SK6712000A3 - Adenosine derivatives, method for their preparation, pharmaceutical composition containing the same and their use - Google Patents

Adenosine derivatives, method for their preparation, pharmaceutical composition containing the same and their use Download PDF

Info

Publication number: SK6712000A3
Authority: SK; Slovakia
Prior art keywords: group; alkyl; adenosine; alk; trifluoromethyladenosine
Prior art date: 1997-11-08

Application number

SK671-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Philip Charles Box

Brian David Judkins

Andrew Michael Kenneth Pennell

Original Assignee

Glaxo Group Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-11-08

Filing date

1998-11-06

Publication date

2001-01-18

1998-11-06 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

2001-01-18 Publication of SK6712000A3 publication Critical patent/SK6712000A3/sk

Links

150000003835 adenosine derivatives Chemical class 0.000 title claims description 31
238000000034 method Methods 0.000 title claims description 20
239000008194 pharmaceutical composition Substances 0.000 title claims description 9
238000002360 preparation method Methods 0.000 title claims description 4
150000001875 compounds Chemical class 0.000 claims abstract description 149
125000000217 alkyl group Chemical group 0.000 claims abstract description 43
150000003839 salts Chemical class 0.000 claims abstract description 27
229910052736 halogen Inorganic materials 0.000 claims abstract description 15
150000002367 halogens Chemical class 0.000 claims abstract description 15
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 14
239000012453 solvate Substances 0.000 claims abstract description 13
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
239000001257 hydrogen Substances 0.000 claims abstract description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 8
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 4
-1 tetrahydro-pyran-4-yl Chemical group 0.000 claims description 43
229910052757 nitrogen Inorganic materials 0.000 claims description 33
125000001424 substituent group Chemical group 0.000 claims description 23
125000000623 heterocyclic group Chemical group 0.000 claims description 18
208000002193 Pain Diseases 0.000 claims description 16
125000005842 heteroatom Chemical group 0.000 claims description 16
238000006243 chemical reaction Methods 0.000 claims description 15
125000006239 protecting group Chemical group 0.000 claims description 13
125000000753 cycloalkyl group Chemical group 0.000 claims description 12
229910052717 sulfur Inorganic materials 0.000 claims description 12
125000004433 nitrogen atom Chemical group N* 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
235000021588 free fatty acids Nutrition 0.000 claims description 9
208000031225 myocardial ischemia Diseases 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
125000004434 sulfur atom Chemical group 0.000 claims description 8
125000001931 aliphatic group Chemical group 0.000 claims description 7
239000000460 chlorine Substances 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
230000000694 effects Effects 0.000 claims description 7
125000005843 halogen group Chemical group 0.000 claims description 7
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 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
208000018262 Peripheral vascular disease Diseases 0.000 claims description 6
229910052731 fluorine Inorganic materials 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 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 claims description 4
125000002619 bicyclic group Chemical group 0.000 claims description 4
208000015114 central nervous system disease Diseases 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
XCFCLFQNWLHHMC-XNIJJKJLSA-N (2r,3r,4s,5r)-2-[6-(3-fluoroanilino)purin-9-yl]-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC(F)(F)F)O[C@H]1N1C2=NC=NC(NC=3C=C(F)C=CC=3)=C2N=C1 XCFCLFQNWLHHMC-XNIJJKJLSA-N 0.000 claims description 3
HNOAXRSDWGOHLH-SDBHATRESA-N (2r,3r,4s,5r)-2-[6-(thian-4-ylamino)purin-9-yl]-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC(F)(F)F)O[C@H]1N1C2=NC=NC(NC3CCSCC3)=C2N=C1 HNOAXRSDWGOHLH-SDBHATRESA-N 0.000 claims description 3
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
208000008784 apnea Diseases 0.000 claims description 3
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000001153 fluoro group Chemical group F* 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
125000004430 oxygen atom Chemical group O* 0.000 claims description 3
208000019116 sleep disease Diseases 0.000 claims description 3
LVXIOWOTQOYMCH-KQYNXXCUSA-N (2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-2-(hydroxymethyl)-4-(trifluoromethoxy)oxolan-3-ol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1OC(F)(F)F LVXIOWOTQOYMCH-KQYNXXCUSA-N 0.000 claims description 2
UYSGCRYMJJMGIM-KQYNXXCUSA-N (2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COC(F)(F)F)[C@@H](O)[C@H]1O UYSGCRYMJJMGIM-KQYNXXCUSA-N 0.000 claims description 2
FQPOPTXHKUUAGF-LSCFUAHRSA-N (2r,3r,4s,5r)-2-[2-chloro-6-(oxan-4-ylamino)purin-9-yl]-5-(3-fluoropropoxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COCCCF)O[C@H]1N1C2=NC(Cl)=NC(NC3CCOCC3)=C2N=C1 FQPOPTXHKUUAGF-LSCFUAHRSA-N 0.000 claims description 2
HIDBVKBAWSBKMO-XNIJJKJLSA-N (2r,3r,4s,5r)-2-[6-(3,4-difluoroanilino)purin-9-yl]-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC(F)(F)F)O[C@H]1N1C2=NC=NC(NC=3C=C(F)C(F)=CC=3)=C2N=C1 HIDBVKBAWSBKMO-XNIJJKJLSA-N 0.000 claims description 2
ZVSMNRNJGJGCHG-SDBHATRESA-N (2r,3r,4s,5r)-2-[6-(oxan-4-ylamino)purin-9-yl]-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC(F)(F)F)O[C@H]1N1C2=NC=NC(NC3CCOCC3)=C2N=C1 ZVSMNRNJGJGCHG-SDBHATRESA-N 0.000 claims description 2
239000002126 C01EB10 - Adenosine Substances 0.000 claims description 2
208000006011 Stroke Diseases 0.000 claims description 2
229960005305 adenosine Drugs 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
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
201000010099 disease Diseases 0.000 claims description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
125000003709 fluoroalkyl group Chemical group 0.000 claims description 2
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
