-23 | 抗炎症剤としてのホウ素含有小分子 |
JP2015082026A Pending JP2015147795A (ja) | 2006-02-16 | 2015-04-13 | 抗炎症剤としてのホウ素含有小分子 |
JP2016139202A Active JP6266708B2 (ja) | 2006-02-16 | 2016-07-14 | 抗炎症剤としてのホウ素含有小分子 |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013173486A Pending JP2013253097A (ja) | 2006-02-16 | 2013-08-23 | 抗炎症剤としてのホウ素含有小分子 |
JP2015082026A Pending JP2015147795A (ja) | 2006-02-16 | 2015-04-13 | 抗炎症剤としてのホウ素含有小分子 |
JP2016139202A Active JP6266708B2 (ja) | 2006-02-16 | 2016-07-14 | 抗炎症剤としてのホウ素含有小分子 |
Country Status (25)
Country | Link |
---|---|
US (11) | US8168614B2 (ja) |
EP (2) | EP2719388B1 (ja) |
JP (4) | JP5419466B2 (ja) |
KR (7) | KR101622870B1 (ja) |
CN (2) | CN101420854B (ja) |
AU (1) | AU2007214421B2 (ja) |
BR (1) | BRPI0708051A2 (ja) |
CA (2) | CA2933994A1 (ja) |
CY (1) | CY1121899T1 (ja) |
DK (2) | DK1988779T5 (ja) |
ES (2) | ES2542342T3 (ja) |
HK (1) | HK1121344A1 (ja) |
HR (1) | HRP20150710T1 (ja) |
HU (2) | HUE025048T2 (ja) |
IL (2) | IL193230A (ja) |
ME (1) | ME02188B (ja) |
MX (2) | MX2008010381A (ja) |
NZ (1) | NZ570257A (ja) |
PL (2) | PL2719388T3 (ja) |
PT (2) | PT2719388T (ja) |
RS (1) | RS54108B1 (ja) |
RU (2) | RU2508113C2 (ja) |
SI (2) | SI2719388T1 (ja) |
WO (1) | WO2007095638A2 (ja) |
ZA (1) | ZA200806754B (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013253097A (ja) * | 2006-02-16 | 2013-12-19 | Anacor Pharmaceuticals Inc | 抗炎症剤としてのホウ素含有小分子 |
Families Citing this family (121)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2597982C (en) | 2005-02-16 | 2014-07-08 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
US7767657B2 (en) | 2005-02-16 | 2010-08-03 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
US8106031B2 (en) | 2006-05-02 | 2012-01-31 | Anacor Pharmaceuticals, Inc. | Hydrolytically-resistant boron-containing therapeutics and methods of use |
JO3598B1 (ar) * | 2006-10-10 | 2020-07-05 | Infinity Discovery Inc | الاحماض والاسترات البورونية كمثبطات اميد هيدروليز الحامض الدهني |
US10265265B2 (en) | 2007-03-15 | 2019-04-23 | Drug Delivery Solutions Limited | Topical composition |
JO3396B1 (ar) * | 2007-06-20 | 2019-10-20 | Anacor Pharmaceuticals Inc | جزيئات صغيرة تحتوي على البورون |
US10125359B2 (en) | 2007-10-25 | 2018-11-13 | Revalesio Corporation | Compositions and methods for treating inflammation |
US9523090B2 (en) | 2007-10-25 | 2016-12-20 | Revalesio Corporation | Compositions and methods for treating inflammation |
US9745567B2 (en) | 2008-04-28 | 2017-08-29 | Revalesio Corporation | Compositions and methods for treating multiple sclerosis |
JP5745279B2 (ja) * | 2008-01-09 | 2015-07-08 | アナコール ファーマシューティカルズ,インコーポレイテッド | 抗炎症剤としてのホウ素含有小分子 |
JP2015178508A (ja) * | 2008-01-09 | 2015-10-08 | アナコール ファーマシューティカルズ,インコーポレイテッド | 抗炎症剤としてのホウ素含有小分子 |
WO2009111676A2 (en) * | 2008-03-06 | 2009-09-11 | Anacor Pharmaceuticals, Inc | Boron-containing small molecules as anti-inflammatory agents |
MX2010009765A (es) | 2008-03-06 | 2013-07-12 | Anacor Pharmaceuticals Inc | Moleculas pequeñas que contienen boro como agentes anti-inflamatorios. |
CN102046179B (zh) | 2008-04-09 | 2015-01-14 | 英菲尼提制药公司 | 脂肪酸酰胺水解酶抑制剂 |
EP2285384A4 (en) * | 2008-05-12 | 2012-04-25 | Anacor Pharmaceuticals Inc | BORN SMALL MOLECULES |
EP2348863A4 (en) * | 2008-09-04 | 2012-03-07 | Anacor Pharmaceuticals Inc | BORN SMALL MOLECULES |
WO2010028005A1 (en) * | 2008-09-04 | 2010-03-11 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
WO2010045505A1 (en) * | 2008-10-15 | 2010-04-22 | Anacor Pharmaceuticals, Inc | Boron-containing small molecules as anti-protozoal agents |
US9493489B2 (en) * | 2008-10-15 | 2016-11-15 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as anti-protozoal agents |
EP2378886A4 (en) | 2008-12-17 | 2012-08-29 | Anacor Pharmaceuticals Inc | (S) -3-Aminomethyl-7- (3-hydroxypropoxy) -3H-benzo [c] [1,2] oxaborole-1-OL-POLYMORPHS |
CA2757679A1 (en) | 2009-04-07 | 2010-10-14 | Infinity Pharmaceuticals, Inc. | Inhibitors of fatty acid amide hydrolase |
