DK200100432A - Adenosin-A3-receptormodulatorer - Google Patents

Adenosin-A3-receptormodulatorer Download PDF

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Publication number: DK200100432A
Authority: DK; Denmark
Prior art keywords: alkyl; substituted; compound; alkenyl; tumor cells
Prior art date: 1998-09-16

Application number

DK200100432A

Other languages

English (en)

Inventor

Pier Giovanni Baraldi

Pier Andrea Borea

Original Assignee

King Pharmaceuticals And Dev I

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.)

1998-09-16

Filing date

2001-03-14

Publication date

2001-03-14

2001-03-14 Application filed by King Pharmaceuticals And Dev I filed Critical King Pharmaceuticals And Dev I

2001-03-14 Publication of DK200100432A publication Critical patent/DK200100432A/da

Links

102000008161 Adenosine A3 Receptor Human genes 0.000 title description 2
108010060261 Adenosine A3 Receptor Proteins 0.000 title description 2
150000001875 compounds Chemical class 0.000 description 17
238000000034 method Methods 0.000 description 10
210000004881 tumor cell Anatomy 0.000 description 9
125000003342 alkenyl group Chemical group 0.000 description 7
125000000217 alkyl group Chemical group 0.000 description 7
125000003118 aryl group Chemical group 0.000 description 7
229910052739 hydrogen Inorganic materials 0.000 description 6
239000001257 hydrogen Substances 0.000 description 6
125000004435 hydrogen atom Chemical class [H]* 0.000 description 6
125000001072 heteroaryl group Chemical group 0.000 description 4
210000004027 cell Anatomy 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
125000000547 substituted alkyl group Chemical group 0.000 description 3
150000003852 triazoles Chemical class 0.000 description 3
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
201000006474 Brain Ischemia Diseases 0.000 description 2
206010008120 Cerebral ischaemia Diseases 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
206010021143 Hypoxia Diseases 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
208000007660 Residual Neoplasm Diseases 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
125000000304 alkynyl group Chemical group 0.000 description 2
150000001408 amides Chemical group 0.000 description 2
-1 amino, substituted amino Chemical group 0.000 description 2
125000003710 aryl alkyl group Chemical group 0.000 description 2
230000000747 cardiac effect Effects 0.000 description 2
206010008118 cerebral infarction Diseases 0.000 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
230000007954 hypoxia Effects 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
125000003226 pyrazolyl group Chemical group 0.000 description 2
125000005017 substituted alkenyl group Chemical group 0.000 description 2
125000004426 substituted alkynyl group Chemical group 0.000 description 2
229940124530 sulfonamide Drugs 0.000 description 2
150000003456 sulfonamides Chemical group 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
125000005309 thioalkoxy group Chemical group 0.000 description 2
150000003556 thioamides Chemical group 0.000 description 2
150000003585 thioureas Chemical group 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
125000006569 (C5-C6) heterocyclic group Chemical group 0.000 description 1
239000002126 C01EB10 - Adenosine Substances 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
125000004442 acylamino group Chemical group 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
229960005305 adenosine Drugs 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
125000002877 alkyl aryl group Chemical group 0.000 description 1
125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
125000004104 aryloxy group Chemical group 0.000 description 1
125000002393 azetidinyl group Chemical group 0.000 description 1
RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical group CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
125000001589 carboacyl group Chemical group 0.000 description 1
125000004181 carboxyalkyl group Chemical group 0.000 description 1
239000006143 cell culture medium Substances 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical group 0.000 description 1
125000005553 heteroaryloxy group Chemical group 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
125000004470 heterocyclooxy group Chemical group 0.000 description 1
210000003630 histaminocyte Anatomy 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
125000005415 substituted alkoxy group Chemical group 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000000725 suspension Substances 0.000 description 1
125000005296 thioaryloxy group Chemical group 0.000 description 1
229930192474 thiophene Chemical group 0.000 description 1
125000004953 trihalomethyl group Chemical group 0.000 description 1

