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WO1998001449A1 - Nouveaux composes - Google Patents

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Publication number
WO1998001449A1
WO1998001449A1 PCT/SE1997/001219 SE9701219W WO9801449A1 WO 1998001449 A1 WO1998001449 A1 WO 1998001449A1 SE 9701219 W SE9701219 W SE 9701219W WO 9801449 A1 WO9801449 A1 WO 9801449A1
Authority
WO
WIPO (PCT)
Prior art keywords
quinazoline
formula
compound
chlorophenyl
alkyl
Prior art date
Application number
PCT/SE1997/001219
Other languages
English (en)
Inventor
John Bantick
Matthew Perry
Philip Thorne
Original Assignee
Astra Pharmaceuticals Ltd.
Astra Aktiebolag
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
Priority claimed from GBGB9614360.7A external-priority patent/GB9614360D0/en
Priority claimed from GBGB9626884.2A external-priority patent/GB9626884D0/en
Application filed by Astra Pharmaceuticals Ltd., Astra Aktiebolag filed Critical Astra Pharmaceuticals Ltd.
Priority to IL12769097A priority Critical patent/IL127690A0/xx
Priority to EEP199900012A priority patent/EE9900012A/xx
Priority to BR9710215A priority patent/BR9710215A/pt
Priority to AU37116/97A priority patent/AU708882B2/en
Priority to EP97933939A priority patent/EP0915879A1/fr
Priority to JP10505146A priority patent/JP2000516206A/ja
Publication of WO1998001449A1 publication Critical patent/WO1998001449A1/fr
Priority to IS4932A priority patent/IS4932A/is
Priority to NO990072A priority patent/NO990072D0/no

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D487/04—Ortho-condensed systems