QSPPRYLTQFCUCH-UHFFFAOYSA-N n-methylethanesulfonamide Chemical compound CCS(=O)(=O)NC QSPPRYLTQFCUCH-UHFFFAOYSA-N 0.000 claims description 2
125000006413 ring segment Chemical group 0.000 claims description 2
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 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
KUUUKOXSYSLSLQ-ZRURSIFKSA-N (2r,3r,4s,5r)-2-[6-(2,3-dihydroxypropylamino)purin-9-yl]-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(NCC(O)CO)=NC=NC=2N1[C@@H]1O[C@H](COC(F)(F)F)[C@@H](O)[C@H]1O KUUUKOXSYSLSLQ-ZRURSIFKSA-N 0.000 claims 1
JZHIJAIIKORZJM-QYVSTXNMSA-N (2r,3r,4s,5r)-2-[6-(tert-butylamino)purin-9-yl]-5-(trifluoromethoxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(NC(C)(C)C)=NC=NC=2N1[C@@H]1O[C@H](COC(F)(F)F)[C@@H](O)[C@H]1O JZHIJAIIKORZJM-QYVSTXNMSA-N 0.000 claims 1
VTGVYJFENKSVFQ-SCFUHWHPSA-N (2r,3s,4r,5r)-2-(3-fluoropropoxymethyl)-5-[6-(oxan-4-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COCCCF)O[C@H]1N1C2=NC=NC(NC3CCOCC3)=C2N=C1 VTGVYJFENKSVFQ-SCFUHWHPSA-N 0.000 claims 1
102000008161 Adenosine A3 Receptor Human genes 0.000 claims 1
108010060261 Adenosine A3 Receptor Proteins 0.000 claims 1
125000004429 atom Chemical group 0.000 claims 1
230000002093 peripheral effect Effects 0.000 claims 1
239000000556 agonist Substances 0.000 abstract description 8
108010060263 Adenosine A1 Receptor Proteins 0.000 abstract description 4
102000030814 Adenosine A1 receptor Human genes 0.000 abstract description 4
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 114
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 83
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 79
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 62
239000000243 solution Substances 0.000 description 50
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
239000000543 intermediate Substances 0.000 description 43
239000000203 mixture Substances 0.000 description 43
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 38
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical class CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
239000002904 solvent Substances 0.000 description 36
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 30
235000019441 ethanol Nutrition 0.000 description 30
238000001819 mass spectrum Methods 0.000 description 30
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
239000000741 silica gel Substances 0.000 description 25
229910002027 silica gel Inorganic materials 0.000 description 25
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 23
238000003818 flash chromatography Methods 0.000 description 23
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
239000000377 silicon dioxide Substances 0.000 description 18
239000003921 oil Substances 0.000 description 17
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
239000006260 foam Substances 0.000 description 16
229910021529 ammonia Inorganic materials 0.000 description 15
239000011734 sodium Substances 0.000 description 15
239000007787 solid Substances 0.000 description 14
ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical group ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 13
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 13
239000012299 nitrogen atmosphere Substances 0.000 description 13
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
239000000284 extract Substances 0.000 description 12
239000002253 acid Substances 0.000 description 11
238000010992 reflux Methods 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
239000003795 chemical substances by application Substances 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
125000006345 2,2,2-trifluoroethoxymethyl group Chemical group [H]C([H])(*)OC([H])([H])C(F)(F)F 0.000 description 9
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
239000003480 eluent Substances 0.000 description 9
238000010828 elution Methods 0.000 description 9
150000002148 esters Chemical class 0.000 description 9
238000004128 high performance liquid chromatography Methods 0.000 description 9
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
229910004298 SiO 2 Inorganic materials 0.000 description 7
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
239000012267 brine Substances 0.000 description 7
239000012312 sodium hydride Substances 0.000 description 7
229910000104 sodium hydride Inorganic materials 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 6
125000004545 purin-9-yl group Chemical group N1=CN=C2N(C=NC2=C1)* 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 6
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 5
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
230000003243 anti-lipolytic effect Effects 0.000 description 5
238000007796 conventional method Methods 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 5
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
208000021070 secondary pulmonary alveolar proteinosis Diseases 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
239000000725 suspension Substances 0.000 description 5
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 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
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
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CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical class N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 4
235000019253 formic acid Nutrition 0.000 description 4
239000010410 layer Substances 0.000 description 4
AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
201000002859 sleep apnea Diseases 0.000 description 4
VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 3
230000001154 acute effect Effects 0.000 description 3
125000002947 alkylene group Chemical group 0.000 description 3
125000001118 alkylidene group Chemical group 0.000 description 3
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
210000003169 central nervous system Anatomy 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
238000011065 in-situ storage Methods 0.000 description 3
208000028867 ischemia Diseases 0.000 description 3
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
229940098779 methanesulfonic acid Drugs 0.000 description 3
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Classifications