US8541581B2 (en) | 2009-04-07 | 2013-09-24 | Infinity Pharmaceuticals, Inc. | Inhibitors of fatty acid amide hydrolase |
BR112012001987A2 (pt) | 2009-07-28 | 2015-09-01 | Anacor Pharmaceuticals Inc | Composto, combinação, formulação farmacêutica, uso de um composto, uma combinação ou um sal farmaceuticamente aceitável dos mesmos, e, métodos para tratar uma infecção bacteriana, para matar ou inibir o crescimento de uma bactéria, e para inibir uma beta-lactamase. |
AP4039A (en) | 2009-08-14 | 2017-02-28 | Daitao Chen | Boron-containing small molecules as antiprotozoal agents |
WO2011019612A1 (en) * | 2009-08-14 | 2011-02-17 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as antiprotozoal agents |
WO2011019616A1 (en) * | 2009-08-14 | 2011-02-17 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as antiprotozoal agents |
WO2011022337A1 (en) | 2009-08-19 | 2011-02-24 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as antiprotozoal agents |
WO2011035174A1 (en) * | 2009-09-17 | 2011-03-24 | Vanderbilt University | Substituted heteroarylamine carboxamide analogs as mglur5 negative allosteric modulators and methods of making and using the same |
US20110124597A1 (en) * | 2009-09-25 | 2011-05-26 | Anacor Pharmaceuticals, Inc. | Boron containing small molecules |
WO2011049971A1 (en) | 2009-10-20 | 2011-04-28 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as antiprotozoal agents |
US20110212918A1 (en) * | 2009-11-11 | 2011-09-01 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
WO2011063293A1 (en) * | 2009-11-20 | 2011-05-26 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as antihelminth agents |
WO2011094450A1 (en) | 2010-01-27 | 2011-08-04 | Anacor Pharmaceuticals, Inc | Boron-containing small molecules |
EP2531511A1 (en) | 2010-02-03 | 2012-12-12 | Infinity Pharmaceuticals, Inc. | Fatty acid amide hydrolase inhibitors |
AP2012006482A0 (en) | 2010-03-19 | 2012-10-31 | Anacor Pharmacueticals Inc | Boron-containing small molecules as anti-protozoalagent |
JP5699030B2 (ja) * | 2010-07-05 | 2015-04-08 | Axis株式会社 | エタネルセプトを含む線維筋痛症の治療剤 |
SG187757A1 (en) | 2010-08-10 | 2013-03-28 | Rempex Pharmaceuticals Inc | Cyclic boronic acid ester derivatives and therapeutic uses thereof |
SG188362A1 (en) | 2010-09-01 | 2013-04-30 | Arena Pharm Inc | Modified-release dosage forms of 5-ht2c agonists useful for weight management |
JP5952280B2 (ja) * | 2010-09-07 | 2016-07-13 | アナコール ファーマシューティカルズ,インコーポレーテッド | 細菌感染治療用のベンゾオキサボロール誘導体 |
AU2011344030B2 (en) | 2010-12-15 | 2017-03-30 | Olatec Therapeutics Llc | 3-methanesulfonylpropionitrile for treating inflammation and pain |
US8927593B2 (en) | 2011-08-19 | 2015-01-06 | Glaxo Group Limited | Benzofuran compounds for the treatment of hepatitis C virus infections |
US9012491B2 (en) | 2011-08-31 | 2015-04-21 | Rempex Pharmaceuticals, Inc. | Heterocyclic boronic acid ester derivatives and therapeutic uses thereof |
AR088669A1 (es) | 2011-11-21 | 2014-06-25 | Lilly Co Eli | Derivados de dihidrodibenzo[c][1,2]oxaborol y dihidroisoxazol utiles para el control de ectoparasitos |
AR088668A1 (es) | 2011-11-21 | 2014-06-25 | Lilly Co Eli | Moleculas pequeñas que contienen boro |
EP2793901A1 (en) * | 2011-12-22 | 2014-10-29 | Micurx Pharmaceuticals, Inc. | Tricyclic boron compounds for antimicrobial therapy |
AU2013226300B2 (en) | 2012-02-27 | 2017-09-28 | Olatec Therapeutics Llc | Process for preparing 3-methylsulfonylpropionitrile |
US9156858B2 (en) | 2012-05-23 | 2015-10-13 | Rempex Pharmaceuticals, Inc. | Boronic acid derivatives and therapeutic uses thereof |
AU2013271773B2 (en) | 2012-06-05 | 2018-03-08 | Olatec Therapeutics Llc | Pharmaceutical composition for treating inflammation and pain |
US10561675B2 (en) | 2012-06-06 | 2020-02-18 | Rempex Pharmaceuticals, Inc. | Cyclic boronic acid ester derivatives and therapeutic uses thereof |
