DE69323643T2 - Hydrazoadenosinen - Google Patents
HydrazoadenosinenInfo
- Publication number
- DE69323643T2 DE69323643T2 DE69323643T DE69323643T DE69323643T2 DE 69323643 T2 DE69323643 T2 DE 69323643T2 DE 69323643 T DE69323643 T DE 69323643T DE 69323643 T DE69323643 T DE 69323643T DE 69323643 T2 DE69323643 T2 DE 69323643T2
- Authority
- DE
- Germany
- Prior art keywords
- amino
- branched
- linear
- ribofuranosyl
- purine
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims description 27
- -1 C3-C7-cycloalkyl Chemical group 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Chemical group OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 claims description 20
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Chemical group OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 claims description 20
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical group OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims description 19
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 15
- 229960005305 adenosine Drugs 0.000 claims description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 8
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical group O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 claims description 8
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Chemical group OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 claims description 8
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Chemical group OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 239000008103 glucose Substances 0.000 claims description 5
- 108020003175 receptors Proteins 0.000 claims description 5
- 102000005962 receptors Human genes 0.000 claims description 5
- 230000024883 vasodilation Effects 0.000 claims description 5
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 4
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical group OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 claims description 4
- 108050000203 Adenosine receptors Proteins 0.000 claims description 4
- 102000009346 Adenosine receptors Human genes 0.000 claims description 4
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical group OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims description 4
- 229930091371 Fructose Chemical group 0.000 claims description 4
- 239000005715 Fructose Chemical group 0.000 claims description 4
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical group OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 4
- 239000005864 Sulphur Substances 0.000 claims description 4
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical group OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 4
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 210000004351 coronary vessel Anatomy 0.000 claims description 4
- 229930182830 galactose Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 229910052698 phosphorus Inorganic materials 0.000 claims description 4
- 239000011574 phosphorus Substances 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 230000000638 stimulation Effects 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 230000010339 dilation Effects 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims 3
- 150000002772 monosaccharides Chemical group 0.000 claims 3
- 230000000916 dilatatory effect Effects 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 64
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 50
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 21
- 206010003677 Atrioventricular block second degree Diseases 0.000 description 17
- 238000004458 analytical method Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 239000000556 agonist Substances 0.000 description 6
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 125000004076 pyridyl group Chemical group 0.000 description 4
- BAYFDGKAUSOEIS-UUOKFMHZSA-N (2r,3r,4s,5r)-2-(6-amino-2-hydrazinylpurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical class C12=NC(NN)=NC(N)=C2N=CN1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O BAYFDGKAUSOEIS-UUOKFMHZSA-N 0.000 description 3
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 150000003838 adenosines Chemical class 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 101150007969 ADORA1 gene Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000001077 hypotensive effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000003379 purinergic P1 receptor agonist Substances 0.000 description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BIXYYZIIJIXVFW-UUOKFMHZSA-N (2R,3R,4S,5R)-2-(6-amino-2-chloro-9-purinyl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O BIXYYZIIJIXVFW-UUOKFMHZSA-N 0.000 description 1
- VHMUQIWMOXQFBP-LSCFUAHRSA-N (2r,3r,4s,5r)-2-[6-amino-2-(2-cyclohexylethoxy)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1OCCC1CCCCC1 VHMUQIWMOXQFBP-LSCFUAHRSA-N 0.000 description 1
- DBFQHWKOYLSNEU-LSCFUAHRSA-N (2r,3r,4s,5r)-2-[6-amino-2-(2-phenylethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1NCCC1=CC=CC=C1 DBFQHWKOYLSNEU-LSCFUAHRSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 108010041368 Adenosine A2 Receptors Proteins 0.000 description 1
