NO318788B1 - Adenosinderivater, samt fremgangsmate for fremstilling og anvendels derav og farmasoytisk preparat. - Google Patents
Adenosinderivater, samt fremgangsmate for fremstilling og anvendels derav og farmasoytisk preparat. Download PDFInfo
- Publication number
- NO318788B1 NO318788B1 NO20006520A NO20006520A NO318788B1 NO 318788 B1 NO318788 B1 NO 318788B1 NO 20006520 A NO20006520 A NO 20006520A NO 20006520 A NO20006520 A NO 20006520A NO 318788 B1 NO318788 B1 NO 318788B1
- Authority
- NO
- Norway
- Prior art keywords
- purin
- diol
- tetrahydrofuran
- chloro
- tetrahydro
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 21
- 238000002360 preparation method Methods 0.000 title claims description 14
- 230000008569 process Effects 0.000 title claims description 9
- 150000003835 adenosine derivatives Chemical class 0.000 title description 4
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 194
- 239000000203 mixture Substances 0.000 claims description 172
- SSYDTHANSGMJTP-UHFFFAOYSA-N oxolane-3,4-diol Chemical compound OC1COCC1O SSYDTHANSGMJTP-UHFFFAOYSA-N 0.000 claims description 42
- 229910052757 nitrogen Inorganic materials 0.000 claims description 36
- 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- -1 N-phenylsulfonylamino Chemical group 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 125000006239 protecting group Chemical group 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 208000002193 Pain Diseases 0.000 claims description 12
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims description 11
- 239000012453 solvate Substances 0.000 claims description 10
- 239000000556 agonist Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 6
- 208000031225 myocardial ischemia Diseases 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- PQDWQMXDAMFTPA-WFXMFSGNSA-N (2r,3r,4s,5s)-2-[2-chloro-6-(2-chloroanilino)purin-9-yl]-5-(3-ethyl-1,2-oxazol-5-yl)oxolane-3,4-diol Chemical compound O1N=C(CC)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC(Cl)=NC(NC=4C(=CC=CC=4)Cl)=C3N=C2)O1 PQDWQMXDAMFTPA-WFXMFSGNSA-N 0.000 claims description 2
- KHQDLRSLCRTLGO-LUXYFRNMSA-N (2r,3r,4s,5s)-2-[2-chloro-6-(2-fluoroanilino)purin-9-yl]-5-[3-(hydroxymethyl)-1,2-oxazol-5-yl]oxolane-3,4-diol Chemical compound O1N=C(CO)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC(Cl)=NC(NC=4C(=CC=CC=4)F)=C3N=C2)O1 KHQDLRSLCRTLGO-LUXYFRNMSA-N 0.000 claims description 2
- AYJNASZSTCYQRC-LUXYFRNMSA-N (2r,3r,4s,5s)-2-[2-chloro-6-(4-chloro-2-fluoroanilino)purin-9-yl]-5-[3-(hydroxymethyl)-1,2-oxazol-5-yl]oxolane-3,4-diol Chemical compound O1N=C(CO)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC(Cl)=NC(NC=4C(=CC(Cl)=CC=4)F)=C3N=C2)O1 AYJNASZSTCYQRC-LUXYFRNMSA-N 0.000 claims description 2
- DQOMTAOIXFYYMS-WFXMFSGNSA-N (2r,3r,4s,5s)-2-[6-(2-chloroanilino)purin-9-yl]-5-[3-(hydroxymethyl)-1,2-oxazol-5-yl]oxolane-3,4-diol Chemical compound O1N=C(CO)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC=4C(=CC=CC=4)Cl)=C3N=C2)O1 DQOMTAOIXFYYMS-WFXMFSGNSA-N 0.000 claims description 2
- IMAKIVMJONPAAR-LDNFRZNASA-N (2r,3r,4s,5s)-2-[6-(4-chloro-2-fluoroanilino)purin-9-yl]-5-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)oxolane-3,4-diol Chemical compound N=1OC([C@H]2O[C@H]([C@H](O)[C@@H]2O)N2C3=NC=NC(NC=4C(=CC(Cl)=CC=4)F)=C3N=C2)=NC=1C1CC1 IMAKIVMJONPAAR-LDNFRZNASA-N 0.000 claims description 2
- YBVMAERCFUQREI-WFXMFSGNSA-N (2s,3s,4r,5r)-2-(3-ethyl-1,2-oxazol-5-yl)-5-[2-methoxy-6-(oxan-4-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O1N=C(CC)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC(OC)=NC(NC4CCOCC4)=C3N=C2)O1 YBVMAERCFUQREI-WFXMFSGNSA-N 0.000 claims description 2
- AWCHZPJYODMTAD-TVKQPGBESA-N (2s,3s,4r,5r)-2-(3-tert-butyl-1,2-oxazol-5-yl)-5-[2-chloro-6-(2-chloro-4-fluoroanilino)purin-9-yl]oxolane-3,4-diol Chemical compound O1N=C(C(C)(C)C)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC(Cl)=NC(NC=4C(=CC(F)=CC=4)Cl)=C3N=C2)O1 AWCHZPJYODMTAD-TVKQPGBESA-N 0.000 claims description 2
- DRGGNPCPVZZQLR-DZCCDHAISA-N (2s,3s,4r,5r)-2-(3-tert-butyl-1,2-oxazol-5-yl)-5-[6-[(1-propan-2-ylsulfonylpiperidin-4-yl)amino]purin-9-yl]oxolane-3,4-diol Chemical compound C1CN(S(=O)(=O)C(C)C)CCC1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](C=2ON=C(C=2)C(C)(C)C)O1 DRGGNPCPVZZQLR-DZCCDHAISA-N 0.000 claims description 2
- CSZAUOGTYXESGJ-MOROJQBDSA-N (2s,3s,4r,5r)-2-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[2-chloro-6-(4-chloro-2-fluoroanilino)purin-9-yl]oxolane-3,4-diol Chemical compound O1C(C(C)(C)C)=NN=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC(Cl)=NC(NC=4C(=CC(Cl)=CC=4)F)=C3N=C2)O1 CSZAUOGTYXESGJ-MOROJQBDSA-N 0.000 claims description 2
- ZQHDCZIERLUDFZ-MOROJQBDSA-N (2s,3s,4r,5r)-2-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[6-(oxan-4-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O1C(C(C)(C)C)=NN=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCOCC4)=C3N=C2)O1 ZQHDCZIERLUDFZ-MOROJQBDSA-N 0.000 claims description 2
- AJEOQIOYFCWGJB-MOROJQBDSA-N (2s,3s,4r,5r)-2-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[6-(piperidin-4-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O1C(C(C)(C)C)=NN=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCNCC4)=C3N=C2)O1 AJEOQIOYFCWGJB-MOROJQBDSA-N 0.000 claims description 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 2
- 150000005072 1,3,4-oxadiazoles Chemical class 0.000 claims description 2
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 230000008901 benefit Effects 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 208000015114 central nervous system disease Diseases 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- QMGJRUZGPDDSAU-PFHKOEEOSA-N ethyl 4-[[9-[(2r,3r,4s,5s)-3,4-dihydroxy-5-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]oxolan-2-yl]purin-6-yl]amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](C=2OC(=NN=2)C(F)(F)F)O1 QMGJRUZGPDDSAU-PFHKOEEOSA-N 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 150000004665 fatty acids Chemical class 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 150000002545 isoxazoles Chemical class 0.000 claims description 2
