KR102692840B1 - 의학적 장애의 예방 및 치료를 위한 화합물 및 이의 용도 - Google Patents
의학적 장애의 예방 및 치료를 위한 화합물 및 이의 용도 Download PDFInfo
- Publication number
- KR102692840B1 KR102692840B1 KR1020207005279A KR20207005279A KR102692840B1 KR 102692840 B1 KR102692840 B1 KR 102692840B1 KR 1020207005279 A KR1020207005279 A KR 1020207005279A KR 20207005279 A KR20207005279 A KR 20207005279A KR 102692840 B1 KR102692840 B1 KR 102692840B1
- Authority
- KR
- South Korea
- Prior art keywords
- compound
- gal
- alkyl
- compounds
- group
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 266
- 238000011282 treatment Methods 0.000 title claims description 25
- 230000002265 prevention Effects 0.000 title 1
- 102000007563 Galectins Human genes 0.000 claims abstract description 65
- 108010046569 Galectins Proteins 0.000 claims abstract description 65
- 238000000034 method Methods 0.000 claims abstract description 50
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 35
- 108010001517 Galectin 3 Proteins 0.000 claims description 158
- 102100039558 Galectin-3 Human genes 0.000 claims description 140
- 230000027455 binding Effects 0.000 claims description 82
- 229910052736 halogen Inorganic materials 0.000 claims description 38
- 150000002367 halogens Chemical group 0.000 claims description 37
- 125000003118 aryl group Chemical group 0.000 claims description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- 206010016654 Fibrosis Diseases 0.000 claims description 31
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 31
- 229910052760 oxygen Inorganic materials 0.000 claims description 31
- 239000001301 oxygen Chemical group 0.000 claims description 31
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 30
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 29
- 150000001412 amines Chemical group 0.000 claims description 29
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
- 230000004761 fibrosis Effects 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 26
- -1 dinitromethyl Chemical group 0.000 claims description 25
- 238000006467 substitution reaction Methods 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 102000000802 Galectin 3 Human genes 0.000 claims description 23
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 23
- 239000011593 sulfur Chemical group 0.000 claims description 23
- 229910052717 sulfur Inorganic materials 0.000 claims description 23
- 125000005842 heteroatom Chemical group 0.000 claims description 22
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical group [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 21
- 230000000694 effects Effects 0.000 claims description 21
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- 229910052711 selenium Chemical group 0.000 claims description 21
- 239000011669 selenium Chemical group 0.000 claims description 21
- 239000012453 solvate Substances 0.000 claims description 21
- 150000001413 amino acids Chemical class 0.000 claims description 18
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 18
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 16
- 206010022489 Insulin Resistance Diseases 0.000 claims description 16
- 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 claims description 16
- 102100036721 Insulin receptor Human genes 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 108010001127 Insulin Receptor Proteins 0.000 claims description 14
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000003277 amino group Chemical group 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 208000035475 disorder Diseases 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 230000009885 systemic effect Effects 0.000 claims description 11
- 150000001408 amides Chemical group 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 10
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 9
- 230000002209 hydrophobic effect Effects 0.000 claims description 9
- 229940124530 sulfonamide Drugs 0.000 claims description 9
- 150000003456 sulfonamides Chemical class 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 208000023275 Autoimmune disease Diseases 0.000 claims description 8
- 102000004877 Insulin Human genes 0.000 claims description 8
- 108090001061 Insulin Proteins 0.000 claims description 8
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 8
- 229940125396 insulin Drugs 0.000 claims description 8
- 150000004702 methyl esters Chemical class 0.000 claims description 8
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 8
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 8
- 230000001575 pathological effect Effects 0.000 claims description 8
- 239000002671 adjuvant Substances 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 6
- 229910019142 PO4 Inorganic materials 0.000 claims description 6
- 239000001177 diphosphate Substances 0.000 claims description 6
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 6
