HRP20000275A2 - Chemical compounds - Google Patents
Chemical compounds Download PDFInfo
- Publication number
- HRP20000275A2 HRP20000275A2 HR20000275A HRP20000275A HRP20000275A2 HR P20000275 A2 HRP20000275 A2 HR P20000275A2 HR 20000275 A HR20000275 A HR 20000275A HR P20000275 A HRP20000275 A HR P20000275A HR P20000275 A2 HRP20000275 A2 HR P20000275A2
- Authority
- HR
- Croatia
- Prior art keywords
- fluoro
- adenosine
- deoxy
- group
- tetrahydro
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 133
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 17
- 208000002193 Pain Diseases 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 239000012453 solvate Substances 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 10
- 235000021588 free fatty acids Nutrition 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 208000031225 myocardial ischemia Diseases 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 9
- 229960005305 adenosine Drugs 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 208000015114 central nervous system disease Diseases 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 201000002859 sleep apnea Diseases 0.000 claims description 7
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 6
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 6
- 208000006011 Stroke Diseases 0.000 claims description 6
- 125000001931 aliphatic group Chemical group 0.000 claims description 6
- 230000009467 reduction Effects 0.000 claims description 6
- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 230000009286 beneficial effect Effects 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000002619 bicyclic group Chemical group 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- RBPOAKLWUKRPLS-QYVSTXNMSA-N (2r,3r,4s,5s)-2-[2-chloro-6-(2,2-dimethylpropylamino)purin-9-yl]-5-(fluoromethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(NCC(C)(C)C)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CF)[C@@H](O)[C@H]1O RBPOAKLWUKRPLS-QYVSTXNMSA-N 0.000 claims description 3
- PLWKJJRKAMRFFZ-NRJACJQQSA-N (2r,3r,4s,5s)-2-[2-chloro-6-(2,3-dihydroxypropylamino)purin-9-yl]-5-(fluoromethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(NCC(O)CO)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CF)[C@@H](O)[C@H]1O PLWKJJRKAMRFFZ-NRJACJQQSA-N 0.000 claims description 3
- GIDVNFOFWFJSTB-QYVSTXNMSA-N (2r,3r,4s,5s)-2-[2-chloro-6-(2-methylpropylamino)purin-9-yl]-5-(fluoromethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(NCC(C)C)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CF)[C@@H](O)[C@H]1O GIDVNFOFWFJSTB-QYVSTXNMSA-N 0.000 claims description 3
- DETMIFBOBYBZCW-IDTAVKCVSA-N (2r,3r,4s,5s)-2-[2-chloro-6-(oxan-4-ylamino)purin-9-yl]-5-(fluoromethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CF)O[C@H]1N1C2=NC(Cl)=NC(NC3CCOCC3)=C2N=C1 DETMIFBOBYBZCW-IDTAVKCVSA-N 0.000 claims description 3
- XASWWGHUXDNPFG-MPXOCVNLSA-N (2r,3r,4s,5s)-2-[2-chloro-6-(oxan-4-ylamino)purin-9-yl]-5-(trifluoromethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](C(F)(F)F)O[C@H]1N1C2=NC(Cl)=NC(NC3CCOCC3)=C2N=C1 XASWWGHUXDNPFG-MPXOCVNLSA-N 0.000 claims description 3
- BSHAKOHLHFGDAH-SDBHATRESA-N (2r,3r,4s,5s)-2-[2-chloro-6-[(1-methylsulfonylpiperidin-4-yl)amino]purin-9-yl]-5-(fluoromethyl)oxolane-3,4-diol Chemical compound C1CN(S(=O)(=O)C)CCC1NC1=NC(Cl)=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](CF)O1 BSHAKOHLHFGDAH-SDBHATRESA-N 0.000 claims description 3
- KRANQOPJUMVYFE-IDTAVKCVSA-N (2r,3r,4s,5s)-2-[6-(2,2-dimethylpropylamino)purin-9-yl]-5-(fluoromethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(NCC(C)(C)C)=NC=NC=2N1[C@@H]1O[C@H](CF)[C@@H](O)[C@H]1O KRANQOPJUMVYFE-IDTAVKCVSA-N 0.000 claims description 3