- OFDYPFPWXVDAAP-DZCCDHAISA-N propan-2-yl 4-[[9-[(2r,3r,4s,5s)-5-(3-tert-butyl-1,2-oxazol-5-yl)-3,4-dihydroxyoxolan-2-yl]purin-6-yl]amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)C)CCC1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](C=2ON=C(C=2)C(C)(C)C)O1 OFDYPFPWXVDAAP-DZCCDHAISA-N 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 230000009467 reduction Effects 0.000 claims description 2
- 201000002859 sleep apnea Diseases 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- WWTYKHQSPLCZDS-LDNFRZNASA-N (2r,3r,4s,5r)-2-[6-(2-chloro-4-fluoroanilino)purin-9-yl]-5-(3-propan-2-yl-1h-1,2,4-triazol-5-yl)oxolane-3,4-diol Chemical compound N1C(C(C)C)=NN=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC=4C(=CC(F)=CC=4)Cl)=C3N=C2)O1 WWTYKHQSPLCZDS-LDNFRZNASA-N 0.000 claims 1
- FBEVIUDXWACJHI-WFXMFSGNSA-N (2r,3r,4s,5s)-2-[6-(2-chloro-4-fluoroanilino)purin-9-yl]-5-[3-(hydroxymethyl)-1,2-oxazol-5-yl]oxolane-3,4-diol Chemical compound O1N=C(CO)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC=4C(=CC(F)=CC=4)Cl)=C3N=C2)O1 FBEVIUDXWACJHI-WFXMFSGNSA-N 0.000 claims 1
- CCLNJQZNGVEFLE-TVKQPGBESA-N (2r,3r,4s,5s)-2-[6-(2-chloroanilino)purin-9-yl]-5-(3-ethyl-1,2-oxazol-5-yl)oxolane-3,4-diol Chemical compound O1N=C(CC)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC=4C(=CC=CC=4)Cl)=C3N=C2)O1 CCLNJQZNGVEFLE-TVKQPGBESA-N 0.000 claims 1
- ITFVSCFLPGZLRD-LDNFRZNASA-N (2r,3r,4s,5s)-2-[6-(3,4-difluoroanilino)purin-9-yl]-5-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)oxolane-3,4-diol Chemical compound CC(C)C1=NOC([C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(NC=4C=C(F)C(F)=CC=4)=C3N=C2)O)=N1 ITFVSCFLPGZLRD-LDNFRZNASA-N 0.000 claims 1
- JAAYQDHSCICGLX-XKGFGPFHSA-N (2r,3r,4s,5s)-2-[6-(4-chloro-2-fluoroanilino)purin-9-yl]-5-(3-cyclopropyl-1,2-oxazol-5-yl)oxolane-3,4-diol Chemical compound N=1OC([C@H]2O[C@H]([C@H](O)[C@@H]2O)N2C3=NC=NC(NC=4C(=CC(Cl)=CC=4)F)=C3N=C2)=CC=1C1CC1 JAAYQDHSCICGLX-XKGFGPFHSA-N 0.000 claims 1
- LVHVPCWNNCWYBN-DZCCDHAISA-N (2r,3r,4s,5s)-2-[6-(4-chloro-2-fluoroanilino)purin-9-yl]-5-(3-pyridin-3-yl-1,2-oxazol-5-yl)oxolane-3,4-diol Chemical compound N=1OC([C@H]2O[C@H]([C@H](O)[C@@H]2O)N2C3=NC=NC(NC=4C(=CC(Cl)=CC=4)F)=C3N=C2)=CC=1C1=CC=CN=C1 LVHVPCWNNCWYBN-DZCCDHAISA-N 0.000 claims 1
- VPFSTFMWEFTGGR-MOROJQBDSA-N (2r,3r,4s,5s)-2-[6-(4-chloro-2-fluoroanilino)purin-9-yl]-5-(5-methyl-1,3,4-oxadiazol-2-yl)oxolane-3,4-diol Chemical compound O1C(C)=NN=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC=4C(=CC(Cl)=CC=4)F)=C3N=C2)O1 VPFSTFMWEFTGGR-MOROJQBDSA-N 0.000 claims 1
- OQRRSDZKYMKLHA-LDNFRZNASA-N (2r,3r,4s,5s)-2-[6-(4-chloro-2-fluoroanilino)purin-9-yl]-5-(5-propan-2-yl-1,3,4-oxadiazol-2-yl)oxolane-3,4-diol Chemical compound O1C(C(C)C)=NN=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC=4C(=CC(Cl)=CC=4)F)=C3N=C2)O1 OQRRSDZKYMKLHA-LDNFRZNASA-N 0.000 claims 1
- FEGPIIQNLVLDBU-SSHHRWTQSA-N (2s,3s,4r,5r)-2-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-5-[6-(oxan-4-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound N=1OC([C@H]2O[C@H]([C@H](O)[C@@H]2O)N2C3=NC=NC(NC4CCOCC4)=C3N=C2)=NC=1C1CC1 FEGPIIQNLVLDBU-SSHHRWTQSA-N 0.000 claims 1
- OSGNFKKRIOGRON-WFXMFSGNSA-N (2s,3s,4r,5r)-2-(3-ethyl-1,2-oxazol-5-yl)-5-[6-(oxan-4-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O1N=C(CC)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCOCC4)=C3N=C2)O1 OSGNFKKRIOGRON-WFXMFSGNSA-N 0.000 claims 1
- GYDXCUKNRHPYGU-TVKQPGBESA-N (2s,3s,4r,5r)-2-(3-tert-butyl-1,2-oxazol-5-yl)-5-[2-chloro-6-(4-chloro-2-fluoroanilino)purin-9-yl]oxolane-3,4-diol Chemical compound O1N=C(C(C)(C)C)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC(Cl)=NC(NC=4C(=CC(Cl)=CC=4)F)=C3N=C2)O1 GYDXCUKNRHPYGU-TVKQPGBESA-N 0.000 claims 1
- VMXLHEWZESYBOS-TVKQPGBESA-N (2s,3s,4r,5r)-2-(3-tert-butyl-1,2-oxazol-5-yl)-5-[6-(oxan-4-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O1N=C(C(C)(C)C)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCOCC4)=C3N=C2)O1 VMXLHEWZESYBOS-TVKQPGBESA-N 0.000 claims 1
- PZFNFKCXHWGRKV-XKGFGPFHSA-N (2s,3s,4r,5r)-2-(3-tert-butyl-1,2-oxazol-5-yl)-5-[6-[(1-methylsulfonylpiperidin-4-yl)amino]purin-9-yl]oxolane-3,4-diol Chemical compound O1N=C(C(C)(C)C)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCN(CC4)S(C)(=O)=O)=C3N=C2)O1 PZFNFKCXHWGRKV-XKGFGPFHSA-N 0.000 claims 1
- GWCWLLHLZSYIKP-DZCCDHAISA-N (2s,3s,4r,5r)-2-(3-tert-butyl-1,2-oxazol-5-yl)-5-[6-[(1-propylsulfonylpiperidin-4-yl)amino]purin-9-yl]oxolane-3,4-diol Chemical compound C1CN(S(=O)(=O)CCC)CCC1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](C=2ON=C(C=2)C(C)(C)C)O1 GWCWLLHLZSYIKP-DZCCDHAISA-N 0.000 claims 1
- FTPXZPUMCDRAGL-SSHHRWTQSA-N (2s,3s,4r,5r)-2-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-5-[6-(oxan-4-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O1C([C@H]2O[C@H]([C@H](O)[C@@H]2O)N2C3=NC=NC(NC4CCOCC4)=C3N=C2)=NN=C1C1CC1 FTPXZPUMCDRAGL-SSHHRWTQSA-N 0.000 claims 1
- RHXPQNKDFQORGZ-QCUYGVNKSA-N (2s,3s,4r,5r)-2-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[6-(2-chloro-4-fluoroanilino)purin-9-yl]oxolane-3,4-diol Chemical compound O1C(C(C)(C)C)=NN=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC=4C(=CC(F)=CC=4)Cl)=C3N=C2)O1 RHXPQNKDFQORGZ-QCUYGVNKSA-N 0.000 claims 1
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
- KNNRMJBGAZFUPQ-QCUYGVNKSA-N ethyl 4-[[9-[(2r,3r,4s,5s)-3,4-dihydroxy-5-(3-methyl-1,2,4-oxadiazol-5-yl)oxolan-2-yl]purin-6-yl]amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](C=2ON=C(C)N=2)O1 KNNRMJBGAZFUPQ-QCUYGVNKSA-N 0.000 claims 1
- ZLQLKNRZWVCJTB-XKGFGPFHSA-N ethyl 4-[[9-[(2r,3r,4s,5s)-5-(3-ethyl-1,2-oxazol-5-yl)-3,4-dihydroxyoxolan-2-yl]-2-methoxypurin-6-yl]amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1NC1=NC(OC)=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](C=2ON=C(CC)C=2)O1 ZLQLKNRZWVCJTB-XKGFGPFHSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 294
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 138
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
