ES2224628T3 - Inhibidores de pde iii/iv a base de ftalazinonas. - Google Patents
Inhibidores de pde iii/iv a base de ftalazinonas.Info
- Publication number
- ES2224628T3 ES2224628T3 ES99914474T ES99914474T ES2224628T3 ES 2224628 T3 ES2224628 T3 ES 2224628T3 ES 99914474 T ES99914474 T ES 99914474T ES 99914474 T ES99914474 T ES 99914474T ES 2224628 T3 ES2224628 T3 ES 2224628T3
- Authority
- ES
- Spain
- Prior art keywords
- formula
- compounds
- compound
- hydrogen
- acid
- 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.)
- Expired - Lifetime
Links
- 239000003112 inhibitor Substances 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 145
- -1 methoxy, ethoxy Chemical group 0.000 claims description 50
- 150000003839 salts Chemical class 0.000 claims description 34
- 239000001257 hydrogen Substances 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000005518 carboxamido group Chemical group 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 14
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
- 208000035475 disorder Diseases 0.000 claims description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 239000011593 sulfur Substances 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 150000007942 carboxylates Chemical class 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 5
- 238000002483 medication Methods 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000005159 cyanoalkoxy group Chemical group 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000003917 carbamoyl group Chemical class [H]N([H])C(*)=O 0.000 claims 3
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 33
- 239000002253 acid Substances 0.000 description 31
- 238000000034 method Methods 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 239000000203 mixture Substances 0.000 description 17
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- 238000006243 chemical reaction Methods 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 14
- 150000003254 radicals Chemical class 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 239000007858 starting material Substances 0.000 description 13
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- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- 101100135868 Dictyostelium discoideum pde3 gene Proteins 0.000 description 10
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- 238000007792 addition Methods 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 9
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 description 8
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 description 8
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
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- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 5
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- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- NSGDYZCDUPSTQT-UHFFFAOYSA-N N-[5-bromo-1-[(4-fluorophenyl)methyl]-4-methyl-2-oxopyridin-3-yl]cycloheptanecarboxamide Chemical compound Cc1c(Br)cn(Cc2ccc(F)cc2)c(=O)c1NC(=O)C1CCCCCC1 NSGDYZCDUPSTQT-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
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- 125000004432 carbon atom Chemical group C* 0.000 description 4
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
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- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
- 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
- C07D417/02—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 two hetero rings
- C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (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)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Furan Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP98104643 | 1998-03-14 | ||
| EP98104643 | 1998-03-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2224628T3 true ES2224628T3 (es) | 2005-03-01 |
Family
ID=8231589
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99914474T Expired - Lifetime ES2224628T3 (es) | 1998-03-14 | 1999-03-04 | Inhibidores de pde iii/iv a base de ftalazinonas. |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6255303B1 (enExample) |
| EP (1) | EP1070056B1 (enExample) |
| JP (1) | JP2002506856A (enExample) |
| AT (1) | ATE270278T1 (enExample) |
| AU (1) | AU3328499A (enExample) |
| CA (1) | CA2323771A1 (enExample) |
| DE (1) | DE69918422T2 (enExample) |
| DK (1) | DK1070056T3 (enExample) |
| ES (1) | ES2224628T3 (enExample) |
| PT (1) | PT1070056E (enExample) |
| SI (1) | SI1070056T1 (enExample) |
| WO (1) | WO1999047505A1 (enExample) |
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| EA200301100A1 (ru) * | 2001-04-25 | 2004-06-24 | Алтана Фарма Аг | Новые фталазиноны |
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| WO2003008396A1 (en) * | 2001-07-16 | 2003-01-30 | Nikken Chemicals Co., Ltd. | Optically active oxazine derivative |
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| US20030073711A1 (en) * | 2001-08-23 | 2003-04-17 | Whitehead Clark M. | Methods for treatment of scleroderma |
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| GB0316290D0 (en) | 2003-07-11 | 2003-08-13 | Glaxo Group Ltd | Novel compounds |
| GB0317374D0 (en) | 2003-07-24 | 2003-08-27 | Glaxo Group Ltd | Medicament dispenser |
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| TWI341836B (en) | 2004-03-11 | 2011-05-11 | Theravance Inc | Biphenyl compounds useful as muscarinic receptor antagonists |
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| ATE517908T1 (de) | 2005-01-10 | 2011-08-15 | Glaxo Group Ltd | Androstan-17-alpha-carbonat-derivate zur verwendung bei der behandlung allergischer und entzündlicher zustände |
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| JP5876051B2 (ja) | 2010-09-08 | 2016-03-02 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | インフルエンザウィルス感染の治療に使用するためのインダゾール誘導体 |
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| EP3497100A1 (en) | 2016-08-08 | 2019-06-19 | GlaxoSmithKline Intellectual Property Development Limited | Chemical compounds |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58116471A (ja) * | 1981-12-29 | 1983-07-11 | Nippon Kayaku Co Ltd | ４−ヒドロキシメチル−１−フタラゾンエステル誘導体およびその塩 |
| ATE234270T1 (de) * | 1992-12-02 | 2003-03-15 | Pfizer | Cathecoldiether als selektive pde iv hemmungsmittel |
| EP0634404A1 (en) * | 1993-07-13 | 1995-01-18 | Rhone Poulenc Agriculture Ltd. | Phtalazin derivatives and their use as pesticides |
| DE19533975A1 (de) * | 1995-09-14 | 1997-03-20 | Merck Patent Gmbh | Arylalkyl-diazinone |
| KR20000070150A (ko) * | 1997-01-15 | 2000-11-25 | 빅 굴덴 롬베르크 케미쉐 파브릭 게엠베하 | 프탈라지논 |
-
1999
- 1999-03-04 SI SI9930652T patent/SI1070056T1/xx unknown
- 1999-03-04 AT AT99914474T patent/ATE270278T1/de not_active IP Right Cessation
- 1999-03-04 DE DE69918422T patent/DE69918422T2/de not_active Expired - Fee Related
- 1999-03-04 WO PCT/EP1999/001413 patent/WO1999047505A1/en not_active Ceased
- 1999-03-04 PT PT99914474T patent/PT1070056E/pt unknown
- 1999-03-04 ES ES99914474T patent/ES2224628T3/es not_active Expired - Lifetime
- 1999-03-04 JP JP2000536702A patent/JP2002506856A/ja not_active Withdrawn
- 1999-03-04 CA CA002323771A patent/CA2323771A1/en not_active Abandoned
- 1999-03-04 US US09/623,477 patent/US6255303B1/en not_active Expired - Fee Related
- 1999-03-04 DK DK99914474T patent/DK1070056T3/da active
- 1999-03-04 EP EP99914474A patent/EP1070056B1/en not_active Expired - Lifetime
- 1999-03-04 AU AU33284/99A patent/AU3328499A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| SI1070056T1 (en) | 2004-12-31 |
| AU3328499A (en) | 1999-10-11 |
| EP1070056B1 (en) | 2004-06-30 |
| DE69918422D1 (de) | 2004-08-05 |
| EP1070056A1 (en) | 2001-01-24 |
| ATE270278T1 (de) | 2004-07-15 |
| CA2323771A1 (en) | 1999-09-23 |
| US6255303B1 (en) | 2001-07-03 |
| JP2002506856A (ja) | 2002-03-05 |
| PT1070056E (pt) | 2004-11-30 |
| DE69918422T2 (de) | 2005-08-11 |
| WO1999047505A1 (en) | 1999-09-23 |
| DK1070056T3 (da) | 2004-11-08 |
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