- 235000011180 diphosphates Nutrition 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 238000001990 intravenous administration Methods 0.000 claims description 6
- 230000001613 neoplastic effect Effects 0.000 claims description 6
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 6
- 235000020824 obesity Nutrition 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 6
- 239000010452 phosphate Substances 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 238000007920 subcutaneous administration Methods 0.000 claims description 6
- 108010001498 Galectin 1 Proteins 0.000 claims description 5
- 230000007882 cirrhosis Effects 0.000 claims description 5
- 210000003734 kidney Anatomy 0.000 claims description 5
- 208000030159 metabolic disease Diseases 0.000 claims description 5
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 5
- 201000002793 renal fibrosis Diseases 0.000 claims description 5
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 230000003510 anti-fibrotic effect Effects 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 230000003176 fibrotic effect Effects 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 208000017520 skin disease Diseases 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 208000004930 Fatty Liver Diseases 0.000 claims description 3
- 102000044445 Galectin-8 Human genes 0.000 claims description 3
- 102100031351 Galectin-9 Human genes 0.000 claims description 3
- 101710121810 Galectin-9 Proteins 0.000 claims description 3
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 3
- 101000608769 Homo sapiens Galectin-8 Proteins 0.000 claims description 3
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 claims description 3
- 101710184277 Insulin-like growth factor 1 receptor Proteins 0.000 claims description 3
- 230000001476 alcoholic effect Effects 0.000 claims description 3
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 3
- 229940124599 anti-inflammatory drug Drugs 0.000 claims description 3
- 206010003246 arthritis Diseases 0.000 claims description 3
- 230000009787 cardiac fibrosis Effects 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 239000002417 nutraceutical Substances 0.000 claims description 3
- 235000021436 nutraceutical agent Nutrition 0.000 claims description 3
- 238000007911 parenteral administration Methods 0.000 claims description 3
- 230000035945 sensitivity Effects 0.000 claims description 3
- 239000013589 supplement Substances 0.000 claims description 3
- 230000003612 virological effect Effects 0.000 claims description 3
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 2
- 208000019693 Lung disease Diseases 0.000 claims description 2
- 208000001280 Prediabetic State Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- 230000006793 arrhythmia Effects 0.000 claims description 2
- 206010003119 arrhythmia Diseases 0.000 claims description 2
- 201000008937 atopic dermatitis Diseases 0.000 claims description 2
- 230000005784 autoimmunity Effects 0.000 claims description 2
- 208000004104 gestational diabetes Diseases 0.000 claims description 2
- 201000009104 prediabetes syndrome Diseases 0.000 claims description 2
- 230000002062 proliferating effect Effects 0.000 claims description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 229930195733 hydrocarbon Natural products 0.000 claims 2
- 150000002430 hydrocarbons Chemical class 0.000 claims 2
- 150000003018 phosphorus compounds Chemical class 0.000 claims 2
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- 102100021736 Galectin-1 Human genes 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 230000003993 interaction Effects 0.000 description 54
- 210000004027 cell Anatomy 0.000 description 40
- 230000005764 inhibitory process Effects 0.000 description 37
- 239000011541 reaction mixture Substances 0.000 description 37
- 108010044426 integrins Proteins 0.000 description 30
- 102000006495 integrins Human genes 0.000 description 30
- 239000003446 ligand Substances 0.000 description 30
- 239000000243 solution Substances 0.000 description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 27
- 210000004185 liver Anatomy 0.000 description 24
- 125000001624 naphthyl group Chemical group 0.000 description 24
- 238000002474 experimental method Methods 0.000 description 23
- 230000003281 allosteric effect Effects 0.000 description 22
- 125000001072 heteroaryl group Chemical group 0.000 description 22
- 230000002829 reductive effect Effects 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 102000003886 Glycoproteins Human genes 0.000 description 20
- 108090000288 Glycoproteins Proteins 0.000 description 20
- 241001465754 Metazoa Species 0.000 description 20
- 238000005481 NMR spectroscopy Methods 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- 238000005160 1H NMR spectroscopy Methods 0.000 description 17
- 235000001014 amino acid Nutrition 0.000 description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 16