- 239000000243 solution Substances 0.000 description 100
- 235000019439 ethyl acetate Nutrition 0.000 description 98
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 84
- 239000000543 intermediate Substances 0.000 description 83
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 81
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 71
- 238000001819 mass spectrum Methods 0.000 description 70
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 63
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 58
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 57
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 56
- 239000002904 solvent Substances 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- 239000007787 solid Substances 0.000 description 51
- 239000000741 silica gel Substances 0.000 description 50
- 229910002027 silica gel Inorganic materials 0.000 description 50
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 49
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 49
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 46
- 238000010992 reflux Methods 0.000 description 44
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 39
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 34
- 235000017557 sodium bicarbonate Nutrition 0.000 description 34
- 238000000746 purification Methods 0.000 description 33
- 238000003818 flash chromatography Methods 0.000 description 31
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- 239000012044 organic layer Substances 0.000 description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
- 239000012267 brine Substances 0.000 description 24
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 21
- 229910004298 SiO 2 Inorganic materials 0.000 description 19
- 239000000284 extract Substances 0.000 description 19
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- 239000003921 oil Substances 0.000 description 17
- 235000019198 oils Nutrition 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 238000001816 cooling Methods 0.000 description 16
- 239000006260 foam Substances 0.000 description 16
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 15
- WACQKHWOTAEEFS-UHFFFAOYSA-N cyclohexane;ethyl acetate Chemical compound CCOC(C)=O.C1CCCCC1 WACQKHWOTAEEFS-UHFFFAOYSA-N 0.000 description 15
- 238000002953 preparative HPLC Methods 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- 235000019441 ethanol Nutrition 0.000 description 12
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- 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 11
- 239000002253 acid Substances 0.000 description 11
- 235000019253 formic acid Nutrition 0.000 description 11
- 238000010898 silica gel chromatography Methods 0.000 description 11
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 11
- 239000012043 crude product Substances 0.000 description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- 238000007792 addition Methods 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- 229910021529 ammonia Inorganic materials 0.000 description 7
- WJYHCYBNUJVCEH-UHFFFAOYSA-N cyclohexane;ethoxyethane Chemical compound CCOCC.C1CCCCC1 WJYHCYBNUJVCEH-UHFFFAOYSA-N 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 7
- SCZNXLWKYFICFV-UHFFFAOYSA-N 1,2,3,4,5,7,8,9-octahydropyrido[1,2-b]diazepine Chemical compound C1CCCNN2CCCC=C21 SCZNXLWKYFICFV-UHFFFAOYSA-N 0.000 description 6
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 6
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- 239000013067 intermediate product Substances 0.000 description 6
- KWZSCXIYGVEHOB-UHFFFAOYSA-N oxan-4-amine;hydrochloride Chemical compound [Cl-].[NH3+]C1CCOCC1 KWZSCXIYGVEHOB-UHFFFAOYSA-N 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- BWQOSYSWEARUOW-MCHASIABSA-N (3ar,4r,6s,6as)-4-(6-chloropurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxylic acid Chemical compound C1=NC2=C(Cl)N=CN=C2N1[C@H](O[C@@H]1C(O)=O)[C@H]2[C@@H]1OC(C)(C)O2 BWQOSYSWEARUOW-MCHASIABSA-N 0.000 description 5
- ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical compound ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 5
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 5
- 230000003243 anti-lipolytic effect Effects 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 239000012047 saturated solution Substances 0.000 description 5
- 208000021070 secondary pulmonary alveolar proteinosis Diseases 0.000 description 5
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 4
- CSFDTBRRIBJILD-UHFFFAOYSA-N 4-chloro-2-fluoroaniline Chemical compound NC1=CC=C(Cl)C=C1F CSFDTBRRIBJILD-UHFFFAOYSA-N 0.000 description 4
- NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-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
- 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
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 4
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 4
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- ZFSXKSSWYSZPGQ-FHAQVOQBSA-N (1s,2s)-2-aminocyclopentan-1-ol;hydrochloride Chemical compound Cl.N[C@H]1CCC[C@@H]1O ZFSXKSSWYSZPGQ-FHAQVOQBSA-N 0.000 description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
- 239000005695 Ammonium acetate Substances 0.000 description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- 235000019502 Orange oil Nutrition 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 235000019257 ammonium acetate Nutrition 0.000 description 3
- 229940043376 ammonium acetate Drugs 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 235000021588 free fatty acids Nutrition 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 208000028867 ischemia Diseases 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 3
- 239000010502 orange oil Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 201000008482 osteoarthritis Diseases 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- KOYZJGPDKBWNRU-UHFFFAOYSA-N 1,3-dioxole-4-carbohydrazide Chemical compound NNC(=O)C1=COCO1 KOYZJGPDKBWNRU-UHFFFAOYSA-N 0.000 description 2
