JP2013515032A - 二置換ヘテロアリール縮合ピリジン類 - Google Patents
二置換ヘテロアリール縮合ピリジン類 Download PDFInfo
- Publication number
- JP2013515032A JP2013515032A JP2012545276A JP2012545276A JP2013515032A JP 2013515032 A JP2013515032 A JP 2013515032A JP 2012545276 A JP2012545276 A JP 2012545276A JP 2012545276 A JP2012545276 A JP 2012545276A JP 2013515032 A JP2013515032 A JP 2013515032A
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- JP
- Japan
- Prior art keywords
- pyridin
- pyrazolo
- yloxy
- acetamide
- ring system
- 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.)
- Pending
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- 150000003222 pyridines Chemical class 0.000 title description 3
- 125000001072 heteroaryl group Chemical group 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 262
- 239000003814 drug Substances 0.000 claims abstract description 17
- -1 C 2-6 halogenalkynyl Chemical group 0.000 claims description 464
- 125000000217 alkyl group Chemical group 0.000 claims description 384
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 359
- 125000004122 cyclic group Chemical group 0.000 claims description 310
- 229910052736 halogen Inorganic materials 0.000 claims description 304
- 150000002367 halogens Chemical class 0.000 claims description 270
- 229910052757 nitrogen Inorganic materials 0.000 claims description 248
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 217
- 125000001188 haloalkyl group Chemical group 0.000 claims description 195
- 125000001424 substituent group Chemical group 0.000 claims description 133
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 125
- 229910052717 sulfur Chemical group 0.000 claims description 125
- 239000011593 sulfur Chemical group 0.000 claims description 125
- 229910052760 oxygen Inorganic materials 0.000 claims description 124
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 123
- 125000005842 heteroatom Chemical group 0.000 claims description 123
- 239000001301 oxygen Chemical group 0.000 claims description 123
- 125000004434 sulfur atom Chemical group 0.000 claims description 119
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 118
- 229910052739 hydrogen Inorganic materials 0.000 claims description 114
- 239000001257 hydrogen Substances 0.000 claims description 114
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 114
- 125000006413 ring segment Chemical group 0.000 claims description 114
- 125000003545 alkoxy group Chemical group 0.000 claims description 103
- 125000000623 heterocyclic group Chemical group 0.000 claims description 100
- 125000002950 monocyclic group Chemical group 0.000 claims description 97
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 94
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 80
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 80
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 76
- 125000002947 alkylene group Chemical group 0.000 claims description 75
- 125000003118 aryl group Chemical group 0.000 claims description 69
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 66
- 229910052799 carbon Inorganic materials 0.000 claims description 65
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 60
- 238000000034 method Methods 0.000 claims description 59
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 50
- 150000002431 hydrogen Chemical class 0.000 claims description 47
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 44
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 42
- 125000004432 carbon atom Chemical group C* 0.000 claims description 41