- USEKNVIVIYWTMA-UHFFFAOYSA-N 7-chloro-2,3-dihydro-1h-pyrrolo[1,2-a]quinazolin-5-one Chemical compound O=C1C2=CC(Cl)=CC=C2N2CCCC2=N1 USEKNVIVIYWTMA-UHFFFAOYSA-N 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 13
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 12
- 230000002757 inflammatory effect Effects 0.000 description 12
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- HCVFBHXQPGDVRD-UHFFFAOYSA-N CC(C)(C)OC(=O)N1CCc2c(C1)c(=O)nc1CCCn21 Chemical compound CC(C)(C)OC(=O)N1CCc2c(C1)c(=O)nc1CCCn21 HCVFBHXQPGDVRD-UHFFFAOYSA-N 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 150000001720 carbohydrates Chemical class 0.000 description 11
- 235000014633 carbohydrates Nutrition 0.000 description 11
- 210000002540 macrophage Anatomy 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 206010061218 Inflammation Diseases 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 230000004054 inflammatory process Effects 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 239000003981 vehicle Substances 0.000 description 9
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 8
- 102000008186 Collagen Human genes 0.000 description 8
- 108010035532 Collagen Proteins 0.000 description 8
- 108010030317 Macrophage-1 Antigen Proteins 0.000 description 8
- 229920001436 collagen Polymers 0.000 description 8
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- OPFTYMRCKYDKLV-UHFFFAOYSA-N 1H-pyrrolo[1,2-a]quinazolin-5-one Chemical compound C12=CC=CC=C2C(=O)N=C2N1CC=C2 OPFTYMRCKYDKLV-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 210000004072 lung Anatomy 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 6
- 102000004856 Lectins Human genes 0.000 description 6
- 108090001090 Lectins Proteins 0.000 description 6
- 206010027476 Metastases Diseases 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 125000003282 alkyl amino group Chemical group 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000013058 crude material Substances 0.000 description 6
- 125000004663 dialkyl amino group Chemical group 0.000 description 6
- 239000002158 endotoxin Substances 0.000 description 6
- 229930182830 galactose Natural products 0.000 description 6
- 150000002256 galaktoses Chemical class 0.000 description 6
- 238000007912 intraperitoneal administration Methods 0.000 description 6
- 230000002503 metabolic effect Effects 0.000 description 6
- 230000009401 metastasis Effects 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- 230000008506 pathogenesis Effects 0.000 description 6
- 230000010287 polarization Effects 0.000 description 6
- 238000002953 preparative HPLC Methods 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- ATPCFYALUHSZQH-UHFFFAOYSA-N BrC1=CC=C2N3CCCC3=NC(=O)C2=C1 Chemical compound BrC1=CC=C2N3CCCC3=NC(=O)C2=C1 ATPCFYALUHSZQH-UHFFFAOYSA-N 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000033115 angiogenesis Effects 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 5
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 5
- 229960002591 hydroxyproline Drugs 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 239000002523 lectin Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 210000001616 monocyte Anatomy 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 230000019491 signal transduction Effects 0.000 description 5
- 230000011664 signaling Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 5
- NUSJOHOXLJHJOM-UHFFFAOYSA-N 2,3-dihydro-1h-pyrrolo[1,2-a]quinazolin-5-one Chemical compound C12=CC=CC=C2C(=O)N=C2N1CCC2 NUSJOHOXLJHJOM-UHFFFAOYSA-N 0.000 description 4
- UOGYCZVTBOYGAE-UHFFFAOYSA-N 4-[(4-methylphenyl)methylsulfanyl]benzaldehyde Chemical compound CC1=CC=C(CSC2=CC=C(C=O)C=C2)C=C1 UOGYCZVTBOYGAE-UHFFFAOYSA-N 0.000 description 4
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 238000002965 ELISA Methods 0.000 description 4
- 102000000795 Galectin 1 Human genes 0.000 description 4
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 4
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 238000012565 NMR experiment Methods 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 4
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 4
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 4
- 235000010724 Wisteria floribunda Nutrition 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 230000002708 enhancing effect Effects 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 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 4
- 239000002904 solvent Substances 0.000 description 4
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 4
- 230000008685 targeting Effects 0.000 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 description 4
- 230000003442 weekly effect Effects 0.000 description 4
- NRLPPGBADQVXSJ-UHFFFAOYSA-N 4-sulfanylbenzaldehyde Chemical compound SC1=CC=C(C=O)C=C1 NRLPPGBADQVXSJ-UHFFFAOYSA-N 0.000 description 3
