CA2113547A1 - Purine derivatives - Google Patents
Purine derivativesInfo
- Publication number
- CA2113547A1 CA2113547A1 CA002113547A CA2113547A CA2113547A1 CA 2113547 A1 CA2113547 A1 CA 2113547A1 CA 002113547 A CA002113547 A CA 002113547A CA 2113547 A CA2113547 A CA 2113547A CA 2113547 A1 CA2113547 A1 CA 2113547A1
- Authority
- CA
- Canada
- Prior art keywords
- adenosine
- chloro
- propyl
- phenoxy
- compound
- 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.)
- Abandoned
Links
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 title description 2
- 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 76
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 7
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
- 239000001257 hydrogen Substances 0.000 claims abstract description 5
- 150000002367 halogens Chemical group 0.000 claims abstract description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 4
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims abstract description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 3
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 3
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract 3
- 229910052760 oxygen Inorganic materials 0.000 claims abstract 3
- 239000001301 oxygen Substances 0.000 claims abstract 3
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 claims abstract 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 55
- -1 2-chloro-N-[(R)-methyl-1-phenoxy-2-butyl]adenosine Chemical compound 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 239000003937 drug carrier Substances 0.000 claims description 10
- 239000003085 diluting agent Substances 0.000 claims description 5
- 208000031225 myocardial ischemia Diseases 0.000 claims description 4
- BKAVPHSMICBLIH-SSFGXONLSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[2-methoxy-6-[[(2r)-1-phenoxypropan-2-yl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound C([C@@H](C)NC=1N=C(N=C2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC2=1)OC)OC1=CC=CC=C1 BKAVPHSMICBLIH-SSFGXONLSA-N 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- ZTOOLSQNKCUHGH-BTBIENRZSA-N (2r,3r,4s,5r)-2-[2-amino-6-(1-phenoxypropan-2-ylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound N=1C(N)=NC=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C=1NC(C)COC1=CC=CC=C1 ZTOOLSQNKCUHGH-BTBIENRZSA-N 0.000 claims description 2
- WTLMQCJUZXGGDW-LSCFUAHRSA-N (2r,3r,4s,5r)-2-[2-chloro-6-(2-phenoxyethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(Cl)=NC(NCCOC=3C=CC=CC=3)=C2N=C1 WTLMQCJUZXGGDW-LSCFUAHRSA-N 0.000 claims description 2
- HSQBVHNDXIRFRF-SCFUHWHPSA-N (2r,3r,4s,5r)-2-[2-chloro-6-(2-phenylmethoxyethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(Cl)=NC(NCCOCC=3C=CC=CC=3)=C2N=C1 HSQBVHNDXIRFRF-SCFUHWHPSA-N 0.000 claims description 2
- LRMPVYGAYJKNJT-UVCRECLJSA-N (2r,3r,4s,5r)-2-[2-chloro-6-(4-phenylbutan-2-ylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound N=1C(Cl)=NC=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C=1NC(C)CCC1=CC=CC=C1 LRMPVYGAYJKNJT-UVCRECLJSA-N 0.000 claims description 2
- DAQLSGVLPPXMSX-LSCFUAHRSA-N (2r,3r,4s,5r)-2-[2-chloro-6-[(2-methoxyphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound COC1=CC=CC=C1CNC1=NC(Cl)=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 DAQLSGVLPPXMSX-LSCFUAHRSA-N 0.000 claims description 2
- DRBXUXWCZWRRNQ-WVFLMPAWSA-N (2r,3r,4s,5r)-2-[2-chloro-6-[[(1r,2r)-2-phenoxycyclopentyl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(Cl)=NC(N[C@H]3[C@@H](CCC3)OC=3C=CC=CC=3)=C2N=C1 DRBXUXWCZWRRNQ-WVFLMPAWSA-N 0.000 claims description 2
