BG65257B1 - 2-фенил-заместени имидазотриазинони като фосфодиестеразни инхибитори - Google Patents
2-фенил-заместени имидазотриазинони като фосфодиестеразни инхибитори Download PDFInfo
- Publication number
- BG65257B1 BG65257B1 BG104406A BG10440600A BG65257B1 BG 65257 B1 BG65257 B1 BG 65257B1 BG 104406 A BG104406 A BG 104406A BG 10440600 A BG10440600 A BG 10440600A BG 65257 B1 BG65257 B1 BG 65257B1
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- Prior art keywords
- compounds
- propyl
- ethoxy
- medicament
- methyl
- Prior art date
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- IJYHVZICHKCLMQ-UHFFFAOYSA-N imidazo[4,5-d]triazin-4-one Chemical class O=C1N=NN=C2N=CN=C12 IJYHVZICHKCLMQ-UHFFFAOYSA-N 0.000 title abstract description 4
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 title description 2
- 239000002571 phosphodiesterase inhibitor Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 50
- 150000001412 amines Chemical class 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 5
- 208000010228 Erectile Dysfunction Diseases 0.000 claims abstract description 4
- 201000010099 disease Diseases 0.000 claims abstract description 4
- 230000002526 effect on cardiovascular system Effects 0.000 claims abstract description 4
- 201000001881 impotence Diseases 0.000 claims abstract description 4
- 208000026106 cerebrovascular disease Diseases 0.000 claims abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 23
- -1 4-ethyl-piperazine-1-sulfonyl Chemical group 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- QMNWYGTWTXOQTP-UHFFFAOYSA-N 1h-triazin-6-one Chemical compound O=C1C=CN=NN1 QMNWYGTWTXOQTP-UHFFFAOYSA-N 0.000 claims description 6
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000012442 inert solvent Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 238000007039 two-step reaction Methods 0.000 claims description 2
- SBAJRNUPCYEFPV-UHFFFAOYSA-N 1h-triazin-6-one;dihydrochloride Chemical compound Cl.Cl.O=C1C=CN=NN1 SBAJRNUPCYEFPV-UHFFFAOYSA-N 0.000 claims 1
- XZLIYCQRASOFQM-UHFFFAOYSA-N 5h-imidazo[4,5-d]triazine Chemical class N1=NC=C2NC=NC2=N1 XZLIYCQRASOFQM-UHFFFAOYSA-N 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- 239000012456 homogeneous solution Substances 0.000 claims 1
- CUGZEDSDRBMZMY-UHFFFAOYSA-N trihydrate;hydrochloride Chemical compound O.O.O.Cl CUGZEDSDRBMZMY-UHFFFAOYSA-N 0.000 claims 1
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- 238000006243 chemical reaction Methods 0.000 abstract description 21
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 abstract description 9
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 abstract description 9
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- 239000013543 active substance Substances 0.000 abstract description 2
- 210000002229 urogenital system Anatomy 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
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- 239000000243 solution Substances 0.000 description 14
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Classifications
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Urology & Nephrology (AREA)
- Biochemistry (AREA)
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- Molecular Biology (AREA)
- Epidemiology (AREA)
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- Pulmonology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19750085A DE19750085A1 (de) | 1997-11-12 | 1997-11-12 | 2-Phenyl-substituierte Imidazotriazinone |
| DE1998112462 DE19812462A1 (de) | 1998-03-23 | 1998-03-23 | 2-[2-Ethoxy-5(4-ethyl-piperazin-1-sulfonyl) -phenyl]-5-methyl-7-prophyl-3H-imidazo[5,1-f][1,2,4]triazin-4-on Dihydrochlorid |
| DE1998140289 DE19840289A1 (de) | 1998-09-04 | 1998-09-04 | 2-Phenyl-substituierte Imidazotriazinone |
Publications (2)
| Publication Number | Publication Date |
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| BG104406A BG104406A (en) | 2001-08-31 |
| BG65257B1 true BG65257B1 (bg) | 2007-10-31 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BG104406A BG65257B1 (bg) | 1997-11-12 | 2000-05-05 | 2-фенил-заместени имидазотриазинони като фосфодиестеразни инхибитори |
Country Status (43)
Families Citing this family (176)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040014761A1 (en) * | 1997-10-28 | 2004-01-22 | Place Virgil A. | Treatment of female sexual dysfunction with phosphodiesterase inhibitors |
| US6403597B1 (en) * | 1997-10-28 | 2002-06-11 | Vivus, Inc. | Administration of phosphodiesterase inhibitors for the treatment of premature ejaculation |
| SK287161B6 (sk) * | 1997-11-12 | 2010-02-08 | Bayer Healthcare Ag | 2-Fenylsubstituované imidazotriazinóny, spôsob ich výroby, liečivá obsahujúce tieto látky a ich použitie |
| DE19827640A1 (de) | 1998-06-20 | 1999-12-23 | Bayer Ag | 7-Alkyl- und Cycloalkyl-substituierte Imidazotriazinone |
| US7235625B2 (en) | 1999-06-29 | 2007-06-26 | Palatin Technologies, Inc. | Multiple agent therapy for sexual dysfunction |
| DE19944161A1 (de) * | 1999-09-15 | 2001-03-22 | Bayer Ag | Neue Kombination zur Behandlung von sexueller Dysfunktion |