- 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
- C07H19/167—Purine radicals with ribosyl as the saccharide radical
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Molecular Biology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Genetics & Genomics (AREA)
Biotechnology (AREA)
Biochemistry (AREA)
Cardiology (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Heart & Thoracic Surgery (AREA)
Neurosurgery (AREA)
Diabetes (AREA)
Obesity (AREA)
Hematology (AREA)
Pain & Pain Management (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

SK671-2000A 1997-11-08 1998-11-06 Adenosine derivatives, method for their preparation, pharmaceutical composition containing the same and their use SK6712000A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9723566.7A GB9723566D0 (en)	1997-11-08	1997-11-08	Chemical compounds
PCT/EP1998/007022 WO1999024450A2 (fr)	1997-11-08	1998-11-06	Composes chimiques

Publications (1)

Publication Number	Publication Date
SK6712000A3 true SK6712000A3 (en)	2001-01-18

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ID=10821742

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK671-2000A SK6712000A3 (en)	1997-11-08	1998-11-06	Adenosine derivatives, method for their preparation, pharmaceutical composition containing the same and their use

Country Status (24)

Country	Link
US (1)	US6407076B1 (fr)
EP (1)	EP1027363B1 (fr)
JP (1)	JP2001522858A (fr)
KR (1)	KR20010031883A (fr)
CN (1)	CN1285842A (fr)
AP (1)	AP2000001803A0 (fr)
AT (1)	ATE242259T1 (fr)
AU (1)	AU1232799A (fr)
BR (1)	BR9813973A (fr)
CA (1)	CA2309199A1 (fr)
DE (1)	DE69815378T2 (fr)
EA (1)	EA200000393A1 (fr)
EE (1)	EE200000284A (fr)
ES (1)	ES2201552T3 (fr)
GB (1)	GB9723566D0 (fr)
HR (1)	HRP20000276A2 (fr)
HU (1)	HUP0004106A2 (fr)
IL (1)	IL135965A0 (fr)
IS (1)	IS5478A (fr)
NO (1)	NO20002360L (fr)
PL (1)	PL341091A1 (fr)
SK (1)	SK6712000A3 (fr)
TR (1)	TR200002157T2 (fr)
WO (1)	WO1999024450A2 (fr)