- DMKMOVNGUCMISX-DPHITLOKSA-N (2r,3r,4s,5r)-2-[2-chloro-6-[[(2r)-1-phenylsulfanylpropan-2-yl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C([C@@H](C)NC=1C=2N=CN(C=2N=C(Cl)N=1)[C@H]1[C@@H]([C@H](O)[C@@H](CO)O1)O)SC1=CC=CC=C1 DMKMOVNGUCMISX-DPHITLOKSA-N 0.000 claims description 2
- SOMISWWETBLUIQ-SEYPNCJNSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[2-methyl-6-[[(2r)-1-phenoxypropan-2-yl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound C([C@@H](C)NC=1C=2N=CN(C=2N=C(C)N=1)[C@H]1[C@@H]([C@H](O)[C@@H](CO)O1)O)OC1=CC=CC=C1 SOMISWWETBLUIQ-SEYPNCJNSA-N 0.000 claims description 2
- KUHMYSFRSOXBKJ-QYVSTXNMSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[6-(2-methoxyethylamino)purin-9-yl]oxolane-3,4-diol Chemical compound C1=NC=2C(NCCOC)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O KUHMYSFRSOXBKJ-QYVSTXNMSA-N 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 2
- GYWXTRVEUURNEW-TVDBPQCTSA-N (2R,3R,4S,5R)-2-[6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9-purinyl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N[C@@H]3[C@H](CCC3)O)=C2N=C1 GYWXTRVEUURNEW-TVDBPQCTSA-N 0.000 claims 1
- CRNZBMDVSSPQJI-BTBIENRZSA-N (2r,3r,4s,5r)-2-[2-chloro-6-(1-phenoxypropan-2-ylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound N=1C(Cl)=NC=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C=1NC(C)COC1=CC=CC=C1 CRNZBMDVSSPQJI-BTBIENRZSA-N 0.000 claims 1
- DRBXUXWCZWRRNQ-COXIEXTQSA-N (2r,3r,4s,5r)-2-[2-chloro-6-[[(1r,2s)-2-phenoxycyclopentyl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(Cl)=NC(N[C@H]3[C@H](CCC3)OC=3C=CC=CC=3)=C2N=C1 DRBXUXWCZWRRNQ-COXIEXTQSA-N 0.000 claims 1
- SWJQVQVCRVONSK-UMGDAMFDSA-N (2r,3r,4s,5r)-2-[2-chloro-6-[[(2r)-1-(2-propan-2-yloxyphenoxy)propan-2-yl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound CC(C)OC1=CC=CC=C1OC[C@@H](C)NC1=NC(Cl)=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 SWJQVQVCRVONSK-UMGDAMFDSA-N 0.000 claims 1
- QKBSBXJLOGEBQC-IUAXGMLLSA-N (2r,3r,4s,5r)-2-[2-chloro-6-[[(2r)-1-(4-fluorophenoxy)propan-2-yl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C([C@@H](C)NC=1C=2N=CN(C=2N=C(Cl)N=1)[C@H]1[C@@H]([C@H](O)[C@@H](CO)O1)O)OC1=CC=C(F)C=C1 QKBSBXJLOGEBQC-IUAXGMLLSA-N 0.000 claims 1
- PELFWPSHULTRNK-VQPBACBFSA-N (2r,3r,4s,5r)-2-[2-chloro-6-[[(2r)-1-hydroxypropan-2-yl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N[C@@H](CO)C)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O PELFWPSHULTRNK-VQPBACBFSA-N 0.000 claims 1
- CRNZBMDVSSPQJI-DPHITLOKSA-N (2r,3r,4s,5r)-2-[2-chloro-6-[[(2r)-1-phenoxypropan-2-yl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C([C@@H](C)NC=1C=2N=CN(C=2N=C(Cl)N=1)[C@H]1[C@@H]([C@H](O)[C@@H](CO)O1)O)OC1=CC=CC=C1 CRNZBMDVSSPQJI-DPHITLOKSA-N 0.000 claims 1
- XQOFIPOEIPAISE-DPHITLOKSA-N (2r,3r,4s,5r)-2-[2-chloro-6-[[(2r)-1-phenylpropan-2-yl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C([C@@H](C)NC=1C=2N=CN(C=2N=C(Cl)N=1)[C@H]1[C@@H]([C@H](O)[C@@H](CO)O1)O)C1=CC=CC=C1 XQOFIPOEIPAISE-DPHITLOKSA-N 0.000 claims 1
- XVAJVUPAVAOMPL-DPHITLOKSA-N (2r,3r,4s,5r)-2-[2-chloro-6-[[(2r)-2-phenoxypropyl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C([C@@H](C)OC=1C=CC=CC=1)NC(C=1N=C2)=NC(Cl)=NC=1N2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O XVAJVUPAVAOMPL-DPHITLOKSA-N 0.000 claims 1
- CRNZBMDVSSPQJI-QHOAOGIMSA-N (2r,3r,4s,5r)-2-[2-chloro-6-[[(2s)-1-phenoxypropan-2-yl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C([C@H](C)NC=1C=2N=CN(C=2N=C(Cl)N=1)[C@H]1[C@@H]([C@H](O)[C@@H](CO)O1)O)OC1=CC=CC=C1 CRNZBMDVSSPQJI-QHOAOGIMSA-N 0.000 claims 1
