KR20200108303A

KR20200108303A - 갈렉틴의 신규 갈락토시드 억제제

갈렉틴의 신규 갈락토시드 억제제 Download PDF

Info

Publication number: KR20200108303A
Authority: KR; South Korea
Prior art keywords: thio; galactopyranoside; deoxy; triazol; hydroxythiazol
Prior art date: 2018-01-10
Legal status : Withdrawn

Application number

KR1020207022591A

Other languages

English (en)

Korean (ko)

Inventor

프레드릭 제터버그

Original Assignee

갈렉토 바이오테크 에이비

Priority date

2018-01-10

Filing date

2019-01-09

Publication date

2020-09-17

2019-01-09 Application filed by 갈렉토 바이오테크 에이비 filed Critical 갈렉토 바이오테크 에이비

2020-09-17 Publication of KR20200108303A publication Critical patent/KR20200108303A/ko

Status Withdrawn legal-status Critical Current

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102000007563 Galectins Human genes 0.000 title description 42
108010046569 Galectins Proteins 0.000 title description 42
239000003112 inhibitor Substances 0.000 title description 31
150000008195 galaktosides Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 255
108010001498 Galectin 1 Proteins 0.000 claims abstract description 58
238000000034 method Methods 0.000 claims abstract description 50
229910052799 carbon Inorganic materials 0.000 claims abstract description 20
241000124008 Mammalia Species 0.000 claims abstract description 15
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 14
230000027455 binding Effects 0.000 claims abstract description 11
239000003446 ligand Substances 0.000 claims abstract description 11
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 9
150000003214 pyranose derivatives Chemical group 0.000 claims abstract description 4
102000000795 Galectin 1 Human genes 0.000 claims abstract 4
-1 D-galactopyranose compound Chemical class 0.000 claims description 144
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 108
229910052736 halogen Inorganic materials 0.000 claims description 61
150000002367 halogens Chemical class 0.000 claims description 61
125000000217 alkyl group Chemical group 0.000 claims description 57
206010028980 Neoplasm Diseases 0.000 claims description 39
229910052739 hydrogen Inorganic materials 0.000 claims description 36
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
201000011510 cancer Diseases 0.000 claims description 31
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 31
229910052801 chlorine Inorganic materials 0.000 claims description 25
229910052794 bromium Inorganic materials 0.000 claims description 22
239000001257 hydrogen Substances 0.000 claims description 21
206010016654 Fibrosis Diseases 0.000 claims description 20
230000004761 fibrosis Effects 0.000 claims description 20
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 18
201000010099 disease Diseases 0.000 claims description 18
239000003814 drug Substances 0.000 claims description 18
150000002431 hydrogen Chemical class 0.000 claims description 17
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
229910052731 fluorine Inorganic materials 0.000 claims description 16
229910052757 nitrogen Inorganic materials 0.000 claims description 16
125000001424 substituent group Chemical group 0.000 claims description 16
WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 15
230000033115 angiogenesis Effects 0.000 claims description 15
239000008194 pharmaceutical composition Substances 0.000 claims description 15
208000035475 disorder Diseases 0.000 claims description 14
125000004076 pyridyl group Chemical group 0.000 claims description 12
206010029113 Neovascularisation Diseases 0.000 claims description 10
229960003082 galactose Drugs 0.000 claims description 10
208000030159 metabolic disease Diseases 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
150000003839 salts Chemical class 0.000 claims description 10
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239000012453 solvate Substances 0.000 claims description 9
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206010039491 Sarcoma Diseases 0.000 claims description 8
230000004054 inflammatory process Effects 0.000 claims description 8
201000009030 Carcinoma Diseases 0.000 claims description 7
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206010025323 Lymphomas Diseases 0.000 claims description 6
206010027406 Mesothelioma Diseases 0.000 claims description 6
208000031737 Tissue Adhesions Diseases 0.000 claims description 6
206010052779 Transplant rejections Diseases 0.000 claims description 6
230000002159 abnormal effect Effects 0.000 claims description 6
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 6
208000011379 keloid formation Diseases 0.000 claims description 6
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 6
208000005069 pulmonary fibrosis Diseases 0.000 claims description 6
231100000241 scar Toxicity 0.000 claims description 6
230000036573 scar formation Effects 0.000 claims description 6
KRFOHZKKGPUCCZ-AHXITHOBSA-N (2R,4S,5R)-2-(3,4-dichlorophenyl)sulfanyl-6-(hydroxymethyl)-4-[4-(4-hydroxy-1,3-thiazol-2-yl)triazol-1-yl]oxane-3,5-diol Chemical compound C1=CC(=C(C=C1S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=NC(=CS4)O)O)Cl)Cl KRFOHZKKGPUCCZ-AHXITHOBSA-N 0.000 claims description 5
FPGQRMSFHPPXIU-BEBHXBEKSA-N (2R,4S,5R)-4-[4-(2-chloro-1,3-thiazol-4-yl)triazol-1-yl]-2-(3,4-dichlorophenyl)sulfanyl-6-(hydroxymethyl)oxane-3,5-diol Chemical compound C1=CC(=C(C=C1S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=N4)Cl)O)Cl)Cl FPGQRMSFHPPXIU-BEBHXBEKSA-N 0.000 claims description 5
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DEZXUKFQGWEBPA-UKTBERIZSA-N 4-[1-[(2R,4S,5R)-2-(3,5-dibromo-4-fluorophenyl)sulfanyl-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]triazol-4-yl]-3H-1,3-thiazol-2-one Chemical compound C1=C(C=C(C(=C1Br)F)Br)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O DEZXUKFQGWEBPA-UKTBERIZSA-N 0.000 claims description 5
GAHICCQTWURYKS-UKTBERIZSA-N 4-[1-[(2R,4S,5R)-2-(3,5-dichloro-4-fluorophenyl)sulfanyl-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]triazol-4-yl]-3H-1,3-thiazol-2-one Chemical compound C1=C(C=C(C(=C1Cl)F)Cl)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O GAHICCQTWURYKS-UKTBERIZSA-N 0.000 claims description 5
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RMROEDKIZLORMI-UKTBERIZSA-N 4-[1-[(2R,4S,5R)-2-(4,5-dichloro-2-fluorophenyl)sulfanyl-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]triazol-4-yl]-3H-1,3-thiazol-2-one Chemical compound C1=C(C(=CC(=C1Cl)Cl)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O)F RMROEDKIZLORMI-UKTBERIZSA-N 0.000 claims description 5
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AAKSNUWBFNMWOT-CDZUSTAJSA-N 5-chloro-3-[(2R,4S,5R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[4-(2-oxo-3H-1,3-thiazol-4-yl)triazol-1-yl]oxan-2-yl]sulfanylpyridine-2-carboxylic acid Chemical compound C1=C(C=NC(=C1S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O)C(=O)O)Cl AAKSNUWBFNMWOT-CDZUSTAJSA-N 0.000 claims description 5
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