SK4842002A3 - Purine derivatives - Google Patents
Purine derivatives Download PDFInfo
- Publication number
- SK4842002A3 SK4842002A3 SK484-2002A SK4842002A SK4842002A3 SK 4842002 A3 SK4842002 A3 SK 4842002A3 SK 4842002 A SK4842002 A SK 4842002A SK 4842002 A3 SK4842002 A3 SK 4842002A3
- Authority
- SK
- Slovakia
- Prior art keywords
- alkyl
- compound
- group
- formula
- phenyl
- Prior art date
Links
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 title description 4
- 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 197
- 238000002360 preparation method Methods 0.000 claims abstract description 60
- 239000000203 mixture Substances 0.000 claims abstract description 54
- 150000003839 salts Chemical class 0.000 claims abstract description 43
- 238000000034 method Methods 0.000 claims abstract description 31
- 239000012453 solvate Substances 0.000 claims abstract description 28
- 230000008569 process Effects 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 63
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 50
- -1 -OR 3 Chemical group 0.000 claims description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 125000006239 protecting group Chemical group 0.000 claims description 38
- 125000001153 fluoro group Chemical group F* 0.000 claims description 26
- 125000001624 naphthyl group Chemical group 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 125000001589 carboacyl group Chemical group 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- 241000124008 Mammalia Species 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 10
- 201000004624 Dermatitis Diseases 0.000 claims description 10
- 208000007882 Gastritis Diseases 0.000 claims description 10
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 10
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 10
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 10
- 206010006451 bronchitis Diseases 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000000579 2,2-diphenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(C1=C([H])C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- 101150051188 Adora2a gene Proteins 0.000 claims description 7
- 208000006673 asthma Diseases 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 7
- 208000023504 respiratory system disease Diseases 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 201000006417 multiple sclerosis Diseases 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 150000003254 radicals Chemical class 0.000 claims description 6
- 229940044601 receptor agonist Drugs 0.000 claims description 6
- 239000000018 receptor agonist Substances 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 5
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 5
- 206010009137 Chronic sinusitis Diseases 0.000 claims description 5
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 5
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 5
- 206010014561 Emphysema Diseases 0.000 claims description 5
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 5
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 5
- 208000028017 Psychotic disease Diseases 0.000 claims description 5
- 206010063837 Reperfusion injury Diseases 0.000 claims description 5
- 206010040070 Septic Shock Diseases 0.000 claims description 5
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 5
- 208000010668 atopic eczema Diseases 0.000 claims description 5
- 201000009267 bronchiectasis Diseases 0.000 claims description 5
- 208000007451 chronic bronchitis Diseases 0.000 claims description 5
- 201000009151 chronic rhinitis Diseases 0.000 claims description 5
- 208000027157 chronic rhinosinusitis Diseases 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 230000006378 damage Effects 0.000 claims description 5
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- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
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- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 5
- 201000001881 impotence Diseases 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 5
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- 206010039083 rhinitis Diseases 0.000 claims description 5
- 230000036303 septic shock Effects 0.000 claims description 5
- 201000006474 Brain Ischemia Diseases 0.000 claims description 4
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 4
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 4
- 125000002393 azetidinyl group Chemical group 0.000 claims description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 206010008118 cerebral infarction Diseases 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000005936 piperidyl group Chemical group 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- 230000029663 wound healing Effects 0.000 claims description 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