- QYGNDKJRRNVSEC-UHFFFAOYSA-N 5-methoxy-3,4-dihydro-2h-pyrrole Chemical compound COC1=NCCC1 QYGNDKJRRNVSEC-UHFFFAOYSA-N 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 3
- YQIISSIVNYSUAQ-UHFFFAOYSA-N CC1=CC=C(CS(=O)(=O)C2=CC=C(C=O)C=C2)C=C1 Chemical compound CC1=CC=C(CS(=O)(=O)C2=CC=C(C=O)C=C2)C=C1 YQIISSIVNYSUAQ-UHFFFAOYSA-N 0.000 description 3
- 102000019034 Chemokines Human genes 0.000 description 3
- 108010012236 Chemokines Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 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 3
- 241000124008 Mammalia Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 108091008606 PDGF receptors Proteins 0.000 description 3
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 3
- 108091008874 T cell receptors Proteins 0.000 description 3
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 3
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 238000007876 drug discovery Methods 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 3
- 150000008195 galaktosides Chemical class 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- 210000003494 hepatocyte Anatomy 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- NFZIRYOGSVRUQE-UHFFFAOYSA-N o-(4-formylphenyl) n,n-dimethylcarbamothioate Chemical compound CN(C)C(=S)OC1=CC=C(C=O)C=C1 NFZIRYOGSVRUQE-UHFFFAOYSA-N 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- AVYSFQMOPSDSBK-UHFFFAOYSA-N s-(4-formylphenyl) n,n-dimethylcarbamothioate Chemical compound CN(C)C(=O)SC1=CC=C(C=O)C=C1 AVYSFQMOPSDSBK-UHFFFAOYSA-N 0.000 description 3
- 108010038196 saccharide-binding proteins Proteins 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- KCDXJAYRVLXPFO-UHFFFAOYSA-N syringaldehyde Chemical compound COC1=CC(C=O)=CC(OC)=C1O KCDXJAYRVLXPFO-UHFFFAOYSA-N 0.000 description 3
- COBXDAOIDYGHGK-UHFFFAOYSA-N syringaldehyde Natural products COC1=CC=C(C=O)C(OC)=C1O COBXDAOIDYGHGK-UHFFFAOYSA-N 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 3
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- WECLXYQORKVHQC-UHFFFAOYSA-N 7-fluoro-2,3-dihydro-1H-pyrrolo[1,2-a]quinazolin-5-one Chemical compound Fc1ccc2n3CCCc3nc(=O)c2c1 WECLXYQORKVHQC-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 108091008875 B cell receptors Proteins 0.000 description 2
- 108010006654 Bleomycin Proteins 0.000 description 2
- GAXYWIOOYJXHGB-YYADALCUSA-N CC1=CC=C(C=C1)C(=O)N(C1=CC=C(\C=C2/CCN3C2=NC(=O)C2=CC=CC=C32)C=C1)S(=O)(=O)C1=CC=C(C)C=C1 Chemical compound CC1=CC=C(C=C1)C(=O)N(C1=CC=C(\C=C2/CCN3C2=NC(=O)C2=CC=CC=C32)C=C1)S(=O)(=O)C1=CC=C(C)C=C1 GAXYWIOOYJXHGB-YYADALCUSA-N 0.000 description 2
- GTIPVXWZOOASHZ-LTGZKZEYSA-N CC1=CC=C(CS(=O)(=O)C2=CC=C(\C=C3/CCN4C3=NC(=O)C3=CC=CC=C43)C=C2)C=C1 Chemical compound CC1=CC=C(CS(=O)(=O)C2=CC=C(\C=C3/CCN4C3=NC(=O)C3=CC=CC=C43)C=C2)C=C1 GTIPVXWZOOASHZ-LTGZKZEYSA-N 0.000 description 2
- 102000049320 CD36 Human genes 0.000 description 2
- 108010045374 CD36 Antigens Proteins 0.000 description 2
- 229940045513 CTLA4 antagonist Drugs 0.000 description 2
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 2
- 102000003849 Cytochrome P450 Human genes 0.000 description 2
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108091008794 FGF receptors Proteins 0.000 description 2
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 2
- 102000016621 Focal Adhesion Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108010067715 Focal Adhesion Protein-Tyrosine Kinases Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 2
- 229930182566 Gentamicin Natural products 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 101000608757 Homo sapiens Galectin-3 Proteins 0.000 description 2
- 206010062016 Immunosuppression Diseases 0.000 description 2
- 102100038225 Lysosome-associated membrane glycoprotein 2 Human genes 0.000 description 2
- 101710116771 Lysosome-associated membrane glycoprotein 2 Proteins 0.000 description 2
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 2
- 238000013231 NASH rodent model Methods 0.000 description 2
- 206010029113 Neovascularisation Diseases 0.000 description 2
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 2
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 108091006299 SLC2A2 Proteins 0.000 description 2
- 208000034189 Sclerosis Diseases 0.000 description 2
- 108010017622 Somatomedin Receptors Proteins 0.000 description 2
- 102000004584 Somatomedin Receptors Human genes 0.000 description 2
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 description 2
- 102100033456 TGF-beta receptor type-1 Human genes 0.000 description 2
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 2
- 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229940125528 allosteric inhibitor Drugs 0.000 description 2
- 230000008841 allosteric interaction Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000007080 aromatic substitution reaction Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000010876 biochemical test Methods 0.000 description 2