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US6258793B1 (en) *	1999-12-03	2001-07-10	Cv Therapeutics, Inc.	N6 heterocyclic 5′ modified adenosine derivatives
US6294522B1 (en) *	1999-12-03	2001-09-25	Cv Therapeutics, Inc.	N6 heterocyclic 8-modified adenosine derivatives
WO2001040799A2 (fr) *	1999-12-03	2001-06-07	Cv Therapeutics, Inc.	Procede d'identification d'agonistes partiels des recepteurs de l'adenosine a1 et utilisation de ces agonistes pour le traitement des arythmies
US6605597B1 (en) *	1999-12-03	2003-08-12	Cv Therapeutics, Inc.	Partial or full A1agonists-N-6 heterocyclic 5′-thio substituted adenosine derivatives
GB9930077D0 (en) *	1999-12-20	2000-02-09	Glaxo Group Ltd	Medicaments
CA2414623A1 (fr) *	2000-08-01	2002-02-07	University Of Virginia Patent Foundation	Utilisation d'agonistes, d'antagonistes et d'amplificateurs allosteriques selectifs du recepteur d'adenosine a1 afin de manipuler l'angiogenese
GB2372742A (en) *	2001-03-03	2002-09-04	Univ Leiden	C2,5'-Disubstituted and N6,C2,5'-trisubstituted adenosine derivatives and their different uses
GB2372741A (en) *	2001-03-03	2002-09-04	Univ Leiden	C2,8-Disubstituted adenosine derivatives and their different uses
GB0106867D0 (en) *	2001-03-20	2001-05-09	Glaxo Group Ltd	Process
US6995148B2 (en) *	2001-04-05	2006-02-07	University Of Pittsburgh	Adenosine cyclic ketals: novel adenosine analogues for pharmacotherapy
US7713946B2 (en)	2002-07-11	2010-05-11	Cv Therapeutics, Inc.	Partial and full agonists A1 adenosine receptors
US7157440B2 (en)	2001-07-13	2007-01-02	Cv Therapeutics, Inc.	Partial and full agonists of A1 adenosine receptors
US6946449B2 (en)	2001-07-13	2005-09-20	Cv Therapeutics, Inc.	Partial and full agonists of A1 adenosine receptors
NZ556354A (en) *	2001-10-01	2008-10-31	Univ Virginia	2-Propynyl adenosine analogs having A2A agonist activity and compositions thereof
EP1496911B1 (fr) *	2002-04-10	2007-12-19	University Of Virginia Patent Foundation	Utilisation d'une combinaison comprenant un agoniste du recepteur d'adenosine a2a et un agent anti-pathogene dans le traitement de maladies inflammatoires
US7265111B2 (en) *	2002-06-27	2007-09-04	Sanofi-Aventis Deutschland Gmbh	Adenosine analogues and their use as pharmaceutical agents
EP1375508A1 (fr) *	2002-06-27	2004-01-02	Aventis Pharma Deutschland GmbH	Dérivés de l'adénosine N6-substitués et leur utilisation comme médicament
NZ541651A (en)	2003-02-03	2009-01-31	Cv Therapeutics Inc	Partial and full agonists of A1 adenosine receptors
AR044519A1 (es)	2003-05-02	2005-09-14	Novartis Ag	Derivados de piridin-tiazol amina y de pirimidin-tiazol amina
GB0401334D0 (en)	2004-01-21	2004-02-25	Novartis Ag	Organic compounds
US20050277615A1 (en) *	2004-05-17	2005-12-15	Can-Fite Biopharma Ltd.	Pharmaceutical compositions having anti-inflammatory activity
GB0411056D0 (en)	2004-05-18	2004-06-23	Novartis Ag	Organic compounds
US7576069B2 (en) *	2004-08-02	2009-08-18	University Of Virginia Patent Foundation	2-polycyclic propynyl adenosine analogs having A2A agonist activity
AU2005267706B2 (en) *	2004-08-02	2011-12-08	University Of Virginia Patent Foundation	2-propynyl adenosine analogs with modified 5'-ribose groups 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
WO2007045477A2 (fr)	2005-10-21	2007-04-26	Novartis Ag	Molecules organiques
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1997
- 1997-11-08 GB GBGB9723566.7A patent/GB9723566D0/en not_active Ceased