Definitions

  • This invention relates to pharmaceutically useful compounds, methods for their preparation, their use as medicaments, and pharmaceutical formulations including them.
  • Ar 1 represents thiazolyl, phenyl, pyridyl, pyrimidinyl, 2-benzothiazolyl, 2- or 3-quinolyl or 0 2-quinoxalinyl, all of which are optionally substituted by one or more substituents selected from halo, nitro, cyano, phenyl, phenylsulfonyl, C ⁇ _ 6 alkyl, -6 alkoxy, C ⁇ _ 6 alkylthio,
  • s W represents CH, CA or N;
  • X represents CH, CA, N or N + -O " ;
  • Y represents CH, CA, N or N + -O " ;
  • Z represents CH, CA, N or N + -O " ;
  • A represents hydroxy, halogen, nitro, cyano, phenyl, C * , thioalkyl, CO 2 R', NR 2 R 3 , 0 NR 4 C(0)R 5 , methoxy (optionally substituted by CO 2 R 6 ), C
  • R 2 represents H or C ⁇ _6 alkyl and R 3 represents H, C ⁇ _ 6 alkyl or CH 2 Ar 2 or R 2 and R 3 together with the nitrogen atom to which they are attached form a pyrrolidinyl or piperidinyl ring; R 5 represents H, C
  • R 1 , R 4 , R 6 and R 7 independently represent H or C ⁇ _ ⁇ alkyl
  • Ar 2 and Ar 3 independently represent phenyl optionally substituted by one or more substituents selected from halogen, hydroxy, methoxy (optionally substituted by fluorine), phenoxy, C 2 - ⁇ alkoxy and C ⁇ _ 6 alkyl (which latter three groups are optionally substituted by one or more substituents selected from halogen, hydroxy or C ⁇ alkyl); provided that:
  • W may only represent N when Y represents N and X and Z both represent CH;
  • X may only represent N when Z represents CH or N, W represents CH and Y represents CH or CA;
  • Y may only represent N when W represents N or CH and X and Z both represent CH;
  • Z may only represent N when X represents N or CH, W represents CH and Y represents CH or CA;
  • compositions includes solvates, salts and N-oxides.
  • the compounds of the formula (I) can form acid addition salts with acids, such as conventional pharmaceutically acceptable acids, for example maleic, hydrochloric, hydrobromic, phosphoric, acetic, fumaric, salicylic, citric, lactic, mandelic, tartaric and methanesulfonic acids.
  • acids such as conventional pharmaceutically acceptable acids, for example maleic, hydrochloric, hydrobromic, phosphoric, acetic, fumaric, salicylic, citric, lactic, mandelic, tartaric and methanesulfonic acids.
  • the compounds of the invention may exhibit tautomerism. All tautomeric forms and mixtures thereof are included within the scope of the invention.
  • the compounds of the invention may also contain one or more asymmetric carbon atoms and may therefore exhibit optical and/or diastereoisomerism. All diastereoisomers may be separated using conventional techniques, e.g. chromatography or fractional crystallisation.
  • the various optical isomers may be isolated by separation of a racemic or other mixture of the compounds using conventional, e.g. fractional crystallisation or HPLC, techniques.
  • the desired optical isomers may be made by reaction of the appropriate optically active starting materials under conditions which will not cause racemisation, or by derivatisation or salt formation, for example with a homochiral acid followed by separation of the diastereomeric derivatives by conventional means (e.g. HPLC, chromatography over silica, or, in the case of salts, crystallisation). All stereoisomers are included within the scope of the invention.
  • Alkyl groups may be linear or branched.
  • Ar 1 represents thiazolyl optionally substituted by methyl, phenyl optionally substitiuted by chloro, CF 3 , CONH 2 , or methyl or Ar 1 represents pyridyl or pyridyl N-oxide optionally substituted by chloro, CF 3 , methyl or methoxy.
  • substituents on phenyl or pyridyl groups are preferably para with respect to the linkage to the remainder of the molecule. Preferred substituents are halo and C ⁇ . 6 alkyl.
  • Ar 1 represents pyridyl substituted by chloro or methyl, particularly 3-pyridyl substituted by methyl.
  • W, X, Y and Z form an optionally substituted phenyl, pyridyl or pyrimidine ring. More preferably W, X, Y and Z are all CH; W is CH, X is N, Y is CH or CA and Z is N; W and Y are both N and X and Z are both CH or one of X, Y or Z is N or N + -0 " , and the others together with W are all CH.
  • Preferred groups A include C ⁇ _ 6 alkyl, alkoxy and amino, particularly methyl, methoxy or amino groups.
  • W and Y are both CH, X is CH or N and Z is N.
  • Preferred compounds of the invention include:
  • Hal represents Cl or Br and Ar 1 is as defined in formula (I). and optionally thereafter (a) or (b): • converting the compound of formula (I) into a further compound of formula (I)
  • L is a suitable leaving group such as OR 8 or N(R 8 ) 2 where R 8 is C[. 6 alkyl such as methyl or ethyl.
  • R 8 is C[. 6 alkyl such as methyl or ethyl.
  • L is NMe 2 .
  • Reaction of compounds of formulae (II) and (III) is suitably carried out in the presence of a base, for example sodium methoxide, in an organic solvent such as methanol or ethanol. The reaction can be carried out at elevated temperature, for example at reflux temperature.
  • L' is a leaving group, preferably thioalkyl, in particular thiomethyl.
  • a suitable catalyst e.g. l,3-bis(disphenylphosphino)propane nickel dichloride
  • an appropriate organic solvent e.g. tetrahydrofuran
  • R 8 groups are as defined in above and R 9 groups are C ⁇ . 6 alkyl.
  • R 8 groups are both methyl and R 9 groups are both methyl or ethyl.
  • Preferred compounds of formula (VII) include N,N-dimethylformamide dimethyl acetal.
  • the compound of formula (VII) is used in excess in the absence of additional solvent and the reaction is carried out at elevated temperature such as reflux temperature.
  • R is as defined in formula (I) with N,N-dimethylformamide dimethyl acetal, for example under reflux.