- ZLDITGRHHSURDN-XNIJJKJLSA-N (2r,3r,4s,5s)-2-[6-(4-chloro-2-fluoroanilino)purin-9-yl]-5-(fluoromethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CF)O[C@H]1N1C2=NC=NC(NC=3C(=CC(Cl)=CC=3)F)=C2N=C1 ZLDITGRHHSURDN-XNIJJKJLSA-N 0.000 claims description 3
- YAAZQLXUDNHORA-QYVSTXNMSA-N (2r,3r,4s,5s)-2-[6-(tert-butylamino)purin-9-yl]-5-(fluoromethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(NC(C)(C)C)=NC=NC=2N1[C@@H]1O[C@H](CF)[C@@H](O)[C@H]1O YAAZQLXUDNHORA-QYVSTXNMSA-N 0.000 claims description 3
- RCTSBQOHOAIMLX-XNIJJKJLSA-N (2s,3s,4r,5r)-2-(fluoromethyl)-5-[2-methyl-6-(oxan-4-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound C=12N=CN([C@H]3[C@@H]([C@H](O)[C@@H](CF)O3)O)C2=NC(C)=NC=1NC1CCOCC1 RCTSBQOHOAIMLX-XNIJJKJLSA-N 0.000 claims description 3
- LESLGDYUXNSVSS-SDBHATRESA-N (2s,3s,4r,5r)-2-(fluoromethyl)-5-[6-(oxan-4-ylamino)purin-9-yl]oxolane-3,4-diol Chemical group O[C@@H]1[C@H](O)[C@@H](CF)O[C@H]1N1C2=NC=NC(NC3CCOCC3)=C2N=C1 LESLGDYUXNSVSS-SDBHATRESA-N 0.000 claims description 3
- KDXBTIOKNAYXSP-SDBHATRESA-N (2s,3s,4r,5r)-2-(fluoromethyl)-5-[6-(thian-4-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CF)O[C@H]1N1C2=NC=NC(NC3CCSCC3)=C2N=C1 KDXBTIOKNAYXSP-SDBHATRESA-N 0.000 claims description 3
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
- 125000006615 aromatic heterocyclic group Chemical class 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 3
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 claims description 3
- JTSIJRVIHJGQHD-GAGZCXQNSA-N (2r,3r,4s,5s)-2-[6-(3-bicyclo[2.2.1]heptanylamino)purin-9-yl]-5-(1,1-difluoroethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](C(F)(F)C)O[C@H]1N1C2=NC=NC(NC3C4CCC(C4)C3)=C2N=C1 JTSIJRVIHJGQHD-GAGZCXQNSA-N 0.000 claims description 2
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
- 229910003827 NRaRb Inorganic materials 0.000 claims description 2
- 229910006069 SO3H Inorganic materials 0.000 claims description 2
- 239000002582 adenosine A1 receptor agonist Substances 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- 229940077122 Adenosine A1 receptor agonist Drugs 0.000 claims 1
- 108010060261 Adenosine A3 Receptor Proteins 0.000 claims 1
- 102000008161 Adenosine A3 Receptor Human genes 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 43
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical class CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- 238000001819 mass spectrum Methods 0.000 description 34
- 239000000543 intermediate Substances 0.000 description 32
- 239000000203 mixture Substances 0.000 description 29
- 239000002904 solvent Substances 0.000 description 26
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- 239000000377 silicon dioxide Substances 0.000 description 14
- 239000013067 intermediate product Substances 0.000 description 13
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 229910052681 coesite Inorganic materials 0.000 description 12
- 229910052906 cristobalite Inorganic materials 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
- 235000012239 silicon dioxide Nutrition 0.000 description 12
- 229910052682 stishovite Inorganic materials 0.000 description 12
- 229910052905 tridymite Inorganic materials 0.000 description 12
- 239000007787 solid Substances 0.000 description 11
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- -1 oxalic Chemical class 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 8
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 7
- 239000000556 agonist Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 235000019253 formic acid Nutrition 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 208000021070 secondary pulmonary alveolar proteinosis Diseases 0.000 description 5