- 229960001561 bleomycin Drugs 0.000 description 2
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 210000004087 cornea Anatomy 0.000 description 2
- 229940109239 creatinine Drugs 0.000 description 2
- 230000008021 deposition Effects 0.000 description 2
- 239000010432 diamond Substances 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 208000016097 disease of metabolism Diseases 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 238000002875 fluorescence polarization Methods 0.000 description 2
- 229960002518 gentamicin Drugs 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000004190 glucose uptake Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000007489 histopathology method Methods 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 238000002991 immunohistochemical analysis Methods 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 230000008611 intercellular interaction Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 210000005228 liver tissue Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 208000037819 metastatic cancer Diseases 0.000 description 2
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000003228 microsomal effect Effects 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- ZJHLLODKYOJMLY-UHFFFAOYSA-N n-(4-formylphenyl)-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC1=CC=C(C=O)C=C1 ZJHLLODKYOJMLY-UHFFFAOYSA-N 0.000 description 2
- VATYWCRQDJIRAI-UHFFFAOYSA-N p-aminobenzaldehyde Chemical compound NC1=CC=C(C=O)C=C1 VATYWCRQDJIRAI-UHFFFAOYSA-N 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 238000013149 parallel artificial membrane permeability assay Methods 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 235000021395 porridge Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000006916 protein interaction Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000003118 sandwich ELISA Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 125000001424 substituent group Chemical group 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
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 230000005748 tumor development Effects 0.000 description 2
- MIPWNNQKZMUIMM-LTGZKZEYSA-N (3E)-3-[[4-[(4-methylphenyl)methylsulfanyl]phenyl]methylidene]-1,2-dihydropyrrolo[1,2-a]quinazolin-5-one Chemical compound CC1=CC=C(CSC2=CC=C(\C=C\3/CCN4C/3=NC(C3=CC=CC=C43)=O)C=C2)C=C1 MIPWNNQKZMUIMM-LTGZKZEYSA-N 0.000 description 1
- CAAZCGQQFQYATF-KPKJPENVSA-N (3E)-7-fluoro-3-[(4-hydroxy-3,5-dimethoxyphenyl)methylidene]-1,2-dihydropyrrolo[1,2-a]quinazolin-5-one Chemical compound COC1=CC(\C=C2/CCN3C2=NC(=O)C2=CC(F)=CC=C32)=CC(OC)=C1O CAAZCGQQFQYATF-KPKJPENVSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- WZRKSPFYXUXINF-UHFFFAOYSA-N 1-(bromomethyl)-4-methylbenzene Chemical compound CC1=CC=C(CBr)C=C1 WZRKSPFYXUXINF-UHFFFAOYSA-N 0.000 description 1
- 238000004834 15N NMR spectroscopy Methods 0.000 description 1
- BJKWHAILFUUIRT-UHFFFAOYSA-N 2,5-difluorobenzamide Chemical compound NC(=O)C1=CC(F)=CC=C1F BJKWHAILFUUIRT-UHFFFAOYSA-N 0.000 description 1
- JEBHLIYFPKISBI-UHFFFAOYSA-N 3,4-dihydro-2h-pyrrol-5-amine;hydrochloride Chemical compound Cl.NC1=NCCC1 JEBHLIYFPKISBI-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- DLHNFALLCPFMPK-UHFFFAOYSA-N 3-ethoxycarbonyl-4-oxopiperidine-1-carboxylic acid Chemical compound CCOC(=O)C1CN(C(O)=O)CCC1=O DLHNFALLCPFMPK-UHFFFAOYSA-N 0.000 description 1
- XYPVBKDHERGKJG-UHFFFAOYSA-N 4-(bromomethyl)benzaldehyde Chemical compound BrCC1=CC=C(C=O)C=C1 XYPVBKDHERGKJG-UHFFFAOYSA-N 0.000 description 1
- NQUVCRCCRXRJCK-UHFFFAOYSA-N 4-methylbenzoyl chloride Chemical compound CC1=CC=C(C(Cl)=O)C=C1 NQUVCRCCRXRJCK-UHFFFAOYSA-N 0.000 description 1
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
- 102100033400 4F2 cell-surface antigen heavy chain Human genes 0.000 description 1
- JYYRNCSCDJYPSN-UHFFFAOYSA-N 5-[(4-hydroxy-3-methoxyphenyl)methylidene]-2,7,11-triazatricyclo[7.4.0.02,6]trideca-1(9),6-dien-8-one Chemical compound OC1=C(C=C(C=C2CCN3C2=NC(C2=C3CCNC2)=O)C=C1)OC JYYRNCSCDJYPSN-UHFFFAOYSA-N 0.000 description 1
- MAGQVUXQRXLNGB-UHFFFAOYSA-N 5-bromo-2-fluorobenzamide Chemical compound NC(=O)C1=CC(Br)=CC=C1F MAGQVUXQRXLNGB-UHFFFAOYSA-N 0.000 description 1
- VTSILFLCXIRODM-UHFFFAOYSA-N 5-chloro-2-fluorobenzamide Chemical compound NC(=O)C1=CC(Cl)=CC=C1F VTSILFLCXIRODM-UHFFFAOYSA-N 0.000 description 1
- VDJKJPMLWJWQIH-UHFFFAOYSA-M 5-ethylphenazin-5-ium;ethyl sulfate Chemical compound CCOS([O-])(=O)=O.C1=CC=C2[N+](CC)=C(C=CC=C3)C3=NC2=C1 VDJKJPMLWJWQIH-UHFFFAOYSA-M 0.000 description 1
- 102100038222 60 kDa heat shock protein, mitochondrial Human genes 0.000 description 1
- 230000035502 ADME Effects 0.000 description 1
- 102100022749 Aminopeptidase N Human genes 0.000 description 1
- 241000272814 Anser sp. Species 0.000 description 1