- 102000000506 Adenosine A2 Receptors Human genes 0.000 description 1
- 229940122614 Adenosine receptor agonist Drugs 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- DUVUQYFYWUDDPW-LSCFUAHRSA-N C1=CC(C)=CC=C1C=NNC1=NC(N)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 Chemical compound C1=CC(C)=CC=C1C=NNC1=NC(N)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 DUVUQYFYWUDDPW-LSCFUAHRSA-N 0.000 description 1
- UKEASMXMANFUQZ-LSCFUAHRSA-N C1=CC(OC)=CC=C1C=NNC1=NC(N)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 Chemical compound C1=CC(OC)=CC=C1C=NNC1=NC(N)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 UKEASMXMANFUQZ-LSCFUAHRSA-N 0.000 description 1
- BUYDXKBPOOYHPY-WVSUBDOOSA-N C1=NC=2C(N)=NC(NN=CC=3C4=CC=CC=C4C=CC=3)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O Chemical compound C1=NC=2C(N)=NC(NN=CC=3C4=CC=CC=C4C=CC=3)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O BUYDXKBPOOYHPY-WVSUBDOOSA-N 0.000 description 1
- DOQXNVBLKUFUIH-LSCFUAHRSA-N C=1C=C(F)C=CC=1C(C)=NNC(N=C12)=NC(N)=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O Chemical compound C=1C=C(F)C=CC=1C(C)=NNC(N=C12)=NC(N)=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O DOQXNVBLKUFUIH-LSCFUAHRSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- CFRIPBAEDXQEHL-XNIJJKJLSA-N N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1NN=CC1=CC=C(Cl)C=C1 Chemical compound N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1NN=CC1=CC=C(Cl)C=C1 CFRIPBAEDXQEHL-XNIJJKJLSA-N 0.000 description 1
- STRJSXCSNWOTCR-XNIJJKJLSA-N N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1NN=CC1=CC=C(F)C=C1 Chemical compound N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1NN=CC1=CC=C(F)C=C1 STRJSXCSNWOTCR-XNIJJKJLSA-N 0.000 description 1
- YQWVYBPTXMCTKB-SDBHATRESA-N N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1NN=CC1=CC=CC=N1 Chemical compound N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1NN=CC1=CC=CC=N1 YQWVYBPTXMCTKB-SDBHATRESA-N 0.000 description 1
- CEBYJLIWMBILKB-IDTAVKCVSA-N N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1NN=CC1=CC=CS1 Chemical compound N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1NN=CC1=CC=CS1 CEBYJLIWMBILKB-IDTAVKCVSA-N 0.000 description 1
- 229910004878 Na2S2O4 Inorganic materials 0.000 description 1
- 108010080192 Purinergic Receptors Proteins 0.000 description 1
- 102000000033 Purinergic Receptors Human genes 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- OIRDTQYFTABQOQ-UHTZMRCNSA-N Vidarabine Chemical class C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O OIRDTQYFTABQOQ-UHTZMRCNSA-N 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 210000001992 atrioventricular node Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 208000006218 bradycardia Diseases 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- 230000000059 bradycardiac effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 230000005792 cardiovascular activity Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000003218 coronary vasodilator agent Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000010829 isocratic elution Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000005246 left atrium Anatomy 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004115 mitral valve Anatomy 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 101150104259 napC gene Proteins 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000000306 qrs interval Methods 0.000 description 1
- 150000003254 radicals Chemical group 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 210000005241 right ventricle Anatomy 0.000 description 1
- XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 201000002932 second-degree atrioventricular block Diseases 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
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
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
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)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (11)
1. Verbindung
der Formel
in der R&sub3; und R&sub4; gleich oder verschieden sind und
Wasserstoff, lineares oder verzweigtes C&sub1;-C&sub1;&sub2;-
Alkyl, C&sub3;-C&sub7;-Cycloalkyl, C&sub6;-C&sub1;&sub0;-Aryl, das
unsubstituiert oder mit mindestens einem aus Halogen,
linearem oder verzweigtem C&sub1;-C&sub6;-Alkyl, linearem
oder verzweigtem C&sub1;-C&sub6;-Alkoxy, Nitro und Amino
ausgewähltem Substituenten substituiert ist, mit
mindestens einem linearen oder verzweigten C&sub1;-C&sub6;-
Alkyl oder Phenyl substituiertes Amino, C&sub2;-C&sub1;&sub0;-
Aralkyl, C&sub4;-C&sub8;-Heteroaryl, wobei das Heteroatom
Stickstoff, Phosphor, Schwefel oder Sauerstoff
ist, bedeuten, und R ein aus der aus Glucose,
Fructose, Ribose, 2-Desoxyribose, Mannose,
Galactose, Xylose und Arabinose bestehenden Gruppe
ausgewählter Monosaccharidrest ist, wobei die
Derivate 9-α-D-Arabinofuranosyl-2-hydrazinadenin und 2-
Hydrazin-6-amino-9-β-D-ribofuranosyl-9H-purin
ausgenommen sind.
2. Verbindung nach Anspruch 1, in der R&sub4; Wasserstoff
oder Methyl ist.