- SCZNXLWKYFICFV-UHFFFAOYSA-N 1,2,3,4,5,7,8,9-octahydropyrido[1,2-b]diazepine Chemical compound C1CCCNN2CCCC=C21 SCZNXLWKYFICFV-UHFFFAOYSA-N 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- JADDQZYHOWSFJD-FLNNQWSLSA-N N-ethyl-5'-carboxamidoadenosine Chemical compound 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 4
- 239000007832 Na2SO4 Substances 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 208000028867 ischemia Diseases 0.000 description 4
- WBQFFOYISYSHLE-UHFFFAOYSA-N isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)[N]C(=O)C2=C1 WBQFFOYISYSHLE-UHFFFAOYSA-N 0.000 description 4
- KWZSCXIYGVEHOB-UHFFFAOYSA-N oxan-4-amine;hydrochloride Chemical compound [Cl-].[NH3+]C1CCOCC1 KWZSCXIYGVEHOB-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- RMFWVOLULURGJI-UHFFFAOYSA-N 2,6-dichloro-7h-purine Chemical compound ClC1=NC(Cl)=C2NC=NC2=N1 RMFWVOLULURGJI-UHFFFAOYSA-N 0.000 description 3
- ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical compound ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 3
- 108010060263 Adenosine A1 Receptor Proteins 0.000 description 3
- 102000030814 Adenosine A1 receptor Human genes 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 230000003243 anti-lipolytic effect Effects 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
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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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Genetics & Genomics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Cardiology (AREA)
- Epidemiology (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 |
|---|---|---|---|
| GBGB9723589.9A GB9723589D0 (en) | 1997-11-08 | 1997-11-08 | Chemical compounds |
| PCT/EP1998/007021 WO1999024449A2 (en) | 1997-11-08 | 1998-11-06 | Adenosine a1 receptor agonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20000275A2 true HRP20000275A2 (en) | 2000-12-31 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20000275A HRP20000275A2 (en) | 1997-11-08 | 2000-05-08 | Chemical compounds |
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| EP (2) | EP1457495A1 (de) |
| JP (1) | JP2001522857A (de) |
| KR (1) | KR20010031875A (de) |
| CN (1) | CN1285843A (de) |
| AP (1) | AP2000001801A0 (de) |
| AR (1) | AR011229A1 (de) |
| AT (1) | ATE273990T1 (de) |
| AU (1) | AU2048399A (de) |
| BR (1) | BR9813976A (de) |
| CA (1) | CA2309200A1 (de) |
| CO (1) | CO5021135A1 (de) |
| DE (1) | DE69825780T2 (de) |
| EA (1) | EA200000392A1 (de) |
| EE (1) | EE200000285A (de) |
| ES (1) | ES2222621T3 (de) |
| GB (1) | GB9723589D0 (de) |
| HR (1) | HRP20000275A2 (de) |
| HU (1) | HUP0004082A2 (de) |
| IL (1) | IL135964A0 (de) |
| IS (1) | IS5477A (de) |
| MA (1) | MA26565A1 (de) |
| NO (1) | NO20002361L (de) |
| PE (1) | PE20000013A1 (de) |
| PL (1) | PL340921A1 (de) |
| SK (1) | SK6722000A3 (de) |
| TR (1) | TR200002131T2 (de) |
| WO (1) | WO1999024449A2 (de) |
| ZA (1) | ZA9810125B (de) |
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| GB9723589D0 (en) * | 1997-11-08 | 1998-01-07 | Glaxo Group Ltd | Chemical compounds |
| GB0106867D0 (en) * | 2001-03-20 | 2001-05-09 | Glaxo Group Ltd | Process |
| US20040162422A1 (en) * | 2001-03-20 | 2004-08-19 | Adrian Hall | Chemical compounds |
| US7157440B2 (en) | 2001-07-13 | 2007-01-02 | Cv Therapeutics, Inc. | Partial and full agonists of A1 adenosine receptors |
| US7713946B2 (en) | 2002-07-11 | 2010-05-11 | Cv Therapeutics, Inc. | Partial and full agonists A1 adenosine receptors |
| US6946449B2 (en) | 2001-07-13 | 2005-09-20 | Cv Therapeutics, Inc. | Partial and full agonists of A1 adenosine receptors |
| EP1434782A2 (de) | 2001-10-01 | 2004-07-07 | University of Virginia Patent Foundation | 2-propynyladenosine-analoge mit a2a-agonistischer aktivität and diese enthaltende gemische |
| US7265111B2 (en) | 2002-06-27 | 2007-09-04 | Sanofi-Aventis Deutschland Gmbh | Adenosine analogues and their use as pharmaceutical agents |
