JP2009515934A - 新規なキナゾリン誘導体及びこれらの医学的使用 - Google Patents
新規なキナゾリン誘導体及びこれらの医学的使用 Download PDFInfo
- Publication number
- JP2009515934A JP2009515934A JP2008540620A JP2008540620A JP2009515934A JP 2009515934 A JP2009515934 A JP 2009515934A JP 2008540620 A JP2008540620 A JP 2008540620A JP 2008540620 A JP2008540620 A JP 2008540620A JP 2009515934 A JP2009515934 A JP 2009515934A
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- quinazolin
- oxo
- isopropyl
- propionamide
- 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.)
- Abandoned
Links
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title abstract 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 56
- 201000010099 disease Diseases 0.000 claims abstract description 29
- 238000000034 method Methods 0.000 claims abstract description 28
- 208000035475 disorder Diseases 0.000 claims abstract description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
- 230000004913 activation Effects 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 4
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 118
- 229910052739 hydrogen Inorganic materials 0.000 claims description 52
- 239000001257 hydrogen Substances 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- 150000003246 quinazolines Chemical class 0.000 claims description 48
- 239000000203 mixture Substances 0.000 claims description 37
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 28
- 125000005843 halogen group Chemical group 0.000 claims description 28
- -1 methylenedioxy group Chemical group 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 28
- 150000002431 hydrogen Chemical class 0.000 claims description 27
- 208000002193 Pain Diseases 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 230000036407 pain Effects 0.000 claims description 24
- 125000001188 haloalkyl group Chemical group 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- 230000002265 prevention Effects 0.000 claims description 16
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 15
- 125000001153 fluoro group Chemical group F* 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 11
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- 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 8
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- 206010027599 migraine Diseases 0.000 claims description 8
- 208000004296 neuralgia Diseases 0.000 claims description 8
- 241001465754 Metazoa Species 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 208000019901 Anxiety disease Diseases 0.000 claims description 6
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- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
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- 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
- VDFDVUDOCJHWBF-UHFFFAOYSA-N 2-(3-fluorophenyl)-n-(4-oxo-2-propan-2-ylquinazolin-3-yl)propanamide Chemical compound CC(C)C1=NC2=CC=CC=C2C(=O)N1NC(=O)C(C)C1=CC=CC(F)=C1 VDFDVUDOCJHWBF-UHFFFAOYSA-N 0.000 claims description 5
- WROKVAVWVKCBMB-UHFFFAOYSA-N 2-(4-methoxyphenyl)-n-[4-oxo-2-propan-2-yl-7-(trifluoromethyl)quinazolin-3-yl]propanamide Chemical compound C1=CC(OC)=CC=C1C(C)C(=O)NN1C(=O)C2=CC=C(C(F)(F)F)C=C2N=C1C(C)C WROKVAVWVKCBMB-UHFFFAOYSA-N 0.000 claims description 5
- LCQQIOWBOMPHSJ-UHFFFAOYSA-N 3-amino-2-propan-2-ylquinazolin-4-one Chemical compound C1=CC=C2C(=O)N(N)C(C(C)C)=NC2=C1 LCQQIOWBOMPHSJ-UHFFFAOYSA-N 0.000 claims description 5
- 208000008548 Tension-Type Headache Diseases 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 206010015037 epilepsy Diseases 0.000 claims description 5
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- 125000003884 phenylalkyl group Chemical group 0.000 claims description 5