WO2013188214A1 (en) | 2012-06-11 | 2013-12-19 | Olatec Industries Llc | Compounds for treating inflammation and pain |
US9114122B2 (en) | 2012-06-14 | 2015-08-25 | Olatec Industries Llc | Compounds for treating inflammation and pain |
US8980544B2 (en) | 2012-11-27 | 2015-03-17 | The Penn State Research Foundation | Boronic and borinic acid compounds as inhibitors of sulfenic acid-containing proteins |
CN104981239B (zh) | 2013-01-04 | 2019-01-04 | 莱姆派克斯制药公司 | 硼酸衍生物及其治疗用途 |
KR20150103269A (ko) | 2013-01-04 | 2015-09-09 | 렘펙스 파머수티클스 인코퍼레이티드 | 보론산 유도체 및 그의 치료적 용도 |
US9101638B2 (en) | 2013-01-04 | 2015-08-11 | Rempex Pharmaceuticals, Inc. | Boronic acid derivatives and therapeutic uses thereof |
US9241947B2 (en) | 2013-01-04 | 2016-01-26 | Rempex Pharmaceuticals, Inc. | Boronic acid derivatives and therapeutic uses thereof |
CN107646865B (zh) | 2013-01-30 | 2020-07-03 | 美国陶氏益农公司 | 苯硼酸半酯作为挥发性抗微生物剂在肉类、植物或植物部分上的用途 |
US9585396B2 (en) | 2013-01-30 | 2017-03-07 | Agrofresh Inc. | Volatile applications against pathogens |
US8669207B1 (en) | 2013-01-30 | 2014-03-11 | Dow Agrosciences, Llc. | Compounds and compositions |
US11039617B2 (en) | 2013-01-30 | 2021-06-22 | Agrofresh Inc. | Large scale methods of uniformly coating packaging surfaces with a volatile antimicrobial to preserve food freshness |
US10070649B2 (en) | 2013-01-30 | 2018-09-11 | Agrofresh Inc. | Volatile applications against pathogens |
AP2015008638A0 (en) | 2013-02-01 | 2015-08-31 | Anacor Pharmaceuticals Inc | Boron-containing small molecules as antiprotozoal agents |
KR101636431B1 (ko) * | 2013-07-30 | 2016-07-05 | 동아에스티 주식회사 | 트리사이클릭 벤즈옥사보롤 화합물, 이의 제조방법 및 용도 |
US20160200743A1 (en) * | 2013-09-23 | 2016-07-14 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as anti-inflammatory agents |
US9585958B2 (en) * | 2013-09-24 | 2017-03-07 | The Regents Of The University Of California | Compositions and methods for reducing lactate levels |
EP3071568A1 (en) | 2013-11-19 | 2016-09-28 | Vanderbilt University | Substituted imidazopyridine and triazolopyridine compounds as negative allosteric modulators of mglur5 |
US9533982B2 (en) | 2014-03-20 | 2017-01-03 | Vanderbilt University | Substituted bicyclic heteroaryl carboxamide analogs as mGluR5 negative allosteric modulators |
EP3139930A4 (en) | 2014-05-05 | 2018-01-17 | Rempex Pharmaceuticals, Inc. | Salts and polymorphs of cyclic boronic acid ester derivatives and therapeutic uses thereof |
LT3140310T (lt) | 2014-05-05 | 2019-11-25 | Rempex Pharmaceuticals Inc | Boronato druskų sintezė ir jų panaudojimas |
EP3145936B1 (en) | 2014-05-19 | 2020-09-30 | Qpex Biopharma, Inc. | Boronic acid derivatives and therapeutic uses thereof |
ES2732465T3 (es) | 2014-07-01 | 2019-11-22 | Daiichi Sankyo Co Ltd | Benzoxaboroles tricíclicos como agentes antibacterianos |
JP6700203B2 (ja) | 2014-07-01 | 2020-05-27 | レンペックス・ファーマシューティカルズ・インコーポレイテッド | ボロン酸誘導体およびその治療的使用 |
US9550778B2 (en) | 2014-10-03 | 2017-01-24 | Vanderbilt University | Substituted 6-aryl-imidazopyridine and 6-aryl-triazolopyridine carboxamide analogs as negative allosteric modulators of mGluR5 |
WO2016081297A1 (en) | 2014-11-18 | 2016-05-26 | Rempex Pharmaceuticals, Inc. | Cyclic boronic acid ester derivatives and therapeutic uses thereof |
AR103397A1 (es) * | 2015-01-13 | 2017-05-10 | Syngenta Participations Ag | Oxoborazoles microbicidas |
EP3244741A1 (en) * | 2015-01-13 | 2017-11-22 | Syngenta Participations AG | Novel microbiocides |
US20180051041A1 (en) | 2015-03-17 | 2018-02-22 | Rempex Pharmaceuticals, Inc. | Boronic acid derivatives and therapeutic uses thereof |
US9737075B2 (en) * | 2015-04-09 | 2017-08-22 | The Penn State Research Foundation | Synergistic benzoxaborole-containing anti-fungicidal composition |
WO2017024022A1 (en) * | 2015-08-06 | 2017-02-09 | The Penn State Research Foundation | Benzoxaborole-containing coating resistant to cellulose-supportable fungus |
KR102106230B1 (ko) | 2015-11-30 | 2020-04-29 | 아나코르 파마슈티칼스 인코포레이티드 | 염증성-관련 상태를 치료하기 위한 국소 제약 제제 |