| CA2323008C (en) * | 1999-10-11 | 2005-07-12 | Pfizer Inc. | Pharmaceutically active compounds |
| US20050070499A1 (en) * | 1999-11-08 | 2005-03-31 | Pfizer Inc. | Compounds for the treatment of female sexual dysfunction |
| IL139457A0 (en) * | 1999-11-08 | 2001-11-25 | Pfizer | Compounds for the treatment of female sexual dysfunction |
| CA2395548A1 (en) | 1999-12-24 | 2001-07-05 | Bayer Aktiengesellschaft | Imidazo 1,3,5 triazinones and the use thereof |
| DE50008549D1 (de) | 1999-12-24 | 2004-12-09 | Bayer Healthcare Ag | Triazolotriazinone und ihre verwendung |
| US6777416B2 (en) | 1999-12-24 | 2004-08-17 | Bayer Aktiengesellschaft | Isoxazolo pyrimidinones and the use thereof |
| DE10010067A1 (de) * | 2000-03-02 | 2001-09-06 | Bayer Ag | Neue Imidazotriazinone und ihre Verwendung |
| WO2001078711A2 (en) | 2000-04-19 | 2001-10-25 | Lilly Icos, Llc. | Pde-v inhibitors for treatment of parkinson's disease |
| US6821978B2 (en) * | 2000-09-19 | 2004-11-23 | Schering Corporation | Xanthine phosphodiesterase V inhibitors |
| ES2275729T3 (es) * | 2000-09-29 | 2007-06-16 | Glaxo Group Limited | Compuestos utiles en el tratamiento de enfermedades inflamatorias. |
| US6548508B2 (en) | 2000-10-20 | 2003-04-15 | Pfizer, Inc. | Use of PDE V inhibitors for improved fecundity in mammals |
| US20020091129A1 (en) * | 2000-11-20 | 2002-07-11 | Mitradev Boolell | Treatment of premature ejaculation |
| DE10063108A1 (de) * | 2000-12-18 | 2002-06-20 | Bayer Ag | Verfahren zur Herstellung von Sulfonamid-substituierten Imidazotriazinonen |
| DE10063106A1 (de) * | 2000-12-18 | 2002-06-20 | Bayer Ag | Verfahren zur Herstellung von 2-(2-Ethoxyphenyl)-substituierten Imidazotriazinonen |
| DE10064105A1 (de) | 2000-12-21 | 2002-06-27 | Bayer Ag | Neue Substituierte Imidazotriazinone |
| JP2004527476A (ja) | 2001-02-02 | 2004-09-09 | ファイザー・インク | 真性糖尿病の処置 |
| DE10107639A1 (de) * | 2001-02-15 | 2002-08-22 | Bayer Ag | 2-Alkoxyphenyl-substituierte Imidazotriazinone |
| DE10108752A1 (de) * | 2001-02-23 | 2002-09-05 | Bayer Ag | Neue Substituierte Imidazotriazinone |
| GB0107751D0 (en) * | 2001-03-28 | 2001-05-16 | Pfizer Ltd | Pharmaceutically active compounds |
| DE10118306A1 (de) | 2001-04-12 | 2002-10-17 | Bayer Ag | Imidazotriazinonhaltige Zusammensetzungen zur nasalen Applikation |
| BR0209541A (pt) * | 2001-05-09 | 2004-04-20 | Bayer Healthcare Ag | Uso das imidazotriazinonas 2-fenil-substituìdas |
| US7458374B2 (en) | 2002-05-13 | 2008-12-02 | Alexza Pharmaceuticals, Inc. | Method and apparatus for vaporizing a compound |
| US7766013B2 (en) | 2001-06-05 | 2010-08-03 | Alexza Pharmaceuticals, Inc. | Aerosol generating method and device |
| US20070122353A1 (en) | 2001-05-24 | 2007-05-31 | Hale Ron L | Drug condensation aerosols and kits |
| US7090830B2 (en) | 2001-05-24 | 2006-08-15 | Alexza Pharmaceuticals, Inc. | Drug condensation aerosols and kits |
| US7585493B2 (en) | 2001-05-24 | 2009-09-08 | Alexza Pharmaceuticals, Inc. | Thin-film drug delivery article and method of use |
| GB0113344D0 (en) | 2001-06-01 | 2001-07-25 | Bayer Ag | Novel heterocycles 3 |
| US7087605B2 (en) | 2001-06-01 | 2006-08-08 | Bayer Aktiengesellschaft | 5-Ethyl-imidazotriazinones |
| DE10130167A1 (de) * | 2001-06-22 | 2003-01-02 | Bayer Ag | Imidazotriazine |
| DE10135815A1 (de) * | 2001-07-23 | 2003-02-06 | Bayer Ag | Verwendung von 2-Alkoxyphenyl-substituierten Imidazotriazinonen |
| DE60226615D1 (instruction) | 2001-08-28 | 2008-06-26 | Schering Corp | |
| WO2003042216A1 (en) * | 2001-11-09 | 2003-05-22 | Schering Corporation | Polycyclic guanine derivative phosphodiesterase v inhibitors |
| GB0129274D0 (en) * | 2001-12-06 | 2002-01-23 | Pfizer Ltd | Novel kit |
| ES2294189T3 (es) * | 2001-12-13 | 2008-04-01 | Asubio Pharma Co., Ltd. | Derivados de pirazolopirimidinona que tienen accion inhibidora de pde7. |
| GB0130219D0 (en) * | 2001-12-18 | 2002-02-06 | Pfizer Ltd | Compounds for the treatment of sexual dysfunction |
| GB0209988D0 (en) * | 2002-05-01 | 2002-06-12 | Bayer Ag | Novel Heterocycles |
| DE10220570A1 (de) | 2002-05-08 | 2003-11-20 | Bayer Ag | Carbamat-substituierte Pyrazolopyridine |
| WO2003101276A2 (en) | 2002-05-22 | 2003-12-11 | Virginia Commonwealth University | Protective effects of pde-5 inhibitors |
| JP2005529927A (ja) * | 2002-05-23 | 2005-10-06 | ファイザー インコーポレイテッド | 新規な組み合わせ |
| EP1719772A1 (en) | 2002-05-31 | 2006-11-08 | Schering Corporation | Process for preparing xanthine phosphodiesterase v inhibitors and precursors thereof |
| GB0214784D0 (en) * | 2002-06-26 | 2002-08-07 | Pfizer Ltd | Novel combination |
| DE10229778A1 (de) * | 2002-07-03 | 2004-01-29 | Bayer Ag | Neue Verwendung von Imidazotriazinonen |
| DE10230605A1 (de) | 2002-07-08 | 2004-01-29 | Bayer Ag | Substituierte Imidazotriazine |
| DE10232113A1 (de) * | 2002-07-16 | 2004-01-29 | Bayer Ag | Vardenafil Hydrochlorid Trihydrat enthaltende Arzneimittel |
| GB0219961D0 (en) | 2002-08-28 | 2002-10-02 | Pfizer Ltd | Oxytocin inhibitors |
| US7323462B2 (en) | 2002-12-10 | 2008-01-29 | Pfizer Inc. | Morpholine dopamine agonists |
| WO2004054560A1 (en) | 2002-12-13 | 2004-07-01 | Warner-Lambert Company Llc | Alpha-2-delta ligand to treat lower urinary tract symptoms |