- 150000003839 salts Chemical group 0.000 claims description 39
- 125000002619 bicyclic group Chemical group 0.000 claims description 33
- 229920006395 saturated elastomer Polymers 0.000 claims description 33
- GVLRTOYGRNLSDW-UHFFFAOYSA-N 1h-pyrazolo[3,4-b]pyridine Chemical group C1=CC=C2C=NNC2=N1 GVLRTOYGRNLSDW-UHFFFAOYSA-N 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 22
- 208000035475 disorder Diseases 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
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- 125000003367 polycyclic group Chemical group 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 125000004429 atom Chemical group 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
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- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- RRXSYZFVDIRTFB-UHFFFAOYSA-N C[CH]C1=CC=C(OC)C=C1 Chemical group C[CH]C1=CC=C(OC)C=C1 RRXSYZFVDIRTFB-UHFFFAOYSA-N 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 4
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 4
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- XUYCYHNBDBGUMX-UHFFFAOYSA-N 2-(3-cyclopropyl-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl)oxy-n-(2-methylpropyl)acetamide Chemical compound N=1N(C)C2=NC(OCC(=O)NCC(C)C)=CC(C)=C2C=1C1CC1 XUYCYHNBDBGUMX-UHFFFAOYSA-N 0.000 claims description 2
- NMCMCGLHCMEIBI-UHFFFAOYSA-N 2-(3-cyclopropyl-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl)oxy-n-(2-phenylethyl)acetamide Chemical compound N=1C=2N(C)N=C(C3CC3)C=2C(C)=CC=1OCC(=O)NCCC1=CC=CC=C1 NMCMCGLHCMEIBI-UHFFFAOYSA-N 0.000 claims description 2
- NMMWQPMWGUPQBP-UHFFFAOYSA-N 2-(3-cyclopropyl-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl)oxy-n-[1-(1-methylpyrrolo[2,3-b]pyridin-5-yl)ethyl]acetamide Chemical compound C=1N=C2N(C)C=CC2=CC=1C(C)NC(=O)COC(N=C1N(C)N=2)=CC(C)=C1C=2C1CC1 NMMWQPMWGUPQBP-UHFFFAOYSA-N 0.000 claims description 2
- NGKRQGAFUPJDRL-UHFFFAOYSA-N 2-(3-cyclopropyl-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl)oxy-n-[1-(4-methoxyphenyl)ethyl]-n-methylacetamide Chemical compound C1=CC(OC)=CC=C1C(C)N(C)C(=O)COC1=CC(C)=C(C(=NN2C)C3CC3)C2=N1 NGKRQGAFUPJDRL-UHFFFAOYSA-N 0.000 claims description 2
- PCEVUHYTSUIWRI-UHFFFAOYSA-N 2-(3-cyclopropyl-1,4-dimethylpyrazolo[3,4-b]pyridin-6-yl)oxy-n-methylacetamide Chemical compound N=1N(C)C2=NC(OCC(=O)NC)=CC(C)=C2C=1C1CC1 PCEVUHYTSUIWRI-UHFFFAOYSA-N 0.000 claims description 2
- GVYPHKXSRUWKBP-UHFFFAOYSA-N 2-[1-methyl-3-phenyl-4-(trifluoromethyl)pyrazolo[3,4-b]pyridin-6-yl]oxy-n-propylacetamide Chemical compound N=1N(C)C2=NC(OCC(=O)NCCC)=CC(C(F)(F)F)=C2C=1C1=CC=CC=C1 GVYPHKXSRUWKBP-UHFFFAOYSA-N 0.000 claims description 2
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 2
- 241000162682 Heterogen Species 0.000 claims 2
- 238000002360 preparation method Methods 0.000 abstract description 7
- 239000000203 mixture Substances 0.000 description 73
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 61
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
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- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
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Classifications
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
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- Neurosurgery (AREA)
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- Addiction (AREA)
- Diabetes (AREA)
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- Obesity (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| IN2664DE2009 | 2009-12-21 | ||
| IN2664/DEL/2009 | 2009-12-21 | ||