- LXYUSXFFUYVKOV-UHFFFAOYSA-N 1,3-dioxole-4-carboxamide Chemical compound NC(=O)C1=COCO1 LXYUSXFFUYVKOV-UHFFFAOYSA-N 0.000 description 2
- BNMNQUBPZZSXQU-UHFFFAOYSA-N 1,3-dioxole-4-carboxylic acid Chemical compound OC(=O)C1=COCO1 BNMNQUBPZZSXQU-UHFFFAOYSA-N 0.000 description 2
- XXMFJKNOJSDQBM-UHFFFAOYSA-N 2,2,2-trifluoroacetic acid;hydrate Chemical compound [OH3+].[O-]C(=O)C(F)(F)F XXMFJKNOJSDQBM-UHFFFAOYSA-N 0.000 description 2
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 2
- OARJXUPBZNUYBG-UHFFFAOYSA-N 2,2-dimethylpropanehydrazide Chemical compound CC(C)(C)C(=O)NN OARJXUPBZNUYBG-UHFFFAOYSA-N 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- RMFWVOLULURGJI-UHFFFAOYSA-N 2,6-dichloro-7h-purine Chemical compound ClC1=NC(Cl)=C2NC=NC2=N1 RMFWVOLULURGJI-UHFFFAOYSA-N 0.000 description 2
- JSWKBJIKVSXWDJ-UHFFFAOYSA-N 2-(oxolan-3-yl)acetic acid Chemical compound OC(=O)CC1CCOC1 JSWKBJIKVSXWDJ-UHFFFAOYSA-N 0.000 description 2
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
- PPWNCLVNXGCGAF-UHFFFAOYSA-N 3,3-dimethylbut-1-yne Chemical compound CC(C)(C)C#C PPWNCLVNXGCGAF-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- 108010060263 Adenosine A1 Receptor Proteins 0.000 description 2
- 102000030814 Adenosine A1 receptor Human genes 0.000 description 2
- 206010002388 Angina unstable Diseases 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 241001480079 Corymbia calophylla Species 0.000 description 2
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 208000001640 Fibromyalgia Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 206010065390 Inflammatory pain Diseases 0.000 description 2
- 235000006552 Liquidambar styraciflua Nutrition 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 208000004550 Postoperative Pain Diseases 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000005708 Sodium hypochlorite Substances 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 208000007814 Unstable Angina Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229960000643 adenine Drugs 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical class N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 229910052681 coesite Inorganic materials 0.000 description 2
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 229910052906 cristobalite Inorganic materials 0.000 description 2
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000008570 general process Effects 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 150000005830 nonesterified fatty acids Chemical class 0.000 description 2
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- KMUONIBRACKNSN-UHFFFAOYSA-N potassium dichromate Chemical compound [K+].[K+].[O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O KMUONIBRACKNSN-UHFFFAOYSA-N 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 230000010410 reperfusion Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 229910052682 stishovite Inorganic materials 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 229910052905 tridymite Inorganic materials 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- ZFSXKSSWYSZPGQ-UHFFFAOYSA-N (2-hydroxycyclopentyl)azanium;chloride Chemical compound Cl.NC1CCCC1O ZFSXKSSWYSZPGQ-UHFFFAOYSA-N 0.000 description 1
- OWNGGLQZBDOGHG-FNOROQBZSA-N (2r,3r,4s,5r)-2-(6-chloropurin-9-yl)-5-(1h-pyrazol-5-yl)oxolane-3,4-diol Chemical compound C1([C@H]2O[C@H]([C@H](O)[C@@H]2O)N2C3=NC=NC(Cl)=C3N=C2)=CC=NN1 OWNGGLQZBDOGHG-FNOROQBZSA-N 0.000 description 1
- ISTJYOHJQIFXAV-IDTAVKCVSA-N (2r,3r,4s,5r)-2-[2-chloro-6-(oxan-4-ylamino)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(NC3CCOCC3)=C2N=C1 ISTJYOHJQIFXAV-IDTAVKCVSA-N 0.000 description 1
- HPGJYSDSXRCOEU-AEISUSGSSA-N (2r,3r,4s,5s)-2-(6-chloropurin-9-yl)-5-(5-ethyl-1,3-oxazol-2-yl)oxolane-3,4-diol Chemical compound O1C(CC)=CN=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(Cl)=C3N=C2)O1 HPGJYSDSXRCOEU-AEISUSGSSA-N 0.000 description 1
- SWKZZLPPAIVEBQ-LUXYFRNMSA-N (2r,3r,4s,5s)-2-[2-chloro-6-(2-chloro-4-fluoroanilino)purin-9-yl]-5-[3-(hydroxymethyl)-1,2-oxazol-5-yl]oxolane-3,4-diol Chemical compound O1N=C(CO)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC(Cl)=NC(NC=4C(=CC(F)=CC=4)Cl)=C3N=C2)O1 SWKZZLPPAIVEBQ-LUXYFRNMSA-N 0.000 description 1
- SKAWUTVEELPTPB-WFXMFSGNSA-N (2r,3r,4s,5s)-2-[2-chloro-6-(2-fluoroanilino)purin-9-yl]-5-(3-ethyl-1,2-oxazol-5-yl)oxolane-3,4-diol Chemical compound O1N=C(CC)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC(Cl)=NC(NC=4C(=CC=CC=4)F)=C3N=C2)O1 SKAWUTVEELPTPB-WFXMFSGNSA-N 0.000 description 1
- AURDVBSSRMSIIK-TVKQPGBESA-N (2r,3r,4s,5s)-2-[6-(2-chloro-4-fluoroanilino)purin-9-yl]-5-(3-ethyl-1,2-oxazol-5-yl)oxolane-3,4-diol Chemical compound O1N=C(CC)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC=4C(=CC(F)=CC=4)Cl)=C3N=C2)O1 AURDVBSSRMSIIK-TVKQPGBESA-N 0.000 description 1
- OAQUCFDQGSENFP-WFXMFSGNSA-N (2r,3r,4s,5s)-2-[6-(2-fluoroanilino)purin-9-yl]-5-[3-(hydroxymethyl)-1,2-oxazol-5-yl]oxolane-3,4-diol Chemical compound O1N=C(CO)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC=4C(=CC=CC=4)F)=C3N=C2)O1 OAQUCFDQGSENFP-WFXMFSGNSA-N 0.000 description 1
- KHKLYPPDHJIXJX-TVKQPGBESA-N (2r,3r,4s,5s)-2-[6-(4-chloro-2-fluoroanilino)-2-methoxypurin-9-yl]-5-(3-ethyl-1,2-oxazol-5-yl)oxolane-3,4-diol Chemical compound O1N=C(CC)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC(OC)=NC(NC=4C(=CC(Cl)=CC=4)F)=C3N=C2)O1 KHKLYPPDHJIXJX-TVKQPGBESA-N 0.000 description 1
- CFMCLHPDQNRURX-JZJXAQOMSA-N (2r,3r,4s,5s)-2-[6-(4-chloro-2-fluoroanilino)purin-9-yl]-5-[3-(4-hydroxybutyl)-1,2-oxazol-5-yl]oxolane-3,4-diol Chemical compound O1N=C(CCCCO)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC=4C(=CC(Cl)=CC=4)F)=C3N=C2)O1 CFMCLHPDQNRURX-JZJXAQOMSA-N 0.000 description 1
- CQFZDPFZSPEIFA-SSHHRWTQSA-N (2r,3r,4s,5s)-2-[6-(oxan-4-ylamino)purin-9-yl]-5-(5-propan-2-yl-1,3,4-oxadiazol-2-yl)oxolane-3,4-diol Chemical compound O1C(C(C)C)=NN=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCOCC4)=C3N=C2)O1 CQFZDPFZSPEIFA-SSHHRWTQSA-N 0.000 description 1