| WO2004087652A2 (en) * | 2003-04-01 | 2004-10-14 | Smithkline Beecham Corporation | Imidazotriazine compounds |
| WO2004096810A1 (en) | 2003-04-29 | 2004-11-11 | Pfizer Limited | 5,7-diaminopyrazolo`4,3-d!pyrimidines useful in the treatment of hypertension |
| US20040220186A1 (en) * | 2003-04-30 | 2004-11-04 | Pfizer Inc. | PDE9 inhibitors for treating type 2 diabetes,metabolic syndrome, and cardiovascular disease |
| JP2007516149A (ja) | 2003-05-21 | 2007-06-21 | アレックザ ファーマシューティカルズ， インコーポレイテッド | 基板温度の均一性を制御する方法、および、内蔵式加熱ユニットおよびそれを使用する薬剤供給ユニット |
| WO2004103407A2 (en) | 2003-05-22 | 2004-12-02 | Altana Pharma Ag | Composition comprising a pde4 inhibitor and a pde5 inhibitor |
| CN100374441C (zh) | 2003-06-06 | 2008-03-12 | 天津倍方科技发展有限公司 | 二氢吡咯[2，3-d]嘧啶-4-酮衍生物，其制备方法及其制药用途 |
| JP2006219374A (ja) * | 2003-06-13 | 2006-08-24 | Daiichi Asubio Pharma Co Ltd | Ｐｄｅ７阻害作用を有するイミダゾトリアジノン誘導体 |
| US20050079548A1 (en) * | 2003-07-07 | 2005-04-14 | Plexxikon, Inc. | Ligand development using PDE4B crystal structures |
| US7291640B2 (en) * | 2003-09-22 | 2007-11-06 | Pfizer Inc. | Substituted triazole derivatives as oxytocin antagonists |
| BRPI0416202A (pt) * | 2003-11-21 | 2006-12-26 | Schering Corp | formulações inibidoras de fosfodiesterase v |
| US7572799B2 (en) * | 2003-11-24 | 2009-08-11 | Pfizer Inc | Pyrazolo[4,3-d]pyrimidines as Phosphodiesterase Inhibitors |
| GB0327323D0 (en) * | 2003-11-24 | 2003-12-31 | Pfizer Ltd | Novel pharmaceuticals |
| BRPI0506994A (pt) | 2004-01-22 | 2007-07-03 | Pfizer | derivados de triazol que inibem a atividade antagonista da vasopressina |
| CA2562251C (en) * | 2004-04-07 | 2009-04-28 | Pfizer Inc. | Pyrazolo'4,3-d pyrimidines |
| DE102004023069A1 (de) | 2004-05-11 | 2005-12-08 | Bayer Healthcare Ag | Neue Darreichungsformen des PDE 5-Inhibitors Vardenafil |
| US7540286B2 (en) | 2004-06-03 | 2009-06-02 | Alexza Pharmaceuticals, Inc. | Multiple dose condensation aerosol devices and methods of forming condensation aerosols |
| JP2008501617A (ja) * | 2004-06-11 | 2008-01-24 | アスビオファーマ株式会社 | Ｐｄｅ７阻害作用を有するイミダゾトリアジノン誘導体 |
| WO2006022714A1 (en) | 2004-08-12 | 2006-03-02 | Alexza Pharmaceuticals, Inc. | Aerosol drug delivery device incorporating percussively activated heat packages |
| DE102005001989A1 (de) * | 2005-01-15 | 2006-07-20 | Bayer Healthcare Ag | Intravenöse Formulierungen von PDE-Inhibitoren |
| ZA200707505B (en) * | 2005-02-18 | 2009-08-26 | Surface Logix Inc | Pharmacokinetically improved compounds |
| MX2007010142A (es) * | 2005-02-18 | 2007-12-07 | Surface Logix Inc | Metodos para fabricar compuestos mejorados farmacocineticamente que comprenden residuos o grupos funcionales y composiciones farmaceuticas que comprenden dichos compuestos. |
| DE102005009241A1 (de) * | 2005-03-01 | 2006-09-07 | Bayer Healthcare Ag | Arzneiformen mit kontrollierter Bioverfügbarkeit |
| DE102005009240A1 (de) | 2005-03-01 | 2006-09-07 | Bayer Healthcare Ag | Arzneiformen mit verbesserten pharmakokinetischen Eigenschaften |
| DE102005016345A1 (de) * | 2005-04-09 | 2006-10-12 | Bayer Healthcare Ag | Neue Verwendung von 2-Phenyl-substituierten Imidazotriazinon-Derivaten |
| KR101358479B1 (ko) | 2005-04-19 | 2014-02-06 | 다케다 게엠베하 | 폐고혈압 치료용 로플루밀라스트 |
| MX2007013215A (es) | 2005-05-12 | 2007-12-12 | Pfizer | Formas cristalinas anhidras de la n-[1-(2-etoxietil)-5-(n-etil-n- metilamino)-7-(4-metilpiridin-2-il-amino)-1h-pirazolo[4,3-d] pirimidina -3-carbonil] metanosulfonamida. |
| US20060264624A1 (en) * | 2005-05-20 | 2006-11-23 | Alexander Heim-Riether | Methods for synthesizing imidazotriazinones |
| US20070010525A1 (en) * | 2005-06-27 | 2007-01-11 | Meyer Jackson | Method and compositions for modulating neuropeptide hormone secretion |
| US20100222365A1 (en) * | 2005-08-10 | 2010-09-02 | Pfizer Inc | Substituted triazole deriviatives as oxytocin antagonists |
| US7678363B2 (en) | 2005-08-26 | 2010-03-16 | Braincells Inc | Methods of treating psychiatric conditions comprising administration of muscarinic agents in combination with SSRIs |
| EP2258359A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation with sabcomelin |
| AU2006299232A1 (en) * | 2005-09-29 | 2007-04-12 | Bayer Schering Pharma Aktiengesellschaft | PDE inhibitors and combinations thereof for the treatment of urological disorders |
| US20070093493A1 (en) * | 2005-10-12 | 2007-04-26 | Lilly Icos Llc | Treatment of benign prostatic hypertrophy and lower urinary tract symptoms |
| CA2625153A1 (en) | 2005-10-21 | 2007-04-26 | Braincells, Inc. | Modulation of neurogenesis by pde inhibition |
| JP2009513672A (ja) | 2005-10-31 | 2009-04-02 | ブレインセルス，インコーポレイティド | 神経発生のｇａｂａ受容体媒介調節 |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| CA2641013A1 (en) * | 2006-02-17 | 2007-08-30 | Wyeth | Methods for preparing sulfonamide substituted alcohols and intermediates thereof |
| EP1984347A1 (en) * | 2006-02-17 | 2008-10-29 | Wyeth a Corporation of the State of Delaware | Selective n-sulfonylation of 2-amino trifluoroalkyl substituted alcohols |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| US7977478B2 (en) * | 2006-03-13 | 2011-07-12 | Dr. Reddy's Laboratories Limited | Polymorphic forms of vardenafil |