| EP1375508A1 (de) * | 2002-06-27 | 2004-01-02 | Aventis Pharma Deutschland GmbH | N6-Substituierte Adenosin Derivate und ihre Verwendung als pharmazeutische Mittel |
| FR2842810B1 (fr) * | 2002-07-25 | 2006-01-27 | Inst Nat Sciences Appliq | Nouveaux composes gem difluores, leur procedes de preparation et leurs applications. |
| CA2495370A1 (en) * | 2002-08-15 | 2004-02-26 | Cv Therapeutics, Inc. | Partial and full agonists of a1 adenosine receptors |
| KR20050097971A (ko) | 2003-02-03 | 2005-10-10 | 씨브이 쎄러퓨틱스, 인코포레이티드 | Ａ₁아데노신 수용체의 부분 및 전 작용제 |
| TW200519106A (en) | 2003-05-02 | 2005-06-16 | Novartis Ag | Organic compounds |
| GB0401334D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
| GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
| CA2601996A1 (en) * | 2004-09-09 | 2006-03-23 | Government Of The United States Of America, Represented By The Secretary , Department Of Health And Human Services | Purine derivatives as a3 and a1 adenosine receptor agonists |
| 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 |
| EP2532679B1 (de) | 2005-10-21 | 2017-04-12 | Novartis AG | Menschliche Antikörper gegen IL13 und therapeutische Verwendungen |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| US8178509B2 (en) * | 2006-02-10 | 2012-05-15 | 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 |
| CA2664378A1 (en) | 2006-09-29 | 2008-04-03 | Novartis Ag | Pyrazolopyrimidines as pi3k lipid kinase inhibitors |
| CN101522682A (zh) | 2006-10-30 | 2009-09-02 | 诺瓦提斯公司 | 作为抗炎剂的杂环化合物 |
| 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 |
| WO2009089425A1 (en) * | 2008-01-09 | 2009-07-16 | Pgxhealth Llc | Intrathecal treatment of neuropathic pain with a2ar agonists |
| PL2231642T3 (pl) | 2008-01-11 | 2014-04-30 | Novartis Ag | Pirymidyny jako inhibitory kinazy |
| WO2010088335A1 (en) | 2009-01-29 | 2010-08-05 | Novartis Ag | Substituted benzimidazoles for the treatment of astrocytomas |
| US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
| BR112012003262A8 (pt) | 2009-08-12 | 2016-05-17 | Novartis Ag | compostos de hidrazona heterocíclica e seus usos para tratar câncer e inflamação |
| BR112012003709B1 (pt) | 2009-08-17 | 2021-05-18 | Intellikine Llc | compostos heterocíclicos e usos dos mesmos |
| KR20120089463A (ko) | 2009-08-20 | 2012-08-10 | 노파르티스 아게 | 헤테로시클릭 옥심 화합물 |
| US8637516B2 (en) | 2010-09-09 | 2014-01-28 | Irm Llc | Compounds and compositions as TRK inhibitors |
| WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| WO2012107500A1 (en) | 2011-02-10 | 2012-08-16 | 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 |
| BR112013021638A2 (pt) | 2011-02-25 | 2016-08-02 | Irm Llc | "compostos inibidores de trk, seu uso e composições que os compreendem" |
| DE102011005232A1 (de) | 2011-03-08 | 2012-09-13 | AristoCon GmbH & Co. KG | Adenosin und seine Derivate zur Verwendung in der Schmerztherapie |
| WO2013038362A1 (en) | 2011-09-15 | 2013-03-21 | Novartis Ag | 6 - substituted 3 - (quinolin- 6 - ylthio) - [1,2,4] triazolo [4, 3 -a] pyradines as tyrosine kinase |
| US9174994B2 (en) | 2011-11-23 | 2015-11-03 | Intellikine, Llc | Enhanced treatment regimens using mTor inhibitors |
| CN104245701A (zh) | 2012-04-03 | 2014-12-24 | 诺华有限公司 | 有酪氨酸激酶抑制剂的组合产品和其应用 |
| EP2968340A4 (de) | 2013-03-15 | 2016-08-10 | Intellikine Llc | Kombination von kinaseinhibitoren und verwendungen davon |
| WO2015084804A1 (en) | 2013-12-03 | 2015-06-11 | Novartis Ag | Combination of mdm2 inhibitor and braf inhibitor and their use |
| WO2016011658A1 (en) | 2014-07-25 | 2016-01-28 | Novartis Ag | Combination therapy |
| JP6526789B2 (ja) | 2014-07-31 | 2019-06-05 | ノバルティス アーゲー | 組み合わせ療法 |
| 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 |