- JEOBRTNQDVLBMP-TVKQPGBESA-N (2s,3s,4r,5r)-2-(3-ethyl-1,2-oxazol-5-yl)-5-[6-(2-fluoroanilino)-2-methoxypurin-9-yl]oxolane-3,4-diol Chemical compound O1N=C(CC)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC(OC)=NC(NC=4C(=CC=CC=4)F)=C3N=C2)O1 JEOBRTNQDVLBMP-TVKQPGBESA-N 0.000 description 1
- RQQXFPOLWQZAJB-TVKQPGBESA-N (2s,3s,4r,5r)-2-(3-ethyl-1,2-oxazol-5-yl)-5-[6-(2-fluoroanilino)purin-9-yl]oxolane-3,4-diol Chemical compound O1N=C(CC)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC=4C(=CC=CC=4)F)=C3N=C2)O1 RQQXFPOLWQZAJB-TVKQPGBESA-N 0.000 description 1
- LHJJWMLUYHLPBP-WFXMFSGNSA-N (2s,3s,4r,5r)-2-(3-tert-butyl-1,2-oxazol-5-yl)-5-[2-chloro-6-(oxan-4-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O1N=C(C(C)(C)C)C=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC(Cl)=NC(NC4CCOCC4)=C3N=C2)O1 LHJJWMLUYHLPBP-WFXMFSGNSA-N 0.000 description 1
- QQMZNTSNPXRLNF-QCUYGVNKSA-N (2s,3s,4r,5r)-2-(5-ethyl-1,3-oxazol-2-yl)-5-[6-(oxan-4-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O1C(CC)=CN=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCOCC4)=C3N=C2)O1 QQMZNTSNPXRLNF-QCUYGVNKSA-N 0.000 description 1
- YFAKWSSZGDGDGN-XLJNPPHCSA-N (3ar,4r,6s,6ar)-4-(6-chloropurin-9-yl)-n-(2-hydroxypropyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxamide Chemical compound C1=NC2=C(Cl)N=CN=C2N1[C@@H]1O[C@H](C(=O)NCC(O)C)[C@@H]2OC(C)(C)O[C@H]21 YFAKWSSZGDGDGN-XLJNPPHCSA-N 0.000 description 1
- SDJCJHKLPLZIDH-UXCLJVHYSA-N (3ar,4r,6s,6ar)-4-methoxy-2,2-dimethyl-n-(2-oxobutyl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxamide Chemical compound O1C(C)(C)O[C@H]2[C@@H](C(=O)NCC(=O)CC)O[C@@H](OC)[C@@H]21 SDJCJHKLPLZIDH-UXCLJVHYSA-N 0.000 description 1
- BJRODYJMYPPHJH-XKTHAWJUSA-N (3ar,4r,6s,6ar)-n-(2-hydroxybutyl)-4-methoxy-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxamide Chemical compound O1C(C)(C)O[C@H]2[C@@H](C(=O)NCC(O)CC)O[C@@H](OC)[C@@H]21 BJRODYJMYPPHJH-XKTHAWJUSA-N 0.000 description 1
- GUGGGWVPDPZVSM-AZKPJATDSA-N (3ar,4r,6s,6as)-4-(6-chloropurin-9-yl)-2,2-dimethyl-n-(2-oxobutyl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxamide Chemical compound C1=NC2=C(Cl)N=CN=C2N1[C@@H]1O[C@H](C(=O)NCC(=O)CC)[C@H]2OC(C)(C)O[C@H]21 GUGGGWVPDPZVSM-AZKPJATDSA-N 0.000 description 1
- IVDGNVFRRKETEC-OZTPJHRESA-N (3ar,4r,6s,6as)-4-[2-chloro-6-(oxan-4-ylamino)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxylic acid Chemical compound N1=C(Cl)N=C2N([C@H]3[C@H]4[C@@H]([C@H](O3)C(O)=O)OC(O4)(C)C)C=NC2=C1NC1CCOCC1 IVDGNVFRRKETEC-OZTPJHRESA-N 0.000 description 1
- KHHJWUBBHYKAGR-RSUWNVLCSA-N (3ar,4r,6s,6as)-4-[6-(cyclopentylamino)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxylic acid Chemical compound N1=CN=C2N([C@H]3[C@H]4[C@@H]([C@H](O3)C(O)=O)OC(O4)(C)C)C=NC2=C1NC1CCCC1 KHHJWUBBHYKAGR-RSUWNVLCSA-N 0.000 description 1
- FZENGILVLUJGJX-NSCUHMNNSA-N (E)-acetaldehyde oxime Chemical compound C\C=N\O FZENGILVLUJGJX-NSCUHMNNSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- NHMPBWJFSNZZLO-DDHJBXDOSA-N 1-[(3ar,4r,6r,6ar)-4-methoxy-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]-1-hydroxyiminopentan-3-one Chemical compound O1C(C)(C)O[C@@H]2[C@@H](C(=NO)CC(=O)CC)O[C@@H](OC)[C@@H]21 NHMPBWJFSNZZLO-DDHJBXDOSA-N 0.000 description 1
- XCSVYPPZGPJGSS-BYTXHCLHSA-N 1-[(3ar,4r,6r,6ar)-4-methoxy-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]pent-1-yn-3-ol Chemical compound O1C(C)(C)O[C@@H]2[C@@H](C#CC(O)CC)O[C@@H](OC)[C@@H]21 XCSVYPPZGPJGSS-BYTXHCLHSA-N 0.000 description 1
- QYRWYKRMUAOEIF-FBHSLPMESA-N 1-[4-[[9-[(2r,3r,4s,5s)-5-(3-tert-butyl-1,2-oxazol-5-yl)-3,4-dihydroxyoxolan-2-yl]purin-6-yl]amino]piperidin-1-yl]butan-1-one Chemical compound C1CN(C(=O)CCC)CCC1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](C=2ON=C(C=2)C(C)(C)C)O1 QYRWYKRMUAOEIF-FBHSLPMESA-N 0.000 description 1
- KODLUXHSIZOKTG-UHFFFAOYSA-N 1-aminobutan-2-ol Chemical compound CCC(O)CN KODLUXHSIZOKTG-UHFFFAOYSA-N 0.000 description 1
- DGSSJZJBCABUMD-UHFFFAOYSA-N 1-aminobutan-2-one;hydrochloride Chemical compound Cl.CCC(=O)CN DGSSJZJBCABUMD-UHFFFAOYSA-N 0.000 description 1
- HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical compound CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-N 0.000 description 1
- WGMHMVLZFAJNOT-UHFFFAOYSA-N 1-ethoxyethylideneazanium;chloride Chemical compound [Cl-].CCOC(C)=[NH2+] WGMHMVLZFAJNOT-UHFFFAOYSA-N 0.000 description 1
- JSZOAYXJRCEYSX-UHFFFAOYSA-N 1-nitropropane Chemical compound CCC[N+]([O-])=O JSZOAYXJRCEYSX-UHFFFAOYSA-N 0.000 description 1
- PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 description 1
- CEPCPXLLFXPZGW-UHFFFAOYSA-N 2,4-difluoroaniline Chemical compound NC1=CC=C(F)C=C1F CEPCPXLLFXPZGW-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- PIZGQSWCZNVPFH-UHFFFAOYSA-N 2-amino-n,n-dimethylethanesulfonamide;hydrochloride Chemical compound Cl.CN(C)S(=O)(=O)CCN PIZGQSWCZNVPFH-UHFFFAOYSA-N 0.000 description 1
- HBAHZZVIEFRTEY-UHFFFAOYSA-N 2-heptylcyclohex-2-en-1-one Chemical compound CCCCCCCC1=CCCCC1=O HBAHZZVIEFRTEY-UHFFFAOYSA-N 0.000 description 1
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
- YEGDMOUGOQDPOK-ZGPJWRFFSA-N 5-[(3ar,4r,6s,6ar)-4-[6-(benzotriazol-1-yloxy)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]-3-tert-butyl-1,2,4-oxadiazole Chemical compound CC(C)(C)C1=NOC([C@@H]2[C@@H]3OC(C)(C)O[C@H]3[C@@H](O2)N2C3=NC=NC(ON4C5=CC=CC=C5N=N4)=C3N=C2)=N1 YEGDMOUGOQDPOK-ZGPJWRFFSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- POLMWTIEXALXRT-XTDOFWJNSA-N 9-[(3ar,4r,6s,6ar)-2,2-dimethyl-6-(3-methyl-1,2,4-oxadiazol-5-yl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-n-cyclopentylpurin-6-amine Chemical compound CC1=NOC([C@@H]2[C@@H]3OC(C)(C)O[C@H]3[C@@H](O2)N2C3=NC=NC(NC4CCCC4)=C3N=C2)=N1 POLMWTIEXALXRT-XTDOFWJNSA-N 0.000 description 1
- YEKSUJJFFKRPLG-XTDOFWJNSA-N 9-[(3ar,4r,6s,6ar)-6-(3-tert-butyl-1,2,4-oxadiazol-5-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-n-(2-methylpropyl)purin-6-amine Chemical compound C1([C@H]2O[C@H]([C@@H]3OC(C)(C)O[C@H]32)N2C=3N=CN=C(C=3N=C2)NCC(C)C)=NC(C(C)(C)C)=NO1 YEKSUJJFFKRPLG-XTDOFWJNSA-N 0.000 description 1
