WO1996038728A1 - Procede permettant de mesurer l'activite de liaison au recepteur a2a de composes d'utilite pharmacologique, a l'aide du ligand tritie (3h)-sch 58261 - Google Patents
Procede permettant de mesurer l'activite de liaison au recepteur a2a de composes d'utilite pharmacologique, a l'aide du ligand tritie (3h)-sch 58261 Download PDFInfo
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- WO1996038728A1 WO1996038728A1 PCT/EP1996/002348 EP9602348W WO9638728A1 WO 1996038728 A1 WO1996038728 A1 WO 1996038728A1 EP 9602348 W EP9602348 W EP 9602348W WO 9638728 A1 WO9638728 A1 WO 9638728A1
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- WO
- WIPO (PCT)
- Prior art keywords
- compound
- receptors
- brain tissue
- receptor
- mammalian brain
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 27
- 230000027455 binding Effects 0.000 title claims abstract description 18
- 238000000034 method Methods 0.000 title claims abstract description 12
- 230000000144 pharmacologic effect Effects 0.000 title claims abstract description 4
- 239000003446 ligand Substances 0.000 title description 4
- UTLPKQYUXOEJIL-UHFFFAOYSA-N LSM-3822 Chemical compound N1=CC=2C3=NC(C=4OC=CC=4)=NN3C(N)=NC=2N1CCC1=CC=CC=C1 UTLPKQYUXOEJIL-UHFFFAOYSA-N 0.000 title 1
- 102000007471 Adenosine A2A receptor Human genes 0.000 claims abstract description 4
- 108010085277 Adenosine A2A receptor Proteins 0.000 claims abstract description 4
- 101150051188 Adora2a gene Proteins 0.000 claims description 19
- 210000005171 mammalian brain Anatomy 0.000 claims description 11
- 238000012360 testing method Methods 0.000 claims description 10
- 239000002287 radioligand Substances 0.000 claims description 9
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 6
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical group [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 claims description 3
- 210000005013 brain tissue Anatomy 0.000 claims 1
- 230000002285 radioactive effect Effects 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract 1
- 102000005962 receptors Human genes 0.000 description 15
- 108020003175 receptors Proteins 0.000 description 15
- 239000012528 membrane Substances 0.000 description 8
- 239000005557 antagonist Substances 0.000 description 7
- JADDQZYHOWSFJD-FLNNQWSLSA-N N-ethyl-5'-carboxamidoadenosine Chemical class O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 JADDQZYHOWSFJD-FLNNQWSLSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 238000003556 assay Methods 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- PAOANWZGLPPROA-RQXXJAGISA-N CGS-21680 Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(NCCC=3C=CC(CCC(O)=O)=CC=3)=NC(N)=C2N=C1 PAOANWZGLPPROA-RQXXJAGISA-N 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000003379 purinergic P1 receptor agonist Substances 0.000 description 3
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 description 3
- CHMUHOFITZIING-XNIJJKJLSA-N (2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-2-cyclohexyl-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@]1(C2CCCCC2)O[C@H](CO)[C@@H](O)[C@H]1O CHMUHOFITZIING-XNIJJKJLSA-N 0.000 description 2
- SCNILGOVBBRMBK-SDBHATRESA-N 2-Phenylaminoadenosine Chemical compound N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1NC1=CC=CC=C1 SCNILGOVBBRMBK-SDBHATRESA-N 0.000 description 2
- FSUNYKAEJIVAHY-UHFFFAOYSA-N 8-(3,4-dimethoxyphenyl)-7-methyl-1,3-dipropylpurine-2,6-dione Chemical compound CN1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1=CC=C(OC)C(OC)=C1 FSUNYKAEJIVAHY-UHFFFAOYSA-N 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- FFBDFADSZUINTG-UHFFFAOYSA-N DPCPX Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1CCCC1 FFBDFADSZUINTG-UHFFFAOYSA-N 0.000 description 2