| PCT/EP2010/070260 WO2011076744A1 (en) | 2009-12-21 | 2010-12-20 | Disubstituted heteroaryl-fused pyridines |
Publications (2)
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| JP2013515032A true JP2013515032A (ja) | 2013-05-02 |
| JP2013515032A5 JP2013515032A5 (enExample) | 2014-01-30 |
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| Country | Link |
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| US (1) | US8742106B2 (enExample) |
| EP (1) | EP2516437B1 (enExample) |
| JP (1) | JP2013515032A (enExample) |
| CN (1) | CN102762560A (enExample) |
| ES (1) | ES2460915T3 (enExample) |
| WO (1) | WO2011076744A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2022504780A (ja) * | 2018-10-18 | 2022-01-13 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 光学活性１－シクロプロピルアルキル－１－アミンのスケーラブルな合成 |
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| US9440982B2 (en) | 2012-02-07 | 2016-09-13 | Eolas Therapeutics, Inc. | Substituted prolines/piperidines as orexin receptor antagonists |
| EP2811997B1 (en) | 2012-02-07 | 2018-04-11 | Eolas Therapeutics Inc. | Substituted prolines/piperidines as orexin receptor antagonists |
| BR102012024778A2 (pt) | 2012-09-28 | 2014-08-19 | Cristalia Prod Quimicos Farm | Compostos heteroaromáticos; processo para preparar os compostos, composições farmacêuticas, usos e método de tratamento para as dores aguda e crônica |
| WO2016025669A1 (en) | 2014-08-13 | 2016-02-18 | Eolas Therapeutics, Inc. | Difluoropyrrolidines as orexin receptor modulators |
| HUE055662T2 (hu) | 2014-12-29 | 2021-12-28 | Us Health | Laktát-dehidrogenáz kismolekulás inhibitorai és alkalmazási eljárásai |
| CN105541719B (zh) * | 2016-02-03 | 2018-06-29 | 安徽工业大学 | 一种以乳清酸为原料制备5-氨基-1,2二氢吡唑-3-酮的方法 |
| PL3414241T3 (pl) | 2016-02-12 | 2022-10-03 | Astrazeneca Ab | Piperydyny podstawione halo jako modulatory receptora oreksyny |
| WO2018054832A1 (en) | 2016-09-22 | 2018-03-29 | Bayer Cropscience Aktiengesellschaft | Novel triazole derivatives |
| EP3515906A1 (en) | 2016-09-22 | 2019-07-31 | Bayer CropScience Aktiengesellschaft | Novel triazole derivatives and their use as fungicides |
| BR112019006441A2 (pt) | 2016-09-29 | 2019-06-25 | Bayer Ag | derivados de 5-imidazol metil dioxolano substituídos como fungicidas |
| CN109982999A (zh) | 2016-09-29 | 2019-07-05 | 拜耳作物科学股份公司 | 新的5-取代的咪唑基甲基衍生物 |
| JP2020506950A (ja) | 2017-02-08 | 2020-03-05 | バイエル アクチェンゲゼルシャフトＢａｙｅｒ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | トリアゾールチオン誘導体 |
| WO2018145932A1 (en) | 2017-02-08 | 2018-08-16 | Bayer Cropscience Aktiengesellschaft | Triazole derivatives and their use as fungicides |
| EP3580218A1 (en) | 2017-02-08 | 2019-12-18 | Bayer CropScience Aktiengesellschaft | Novel triazole derivatives |
| JP2020507579A (ja) | 2017-02-10 | 2020-03-12 | バイエル アクチェンゲゼルシャフトＢａｙｅｒ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | １−（フェノキシ−ピリジニル）−２−（１，２，４−トリアゾール−１−イル）−エタノール誘導体を含む有害微生物を制御するための組成物 |
| WO2020020816A1 (en) | 2018-07-26 | 2020-01-30 | Bayer Aktiengesellschaft | Novel triazole derivatives |
| MX2023005073A (es) * | 2020-11-02 | 2023-05-16 | Merck Sharp & Dohme Llc | Agonistas macrociclicos de los receptores de urea orexina. |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001098301A1 (en) * | 2000-06-20 | 2001-12-27 | Japan Tobacco Inc. | Pyrazolopyridine compounds and use thereof as drugs |
| WO2009003993A1 (en) * | 2007-07-03 | 2009-01-08 | Glaxo Group Limited | Piperidine derivatives useful as orexin receptor antagonists |
| WO2009017848A1 (en) * | 2007-03-05 | 2009-02-05 | Proteo Tech Inc. | Compounds, compositions, and methods for the treatment of amyloid diseases such as systemic aa amyloidosis |