- GPCWPCKTTLMDSV-UHFFFAOYSA-N 9-[6-(hydroxymethyl)-2,2-dimethyl-4,5,6,6a-tetrahydro-3ah-cyclopenta[d][1,3]dioxol-4-yl]-3h-purin-6-one Chemical compound C1=NC(C(NC=N2)=O)=C2N1C1CC(CO)C2OC(C)(C)OC21 GPCWPCKTTLMDSV-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 108050000203 Adenosine receptors Proteins 0.000 description 1
- 102000009346 Adenosine receptors Human genes 0.000 description 1
- 102100024321 Alkaline phosphatase, placental type Human genes 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical group CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 208000006561 Cluster Headache Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical group C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 241000400611 Eucalyptus deanei Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 101000783645 Homo sapiens Adenosine receptor A3 Proteins 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- STVVMTBJNDTZBF-VIFPVBQESA-N L-phenylalaninol Chemical compound OC[C@@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-VIFPVBQESA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920001367 Merrifield resin Polymers 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- BXDZOYLPNAIDOC-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide Chemical compound CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5C(=O)N(C6CCC(=O)NC6=O)C(=O)c45)CC3)s2)o1 BXDZOYLPNAIDOC-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102100028255 Renin Human genes 0.000 description 1
- 108090000783 Renin Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 208000007718 Stable Angina Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QYTDEUPAUMOIOP-UHFFFAOYSA-N TEMPO Chemical group CC1(C)CCCC(C)(C)N1[O] QYTDEUPAUMOIOP-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010043269 Tension headache Diseases 0.000 description 1
- 208000008548 Tension-Type Headache Diseases 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- HYBSFKWYRVJQLG-QTQZEZTPSA-N [(2r,3r,4r,5r)-3,4-diacetyloxy-5-[2-chloro-6-(4-chloro-2-fluoroanilino)purin-9-yl]oxolan-2-yl]methyl acetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](COC(=O)C)O[C@H]1N1C2=NC(Cl)=NC(NC=3C(=CC(Cl)=CC=3)F)=C2N=C1 HYBSFKWYRVJQLG-QTQZEZTPSA-N 0.000 description 1
- XWOCGTOOCPHJDB-GWOFURMSSA-N [(2r,3r,4r,5r)-4-acetyloxy-2-ethynyl-5-methoxyoxolan-3-yl] acetate Chemical compound CO[C@@H]1O[C@H](C#C)[C@@H](OC(C)=O)[C@H]1OC(C)=O XWOCGTOOCPHJDB-GWOFURMSSA-N 0.000 description 1
- KQVSRIJPLDMUSG-VMUDFCTBSA-N [(2r,3r,4r,5r)-4-acetyloxy-5-(2,6-dichloropurin-9-yl)-2-(5-ethyl-1,2-oxazol-3-yl)oxolan-3-yl] acetate Chemical compound O1C(CC)=CC([C@@H]2[C@H]([C@@H](OC(C)=O)[C@@H](O2)N2C3=NC(Cl)=NC(Cl)=C3N=C2)OC(C)=O)=N1 KQVSRIJPLDMUSG-VMUDFCTBSA-N 0.000 description 1
- WKPBIFHRPZDBEG-SDBHATRESA-N [(2r,3r,4r,5r)-4-acetyloxy-5-(6-chloropurin-9-yl)-2-ethynyloxolan-3-yl] acetate Chemical compound O1[C@H](C#C)[C@@H](OC(=O)C)[C@@H](OC(C)=O)[C@@H]1N1C2=NC=NC(Cl)=C2N=C1 WKPBIFHRPZDBEG-SDBHATRESA-N 0.000 description 1
- MLGIHDBBWUOIOH-QTQZEZTPSA-N [(2r,3r,4r,5r)-4-acetyloxy-5-[6-(4-chloro-2-fluoroanilino)purin-9-yl]-2-ethynyloxolan-3-yl] acetate Chemical compound O1[C@H](C#C)[C@@H](OC(=O)C)[C@@H](OC(C)=O)[C@@H]1N1C2=NC=NC(NC=3C(=CC(Cl)=CC=3)F)=C2N=C1 MLGIHDBBWUOIOH-QTQZEZTPSA-N 0.000 description 1
- MSAPDWLQPDBPBA-QTQZEZTPSA-N [(2r,3r,4r,5r)-4-acetyloxy-5-[6-(benzotriazol-1-yloxy)purin-9-yl]-2-ethynyloxolan-3-yl] acetate Chemical compound O1[C@H](C#C)[C@@H](OC(=O)C)[C@@H](OC(C)=O)[C@@H]1N1C2=NC=NC(ON3C4=CC=CC=C4N=N3)=C2N=C1 MSAPDWLQPDBPBA-QTQZEZTPSA-N 0.000 description 1
- BZNMYNOLERLXAQ-NMOFPLQQSA-N [(2s,3r,4r,5r)-4-acetyloxy-2-(3-tert-butyl-1,2-oxazol-5-yl)-5-[6-[(1-methylsulfonylpiperidin-4-yl)amino]purin-9-yl]oxolan-3-yl] acetate Chemical compound C1([C@H]2O[C@H]([C@H](OC(C)=O)[C@@H]2OC(=O)C)N2C3=NC=NC(NC4CCN(CC4)S(C)(=O)=O)=C3N=C2)=CC(C(C)(C)C)=NO1 BZNMYNOLERLXAQ-NMOFPLQQSA-N 0.000 description 1
- SWAPZTDQDBCLDU-UYAYXHRUSA-N [(2s,3r,4r,5r)-4-acetyloxy-5-(6-chloropurin-9-yl)-2-(5-ethyl-1,3-oxazol-2-yl)oxolan-3-yl] acetate Chemical compound O1C(CC)=CN=C1[C@@H]1[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@H](N2C3=NC=NC(Cl)=C3N=C2)O1 SWAPZTDQDBCLDU-UYAYXHRUSA-N 0.000 description 1
- GTCSOAXQGGUSKV-QVHKTLOISA-N [(2s,3r,4r,5s)-4,5-diacetyloxy-2-(5-ethyl-1,3-oxazol-2-yl)oxolan-3-yl] acetate Chemical compound O1C(CC)=CN=C1[C@@H]1[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)O1 GTCSOAXQGGUSKV-QVHKTLOISA-N 0.000 description 1
- RYXZOQOZERSHHQ-UHFFFAOYSA-N [2-(2-diphenylphosphanylphenoxy)phenyl]-diphenylphosphane Chemical compound C=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1OC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RYXZOQOZERSHHQ-UHFFFAOYSA-N 0.000 description 1
- UFJPBJVMOXZRHQ-YKTARERQSA-N [5-[(2s,3r,4r,5r)-3,4-diacetyloxy-5-(6-chloropurin-9-yl)oxolan-2-yl]-1,2-oxazol-3-yl]methyl acetate Chemical compound O1N=C(COC(=O)C)C=C1[C@@H]1[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@H](N2C3=NC=NC(Cl)=C3N=C2)O1 UFJPBJVMOXZRHQ-YKTARERQSA-N 0.000 description 1
- FHYKELUMXGCSTF-UHFFFAOYSA-M [Cl-].CC(C)(C)C#C[Mg+] Chemical compound [Cl-].CC(C)(C)C#C[Mg+] FHYKELUMXGCSTF-UHFFFAOYSA-M 0.000 description 1
- SXGRGWQCOHUYDS-UHFFFAOYSA-N [N].ClP(Cl)(Cl)=O Chemical compound [N].ClP(Cl)(Cl)=O SXGRGWQCOHUYDS-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000002582 adenosine A1 receptor agonist Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000000879 anti-atherosclerotic effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002253 anti-ischaemic effect Effects 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
- 235000010233 benzoic acid Nutrition 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
- ZDZHCHYQNPQSGG-UHFFFAOYSA-N binaphthyl group Chemical group C1(=CC=CC2=CC=CC=C12)C1=CC=CC2=CC=CC=C12 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight 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
- 239000000337 buffer salt Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000003293 cardioprotective effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 208000018912 cluster headache syndrome Diseases 0.000 description 1