| EP2586434B3 (en) * | 2006-03-17 | 2022-04-06 | The Johns Hopkins University | N-hydroxylsulfonamide derivatives as new physiologically useful nitroxyl donors |
| WO2007124045A2 (en) * | 2006-04-20 | 2007-11-01 | Ampla Pharmaceuticals, Inc. | Piperidine and piperazine compounds for use in the treatment of obesity, eating disorders and sexual dysfunction by potentiation of mc4 receptor activity |
| JP2009536667A (ja) | 2006-05-09 | 2009-10-15 | ブレインセルス，インコーポレイティド | ５ｈｔ受容体介在性の神経新生 |
| JP2009536669A (ja) | 2006-05-09 | 2009-10-15 | ブレインセルス，インコーポレイティド | アンジオテンシン調節による神経新生 |
| SI2032521T1 (sl) | 2006-06-27 | 2010-02-26 | Sandoz Ag | Nov postopek za pripravo soli |
| WO2008008398A2 (en) * | 2006-07-14 | 2008-01-17 | Shionogi & Co., Ltd. | Oxime compounds and the use thereof |
| CA2661483A1 (en) * | 2006-08-24 | 2008-02-28 | Surface Logix, Inc. | Pharmacokinetically improved 2-phenyl-substituted imidazotriazinone derivatives and their use |
| AR062501A1 (es) | 2006-08-29 | 2008-11-12 | Actelion Pharmaceuticals Ltd | Composiciones terapeuticas |
| AU2007292848A1 (en) | 2006-09-08 | 2008-03-13 | Braincells, Inc. | Combinations containing a 4-acylaminopyridine derivative |
| DE102006043443A1 (de) * | 2006-09-15 | 2008-03-27 | Bayer Healthcare Ag | Neue aza-bicyclische Verbindungen und ihre Verwendung |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| US8314119B2 (en) | 2006-11-06 | 2012-11-20 | Abbvie Inc. | Azaadamantane derivatives and methods of use |
| DK2101777T3 (en) | 2006-12-12 | 2015-08-17 | Gilead Sciences Inc | COMPOSITION FOR TREATMENT OF PULMONAL HYPERTENSION |
| US20080194529A1 (en) * | 2007-02-12 | 2008-08-14 | Auspex Pharmaceuticals, Inc. | HIGHLY SELECTIVE and LONG-ACTING PDE5 MODULATORS |
| CA2677691C (en) | 2007-02-12 | 2012-07-31 | David Bar-Or | Reducing side effects of tramadol |
| CN101657101B (zh) * | 2007-02-12 | 2013-12-11 | Dmi生物科学公司 | 并存早泄和勃起功能障碍的治疗 |
| WO2008112661A2 (en) | 2007-03-09 | 2008-09-18 | Alexza Pharmaceuticals, Inc. | Heating unit for use in a drug delivery device |
| DE102007027067A1 (de) | 2007-06-12 | 2008-12-18 | Ratiopharm Gmbh | Verfahren zur Herstellung eines Arzneimittels enthaltend Vardenafil Hydrochlorid Trihydrat |
| WO2008151734A1 (en) * | 2007-06-13 | 2008-12-18 | Bayer Schering Pharma Aktiengesellschaft | Pde inhibitors for the treatment of hearing impairment |
| WO2009030095A1 (en) * | 2007-09-06 | 2009-03-12 | Topharman Shanghai Co., Ltd. | Process for preparing vardenafil and its intermediates |
| EP2228370B1 (en) | 2007-12-28 | 2012-05-23 | Topharman Shanghai Co., Ltd. | N-{1-[3-(2-ethoxy-5-(4-ethylpiperazinyl)benzenesulfonyl)-4,5-dihydro-5-oxo-1,2,4-triazin-6-yl]ethyl}butyramide, the preparation method and use thereof |
| US20090181975A1 (en) * | 2008-01-15 | 2009-07-16 | Forest Laboratories Holdings Limited | Nebivolol in the treatment of sexual dysfunction |
| DE102008063992A1 (de) | 2008-12-19 | 2010-09-02 | Lerner, Zinoviy, Dipl.-Ing. | Neue aliphatisch substituierte Pyrazolopyridine und ihre Verwendung |
| JP2012513464A (ja) | 2008-12-23 | 2012-06-14 | ザ トラスティーズ オブ コロンビア ユニヴァーシティ イン ザ シティ オブ ニューヨーク | ホスホジエステラーゼ阻害剤及びその使用 |
| US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| GB0903493D0 (en) | 2009-02-27 | 2009-04-08 | Vantia Ltd | New compounds |
| DE102009020888A1 (de) | 2009-05-12 | 2010-11-18 | Ratiopharm Gmbh | Schmelztablette, enthaltend ein Vardenafil-Salz |
| AU2010280358A1 (en) | 2009-08-07 | 2012-03-08 | Ranbaxy Laboratories Limited | Processes for the preparation of vardenafil |
| NZ625983A (en) | 2009-11-27 | 2016-02-26 | Adverio Pharma Gmbh | Method for producing methyl-{ 4,6-diamino-2-[1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridino-3-yl]pyrimidino-5-yl} methyl carbamate and its purification for use thereof as pharmaceutical substance |
| UY33041A (es) | 2009-11-27 | 2011-06-30 | Bayer Schering Pharma Aktienegesellschaft | Procedimiento para la preparaciòn de {4,6-diamino-2-[1-(2-fluorobencil)-1h-pirazolo[3,4-b]piridin-3-il]pirimidin-5-il}carbamato de metilo y su purificaciòn para el uso como principio activo farmacèutico |
| WO2011075801A1 (pt) | 2009-12-21 | 2011-06-30 | Acef S.A. | Cubebina, lignana dibenzilbutirolactólica, seus derivados semi-sintéticos e sintéticos, bem como outras lignanas e neolignanas como agente vasodilatador na terapia da disfunção erétil |
| PL390079A1 (pl) | 2009-12-30 | 2011-07-04 | Zakłady Farmaceutyczne POLPHARMA Spółka Akcyjna | Sposób otrzymywania wardenafilu i jego izolacji jako soli z kwasem cytrynowym oraz krystaliczna postać tej soli |
| EP2556820A4 (en) | 2010-04-05 | 2015-01-21 | Sk Chemicals Co Ltd | COMPOSITION CONTAINING PDE5 INHIBITOR FOR MITIGATION OF SKIN WRINKLES |
| DE102010021637A1 (de) | 2010-05-26 | 2011-12-01 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 5-Fluor-1H-Pyrazolopyridine und ihre Verwendung |
| CN102382129B (zh) * | 2010-08-19 | 2014-02-26 | 山东轩竹医药科技有限公司 | 螺环取代的磷酸二酯酶抑制剂 |
| CN102372730B (zh) * | 2010-08-19 | 2014-03-26 | 山东轩竹医药科技有限公司 | 桥环取代的磷酸二酯酶抑制剂 |
| CN103313988B (zh) | 2010-09-20 | 2016-06-08 | 论坛医药有限公司 | 咪唑并三嗪酮化合物 |