WO2017151492A1 (en) | 2016-03-02 | 2017-09-08 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
US10874679B2 (en) | 2016-03-02 | 2020-12-29 | Bill & Melinda Gates Foundation | Boron-containing small molecules |
CN113321672A (zh) | 2016-03-02 | 2021-08-31 | 比尔及梅琳达盖茨基金会 | 含硼小分子 |
TW201735792A (zh) | 2016-03-07 | 2017-10-16 | 農業保鮮股份有限公司 | 使用苯并氧雜硼雜環戊烯化合物和防腐氣體作為作物的抗微生物劑之協同方法 |
US11447506B2 (en) | 2016-05-09 | 2022-09-20 | Anacor Pharmaceuticals, Inc. | Crystal forms of crisaborole in free form and preparation method and use thereof |
MX2018013742A (es) * | 2016-05-09 | 2019-08-01 | Anacor Pharmaceuticals Inc | Formas cristalinas de crisaborol en forma libre, metodo de preparacion y uso de las mismas. |
CN109219351A (zh) | 2016-06-03 | 2019-01-15 | 巴斯夫欧洲公司 | 苯并氧杂硼戊环化合物 |
MY196909A (en) | 2016-06-30 | 2023-05-09 | Qpex Biopharma Inc | Boronic acid derivatives and therapeutic uses thereof |
CN107759625B (zh) * | 2016-08-22 | 2020-12-29 | 药源药物化学(上海)有限公司 | 4-(1-羟基-1,3-二氢苯并[c][1,2]氧杂硼杂环戊二烯-5-基氧基)苯氰的制备方法 |
WO2019190503A1 (en) * | 2018-03-28 | 2019-10-03 | Cove Bio Llc | Methods and compositions for treating parkinson's disease |
GB201701583D0 (en) * | 2017-01-31 | 2017-03-15 | Drug Delivery Solutions Ltd | Topical composition |
WO2018150327A1 (en) * | 2017-02-14 | 2018-08-23 | Wavelength Enterprises Ltd | Crisaborole production process |
US10961261B2 (en) | 2017-03-01 | 2021-03-30 | Anacor Pharmaceuticals, Inc. | Oxaborole analogs and uses thereof |
US10973835B2 (en) * | 2017-03-09 | 2021-04-13 | The Penn State Research Foundation | Boron-containing small molecules for inhibiting activity of a receptor-like protein tyrosine phosphatase |
US10981939B2 (en) | 2017-05-12 | 2021-04-20 | Biophore India Pharmaceuticals Pvt. Ltd. | Process for the preparation of 4-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-5-yl) oxy] benzonitrile (Crisaborole) |
CN108864160A (zh) * | 2017-05-16 | 2018-11-23 | 苏州旺山旺水生物医药有限公司 | 含硼小分子的制备方法 |
EP3694864A4 (en) | 2017-10-11 | 2021-10-13 | Qpex Biopharma, Inc. | BORONIC ACID DERIVATIVES AND THEIR SYNTHESIS |
WO2019096113A1 (zh) * | 2017-11-14 | 2019-05-23 | 深圳市塔吉瑞生物医药有限公司 | 一种氘代的含硼的化合物及药物组合物和用途 |
US11834466B2 (en) | 2017-11-30 | 2023-12-05 | 5Metis, Inc. | Benzoxaborole compounds and formulations thereof |
US10329311B1 (en) * | 2017-12-21 | 2019-06-25 | Olon S.P.A. | Process for the preparation of crisaborole |
PL3737685T3 (pl) | 2018-01-09 | 2023-10-02 | Halcyon Labs Private Limited | Sposób wytwarzania kryzaborolu i jego związków pośrednich |
WO2019173814A1 (en) | 2018-03-09 | 2019-09-12 | University Of The Sciences | Protective groups and methods for protecting benzoxaboroles or oxaboroles |
EP3542788A1 (en) | 2018-03-19 | 2019-09-25 | MC2 Therapeutics Limited | Topical composition comprising calcipotriol and betamethasone dipropionate |
CN112424209A (zh) | 2018-04-20 | 2021-02-26 | Qpex生物制药有限公司 | 硼酸衍生物及其治疗用途 |
CN108997394A (zh) * | 2018-06-12 | 2018-12-14 | 广州百霆医药科技有限公司 | 苯并氧杂硼杂环戊烷类化合物及其制备方法 |
CN108659024A (zh) * | 2018-07-24 | 2018-10-16 | 武汉轻工大学 | 克立硼罗的制备方法 |
CN112384201A (zh) * | 2018-07-31 | 2021-02-19 | Mc2疗法有限公司 | 局部组合物 |
AU2019325436B2 (en) | 2018-08-18 | 2023-10-26 | 5Metis, Inc. | Solid forms of substituted benzoxaborole and compositions thereof |
KR102038146B1 (ko) | 2018-10-25 | 2019-11-04 | 김준희 | 밸런스 웨이트 위치 이동형 크레인을 포함하는 수중 촬영 시스템 |
KR102007887B1 (ko) | 2018-10-25 | 2019-08-07 | (주)씨플렉스필름 | 회전기능을 갖는 수중 촬영장치 |
CN109456347B (zh) * | 2018-10-29 | 2021-02-05 | 安徽省庆云医药股份有限公司 | 一种克立硼罗的制备方法 |
CN112174989B (zh) | 2019-07-02 | 2023-06-20 | 江西同和药业股份有限公司 | 一种克立硼罗的制备方法 |
CN110664756B (zh) * | 2019-10-09 | 2020-11-17 | 吉林大学 | 一种小儿外伤喷雾剂及其制备方法 |
CN111303195B (zh) * | 2020-04-07 | 2022-09-27 | 中国医学科学院放射医学研究所 | 一类含硼小分子化合物、其制备方法及应用 |
EP4204012A1 (en) | 2020-08-31 | 2023-07-05 | Pfizer Inc. | Methods of protecting rna |
US11766369B1 (en) | 2020-09-30 | 2023-09-26 | Douglas Dillon | Single use protective cover for patient transport device |