- 238000010549 co-Evaporation Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 229940095074 cyclic amp Drugs 0.000 description 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- VRXPAIXZAQCRRX-TVKQPGBESA-N ethyl 4-[[2-chloro-9-[(2r,3r,4s,5s)-5-(3-ethyl-1,2-oxazol-5-yl)-3,4-dihydroxyoxolan-2-yl]purin-6-yl]amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1NC1=NC(Cl)=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](C=2ON=C(CC)C=2)O1 VRXPAIXZAQCRRX-TVKQPGBESA-N 0.000 description 1
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
- OZECFIJVSAYAPH-UHFFFAOYSA-N ethyl-di(propan-2-yl)azanium;chloride Chemical compound Cl.CCN(C(C)C)C(C)C OZECFIJVSAYAPH-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- ULYSABNRLLVZCE-UHFFFAOYSA-N furan-3,4-diol Chemical compound OC1=COC=C1O ULYSABNRLLVZCE-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 102000046278 human ADORA3 Human genes 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 1
- 230000000055 hyoplipidemic effect Effects 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 230000004130 lipolysis Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- GRWIABMEEKERFV-UHFFFAOYSA-N methanol;oxolane Chemical compound OC.C1CCOC1 GRWIABMEEKERFV-UHFFFAOYSA-N 0.000 description 1
- KZRAAPTWXAMZHQ-UHFFFAOYSA-N methoxymethanamine Chemical compound COCN KZRAAPTWXAMZHQ-UHFFFAOYSA-N 0.000 description 1
- CLPNUBASBBBOCT-OZTPJHRESA-N methyl (3ar,4r,6s,6as)-2,2-dimethyl-4-[6-(propan-2-ylamino)purin-9-yl]-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxylate Chemical compound C1=NC2=C(NC(C)C)N=CN=C2N1[C@@H]1O[C@H](C(=O)OC)[C@H]2OC(C)(C)O[C@H]21 CLPNUBASBBBOCT-OZTPJHRESA-N 0.000 description 1
- XBXFXJPJCIDXEZ-QDEZUTFSSA-N methyl (3ar,4r,6s,6as)-4-[6-(cyclopentylamino)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxylate Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]4OC(C)(C)O[C@H]43)C(=O)OC)C=NC2=C1NC1CCCC1 XBXFXJPJCIDXEZ-QDEZUTFSSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- DTRXYXLSDNJYKF-UHFFFAOYSA-N n'-(2,2-dimethylpropanoyl)-1,3-dioxole-4-carbohydrazide Chemical compound CC(C)(C)C(=O)NNC(=O)C1=COCO1 DTRXYXLSDNJYKF-UHFFFAOYSA-N 0.000 description 1
- NUVUYAGKANIOPX-UHFFFAOYSA-N n'-hydroxy-3,3-dimethylbutanimidamide Chemical compound CC(C)(C)CC(N)=NO NUVUYAGKANIOPX-UHFFFAOYSA-N 0.000 description 1
- AWBKQZSYNWLCMW-UHFFFAOYSA-N n-(dibromomethylidene)hydroxylamine Chemical compound ON=C(Br)Br AWBKQZSYNWLCMW-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- AHVQYHFYQWKUKB-UHFFFAOYSA-N oxan-4-amine Chemical compound NC1CCOCC1 AHVQYHFYQWKUKB-UHFFFAOYSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- DIRLDPKYOATBIA-UHFFFAOYSA-N oxolan-3-yl acetate Chemical compound CC(=O)OC1CCOC1 DIRLDPKYOATBIA-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- PQPFFKCJENSZKL-UHFFFAOYSA-N pentan-3-amine Chemical compound CCC(N)CC PQPFFKCJENSZKL-UHFFFAOYSA-N 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 108010031345 placental alkaline phosphatase Proteins 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 1
- UNHKSXOTUHOTAB-UHFFFAOYSA-N sodium;sulfane Chemical compound [Na].S UNHKSXOTUHOTAB-UHFFFAOYSA-N 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 208000024535 susceptibility to myocardial infarction Diseases 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- QPDPRBISONCLIP-ANNHOSHMSA-N tert-butyl 4-[[9-[(2r,3r,4r,5s)-3,4-diacetyloxy-5-(3-tert-butyl-1,2-oxazol-5-yl)oxolan-2-yl]purin-6-yl]amino]piperidine-1-carboxylate Chemical compound C1([C@H]2O[C@H]([C@H](OC(C)=O)[C@@H]2OC(=O)C)N2C3=NC=NC(NC4CCN(CC4)C(=O)OC(C)(C)C)=C3N=C2)=CC(C(C)(C)C)=NO1 QPDPRBISONCLIP-ANNHOSHMSA-N 0.000 description 1
- LZRDHSFPLUWYAX-UHFFFAOYSA-N tert-butyl 4-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)CC1 LZRDHSFPLUWYAX-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- 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
- A61P11/00—Drugs for disorders of the respiratory 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
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Pulmonology (AREA)
- Anesthesiology (AREA)
- Rheumatology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9813554.4A GB9813554D0 (en) | 1998-06-23 | 1998-06-23 | Chemical compounds |
PCT/EP1999/004182 WO1999067262A1 (fr) | 1998-06-23 | 1999-06-21 | Derives d'adenosine |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20006520D0 NO20006520D0 (no) | 2000-12-20 |
NO20006520L NO20006520L (no) | 2001-02-14 |
NO318788B1 true NO318788B1 (no) | 2005-05-09 |
Family
ID=10834247
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20006520A NO318788B1 (no) | 1998-06-23 | 2000-12-20 | Adenosinderivater, samt fremgangsmate for fremstilling og anvendels derav og farmasoytisk preparat. |
Country Status (40)
Country | Link |
---|---|
US (2) | US6492348B1 (fr) |
EP (2) | EP1447407A1 (fr) |
JP (2) | JP3378240B2 (fr) |
KR (1) | KR100612797B1 (fr) |
CN (2) | CN1616459A (fr) |
AP (1) | AP2000002014A0 (fr) |
AR (1) | AR018917A1 (fr) |
AT (1) | ATE277941T1 (fr) |
AU (1) | AU758018B2 (fr) |
BG (1) | BG65064B1 (fr) |
BR (1) | BR9911498A (fr) |
CA (1) | CA2335520C (fr) |
CO (1) | CO5040216A1 (fr) |
DE (1) | DE69920697T2 (fr) |
EA (1) | EA003828B1 (fr) |
EE (1) | EE04853B1 (fr) |
ES (1) | ES2226399T3 (fr) |
GB (1) | GB9813554D0 (fr) |
GE (1) | GEP20032958B (fr) |
HK (1) | HK1034978A1 (fr) |
HR (1) | HRP20000896B1 (fr) |
HU (1) | HUP0102453A3 (fr) |
ID (1) | ID27484A (fr) |
IL (2) | IL140284A0 (fr) |
IS (1) | IS5773A (fr) |
MY (1) | MY122481A (fr) |
NO (1) | NO318788B1 (fr) |
NZ (1) | NZ508915A (fr) |
OA (1) | OA11574A (fr) |
PE (1) | PE20000704A1 (fr) |
PL (1) | PL194087B1 (fr) |
PT (1) | PT1090019E (fr) |
RS (1) | RS50042B (fr) |
SI (1) | SI1090019T1 (fr) |
SK (1) | SK19582000A3 (fr) |
TR (1) | TR200100449T2 (fr) |
TW (1) | TW541312B (fr) |
UA (1) | UA64794C2 (fr) |
WO (1) | WO1999067262A1 (fr) |
ZA (1) | ZA200007514B (fr) |
Families Citing this family (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9813554D0 (en) * | 1998-06-23 | 1998-08-19 | Glaxo Group Ltd | Chemical compounds |
WO2001064202A2 (fr) * | 2000-03-01 | 2001-09-07 | Euro-Celtique S.A. | Traitement de troubles gastro-intestinaux fonctionnels |