- 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 claims description 2
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 2
- 206010012434 Dermatitis allergic Diseases 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 201000008937 atopic dermatitis Diseases 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 238000003307 slaughter Methods 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- 206010052428 Wound Diseases 0.000 claims 1
- 208000027418 Wounds and injury Diseases 0.000 claims 1
- 238000011292 agonist therapy Methods 0.000 claims 1
- ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 claims 1
- 125000006413 ring segment Chemical group 0.000 claims 1
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 7
- 239000002465 adenosine A2a receptor agonist Substances 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 239000000243 solution Substances 0.000 description 48
- 239000002904 solvent Substances 0.000 description 47
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 37
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 230000002829 reductive effect Effects 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 238000005160 1H NMR spectroscopy Methods 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
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- 239000002585 base Chemical class 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
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- 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 8
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
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- RMFWVOLULURGJI-UHFFFAOYSA-N 2,6-dichloro-7h-purine Chemical compound ClC1=NC(Cl)=C2NC=NC2=N1 RMFWVOLULURGJI-UHFFFAOYSA-N 0.000 description 3
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- LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 2
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- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
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- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
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Classifications
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- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
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- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
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- C07H19/16—Purine radicals
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Landscapes
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9924363.6A GB9924363D0 (en) | 1999-10-14 | 1999-10-14 | Purine derivatives |
| PCT/IB2000/001444 WO2001027130A1 (en) | 1999-10-14 | 2000-10-06 | Purine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK4842002A3 true SK4842002A3 (en) | 2003-06-03 |
Family
ID=10862760
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK484-2002A SK4842002A3 (en) | 1999-10-14 | 2000-10-06 | Purine derivatives |
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Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7427606B2 (en) * | 1999-02-01 | 2008-09-23 | University Of Virginia Patent Foundation | Method to reduce inflammatory response in transplanted tissue |
| US7378400B2 (en) * | 1999-02-01 | 2008-05-27 | University Of Virginia Patent Foundation | Method to reduce an inflammatory response from arthritis |
| GB0003960D0 (en) | 2000-02-18 | 2000-04-12 | Pfizer Ltd | Purine derivatives |
| US6921753B2 (en) | 2000-06-27 | 2005-07-26 | Pfizer Inc | Purine derivatives |
| GB0015727D0 (en) * | 2000-06-27 | 2000-08-16 | Pfizer Ltd | Purine derivatives |
| GB0022695D0 (en) | 2000-09-15 | 2000-11-01 | Pfizer Ltd | Purine Derivatives |
| WO2002096462A1 (en) * | 2001-05-25 | 2002-12-05 | Pfizer Inc. | An adenosine a2a receptor agonist and an anticholinergic agent in combination for treating obstructive airways diseases |
| CA2460911C (en) * | 2001-10-01 | 2011-08-30 | University Of Virginia Patent Foundation | 2-propynyl adenosine analogs having a2a agonist activity and compositions thereof |
| ATE381336T1 (de) * | 2002-04-10 | 2008-01-15 | Univ Virginia | Verwendung von a2a adenosin rezeptor agonisten und anti-pathogene mittel enthaltenden kombinationen zur behandlung von entzündungskrankheiten |
| AR044519A1 (es) | 2003-05-02 | 2005-09-14 | Novartis Ag | Derivados de piridin-tiazol amina y de pirimidin-tiazol amina |
| US20050033044A1 (en) * | 2003-05-19 | 2005-02-10 | Bristol-Myers Squibb Pharma Company | Methods for preparing 2-alkynyladenosine derivatives |
| GB0401334D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
| GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
| US7605143B2 (en) * | 2004-08-02 | 2009-10-20 | University Of Virginia Patent Foundation | 2-propynyl adenosine analogs with modified 5′-ribose groups having A2A agonist activity |
| WO2006028618A1 (en) * | 2004-08-02 | 2006-03-16 | University Of Virginia Patent Foundation | 2-polycyclic propynyl adenosine analogs with modified 5'-ribose groups having a2a agonist activity |
| US7442687B2 (en) * | 2004-08-02 | 2008-10-28 | The University Of Virginia Patent Foundation | 2-polycyclic propynyl adenosine analogs having A2A agonist activity |
| GB0424284D0 (en) | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
| GB0426164D0 (en) | 2004-11-29 | 2004-12-29 | Novartis Ag | Organic compounds |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| EP1893593A1 (en) * | 2005-06-15 | 2008-03-05 | Pfizer Limited | 3-phenylazetidine derivatives as dopamine agonists |
| CN100352823C (zh) * | 2005-08-19 | 2007-12-05 | 浙江车头制药有限公司 | 一种腺嘌呤衍生物的制备方法 |
| KR20080049113A (ko) | 2005-10-21 | 2008-06-03 | 노파르티스 아게 | Ｉｌ-13에 대항한 인간 항체 및 치료적 용도 |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| WO2007092936A2 (en) * | 2006-02-08 | 2007-08-16 | University Of Virginia Patent Foundation | Method to treat gastric lesions |
| WO2007120972A2 (en) | 2006-02-10 | 2007-10-25 | University Of Virginia Patent Foundation | Method to treat sickle cell disease |
| US8188063B2 (en) * | 2006-06-19 | 2012-05-29 | University Of Virginia Patent Foundation | Use of adenosine A2A modulators to treat spinal cord injury |
| ATE502943T1 (de) | 2006-09-29 | 2011-04-15 | Novartis Ag | Pyrazolopyrimidine als pi3k-lipidkinasehemmer |
| RU2009120389A (ru) | 2006-10-30 | 2010-12-10 | Новартис АГ (CH) | Гетероциклические соединения в качестве противовоспалительных агентов |
| US8058259B2 (en) * | 2007-12-20 | 2011-11-15 | University Of Virginia Patent Foundation | Substituted 4-{3-[6-amino-9-(3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-piperidine-1-carboxylic acid esters as A2AR agonists |
| WO2009087224A1 (en) | 2008-01-11 | 2009-07-16 | Novartis Ag | Pyrimidines as kinase inhibitors |
| SI2391366T1 (sl) | 2009-01-29 | 2013-01-31 | Novartis Ag | Substituirani benzimidazoli za zdravljenje astrocitomov |
| US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
| CA2770873A1 (en) | 2009-08-12 | 2011-02-17 | Novartis Ag | Heterocyclic hydrazone compounds and their uses to treat cancer and inflammation |
| SG178454A1 (en) | 2009-08-17 | 2012-03-29 | Intellikine Inc | Heterocyclic compounds and uses thereof |
| IN2012DN01453A (et) | 2009-08-20 | 2015-06-05 | Novartis Ag | |
| WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| US8637516B2 (en) | 2010-09-09 | 2014-01-28 | Irm Llc | Compounds and compositions as TRK inhibitors |
| US20130324526A1 (en) | 2011-02-10 | 2013-12-05 | Novartis Ag | [1,2,4] triazolo [4,3-b] pyridazine compounds as inhibitors of the c-met tyrosine kinase |
| JP5808826B2 (ja) | 2011-02-23 | 2015-11-10 | インテリカイン， エルエルシー | 複素環化合物およびその使用 |
| MA34969B1 (fr) | 2011-02-25 | 2014-03-01 | Irm Llc | Composes et compositions en tant qu inibiteurs de trk |
| CA2848809A1 (en) | 2011-09-15 | 2013-03-21 | Novartis Ag | 6-substituted 3-(quinolin-6-ylthio)-[1,2,4]triazolo[4,3-a]pyradines as c-met tyrosine kinase |
| CA2856803A1 (en) | 2011-11-23 | 2013-05-30 | Intellikine, Llc | Enhanced treatment regimens using mtor inhibitors |
| EP3964513A1 (en) | 2012-04-03 | 2022-03-09 | Novartis AG | Combination products with tyrosine kinase inhibitors and their use |
| WO2014151147A1 (en) | 2013-03-15 | 2014-09-25 | Intellikine, Llc | Combination of kinase inhibitors and uses thereof |
| TW201605450A (zh) | 2013-12-03 | 2016-02-16 | 諾華公司 | Ｍｄｍ２抑制劑與ＢＲＡＦ抑制劑之組合及其用途 |
| WO2016011658A1 (en) | 2014-07-25 | 2016-01-28 | Novartis Ag | Combination therapy |
| AU2015294889B2 (en) | 2014-07-31 | 2018-03-15 | Novartis Ag | Combination therapy |
| TW202140550A (zh) | 2020-01-29 | 2021-11-01 | 瑞士商諾華公司 | 使用抗ｔｓｌｐ抗體治療炎性或阻塞性氣道疾病之方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5536419A (en) * | 1978-09-08 | 1980-03-14 | Yamasa Shoyu Co Ltd | 2-substituted adenosine derivative and its preparation |
| WO1988003147A1 (en) * | 1986-10-31 | 1988-05-05 | Warner-Lambert Company | Selected n6-substituted adenosines having selective a2 binding activity |
| US5376645A (en) | 1990-01-23 | 1994-12-27 | University Of Kansas | Derivatives of cyclodextrins exhibiting enhanced aqueous solubility and the use thereof |
| KR0166088B1 (ko) | 1990-01-23 | 1999-01-15 | . | 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도 |
| US5877180A (en) * | 1994-07-11 | 1999-03-02 | University Of Virginia Patent Foundation | Method for treating inflammatory diseases with A2a adenosine receptor agonists |
| GB9711643D0 (en) | 1997-06-05 | 1997-07-30 | Janssen Pharmaceutica Nv | Glass thermoplastic systems |
| EP1121372B1 (en) * | 1998-10-16 | 2006-06-28 | Pfizer Limited | Adenine derivatives |
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1999
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