  • Ar 1 is as hereinbefore defined with ammonium chloride, for example at about 90°C in the presence of trimethylaluminium and an appropriate organic solvent (e.g. toluene).
  • an appropriate organic solvent e.g. toluene
  • Compounds of formula (IV) may be prepared by reaction of a corresponding compound of formula II wherein Y represents N or CR 3a and R 3a is as hereinbefore defined with 2- methyl-2-thiopseudourea or a hydrohalide salt thereof, for example at reflux in the presence of a suitable base (e.g. sodium ethoxide) and an appropriate organic solvent (e.g. ethanol).
  • a suitable base e.g. sodium ethoxide
  • an appropriate organic solvent e.g. ethanol
  • R 4a Hal Xm wherein R a represents C ⁇ _ 6 alkyl and Hal represents Cl, Br or I, for example at room temperature in the presence of a suitable base (e.g. potassium carbonate) and an appropriate organic solvent (e.g. dimethylfor amide);
  • a suitable base e.g. potassium carbonate
  • an appropriate organic solvent e.g. dimethylfor amide
  • R 5 C(O)OH XIV wherein R 5 is as hereinbefore defined, for example at room temperature in the presence of an appropriate peptide synthesis agent (e.g. dicyclohexylcarbodiimide and catalytic 4-dimethylaminopyridine) and a suitable organic solvent (e.g. dichloromethane or dimethylformamide);
  • an appropriate peptide synthesis agent e.g. dicyclohexylcarbodiimide and catalytic 4-dimethylaminopyridine
  • a suitable organic solvent e.g. dichloromethane or dimethylformamide
  • R x CHO XV wherein R x represents _ 5 alkyl or HC(O)Z', wherein Z 1 represents C 2 _ 3 alkylene, and a suitable reducing agent (e.g. sodium cyanoborohydride) for example at room temperature in the presence of zinc chloride and appropriate organic solvent (e.g. methanol);
  • a suitable reducing agent e.g. sodium cyanoborohydride
  • R and Ar 1 are as hereinbefore defined, with sodium tetrafluoroborate, for example by heating to 170 °C in the presence of a suitable organic solvent (e.g. 1 ,2-dichlorobenzene); or. alternatively, when the counter-ion is tetrafluoroborate, preparation of such a compound of formula I by heating the diazonium salt to 170 °C, in the presence of a suitable organic solvent (e.g. 1,2-dichlorobenzene);
  • a suitable organic solvent e.g. 1,2-dichlorobenzene
  • R la OH xv ⁇ wherein R la represents C ⁇ alkyl, and a suitable acid or base catalyst or activating agent (e.g. thionyl chloride);
  • a suitable acid or base catalyst or activating agent e.g. thionyl chloride
  • R (R " ) 3 Sn XIX wherein R" represents C1-4 alkyl and R' is as hereinbefore defined, for example by heating up to reflux temperature in the presence of a suitable catalyst system (e.g. palladium on activated carbon and triphenylphosphine or dichloro(triphenylphosphine)palladium, lithium chloride and 2,6-di-tert-butyl-4-methylphenoI) and an appropriate organic solvent (e.g. dimethylformamide or dioxane); or alternatively activating the OH group with the use of an appropriate activating agent (e.g. trifluoromethanesulphonic anhydride);
  • a suitable catalyst system e.g. palladium on activated carbon and triphenylphosphine or dichloro(triphenylphosphine)palladium, lithium chloride and 2,6-di-tert-butyl-4-methylphenoI
  • an appropriate organic solvent e.g. dimethylformamide or di
  • the compounds of the invention may be isolated from their reaction mixtures using conventional techniques.
  • the compounds of the invention are useful because they possess pharmacological activity.
  • the invention therefoer provides a compound of formula (I) for use in therapy.
  • the compounds of the invention possess antiallergic and antiinflammatory activity, for example as shown in the tests described below.
  • the compounds of the invention are thus indicated for use in the treatment of allergic and inflammatory diseases of the airways such as asthma (e.g. bronchial asthma, allergic asthma, intrinsic asthma, extrinsic asthma and dust asthma), particularly chronic or inveterate asthma (e.g. late asthma and airway hyper-responsiveness), bronchitis and the like.
  • asthma e.g. bronchial asthma, allergic asthma, intrinsic asthma, extrinsic asthma and dust asthma
  • chronic or inveterate asthma e.g. late asthma and airway hyper-responsiveness
  • bronchitis e.g. bronchial asthma, allergic asthma, intrinsic asthma, extrinsic asthma and dust asthma
  • chronic or inveterate asthma e.g. late asthma and airway hyper-responsiveness
  • the compounds of the invention are indicated in the treatment of diseases including inflammations/allergies such as rhinitis, including all conditions characterised by inflammation of the nasal mucus membrane, such as acute rhinitis, allergic rhinitis, atrophic rhinitis, chronic rhinitis including rhinitis caseosa, hypertrophic rhinitis, rhinitis purulenta and rhinitis sicca, rhinitis medicamentosa, membranous rhinitis including croupous, fibrinous and pseudomembranous rhinitis, scrofoulous rhinitis, seasonal rhinitis including rhinitis nervosa (hay fever) and vasomotor rhinitis.
  • diseases including inflammations/allergies such as rhinitis, including all conditions characterised by inflammation of the nasal mucus membrane, such as acute rhinitis, allergic rhinitis, atrophic rhinitis, chronic
  • the compounds of the invention are also indicated for use in the treatment of chronic allergic disorders, atopic dermatitis, cutaneous eosinophilias, eosinophilic fascitis, hyper IgE syndrome, vernal conjunctivitis, systemic lupus erythematosis, thyroiditis, lepromatous leprosy, sezary syndrome, chronic graft versus host disease, myasthenia gravis, idiopathic thrombocytopenia pupura and the like.
  • the compounds of the invention may also have activity in both the prophylactic and therapeutic treatment of acquired immunodeficiency syndrome (ALDS), the prevention of chronic rejection of allografts mediated by humoral immunity, and in the treatment of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.
