TWI791018B - 治療細菌感染之化合物及方法 - Google Patents
治療細菌感染之化合物及方法 Download PDFInfo
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- TWI791018B TWI791018B TW107115559A TW107115559A TWI791018B TW I791018 B TWI791018 B TW I791018B TW 107115559 A TW107115559 A TW 107115559A TW 107115559 A TW107115559 A TW 107115559A TW I791018 B TWI791018 B TW I791018B
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- methyl
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 134
- 208000035143 Bacterial infection Diseases 0.000 title claims description 22
- 208000022362 bacterial infectious disease Diseases 0.000 title claims description 22
- 238000000034 method Methods 0.000 title description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 46
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 122
- -1 C(O)NR d Re Inorganic materials 0.000 claims description 92
- 229910052739 hydrogen Inorganic materials 0.000 claims description 68
- 239000001257 hydrogen Substances 0.000 claims description 64
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 50
- 229910052757 nitrogen Inorganic materials 0.000 claims description 49
- 239000000203 mixture Substances 0.000 claims description 47
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 25
- 125000000623 heterocyclic group Chemical group 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
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- 125000005842 heteroatom Chemical group 0.000 claims description 5
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- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
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- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000006413 ring segment Chemical group 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
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- 238000002360 preparation method Methods 0.000 claims description 2
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 40
- 239000012267 brine Substances 0.000 description 37
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 37
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 34
- 239000000706 filtrate Substances 0.000 description 34
- 238000003818 flash chromatography Methods 0.000 description 31
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
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- 238000004366 reverse phase liquid chromatography Methods 0.000 description 28
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 26
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- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 25
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 24
- 239000012298 atmosphere Substances 0.000 description 23
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 23
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- 101710167893 Penicillin-binding protein 3 Proteins 0.000 description 16
- 101710146026 Peptidoglycan D,D-transpeptidase FtsI Proteins 0.000 description 16
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- 125000001841 imino group Chemical group [H]N=* 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 15
- 238000011282 treatment Methods 0.000 description 15
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- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
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- 239000000047 product Substances 0.000 description 13
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- PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 description 8
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Images
Classifications
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- 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
- C07D471/18—Bridged 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
- C07D471/02—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
- C07D471/08—Bridged systems
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- A—HUMAN NECESSITIES
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- 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
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| Publication number | Priority date | Publication date | Assignee | Title |
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| DK3833665T3 (da) | 2018-08-09 | 2023-10-09 | Antabio Sas | Diazabicyclooctanoner som hæmmere af serin-beta-lactamaser |
| US11905286B2 (en) | 2018-08-09 | 2024-02-20 | Antabio Sas | Diazabicyclooctanones as inhibitors of serine beta-lactamases |
| CN111675641B (zh) * | 2020-06-04 | 2023-09-08 | 宁夏农林科学院农业资源与环境研究所（宁夏土壤与植物营养重点实验室） | 单环β-内酰胺类化合物、单环内酰胺类化合物盐及其制备方法 |
| EP4146651A4 (en) | 2021-05-07 | 2024-06-05 | Ningxia Academy of Agriculture and Forestry Sciences | SULFONYLAMIDINE SUBSTITUTED COMPOUNDS AND THEIR USE AS BETA-LACTAMASE INHIBITORS |
| US11814385B2 (en) | 2021-06-25 | 2023-11-14 | University Of South Florida | Small molecule inhibitors targeting Clostridioides difficile sporulation |
| WO2025064681A1 (en) * | 2023-09-19 | 2025-03-27 | Entasis Therapeutics Inc. | Compounds and methods for treating bacterial infections |
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