CN114685537A (zh) * | 2020-12-28 | 2022-07-01 | 南京理工大学 | 丁苯酞衍生物g-3702在制备脑缺血再灌注损伤预防和治疗药物中的应用 |
CN113136023B (zh) * | 2021-04-25 | 2021-11-30 | 盐城海关综合技术服务中心 | 含羟甲基多孔芳香骨架的制备方法及其功能化材料和应用 |
IL311444A (en) | 2021-10-01 | 2024-05-01 | Nuvalent Inc | Solid forms, pharmaceutical preparations and preparation of macrocyclic heteroaromatic ether compounds |
WO2023076453A1 (en) * | 2021-10-29 | 2023-05-04 | An2 Therapeutics, Inc. | Treating neuroinflammatory conditions |
US20240132525A1 (en) * | 2022-06-17 | 2024-04-25 | Boehringer Ingelheim Animal Health USA Inc. | Boron containing pyrimidine compounds, compositions comprising them, methods and uses thereof |
Family Cites Families (74)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2260336A (en) | 1939-10-16 | 1941-10-28 | Dow Chemical Co | Method of preparation of organic borates |
US3686398A (en) | 1970-07-20 | 1972-08-22 | Chevron Res | 10,9-boroxarophenanthrene as fungicides |
GB1396904A (en) | 1972-08-11 | 1975-06-11 | Ici Ltd | Method for the control of micro-organisms |
US4766113A (en) | 1975-10-24 | 1988-08-23 | Chapman Chemical Company | Antimicrobial compositions and methods of using same |
US4602011A (en) | 1975-10-24 | 1986-07-22 | Chapman Chemical Company | Antimicrobial compositions and methods of using same |
US4716035A (en) | 1985-05-24 | 1987-12-29 | The Procter & Gamble Company | Oral compositions and methods for treating gingivitis |
US5962498A (en) * | 1986-06-11 | 1999-10-05 | Procyon Pharmaceuticals, Inc. | Protein kinase C modulators. C. indolactam structural-types with anti-inflammatory activity |
US4894220A (en) | 1987-01-30 | 1990-01-16 | Colgate-Palmolive Company | Antibacterial antiplaque oral composition |
US4919934A (en) | 1989-03-02 | 1990-04-24 | Richardson-Vicks Inc. | Cosmetic sticks |
SG47101A1 (en) | 1992-07-31 | 1998-03-20 | Us Bioscience | Crystalline amifostine compositions and methods for the preparation and use of same |
US5348948A (en) | 1993-05-07 | 1994-09-20 | American Cyanamid Company | 2,2-diaryl-1-(oxa and thia)-2a-azonia-2-borataacenaphthene fungicidal |
US5348947A (en) | 1993-05-07 | 1994-09-20 | American Cyanamid Company | Diarylboron ester and thioester fungicidal agents |
US5594151A (en) * | 1994-01-28 | 1997-01-14 | Prolinx, Inc. | Phenylboronic acid complexing reagents derived from aminosalicylic acid |
GB9411587D0 (en) * | 1994-06-09 | 1994-08-03 | Zeneca Ltd | Compound, composition and use |
US6083903A (en) | 1994-10-28 | 2000-07-04 | Leukosite, Inc. | Boronic ester and acid compounds, synthesis and uses |
GB9500856D0 (en) | 1995-01-17 | 1995-03-08 | Zeneca Ltd | Composition and use |
GB9604926D0 (en) | 1996-03-08 | 1996-05-08 | Sandoz Ltd | Organic compounds |
EP0934307B1 (en) | 1996-06-19 | 2011-04-27 | Aventis Pharma Limited | Substituted azabicylic compounds and their use as inhibitors of the production of tnf and cyclic amp phosphodiesterase |
US5831046A (en) | 1996-08-05 | 1998-11-03 | Prolinx, Incorporated | Boronic acid-contaning nucleic acid monomers |
WO1998012206A1 (en) | 1996-09-19 | 1998-03-26 | The Board Of Trustees Of Leland Stanford Jr. University | Dna adenine methyltransferases and uses thereof |
AU4967997A (en) | 1996-12-02 | 1998-06-29 | Chisso Corporation | Optically active nitro alcohol derivatives, optically active amino alcohol derivates, and process for preparing the same |
US6221640B1 (en) | 1997-05-14 | 2001-04-24 | Cubist Pharmaceuticals, Inc. | Enterococcal aminoacyl-trna synthetase proteins, nucleic acids and strains comprising same |
DE19829947A1 (de) | 1998-07-04 | 2000-01-05 | Bayer Ag | Elektrolumineszierende Anordnungen mit Bor-Chelaten |
KR20010086005A (ko) | 1998-11-06 | 2001-09-07 | 스타르크, 카르크 | 트리사이클릭 피라졸 유도체 |
US6462036B1 (en) * | 1998-11-06 | 2002-10-08 | Basf Aktiengesellschaft | Tricyclic pyrazole derivatives |