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- BHOLSJRZWUBCQE-FQEVSTJZSA-N (2s)-2-fluoro-n-[4-oxo-2-propan-2-yl-7-(trifluoromethyl)quinazolin-3-yl]-2-phenylpropanamide Chemical compound C1([C@](C)(F)C(=O)NN2C(=O)C3=CC=C(C=C3N=C2C(C)C)C(F)(F)F)=CC=CC=C1 BHOLSJRZWUBCQE-FQEVSTJZSA-N 0.000 claims description 4
- OROKJPUPTSURJR-AWEZNQCLSA-N (2s)-n-(4-oxo-2-propan-2-ylquinazolin-3-yl)-2-phenylpropanamide Chemical compound C1([C@H](C)C(=O)NN2C(=O)C3=CC=CC=C3N=C2C(C)C)=CC=CC=C1 OROKJPUPTSURJR-AWEZNQCLSA-N 0.000 claims description 4
- IYDDSFBOKZHXOS-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-n-(4-oxo-2-propan-2-ylquinazolin-3-yl)propanamide Chemical compound CC(C)C1=NC2=CC=CC=C2C(=O)N1NC(=O)C(C)C1=CC=C(Cl)C(Cl)=C1 IYDDSFBOKZHXOS-UHFFFAOYSA-N 0.000 claims description 4
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- QQTMXYFMWZRMFQ-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-n-(4-oxo-2-propan-2-ylquinazolin-3-yl)propanamide Chemical compound C1=C(OC)C(OC)=CC=C1C(C)C(=O)NN1C(=O)C2=CC=CC=C2N=C1C(C)C QQTMXYFMWZRMFQ-UHFFFAOYSA-N 0.000 claims description 4
- JPNTWYHCJJZYGR-UHFFFAOYSA-N 2-(3,5-difluorophenyl)-n-[2-methylsulfanyl-4-oxo-7-(trifluoromethyl)quinazolin-3-yl]propanamide Chemical compound CSC1=NC2=CC(C(F)(F)F)=CC=C2C(=O)N1NC(=O)C(C)C1=CC(F)=CC(F)=C1 JPNTWYHCJJZYGR-UHFFFAOYSA-N 0.000 claims description 4
- LTRXRADCHHPVOT-UHFFFAOYSA-N 2-(3-benzoylphenyl)-n-(4-oxo-2-propan-2-ylquinazolin-3-yl)propanamide Chemical compound CC(C)C1=NC2=CC=CC=C2C(=O)N1NC(=O)C(C)C(C=1)=CC=CC=1C(=O)C1=CC=CC=C1 LTRXRADCHHPVOT-UHFFFAOYSA-N 0.000 claims description 4
- DSULTIFNKXJRMQ-UHFFFAOYSA-N 2-(3-fluoro-4-methylphenyl)-n-(4-oxo-2-propan-2-ylquinazolin-3-yl)propanamide Chemical compound CC(C)C1=NC2=CC=CC=C2C(=O)N1NC(=O)C(C)C1=CC=C(C)C(F)=C1 DSULTIFNKXJRMQ-UHFFFAOYSA-N 0.000 claims description 4
- LHRUVJUUAYKQAQ-UHFFFAOYSA-N 2-(3-fluoro-4-methylphenyl)-n-[4-oxo-2-propan-2-yl-7-(trifluoromethyl)quinazolin-3-yl]propanamide Chemical compound CC(C)C1=NC2=CC(C(F)(F)F)=CC=C2C(=O)N1NC(=O)C(C)C1=CC=C(C)C(F)=C1 LHRUVJUUAYKQAQ-UHFFFAOYSA-N 0.000 claims description 4
- OYYHCWMEVPLFAQ-UHFFFAOYSA-N 2-(4-chlorophenyl)-n-(2-ethoxy-4-oxoquinazolin-3-yl)propanamide Chemical compound CCOC1=NC2=CC=CC=C2C(=O)N1NC(=O)C(C)C1=CC=C(Cl)C=C1 OYYHCWMEVPLFAQ-UHFFFAOYSA-N 0.000 claims description 4
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- HWGRLKLVQSJHNN-UHFFFAOYSA-N 2-cyclohexyl-n-(4-oxo-2-propan-2-ylquinazolin-3-yl)-2-phenylacetamide Chemical compound CC(C)C1=NC2=CC=CC=C2C(=O)N1NC(=O)C(C=1C=CC=CC=1)C1CCCCC1 HWGRLKLVQSJHNN-UHFFFAOYSA-N 0.000 claims description 4
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
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- 230000008569 process Effects 0.000 description 1
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- 230000002035 prolonged effect Effects 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 239000002002 slurry Substances 0.000 description 1
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- 229940075554 sorbate Drugs 0.000 description 1
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- 235000010199 sorbic acid Nutrition 0.000 description 1
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- 239000008117 stearic acid Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
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- 125000001424 substituent group Chemical group 0.000 description 1
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- 229940086735 succinate Drugs 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000003463 sulfur Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
-
- 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
-
- 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
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/90—Oxygen atoms with acyclic radicals attached in position 2 or 3
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA200501615 | 2005-11-18 | ||
| US73805205P | 2005-11-21 | 2005-11-21 | |