| CN103180321A (zh) | 2010-09-23 | 2013-06-26 | Abbvie公司 | 氮杂金刚烷衍生物的一水合物 |
| EA201691759A1 (ru) | 2010-10-15 | 2017-05-31 | Джилид Сайэнс, Инк. | Композиции и способы лечения легочной гипертензии |
| TWI462739B (zh) | 2010-11-02 | 2014-12-01 | Univ Kaohsiung Medical | Ｓｉｌｄｅｎａｆｉｌ－同族物四級銨哌嗪鹽類之製備及醫療用途 |
| CN102134242B (zh) * | 2011-01-21 | 2013-08-28 | 浙江大德药业集团有限公司 | 一种用于治疗阳痿的快速长效的化合物 |
| MA37958B1 (fr) | 2011-10-10 | 2018-10-31 | H Lundbeck As | Pde9i ayant un squelette imidazo pyrazinone |
| AT512084A1 (de) | 2011-10-20 | 2013-05-15 | Univ Wien Tech | Diazabicyclo- und diazaspiro-alkanderivate als phosphodiesterase-5 inhibitoren |
| WO2013067309A1 (en) | 2011-11-04 | 2013-05-10 | Xion Pharmaceutical Corporation | Methods and compositions for oral administration of melanocortin receptor agonist compounds |
| CZ303877B6 (cs) | 2011-11-24 | 2013-06-05 | Zentiva, K.S. | Zpusob prípravy a izolace solí vardenafilu s kyselinami |
| WO2013106547A1 (en) | 2012-01-10 | 2013-07-18 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| WO2013109738A1 (en) | 2012-01-17 | 2013-07-25 | The Trustees Of Columbia University In The City Of New York | Novel phosphodiesterase inhibitors and uses thereof |
| BR112014018199A8 (pt) | 2012-01-26 | 2021-03-02 | H Lundbeck As | inibidores da pde9 com cadeia principal imidazo triazinona, composição farmacêutica que os compreende, uso dos referidos inibidores e processo para sua preparação |
| CN104168895B (zh) | 2012-02-28 | 2020-02-21 | 首尔制药株式会社 | 包含西地那非作为活性成分的掩蔽苦味的高含量快速溶解膜 |
| EP2828262A4 (en) | 2012-03-19 | 2015-09-23 | Forum Pharmaceuticals Inc | IMIDAZOTRIAZINONVERBINDUNGEN |
| CN103374002B (zh) * | 2012-04-19 | 2015-07-15 | 山东轩竹医药科技有限公司 | 磷酸二酯酶-5抑制剂 |
| CZ307091B6 (cs) | 2012-09-14 | 2018-01-10 | Zentiva, K.S. | Stabilní farmaceutický přípravek obsahující Vardenafil hydrochlorid |
| CN105025900B (zh) | 2012-12-04 | 2018-11-02 | 株式会社阿丽浱欧 | 包含5型磷酸二酯酶抑制剂的神经细胞的细胞凋亡抑制用组合物 |
| KR101953735B1 (ko) | 2012-12-14 | 2019-03-04 | 한미약품 주식회사 | 포스포다이에스터라제-5 억제제를 포함하는 츄정 |
| BR112015019571A2 (pt) | 2013-02-21 | 2017-07-18 | Adverio Pharma Gmbh | formas de {4,6-diamino-2-[1-(2-fluorobenzil)-1h-pirazolo[3,4-b]piridino-3-il]pirimidino-5-il}metilcarbamato de metila |
| CN104109164B (zh) * | 2013-04-18 | 2016-05-25 | 广州朗圣药业有限公司 | 一种适合工业化的高纯度盐酸伐地那非三水合物的制备方法 |
| US10899756B2 (en) | 2013-07-17 | 2021-01-26 | The Trustees Of Columbia University In The City Of New York | Phosphodiesterase inhibitors and uses thereof |
| EP3082428A4 (en) | 2013-12-09 | 2017-08-02 | Respira Therapeutics, Inc. | Pde5 inhibitor powder formulations and methods relating thereto |
| PL223869B1 (pl) | 2013-12-16 | 2016-11-30 | Starogardzkie Zakłady Farm Polpharma Spółka Akcyjna | Sposób otrzymywania wardenafilu i jego soli |
| KR101645652B1 (ko) | 2014-11-03 | 2016-08-08 | (주)퓨젠바이오농업회사법인 | 세리포리아 락세라타에 의해 생산되는 세포외다당체를 유효성분으로 함유하는 성기능개선용 조성물 |
| CN107810187B (zh) | 2015-07-07 | 2020-09-15 | H.隆德贝克有限公司 | 用于治疗外周疾病的具有咪唑并三嗪酮骨架和咪唑并吡嗪酮骨架的pde9抑制剂 |
| DK3377495T3 (da) * | 2015-11-16 | 2022-05-09 | Topadur Pharma Ag | 2-phenyl-3,4-dihydropyrrolo[2,1-f] [1,2,4]triazinon-derivativer som phosphodiesterasehæmmere og anvendelser deraf |
| WO2017168174A1 (en) | 2016-04-02 | 2017-10-05 | N4 Pharma Uk Limited | New pharmaceutical forms of sildenafil |
| RU2019121646A (ru) | 2016-12-14 | 2021-01-15 | Респира Терапьютикс, Инк. | Способы и композиции для лечения легочной гипертензии и других заболеваний легких |
| AU2018274599B9 (en) | 2017-05-22 | 2022-04-07 | Topadur Pharma Ag | Novel dual mode of action soluble guanylate cyclase activators and phosphodiesterase inhibitors and uses thereof |
| CN107445964A (zh) * | 2017-07-29 | 2017-12-08 | 合肥创新医药技术有限公司 | 一种盐酸伐地那非杂质的合成方法 |
| CA3085219A1 (en) | 2017-12-20 | 2019-06-27 | Klaria Pharma Holding Ab | Film formulation comprising vardenafil, method for its preparation, and use thereof |
| EP3746138A4 (en) | 2018-02-02 | 2021-11-03 | Alexza Pharmaceuticals, Inc. | ELECTRIC CONDENSING AEROSOL DEVICE |
| EP4349403A3 (en) | 2018-05-25 | 2024-06-05 | Cardurion Pharmaceuticals, Inc. | Monohydrate and crystalline forms of 6-[(3s,4s)-4-methyl-1- (pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-3-tetrahydropyran-4-yl- 7h-imid azo [1,5- a] pyrazin-8-one |
| CN112997258A (zh) | 2018-06-14 | 2021-06-18 | 阿斯利康(英国)有限公司 | 用cGMP特异性磷酸二酯酶5抑制剂药物组合物治疗勃起功能障碍的方法 |
| AU2019287546A1 (en) | 2018-06-14 | 2021-01-21 | Astrazeneca Uk Limited | Methods for treating erectile dysfunction with a cGMP-specific phosphodiesterase 5 inhibitor pharmaceutical composition |
| BR112021003686A2 (pt) | 2018-08-31 | 2021-05-18 | Imara Inc. | inibidores de pde9 para tratar doença falciforme |
| BR112021009958A2 (pt) * | 2018-11-28 | 2021-08-17 | Topadur Pharma Ag | modo duplo de ação de ativadores de guanilato ciclase solúveis e inibidores de fosfodiesterase e seus usos |
| EP3939954B1 (en) | 2019-03-13 | 2025-07-23 | Otsuka Pharmaceutical Co., Ltd. | Method for introducing deuterated lower alkyl into amine moiety of compound containing secondary amine |
| US11590209B2 (en) | 2020-01-21 | 2023-02-28 | Palatin Technologies, Inc. | Use of bremelanotide in patients with controlled hypertension |