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| US3575959A (en) * | 1969-05-13 | 1971-04-20 | Merck & Co Inc | 5'-substituted ribofuranosyl nucleosides |
| US5589467A (en) * | 1993-09-17 | 1996-12-31 | Novo Nordisk A/S | 2,5',N6-trisubstituted adenosine derivatives |
| WO1997033591A1 (en) * | 1996-03-13 | 1997-09-18 | Novo Nordisk A/S | A method of treating disorders related to cytokines in mammals |
| GB9610031D0 (en) | 1996-05-14 | 1996-07-17 | Glaxo Group Ltd | Chemical compounds |
| GB9723589D0 (en) * | 1997-11-08 | 1998-01-07 | Glaxo Group Ltd | Chemical compounds |
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1997
- 1997-11-08 GB GBGB9723589.9A patent/GB9723589D0/en not_active Ceased
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1998
- 1998-11-05 ZA ZA9810125A patent/ZA9810125B/xx unknown
- 1998-11-05 AR ARP980105590A patent/AR011229A1/es unknown
- 1998-11-05 PE PE1998001065A patent/PE20000013A1/es not_active Application Discontinuation
- 1998-11-05 CO CO98065179A patent/CO5021135A1/es unknown
- 1998-11-05 MA MA25336A patent/MA26565A1/fr unknown
- 1998-11-06 DE DE1998625780 patent/DE69825780T2/de not_active Expired - Fee Related
- 1998-11-06 AU AU20483/99A patent/AU2048399A/en not_active Abandoned
- 1998-11-06 EP EP04076482A patent/EP1457495A1/de not_active Withdrawn
- 1998-11-06 EE EEP200000285A patent/EE200000285A/xx unknown
- 1998-11-06 EP EP98965151A patent/EP1030857B1/de not_active Expired - Lifetime
- 1998-11-06 AP APAP/P/2000/001801A patent/AP2000001801A0/en unknown
- 1998-11-06 IL IL13596498A patent/IL135964A0/xx unknown
- 1998-11-06 US US09/530,573 patent/US6455510B1/en not_active Expired - Fee Related
- 1998-11-06 HU HU0004082A patent/HUP0004082A2/hu unknown
- 1998-11-06 EA EA200000392A patent/EA200000392A1/ru unknown
- 1998-11-06 CA CA002309200A patent/CA2309200A1/en not_active Abandoned
- 1998-11-06 AT AT98965151T patent/ATE273990T1/de not_active IP Right Cessation
- 1998-11-06 SK SK672-2000A patent/SK6722000A3/sk unknown
- 1998-11-06 CN CN98812979A patent/CN1285843A/zh active Pending
- 1998-11-06 ES ES98965151T patent/ES2222621T3/es not_active Expired - Lifetime
- 1998-11-06 PL PL98340921A patent/PL340921A1/xx unknown
- 1998-11-06 KR KR1020007004959A patent/KR20010031875A/ko not_active Application Discontinuation
- 1998-11-06 JP JP2000520457A patent/JP2001522857A/ja active Pending
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- 2000-05-05 NO NO20002361A patent/NO20002361L/no not_active Application Discontinuation
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Also Published As
| Publication number | Publication date |
|---|---|
| NO20002361D0 (no) | 2000-05-05 |
| CN1285843A (zh) | 2001-02-28 |
| PL340921A1 (en) | 2001-03-12 |
| TR200002131T2 (tr) | 2001-01-22 |
| ES2222621T3 (es) | 2005-02-01 |
| GB9723589D0 (en) | 1998-01-07 |
| PE20000013A1 (es) | 2000-01-21 |
| EA200000392A1 (ru) | 2000-12-25 |
| EE200000285A (et) | 2001-08-15 |
| DE69825780D1 (de) | 2004-09-23 |
| IL135964A0 (en) | 2001-05-20 |
| WO1999024449A3 (en) | 1999-08-19 |
| EP1030857A2 (de) | 2000-08-30 |
| NO20002361L (no) | 2000-07-05 |
| HUP0004082A2 (hu) | 2001-04-28 |
| CA2309200A1 (en) | 1999-05-20 |
| EP1030857B1 (de) | 2004-08-18 |
| SK6722000A3 (en) | 2001-01-18 |
| MA26565A1 (fr) | 2004-12-20 |
| ATE273990T1 (de) | 2004-09-15 |
| WO1999024449A2 (en) | 1999-05-20 |
| DE69825780T2 (de) | 2005-01-13 |
| AR011229A1 (es) | 2000-08-02 |
| AU2048399A (en) | 1999-05-31 |
| KR20010031875A (ko) | 2001-04-16 |
| AP2000001801A0 (en) | 2000-06-30 |
| BR9813976A (pt) | 2000-09-26 |
| US6455510B1 (en) | 2002-09-24 |
| JP2001522857A (ja) | 2001-11-20 |
| EP1457495A1 (de) | 2004-09-15 |
| ZA9810125B (en) | 2000-05-05 |
| CO5021135A1 (es) | 2001-03-27 |
| IS5477A (is) | 2000-05-03 |
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