- 101100244969 Arabidopsis thaliana PRL1 gene Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 206010004664 Biliary fibrosis Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 239000011547 Bouin solution Substances 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- GAQIZLNOYKJKOK-UHFFFAOYSA-N CCC1CN(CCC1=O)C(C)(C)C Chemical compound CCC1CN(CCC1=O)C(C)(C)C GAQIZLNOYKJKOK-UHFFFAOYSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108010058432 Chaperonin 60 Proteins 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- 229910016860 FaSSIF Inorganic materials 0.000 description 1
- 229910005429 FeSSIF Inorganic materials 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 229940126043 Galectin-3 inhibitor Drugs 0.000 description 1
- 208000002705 Glucose Intolerance Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 1
- 101000800023 Homo sapiens 4F2 cell-surface antigen heavy chain Proteins 0.000 description 1
- 101000757160 Homo sapiens Aminopeptidase N Proteins 0.000 description 1
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 1
- 101100066427 Homo sapiens FCGR1A gene Proteins 0.000 description 1
- 101001042451 Homo sapiens Galectin-1 Proteins 0.000 description 1
- 101000852815 Homo sapiens Insulin receptor Proteins 0.000 description 1
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 1
- 101100454448 Homo sapiens LGALS3 gene Proteins 0.000 description 1
- 101000605020 Homo sapiens Large neutral amino acids transporter small subunit 1 Proteins 0.000 description 1
- 101001074035 Homo sapiens Zinc finger protein GLI2 Proteins 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 206010023421 Kidney fibrosis Diseases 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 108010085895 Laminin Proteins 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 101150051246 MAC2 gene Proteins 0.000 description 1
- 101710091439 Major capsid protein 1 Proteins 0.000 description 1
- 206010064912 Malignant transformation Diseases 0.000 description 1
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 1
- AGUDPJKIHCQYFD-LVZFUZTISA-N N,4-dimethyl-N-[4-[(E)-(5-oxo-1,2-dihydropyrrolo[1,2-a]quinazolin-3-ylidene)methyl]phenyl]benzenesulfonamide Chemical compound CN(S(=O)(=O)C1=CC=C(C=C1)C)C1=CC=C(C=C1)/C=C/1\CCN2C\1=NC(C1=CC=CC=C21)=O AGUDPJKIHCQYFD-LVZFUZTISA-N 0.000 description 1
- 206010061309 Neoplasm progression Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 102100021768 Phosphoserine aminotransferase Human genes 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 1
- 206010038687 Respiratory distress Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- YIQKLZYTHXTDDT-UHFFFAOYSA-H Sirius red F3B Chemical compound C1=CC(=CC=C1N=NC2=CC(=C(C=C2)N=NC3=C(C=C4C=C(C=CC4=C3[O-])NC(=O)NC5=CC6=CC(=C(C(=C6C=C5)[O-])N=NC7=C(C=C(C=C7)N=NC8=CC=C(C=C8)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)[O-])S(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+] YIQKLZYTHXTDDT-UHFFFAOYSA-H 0.000 description 1
- 102000007374 Smad Proteins Human genes 0.000 description 1
- 108010007945 Smad Proteins Proteins 0.000 description 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 101710084191 TGF-beta receptor type-1 Proteins 0.000 description 1
- 108091005735 TGF-beta receptors Proteins 0.000 description 1
- 108010031374 Tissue Inhibitor of Metalloproteinase-1 Proteins 0.000 description 1
- 108010092867 Transforming Growth Factor beta Receptors Proteins 0.000 description 1
- 108010011702 Transforming Growth Factor-beta Type I Receptor Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 1
- 102100035558 Zinc finger protein GLI2 Human genes 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000008856 allosteric binding Effects 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 230000006481 angiogenic pathway Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 238000011394 anticancer treatment Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 239000012911 assay medium Substances 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037180 bone health Effects 0.000 description 1
- 230000008195 breast development Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 102000023852 carbohydrate binding proteins Human genes 0.000 description 1
- 108091008400 carbohydrate binding proteins Proteins 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000034196 cell chemotaxis Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000008619 cell matrix interaction Effects 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 238000002783 cell motility assay Methods 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 231100000045 chemical toxicity Toxicity 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000010205 computational analysis Methods 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- RVIXKDRPFPUUOO-UHFFFAOYSA-N dimethylselenide Chemical compound C[Se]C RVIXKDRPFPUUOO-UHFFFAOYSA-N 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- XIMIGUBYDJDCKI-UHFFFAOYSA-N diselenium Chemical compound [Se]=[Se] XIMIGUBYDJDCKI-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- MAHNFPMIPQKPPI-UHFFFAOYSA-N disulfur Chemical compound S=S MAHNFPMIPQKPPI-UHFFFAOYSA-N 0.000 description 1