1998
- 1998-11-06 ES ES98955538T patent/ES2201552T3/es not_active Expired - Lifetime
- 1998-11-06 DE DE69815378T patent/DE69815378T2/de not_active Expired - Fee Related
- 1998-11-06 BR BR9813973-8A patent/BR9813973A/pt not_active Application Discontinuation
- 1998-11-06 AU AU12327/99A patent/AU1232799A/en not_active Abandoned
- 1998-11-06 AT AT98955538T patent/ATE242259T1/de not_active IP Right Cessation
- 1998-11-06 SK SK671-2000A patent/SK6712000A3/sk unknown
- 1998-11-06 HR HR20000276A patent/HRP20000276A2/hr not_active Application Discontinuation
- 1998-11-06 AP APAP/P/2000/001803A patent/AP2000001803A0/en unknown
- 1998-11-06 KR KR1020007004974A patent/KR20010031883A/ko not_active Withdrawn
- 1998-11-06 HU HU0004106A patent/HUP0004106A2/hu unknown
- 1998-11-06 US US09/530,574 patent/US6407076B1/en not_active Expired - Fee Related
- 1998-11-06 TR TR2000/02157T patent/TR200002157T2/xx unknown
- 1998-11-06 CA CA002309199A patent/CA2309199A1/fr not_active Abandoned
- 1998-11-06 EA EA200000393A patent/EA200000393A1/ru unknown
- 1998-11-06 PL PL98341091A patent/PL341091A1/xx unknown
- 1998-11-06 WO PCT/EP1998/007022 patent/WO1999024450A2/fr not_active Ceased
- 1998-11-06 JP JP2000520458A patent/JP2001522858A/ja active Pending
- 1998-11-06 EP EP98955538A patent/EP1027363B1/fr not_active Expired - Lifetime
- 1998-11-06 IL IL13596598A patent/IL135965A0/xx unknown
- 1998-11-06 CN CN98812978A patent/CN1285842A/zh active Pending
- 1998-11-06 EE EEP200000284A patent/EE200000284A/xx unknown
2000
- 2000-05-03 IS IS5478A patent/IS5478A/is unknown
- 2000-05-05 NO NO20002360A patent/NO20002360L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
CN1285842A (zh)	2001-02-28
WO1999024450A3 (fr)	1999-08-19
AU1232799A (en)	1999-05-31
NO20002360D0 (no)	2000-05-05
HUP0004106A2 (hu)	2001-04-28
CA2309199A1 (fr)	1999-05-20
PL341091A1 (en)	2001-03-26
EP1027363B1 (fr)	2003-06-04
EE200000284A (et)	2001-08-15
IL135965A0 (en)	2001-05-20
DE69815378D1 (de)	2003-07-10
US6407076B1 (en)	2002-06-18
BR9813973A (pt)	2000-09-26
IS5478A (is)	2000-05-03
AP2000001803A0 (en)	2000-06-30
HRP20000276A2 (en)	2000-12-31
JP2001522858A (ja)	2001-11-20
ATE242259T1 (de)	2003-06-15
ES2201552T3 (es)	2004-03-16
NO20002360L (no)	2000-07-05
TR200002157T2 (tr)	2000-11-21
WO1999024450A2 (fr)	1999-05-20
GB9723566D0 (en)	1998-01-07
KR20010031883A (ko)	2001-04-16
EA200000393A1 (ru)	2000-12-25
DE69815378T2 (de)	2004-04-29
EP1027363A2 (fr)	2000-08-16

Publication	Publication Date	Title
SK6712000A3 (en)	2001-01-18	Adenosine derivatives, method for their preparation, pharmaceutical composition containing the same and their use
SK6722000A3 (en)	2001-01-18	Adenosine derivatives, method for their preparation, pharmaceutical composition containing the same and their use
SK6702000A3 (en)	2001-01-18	Adenosine derivatives, method for their preparation, pharmaceutical composition containing the same and their use
US20040162422A1 (en)	2004-08-19	Chemical compounds
EP0901499B1 (fr)	2002-04-10	Derives d'adenosine
CZ20001666A3 (cs)	2000-10-11	Deriváty adenosinu
WO2004026890A1 (fr)	2004-04-01	Composes acetyleniques
MXPA00004428A (en)	2001-05-17	Adensine a1 receptor agonists
CZ20001665A3 (cs)	2000-10-11	Deriváty adenosinu
CZ20001667A3 (cs)	2000-10-11	Deriváty adenosinu
MXPA00004429A (en)	2001-05-17	Adenosine a1 receptor agonists
MXPA00004431A (en)	2001-05-17	Adenosine a1 receptor agonists