JP7060579B2 - 抗微生物化合物 - Google Patents
抗微生物化合物 Download PDFInfo
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- JP7060579B2 JP7060579B2 JP2019508251A JP2019508251A JP7060579B2 JP 7060579 B2 JP7060579 B2 JP 7060579B2 JP 2019508251 A JP2019508251 A JP 2019508251A JP 2019508251 A JP2019508251 A JP 2019508251A JP 7060579 B2 JP7060579 B2 JP 7060579B2
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- alkenyl
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- 239000004599 antimicrobial Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 216
- 229910052739 hydrogen Inorganic materials 0.000 claims description 59
- 229910052736 halogen Inorganic materials 0.000 claims description 56
- 150000002367 halogens Chemical class 0.000 claims description 56
- 125000003342 alkenyl group Chemical group 0.000 claims description 54
- 125000000217 alkyl group Chemical group 0.000 claims description 54
- -1 OEt Inorganic materials 0.000 claims description 53
- 239000001257 hydrogen Substances 0.000 claims description 50
- 239000000203 mixture Substances 0.000 claims description 50
- 238000000034 method Methods 0.000 claims description 45
- 125000001424 substituent group Chemical group 0.000 claims description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
- 239000011737 fluorine Substances 0.000 claims description 27
- 229910052731 fluorine Inorganic materials 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 26
- 241000725643 Respiratory syncytial virus Species 0.000 claims description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 239000012453 solvate Substances 0.000 claims description 18
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 17
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 15
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- 238000011282 treatment Methods 0.000 claims description 14
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- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 241000700605 Viruses Species 0.000 description 13
- 239000007864 aqueous solution Substances 0.000 description 13
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 13
- 239000007788 liquid Substances 0.000 description 13
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 13
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- 238000003818 flash chromatography Methods 0.000 description 12
- 125000004076 pyridyl group Chemical group 0.000 description 12
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 11
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
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- 230000037396 body weight Effects 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 235000001014 amino acid Nutrition 0.000 description 8
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- 150000001413 amino acids Chemical group 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 239000012091 fetal bovine serum Substances 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 7
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- 238000011534 incubation Methods 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- 238000002962 plaque-reduction assay Methods 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
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- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
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- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
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Images
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- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
- C07D243/26—Preparation from compounds already containing the benzodiazepine skeleton
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- 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
- C07D401/12—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 chain containing hetero atoms as chain links
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- 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
- C07D401/14—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 three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1613942.0A GB201613942D0 (en) | 2016-08-15 | 2016-08-15 | An antimicrobial compound |
| GB1613942.0 | 2016-08-15 | ||
| PCT/GB2017/052393 WO2018033714A1 (en) | 2016-08-15 | 2017-08-15 | An antimicrobial compound |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019527724A JP2019527724A (ja) | 2019-10-03 |
| JP2019527724A5 JP2019527724A5 (enExample) | 2020-09-24 |
| JP7060579B2 true JP7060579B2 (ja) | 2022-04-26 |
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| GB201915932D0 (en) | 2019-11-01 | 2019-12-18 | Reviral Ltd | Pharmaceutical compounds |
| GB202010408D0 (en) | 2020-07-07 | 2020-08-19 | Reviral Ltd | Pharmaceutical compounds |
| GB202010409D0 (en) | 2020-07-07 | 2020-08-19 | Reviral Ltd | Pharmaceutical compounds |
| GB202102602D0 (en) | 2021-02-24 | 2021-04-07 | Reviral Ltd | Pharmaceutical compounds |
| WO2024252355A1 (en) | 2023-06-08 | 2024-12-12 | Pfizer Inc. | Pediatric dosing regimens comprising a fusion inhibitor for the treatment of rsv |
| WO2025120500A1 (en) | 2023-12-06 | 2025-06-12 | Pfizer Inc. | Benzodiazepine compounds as n-protein inhibitors |
| WO2025153942A1 (en) | 2024-01-16 | 2025-07-24 | Pfizer Inc. | Benzodiazepine pyrazolo carboxamides as n-protein inhibitors |
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| US4820834A (en) * | 1984-06-26 | 1989-04-11 | Merck & Co., Inc. | Benzodiazepine analogs |
| US5004741A (en) * | 1984-06-26 | 1991-04-02 | Merck & Co., Inc. | Methods of antagonizing CCK or gastrin with benzodiazepine analogs |
| US5428031A (en) * | 1991-12-03 | 1995-06-27 | Merck & Co., Inc. | Methods of treating cardiac arrhythmia |
| US5426185A (en) * | 1993-11-22 | 1995-06-20 | Merck & Co., Inc. | Antiarrhythmic benzodiazepines |
| AU3400797A (en) * | 1996-06-27 | 1998-01-14 | Merck & Co., Inc. | A method for treating meniere's disease |
| US5776930A (en) * | 1996-06-28 | 1998-07-07 | Merck & Company, Inc. | Pharmaceutical preparation |
| US5817658A (en) | 1997-03-14 | 1998-10-06 | Merck & Company, Inc. | Method for treating Meniere's disease |
| EP1107983A2 (en) * | 1998-09-01 | 2001-06-20 | Innogenetics N.V. | Benzodiazepine and benzothiazepine derivatives and hbsag peptides binding to annexins, their compositions and use |
| PL375860A1 (en) * | 2002-09-20 | 2005-12-12 | Arrow Therapeutics Limited | Benzodiazepine derivatives and pharmaceutical compositions containing them |
| GB0406280D0 (en) * | 2004-03-19 | 2004-04-21 | Arrow Therapeutics Ltd | Chemical compounds |
| GB0406279D0 (en) | 2004-03-19 | 2004-04-21 | Arrow Therapeutics Ltd | Therapeutic compounds |
| US20070293482A1 (en) | 2004-03-19 | 2007-12-20 | Novartis Pharmaceuticals Corporation | Process for Preparing Benzodiazepines |
| GB0406282D0 (en) | 2004-03-19 | 2004-04-21 | Arrow Therapeutics Ltd | Therapeutic compounds |
| US8039616B2 (en) * | 2005-09-19 | 2011-10-18 | Astrazeneca Ab | Benzodiazepine derivatives for treating hepatitis C infection |
| PT2094308E (pt) * | 2006-11-21 | 2011-04-14 | Novartis Ag | Formulação parentérica estável contendo um inibidor de vsr com estrutura de benzodiazepina |
| WO2011151652A1 (en) * | 2010-06-03 | 2011-12-08 | Arrow Therapeutics Limited | Benzodiazepine compounds useful for the treatment of hepatitis c |
| WO2011151651A1 (en) * | 2010-06-03 | 2011-12-08 | Arrow Therapeutics Limited | Benzodiazepine compounds useful for the treatment of hepatitis c |
| GB201506448D0 (en) * | 2015-04-16 | 2015-06-03 | Univ Durham | An antimicrobial compound |
| CA2992839A1 (en) * | 2015-07-22 | 2017-01-26 | Enanta Pharmaceuticals, Inc. | Benzodiazepine derivatives as rsv inhibitors |
| GB201911944D0 (en) * | 2019-08-20 | 2019-10-02 | Reviral Ltd | Pharmaceutical compounds |
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| GB201613942D0 (en) | 2016-09-28 |
| US20210017138A1 (en) | 2021-01-21 |
| JP2019527724A (ja) | 2019-10-03 |
| WO2018033714A1 (en) | 2018-02-22 |
| US11247973B2 (en) | 2022-02-15 |
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