- 230000002828 effect on organs or tissue Effects 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- RIOSMHYBRAQVHD-UHFFFAOYSA-N ethyl 4-oxopiperidine-3-carboxylate Chemical compound CCOC(=O)C1CNCCC1=O RIOSMHYBRAQVHD-UHFFFAOYSA-N 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 230000003352 fibrogenic effect Effects 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- JYVHOGDBFNJNMR-UHFFFAOYSA-N hexane;hydrate Chemical compound O.CCCCCC JYVHOGDBFNJNMR-UHFFFAOYSA-N 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 102000045521 human LGALS1 Human genes 0.000 description 1
- 102000048551 human LGALS3 Human genes 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000008798 inflammatory stress Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 150000002597 lactoses Chemical class 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 210000001853 liver microsome Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000009115 maintenance therapy Methods 0.000 description 1
- 230000036212 malign transformation Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000003990 molecular pathway Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- PHWISQNXPLXQRU-UHFFFAOYSA-N n,n-dimethylcarbamothioyl chloride Chemical compound CN(C)C(Cl)=S PHWISQNXPLXQRU-UHFFFAOYSA-N 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000013116 obese mouse model Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000006995 pathophysiological pathway Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000010399 physical interaction Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000013636 protein dimer Substances 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 238000001472 pulsed field gradient Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000026267 regulation of growth Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002165 resonance energy transfer Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 208000011571 secondary malignant neoplasm Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 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
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- OMAKOEQWTUPCFW-UHFFFAOYSA-N tert-butyl 5-[(4-hydroxy-3-methoxyphenyl)methylidene]-8-oxo-2,7,11-triazatricyclo[7.4.0.02,6]trideca-1(9),6-diene-11-carboxylate Chemical compound OC1=C(C=C(C=C2CCN3C2=NC(C2=C3CCN(C2)C(=O)OC(C)(C)C)=O)C=C1)OC OMAKOEQWTUPCFW-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- 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
- A61P11/06—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
- 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
- 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
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762540860P | 2017-08-03 | 2017-08-03 | |
| US62/540,860 | 2017-08-03 | ||
| PCT/US2018/045175 WO2019028357A1 (en) | 2017-08-03 | 2018-08-03 | COMPOUNDS FOR THE PREVENTION AND TREATMENT OF MEDICAL DISORDERS AND USES THEREOF |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20200035982A KR20200035982A (ko) | 2020-04-06 |
| KR102692840B1 true KR102692840B1 (ko) | 2024-08-07 |
Family
ID=65233534
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020207005279A Active KR102692840B1 (ko) | 2017-08-03 | 2018-08-03 | 의학적 장애의 예방 및 치료를 위한 화합물 및 이의 용도 |
Country Status (12)
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI744300B (zh) * | 2016-03-23 | 2021-11-01 | 里爾中央醫學中心 | 改良性熱處理的血小板顆粒裂解液在製備用於治療神經系統疾病的組合物的用途 |
| CN111201030B (zh) | 2017-07-25 | 2024-11-01 | 真和制药有限公司 | 通过阻断tim-3和其配体的相互作用治疗癌症 |
| CN111032039B (zh) | 2017-08-03 | 2024-03-26 | 卡莱克汀科学有限责任公司 | 用于预防和治疗医学障碍的化合物及其用途 |
| KR20210124308A (ko) | 2019-01-30 | 2021-10-14 | 트루바인딩 아이엔씨. | 항-gal3 항체 및 이의 용도 |
| MX2022014786A (es) | 2020-05-26 | 2023-01-16 | Truebinding Inc | Metodos para tratar enfermedades inflamatorias mediante el bloqueo de galectina-3. |
| CN117897406A (zh) * | 2021-06-08 | 2024-04-16 | 真和制药有限公司 | 抗gal3抗体及其用于胰岛素抵抗的方法 |
| CN113476442A (zh) * | 2021-07-28 | 2021-10-08 | 上海交通大学医学院附属第九人民医院 | 化合物gb-0139在治疗心肌梗死后心肌过度纤维化的药物中的应用 |
| GB2631509A (en) * | 2023-07-04 | 2025-01-08 | Univ Liverpool | Compositions |
| GB2631507A (en) * | 2023-07-04 | 2025-01-08 | Univ Liverpool | Compositions |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT377586B (de) * | 1981-06-30 | 1985-04-10 | Erba Farmitalia | Verfahren zur herstellung von substituierten pyrrolo-(2,1-b)-chinazolinen und pyrido(2,1-b)chinazolinen |
| IL69274A (en) * | 1982-08-05 | 1986-08-31 | Erba Farmitalia | (substituted amino)derivatives of 3-benzylidene-pyrrolo(2,1-b)quinazolin-9-ones and 6-benzylidene-pyrido(2,1-b)quinazolin-11-ones,their preparation and pharmaceutical compositions containing them |