| JP2009535324A (ja) * | 2006-04-26 | 2009-10-01 | アクテリオン ファーマシューティカルズ リミテッド | 新規なピラゾロ−テトラヒドロピリジン誘導体 |
Family Cites Families (13)
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| DE2232038A1 (de) | 1972-06-30 | 1974-01-10 | Hoechst Ag | 3-amino-1h-pyrazolo eckige klammer auf 3,4-b eckige klammer zu pyridine, ihre herstellung und verwendung |
| PT72878B (en) | 1980-04-24 | 1983-03-29 | Merck & Co Inc | Process for preparing mannich-base hydroxamic acid pro-drugs for the improved delivery of non-steroidal anti-inflammatory agents |
| US6962926B2 (en) | 2001-01-31 | 2005-11-08 | Telik, Inc. | Antagonist of MCP-1 function, and compositions and methods of use thereof |
| US6670364B2 (en) | 2001-01-31 | 2003-12-30 | Telik, Inc. | Antagonists of MCP-1 function and methods of use thereof |
| US20030187026A1 (en) | 2001-12-13 | 2003-10-02 | Qun Li | Kinase inhibitors |
| JP2007524596A (ja) | 2003-02-28 | 2007-08-30 | トランスフォーム・ファーマシューティカルズ・インコーポレイテッド | 共結晶医薬組成物 |
| DE102004061288A1 (de) | 2004-12-14 | 2006-06-29 | Schering Ag | 3-Amino-Pyrazolo[3,4b]pyridine als Inhibitoren von Proteintyrosinkinasen, deren Herstellung und Verwendung als Arzneimittel |
| AR057455A1 (es) | 2005-07-22 | 2007-12-05 | Merck & Co Inc | Inhibidores de la transcriptasa reversa de vih y composicion farmaceutica |
| EP1764099A3 (en) | 2005-09-17 | 2007-05-09 | Speedel Experimenta AG | Diaminoalcohol derivatives for the treatment of Alzheimer, malaria, HIV |
| JP2007099640A (ja) | 2005-09-30 | 2007-04-19 | Tsumura & Co | 含窒素複素環化合物、その製造方法およびそれを用いた医薬組成物 |
| EP1870410A1 (en) | 2006-06-13 | 2007-12-26 | Bayer Schering Pharma Aktiengesellschaft | Substituted arylpyrazolopyridines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
| TW200815438A (en) | 2006-06-13 | 2008-04-01 | Bayer Schering Pharma Ag | Substituted pyrazolopyridines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
| GB0617161D0 (en) | 2006-08-31 | 2006-10-11 | Vernalis R&D Ltd | Enzyme inhibitors |
-
2010
- 2010-12-20 WO PCT/EP2010/070260 patent/WO2011076744A1/en not_active Ceased
- 2010-12-20 US US13/517,115 patent/US8742106B2/en not_active Expired - Fee Related
- 2010-12-20 EP EP10805785.2A patent/EP2516437B1/en not_active Not-in-force
- 2010-12-20 CN CN2010800643114A patent/CN102762560A/zh active Pending
- 2010-12-20 ES ES10805785.2T patent/ES2460915T3/es active Active
- 2010-12-20 JP JP2012545276A patent/JP2013515032A/ja active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001098301A1 (en) * | 2000-06-20 | 2001-12-27 | Japan Tobacco Inc. | Pyrazolopyridine compounds and use thereof as drugs |
| JP2009535324A (ja) * | 2006-04-26 | 2009-10-01 | アクテリオン ファーマシューティカルズ リミテッド | 新規なピラゾロ−テトラヒドロピリジン誘導体 |
| WO2009017848A1 (en) * | 2007-03-05 | 2009-02-05 | Proteo Tech Inc. | Compounds, compositions, and methods for the treatment of amyloid diseases such as systemic aa amyloidosis |
| WO2009003993A1 (en) * | 2007-07-03 | 2009-01-08 | Glaxo Group Limited | Piperidine derivatives useful as orexin receptor antagonists |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2022504780A (ja) * | 2018-10-18 | 2022-01-13 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 光学活性１－シクロプロピルアルキル－１－アミンのスケーラブルな合成 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2516437B1 (en) | 2014-01-29 |
| EP2516437A1 (en) | 2012-10-31 |
| US20120258973A1 (en) | 2012-10-11 |
| US8742106B2 (en) | 2014-06-03 |
| CN102762560A (zh) | 2012-10-31 |
| ES2460915T3 (es) | 2014-05-16 |
| WO2011076744A1 (en) | 2011-06-30 |
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