  • ADS acquired immunodeficiency syndrome
  • autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.
  • a method of treatment or prophylaxis of an allergic or an inflammatory disorder comprises administration of a therapeutically effective amount of a compound of formula I as defined above, or a pharmaceutically acceptable derivative thereof, to a person suffering from, or susceptible to such a disorder.
  • the invention provides use of a compound of formula (I) or a pharmaceutically acceptable derivative thereof in the manufacture of a medicament for the treatment or prophylaxis of the above disorders, especially asthma, and in rhinitis, most particularly allergic rhinitis and seasonal rhinitis including rhinitis nervosa (hay fever).
  • Administration of the compounds of the invention may be topical (for example by inhalation to the lung).
  • the compounds of the invention may be inhaled as a dry powder which may be pressurized or non-pressurized.
  • the active ingredient in finely divided form may be used in admixture with a larger sized pharmaceutically acceptable inert carrier
  • the composition may alternatively be pressurized and contain a compressed gas, e.g. nitrogen, or a liquefied gas propellant.
  • a compressed gas e.g. nitrogen
  • a liquefied gas propellant e.g. a liquefied gas propellant
  • the active ingredient is preferably finely divided.
  • the pressurized composition may also contain a surface active agent.
  • the pressurized compositions may be made by conventional methods.
  • the compounds of the invention may be administered systemically (for example by oral administration to the gastrointestinal tract).
  • the active ingredient may be formulated together with known adjuvants, diluents or carriers using conventional techniques to produce tablets or capsules for oral administration to the gastrointestinal tract.
  • Suitable adjuvants, diluents or carriers for oral administration in the form of tablets, capsules and dragees include microcrystalline cellulose, calcium phosphate, diatomaceous earth, a sugar such as lactose, dextrose or mannitol, talc, stearic acid, starch, sodium bicarbonate and/or gelatine.
  • a pharmaceutical composition including a compound of formula I as hereinbefore defined, or a pharmaceutically acceptable derivative thereof, in association with a pharmaceutically acceptable adjuvant diluent or carrier.
  • Suitable doses for administration topical or orally are in the range 0.01 to 30mgkg " 'day ⁇ 1 , for example 0.3mgkg '1 day "1 .
  • Trimethylaluminium (2M in hexanes; 15ml) was added to a vigorously stirred suspension of ammonium chloride ( 1.65g) in toluene (25ml) cooled in an ice bath. The cooling bath was removed and the reaction allowed to attain room temperature. 6-Methyl-pyridine-3- carbonitrile (1.18g) was added and the reaction was heated to 90°C overnight. The reaction was allowed to cool to room temperature then methanol was added dropwise. The mixture was poured onto a slurry of alumina (25g) in chloroform (225ml). Methanol (100ml) was added and the slurry was stirred for 30 minutes. The mixture was filtered, the solid was washed with methanol and the combined filtrates were concentrated to give the sub-title compound (2.78g) contaminated with ammonium chloride. MS(APCI) 136 ((M + H) + )
  • Example 16 2-(Pyridin-3-yl)-5,6-dihydropyrido[2,3-h]quinazoline Prepared following the method of Example 1 above from 6,7-dihydroquinoline-5-(8H)-one (Arch. Pharm. (1961) 294, 759; 150mg) and dimethylformamide dimethylacetal (0.5ml), followed by 3-amidinopyridine hydrochloride (125mg) and sodium methoxide (43mg) to give the title compound (47mg).
  • MS(APCI ) 261 ((M + Hf) mp 101-102-C
  • Example 20 5,6-Dihydro-2-(pyridin-3-yI)-pyrido[4,3-h]quinazoline Prepared following the method of Example 1 above using 6,7-dihydroisoquinoline-8-(5H)- one (J. Pharm. Soc Jpn., ( 1956) 76, 1308; 400mg) dimethylformamide dimethylacetal (2ml), 3-amidinopyridine hydrochloride (390mg) and sodium methoxide (135mg) to give, after chromatography, the title compound (124mg).
  • Example 21 2-(Pyridin-3-yl)-pyrido[4,3-h]quinazoline The title compound ( 1 lmg) also was isolated from the previous Example. MS(APCI ) 259 ((M + H) * ) mp 243-244°C l H NMR (d6-DMSO) ⁇ 7.59-7.63 (dd, IH), 7.98 (d, IH), 8.04 (d, IH), 8.23 (d, IH), 8.7 (dd, IH), 8.92 (d, IH), 9.01-9.05 (m, IH), 9.72 (s, IH), 9.87 (d, IH), 10.59 (s, IH)
  • 6-chloroypyridin-3-ylamidine (liberated from the hydrochloride (290mg) from step (a) above by dissolution in excess aqueous sodium bicarbonate solution, then evaporation to give a solid, extraction of the solid with ethanol, filtration and evaporation) to give the title compound (62mg). mp 186-187°C
  • the subtitle compound was prepared analogously to method described in Example 26(a) from indan-1 -one.
  • Pharmacological activity of the compounds of the invention may be demonstrated using the method of J M Doutrelepont et al ([Clin. Exp. Immunol., 1991 , vol. 83, 133-6; Inhibition of chronic graft-versus-host (c-GVH) disease in the mouse].
  • Test compound was administered to mice subcutaneously as a suspension in saline with TWEEN-80 every day for 21 days.
  • mice Male Balb/c mice were sensitised to ovalbumin/Al(OH) 3 mixture.
  • Compound was administered daily either orally or subcutaneously as a suspension or solution (depending on dose and compound solubility) in 5% Tween 80.
  • mice 17 days after sensitisation and one hour after the fourth dose of compound, the mice were placed in perspex chambers into which a solution of ovalbumin (2%w/v) was nebulised. The mice were allowed to inhale the ovalbumin for a period of 30-40 in. This challenge was repeated daily at the same time for a further 3 or 7 days.
  • Certain compounds of the invention show activities in the chronic graft versus host test and the inhibition of eosinophilia test with EDso's in the range of 0.1 - 10 mg/kg.