WO2000044387A1 (fr) | 1999-01-29 | 2000-08-03 | Nitto Kasei Co., Ltd. | Composes organobores presentant une activite de coccidiostats |
CA2373279A1 (en) | 1999-05-25 | 2000-12-14 | The Penn State Research Foundation | Dna methyltransferase inhibitors |
CN1249025C (zh) * | 1999-07-16 | 2006-04-05 | 里奥药物制品有限公司 | 作为IL-1β和TNF-α的抑制剂的氨基二苯酮 |
US6306628B1 (en) | 1999-08-25 | 2001-10-23 | Ambergen, Incorporated | Methods for the detection, analysis and isolation of Nascent proteins |
CA2383554C (en) | 1999-08-25 | 2008-03-18 | Ambergen, Inc. | Methods for the detection, analysis and isolation of nascent proteins |
US6369098B1 (en) * | 1999-10-05 | 2002-04-09 | Bethesda Pharmaceuticals, Inc. | Dithiolane derivatives |
WO2001049303A1 (en) | 2000-01-06 | 2001-07-12 | Marantech Holding, Llc | Multivalent electron active compositions and methods of making and using same |
US6521619B2 (en) | 2000-06-29 | 2003-02-18 | Icos Corporation | Aryl phenylcyclopropyl sulfide derivatives and their use as cell adhesion inhibiting anti-inflammatory and immune suppressive agents |
AU2001275930B2 (en) | 2000-07-14 | 2007-05-10 | Eisai Inc. | Alpha-msh related compounds and methods of use |
JP2004524281A (ja) | 2000-11-30 | 2004-08-12 | ザ ペン ステート リサーチ ファウンデイション | Dnaメチルトランスフェラーゼ阻害剤 |
DE10110051C2 (de) | 2001-03-02 | 2003-07-03 | Clariant Gmbh | Verfahren zur Herstellung von Boron- und Borinsäuren |
GB0117645D0 (en) | 2001-07-19 | 2001-09-12 | Isis Innovation | Therapeutic stratergies for prevention and treatment of alzheimers disease |
DE10143979A1 (de) | 2001-09-07 | 2003-03-27 | Clariant Gmbh | Verfahren zur Herstellung von Bisallylboranen und nicht-aromatischen Boronsäuren |
WO2003033002A1 (fr) * | 2001-10-11 | 2003-04-24 | Ono Pharmaceutical Co | Inhibiteurs de l'augmentation de la concentration du calcium intracellulaire |
CA2473238A1 (en) | 2002-01-10 | 2003-07-24 | The Penn State Research Foundation | Methods for the preparation of alkyl diaryl borinates and complexed diarylboronic acids |
JP2005538953A (ja) * | 2002-05-28 | 2005-12-22 | 3−ディメンショナル ファーマシューティカルズ, インコーポレイテッド | 新規チオフェンアミジン、それらの組成物、および補体媒介疾患および病気を治療する方法 |
EP1578434A2 (en) | 2002-07-09 | 2005-09-28 | Point Therapeutics, Inc. | Methods and compositions relating to isoleucine boroproline compounds |
US7446236B2 (en) | 2002-12-02 | 2008-11-04 | Solvias Ag | Catalytic hydrogenation of carbon-heteroatom double bonds |
US7390806B2 (en) | 2002-12-18 | 2008-06-24 | Anacor Pharmaceuticals, Inc. | Antibiotics containing borinic acid complexes and methods of use |
EP1980564A1 (en) | 2002-12-18 | 2008-10-15 | Anacor Pharmaceuticals, Inc. | Antibiotics containing borinic acid complexes and methods of use |
WO2005000200A2 (en) | 2003-05-09 | 2005-01-06 | Sugen, Inc. | Novel kinases |
BRPI0411582A (pt) | 2003-06-16 | 2006-08-08 | Anacor Pharmaceuticals Inc | substáncias terapêuticas contendo boro hidroliticamente resistentes e método de uso |
WO2005112970A2 (en) | 2004-05-12 | 2005-12-01 | The Brigham And Women's Hospital, Inc. | Use of gelsolin to treat infections |
DE602005017626D1 (de) | 2004-06-14 | 2009-12-24 | Anacor Pharmaceuticals Inc | Antivirale verwendung von borinsäurekomplexen |
AR049915A1 (es) | 2004-06-14 | 2006-09-13 | Anacor Pharmaceuticals Inc | Compuestos con contenido de boro y metodos de uso de los mismos |
WO2006062731A1 (en) | 2004-11-19 | 2006-06-15 | University Of North Texas Health Science Center At Fort Worth | Phenanthroline and derivatives thereof used to lower intraocular pressure in an affected eye |
GB0501944D0 (en) | 2005-01-31 | 2005-03-09 | Univ Cambridge Tech | Compounds for use in chemical detection and/or quantitation |
CA2597982C (en) * | 2005-02-16 | 2014-07-08 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
US7767657B2 (en) | 2005-02-16 | 2010-08-03 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
US7919422B2 (en) | 2005-03-08 | 2011-04-05 | Agency For Science, Technology And Research | Chiral bisoxazoline catalysts |