Classifications

- 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
- C07D487/12—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 three hetero rings
- C07D487/14—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0459—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0491—Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
- 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
- A61P35/00—Antineoplastic agents
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- 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
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- 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
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/72—Assays involving receptors, cell surface antigens or cell surface determinants for hormones
- G01N2333/726—G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value

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Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Epidemiology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Optics & Photonics (AREA)
Physics & Mathematics (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biotechnology (AREA)
Biomedical Technology (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Vascular Medicine (AREA)
Immunology (AREA)
Urology & Nephrology (AREA)
Hospice & Palliative Care (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Saccharide Compounds (AREA)
Investigating Or Analysing Biological Materials (AREA)
Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Description

PATENTKRAV 1. Forbindelse med formlen: hvori:

A er imidazol, pyrazol eller triazol; R er -C(X)R" -C(X)-N(R,)a, -C(X)OR,, -C(X)SRt, -SO&, -SOaORu -SO^Rj eller SOa-NCRj^; R, er hydrogen, alkyl, substitueret alkyl, alkenyl, substitueret alkenyl, alkynyl, substitu¬ eret alkynyl, aryl, heteroaryl, heterocyclyl, lavere alkenyl, lavere alkanoyl eller danner, såfremt den er bundet til et nitrogenatom og derefter tages sammen med nitrogenatomet, en azetidinring eller en 5-6-leddet heterocyklisk ring indeholdende et eller flere heteroa- tomer, såsom N, O eller S; R2 er hydrogen, alkyl, substitueret alkyl, aralkyl, substitueret aralkyl, heteroaryl, substi¬ tueret heteroaryl eller aryl; R3 er furan, pyrrol, thiophen, benzofuran, benzypyrrol, benzothiophen, eventuelt substi¬ tueret med en eller flere substituenter valgt fra gruppen bestående af hydroxy, acyl, al¬ kyl, alkoxy, alkenyl, alkynyl, substitueret alkyl, substitueret alkoxy, substitueret alkenyl, substitueret alkynyl, amino, substitueret amino, aminoacyl, acyloxy, acylamino, alkaryl, aryl, aryloxy, azido, carboxyl, carboxylalkyl, cyano, halogen, nitro, heteroaryl, hetero- aryloxy, heterocyclyl, heterocyclooxy, aminoacyloxy, oxyacylamino, thioalkoxy, substi¬ tueret thioalkoxy, thioaryloxy, thioheteroaryloxy, -SO-alkyl,-SO-substitueretalkyl, -SO- aryl, -SO-heteroaryl, -S02-alkyl-, -S02-substimeret alkyl, -S02-aryl, -S02-heteroaryl og trihalogenmethyl; X er O, S eller NR1; n er 1 eller 2; og farmaceutisk acceptable salte deraf. 2. Forbindelse ifølge krav 1, hvori R er valgt fra gruppen bestående af urinstofforbin- delser, amider, thiourinstofforbindelser, thioamider og sulfonamider. 3. Forbindelse ifølge krav 1, hvori R1 er valgt fra gruppen bestående af hydrogen, alkyl, alkenyl og aryl. 4. Forbindelse ifølge krav 1, hvori R2 er valgt fra gruppen bestående af hydrogen, alkyl, alkenyl og aryl. 5. Forbindelse ifølge krav 1, hvori R3 er foran. 6. Forbindelse ifølge krav 1, hvori X er O. 7. Forbindelse ifølge krav 1, hvori A er en triazolring. 8. Forbindelse ifølge krav 1, hvori A er en pyrazolring. 9. Fremgangsmåde til behandling af hypertension, inflammation, allergiske reaktioner, mastcelledegranulering, tumorer og cardial hypoxi og beskyttelse mod cerebral iskæmi, omfattende administration til en patient med behov for behandling deraf af en effektiv mængde af en forbindelse ifølge krav 1. 10. Fremgangsmåde ifølge krav 9, hvori R er valgt fra gruppen bestående af urinstof¬ forbindelser, amider, thiourinstofforbindelser, thioamider og sulfonamider. 11. Fremgangsmåde ifølge krav 9, hvori R1 valgt fra gruppen bestående af hydrogen, alkyl, alkenyl og aryl. 12. Fremgangsmåde ifølge krav 9, hvori R2 er valgt fra gruppen bestående af hydro¬ gen, alkyl, alkenyl og aryl. 13. Fremgangsmåde ifølge krav 9, hvori X er O. 14. Fremgangsmåde ifølge krav 9, hvori A er en pyrazolring. 15. Fremgangsmåde ifølge krav 9, hvori A er en triazolring. 16. Fremgangsmåde ifølge krav 9, hvori den forstyrrelse, der skal behandles, er valgt fra gruppen bestående af cardial hypoxi og cerebral iskæmi. 17. Fremgangsmåde til bestemmelse af nærvær af tumorceller, som besidder en høj koncentration af adenosin-A3-receptorer i en patient, hvilken fremgangsmåde omfatter, at man: a) til patienten administrerer en forbindelse ifølge krav 1, som omfatter et mærke, der kan påvises efter binding af forbindelsen til tumorceller, b) lader forbindelsen binde til tumorcelleme, og c) påviser mærket. 18. Fremgangsmåde til bestemmelse af nærvær af tumorceller, som har en høj koncen¬ tration af adenosin-Aj-receptorer i en celleprøve, hvilken fremgangsmåde omfatter, at man: a) fremstiller en suspension af cellerne i et cellekulturmedium, b) til cellerne administrerer en forbindelse ifølge krav 1, som omfatter et mærke, der kan påvises efter binding af forbindelsen til tumorceller, c) lader forbindelsen binde til tumorcelleme, og d) påviser mærket. 19. Fremgangsmåde til bestemmelse af tilstedeværelse af resterende tumorceller efter kirurgisk fjernelse af en tumor, hvilken fremgangsmåde omfatter, at man: a) til patienten før, efter eller under kirurgisk fjernelse af en tumor administrerer en for¬ bindelse ifølge krav 1, som omfatter et mærke, der kan påvises efter binding af forbin¬ delsen til resterende tumorceller, b) lader forbindelsen binde til de resterende tumorceller, og c) påviser mærket.

DK200100432A 1998-09-16 2001-03-14 Adenosin-A3-receptormodulatorer DK200100432A (da)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US09/154,435 US6448253B1 (en)	1998-09-16	1998-09-16	Adenosine A3 receptor modulators
US09/379,300 US6407236B1 (en)	1998-09-16	1999-08-23	Adenosine A3 receptor modulators
PCT/US1999/021103 WO2000015231A1 (en)	1998-09-16	1999-09-15	Adenosine a3 receptor modulators

Publications (1)

Publication Number	Publication Date
DK200100432A true DK200100432A (da)	2001-03-14

Family

ID=22551355

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK200100432A DK200100432A (da)	1998-09-16	2001-03-14	Adenosin-A3-receptormodulatorer

Country Status (27)

Country	Link
US (2)	US6448253B1 (da)
JP (1)	JP2002524519A (da)
KR (1)	KR100448555B1 (da)
CN (1)	CN1154494C (da)
AT (2)	AT414240B (da)
AU (1)	AU749211B2 (da)
BR (1)	BR9913766A (da)
CA (1)	CA2332007C (da)
CH (1)	CH692132A5 (da)
DE (1)	DE19983530T1 (da)
DK (1)	DK200100432A (da)
ES (1)	ES2204262B1 (da)
FI (1)	FI116624B (da)
GB (1)	GB2353527B (da)
HU (1)	HUP0102589A3 (da)
ID (1)	ID28100A (da)
IL (1)	IL156851A (da)
LU (1)	LU90687B1 (da)
NO (1)	NO318078B1 (da)
NZ (1)	NZ509149A (da)
RO (1)	RO121030B1 (da)
RU (1)	RU2250904C2 (da)
SE (1)	SE522578C2 (da)
TR (1)	TR200003461T2 (da)
WO (1)	WO2000015231A1 (da)
YU (1)	YU83600A (da)
ZA (1)	ZA200101626B (da)

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KR20030076633A (ko) *	2001-02-05	2003-09-26	가부시키 가이샤 오오쯔카 세이야쿠 고우죠우	트리아조로퀴나졸린 및 피라졸로 트리아조로피리미딘유도체, 의약조성물,아데노신 에이3 수용체 친화제,안압저하제, 녹내장의 예방 및 치료를 위한 제제 및안압저하 방법
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HUP0105407A3 (en) *	2001-12-21	2004-04-28	Sanofi Aventis	Triazolo[1,5-a]quinolin derivatives, process for their preparation, pharmaceutical compositions thereof and intermediates
IL160133A0 (en) *	2002-05-30	2004-06-20	King Pharmaceuticals Res & Dev	Pharmaceutically active compounds having a tricyclic pyrazolotriazolopyrimidine ring structure and methods of use
US20060100168A1 (en) *	2002-09-30	2006-05-11	The Trustee Of Boston University	Method of treating cancer using adenosine and its analogs
US20040167212A1 (en) *	2002-10-07	2004-08-26	Bednarski Mark D.	X-nitro compounds, pharmaceutical compositions thereof and uses thereof
EP1554583B1 (en) *	2002-10-22	2007-08-22	Can-Fite Biopharma Ltd.	The use of the a3 adenosine receptor as a marker for a disease state
HUP0203976A3 (en) *	2002-11-15	2004-08-30	Sanofi Aventis	Adenozine a3 receptors, process for their preparation and pharmaceutical compositions containing them
US8236874B2 (en) *	2003-06-11	2012-08-07	3M Innovative Properties Company	Compositions and method for improving the processing of polymer composites
US7402625B2 (en) *	2003-06-11	2008-07-22	3M Innovative Properties Company	Compositions and method for improving the processing of polymer composites
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1998
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CN1154494C (zh)	2004-06-23
FI20002367L (fi)	2001-01-19
SE522578C2 (sv)	2004-02-17
ID28100A (id)	2001-05-03
KR20010089154A (ko)	2001-09-29
CA2332007C (en)	2007-08-07
CA2332007A1 (en)	2000-03-23
YU83600A (sh)	2003-12-31
SE0003984D0 (sv)	2000-11-01
AU749211B2 (en)	2002-06-20
ATA904399A (de)	2006-01-15
HK1035671A1 (en)	2001-12-07
AT503591A2 (de)	2007-11-15
FI116624B (fi)	2006-01-13
CN1303289A (zh)	2001-07-11
NO318078B1 (no)	2005-01-31
RO121030B1 (ro)	2006-11-30
NZ509149A (en)	2003-08-29
NO20005508D0 (no)	2000-11-01
HUP0102589A2 (hu)	2001-11-28
KR100448555B1 (ko)	2004-09-13
AT414240B (de)	2006-10-15
WO2000015231A8 (en)	2000-06-15
US6407236B1 (en)	2002-06-18
DE19983530T1 (de)	2001-11-08
TR200003461T2 (tr)	2001-06-21
WO2000015231A9 (en)	2000-08-17
ZA200101626B (en)	2001-12-13
RU2250904C2 (ru)	2005-04-27
BR9913766A (pt)	2001-06-05
GB2353527A (en)	2001-02-28
AU6248299A (en)	2000-04-03
LU90687B1 (en)	2000-12-19
GB2353527B (en)	2004-02-25
ES2204262A1 (es)	2004-04-16
WO2000015231A1 (en)	2000-03-23
IL156851A (en)	2006-08-20
HUP0102589A3 (en)	2002-01-28
JP2002524519A (ja)	2002-08-06
SE0003984L (sv)	2000-12-22
CH692132A5 (de)	2002-02-28
ES2204262B1 (es)	2005-03-01
NO20005508L (no)	2001-03-15
GB0027879D0 (en)	2000-12-27
US6448253B1 (en)	2002-09-10

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