ES2433228T3 - Dihidroisoxazolopiridinas sustituidas con indazolilo y procedimientos de uso de las mismas - Google Patents
Dihidroisoxazolopiridinas sustituidas con indazolilo y procedimientos de uso de las mismas Download PDFInfo
- Publication number
- ES2433228T3 ES2433228T3 ES10730728T ES10730728T ES2433228T3 ES 2433228 T3 ES2433228 T3 ES 2433228T3 ES 10730728 T ES10730728 T ES 10730728T ES 10730728 T ES10730728 T ES 10730728T ES 2433228 T3 ES2433228 T3 ES 2433228T3
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- Prior art keywords
- alkyl
- group
- optionally substituted
- fluorine
- alkoxy
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 73
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 135
- -1 hydroxy, difluoromethoxy Chemical group 0.000 claims abstract description 91
- 239000011737 fluorine Substances 0.000 claims abstract description 63
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 63
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 61
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 58
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 56
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 55
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 48
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 47
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 46
- 125000001424 substituent group Chemical group 0.000 claims abstract description 46
- 239000001257 hydrogen Substances 0.000 claims abstract description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 42
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 39
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 38
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 33
- 239000000460 chlorine Chemical group 0.000 claims abstract description 32
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 31
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 31
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 29
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 28
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 26
- 125000006568 (C4-C7) heterocycloalkyl group Chemical group 0.000 claims abstract description 23
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims abstract description 22
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 21
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 20
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 18
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 11
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 10
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- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 8
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 8
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- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 6
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
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- 125000004076 pyridyl group Chemical group 0.000 claims description 10
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- 229940124597 therapeutic agent Drugs 0.000 claims description 8
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 7
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- 150000007513 acids Chemical class 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 230000018044 dehydration Effects 0.000 claims description 3
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- 230000002265 prevention Effects 0.000 claims description 3
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 2
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- GTBRTGPZZALPNS-MXHVRSFHSA-N cyanoketone Chemical compound C1C=C2C(C)(C)C(=O)[C@H](C#N)C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 GTBRTGPZZALPNS-MXHVRSFHSA-N 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
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- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 38
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
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- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 14
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Classifications
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- 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
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- 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
- A61K31/435—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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
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- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
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- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09008996 | 2009-07-10 | ||
| EP09008996 | 2009-07-10 | ||
| PCT/EP2010/004147 WO2011003604A1 (en) | 2009-07-10 | 2010-07-07 | Indazolyl-substituted dihydroisoxa-zolopyridines and methods of use thereof |
Publications (1)
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|---|---|
| ES2433228T3 true ES2433228T3 (es) | 2013-12-10 |
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| ES10730728T Active ES2433228T3 (es) | 2009-07-10 | 2010-07-07 | Dihidroisoxazolopiridinas sustituidas con indazolilo y procedimientos de uso de las mismas |
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| Country | Link |
|---|---|
| US (1) | US9073939B2 (enExample) |
| EP (1) | EP2451817B1 (enExample) |
| JP (1) | JP5674211B2 (enExample) |
| CN (1) | CN102639537B (enExample) |
| CA (1) | CA2767476A1 (enExample) |
| ES (1) | ES2433228T3 (enExample) |
| WO (1) | WO2011003604A1 (enExample) |
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| US3635977A (en) | 1969-11-03 | 1972-01-18 | American Cyanamid Co | Certain 6-trifluoromethylcytosines and thiocytosines their synthesis and their use in the synthesis of uracisls and thiouracil |
| JP2634640B2 (ja) | 1988-07-29 | 1997-07-30 | 三共株式会社 | 縮環ジヒドロピリジン誘導体 |
| US5274167A (en) | 1989-01-26 | 1993-12-28 | Bayer Aktiengesellschaft | Polymeriable optically active (meth) acrylic acid derivatives |
| DK0379917T3 (da) | 1989-01-26 | 1995-12-11 | Bayer Ag | Optisk aktive (meth)acrylsyre-drivater, deres fremstilling, deres polymerisation til optisk aktive polymere og disses anvendelse |
| DE19546136A1 (de) | 1995-12-11 | 1997-06-12 | Bayer Ag | Chirale stationäre Phasen für die chromatographische Trennung von optischen Isomeren |
| WO2001066544A2 (en) | 2000-03-03 | 2001-09-13 | Abbott Laboratories | Tricyclic dihydropyrazolone and tricyclic dihydroisoxazolone potassium channel openers |
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| GB0220962D0 (en) * | 2002-09-10 | 2002-10-23 | Bayer Ag | Heterocyclic derivatives |
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| WO2005084672A1 (de) | 2004-03-03 | 2005-09-15 | Boehringer Ingelheim International Gmbh | Ausgewählte cgrp-antagonisten, verfahren zu deren herstellung sowie deren verwendung als arzneimittel |
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| JP5506788B2 (ja) * | 2008-06-09 | 2014-05-28 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 置換４−（インダゾリル）−１，４−ジヒドロピリジン類およびそれらの使用方法 |
| CA2727199C (en) * | 2008-06-09 | 2016-11-22 | Bayer Schering Pharma Aktiengesellschaft | Annellated 4-(indazolyl)-1,4-dihydropyridine derivatives and methods of use thereof |
| JP5753174B2 (ja) | 2009-10-06 | 2015-07-22 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ | フッ化２，６−ジアルキル−３，５−ジシアノ−４−（１ｈ−インダゾール−５−イル）−１，４−ジヒドロピリジン類およびそれらの使用方法 |
-
2010
- 2010-07-07 US US13/383,223 patent/US9073939B2/en not_active Expired - Fee Related
- 2010-07-07 EP EP10730728.2A patent/EP2451817B1/en not_active Not-in-force
- 2010-07-07 CN CN201080039898.3A patent/CN102639537B/zh not_active Expired - Fee Related
- 2010-07-07 ES ES10730728T patent/ES2433228T3/es active Active
- 2010-07-07 CA CA2767476A patent/CA2767476A1/en not_active Abandoned
- 2010-07-07 WO PCT/EP2010/004147 patent/WO2011003604A1/en not_active Ceased
- 2010-07-07 JP JP2012518822A patent/JP5674211B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP2451817A1 (en) | 2012-05-16 |
| US20120190709A1 (en) | 2012-07-26 |
| HK1174620A1 (zh) | 2013-06-14 |
| US9073939B2 (en) | 2015-07-07 |
| CN102639537B (zh) | 2015-07-22 |
| JP5674211B2 (ja) | 2015-02-25 |
| EP2451817B1 (en) | 2013-09-04 |
| CN102639537A (zh) | 2012-08-15 |
| CA2767476A1 (en) | 2011-01-13 |
| JP2012532170A (ja) | 2012-12-13 |
| WO2011003604A1 (en) | 2011-01-13 |
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