| PCT/EP2006/068627 WO2007057447A1 (en) | 2005-11-18 | 2006-11-17 | Novel quinazoline derivatives and their medical use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009515934A true JP2009515934A (ja) | 2009-04-16 |
| JP2009515934A5 JP2009515934A5 (enExample) | 2009-11-26 |
Family
ID=37685593
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008540620A Abandoned JP2009515934A (ja) | 2005-11-18 | 2006-11-17 | 新規なキナゾリン誘導体及びこれらの医学的使用 |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US20090291973A1 (enExample) |
| EP (1) | EP1951685A1 (enExample) |
| JP (1) | JP2009515934A (enExample) |
| WO (1) | WO2007057447A1 (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012512134A (ja) * | 2008-08-19 | 2012-05-31 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 冷感−メントール受容体拮抗剤 |
| JP2012521966A (ja) * | 2009-03-10 | 2012-09-20 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | Ｋｃｎｑ２／３モジュレータとしての置換された３−アミノ−２−メルカプトキノリン |
| JP2022543230A (ja) * | 2019-08-02 | 2022-10-11 | ハー・ルンドベック・アクチエゼルスカベット | てんかん又はてんかん発作において使用するためのＫｖ７カリウムチャネル開口薬としてのアルコール誘導体 |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2152272A2 (en) | 2007-05-23 | 2010-02-17 | NeuroSearch A/S | Novel 2,3-diamino-quinazolinone derivatives and their medical use |
| WO2010026104A1 (en) * | 2008-09-03 | 2010-03-11 | Neurosearch A/S | 4-tetrahydropyran-aminopyridine derivatives and their medical use |
| TW201038565A (en) | 2009-03-12 | 2010-11-01 | Gruenenthal Gmbh | Substituted 2-mercapto-3-aminopyridines as KCNQ2/3 modulators |
| TWI475020B (zh) | 2009-03-12 | 2015-03-01 | The substituted nicotine amide as a KCNQ2 / 3 modifier | |
| TWI461197B (zh) | 2009-03-12 | 2014-11-21 | 2-mercaptoquinoline-3-carboxamide as a KCNQ2 / 3 modifier | |
| CA2805932A1 (en) | 2010-08-27 | 2012-03-01 | Gruenenthal Gmbh | Substituted 2-amino-quinoline-3-carboxamides as kcnq2/3 modulators |
| MX342119B (es) | 2010-08-27 | 2016-09-14 | Grünenthal Gmbh * | 2-oxi-quinolin-3-carboxamidas sustituidas como moduladores de kcnq2/3. |
| US8653102B2 (en) | 2010-08-27 | 2014-02-18 | Gruenenthal Gmbh | Substituted 2-oxo- and 2-thioxo-dihydroquinoline-3-carboxamides as KCNQ2/3 modulators |
| EP2611780A1 (en) | 2010-09-01 | 2013-07-10 | Grünenthal GmbH | Substituted 1-oxo-dihydroisoquinoline-3-carboxamides as kcnq2/3 modulators |
| US8609674B2 (en) | 2010-11-16 | 2013-12-17 | Abbvie Inc. | Potassium channel modulators |
| CN114605305A (zh) * | 2020-12-04 | 2022-06-10 | 杭州中美华东制药有限公司 | 一种吲哚布芬乙酯化物的合成方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003303484C1 (en) * | 2002-12-23 | 2012-06-14 | Icagen, Inc. | Quinazolinones as potassium channel modulators |
| WO2005025293A2 (en) * | 2003-09-10 | 2005-03-24 | Icagen, Inc. | Fused ring heterocycles as potassium channel modulators |
-
2006
- 2006-11-17 JP JP2008540620A patent/JP2009515934A/ja not_active Abandoned
- 2006-11-17 WO PCT/EP2006/068627 patent/WO2007057447A1/en not_active Ceased
- 2006-11-17 EP EP06830034A patent/EP1951685A1/en not_active Withdrawn
- 2006-11-17 US US12/085,188 patent/US20090291973A1/en not_active Abandoned
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012512134A (ja) * | 2008-08-19 | 2012-05-31 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 冷感−メントール受容体拮抗剤 |
| JP2012521966A (ja) * | 2009-03-10 | 2012-09-20 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | Ｋｃｎｑ２／３モジュレータとしての置換された３−アミノ−２−メルカプトキノリン |
| JP2022543230A (ja) * | 2019-08-02 | 2022-10-11 | ハー・ルンドベック・アクチエゼルスカベット | てんかん又はてんかん発作において使用するためのＫｖ７カリウムチャネル開口薬としてのアルコール誘導体 |
| JP7591036B2 (ja) | 2019-08-02 | 2024-11-27 | ハー・ルンドベック・アクチエゼルスカベット | てんかん又はてんかん発作において使用するためのＫｖ７カリウムチャネル開口薬としてのアルコール誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2007057447A1 (en) | 2007-05-24 |
| EP1951685A1 (en) | 2008-08-06 |
| US20090291973A1 (en) | 2009-11-26 |
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