- XKMLYUALXHKNFT-UUOKFMHZSA-N Guanosine-5'-triphosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XKMLYUALXHKNFT-UUOKFMHZSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000001577 neostriatum Anatomy 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 229910052722 tritium Inorganic materials 0.000 description 2
- 229940075420 xanthine Drugs 0.000 description 2
- LTBJWRARHRHEGZ-MCDZGGTQSA-N (2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol;3,7-dihydropurine-2,6-dione Chemical compound O=C1NC(=O)NC2=C1NC=N2.C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O LTBJWRARHRHEGZ-MCDZGGTQSA-N 0.000 description 1
- LVSWNSHUTPWCNF-UHFFFAOYSA-N 1,3-diethyl-8-phenyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CC)C(=O)N(CC)C=2N=C1C1=CC=CC=C1 LVSWNSHUTPWCNF-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
- MSJODEOZODDVGW-UHFFFAOYSA-N 9-chloro-2-(2-furanyl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amine Chemical compound N=1N2C(N)=NC3=CC=C(Cl)C=C3C2=NC=1C1=CC=CO1 MSJODEOZODDVGW-UHFFFAOYSA-N 0.000 description 1
- 102000055025 Adenosine deaminases Human genes 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 241001432959 Chernes Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229940121359 adenosine receptor antagonist Drugs 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000000039 congener Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- -1 polypropylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000009834 selective interaction Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/94—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/566—Immunoassay; Biospecific binding assay; Materials therefor using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
- G01N33/5735—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes co-enzymes or co-factors, e.g. NAD, ATP
-
- 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
Definitions
- Adenosine modulates a wide range of physiological functions by interaction with different receptor subtypes named Al, A2a, A2b and A3 [Pharmacol. Rev., 46, 143, (1994)]. While the availability of Al receptor ligands led to rapid progress in the characterization of this receptor subtype, the pharmacology of A2a adenosine receptors was hampered by the lack of selective ligands [Med. Res. Rev., 12, 423, (1992)]. In the past, using different strategies to block the interaction with Al receptors [Naunyn-Schmiedeberg's Arch. Pharmacol., 325, 218, (1984); Mol.
- the A2a selective antagonist ( 3 H)-(E,18%-Z,82%)-8-(3,4-dimethoxystyryl)-l,3-dipro- pylxanthine [( 3 H)-KF 17837S] has been indicated to interact directly with the A2a adenosine receptor in rat striatal tissue, showing a specific binding of 60-70% [Mol. Pharmacol., 46, 817, (1995)].
- One aspect of the present invention is the preparation of the labeled compound 5-amino-7-[2- (2 1 ,4' ,5' 3 H) ⁇ henetyl]-2-(2-furyl)-pyrazolo-[4,3-e]- -1,2,4-triazolo[l,5-c]pyrimidine (hereinafter referred to as ( 3 H)-Compound) .
- the preferred label of the invention has the purpose of facilitating the measurement of the relative binding affinity values, preferably by introducing tritium ( H) atoms, and more preferably, located on the phenethyl group at the positions 2', 4' and 5'.
- the second aspect of the invention is a method for determining the adenosine A2a receptor binding affinity of a test compound; said method consisting in:
- test compound may be synthesized and/or purified from natural source such as animal or plant tissue.
- kit for determining the A2a binding activity of a test compound comprising:
- the tissue was homogenised in a Polytron PTA 10 Probe (setting 5, 20 sec) in 25 volumes (v/v) of 50 mM Tris-HCl buffer, pH 7,4, centrifuged at 48,000 x g for 10 min at 4°C and resuspended in Tris-HCl containing 2 units/ml of adenosine deaminase. After 30 min of incubation at 37°C, the membranes were centrifuged and pellet was stored at -70°C.
- Binding Assay Saturation binding experiments were carried out in polypropylene test tubes containing an aliquot of striatal membranes (100 ug of protein /assay) in incubation buffer (50 mM Tris-HCl, pH 7.4) and 11 different concentrations of ( 3 H)-Compound (0.0625-64 nM) , in a final volume of 0.5 ml Non specific binding was defined in the presence of NECA 50 uM. All assays were performed at 25°C for 30 min, the separation of the free radioligand from the one bound to the receptor was carried out by fast filtration through Whatman GF/B filters using the Brandel cell harvester (Gaithersburg, MD, USA) .
- Binding parameters were estimated by using the computerized program LIGAND [Anal. Biochem. , 107, 220, (1980)]. Results
- ( 3 H)-Compound labeling directly the adenosine A2a striatal receptor, proves to be an excellent means for studying this adenosine A2a receptor subtype in mammalian brain.
- Clear advantages over other A2a antagonist radioligand proposed for this purpose are the high receptor affinity and the low non specific binding.
- a kit containing the necessary components to perform the assays as described above, as well as a method to utilize such kit, can be considered essential for evaluating the interaction of a test compound with A2a adenosine receptors in mammalian brain tissues.
- the ( 3 H)-Compound has the characteristics to become a useful tool for the investigation of A2a receptors distributed in peripheral tissues, such as vascular preparations, platelets and neutrophils, in which their presence has been clearly demonstrated [TiPS, 14, 360, (1993)].
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
L'invention concerne un procédé permettant d'évaluer l'affinité de liaison du récepteur A2a d'adénosine de composés d'utilité pharmacologique. L'invention concerne en outre des réactifs et un kit particulièrement approprié aux mesures précitées.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU61238/96A AU6123896A (en) | 1995-06-02 | 1996-06-01 | A method for measuring the a2a receptor binding activity of compounds of pharmacological interest by the use of the trit iated ligand (3h)-sch 58261 |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI95A001155 | 1995-06-02 | ||
| ITMI951155A IT1275420B (it) | 1995-06-02 | 1995-06-02 | Metodo per misurare l'affinita' di legame al recettore a2a dell'adenosina di componenti di interesse farmacologico mediante l'uso del ligando triziato (3h)-sch 58261 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1996038728A1 true WO1996038728A1 (fr) | 1996-12-05 |
Family
ID=11371733
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1996/002348 WO1996038728A1 (fr) | 1995-06-02 | 1996-06-01 | Procede permettant de mesurer l'activite de liaison au recepteur a2a de composes d'utilite pharmacologique, a l'aide du ligand tritie (3h)-sch 58261 |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU6123896A (fr) |
| IT (1) | IT1275420B (fr) |
| WO (1) | WO1996038728A1 (fr) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6407236B1 (en) | 1998-09-16 | 2002-06-18 | Medco Research, Inc. | Adenosine A3 receptor modulators |
| WO2004079329A3 (fr) * | 2003-03-07 | 2004-12-09 | Cambridge Biotechnology Ltd | Identification de composes therapeutiques |
| US6921825B2 (en) | 1998-09-16 | 2005-07-26 | King Pharmaceuticuals Research & Development, Inc. | Adenosine A3 receptor modulators |
| WO2007038284A1 (fr) | 2005-09-23 | 2007-04-05 | Schering Corporation | 7-[2-[4-(6-FLUORO-3-MÉTHYL-1,2-BENZISOXAZOL-5-YL)-1-PIPÉRAZINYL]ÉTHYL]-2-(1-PROPYNYL)-7H-PYRAZOLO-[4,3-e]-[1,2,4]-TRIAZOLO-[1,5-c]-PYRIMIDIN-5 AMINE |
| US7759321B2 (en) | 2003-03-07 | 2010-07-20 | Cambridge Biotechnology Ltd | Compounds for the treatment of pain |
| US7790698B2 (en) | 2003-03-07 | 2010-09-07 | Cambridge Biotechnology Ltd | Use of adenosine receptor agonists in therapy |
| US8252766B2 (en) | 2002-12-09 | 2012-08-28 | Cbt Development Limited | Use of spongosine for the treatment of pain |
| WO2018089901A3 (fr) * | 2016-11-14 | 2019-06-06 | Joslin Diabetes Center | Système de livraison par des exosomes |
-
1995
- 1995-06-02 IT ITMI951155A patent/IT1275420B/it active IP Right Grant
-
1996
- 1996-06-01 WO PCT/EP1996/002348 patent/WO1996038728A1/fr active Application Filing
- 1996-06-01 AU AU61238/96A patent/AU6123896A/en not_active Abandoned
Non-Patent Citations (3)
| Title |
|---|
| A. NEGRETTI ET AL.: "In vitro pharmacological profile of the new non-xanthine A2a adenosine antagonist 8FB-PTP", RESEARCH COMMUNICATIONS IN MOLECULAR PATHOLOGY AND PHARMACOLOGY, vol. 87, no. 1, 1 January 1995 (1995-01-01), WSETBURY NY USA, pages 87 - 88, XP000603784 * |
| C. ZOCCHI ET AL.: "Binding of the radioligand (3H)-SCH 58261, a new non-xanthine A2a adenosine receptor antagonist, to rat striatal membranes", BRITISH JOURNAL OF PHARMACOLOGY, vol. 117, no. 7, 1 April 1996 (1996-04-01), LONDON UK, pages 1381 - 1386, XP000603818 * |
| P.G. BARALDI ET AL.: "Synthesis of new pyrazolo(4,3-e)1,2,4-triazolo(1,5-c) pyrimidine and 1,2,3-triazolo(4,5-c)pyrimidine displaying potent and selective activity as A2a adenosine receptor antagonists.", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 4, no. 21, 1 January 1994 (1994-01-01), LONDON UK, pages 2539 - 2544, XP000603773 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6407236B1 (en) | 1998-09-16 | 2002-06-18 | Medco Research, Inc. | Adenosine A3 receptor modulators |
| US6448253B1 (en) | 1998-09-16 | 2002-09-10 | King Pharmaceuticals Research And Development, Inc. | Adenosine A3 receptor modulators |
| US6921825B2 (en) | 1998-09-16 | 2005-07-26 | King Pharmaceuticuals Research & Development, Inc. | Adenosine A3 receptor modulators |
| US8252766B2 (en) | 2002-12-09 | 2012-08-28 | Cbt Development Limited | Use of spongosine for the treatment of pain |
| WO2004079329A3 (fr) * | 2003-03-07 | 2004-12-09 | Cambridge Biotechnology Ltd | Identification de composes therapeutiques |
| JP2006519602A (ja) * | 2003-03-07 | 2006-08-31 | ケンブリッジ・バイオテクノロジー・リミテッド | 治療用化合物の同定 |
| US7759321B2 (en) | 2003-03-07 | 2010-07-20 | Cambridge Biotechnology Ltd | Compounds for the treatment of pain |
| US7790698B2 (en) | 2003-03-07 | 2010-09-07 | Cambridge Biotechnology Ltd | Use of adenosine receptor agonists in therapy |
| WO2007038284A1 (fr) | 2005-09-23 | 2007-04-05 | Schering Corporation | 7-[2-[4-(6-FLUORO-3-MÉTHYL-1,2-BENZISOXAZOL-5-YL)-1-PIPÉRAZINYL]ÉTHYL]-2-(1-PROPYNYL)-7H-PYRAZOLO-[4,3-e]-[1,2,4]-TRIAZOLO-[1,5-c]-PYRIMIDIN-5 AMINE |
| WO2018089901A3 (fr) * | 2016-11-14 | 2019-06-06 | Joslin Diabetes Center | Système de livraison par des exosomes |
| US11519008B2 (en) | 2016-11-14 | 2022-12-06 | Joslin Diabetes Center | Exosome delivery system |
Also Published As
| Publication number | Publication date |
|---|---|
| ITMI951155A1 (it) | 1996-12-02 |
| AU6123896A (en) | 1996-12-18 |
| IT1275420B (it) | 1997-08-05 |
| ITMI951155A0 (it) | 1995-06-02 |
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