3. Verbindung nach Anspruch 2, in der R&sub3;
C&sub3;-C&sub7;-Cycloalkyl ist.
4. Verbindung nach Anspruch 2, in der R&sub3;
unsubstituiertes C&sub6;-C&sub1;&sub0;-Aryl ist.
5. Verbindung nach Anspruch 4, in der R&sub3; mit
mindestens einem linearen oder verzweigten C&sub1;-C&sub6;-Alkyl
substituiertes C&sub6;-C&sub1;&sub0;-Aryl ist.
6. Verbindung nach Anspruch 2, in der R&sub3; mit
mindestens einem aus Halogen, linearem oder verzweigtem
C&sub1;-C&sub6;-Alkoxy, Nitro und Amino ausgewählten
Substituenten substituiertes C&sub6;-C&sub1;&sub0;-Aryl ist.
7. Verbindung nach Anspruch 2, in der R&sub3;
C&sub4;-C&sub8;-Heteroaryl bedeutet, in dem das Heteroatom Stickstoff
oder Schwefel ist.
8. Verbindung nach einem der Ansprüche 1 bis 7 zur
Verwendung in einem Therapieverfahren zur
selektiven Stimulation des A&sub2;-Adenosinrezeptors.
9. Verbindung nach einem der Ansprüche 1 bis 7 zur
Verwendung in einem Therapieverfahren zur
Erweiterung der Herzkranzgefäße bei einem Säuger.
10. Verwendung einer nachstehend charakterisierten
Verbindung zur Herstellung eines Medikaments für
die therapeutisch selektive Stimulation des A&sub2;-
Adenosinrezeptors
in der R&sub3; und R&sub4; gleich oder verschieden sind und
Wasserstoff, lineares oder verzweigtes C&sub1;-C&sub1;&sub2;-
Alkyl, C&sub3;-C&sub7;-Cycloalkyl, C&sub6;-C&sub1;&sub0;-Aryl, das
unsubstituiert oder mit mindestens einem aus Halogen,
linearem oder verzweigtem C&sub1;-C&sub6;-Alkyl, linearem
oder verzweigtem C&sub1;-C&sub6;-Alkoxy, Nitro und Amino
ausgewähltem Substituenten substituiert ist, mit
mindestens einem linearen oder verzweigten C&sub1;-C&sub6;-
Alkyl oder Phenyl substituiertes Amino, C&sub2;-C&sub1;&sub0;-
Aralkyl, C&sub4;-C&sub8;-Heteroaryl, wobei das Heteroatom
Stickstoff, Phosphor, Schwefel oder Sauerstoff
ist, bedeuten, und R ein aus der aus Glucose,
Fructose, Ribose, 2-Desoxyribose, Mannose,
Galactose, Xylose und Arabinose bestehenden Gruppe
ausgewählter Monosaccharidrest ist.
11. Verwendung einer nachstehend charakterisierten
Verbindung zur Herstellung eines Medikaments für
die therapeutische Erweiterung der Herzkranzgefäße
bei einem Säuger, der einer solchen
Gefäßerweiterung bedarf
in der R&sub3; und R&sub4; gleich oder verschieden sind und
Wasserstoff, lineares oder verzweigtes C&sub1;-C&sub1;&sub2;-
Alkyl, C&sub3;-C&sub7;-Cycloalkyl, C&sub6;-C&sub1;&sub0;-Aryl, das
unsubstituiert oder mit mindestens einem aus Halogen,
linearem oder verzweigtem C&sub1;-C&sub6;-Alkyl, linearem
oder verzweigtem C&sub1;-C&sub6;-Alkoxy, Nitro und Amino
ausgewähltem Substituenten substituiert ist, mit
mindestens einem linearen oder verzweigten C&sub1;-C&sub6;-
Alkyl oder Phenyl substituiertes Amino, C&sub2;-C&sub1;&sub0;-
Aralkyl, C&sub4;-C&sub8;-Heteroaryl, wobei das Heteroatom
Stickstoff, Phosphor, Schwefel oder Sauerstoff
ist, bedeuten, und R ein aus der aus Glucose,
Fructose, Ribose, 2-Desoxyribose, Mannose,
Galactose, Xylose und Arabinose bestehenden Gruppe
ausgewählter Monosaccharidrest ist.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/873,440 US5278150A (en) | 1992-04-24 | 1992-04-24 | 2-hydrazoadenosines and their utility for the treatmeat of vascular conditions |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69323643D1 DE69323643D1 (de) | 1999-04-08 |
| DE69323643T2 true DE69323643T2 (de) | 1999-07-29 |
Family
ID=25361637
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69323643T Expired - Lifetime DE69323643T2 (de) | 1992-04-24 | 1993-04-21 | Hydrazoadenosinen |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US5278150A (de) |
| EP (1) | EP0567094B1 (de) |
| JP (1) | JP3395912B2 (de) |
| CA (1) | CA2093502C (de) |
| DE (1) | DE69323643T2 (de) |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5477857A (en) * | 1993-09-10 | 1995-12-26 | Discovery Therapeutics, Inc. | Diagnostic uses of hydrazinoadenosines |
| US5877180A (en) * | 1994-07-11 | 1999-03-02 | University Of Virginia Patent Foundation | Method for treating inflammatory diseases with A2a adenosine receptor agonists |
| US6514949B1 (en) | 1994-07-11 | 2003-02-04 | University Of Virginia Patent Foundation | Method compositions for treating the inflammatory response |
| US6448235B1 (en) | 1994-07-11 | 2002-09-10 | University Of Virginia Patent Foundation | Method for treating restenosis with A2A adenosine receptor agonists |
| US5817641A (en) * | 1994-07-21 | 1998-10-06 | Thomas Jefferson University | Treatment of enterotoxigenic diarrhea with 2-substituted adenosine derivatives |
| WO1998057651A1 (en) | 1997-06-18 | 1998-12-23 | Discovery Therapeutics, Inc. | Compositions and methods for preventing restenosis following revascularization procedures |
| US5972903A (en) * | 1997-10-07 | 1999-10-26 | Regents Of The University Of California Corporation | Method for promoting angiogenesis using heparin and adenosine |
| WO1999017784A1 (en) | 1997-10-07 | 1999-04-15 | Regents Of The University Of California Corporation | Treating occlusive peripheral vascular disease and coronary disease with combinations of heparin and an adenoside a2 agonist, or with adenosine |
| US6117878A (en) * | 1998-02-24 | 2000-09-12 | University Of Virginia | 8-phenyl- or 8-cycloalkyl xanthine antagonists of A2B human adenosine receptors |
| US7378400B2 (en) * | 1999-02-01 | 2008-05-27 | University Of Virginia Patent Foundation | Method to reduce an inflammatory response from arthritis |
| US6232297B1 (en) | 1999-02-01 | 2001-05-15 | University Of Virginia Patent Foundation | Methods and compositions for treating inflammatory response |
| US7427606B2 (en) * | 1999-02-01 | 2008-09-23 | University Of Virginia Patent Foundation | Method to reduce inflammatory response in transplanted tissue |
| US6322771B1 (en) | 1999-06-18 | 2001-11-27 | University Of Virginia Patent Foundation | Induction of pharmacological stress with adenosine receptor agonists |
| DE10041478A1 (de) * | 2000-08-24 | 2002-03-14 | Sanol Arznei Schwarz Gmbh | Neue pharmazeutische Zusammensetzung |
| US6670334B2 (en) | 2001-01-05 | 2003-12-30 | University Of Virginia Patent Foundation | Method and compositions for treating the inflammatory response |
| 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 |
| US20030027793A1 (en) * | 2001-05-08 | 2003-02-06 | Thomas Lauterback | Transdermal treatment of parkinson's disease |
| US20030026830A1 (en) * | 2001-05-08 | 2003-02-06 | Thomas Lauterback | Transdermal therapeutic system for parkinson's disease inducing high plasma levels of rotigotine |
| CA2460911C (en) * | 2001-10-01 | 2011-08-30 | University Of Virginia Patent Foundation | 2-propynyl adenosine analogs having a2a agonist activity and compositions thereof |
| DE60315164T2 (de) * | 2002-08-15 | 2008-04-30 | CV Therapeutics, Inc., Palo Alto | Partielle und volle agonisten von a1-adenosinrezeptoren |
| US20050033044A1 (en) * | 2003-05-19 | 2005-02-10 | Bristol-Myers Squibb Pharma Company | Methods for preparing 2-alkynyladenosine derivatives |
| US7423144B2 (en) | 2004-05-26 | 2008-09-09 | Inotek Pharmaceuticals Corporation | Purine Derivatives as adenosine A1 receptor agonists and methods of use thereof |
| US7442687B2 (en) * | 2004-08-02 | 2008-10-28 | The University Of Virginia Patent Foundation | 2-polycyclic propynyl adenosine analogs having A2A agonist activity |
| US7605143B2 (en) * | 2004-08-02 | 2009-10-20 | University Of Virginia Patent Foundation | 2-propynyl adenosine analogs with modified 5′-ribose groups having A2A agonist activity |
| WO2006028618A1 (en) * | 2004-08-02 | 2006-03-16 | University Of Virginia Patent Foundation | 2-polycyclic propynyl adenosine analogs with modified 5'-ribose groups having a2a agonist activity |
| EP1802316B1 (de) * | 2004-09-20 | 2011-11-02 | Inotek Pharmaceuticals Corporation | Purin-derivate und anwendungsverfahren |
| JP2008527003A (ja) * | 2005-01-12 | 2008-07-24 | キング・ファーマシューティカルズ・リサーチ・アンド・デベロプメント・インコーポレイティッド | 喘息又は気管支痙攣の既往歴を有する患者における心筋機能不全を検出する方法 |
| EP2218442A1 (de) | 2005-11-09 | 2010-08-18 | CombinatoRx, Inc. | Verfahren, Zusammensetzungen und Kits zur Behandlung von ophthalmologischen Erkrankungen |
| AU2006320578B2 (en) * | 2005-11-30 | 2013-01-31 | Inotek Pharmaceuticals Corporation | Purine derivatives and methods of use thereof |
| WO2007092936A2 (en) * | 2006-02-08 | 2007-08-16 | University Of Virginia Patent Foundation | Method to treat gastric lesions |
| WO2007120972A2 (en) | 2006-02-10 | 2007-10-25 | University Of Virginia Patent Foundation | Method to treat sickle cell disease |
| US8188063B2 (en) * | 2006-06-19 | 2012-05-29 | University Of Virginia Patent Foundation | Use of adenosine A2A modulators to treat spinal cord injury |
| JP2008285478A (ja) * | 2007-04-16 | 2008-11-27 | Santen Pharmaceut Co Ltd | アデノシンａ２ａ受容体アゴニストを有効成分として含有する緑内障治療剤 |
| US7558455B2 (en) * | 2007-06-29 | 2009-07-07 | Ethicon Endo-Surgery, Inc | Receiver aperture broadening for scanned beam imaging |
| 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 |
| WO2009114533A2 (en) | 2008-03-10 | 2009-09-17 | Cornell University | Modulation of blood brain barrier permeability |
| US20110044904A1 (en) * | 2008-02-29 | 2011-02-24 | Moorman Allan R | Crystal forms of 2--adenosine |
| CN102711771B (zh) | 2010-01-11 | 2016-05-18 | 伊诺泰克制药公司 | 降低眼压的组合、试剂盒和方法 |
| CN102933593A (zh) | 2010-03-26 | 2013-02-13 | 伊诺泰克制药公司 | 使用n6-环戊基腺苷（cpa）、cpa衍生物或其前药降低人眼内压的方法 |
| EA027109B1 (ru) | 2012-01-26 | 2017-06-30 | Инотек Фармасьютикалс Корпорейшн | Безводные полиморфы [(2r,3s,4r,5r)-5-(6-(циклопентиламино)-9h-пурин-9-ил)-3,4-дигидрокситетрагидрофуран-2-ил]метилнитрата и способы их получения |
| MX2015013234A (es) | 2013-03-15 | 2016-04-15 | Inotek Pharmaceuticals Corp | Formulaciones oftalmicas. |
| CN114096551B (zh) * | 2019-06-21 | 2024-08-13 | 中国人民解放军军事科学院军事医学研究院 | 具有a2a腺苷受体激动活性的2-苄叉肼基腺苷类化合物 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4224438A (en) * | 1970-07-14 | 1980-09-23 | Boehringer Mannheim Gmbh | Adenosine-5'-carboxylic acid amides |
| DE2034785A1 (de) * | 1970-07-14 | 1972-01-20 | Boehnnger Mannheim GmbH, 6800 Mann heim Waldhof | Adenosin 5 carbonsäurederivate |
| JPS4935635B1 (de) * | 1970-12-28 | 1974-09-25 | ||
| US4140851A (en) * | 1977-11-21 | 1979-02-20 | The United States Of America As Represented By The Department Of Health, Education And Welfare | Synthesis and antitumor activity of 2,4,5-trisubstituted-pyrrolo2,3-d]-pyrimidine nucleosides |
| JP2619710B2 (ja) * | 1989-02-27 | 1997-06-11 | 日本製紙 株式会社 | ２′，３′−ジデオキシプリンヌクレオシド類の製造方法 |
| US5155098A (en) * | 1989-06-09 | 1992-10-13 | Hoechst-Roussel Pharmaceuticals Inc. | N-heteroaryl-purin-6-amines, and pharmaceutical compositions and methods employing them |
-
1992
- 1992-04-24 US US07/873,440 patent/US5278150A/en not_active Expired - Lifetime
-
1993
- 1993-04-06 CA CA002093502A patent/CA2093502C/en not_active Expired - Lifetime
- 1993-04-21 JP JP11666393A patent/JP3395912B2/ja not_active Expired - Lifetime
- 1993-04-21 DE DE69323643T patent/DE69323643T2/de not_active Expired - Lifetime
- 1993-04-21 EP EP93106460A patent/EP0567094B1/de not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH06128281A (ja) | 1994-05-10 |
| CA2093502C (en) | 2004-06-22 |
| EP0567094A2 (de) | 1993-10-27 |
| EP0567094A3 (de) | 1994-03-30 |
| CA2093502A1 (en) | 1993-10-25 |
| US5278150A (en) | 1994-01-11 |
| DE69323643D1 (de) | 1999-04-08 |
| JP3395912B2 (ja) | 2003-04-14 |
| EP0567094B1 (de) | 1999-03-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69323643T2 (de) | Hydrazoadenosinen | |
| CA2264155C (en) | N6 heterocyclic substituted adenosine derivatives | |
| DE69306298T2 (de) | Anticonvulsive Fructopyranose zyklische Sulfate und Sulfite | |
| DE69109631T2 (de) | 2-Substituierte Adenosinderivate und pharmazeutische Zusammensetzungen zur Verwendung gegen Infektionskrankheiten. | |
| EP0254268B2 (de) | Fluorierte Nucleoside, ihre Herstellung und ihre pharmazeutische Verwendung gegen AIDS | |
| DE69132389T2 (de) | 2-aralkoxy und 2-alkoxy-adenosinderivate als koronarvasodilatoren und antihypertensive stoffe | |
| Furuta et al. | Photochemical properties of new photolabile cAMP derivatives in a physiological saline solution | |
| DE69012840T2 (de) | Adenosin-Derivate, die eine Aktivität gegen Bluthochdruck haben. | |
| DD284679A5 (de) | Verfahren zur herstellung von adenosin 5'-carboamidderivate | |
| DE69833797T2 (de) | Substituierte 2-benzylamino-2-phenyl-acetamid-verbindungen | |
| DE68923913T2 (de) | Neplanocinderivate. | |
| EP0277611B1 (de) | Alkylsubstituierte N-Benzopyranyllactame, Verfahren zu ihrer Herstellung, ihre Verwendung sowie pharmazeutische Präparate auf Basis dieser Verbindungen | |
| DE3940021C2 (de) | Adenosin-Derivate, deren Herstellung und Verwendung | |
| DE60117131T2 (de) | Pyridazinyl phenyl hydrazone nützlich gegen kongestives herzversagen | |
| DE69714358T2 (de) | 9,10-disubstituierte campothecinderivate mit antitumoraktivität | |
| DE3425404C2 (de) | Verwendung von Germaniumsesquisulfiden als Antineoplastikum | |
| DE69413333T2 (de) | Benzospiroalken-Derivate, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen | |
| DE4422685A1 (de) | Ortho-amino-substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament | |
| DE69907161T2 (de) | 5' deoxycytidin-derivative | |
| CH643830A5 (de) | Bis-moranolin-derivate. | |
| SU1468424A3 (ru) | Способ получени производных гидантоина | |
| DE3877658T2 (de) | 4'-deshydroxyepipodophyllotoxinglucoside und ihre verwendung. | |
| EP0054873B1 (de) | 3,4-Disubstituierte 1,2,5-Oxadiazol-2-oxide, Verfahren zu ihrer Herstellung und sie enthaltende pharmazeutische Zubereitungen | |
| DE68910165T2 (de) | Antihypertensive Sulfonanilide. | |
| DE68924416T2 (de) | Carboximidamid-Derivate. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8327 | Change in the person/name/address of the patent owner |
Owner name: ADERIS PHARMACEUTICALS, INC. (N.D.GES.D. STAATES D |