US20060222671A1 (en) | 2005-03-30 | 2006-10-05 | Astion Development A/S | Dermatological compositions and salts for the treatment of dermatological diseases |
US20080234229A1 (en) | 2005-08-18 | 2008-09-25 | Auspex Pharmaceuticals, Inc. | Novel Therapeutic Agents for the Treatment of Cancer, Metabolic Diseases and Skin Disorders |
SI2719388T1 (sl) * | 2006-02-16 | 2019-06-28 | Anacor Pharmaceuticals, Inc. | Majhne molekule, polnjene z borom, kot učinkovine proti vnetjem |
WO2007146965A2 (en) | 2006-06-12 | 2007-12-21 | Anacor Pharmaceuticals, Inc. | Compounds for the treatment of periodontal disease |
US20070286822A1 (en) | 2006-06-12 | 2007-12-13 | Anacor Pharmaceuticals Inc. | Compounds for the Treatment of Periodontal Disease |
KR100848491B1 (ko) | 2007-01-16 | 2008-07-28 | 영진약품공업주식회사 | 베타아미노기를 갖는 2-싸이아졸리딘 유도체, 이의약학적으로 허용 가능한 염 및 이의 제조 방법 |
JO3396B1 (ar) | 2007-06-20 | 2019-10-20 | Anacor Pharmaceuticals Inc | جزيئات صغيرة تحتوي على البورون |
KR100895300B1 (ko) | 2007-07-20 | 2009-05-07 | 한국전자통신연구원 | 생체신호 측정의복과 생체신호 처리시스템 |
WO2009111676A2 (en) | 2008-03-06 | 2009-09-11 | Anacor Pharmaceuticals, Inc | Boron-containing small molecules as anti-inflammatory agents |
MX2010009765A (es) | 2008-03-06 | 2013-07-12 | Anacor Pharmaceuticals Inc | Moleculas pequeñas que contienen boro como agentes anti-inflamatorios. |
EP2285384A4 (en) | 2008-05-12 | 2012-04-25 | Anacor Pharmaceuticals Inc | BORN SMALL MOLECULES |
EP2348863A4 (en) | 2008-09-04 | 2012-03-07 | Anacor Pharmaceuticals Inc | BORN SMALL MOLECULES |
WO2010028005A1 (en) | 2008-09-04 | 2010-03-11 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
WO2010045505A1 (en) | 2008-10-15 | 2010-04-22 | Anacor Pharmaceuticals, Inc | Boron-containing small molecules as anti-protozoal agents |
US9493489B2 (en) | 2008-10-15 | 2016-11-15 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules as anti-protozoal agents |
EP2378886A4 (en) | 2008-12-17 | 2012-08-29 | Anacor Pharmaceuticals Inc | (S) -3-Aminomethyl-7- (3-hydroxypropoxy) -3H-benzo [c] [1,2] oxaborole-1-OL-POLYMORPHS |
BR112012001987A2 (pt) | 2009-07-28 | 2015-09-01 | Anacor Pharmaceuticals Inc | Composto, combinação, formulação farmacêutica, uso de um composto, uma combinação ou um sal farmaceuticamente aceitável dos mesmos, e, métodos para tratar uma infecção bacteriana, para matar ou inibir o crescimento de uma bactéria, e para inibir uma beta-lactamase. |
US20110212918A1 (en) | 2009-11-11 | 2011-09-01 | Anacor Pharmaceuticals, Inc. | Boron-containing small molecules |
WO2011094450A1 (en) | 2010-01-27 | 2011-08-04 | Anacor Pharmaceuticals, Inc | Boron-containing small molecules |
-
2007
- 2007-02-16 SI SI200732111T patent/SI2719388T1/sl unknown
- 2007-02-16 PT PT13179945T patent/PT2719388T/pt unknown
- 2007-02-16 DK DK07757149.5T patent/DK1988779T5/en active
- 2007-02-16 ME MEP-2015-97A patent/ME02188B/me unknown
- 2007-02-16 KR KR1020147035518A patent/KR101622870B1/ko active IP Right Grant
- 2007-02-16 AU AU2007214421A patent/AU2007214421B2/en active Active
- 2007-02-16 KR KR1020177001541A patent/KR101819869B1/ko active IP Right Grant
- 2007-02-16 PL PL13179945T patent/PL2719388T3/pl unknown
- 2007-02-16 NZ NZ570257A patent/NZ570257A/en unknown
- 2007-02-16 KR KR1020137025594A patent/KR20130120552A/ko not_active Application Discontinuation
- 2007-02-16 ES ES07757149.5T patent/ES2542342T3/es active Active
- 2007-02-16 MX MX2008010381A patent/MX2008010381A/es active IP Right Grant
- 2007-02-16 KR KR1020157000589A patent/KR20150013941A/ko not_active Application Discontinuation
- 2007-02-16 PT PT77571495T patent/PT1988779E/pt unknown
- 2007-02-16 US US11/676,120 patent/US8168614B2/en active Active
- 2007-02-16 EP EP13179945.4A patent/EP2719388B1/en active Active
- 2007-02-16 KR KR1020087022631A patent/KR20080110751A/ko active Application Filing
- 2007-02-16 RU RU2008137086/15A patent/RU2508113C2/ru active
- 2007-02-16 EP EP07757149.5A patent/EP1988779B1/en active Active