- NDLJHYLDKYUDMJ-DPHITLOKSA-N (2r,3r,4s,5r)-2-[2-fluoro-6-[[(2r)-1-phenoxypropan-2-yl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C([C@@H](C)NC=1C=2N=CN(C=2N=C(F)N=1)[C@H]1[C@@H]([C@H](O)[C@@H](CO)O1)O)OC1=CC=CC=C1 NDLJHYLDKYUDMJ-DPHITLOKSA-N 0.000 claims 1
- GYWXTRVEUURNEW-QDYOZFCWSA-N (2r,3r,4s,5r)-2-[6-[[(1r,2r)-2-hydroxycyclopentyl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N[C@H]3[C@@H](CCC3)O)=C2N=C1 GYWXTRVEUURNEW-QDYOZFCWSA-N 0.000 claims 1
- DCJGMPFPBKAUIA-DPHITLOKSA-N (2r,3r,4s,5r)-2-[6-[[(2r)-1-(benzenesulfonyl)propan-2-yl]amino]-2-chloropurin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C([C@@H](C)NC=1C=2N=CN(C=2N=C(Cl)N=1)[C@H]1[C@@H]([C@H](O)[C@@H](CO)O1)O)S(=O)(=O)C1=CC=CC=C1 DCJGMPFPBKAUIA-DPHITLOKSA-N 0.000 claims 1
- GBYFCKIMUHSNDH-UVCRECLJSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[6-(1-phenoxypropan-2-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound N=1C=NC=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C=1NC(C)COC1=CC=CC=C1 GBYFCKIMUHSNDH-UVCRECLJSA-N 0.000 claims 1
- OOEMZCZWZXHBKW-SCFUHWHPSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[6-[(2-methylphenyl)methylamino]purin-9-yl]oxolane-3,4-diol Chemical compound CC1=CC=CC=C1CNC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 OOEMZCZWZXHBKW-SCFUHWHPSA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 239000005864 Sulphur Substances 0.000 claims 1
- 229940116592 central nervous system diagnostic radiopharmaceuticals Drugs 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- 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 118
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 59
- 229960005305 adenosine Drugs 0.000 description 59
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 46
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 25
- 239000000203 mixture Substances 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 229910001868 water Inorganic materials 0.000 description 18
- 239000006260 foam Substances 0.000 description 17
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 16
- 238000003818 flash chromatography Methods 0.000 description 16
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 229940093499 ethyl acetate Drugs 0.000 description 14
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- 239000000047 product Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 208000002193 Pain Diseases 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 238000010511 deprotection reaction Methods 0.000 description 10
- 235000002639 sodium chloride Nutrition 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 206010015037 epilepsy Diseases 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 206010008120 Cerebral ischaemia Diseases 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 208000028867 ischemia Diseases 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- GADIKQPUNWAMEB-UHFFFAOYSA-N methyl 4-ethyl-6,7-dimethoxy-9H-pyrido[5,4-b]indole-3-carboxylate Chemical compound N1C2=CC(OC)=C(OC)C=C2C2=C1C=NC(C(=O)OC)=C2CC GADIKQPUNWAMEB-UHFFFAOYSA-N 0.000 description 6
- 241000282414 Homo sapiens Species 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
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- 230000008020 evaporation Effects 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
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- 206010010904 Convulsion Diseases 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 230000036772 blood pressure Effects 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- PUXJKAXYRIPWJM-UHFFFAOYSA-N 2,9-dichloropurine Chemical compound ClN1C2=NC(=NC=C2N=C1)Cl PUXJKAXYRIPWJM-UHFFFAOYSA-N 0.000 description 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 3
