CA2309332A1 - 2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors - Google Patents

2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors Download PDF

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Publication number
CA2309332A1
CA2309332A1 CA002309332A CA2309332A CA2309332A1 CA 2309332 A1 CA2309332 A1 CA 2309332A1 CA 002309332 A CA002309332 A CA 002309332A CA 2309332 A CA2309332 A CA 2309332A CA 2309332 A1 CA2309332 A1 CA 2309332A1
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CA
Canada
Prior art keywords
imidazotriazinones
phenyl substituted
phosphodiesterase inhibitors
phenyl
substituted imidazotriazinones
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.)
Granted
Application number
CA002309332A
Other languages
French (fr)
Other versions
CA2309332C (en
Inventor
Ulrich Niewohner
Mazen Es-Sayed
Helmut Haning
Thomas Schenke
Karl-Heinz Schlemmer
Jorg Keldenich
Erwin Bischoff
Elisabeth Perzborn
Klaus Dembowsky
Peter Serno
Marc Nowakowski
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Intellectual Property GmbH
Original Assignee
Bayer Aktiengesellschaft
Ulrich Niewohner
Mazen Es-Sayed
Helmut Haning
Thomas Schenke
Karl-Heinz Schlemmer
Jorg Keldenich
Erwin Bischoff
Elisabeth Perzborn
Klaus Dembowsky
Peter Serno
Marc Nowakowski
Bayer Healthcare Ag
Bayer Schering Pharma Aktiengesellschaft
Bayer Pharma Aktiengesellschaft
Bayer Intellectual Property Gmbh
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
Priority to DE19750085A priority Critical patent/DE19750085A1/en
Priority to DE19750085.4 priority
Priority to DE19812462.7 priority
Priority to DE1998112462 priority patent/DE19812462A1/en
Priority to DE19840289.9 priority
Priority to DE1998140289 priority patent/DE19840289A1/en
Priority to PCT/EP1998/006910 priority patent/WO1999024433A1/en
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27217917&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2309332(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Bayer Aktiengesellschaft, Ulrich Niewohner, Mazen Es-Sayed, Helmut Haning, Thomas Schenke, Karl-Heinz Schlemmer, Jorg Keldenich, Erwin Bischoff, Elisabeth Perzborn, Klaus Dembowsky, Peter Serno, Marc Nowakowski, Bayer Healthcare Ag, Bayer Schering Pharma Aktiengesellschaft, Bayer Pharma Aktiengesellschaft, Bayer Intellectual Property Gmbh filed Critical Bayer Aktiengesellschaft
Publication of CA2309332A1 publication Critical patent/CA2309332A1/en
Publication of CA2309332C publication Critical patent/CA2309332C/en
Application granted granted Critical
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/53Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/08Bronchodilators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/02Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/08Drugs for disorders of the urinary system of the prostate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/10Drugs for disorders of the urinary system of the bladder
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10Drugs for genital or sexual disorders; Contraceptives for impotence
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/06Antiarrhythmics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/08Vasodilators for multiple indications
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02Phosphorus compounds
    • C07F9/547Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561Heterocyclic 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

Abstract

The 2-phenyl-substituted imidazotriazinones having short, unbranched alkyl radicals in the 9-position are prepared from the corresponding 2-phenyl-imidazotriazinones by chlorosulphonation and subsequent reaction with the amines. The compounds inhibit cGMP-metabolizing phosphodiesterases and are suitable for use as active compounds in pharmaceuticals, for the treatment of cardiovascular and cerebrovascular disorders and/or disorders of the urogenital system, in particular for the treatment of erectile dysfunction.
CA002309332A 1997-11-12 1998-10-31 2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors Expired - Lifetime CA2309332C (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
DE19750085A DE19750085A1 (en) 1997-11-12 1997-11-12 New 2-phenyl-imidazotriazinone derivatives used for treating cardiovascular, cerebrovascular and urogenital disorders
DE19750085.4 1997-11-12
DE19812462.7 1998-03-23
DE1998112462 DE19812462A1 (en) 1998-03-23 1998-03-23 New phosphodiesterase inhibiting 2-phenyl-imidazotriazinone derivatives useful for treating e.g. cardiovascular, cerebrovascular and/or urogenital diseases
DE19840289.9 1998-09-04
DE1998140289 DE19840289A1 (en) 1998-09-04 1998-09-04 New phosphodiesterase inhibiting 2-phenyl-imidazotriazinone derivatives useful for treating e.g. cardiovascular, cerebrovascular and/or urogenital diseases
PCT/EP1998/006910 WO1999024433A1 (en) 1997-11-12 1998-10-31 2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CA002395558A CA2395558C (en) 1997-11-12 1998-10-31 Intermediates for 2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors

Publications (2)

Publication Number Publication Date
CA2309332A1 true CA2309332A1 (en) 1999-05-20
CA2309332C CA2309332C (en) 2002-12-03

Family

ID=27217917

Family Applications (2)

Application Number Title Priority Date Filing Date
CA002309332A Expired - Lifetime CA2309332C (en) 1997-11-12 1998-10-31 2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors
CA002395558A Expired - Fee Related CA2395558C (en) 1997-11-12 1998-10-31 Intermediates for 2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors

Family Applications After (1)

Application Number Title Priority Date Filing Date
CA002395558A Expired - Fee Related CA2395558C (en) 1997-11-12 1998-10-31 Intermediates for 2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors

Country Status (44)

Country Link
US (9) US6362178B1 (en)
EP (3) EP1049695B1 (en)
JP (2) JP3356428B2 (en)
KR (2) KR100548120B1 (en)
CN (2) CN100430396C (en)
AR (2) AR013759A1 (en)
AT (1) AT213246T (en)
AU (1) AU738675B2 (en)
BG (1) BG65257B1 (en)
BR (2) BR9812785A (en)
CA (2) CA2309332C (en)
CH (1) CH693954A5 (en)
CO (1) CO4980861A1 (en)
CU (1) CU23063A3 (en)
CY (1) CY1112949T1 (en)
CZ (1) CZ301911B6 (en)
DE (3) DE19881732D2 (en)
DK (3) DK1049695T3 (en)
EE (1) EE04781B1 (en)
ES (3) ES2172945T3 (en)
FI (1) FI113772B (en)
GB (1) GB2346877B (en)
HK (2) HK1031730A1 (en)
HN (1) HN1998000175A (en)
HR (2) HRP20000292B1 (en)
HU (3) HU230154B1 (en)
ID (1) ID25871A (en)
IL (3) IL135462D0 (en)
IN (1) IN188419B (en)
LU (1) LU90561A1 (en)
MY (1) MY138535A (en)
NO (2) NO314940B1 (en)
NZ (1) NZ504436A (en)
PE (1) PE131799A1 (en)
PL (2) PL201336B1 (en)
PT (2) PT1049695E (en)
SE (1) SE522809C2 (en)
SI (2) SI1174431T1 (en)
SK (1) SK287161B6 (en)
TR (1) TR200001338T2 (en)
TW (2) TWI229081B (en)
UA (1) UA46166C2 (en)
UY (2) UY25246A1 (en)
WO (1) WO1999024433A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8501945B2 (en) 2009-11-27 2013-08-06 Bayer Intellectual Property Gmbh Process for preparing methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate and its purification for use as pharmaceutically active compound

Families Citing this family (154)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6403597B1 (en) * 1997-10-28 2002-06-11 Vivus, Inc. Administration of phosphodiesterase inhibitors for the treatment of premature ejaculation
US20040014761A1 (en) * 1997-10-28 2004-01-22 Place Virgil A. Treatment of female sexual dysfunction with phosphodiesterase inhibitors
CA2309332C (en) * 1997-11-12 2002-12-03 Bayer Aktiengesellschaft 2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors
DE19827640A1 (en) * 1998-06-20 1999-12-23 Bayer Ag New imidazotriazine derivatives useful as smooth muscle relaxants for treating e.g. cardiovascular disorders, cerebrovascular disorders, or erectile dysfunction
US7235625B2 (en) 1999-06-29 2007-06-26 Palatin Technologies, Inc. Multiple agent therapy for sexual dysfunction
DE19944161A1 (en) * 1999-09-15 2001-03-22 Bayer Ag New combination for the treatment of sexual dysfunction
US6503908B1 (en) 1999-10-11 2003-01-07 Pfizer Inc Pharmaceutically active compounds
IL139454D0 (en) * 1999-11-08 2001-11-25 Pfizer Compounds for the treatment of female sexual dysfunction
US20050070499A1 (en) * 1999-11-08 2005-03-31 Pfizer Inc. Compounds for the treatment of female sexual dysfunction
US6777416B2 (en) 1999-12-24 2004-08-17 Bayer Aktiengesellschaft Isoxazolo pyrimidinones and the use thereof
TR200201638T2 (en) 1999-12-24 2002-11-21 Bayer Aktiengesellschaft New imidazo [1,3,5] triazinones and uses
US6683081B2 (en) 1999-12-24 2004-01-27 Bayer Aktiengesellschaft Triazolotriazinones and the use thereof
DE10010067A1 (en) 2000-03-02 2001-09-06 Bayer Ag New 2-phenyl-imidazo (5,1-f) (1,2,4) triazin-4-one derivatives, are phosphodiesterase inhibitors useful for treating cardiovascular, cerebrovascular or urogenital disorders
US20020006926A1 (en) 2000-04-19 2002-01-17 Roylance H. H. Use of cyclic GMP-specific phosphodiesterase inhibitors for treatment of parkinson's disease
US6821978B2 (en) 2000-09-19 2004-11-23 Schering Corporation Xanthine phosphodiesterase V inhibitors
CZ20031194A3 (en) * 2000-09-29 2003-08-13 Glaxo Group Limited Urea derivatives
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 (en) * 2000-12-18 2002-06-20 Bayer Ag Process for the preparation of sulfonamide-substituted imidazotriazinones
DE10063106A1 (en) * 2000-12-18 2002-06-20 Bayer Ag Process for the preparation of 2- (2-ethoxyphenyl) substituted imidazotriazinones
DE10064105A1 (en) 2000-12-21 2002-06-27 Bayer Ag New substituted imidazotriazinones
EP1355651A2 (en) * 2001-02-02 2003-10-29 Pfizer Inc. Treatment of diabetes mellitus using vardenafil
DE10107639A1 (en) * 2001-02-15 2002-08-22 Bayer Ag 2-alkoxyphenyl substituted imidazotriazinones
DE10108752A1 (en) 2001-02-23 2002-09-05 Bayer Ag New substituted imidazotriazinones
GB0107751D0 (en) * 2001-03-28 2001-05-16 Pfizer Ltd Pharmaceutically active compounds
DE10118306A1 (en) 2001-04-12 2002-10-17 Bayer Ag Composition for intranasal administration of imidazo-triazinone derivative cGMP PDE inhibitor for treatment of erectile dysfunction, also containing local anesthetic to prevent nasal blockage and improve absorption
PL363679A1 (en) * 2001-05-09 2004-11-29 Bayer Healthcare Ag Novel use of 2-phenyl-substituted imidazotriazinones
US20070122353A1 (en) 2001-05-24 2007-05-31 Hale Ron L Drug condensation aerosols and kits
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
US20030051728A1 (en) 2001-06-05 2003-03-20 Lloyd Peter M. Method and device for delivering a physiologically active compound
DE10130167A1 (en) * 2001-06-22 2003-01-02 Bayer Ag imidazotriazines
DE10135815A1 (en) * 2001-07-23 2003-02-06 Bayer Ag Use of imidazo-triazinone derivative phosphodiesterase 5 inhibitors e.g. for treatment of cardiac insufficiency, psoriasis, diabetes, cancer, glaucoma, bladder disease, Parkinson's disease or pain
AT395349T (en) 2001-08-28 2008-05-15 Schering Corp Polycyclic guanine phosphodiesterase inhibitors
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
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 (en) 2002-05-08 2003-11-20 Bayer Ag Carbamate-substituted pyrazolopyridines
US7091207B2 (en) 2002-05-22 2006-08-15 Virginia Commonwealth University Method of treating myocardial infarction with PDE-5 inhibitors
BR0311191A (en) * 2002-05-23 2005-03-01 Pfizer Combination
SI1509525T1 (en) 2002-05-31 2006-12-31 Schering Corp Process for preparing xanthine phosphodiesterase v inhibitors and precursors thereof
GB0214784D0 (en) * 2002-06-26 2002-08-07 Pfizer Ltd Novel combination
DE10229778A1 (en) * 2002-07-03 2004-01-29 Bayer Ag New use of imidazotriazinones
DE10230605A1 (en) * 2002-07-08 2004-01-29 Bayer Ag Substituted imidazotriazines
DE10232113A1 (en) * 2002-07-16 2004-01-29 Bayer Ag Medicinal products containing vardenafil hydrochloride trihydrate
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
DE60332387D1 (en) 2002-12-13 2010-06-10 Warner Lambert Co Alpha-2-delta ligand for the treatment of lower harness symptoms
WO2004087652A2 (en) 2003-04-01 2004-10-14 Smithkline Beecham Corporation Imidazotriazine compounds
EA008596B1 (en) 2003-04-29 2007-06-29 Пфайзер Инк. 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
CA2526478A1 (en) 2003-05-21 2004-12-02 Alexza Pharmaceuticals, Inc. Methods of controlling uniformity of substrate temperature and self-contained heating unit and drug-supply unit employing same
WO2004103407A2 (en) 2003-05-22 2004-12-02 Altana Pharma Ag Composition comprising a pde4 inhibitor and a pde5 inhibitor
CN100374441C (en) 2003-06-06 2008-03-12 天津倍方科技发展有限公司 2-substituted benzyl-5,7-dihydrocarbyl-3,7-dihydro pyrroline [2,3-d] pyromidine-4-one derivative ,its preparation and medicinal use
JP2008501617A (en) * 2004-06-11 2008-01-24 アスビオファーマ株式会社 Imidazotriazinone derivatives having PDE7 inhibitory action
JP2006219374A (en) * 2003-06-13 2006-08-24 Daiichi Asubio Pharma Co Ltd Imidazotriazinone derivative having pde 7 inhibition
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
AU2004292991A1 (en) * 2003-11-21 2005-06-09 Schering Corporation Phosphodiesterase v inhibitor formulations
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 (en) 2004-01-22 2007-07-03 Pfizer triazole derivatives that inhibit vasopressin antagonist activity
WO2005097799A1 (en) * 2004-04-07 2005-10-20 Pfizer Limited Pyrazolo`4,3-d! pyrimidines
DE102004023069A1 (en) * 2004-05-11 2005-12-08 Bayer Healthcare Ag New dosage forms of the PDE 5 inhibitor vardenafil
DE102005001989A1 (en) * 2005-01-15 2006-07-20 Bayer Healthcare Ag Intravenous formulations of PDE inhibitors
MX2007010144A (en) * 2005-02-18 2008-02-15 Surface Logix Inc Pharmacokinetically improved compounds.
US20110172422A1 (en) * 2005-02-18 2011-07-14 Surface Logix, Inc. Methods of Making Pharmacokinetically Improved Compounds Comprising Functional Residues or Groups and Pharmaceutical Compositions Comprising Said Compounds
DE102005009240A1 (en) * 2005-03-01 2006-09-07 Bayer Healthcare Ag Dosage forms with improved pharmacokinetic properties
DE102005009241A1 (en) * 2005-03-01 2006-09-07 Bayer Healthcare Ag Dosage forms with controlled bioavailability
DE102005016345A1 (en) * 2005-04-09 2006-10-12 Bayer Healthcare Ag New use of 2-phenyl-substituted imidazotriazinone derivatives
CN102614176A (en) 2005-04-19 2012-08-01 奈科明有限责任公司 Roflumilast for the treatment of pulmonary hypertension
AT493413T (en) 2005-05-12 2011-01-15 Pfizer Aqueous Crystalline Forms of N-Ä1,2-ETHOXYETHYL) -5- (N-ETHYL-N-METHYLAMINOÜ-7- (4-METHYLPYRIDIN-2-YL-AMINOÜ-1H-PYRAZOLOÄ4,3-
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
WO2007017752A1 (en) * 2005-08-10 2007-02-15 Pfizer Limited Substituted triazole derivatives as oxytocin antagonists
EP1928437A2 (en) 2005-08-26 2008-06-11 Braincells, Inc. Neurogenesis by muscarinic receptor modulation
EP2258357A3 (en) 2005-08-26 2011-04-06 Braincells, Inc. Neurogenesis with acetylcholinesterase inhibitor
EP1931797A2 (en) * 2005-09-29 2008-06-18 Bayer HealthCare AG Pde inhibitors and combinations thereof for the treatment of urological disorders
WO2007047282A1 (en) * 2005-10-12 2007-04-26 Lilly Icos Llc Treatment of benign prostatic hypertrophy and lower urinary tract symptoms
AU2006304787A1 (en) 2005-10-21 2007-04-26 Braincells, Inc. Modulation of neurogenesis by PDE inhibition
EP2382975A3 (en) 2006-05-09 2012-02-29 Braincells, Inc. Neurogenesis by modulating angiotensin
JP2009513672A (en) 2005-10-31 2009-04-02 ブレインセルス,インコーポレイティド GABA receptor-mediated regulation of neurogenesis
GB0601951D0 (en) 2006-01-31 2006-03-15 Novartis Ag Organic compounds
CN101415670A (en) * 2006-02-17 2009-04-22 惠氏公司 Methods for preparing sulfonamide substituted alcohols and intermediates thereof
PE20080109A1 (en) * 2006-02-17 2008-04-01 Wyeth Corp N-sulfonylation of alcohols selectively substituted 2-aminotrifluoralquilo
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
BRPI0708804B1 (en) * 2006-03-17 2019-12-17 Cardioxyl Pharmaceuticals Inc n-hydroxylsulfonamide-derived compounds as nitroxyl donors, pharmaceutical composition and kit
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
AU2007249435A1 (en) 2006-05-09 2007-11-22 Braincells, Inc. 5 HT receptor mediated neurogenesis
EP2032521B1 (en) 2006-06-27 2009-10-28 Sandoz AG New method for salt preparation
WO2008008398A2 (en) * 2006-07-14 2008-01-17 Shionogi & Co., Ltd. Oxime compounds and the use thereof
ZA200901462B (en) * 2006-08-24 2010-07-28 Surface Logix Inc Pharmacokinetically improved compounds
AR062501A1 (en) 2006-08-29 2008-11-12 Actelion Pharmaceuticals Ltd therapeutic compositions
MX2009002496A (en) 2006-09-08 2009-07-10 Braincells Inc Combinations containing a 4-acylaminopyridine derivative.
DE102006043443A1 (en) * 2006-09-15 2008-03-27 Bayer Healthcare Ag Novel aza-bicyclic compounds and their use
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
CA2669536C (en) 2006-12-12 2016-05-31 Gilead Colorado, Inc. Combinations of ambrisentan and pde5 inhibitors for treating pulmonary arterial hypertension
CA2677690C (en) * 2007-02-12 2012-05-15 James V. Winkler Treatment of comorbid premature ejaculation and erectile dysfunction
AU2008216363B2 (en) * 2007-02-12 2014-05-08 Aytu Bioscience, Inc. Reducing side effects of tramadol
US20080194529A1 (en) * 2007-02-12 2008-08-14 Auspex Pharmaceuticals, Inc. HIGHLY SELECTIVE and LONG-ACTING PDE5 MODULATORS
DE102007027067A1 (en) 2007-06-12 2008-12-18 Ratiopharm Gmbh Process for the preparation of a medicament containing vardenafil hydrochloride trihydrate
WO2008151734A1 (en) * 2007-06-13 2008-12-18 Bayer Schering Pharma Aktiengesellschaft Pde inhibitors for the treatment of hearing impairment
CN101965348B (en) * 2007-09-06 2013-11-13 上海特化医药科技有限公司 Process for preparing vardenafil and intermediates thereof
WO2009082845A1 (en) 2007-12-28 2009-07-09 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
JP2012513464A (en) 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 Phosphodiesterase inhibitors and uses thereof
DE102008063992A1 (en) 2008-12-19 2010-09-02 Lerner, Zinoviy, Dipl.-Ing. New aliphatic substituted pyrazolopyridines and their use
WO2010099217A1 (en) 2009-02-25 2010-09-02 Braincells, Inc. Modulation of neurogenesis using d-cycloserine combinations
GB0903493D0 (en) 2009-02-27 2009-04-08 Vantia Ltd New compounds
DE102009020888A1 (en) 2009-05-12 2010-11-18 Ratiopharm Gmbh Orodispersible tablet containing a vardenafil salt
EP2462127A1 (en) 2009-08-07 2012-06-13 Ranbaxy Laboratories Limited Processes for the preparation of vardenafil
ES2553035T3 (en) 2009-11-27 2015-12-03 Adverio Pharma Gmbh Process for the preparation of {4,6-diamino-2- [1- (2-fluorobenzyl) -1H-pyrazolo [3,4-b] pyridin-3-yl] pyrimidin-5-yl} -methylcarbamate methyl and its purification for use as a pharmaceutical active ingredient
US8829049B2 (en) 2009-12-21 2014-09-09 Acef S.A. Medicinal composition intended for the treatment of erectile dysfunction in mammals and use of the composition
PL390079A1 (en) 2009-12-30 2011-07-04 Zakłady Farmaceutyczne POLPHARMA Spółka Akcyjna Process for the preparation of vardenafil and its isolation as a salt with citric acid and a crystalline form of this salt
CN102970965A (en) 2010-04-05 2013-03-13 Sk化学公司 Composition containing PDE5 inhibitor for relieving skin wrinkles
DE102010021637A1 (en) 2010-05-26 2011-12-01 Bayer Schering Pharma Aktiengesellschaft Substituted 5-fluoro-1H-pyrazolopyridines and their use
CN102382129B (en) * 2010-08-19 2014-02-26 山东轩竹医药科技有限公司 Spirocycles-substituted phosphodiesterase inhibitor
CN102372730B (en) * 2010-08-19 2014-03-26 山东轩竹医药科技有限公司 Bridged ring substituted phosphodiesterase inhibitor
AR083058A1 (en) 2010-09-20 2013-01-30 Envivo Pharmaceuticals Inc Compounds of structure imidazotriazinona
RU2579121C2 (en) 2010-09-23 2016-03-27 Эббви Бахамаз Лтд. Aza-adamantane derivative monohydrate
EP2637664B1 (en) 2010-10-15 2017-03-29 Gilead Sciences, Inc. Compositions and methods of treating pulmonary hypertension
TWI462739B (en) 2010-11-02 2014-12-01 Univ Kaohsiung Medical Processes for preparing piperazinium salts of sildenafil-analogues and use thereof
CN102134242B (en) * 2011-01-21 2013-08-28 浙江大德药业集团有限公司 Novel compounds for quickly treating impotence with long-lasting action
MX370433B (en) 2011-10-10 2019-12-13 H Lundbeck As Pde9i with imidazo pyrazinone backbone.
AT512084A1 (en) 2011-10-20 2013-05-15 Univ Wien Tech Diazabicyclo and diazaspiro alkan derivatives as phosphodiesterase-5 inhibitors
WO2013067309A1 (en) 2011-11-04 2013-05-10 Xion Pharmaceutical Corporation Methods and compositions for oral administration of melanocortin receptor agonist compounds
CZ2011767A3 (en) * 2011-11-24 2013-06-05 Zentiva, K.S. Processfor preparing and isolation of acid vardenafil salts
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
EP3178820B1 (en) 2012-01-26 2017-12-20 H. Lundbeck A/S Pde9- inhibitors with imidazo triazinone backbone
EP2821066B1 (en) 2012-02-28 2018-04-25 Seoul Pharma. Co. Ltd. High-content fast dissolving film with masking of bitter taste comprising sildenafil as active ingredient
EP2828262A4 (en) 2012-03-19 2015-09-23 Forum Pharmaceuticals Inc Imidazotriazinone compounds
CN103374002B (en) * 2012-04-19 2015-07-15 山东轩竹医药科技有限公司 Phosphodiesterase-5 inhibitor
CZ307091B6 (en) 2012-09-14 2018-01-10 Zentiva, K.S. A stable pharmaceutical preparation containing Vardenafil hydrochloride
KR20140072819A (en) 2012-12-04 2014-06-13 주식회사 아리바이오 Composition for inhibiting neural apoptosis comprising a PDE 5 inhibitor
KR101953735B1 (en) 2012-12-14 2019-03-04 한미약품 주식회사 Chewable tablet comprising a phosphodiesterase-5 inhibitor
JP6386478B2 (en) 2013-02-21 2018-09-05 アドヴェリオ・ファーマ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング Form of methyl {4,6-diamino-2- [1- (2-fluorobenzyl) -1H-pyrazolo [3,4-B] pyridino-3-yl] pyrimidino-5-yl} methylcarbamate
CN104109164B (en) * 2013-04-18 2016-05-25 广州朗圣药业有限公司 A kind of preparation method who is applicable to industrialized high-purity hydrochloric acid Vardenafil trihydrate
EP3022205B1 (en) 2013-07-17 2020-02-05 The Trustees of Columbia University in the City of New York Novel phosphodiesterase inhibitors and uses thereof
PL223869B1 (en) 2013-12-16 2016-11-30 Starogardzkie Zakłady Farmaceutyczne Polpharma Spółka Akcyjna Method for obtaining Vardenafil and its salts
KR101645652B1 (en) 2014-11-03 2016-08-08 (주)퓨젠바이오농업회사법인 Sexual function improvement composition comprising exopolysaccharide produced by ceriporia lacerata as an active ingredient
EP3303339A1 (en) 2015-07-07 2018-04-11 H. Lundbeck A/S Pde9 inhibitors with imidazo triazinone backbone and imidazo pyrazinone backbone for treatment of peripheral diseases
WO2017085056A1 (en) * 2015-11-16 2017-05-26 Topadur Pharma Ag 2-phenyl-3,4-dihydropyrrolo[2,1 -f] [1,2,4]triazinone derivatives as phosphodiesterase inhibitors and uses thereof
WO2017168174A1 (en) 2016-04-02 2017-10-05 N4 Pharma Uk Limited New pharmaceutical forms of sildenafil
EP3554507A1 (en) 2016-12-14 2019-10-23 Respira Therapeutics, Inc. Methods and compositions for treatment of pulmonary hypertension and other lung disorders
WO2018215433A1 (en) 2017-05-22 2018-11-29 Topadur Pharma Ag Novel dual mode of action soluble guanylate cyclase activators and phosphodiesterase inhibitors and uses thereof
CN107445964A (en) * 2017-07-29 2017-12-08 合肥创新医药技术有限公司 A kind of synthetic method of Vardenafil hydrochloric acid impurity
WO2019122245A1 (en) 2017-12-20 2019-06-27 Karessa Pharma Ab Film formulation comprising vardenafil, method for its preparation, and use thereof
US20190385719A1 (en) 2018-06-14 2019-12-19 Astrazeneca Uk Limited Methods for treating erectile dysfunction with a cgmp-specific phosphodiesterase 5 inhibitor pharmaceutical composition
WO2019241588A1 (en) 2018-06-14 2019-12-19 Astrazeneca Uk Limited Methods for treating erectile dysfunction with a cgmp-specific phosphodiesterase 5 inhibitor pharmaceutical composition
WO2020109354A1 (en) * 2018-11-28 2020-06-04 Topadur Pharma Ag Novel dual mode of action soluble guanylate cyclase activators and phosphodiesterase inhibitors and uses thereof

Family Cites Families (65)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US26565A (en) * 1859-12-27 Improved register for railroad-cars
DE812845C (en) 1944-12-07 1951-09-06 Georges Lissac glasses
US2705715A (en) 1952-10-29 1955-04-05 American Cyanamid Co Purine compounds and methods of preparing the same
CH367510A (en) 1957-11-27 1963-02-28 Ciba Geigy Process for the production of new sulfonamides
GB1042471A (en) 1963-01-16 1966-09-14 Ilford Ltd Penta-azaindenes, their production and use in photographic emulsions
GB1051734A (en) 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
BE791025A (en) * 1971-11-19 1973-05-07 Allen & Hanburys Ltd heterocyclic compounds
GB1457873A (en) 1973-01-04 1976-12-08 Allen & Hanburys Ltd Imidazotriazines
US4052390A (en) 1973-06-12 1977-10-04 May & Baker Limited Azapurinones
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
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
DK109578A (en) 1977-03-25 1978-09-26 Allen & Hanburys Ltd Process for the preparation of heterocyclic compounds
GB1584461A (en) 1977-03-25 1981-02-11 Allen & Hanburys Ltd Imidazotriazines imidazotriazinones and pharmaceutical compositions containing them
US4308384A (en) 1978-09-18 1981-12-29 Glaxo Group Limited Production of triazinones
US4287673A (en) * 1980-01-11 1981-09-08 Sunbeam Corporation Hair dryer diffuser
EP0054132B1 (en) 1980-12-12 1984-10-10 Dr. Karl Thomae GmbH Pyrimidones, their preparation and medicines containing them
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
JPH0359913B2 (en) 1984-05-22 1991-09-12 Sankyo Co
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
EP0347146B1 (en) 1988-06-16 1993-09-01 SMITH KLINE & FRENCH LABORATORIES LIMITED Fused pyrimidine derivatives, process and intermediates for their preparation and pharmaceutical compositions containing them
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
AU639988B2 (en) * 1990-04-11 1993-08-12 Pharmacia & 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
US5734053A (en) 1992-06-26 1998-03-31 Pfizer Inc Purinone antianginal agents
GB9213623D0 (en) * 1992-06-26 1992-08-12 Pfizer Ltd Therapeutic agents
GB9218322D0 (en) 1992-08-28 1992-10-14 Pfizer Ltd Therapeutic agents
GB9311920D0 (en) 1993-06-09 1993-07-28 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
CA2148260A1 (en) 1993-09-10 1995-03-16 Yasutaka Takase Quinazoline cpompounds
US5374053A (en) * 1994-01-21 1994-12-20 Heidelberger Druckmaschinen Ag Device for changing the transport position of products
US6143746A (en) * 1994-01-21 2000-11-07 Icos Corporation Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use
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
US6221402B1 (en) * 1997-11-20 2001-04-24 Pfizer Inc. Rapidly releasing and taste-masking pharmaceutical dosage form
CA2309332C (en) 1997-11-12 2002-12-03 Bayer Aktiengesellschaft 2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors
DE19827640A1 (en) * 1998-06-20 1999-12-23 Bayer Ag New imidazotriazine derivatives useful as smooth muscle relaxants for treating e.g. cardiovascular disorders, cerebrovascular disorders, or erectile dysfunction
TW577756B (en) * 1998-10-23 2004-03-01 Pfizer Res & Dev Controlled-release pharmaceutical formulations
US6075028A (en) * 1999-09-23 2000-06-13 Graham; Richard Method of treating Tourette's syndrome and related CNS disorders
US6503908B1 (en) * 1999-10-11 2003-01-07 Pfizer Inc Pharmaceutically active compounds
TR200201638T2 (en) * 1999-12-24 2002-11-21 Bayer Aktiengesellschaft New imidazo [1,3,5] triazinones and uses
PL363679A1 (en) 2001-05-09 2004-11-29 Bayer Healthcare Ag Novel use of 2-phenyl-substituted imidazotriazinones
DE10232113A1 (en) 2002-07-16 2004-01-29 Bayer Ag Medicinal products containing vardenafil hydrochloride trihydrate

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8501945B2 (en) 2009-11-27 2013-08-06 Bayer Intellectual Property Gmbh Process for preparing methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate and its purification for use as pharmaceutically active compound

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