| WO2021245192A1 (en) | 2020-06-04 | 2021-12-09 | Topadur Pharma Ag | Novel dual mode of action soluble guanylate cyclase activators and phosphodiesterase inhibitors and uses thereof |
| JP2023552632A (ja) * | 2020-12-11 | 2023-12-18 | イルドン ファーマシューティカル カンパニー リミテッド | アンドロゲン受容体及びホスホジエステラーゼ二重阻害剤としての新規化合物 |
| US20240228501A1 (en) * | 2021-04-21 | 2024-07-11 | Changchun Genescience Pharmaceutical Co., Ltd. | Imidazole-containing condensed ring derivative, preparation method therefor, and application thereof in medicine |
| CN114085225A (zh) * | 2021-06-04 | 2022-02-25 | 广东西捷药业有限公司 | 一种伐地那非类似物及其合成方法和应用 |
| AU2022354094A1 (en) | 2021-09-29 | 2024-02-15 | Topadur Pharma Ag | Topical compositions of 2-phenyl-3,4-dihydropyrrolo[2,l-f] [1,2,4]triazinone derivatives and uses thereof |
| KR20230129639A (ko) | 2022-03-02 | 2023-09-11 | 연세대학교 산학협력단 | 이중작용 pde5 억제제/질산유기에스터의 국소 혈류 증진을 위한 경피 투약 형태 |
| KR20240154529A (ko) | 2022-03-02 | 2024-10-25 | 토파두르 파마 아게 | 국소 조성물 및 이들의 용도 |
| WO2024173675A1 (en) | 2023-02-16 | 2024-08-22 | University Of Rochester | Improving glymphatic-lymphatic efflux |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2255172A1 (de) * | 1971-11-19 | 1973-05-24 | Allen & Hanburys Ltd | Imidazotriazinone, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneipraeparate |
| DE2364076A1 (de) * | 1973-01-04 | 1974-07-18 | Allen & Hanburys Ltd | Imidazotriazine, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneipraeparate |
| DE2811780A1 (de) * | 1977-03-25 | 1978-09-28 | Allen & Hanburys Ltd | Neue triazinverbindungen, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| EP0009384A1 (en) * | 1978-09-18 | 1980-04-02 | Glaxo Group Limited | Processes for the preparation of triazinones and condensed triazinones, and compounds so obtained |
| WO1994028902A1 (en) * | 1993-06-09 | 1994-12-22 | Pfizer Limited | Pyrazolopyrimidinones for the treatment of impotence |
Family Cites Families (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US26565A (en) * | 1859-12-27 | Improved register for railroad-cars | ||
| DE812845C (de) | 1944-12-07 | 1951-09-06 | Georges Lissac | Brille |
| US2705715A (en) | 1952-10-29 | 1955-04-05 | American Cyanamid Co | Purine compounds and methods of preparing the same |
| CH367510A (de) | 1957-11-27 | 1963-02-28 | Ciba Geigy | Verfahren zur Herstellung neuer Sulfonamide |
| GB1042471A (en) | 1963-01-16 | 1966-09-14 | Ilford Ltd | Penta-azaindenes, their production and use in photographic emulsions |
| GB1051734A (instruction) | 1963-01-16 | |||
| US3169129A (en) | 1963-05-10 | 1965-02-09 | American Cyanamid Co | 2-ortho-hydroxy-phenyl-4-(3h)-quinazolinones |
| USRE26565E (en) | 1966-03-02 | 1969-04-29 | Table iii | |
| GB1493685A (en) | 1970-12-15 | 1977-11-30 | May & Baker Ltd | 8-azapurinones |
| GB1338235A (en) | 1970-12-15 | 1973-11-21 | May & Baker Ltd | Azapurinones |
| US4052390A (en) | 1973-06-12 | 1977-10-04 | May & Baker Limited | Azapurinones |
| US4060615A (en) | 1976-02-18 | 1977-11-29 | Mead Johnson & Company | 2-Piperazinyl-6,7-dimethoxyquinazolines |
| GB1561345A (en) | 1976-10-22 | 1980-02-20 | May & Baker Ltd | 8 - azapuring - 6 - ones |
| US4159330A (en) | 1976-11-02 | 1979-06-26 | Carlo Erba S.P.A. | 2-Disubstituted phenyl-3,4-dihydro-4-oxo-quinazoline derivatives and process for their preparation |
| GB1584461A (en) | 1977-03-25 | 1981-02-11 | Allen & Hanburys Ltd | Imidazotriazines imidazotriazinones and pharmaceutical compositions containing them |
| US4287673A (en) * | 1980-01-11 | 1981-09-08 | Sunbeam Corporation | Hair dryer diffuser |
| EP0054132B1 (de) | 1980-12-12 | 1984-10-10 | Dr. Karl Thomae GmbH | Neue Pyrimidinone, ihre Herstellung und Arzneimittel mit einem Gehalt an diesen Stoffen |
| US4431440A (en) | 1981-02-20 | 1984-02-14 | American Cyanamid Company | Method to alter or control the development and/or the life cycle of various plant species |
| JPS60246396A (ja) | 1984-05-22 | 1985-12-06 | Sankyo Co Ltd | 酵素阻害物質ジヒドロデスオキシグリゼオ−ル酸及びその塩類 |
| US4666908A (en) | 1985-04-05 | 1987-05-19 | Warner-Lambert Company | 5-Substituted pyrazolo[4,3-d]pyrimidine-7-ones and methods of use |
| CA1303037C (en) | 1987-02-02 | 1992-06-09 | Smith Kline & French Laboratories Limited | Purinone derivatives as bronchodilators vasodilators and anti-allergic agents |
| US5254571A (en) | 1988-04-21 | 1993-10-19 | Smith Kline & French Laboratories Ltd. | Chemical compounds |
| DE68908786T2 (de) | 1988-06-16 | 1994-03-17 | Smith Kline French Lab | Condensierte Pyrimidinderivate, Verfahren und Zwischenprodukte zu ihrer Herstellung und diese enthaltende pharmazeutische Zubereitungen. |
| GB8814352D0 (en) | 1988-06-16 | 1988-07-20 | Smith Kline French Lab | Chemical compounds |
| US5075310A (en) | 1988-07-01 | 1991-12-24 | Smith Kline & French Laboratories, Ltd. | Pyrimidone derivatives as bronchodilators |
| US4923874A (en) | 1988-07-21 | 1990-05-08 | G. D. Searle & Co. | Use of 8-azapurin-6-one derivatives for control of hypertension |
| GB8817651D0 (en) | 1988-07-25 | 1988-09-01 | Smith Kline French Lab | Chemical compounds |
| GB8827988D0 (en) | 1988-11-30 | 1989-01-05 | Smith Kline French Lab | Chemical compounds |
| US5574020A (en) * | 1989-09-28 | 1996-11-12 | Eli Lilly And Company | Tilmicosin formulation |
| GB8928346D0 (en) | 1989-12-15 | 1990-02-21 | Smith Kline French Lab | Chemical compounds |
| EP0524180B1 (en) * | 1990-04-11 | 1995-04-26 | The Upjohn Company | Taste masking of ibuprofen by fluid bed coating |
| US5250534A (en) | 1990-06-20 | 1993-10-05 | Pfizer Inc. | Pyrazolopyrimidinone antianginal agents |
| GB9013750D0 (en) | 1990-06-20 | 1990-08-08 | Pfizer Ltd | Therapeutic agents |
| GB9114760D0 (en) | 1991-07-09 | 1991-08-28 | Pfizer Ltd | Therapeutic agents |
| US5316906A (en) | 1991-08-23 | 1994-05-31 | Molecular Probes, Inc. | Enzymatic analysis using substrates that yield fluorescent precipitates |
| GB9119704D0 (en) * | 1991-09-14 | 1991-10-30 | Pfizer Ltd | Therapeutic agents |
| GB9121028D0 (en) * | 1991-10-03 | 1991-11-13 | Pfizer Ltd | Therapeutic agents |
| GB9126260D0 (en) | 1991-12-11 | 1992-02-12 | Pfizer Ltd | Therapeutic agents |
| US5294612A (en) | 1992-03-30 | 1994-03-15 | Sterling Winthrop Inc. | 6-heterocyclyl pyrazolo [3,4-d]pyrimidin-4-ones and compositions and method of use thereof |
| GB9213623D0 (en) * | 1992-06-26 | 1992-08-12 | Pfizer Ltd | Therapeutic agents |
| US5734053A (en) | 1992-06-26 | 1998-03-31 | Pfizer Inc | Purinone antianginal agents |
| GB9218322D0 (en) * | 1992-08-28 | 1992-10-14 | Pfizer Ltd | Therapeutic agents |
| GB9312210D0 (en) | 1993-06-14 | 1993-07-28 | Smithkline Beecham Plc | Chemical compounds |
| GB9315017D0 (en) | 1993-07-20 | 1993-09-01 | Glaxo Lab Sa | Chemical compounds |
| US5614627A (en) | 1993-09-10 | 1997-03-25 | Eisai Co., Ltd. | Quinazoline compounds |
| US6143746A (en) * | 1994-01-21 | 2000-11-07 | Icos Corporation | Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use |
| US5374053A (en) * | 1994-01-21 | 1994-12-20 | Heidelberger Druckmaschinen Ag | Device for changing the transport position of products |
| US5556847A (en) * | 1994-10-27 | 1996-09-17 | Duquesne University Of The Holy Ghost | Methods of effecting memory enhancement mediated by steroid sulfatase inhibitors |
| GB9423911D0 (en) * | 1994-11-26 | 1995-01-11 | Pfizer Ltd | Therapeutic agents |
| GB9514464D0 (en) | 1995-07-14 | 1995-09-13 | Glaxo Lab Sa | Medicaments |
| GB9612514D0 (en) * | 1996-06-14 | 1996-08-14 | Pfizer Ltd | Novel process |
| SK287161B6 (sk) * | 1997-11-12 | 2010-02-08 | Bayer Healthcare Ag | 2-Fenylsubstituované imidazotriazinóny, spôsob ich výroby, liečivá obsahujúce tieto látky a ich použitie |
| US6221402B1 (en) * | 1997-11-20 | 2001-04-24 | Pfizer Inc. | Rapidly releasing and taste-masking pharmaceutical dosage form |
| DE19827640A1 (de) * | 1998-06-20 | 1999-12-23 | Bayer Ag | 7-Alkyl- und Cycloalkyl-substituierte Imidazotriazinone |
| UA67802C2 (uk) * | 1998-10-23 | 2004-07-15 | Пфайзер Рісьоч Енд Дівелепмент Компані, Н.В./С.А. | Фармацевтична композиція з контрольованим вивільненням інгібітора цгмф фде-5 (варіанти), спосіб її одержання та спосіб лікування еректильної дисфункції |
| US6075028A (en) * | 1999-09-23 | 2000-06-13 | Graham; Richard | Method of treating Tourette's syndrome and related CNS disorders |
| CA2323008C (en) * | 1999-10-11 | 2005-07-12 | Pfizer Inc. | Pharmaceutically active compounds |
| CA2395548A1 (en) * | 1999-12-24 | 2001-07-05 | Bayer Aktiengesellschaft | Imidazo 1,3,5 triazinones and the use thereof |
| BR0209541A (pt) * | 2001-05-09 | 2004-04-20 | Bayer Healthcare Ag | Uso das imidazotriazinonas 2-fenil-substituìdas |
| DE10232113A1 (de) * | 2002-07-16 | 2004-01-29 | Bayer Ag | Vardenafil Hydrochlorid Trihydrat enthaltende Arzneimittel |
-
1998
- 1998-10-31 SK SK709-2000A patent/SK287161B6/sk not_active IP Right Cessation
- 1998-10-31 AU AU15587/99A patent/AU738675B2/en not_active Expired
- 1998-10-31 DE DE59803108T patent/DE59803108D1/de not_active Expired - Lifetime
- 1998-10-31 SI SI9830140T patent/SI1049695T1/xx unknown
- 1998-10-31 KR KR10-2000-7005051A patent/KR100430355B1/ko not_active Expired - Lifetime
- 1998-10-31 CN CNB031199402A patent/CN100430396C/zh not_active Expired - Lifetime
- 1998-10-31 ES ES01123321T patent/ES2386420T3/es not_active Expired - Lifetime
- 1998-10-31 PL PL340400A patent/PL201336B1/pl unknown
- 1998-10-31 CH CH00932/00A patent/CH693954A5/de not_active IP Right Cessation
- 1998-10-31 CZ CZ20001759A patent/CZ301911B6/cs not_active IP Right Cessation
- 1998-10-31 HU HU0100394A patent/HU227841B1/hu unknown
- 1998-10-31 CA CA002395558A patent/CA2395558C/en not_active Expired - Fee Related
- 1998-10-31 PT PT01123321T patent/PT1174431E/pt unknown
- 1998-10-31 JP JP2000520443A patent/JP3356428B2/ja not_active Expired - Lifetime
- 1998-10-31 US US09/554,162 patent/US6362178B1/en not_active Expired - Lifetime
- 1998-10-31 NZ NZ504436A patent/NZ504436A/en not_active IP Right Cessation
- 1998-10-31 BR BR9812785-3A patent/BR9812785A/pt not_active IP Right Cessation
- 1998-10-31 ID IDW20000881A patent/ID25871A/id unknown
- 1998-10-31 CU CU20000100A patent/CU23063A3/es unknown
- 1998-10-31 IL IL13546298A patent/IL135462A0/xx active IP Right Grant
- 1998-10-31 HR HRP20020585AA patent/HRP20020585B1/hr not_active IP Right Cessation
- 1998-10-31 GB GB0010974A patent/GB2346877B/en not_active Expired - Lifetime
- 1998-10-31 DE DE19881732D patent/DE19881732D2/de not_active Expired - Lifetime
- 1998-10-31 DK DK98959821T patent/DK1049695T3/da active
- 1998-10-31 SI SI9830936T patent/SI1174431T1/sl unknown
- 1998-10-31 ES ES98959821T patent/ES2172945T3/es not_active Expired - Lifetime
- 1998-10-31 BR BRPI9816155-5A patent/BR9816155B1/pt not_active IP Right Cessation
- 1998-10-31 WO PCT/EP1998/006910 patent/WO1999024433A1/de active IP Right Grant
- 1998-10-31 EP EP10182939A patent/EP2295436A1/de not_active Withdrawn
- 1998-10-31 HU HU0100394A patent/HU228196B1/hu unknown
- 1998-10-31 UA UA2000063402A patent/UA46166C2/uk unknown
- 1998-10-31 AT AT98959821T patent/ATE213246T1/de active
- 1998-10-31 DE DE19881732A patent/DE19881732C1/de not_active Expired - Lifetime
- 1998-10-31 HR HR20000292A patent/HRP20000292B1/xx not_active IP Right Cessation
- 1998-10-31 CA CA002309332A patent/CA2309332C/en not_active Expired - Lifetime
- 1998-10-31 EE EEP200000291A patent/EE04781B1/xx unknown
- 1998-10-31 PT PT98959821T patent/PT1049695E/pt unknown
- 1998-10-31 EP EP01123321A patent/EP1174431B1/de not_active Expired - Lifetime
- 1998-10-31 PL PL359442A patent/PL194801B1/pl unknown
- 1998-10-31 KR KR1020037017067A patent/KR100548120B1/ko not_active Expired - Lifetime
- 1998-10-31 HU HU1200113A patent/HU230154B1/hu unknown
- 1998-10-31 ES ES200050033A patent/ES2194567B1/es not_active Expired - Fee Related
- 1998-10-31 DK DK01123321.0T patent/DK1174431T3/da active
- 1998-10-31 CN CN98811092A patent/CN1123573C/zh not_active Expired - Lifetime
- 1998-10-31 EP EP98959821A patent/EP1049695B1/de not_active Expired - Lifetime
- 1998-10-31 TR TR2000/01338T patent/TR200001338T2/xx unknown
- 1998-11-05 IN IN3276DE1998 patent/IN188419B/en unknown
- 1998-11-11 TW TW087118724A patent/TW513431B/zh not_active IP Right Cessation
- 1998-11-11 PE PE1998001090A patent/PE131799A1/es not_active IP Right Cessation
- 1998-11-11 MY MYPI98005123A patent/MY138535A/en unknown
- 1998-11-11 TW TW089124605A patent/TWI229081B/zh not_active IP Right Cessation
- 1998-11-12 AR ARP980105724A patent/AR013759A1/es active IP Right Grant
- 1998-11-12 UY UY25246A patent/UY25246A1/es not_active IP Right Cessation
- 1998-11-12 CO CO98066900A patent/CO4980861A1/es unknown
- 1998-11-12 HN HN1998000175A patent/HN1998000175A/es unknown
-
1999
- 1999-08-19 UY UY25671A patent/UY25671A1/es not_active Application Discontinuation
-
2000
- 2000-04-04 IL IL135462A patent/IL135462A/en not_active IP Right Cessation
- 2000-04-05 LU LU90561A patent/LU90561B1/de active
- 2000-05-05 BG BG104406A patent/BG65257B1/bg unknown
- 2000-05-09 DK DK200000766A patent/DK176852B1/da not_active IP Right Cessation
- 2000-05-09 FI FI20001086A patent/FI113772B/fi not_active IP Right Cessation
- 2000-05-11 SE SE0001745A patent/SE522809C2/sv not_active IP Right Cessation
- 2000-05-11 NO NO20002444A patent/NO314940B1/no not_active IP Right Cessation
-
2001
- 2001-08-30 US US09/943,530 patent/US6566360B1/en not_active Expired - Lifetime
-
2002
- 2002-04-11 NO NO20021714A patent/NO20021714D0/no not_active Application Discontinuation
- 2002-05-02 JP JP2002130480A patent/JP4388729B2/ja not_active Expired - Lifetime
- 2002-05-15 AR ARP020101786A patent/AR035972A2/es active IP Right Grant
-
2003
- 2003-02-12 US US10/365,740 patent/US6890922B2/en not_active Expired - Lifetime
-
2004
- 2004-08-12 IL IL163475A patent/IL163475A/en not_active IP Right Cessation
- 2004-08-20 US US10/923,544 patent/US7122540B2/en not_active Expired - Lifetime
-
2006
- 2006-04-21 US US11/409,417 patent/US7314871B2/en not_active Expired - Fee Related
-
2007
- 2007-12-21 US US12/004,933 patent/US7704999B2/en not_active Expired - Fee Related
-
2009
- 2009-09-29 US US12/569,720 patent/US7696206B2/en not_active Expired - Fee Related
-
2010
- 2010-03-04 US US12/717,443 patent/US20110009367A1/en not_active Abandoned
-
2012
- 2012-03-26 US US13/429,588 patent/US20130059844A1/en not_active Abandoned
- 2012-08-03 CY CY20121100695T patent/CY1112949T1/el unknown
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2255172A1 (de) * | 1971-11-19 | 1973-05-24 | Allen & Hanburys Ltd | Imidazotriazinone, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneipraeparate |
| CH594671A5 (instruction) * | 1971-11-19 | 1978-01-13 | Allen & Hanburys Ltd | |
| DE2364076A1 (de) * | 1973-01-04 | 1974-07-18 | Allen & Hanburys Ltd | Imidazotriazine, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneipraeparate |
| FR2213058A1 (instruction) * | 1973-01-04 | 1974-08-02 | Allen & Hanburys Ltd | |
| DE2811780A1 (de) * | 1977-03-25 | 1978-09-28 | Allen & Hanburys Ltd | Neue triazinverbindungen, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| EP0009384A1 (en) * | 1978-09-18 | 1980-04-02 | Glaxo Group Limited | Processes for the preparation of triazinones and condensed triazinones, and compounds so obtained |
| WO1994028902A1 (en) * | 1993-06-09 | 1994-12-22 | Pfizer Limited | Pyrazolopyrimidinones for the treatment of impotence |
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