- 108050000203 Adenosine receptors Proteins 0.000 description 3
- 102000009346 Adenosine receptors Human genes 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000002566 clonic effect Effects 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000002858 neurotransmitter agent Substances 0.000 description 3
- 239000002777 nucleoside Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
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- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- QKIWHADSHFVRFN-UHFFFAOYSA-N n-propan-2-ylbenzenesulfonamide Chemical compound CC(C)NS(=O)(=O)C1=CC=CC=C1 QKIWHADSHFVRFN-UHFFFAOYSA-N 0.000 description 1
- 229940105631 nembutal Drugs 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000003961 neuronal insult Effects 0.000 description 1
- 150000005338 nitrobenzoic acids Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000001272 nitrous oxide Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 208000027753 pain disease Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 102000008344 purinergic nucleotide receptor activity proteins Human genes 0.000 description 1
- 108040002778 purinergic nucleotide receptor activity proteins Proteins 0.000 description 1
- 239000003422 purinergic receptor affecting agent Substances 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
-
- 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
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK92626A DK62692D0 (cs) | 1992-05-14 | 1992-05-14 | |
| DK0626/92 | 1992-05-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2113547A1 true CA2113547A1 (en) | 1993-11-25 |
Family
ID=8095717
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002113547A Abandoned CA2113547A1 (en) | 1992-05-14 | 1993-05-12 | Purine derivatives |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0603348A1 (cs) |
| JP (1) | JPH06508855A (cs) |
| AU (1) | AU671995B2 (cs) |
| CA (1) | CA2113547A1 (cs) |
| DK (1) | DK62692D0 (cs) |
| FI (1) | FI940167A7 (cs) |
| IL (1) | IL105673A (cs) |
| NZ (1) | NZ252110A (cs) |
| WO (1) | WO1993023418A1 (cs) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK155292D0 (da) * | 1992-12-23 | 1992-12-23 | Novo Nordisk As | Kemiske forbindelser, deres fremstilling og anvendelse |
| US5589467A (en) * | 1993-09-17 | 1996-12-31 | Novo Nordisk A/S | 2,5',N6-trisubstituted adenosine derivatives |
| CN1147815A (zh) * | 1994-05-10 | 1997-04-16 | 山道士有限公司 | 腺苷衍生物 |
| EP0704215A3 (en) * | 1994-06-02 | 1998-04-01 | Takeda Chemical Industries, Ltd. | Inhibitor of vascular permeability enhancer |
| GB9421133D0 (en) * | 1994-10-20 | 1994-12-07 | Glaxo Group Ltd | Medicaments |
| US6110902A (en) * | 1997-06-23 | 2000-08-29 | Moehler; Hanns | Method for the inhibition of neuronal activity leading to a focal epileptic seizure by local delivery of adenosine |
| CO5180581A1 (es) * | 1999-09-30 | 2002-07-30 | Pfizer Prod Inc | Compuestos para el tratamiento de la isquemia ciones farmaceuticas que los contienen para el tratamiento de la isquemia |
| US6803457B1 (en) | 1999-09-30 | 2004-10-12 | Pfizer, Inc. | Compounds for the treatment of ischemia |
| AU2001260076A1 (en) * | 2000-05-15 | 2001-11-26 | Novo-Nordisk A/S | Compounds for treating disorders where a decreased level of plasma ffa is desired |
| US7414036B2 (en) | 2002-01-25 | 2008-08-19 | Muscagen Limited | Compounds useful as A3 adenosine receptor agonists |
| US20100048501A1 (en) | 2006-03-21 | 2010-02-25 | Heinrich-Heine-Universitat Dusseldorf | Phosphorylated A2A Receptor Agonists |
| CZ2009298A3 (cs) * | 2009-05-14 | 2010-11-24 | Univerzita Palackého v Olomouci | Substituované 6-benzylaminopurin ribosidy, jejich použití a farmaceutický prípravek tyto slouceniny obsahující |
| EP2523669B1 (en) | 2010-01-11 | 2016-12-07 | Inotek Pharmaceuticals Corporation | Combination, kit and method of reducing intraocular pressure |
| KR20130029050A (ko) | 2010-03-26 | 2013-03-21 | 이노텍 파마슈티컬스 코포레이션 | Ｎ6-시클로펜틸아데노신(ｃｐａ), ｃｐａ 유도체 또는 이의 전구 약물을 사용하여 사람의 안압을 감소시키는 방법 |
| CN102822188A (zh) * | 2010-03-26 | 2012-12-12 | 伊诺泰克制药公司 | 腺苷化合物及其用途 |
| ES2637332T3 (es) | 2012-01-26 | 2017-10-11 | Inotek Pharmaceuticals Corporation | Polimorfos anhidros de nitrato de (2R,3S,4R,5R)-5-(6-(ciclopentilamino)-9H-purin-9-il)-3,4-dihidroxitetrahidrofuran-2-il)}metilo y procedimientos de preparación del mismo |
| JP2016513706A (ja) | 2013-03-15 | 2016-05-16 | イノテック ファーマシューティカルズ コーポレイション | 点眼用製剤 |
| JP2015172077A (ja) * | 2015-06-24 | 2015-10-01 | 中国医学科学院葯物研究所 | Ｎ６−置換アデノシン誘導体とｎ６−置換アデニン誘導体の鎮静、催眠、抗うつ、抗痙攣、抗てんかん、抗パーキンソン病と認知証予防・治療の用途 |
| GB2582361A (en) * | 2019-03-21 | 2020-09-23 | Univ Warwick | Adenosine receptor agonists |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1670077C3 (de) * | 1966-05-07 | 1975-04-24 | Boehringer Mannheim Gmbh, 6800 Mannheim | Adenosin-Derivate und Verfahren zu ihrer Herstellung |
| NL128629C (cs) * | 1966-05-07 | |||
| NL6717061A (cs) * | 1966-12-21 | 1968-06-24 | ||
| DE2052596A1 (de) * | 1970-10-27 | 1972-05-04 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neuartige Verwendung von N(6)-substituierten Adenosin-Derivaten |
| DE3406533A1 (de) * | 1984-02-23 | 1985-08-29 | Boehringer Mannheim Gmbh, 6800 Mannheim | Verwendung von adenosin-derivaten als antiallergica und arzneimittel, die diese enthalten |
| JPH0655756B2 (ja) * | 1984-04-18 | 1994-07-27 | ネルソン・リサ−チ・アンド・デベロツプメント・カンパニ− | 心臓血管拡張薬としてのｎ−６置換アデノシン誘導体 |
| US4791103A (en) * | 1985-02-08 | 1988-12-13 | Warner-Lambert Company | 2,N6 -disubstituted adenosines, derivatives and methods of use |
| JPH0696534B2 (ja) * | 1986-04-25 | 1994-11-30 | ヘキストジヤパン株式会社 | 抗痴呆剤 |
| GB8729994D0 (en) * | 1987-12-23 | 1988-02-03 | Glaxo Group Ltd | Chemical compounds |
| HUT61567A (en) * | 1990-12-07 | 1993-01-28 | Sandoz Ag | Process for producing new pharmaceutical compositions comprising 2'-o-alkyladenosine derivatives and for producing 6-cyclohexyl-2'-o-methyladenosinehydrate |
| DK62592D0 (cs) * | 1992-05-14 | 1992-05-14 | Novo Nordisk As |
-
1992
- 1992-05-14 DK DK92626A patent/DK62692D0/da unknown
-
1993
- 1993-05-11 IL IL105673A patent/IL105673A/en not_active IP Right Cessation
- 1993-05-12 AU AU40612/93A patent/AU671995B2/en not_active Ceased
- 1993-05-12 FI FI940167A patent/FI940167A7/fi not_active Application Discontinuation
- 1993-05-12 WO PCT/DK1993/000158 patent/WO1993023418A1/en not_active Application Discontinuation
- 1993-05-12 CA CA002113547A patent/CA2113547A1/en not_active Abandoned
- 1993-05-12 JP JP5519787A patent/JPH06508855A/ja active Pending
- 1993-05-12 EP EP93909822A patent/EP0603348A1/en not_active Withdrawn
- 1993-05-12 NZ NZ252110A patent/NZ252110A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPH06508855A (ja) | 1994-10-06 |
| IL105673A (en) | 1998-01-04 |
| DK62692D0 (cs) | 1992-05-14 |
| EP0603348A1 (en) | 1994-06-29 |
| NZ252110A (en) | 1996-07-26 |
| FI940167L (fi) | 1994-03-03 |
| IL105673A0 (en) | 1993-09-22 |
| AU671995B2 (en) | 1996-09-19 |
| WO1993023418A1 (en) | 1993-11-25 |
| FI940167A7 (fi) | 1994-03-03 |
| AU4061293A (en) | 1993-12-13 |
| FI940167A0 (fi) | 1994-01-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued | ||
| FZDE | Discontinued |
Effective date: 19990512 |