- 2007-02-16 DK DK13179945.4T patent/DK2719388T3/da active
- 2007-02-16 WO PCT/US2007/062350 patent/WO2007095638A2/en active Application Filing
- 2007-02-16 BR BRPI0708051-4A patent/BRPI0708051A2/pt not_active Application Discontinuation
- 2007-02-16 HU HUE07757149A patent/HUE025048T2/en unknown
- 2007-02-16 JP JP2008555528A patent/JP5419466B2/ja active Active
- 2007-02-16 KR KR1020157027015A patent/KR20150113219A/ko active Application Filing
- 2007-02-16 ES ES13179945T patent/ES2728455T3/es active Active
- 2007-02-16 HU HUE13179945 patent/HUE044941T2/hu unknown
- 2007-02-16 MX MX2013015092A patent/MX360301B/es unknown
- 2007-02-16 CA CA2933994A patent/CA2933994A1/en not_active Abandoned
- 2007-02-16 PL PL07757149T patent/PL1988779T3/pl unknown
- 2007-02-16 RU RU2013152132A patent/RU2642628C2/ru not_active Application Discontinuation
- 2007-02-16 CN CN2007800133393A patent/CN101420854B/zh active Active
- 2007-02-16 CA CA2642583A patent/CA2642583C/en active Active
- 2007-02-16 KR KR1020147013817A patent/KR20140082842A/ko not_active Application Discontinuation
- 2007-02-16 CN CN201310283871.4A patent/CN103479654B/zh active Active
- 2007-02-16 SI SI200731663T patent/SI1988779T1/sl unknown
- 2007-02-16 RS RS20150474A patent/RS54108B1/en unknown
-
2008
- 2008-08-04 IL IL193230A patent/IL193230A/en active IP Right Grant
- 2008-08-04 ZA ZA2008/06754A patent/ZA200806754B/en unknown
-
2009
- 2009-02-19 HK HK09101607.4A patent/HK1121344A1/xx unknown
-
2012
- 2012-04-23 US US13/453,682 patent/US8501712B2/en active Active
-
2013
- 2013-07-30 US US13/954,770 patent/US9029353B2/en active Active
- 2013-08-23 JP JP2013173486A patent/JP2013253097A/ja active Pending
-
2015
- 2015-04-13 JP JP2015082026A patent/JP2015147795A/ja active Pending
- 2015-04-16 US US14/688,581 patent/US9682092B2/en active Active
- 2015-07-01 HR HRP20150710TT patent/HRP20150710T1/hr unknown
- 2015-09-21 IL IL241792A patent/IL241792B/en active IP Right Grant
-
2016
- 2016-07-14 JP JP2016139202A patent/JP6266708B2/ja active Active
-
2017
- 2017-05-18 US US15/599,203 patent/US20170258819A1/en not_active Abandoned
-
2019
- 2019-02-01 US US16/265,006 patent/US20190160081A1/en not_active Abandoned
- 2019-05-14 CY CY20191100519T patent/CY1121899T1/el unknown
- 2019-05-31 US US16/427,621 patent/US20190282594A1/en not_active Abandoned
- 2019-10-08 US US16/595,633 patent/US20200046745A1/en not_active Abandoned
-
2020
- 2020-02-13 US US16/789,777 patent/US20200179418A1/en not_active Abandoned
- 2020-08-27 US US17/004,047 patent/US20210000847A1/en not_active Abandoned
-
2022
- 2022-07-20 US US17/869,351 patent/US20230008130A1/en not_active Abandoned
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2013253097A (ja) * | 2006-02-16 | 2013-12-19 | Anacor Pharmaceuticals Inc | 抗炎症剤としてのホウ素含有小分子 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6266708B2 (ja) | 抗炎症剤としてのホウ素含有小分子 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100216 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20100216 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120823 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20121119 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20121127 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20121213 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20121220 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130225 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130226 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130423 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130723 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130730 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130823 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20131022 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20131119 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5419466 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |