FI90429C - Menetelmä uusien terapeuttisesti käyttökelpoisten adenosiinijohdannaisten valmistamiseksi ja välituotteita - Google Patents
Menetelmä uusien terapeuttisesti käyttökelpoisten adenosiinijohdannaisten valmistamiseksi ja välituotteita Download PDFInfo
- Publication number
- FI90429C FI90429C FI885943A FI885943A FI90429C FI 90429 C FI90429 C FI 90429C FI 885943 A FI885943 A FI 885943A FI 885943 A FI885943 A FI 885943A FI 90429 C FI90429 C FI 90429C
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- Finland
- Prior art keywords
- formula
- compound
- group
- salt
- adenosine
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 25
- 230000008569 process Effects 0.000 title claims description 14
- 238000002360 preparation method Methods 0.000 title claims description 12
- 150000003835 adenosine derivatives Chemical class 0.000 title claims description 3
- 239000000543 intermediate Substances 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims description 89
- 239000000203 mixture Substances 0.000 claims description 51
- 150000003839 salts Chemical class 0.000 claims description 36
- -1 2-hydroxycyclopentyl Chemical group 0.000 claims description 22
- 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 claims description 16
- GYWXTRVEUURNEW-TVDBPQCTSA-N (2R,3R,4S,5R)-2-[6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9-purinyl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N[C@@H]3[C@H](CCC3)O)=C2N=C1 GYWXTRVEUURNEW-TVDBPQCTSA-N 0.000 claims description 12
- 125000006239 protecting group Chemical group 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 8
- 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 claims description 8
- 229960005305 adenosine Drugs 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 7
- GYWXTRVEUURNEW-QDYOZFCWSA-N (2r,3r,4s,5r)-2-[6-[[(1r,2r)-2-hydroxycyclopentyl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N[C@H]3[C@@H](CCC3)O)=C2N=C1 GYWXTRVEUURNEW-QDYOZFCWSA-N 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 claims description 2
- 239000002168 alkylating agent Substances 0.000 claims description 2
- 229940100198 alkylating agent Drugs 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 2
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 claims description 2
- IBNQDHKTFAETFU-TVDBPQCTSA-N (2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-2-[(1S,2S)-2-hydroxycyclopentyl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](CCC1)[C@@]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C=NC=2C(N)=NC=NC12 IBNQDHKTFAETFU-TVDBPQCTSA-N 0.000 claims 1
- 229920002807 Thiomer Polymers 0.000 claims 1
- NPXOOYRZYVUPPV-WILZBUOQSA-N [(2r,3r,4r,5r)-3,4-diacetyloxy-5-[6-[[(1s,2s)-2-hydroxycyclopentyl]amino]purin-9-yl]oxolan-2-yl]methyl acetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](COC(=O)C)O[C@H]1N1C2=NC=NC(N[C@@H]3[C@H](CCC3)O)=C2N=C1 NPXOOYRZYVUPPV-WILZBUOQSA-N 0.000 claims 1
- 229940125810 compound 20 Drugs 0.000 claims 1
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- 230000008707 rearrangement Effects 0.000 claims 1
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 238000007796 conventional method Methods 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical compound ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 5
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- 125000002252 acyl group Chemical group 0.000 description 3
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
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- 229910000071 diazene Inorganic materials 0.000 description 1
- 125000005982 diphenylmethyl 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] 0.000 description 1
- 125000001303 disiloxanyl group Chemical group [H][Si]([*])([H])O[Si]([H])([H])[H] 0.000 description 1
- MWEQTWJABOLLOS-UHFFFAOYSA-L disodium;[[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-oxidophosphoryl] hydrogen phosphate;trihydrate Chemical compound O.O.O.[Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP([O-])(=O)OP(O)([O-])=O)C(O)C1O MWEQTWJABOLLOS-UHFFFAOYSA-L 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
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- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
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- 125000005843 halogen group Chemical group 0.000 description 1
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- 150000004677 hydrates Chemical class 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
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- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
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- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 1
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- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
Classifications
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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
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Vascular Medicine (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB878729994A GB8729994D0 (en) | 1987-12-23 | 1987-12-23 | Chemical compounds |
| GB8729994 | 1987-12-23 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI885943L FI885943L (fi) | 1989-06-24 |
| FI90429B FI90429B (fi) | 1993-10-29 |
| FI90429C true FI90429C (fi) | 1994-02-10 |
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| Application Number | Title | Priority Date | Filing Date |
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| FI885943A FI90429C (fi) | 1987-12-23 | 1988-12-22 | Menetelmä uusien terapeuttisesti käyttökelpoisten adenosiinijohdannaisten valmistamiseksi ja välituotteita |
Country Status (36)
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| GB2226027B (en) * | 1988-12-13 | 1992-05-20 | Sandoz Ltd | Adenosine derivatives,their production and use |
| FR2665362B1 (fr) * | 1990-08-03 | 1994-12-09 | Cepbepe | Substance contenant, comme principe actif, une adenosine substitutee en n6 et son application. |
| US5561134A (en) * | 1990-09-25 | 1996-10-01 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Compounds having antihypertensive, cardioprotective, anti-ischemic and antilipolytic properties |
| CA2092305C (en) * | 1990-09-25 | 2003-02-11 | Alfred P. Spada | Compounds having antihypertensive and anti-ischemic properties |
| GB9111580D0 (en) * | 1991-05-30 | 1991-07-24 | Wellcome Found | Nucleoside derivative |
| DK62692D0 (forum.php) * | 1992-05-14 | 1992-05-14 | Novo Nordisk As | |
| US5672588A (en) * | 1992-05-20 | 1997-09-30 | Novo Nordisk A/S | Purine derivatives |
| US5443836A (en) * | 1993-03-15 | 1995-08-22 | Gensia, Inc. | Methods for protecting tissues and organs from ischemic damage |
| CZ327896A3 (en) * | 1994-05-10 | 1997-03-12 | Sandoz Ltd | Adenosine derivatives, process of their preparation, the use of said derivatives for preparing medicaments, the derivatives used for therapy and pharmaceutical composition containing thereof |
| GB9421133D0 (en) * | 1994-10-20 | 1994-12-07 | Glaxo Group Ltd | Medicaments |
| WO1997033590A1 (en) * | 1996-03-13 | 1997-09-18 | Novo Nordisk A/S | A method of treating disorders related to cytokines in mammals |
| AU2022597A (en) * | 1996-03-13 | 1997-10-01 | Novo Nordisk A/S | A method of treating disorders related to cytokines in mammals |
| US6376472B1 (en) * | 1996-07-08 | 2002-04-23 | Aventis Pharmaceuticals, Inc. | Compounds having antihypertensive, cardioprotective, anti-ischemic and antilipolytic properties |
| US6686366B1 (en) | 1998-06-02 | 2004-02-03 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
| EA003604B1 (ru) | 1998-06-02 | 2003-06-26 | Оси Фармасьютикалз, Инк. | КОМПОЗИЦИИ НА ОСНОВЕ ПИРРОЛО [2,3d] ПИРИМИДИНОВ И ИХ ПРИМЕНЕНИЕ |
| US6878716B1 (en) | 1998-06-02 | 2005-04-12 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 receptor and uses thereof |
| US6784165B1 (en) * | 1999-11-23 | 2004-08-31 | Aderis Pharmaceuticals, Inc. | Treatment of heart rhythm disturbances with N6-substituted-5′-(N-substituted) carboxamidoadenosines |
| US6680322B2 (en) | 1999-12-02 | 2004-01-20 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 receptors and uses thereof |
| US7160890B2 (en) | 1999-12-02 | 2007-01-09 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
| US6664252B2 (en) | 1999-12-02 | 2003-12-16 | Osi Pharmaceuticals, Inc. | 4-aminopyrrolo[2,3-d]pyrimidine compounds specific to adenosine A2a receptor and uses thereof |
| US6294522B1 (en) * | 1999-12-03 | 2001-09-25 | Cv Therapeutics, Inc. | N6 heterocyclic 8-modified adenosine derivatives |
| GB9930083D0 (en) * | 1999-12-20 | 2000-02-09 | Glaxo Group Ltd | Medicaments |
| GB9930077D0 (en) * | 1999-12-20 | 2000-02-09 | Glaxo Group Ltd | Medicaments |
| US6680324B2 (en) | 2000-12-01 | 2004-01-20 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 receptors and uses thereof |
| US6673802B2 (en) | 2000-12-01 | 2004-01-06 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A3 receptor and uses thereof |
| GB0106867D0 (en) * | 2001-03-20 | 2001-05-09 | Glaxo Group Ltd | Process |
| EP1258247A1 (en) * | 2001-05-14 | 2002-11-20 | Aventis Pharma Deutschland GmbH | Adenosine analogues for the treatment of insulin resistance syndrome and diabetes |
| US7504407B2 (en) | 2001-11-30 | 2009-03-17 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 and A3 receptors and uses thereof |
| DE60235500D1 (de) | 2001-12-20 | 2010-04-08 | Osi Pharm Inc | Selektive pyrimidin-a2b-antagonistenverbindungen, ihre synthese und verwendung |
| CN1816551A (zh) | 2001-12-20 | 2006-08-09 | Osi药物公司 | 吡咯并嘧啶A2b选择性拮抗剂化合物,它们的合成及用途 |
| CA2523746A1 (en) * | 2003-04-24 | 2004-11-25 | Aderis Pharmaceuticals, Inc. | Method of treating atrial fibrillation or atrial flutter |
| TWI494102B (zh) * | 2003-05-02 | 2015-08-01 | Japan Tobacco Inc | 包含ｓ-〔２（〔〔１-（２-乙基丁基）環己基〕羰基〕胺基）苯基〕２-甲基丙烷硫酯及ｈｍｇ輔酶ａ還原酶抑制劑之組合 |
| US20050118262A1 (en) * | 2003-09-17 | 2005-06-02 | Jack Aurora | Controlled release formulation |
| CA2627319A1 (en) | 2005-11-30 | 2007-06-07 | Prakash Jagtap | Purine derivatives and methods of use thereof |
| CN101712709A (zh) * | 2008-10-06 | 2010-05-26 | 中国医学科学院药物研究所 | 三乙酰基-3-羟基苯基腺苷及其调血脂的用途 |
| SI2473492T1 (sl) | 2009-08-31 | 2016-01-29 | Lonza Ltd. | Postopek za pripravo(1S,4R)-2-oksa-3-azabiciklo(2.2.1)hept-5-enov |
| TWI677489B (zh) | 2014-06-20 | 2019-11-21 | 美商基利科學股份有限公司 | 多環型胺甲醯基吡啶酮化合物之合成 |
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|---|---|---|---|---|
| NL130136C (forum.php) * | 1966-10-20 | |||
| NL6717061A (forum.php) * | 1966-12-21 | 1968-06-24 | ||
| DE2052596A1 (de) * | 1970-10-27 | 1972-05-04 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neuartige Verwendung von N(6)-substituierten Adenosin-Derivaten |
| NL7203984A (forum.php) * | 1971-04-10 | 1972-10-12 | ||
| BE788958A (fr) * | 1971-09-18 | 1973-03-19 | Schering Ag | Derives d'adenosine et leur procede de preparation |
| DE2148838A1 (de) * | 1971-09-30 | 1973-04-05 | Boehringer Mannheim Gmbh | Neue n(6)-disubstituierte adenosinderivate und verfahren zur herstellung derselben |
| DE2157036A1 (de) * | 1971-11-17 | 1973-05-24 | Boehringer Mannheim Gmbh | Neue heterocyclisch substituierte nebularin-derivate und verfahren zu deren herstellung |
| DE2244328A1 (de) * | 1972-09-09 | 1974-03-21 | Boehringer Mannheim Gmbh | Neue n(6)-disubstituierte adenosinderivate und verfahren zur herstellung derselben |
| DE2338705A1 (de) * | 1973-07-31 | 1975-02-13 | Boehringer Mannheim Gmbh | Neue n(6)-disubstituierte adenosinderivate und verfahren zur herstellung derselben |
| DE2338963A1 (de) * | 1973-08-01 | 1975-02-13 | Boehringer Mannheim Gmbh | Neue n(6)-disubstituierte adenosinderivate und verfahren zur herstellung derselben |
| DE2426682A1 (de) * | 1974-06-01 | 1975-12-11 | Boehringer Mannheim Gmbh | Neue n(6)-disubstituierte adenosinderivate und verfahren zur herstellung derselben |
| ZA857998B (en) * | 1984-10-26 | 1986-05-28 | Warner Lambert Co | N6-substituted adenosines |
| AU579412B2 (en) * | 1984-10-26 | 1988-11-24 | Warner-Lambert Company | N` - substituted adenosines |
-
1987
- 1987-12-23 GB GB878729994A patent/GB8729994D0/en active Pending
-
1988
- 1988-12-21 SE SE8804609A patent/SE8804609L/xx not_active Application Discontinuation
- 1988-12-21 DK DK713488A patent/DK170894B1/da not_active IP Right Cessation
- 1988-12-22 HU HU886569A patent/HU203364B/hu not_active IP Right Cessation
- 1988-12-22 IE IE384588A patent/IE61302B1/en not_active IP Right Cessation
- 1988-12-22 DE DE3856154T patent/DE3856154T2/de not_active Expired - Lifetime
- 1988-12-22 NZ NZ227485A patent/NZ227485A/en unknown
- 1988-12-22 EP EP88312231A patent/EP0322242B1/en not_active Expired - Lifetime
- 1988-12-22 PT PT89328A patent/PT89328B/pt not_active IP Right Cessation
- 1988-12-22 CA CA000586787A patent/CA1320195C/en not_active Expired - Lifetime
- 1988-12-22 BE BE8801427A patent/BE1002167A5/fr not_active IP Right Cessation
- 1988-12-22 SG SG1996005914A patent/SG44701A1/en unknown
- 1988-12-22 NO NO885719A patent/NO171506C/no unknown
- 1988-12-22 IL IL88765A patent/IL88765A/xx not_active IP Right Cessation
- 1988-12-22 NL NL8803140A patent/NL8803140A/nl not_active Application Discontinuation
- 1988-12-22 ZA ZA889593A patent/ZA889593B/xx unknown
- 1988-12-22 ES ES8803906A patent/ES2012927A6/es not_active Expired - Fee Related
- 1988-12-22 GR GR880100856A patent/GR1000307B/el unknown
- 1988-12-22 RU SU884613189A patent/RU1826971C/ru active
- 1988-12-22 GB GB8829983A patent/GB2212498B/en not_active Expired - Lifetime
- 1988-12-22 FI FI885943A patent/FI90429C/fi not_active IP Right Cessation
- 1988-12-23 YU YU02341/88A patent/YU234188A/xx unknown
- 1988-12-23 CH CH4777/88A patent/CH677495A5/de not_active IP Right Cessation
- 1988-12-23 FR FR888817132A patent/FR2629715B1/fr not_active Expired - Lifetime
- 1988-12-23 AU AU27401/88A patent/AU612747B2/en not_active Expired
- 1988-12-23 JP JP63323836A patent/JP2736088B2/ja not_active Expired - Lifetime
- 1988-12-23 IT IT8848714A patent/IT1224840B/it active
- 1988-12-23 PL PL1988276697A patent/PL158800B1/pl unknown
- 1988-12-23 PH PH37978A patent/PH25932A/en unknown
- 1988-12-23 LU LU87414A patent/LU87414A1/fr unknown
- 1988-12-23 MX MX1433188A patent/MX14331A/es unknown
- 1988-12-23 AT AT0315488A patent/ATA315488A/de not_active Application Discontinuation
- 1988-12-23 DE DE3843609A patent/DE3843609A1/de not_active Withdrawn
- 1988-12-23 CN CN88108757A patent/CN1024198C/zh not_active Expired - Fee Related
- 1988-12-23 KR KR1019880017330A patent/KR890009967A/ko not_active Withdrawn
-
1989
- 1989-11-03 US US07/431,089 patent/US5032583A/en not_active Expired - Lifetime
-
1991
- 1991-10-16 AU AU85894/91A patent/AU8589491A/en not_active Abandoned
- 1991-12-23 CZ CS914039A patent/CZ403991A3/cs unknown
-
1992
- 1992-02-24 RU SU925010893A patent/RU2060996C1/ru active
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1998
- 1998-09-01 HK HK98110345A patent/HK1009650A1/en not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
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| BB | Publication of examined application | ||
| MM | Patent lapsed |
Owner name: GLAXO GROUP LIMITED |