| SE0100172D0 (sv) * | 2001-01-22 | 2001-01-22 | Ulf Nilsson | New inhibitors against galectins |
| EP1363638A4 (en) | 2001-01-31 | 2010-01-06 | Lundbeck & Co As H | USE OF GAL3 RECEPTOR ANTAGONISTS FOR THE TREATMENT OF DEPRESSION AND / OR ANXIETIES AND USEFUL CONNECTIONS FOR SUCH PROCEDURES |
| US20030078271A1 (en) | 2001-01-31 | 2003-04-24 | Blackburn Thomas P. | Use of GAL3 receptor antagonists for the treatment of depression and/or anxiety and compounds useful in such methods |
| JP4498922B2 (ja) * | 2002-07-09 | 2010-07-07 | アクテリオン ファーマシューティカルズ リミテッド | ７，８，９，１０−テトラヒドロ−６Ｈ−アゼピノ、６，７，８，９−テトラヒドロ−ピリドおよび２，３−ジヒドロ−２Ｈ−ピロロ［２，１−ｂ］−キナゾリノン誘導体 |
| US7220775B2 (en) | 2002-08-07 | 2007-05-22 | H. Lundbeck A/S | Compound useful for the treatment of neuropathic pain |
| DE10304141B4 (de) * | 2003-02-03 | 2006-03-09 | Hf Arzneimittelforschung Gmbh | Verfahren zur Herstellung von Chinazolin-Alkaloiden |
| WO2012158913A2 (en) * | 2011-05-17 | 2012-11-22 | Discoverybiomed Inc. | Treating protein folding disorders with small molecule cftr correctors |
| ES2562903T3 (es) * | 2011-07-13 | 2016-03-09 | Santen Pharmaceutical Co., Ltd | Nuevo compuesto que tiene actividad inhibidora de PARP |
| WO2016004093A2 (en) * | 2014-07-01 | 2016-01-07 | Stealth Biotherapeutics Corp | Therapeutic compositions including galectin-3 inhibitors and uses thereof |
| CA2970062C (en) | 2015-01-30 | 2023-02-28 | Galecto Biotech Ab | Alpha-d-galactoside inhibitors of galectins |
| CN105272986A (zh) * | 2015-06-15 | 2016-01-27 | 厦门医学高等专科学校 | 一种可抑制乙酰胆碱酯酶活性的化合物或其制备方法和应用 |
| CN106220631B (zh) * | 2016-07-26 | 2019-02-05 | 中山大学 | 一种7位氟取代Isaindigotone衍生物及其制备方法和在制备抗癌药物中的应用 |
| CN111032039B (zh) | 2017-08-03 | 2024-03-26 | 卡莱克汀科学有限责任公司 | 用于预防和治疗医学障碍的化合物及其用途 |
-
2018
- 2018-08-03 CN CN201880050555.3A patent/CN111032039B/zh active Active
- 2018-08-03 KR KR1020207005279A patent/KR102692840B1/ko active Active
- 2018-08-03 AU AU2018309085A patent/AU2018309085B2/en active Active
- 2018-08-03 EP EP18841404.9A patent/EP3661502A4/en active Pending
- 2018-08-03 BR BR112020001698-5A patent/BR112020001698A2/pt not_active Application Discontinuation
- 2018-08-03 US US16/629,373 patent/US11583530B2/en active Active
- 2018-08-03 WO PCT/US2018/045175 patent/WO2019028357A1/en not_active Ceased
- 2018-08-03 MX MX2020001256A patent/MX2020001256A/es unknown
- 2018-08-03 IL IL272097A patent/IL272097B2/en unknown
- 2018-08-03 CA CA3069745A patent/CA3069745A1/en active Pending
- 2018-08-03 JP JP2020505233A patent/JP7498108B2/ja active Active
-
2020
- 2020-01-20 ZA ZA2020/00375A patent/ZA202000375B/en unknown
-
2022
- 2022-07-08 US US17/861,023 patent/US12377102B2/en active Active
-
2025
- 2025-07-08 US US19/262,346 patent/US20260060985A1/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| Chemistry of Natural Compounds, vol. 40, pp. 496-498(2004)* |
| Synthesis, vol. 48, pp. A-J(2016)* |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2020529988A (ja) | 2020-10-15 |
| US20260060985A1 (en) | 2026-03-05 |
| IL272097B2 (en) | 2024-06-01 |
| CN111032039B (zh) | 2024-03-26 |
| JP7498108B2 (ja) | 2024-06-11 |
| KR20200035982A (ko) | 2020-04-06 |
| IL272097A (en) | 2020-03-31 |
| EP3661502A1 (en) | 2020-06-10 |
| US20200147088A1 (en) | 2020-05-14 |
| US20230116370A1 (en) | 2023-04-13 |
| IL272097B1 (en) | 2024-02-01 |
| MX2020001256A (es) | 2020-08-17 |
| US12377102B2 (en) | 2025-08-05 |
| CN111032039A (zh) | 2020-04-17 |
| ZA202000375B (en) | 2025-04-30 |
| US11583530B2 (en) | 2023-02-21 |
| CA3069745A1 (en) | 2019-02-07 |
| AU2018309085A1 (en) | 2020-02-06 |
| BR112020001698A2 (pt) | 2020-07-21 |
| EP3661502A4 (en) | 2020-12-02 |
| WO2019028357A1 (en) | 2019-02-07 |
| AU2018309085B2 (en) | 2022-12-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7498108B2 (ja) | 医学的障害の予防および治療のための化合物およびその使用 | |
| US20230132265A1 (en) | Compounds for the prevention and treatment of diseases and the use thereof | |
| AU2018265813A1 (en) | Compounds for the treatment of systemic insulin resistance disorders and the use thereof | |
| WO2019089080A9 (en) | Selenogalactoside compounds for the treatment of systemic insulin resistance disorders and the use thereof | |
| US20230127345A1 (en) | Selenogalactoside compounds for the prevention and treatment of diseases associated with galectin and the use thereof | |
| BR112018067693B1 (pt) | Selenogalactosídeos, seus usos, e composição |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20200224 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20210726 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20230831 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20240502 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20240802 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20240802 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration |