EP1513827A1 - 1,3,5-triazine derivatives as ligands for human adenosine-a3 receptors - Google Patents
1,3,5-triazine derivatives as ligands for human adenosine-a3 receptorsInfo
- Publication number
- EP1513827A1 EP1513827A1 EP03755982A EP03755982A EP1513827A1 EP 1513827 A1 EP1513827 A1 EP 1513827A1 EP 03755982 A EP03755982 A EP 03755982A EP 03755982 A EP03755982 A EP 03755982A EP 1513827 A1 EP1513827 A1 EP 1513827A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- alkyl
- general formula
- compounds
- group
- disorders
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/40—Nitrogen atoms
- C07D251/48—Two nitrogen atoms
- C07D251/50—Two nitrogen atoms with a halogen atom attached to the third ring carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Definitions
- the present invention relates to a group of novel triazine derivatives which are ligands for human adenosine-A 3 receptors.
- the invention also relates to pharmaceutical compositions containing a pharmacologically active amount of at least one of these novel triazine derivatives as an active ingredient.
- Ligands for the various adenosine receptors are the subject of a large number of patent applications and patents. In only two of those triazines are described.
- WO 991163 describes a series of 2,4-bisphenyl substituted triazines showing nanomolar affinity for human adenosine-A-i receptors.
- JP 11158073 The second patent application describing triazines, JP 11158073, is the closest prior art. It describes a series of substituted 1 ,3,5-triazines which are ligands for human adenosine-A 3 receptors, the most potent of which having affinities around 15 nM.
- Ri represents halogen, alkyl(1-3C), O-alkyl(1-3C), CF 3 , NH 2 , N-(di)-alkyl(1-3C), N-(di)-alkenyl(1-3C), N-(di)-alkynyl(1-3C), N-alkyl(1-3C)alkenyl(1-3C), N-alkyl(1-3C)alkynyl(1-3C), N-alkenyl(1-3C)alkynyl(1-3C) or an optionally substituted C 2 -C 8 cycloalkylamino group,
- R 2 , R 3 and R 4 independently represent H, halogen, alkyl(1-3C), CF 3 , OH, O-alkyl(1-
- 1-morpholinyl, 1-piperidinyI, 1-piperazinyl, OCF 3 , SCH 3 , SOCH 3 , SO 2 CH 3 or R 2 and R together with the phenyl ring to which they are attached, represent an optionally substituted benzofuran, dihydrobenzofuran, benzodioxane, benzodioxolane or naphthalene ring system,
- X represents NH, N-aIkyl(1-3C), CH 2 , O, S or a carbon-carbon bond
- Y represents a group of the general formula (A), (B) or (C):
- R 5 is either OH or CH 2 OH
- R 6 represents H, alkyl(1-3C), phenyl, NH 2 , N-(di)-alkyl(1-3C), OH, O-alkyl(1-3C) or hydroxyalkyl(1-2C);
- n has the value of 0, 1 or 2;
- R 7 represents alkyl(1-3C), benzyl, hydroxyalkyl(1-2C) or methoxyalkyl(1-2C),
- R 8 and R 9 independently represent H, halogen, alkyl(1-3C), CF 3 , OH, O-alkyl(1-3C), N-(di)-alkyl(1-3C), 1-morpholinyl, 1-piperidinyl, 1-piperazinyI, OCF 3 , SCH 3 , SOCHs, or SO 2 CH 3 ,
- R-io represents H or alkyl(1-3C),
- R 11 represents H, alkyI(1-3C), benzyl, hydroxyalkyl(1-2C) or methoxyalkyl(1-2C),
- Z represents NOH, NOalkyl(1-3C), O or S,
- 'alkyl(1-3C)' means 'methyl, ethyl, n-propyl or isopropyl'.
- C 2 -C 8 cycloalkylamino means any cyclic amine containing from 2 to 8 carbons in the ring.
- the cycloalkylamino ring may contain other atoms and may be optionally substituted.
- Examples of C 2 -C 8 cycloalkylamino include pyrrolidinyl, piperidinyl, morpholinyl, aziridinyl, pyrrolinyl and the like.
- Optionally substituted' means that a group may or may not be further substituted by one or more groups selected from alkyl, alkenyl, alkynyl, aryl, fluoro, chloro, bromo, hydroxyl, alkyloxy, alkenyloxy, aryloxy, acyloxy, amino, alkylamino, dialkylamino, arylamino, thio, alkylthio, arylthio, cyano, oxo, nitro, acyl, amido, aikylamido, dialkylamido, carboxyl, or two optional substituents may together with the carbon atoms to which they are attached form a 5- or 6-membered aromatic or non-aromatic ring containing 0, 1 or 2 heteroatoms selected from nitrogen, oxygen or sulphur.
- Optional substituents may themselves bear additional optional substituents.
- Preferred optional substituents include
- C ⁇ _ 3 alkyl such as for example methyl, ethyl, and trifluoromethyl, fluoro, chloro, bromo, hydroxyl, C- ⁇ - 3 alkyloxy such as for example methoxy, ethoxy and trifluoromethoxy, and amino.
- prodrugs i.e. compounds which when administered to humans by any known route, are metabolized to compounds having formula (1), belong to the invention.
- this relates to compounds with primary or secondary amino groups or hydroxy groups, a typical example being the compound with formula (9) and its enantiomers (see below).
- Such compounds can be reacted with organic acids to yield compounds which can be metabolized to compounds having formula (1).
- the invention particularly relates to compounds having formula (1) wherein R-i represents halogen, alkyl(1-3C), O-alkyl(1-3C), CF 3 , NH 2 or N-(di)-alkyl(1-3C), and all other symbols have the meanings as given above.
- This compound has an affinity for human adenosine-A 3 receptors of pKj 9.0 + 0.3.
- R-i O-alkyl(1-3C) or any of the amine substituents: NH 2, N-(di)-alkyl(1-3C), N-(di)-alkenyl(1-3C), N-(di)-alkynyl(1-3C), N- alkyl(1-3C)alkenyl(1-3C), N-alkyl(1-3C) alkynyl(1-3C), N-alkenyl(1-3C)alkynyl(1-3C) or an optionally substituted C 2 -C 8 cycloalkylamino group, can be obtained by further substitution of the chloro-derivatives as outlined below in scheme 2:
- compositions may be obtained using standard procedures well known in the art, for example by mixing a compound of the present invention with a suitable acid.
- Suitable acid addition salts can be formed with inorganic acids such as hydrochloric acid, sulphuric acid, phosphoric acid and nitric acid, or with organic acids such as citric acid, fumaric acid, maleic acid, tartaric acid, acetic acid, trifluoro acetic acid, benzoic acid, p-toluene sulphonic acid, methanesulphonic acid and naphthalene sulphonic acid.
- inorganic acids such as hydrochloric acid, sulphuric acid, phosphoric acid and nitric acid
- organic acids such as citric acid, fumaric acid, maleic acid, tartaric acid, acetic acid, trifluoro acetic acid, benzoic acid, p-toluene sulphonic acid, methanesulphonic acid and naphthalene sulphonic acid.
- the compounds of the invention of the general formula (1), as well as the salts thereof, have adenosine-A 3 (ant)agonistic activity. They are useful in the treatment of disorders in which adenosine-A 3 receptors are involved, or that can be treated via manipulation of those receptors.
- inflammatory diseases including, arthritis, multiple sclerosis, asthma and psoriasis; gastro-intestinal disorders such as ulcers, inflammatory bowel disease (Crohn's disease) and ulcerative colitis; allergic responses such as eczema, atopic dermatitis and rhinitis; cardio-vascular disorders such as myocardial infarction, arrhythmias, hypertension, thrombosis, anaemia, arteriosclerosis, angina pectoris, cutaneous diseases such as urticaria, lupus erythematosus and pruritus; opthalmological disorders like glaucoma; respiratory disorders including chronic obstructive pulmonary disease, bronchitis and cystic fibrosis; central nervous system disorders including various forms of epilepsy, stroke, depression, sleep apnoea; disorders characterized by impairment of cognition and memory such as Alzheimer's disease, Creutzfeldt-Jacob disease, Huntington's disease, Parkinson'
- adenosine-A 3 receptor (ant)agonistic properties of the compounds of the invention were determined using the method outlined below.
- Affinity of the compounds for human adenosine-A 3 receptors was determined using the receptor binding assay described by CA. Salvatore et al.: Molecular cloning and characterization of the human A 3 adenosine receptor, Proc. Natl. Acad. Sci. USA, 90, 10365-10369, 1993. Briefly, membrane preparations were obtained from human recombinant (HEK 293) cells in which the human adenosine-A 3 receptor was stably expressed. Membranes were incubated at 22°C for 90 minutes with [ 125 I]-AB-MECA in the absence or presence of testcompounds in a concentration range from 10 ⁇ M down to 0.1 nM, diluted in a suitable buffer.
- S is the concentration r [125r IJ-AB-MECA used in the assay expressed in mol/l (typically 0.1 nM)
- K d is the equilibrium dissociation constant of [ 125 1]-AB-MECA for human adenosine-A 3 receptors (0.22 nM).
- the compounds of the invention have a high affinity for adenosine-A 3 receptors in the binding assay described above. This property makes them useful in the treatment of disorders in which adenosine-A 3 receptors are involved, or that can be treated via manipulation of these receptors.
- Y represents a group of the general formula (A), (B) or (C):
- Prodrugs having formula (10) have no affinity for human adenosine-A3 receptors, but after hydrolysis they generate the compound with formula (9) (see above) which is highly active.
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Psychology (AREA)
- Virology (AREA)
- Hospice & Palliative Care (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03755982A EP1513827A1 (en) | 2002-05-30 | 2003-05-28 | 1,3,5-triazine derivatives as ligands for human adenosine-a3 receptors |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP02077310 | 2002-05-30 | ||
EP02077310 | 2002-05-30 | ||
PCT/EP2003/050203 WO2003101980A1 (en) | 2002-05-30 | 2003-05-28 | 1,3,5-triazine derivatives as ligands for human adenosine-a3 receptors |
EP03755982A EP1513827A1 (en) | 2002-05-30 | 2003-05-28 | 1,3,5-triazine derivatives as ligands for human adenosine-a3 receptors |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1513827A1 true EP1513827A1 (en) | 2005-03-16 |
Family
ID=29595045
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP03755982A Withdrawn EP1513827A1 (en) | 2002-05-30 | 2003-05-28 | 1,3,5-triazine derivatives as ligands for human adenosine-a3 receptors |
Country Status (16)
Country | Link |
---|---|
EP (1) | EP1513827A1 (en) |
JP (1) | JP4590260B2 (en) |
CN (1) | CN1329388C (en) |
AR (1) | AR040231A1 (en) |
AU (1) | AU2003250232B2 (en) |
BR (1) | BR0304925A (en) |
CA (1) | CA2484981C (en) |
HK (1) | HK1075045A1 (en) |
HR (1) | HRP20040970A2 (en) |
IL (1) | IL164240A (en) |
MX (1) | MXPA04011948A (en) |
PL (1) | PL372418A1 (en) |
RU (1) | RU2312859C2 (en) |
UA (1) | UA77816C2 (en) |
WO (1) | WO2003101980A1 (en) |
ZA (1) | ZA200408029B (en) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2533397A1 (en) * | 2003-07-22 | 2005-02-03 | Neurogen Corporation | Substituted pyridin-2-ylamine analogues |
WO2005028467A1 (en) | 2003-09-15 | 2005-03-31 | Anadys Pharmaceuticals, Inc. | Antibacterial 3,5-diaminopiperidine-substitute aromatic and heteroaromatic compounds |
GB2465405A (en) * | 2008-11-10 | 2010-05-19 | Univ Basel | Triazine, pyrimidine and pyridine analogues and their use in therapy |
ES2665561T3 (en) | 2012-07-04 | 2018-04-26 | Agro-Kanesho Co., Ltd. | Ester derivative of 2-aminonicotinic acid and bactericide containing the same as active ingredient |
GB201810668D0 (en) | 2018-06-28 | 2018-08-15 | Stiftelsen Alzecure | New compounds |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9226735D0 (en) * | 1992-12-22 | 1993-02-17 | Ici Plc | Azole derivatives |
DE19735800A1 (en) * | 1997-08-18 | 1999-02-25 | Boehringer Ingelheim Pharma | Use of known and new triazine derivatives |
JPH11158073A (en) * | 1997-09-26 | 1999-06-15 | Takeda Chem Ind Ltd | Adenosine a3 antagonist |
-
2003
- 2003-05-28 RU RU2004138803/04A patent/RU2312859C2/en not_active IP Right Cessation
- 2003-05-28 UA UA20041210642A patent/UA77816C2/en unknown
- 2003-05-28 AU AU2003250232A patent/AU2003250232B2/en not_active Ceased
- 2003-05-28 PL PL03372418A patent/PL372418A1/en not_active Application Discontinuation
- 2003-05-28 WO PCT/EP2003/050203 patent/WO2003101980A1/en active Application Filing
- 2003-05-28 EP EP03755982A patent/EP1513827A1/en not_active Withdrawn
- 2003-05-28 BR BR0304925-6A patent/BR0304925A/en not_active IP Right Cessation
- 2003-05-28 MX MXPA04011948A patent/MXPA04011948A/en active IP Right Grant
- 2003-05-28 JP JP2004509671A patent/JP4590260B2/en not_active Expired - Fee Related
- 2003-05-28 CN CNB038090937A patent/CN1329388C/en not_active Expired - Fee Related
- 2003-05-28 CA CA2484981A patent/CA2484981C/en not_active Expired - Fee Related
- 2003-05-30 AR ARP030101920A patent/AR040231A1/en unknown
-
2004
- 2004-09-23 IL IL164240A patent/IL164240A/en not_active IP Right Cessation
- 2004-10-05 ZA ZA200408029A patent/ZA200408029B/en unknown
- 2004-10-15 HR HR20040970A patent/HRP20040970A2/en not_active Application Discontinuation
-
2005
- 2005-08-22 HK HK05107314A patent/HK1075045A1/en not_active IP Right Cessation
Non-Patent Citations (1)
Title |
---|
IAN SMITH ET AL: "A novel stable inhibitorof endopeptidase EC 3.4.24.15 and 3.4.24.16 potentiates bradykinin induced hypotension", Retrieved from the Internet <URL:http://www.springerlink.com/content/t74uu1w15276484k/> * |
Also Published As
Publication number | Publication date |
---|---|
AR040231A1 (en) | 2005-03-23 |
AU2003250232A1 (en) | 2003-12-19 |
JP2005531600A (en) | 2005-10-20 |
IL164240A (en) | 2010-12-30 |
AU2003250232B2 (en) | 2008-09-11 |
CA2484981A1 (en) | 2003-12-11 |
ZA200408029B (en) | 2005-10-06 |
UA77816C2 (en) | 2007-01-15 |
PL372418A1 (en) | 2005-07-25 |
CA2484981C (en) | 2011-07-26 |
WO2003101980A1 (en) | 2003-12-11 |
RU2004138803A (en) | 2005-06-10 |
RU2312859C2 (en) | 2007-12-20 |
CN1646520A (en) | 2005-07-27 |
MXPA04011948A (en) | 2005-03-31 |
CN1329388C (en) | 2007-08-01 |
BR0304925A (en) | 2004-09-28 |
JP4590260B2 (en) | 2010-12-01 |
HRP20040970A2 (en) | 2005-06-30 |
IL164240A0 (en) | 2005-12-18 |
HK1075045A1 (en) | 2005-12-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
RU2309154C2 (en) | 3-phenylsulfonyl-8-piperazin-1-yl-quinolines having affinity to 5-ht6 receptor, methods for production thereof (variants) | |
KR101086678B1 (en) | Processes for the preparation of 4-[[4-[[4- (2-cyanoethenyl)-2, 6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile | |
CN110546151B (en) | Apoptosis inducer | |
EP2927231B1 (en) | Imidazopyridine compounds | |
CA2268051A1 (en) | Neuropeptide-y ligands | |
FI120145B (en) | Process for preparing blood vessel contracting substituted aryloxyalkyl diamines | |
EA005561B1 (en) | Processes and intermediates for preparing anti-cancer compounds | |
US20210024506A1 (en) | Polymorphic forms of afatinib free base and afatinib dimaleate | |
HU225270B1 (en) | 2,4-diamino-1,3,5-triazine derivatives, process for their preparation, their use for the preparation of pharmaceutical compositions and the pharmaceutical compositions containing them | |
PH12015500716B1 (en) | N-prop-2-ynyl carboxamide derivatives and their use as trpa1 antagonists | |
JP2008502667A (en) | Tetrahydroquinolone and its aza analogs for use as DPP-IV inhibitors in the treatment of diabetes | |
JPH0320263A (en) | Tertiary alkylated piperazin derivative | |
KR100812586B1 (en) | Quinazoline compounds useful as p38 kinase inhibitors | |
JP2008544965A (en) | Bicyclic derivatives as p38 kinase inhibitors | |
EP1572209A1 (en) | Novel quinoxalinone derivatives as bradykinin b1 antagonists | |
EP0018151B1 (en) | 6-substituted-arylpyrido(2,3-d)pyrimidin-7-amines, derivatives and salts thereof, pharmaceutical compositions containing any of the foregoing, and processes for producing any of the foregoing | |
US7307079B2 (en) | 1,3,5-Triazine derivatives as ligands for human adenosine-A3 receptors | |
WO2003101980A1 (en) | 1,3,5-triazine derivatives as ligands for human adenosine-a3 receptors | |
WO2019091503A1 (en) | Solid forms of tenapanor and method of preparation of tenapanor | |
KR20030024919A (en) | N-(3,5-dichloro-2-methoxyphenyl)-4-methoxy-3-piperazin-1-yl-benzenesulfonamide | |
US20120157482A1 (en) | Compounds and methods | |
KR20050019724A (en) | 1,3,5-Triazine derivatives as ligands for human adenosine-A3 receptors | |
FI82456C (en) | Process for the preparation of novel therapeutically useful 1-phenyl-1,2,4-thiadiazine-1-oxide derivatives | |
NO326697B1 (en) | Novel 1,3,5-triazine derivatives as ligands for human adenosine A3 receptors, and pharmaceutical compositions containing such | |
FI78078B (en) | FOERFARANDE FOER FRAMSTAELLNING AV TERAPEUTISKT ANVAENDBARA P-OXO-OXAZOLINDINYLBENSENSULFONAMIDER. |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20041230 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PT RO SE SI SK TR |
|
AX | Request for extension of the european patent |
Extension state: AL LT LV MK |
|
RAX | Requested extension states of the european patent have changed |
Extension state: MK Payment date: 20041230 Extension state: AL Payment date: 20041230 |
|
17Q | First examination report despatched |
Effective date: 20090902 |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: ARQULE, INC. Owner name: ABBOTT HEALTHCARE PRODUCTS B.V. |
|
GRAP | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOSNIGR1 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20120417 |