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Pulmonology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Quinoline Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)

Abstract

Composés pyrimidiques utilisables en pharmacie et répondant à la formule (I), leurs procédés de préparation, leur utilisation à titre de médicaments, et formulations pharmaceutiques les comprenant.
PCT/SE1997/001219 1996-07-09 1997-07-04 Nouveaux composes WO1998001449A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
IL12769097A IL127690A0 (en) 1996-07-09 1997-07-04 Pyridinocyclohexano-1,3- pyrimidine derivatives their preparation their use as medicaments and pharmaceutical formulations including them
EEP199900012A EE9900012A (et) 1996-07-09 1997-07-04 Uudsed ühendid
BR9710215A BR9710215A (pt) 1996-07-09 1997-07-04 Composto processo para sua preparação e formulação farmacéutica
AU37116/97A AU708882B2 (en) 1996-07-09 1997-07-04 Novel compounds
EP97933939A EP0915879A1 (fr) 1996-07-09 1997-07-04 Nouveaux composes
JP10505146A JP2000516206A (ja) 1996-07-09 1997-07-04 新規な化合物
IS4932A IS4932A (is) 1996-07-09 1998-12-23 Ný efnasambönd
NO990072A NO990072D0 (no) 1996-07-09 1999-01-08 Nye forbindelser

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GBGB9614360.7A GB9614360D0 (en) 1996-07-09 1996-07-09 Compounds
GB9614360.7 1996-07-09
GB9626884.2 1996-12-24
GBGB9626884.2A GB9626884D0 (en) 1996-12-24 1996-12-24 Compounds

Publications (1)

Publication Number Publication Date
WO1998001449A1 true WO1998001449A1 (fr) 1998-01-15

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Country Status (16)

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EP (1) EP0915879A1 (fr)
JP (1) JP2000516206A (fr)
KR (1) KR20000023644A (fr)
AR (1) AR008395A1 (fr)
AU (1) AU708882B2 (fr)
BR (1) BR9710215A (fr)
CA (1) CA2260057A1 (fr)
CZ (1) CZ3699A3 (fr)
EE (1) EE9900012A (fr)
ID (1) ID18889A (fr)
IL (1) IL127690A0 (fr)
IS (1) IS4932A (fr)
NO (1) NO990072D0 (fr)
PL (1) PL331090A1 (fr)
TR (1) TR199900013T2 (fr)
WO (1) WO1998001449A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003015776A1 (fr) * 2001-08-13 2003-02-27 Janssen Pharmaceutica N.V. Derives de thiazolyl 2,4,5-trisubstitue et activite anti-inflammatoire associee
WO2011063927A1 (fr) * 2009-11-24 2011-06-03 Novaled Ag Dispositif électronique organique comprenant un matériau semi-conducteur organique
CN108484606A (zh) * 2018-03-16 2018-09-04 江南大学 一种嘧啶并[4,5-f]喹唑啉类化合物及其应用
US10790453B2 (en) 2012-11-30 2020-09-29 Lg Chem, Ltd. Compounds and organic electronic device using the same
US12016689B2 (en) 2016-04-22 2024-06-25 Vioptix, Inc. Determining absolute and relative tissue oxygen saturation

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Publication number Priority date Publication date Assignee Title
KR102153040B1 (ko) 2013-11-28 2020-09-07 삼성전자주식회사 축합환 화합물 및 이를 포함한 유기 발광 소자

Citations (4)

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Publication number Priority date Publication date Assignee Title
DE1670577A1 (de) * 1967-10-05 1971-05-19 Akad Wissenschaften Ddr Verfahren zur Herstellung von 5-oxo-5.6.7.8-tetrahydro-chinazelinen
US4272535A (en) * 1978-07-31 1981-06-09 Schering Corporation 2,4-[1H,3H,5H]-(1)-Benzopyrano-[2,3-d]-pyrimidinediones and their use as anti-allergy agents
EP0260642A2 (fr) * 1986-09-15 1988-03-23 Warner-Lambert Company Dérivés d'hexahydroquinoline condensés en [f] avec thiazolo comme agents dopaminergiques
WO1996022992A1 (fr) * 1995-01-27 1996-08-01 Abbott Laboratories Antagonistes alpha-1-adrenergiques d'hexahydrobenzeisoindol tricyclique substitue

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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WO2003015776A1 (fr) * 2001-08-13 2003-02-27 Janssen Pharmaceutica N.V. Derives de thiazolyl 2,4,5-trisubstitue et activite anti-inflammatoire associee
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AU2002331227B2 (en) * 2001-08-13 2008-01-24 Janssen Pharmaceutica N.V. 2,4,5-trisubstituted thiazolyl derivatives and their antiinflammatory activity
KR100922538B1 (ko) * 2001-08-13 2009-10-21 얀센 파마슈티카 엔.브이. 2,4,5-삼치환된 티아졸릴 유도체 및 그의 항염증성 활성
HRP20040098B1 (en) * 2001-08-13 2012-08-31 Janssen Pharmaceutica N.V. 2,4,5-TRlSUBSTITUTED THIAZOLYL DERIVATIVES AND THEIR ANTIINFLAMMATORY ACTIVITY
WO2011063927A1 (fr) * 2009-11-24 2011-06-03 Novaled Ag Dispositif électronique organique comprenant un matériau semi-conducteur organique
US8686139B2 (en) 2009-11-24 2014-04-01 Novaled Ag Organic electronic device comprising an organic semiconducting material
US10790453B2 (en) 2012-11-30 2020-09-29 Lg Chem, Ltd. Compounds and organic electronic device using the same
US12016689B2 (en) 2016-04-22 2024-06-25 Vioptix, Inc. Determining absolute and relative tissue oxygen saturation
CN108484606A (zh) * 2018-03-16 2018-09-04 江南大学 一种嘧啶并[4,5-f]喹唑啉类化合物及其应用

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AU708882B2 (en) 1999-08-12
IS4932A (is) 1998-12-23
BR9710215A (pt) 1999-08-10
EP0915879A1 (fr) 1999-05-19
KR20000023644A (ko) 2000-04-25
ID18889A (id) 1998-05-20
IL127690A0 (en) 1999-10-28
JP2000516206A (ja) 2000-12-05
AR008395A1 (es) 2000-01-19
AU3711697A (en) 1998-02-02
NO990072D0 (no) 1999-01-08
TR199900013T2 (xx) 1999-04-21
CZ3699A3 (cs) 1999-06-16

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