US20040162422A1 (en) * | 2001-03-20 | 2004-08-19 | Adrian Hall | Chemical compounds |
GB0106867D0 (en) * | 2001-03-20 | 2001-05-09 | Glaxo Group Ltd | Process |
GB0115178D0 (en) * | 2001-06-20 | 2001-08-15 | Glaxo Group Ltd | Compounds |
GB0115182D0 (en) * | 2001-06-20 | 2001-08-15 | Glaxo Group Ltd | Medicaments |
US6946449B2 (en) | 2001-07-13 | 2005-09-20 | Cv Therapeutics, Inc. | Partial and full agonists of A1 adenosine receptors |
US7713946B2 (en) | 2002-07-11 | 2010-05-11 | Cv Therapeutics, Inc. | Partial and full agonists A1 adenosine receptors |
US7157440B2 (en) | 2001-07-13 | 2007-01-02 | Cv Therapeutics, Inc. | Partial and full agonists of A1 adenosine receptors |
MXPA04008008A (es) | 2002-02-19 | 2005-03-23 | Cv Therapeutics Inc | Agonistas parciales y completos de receptores de adenosina a1. |
WO2003106475A2 (fr) * | 2002-06-17 | 2003-12-24 | Glaxo Group Limited | Procede |
DE60315164T2 (de) * | 2002-08-15 | 2008-04-30 | CV Therapeutics, Inc., Palo Alto | Partielle und volle agonisten von a1-adenosinrezeptoren |
WO2004055034A1 (fr) * | 2002-12-18 | 2004-07-01 | Glaxo Group Limited | Polymorphe |
WO2004055032A1 (fr) * | 2002-12-18 | 2004-07-01 | Glaxo Group Limited | Derive d'adenosine present dans une forme v polymorphe |
WO2004055033A1 (fr) * | 2002-12-18 | 2004-07-01 | Glaxo Group Limited | Derive d'adenosine dans sa forme polymorphe iv |
NZ541651A (en) | 2003-02-03 | 2009-01-31 | Cv Therapeutics Inc | Partial and full agonists of A1 adenosine receptors |
WO2005053712A1 (fr) * | 2003-12-02 | 2005-06-16 | Glaxo Group Limited | Utilisation de derives d'adenosine aux fins de traitement de la dyslipidemie, de l'obesite, des facteurs de risque cardiovasculaire, du syndrome metabolique, du syndrome des ovaires polykystiques et du niddm |
GT200500281A (es) * | 2004-10-22 | 2006-04-24 | Novartis Ag | Compuestos organicos. |
GB0500785D0 (en) * | 2005-01-14 | 2005-02-23 | Novartis Ag | Organic compounds |
GB0607954D0 (en) * | 2006-04-21 | 2006-05-31 | Novartis Ag | Organic compounds |
ES2440317T3 (es) * | 2006-04-21 | 2014-01-28 | Novartis Ag | Derivados de purina para su uso como agonistas del receptor de adenosina A2A |
GB0607944D0 (en) * | 2006-04-21 | 2006-05-31 | Novartis Ag | Organic compounds |
GB0607953D0 (en) * | 2006-04-21 | 2006-05-31 | Novartis Ag | Organic compounds |
GB0607950D0 (en) * | 2006-04-21 | 2006-05-31 | Novartis Ag | Organic compounds |
GB0607948D0 (en) * | 2006-04-21 | 2006-05-31 | Novartis Ag | Organic compounds |
EP1889846A1 (fr) | 2006-07-13 | 2008-02-20 | Novartis AG | Dérivés de purine comme agonistes du recepteur A2a |
EP1903044A1 (fr) * | 2006-09-14 | 2008-03-26 | Novartis AG | Derivés de l'adénosine en tant qu' agonistes du récepteur A2A |
AU2007316715A1 (en) * | 2006-11-10 | 2008-05-15 | Novartis Ag | Cyclopentene diol monoacetate derivatives |
US20090088403A1 (en) * | 2007-05-07 | 2009-04-02 | Randy Blakely | A3 adenosine receptors as targets for the modulation of central serotonergic signaling |
CN101712709A (zh) | 2008-10-06 | 2010-05-26 | 中国医学科学院药物研究所 | 三乙酰基-3-羟基苯基腺苷及其调血脂的用途 |
EP2849566B1 (fr) * | 2012-02-11 | 2018-04-04 | Academia Sinica | Analogues de l'adenosine destinées au traitement de la douleur |
CR20170384A (es) | 2015-02-24 | 2017-11-16 | Pfizer | Derivados de nucleosidos sustituidos utiles como agentes antineoplasicos |
CN108864099A (zh) * | 2018-09-08 | 2018-11-23 | 湖北荆洪生物科技股份有限公司 | 一种高纯6-糠氨基嘌呤的合成方法 |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4962194A (en) * | 1987-04-02 | 1990-10-09 | Warner-Lambert Company | Method of preparing 51,N6-disubstituted adenosines from inosines |
US5646128A (en) * | 1989-09-15 | 1997-07-08 | Gensia, Inc. | Methods for treating adenosine kinase related conditions |
US5244896A (en) * | 1990-09-14 | 1993-09-14 | Marion Merrell Dow Inc. | Carbocyclic adenosine analogs useful as immunosuppressants |
DK62592D0 (fr) * | 1992-05-14 | 1992-05-14 | Novo Nordisk As | |
GB9301000D0 (en) * | 1993-01-20 | 1993-03-10 | Glaxo Group Ltd | Chemical compounds |
ATE176668T1 (de) * | 1993-07-23 | 1999-02-15 | Merrell Pharma Inc | Neue 9-n-bicyclische nucleosidverbindungen nützlich als selektive inhibitoren von proinflammatorische cytokinen |
AU3255097A (en) * | 1996-07-05 | 1998-02-02 | Novo Nordisk A/S | Novel (n)-alkoxyadenine derivatives acting as cytokine inhibitors |
UA51716C2 (uk) * | 1996-07-08 | 2002-12-16 | Авентіс Фармасьютікалз Продактс Інк. | Сполуки, що мають гіпотензивну, кардіопротекторну, анти-ішемічну та антиліполітичну властивості, фармацевтична композиція та способи лікування |
AU4377397A (en) | 1996-10-14 | 1998-05-11 | Novo Nordisk A/S | Novel therapeutically active adenosine derivatives |
TW528755B (en) | 1996-12-24 | 2003-04-21 | Glaxo Group Ltd | 2-(purin-9-yl)-tetrahydrofuran-3,4-diol derivatives |
YU44900A (sh) | 1998-01-31 | 2003-01-31 | Glaxo Group Limited | Derivati 2-(purin-9-il)tetrahidrofuran-3,4-diola |
AR017457A1 (es) | 1998-02-14 | 2001-09-05 | Glaxo Group Ltd | Compuestos derivados de 2-(purin-9-il)-tetrahidrofuran-3,4-diol, procesos para su preparacion, composiciones que los contienen y su uso en terapia para el tratamiento de enfermedades inflamatorias. |
GB9813554D0 (en) * | 1998-06-23 | 1998-08-19 | Glaxo Group Ltd | Chemical compounds |
-
1998
- 1998-06-23 GB GBGB9813554.4A patent/GB9813554D0/en not_active Ceased
-
1999
- 1999-06-21 PE PE1999000547A patent/PE20000704A1/es not_active Application Discontinuation
- 1999-06-21 RS YUP-828/00A patent/RS50042B/sr unknown
- 1999-06-21 AP APAP/P/2000/002014A patent/AP2000002014A0/en unknown
- 1999-06-21 DE DE69920697T patent/DE69920697T2/de not_active Expired - Lifetime
- 1999-06-21 ID IDW20010186A patent/ID27484A/id unknown
- 1999-06-21 WO PCT/EP1999/004182 patent/WO1999067262A1/fr active IP Right Grant
- 1999-06-21 EP EP04076465A patent/EP1447407A1/fr not_active Withdrawn
- 1999-06-21 EE EEP200000784A patent/EE04853B1/xx not_active IP Right Cessation
- 1999-06-21 HU HU0102453A patent/HUP0102453A3/hu unknown
- 1999-06-21 NZ NZ508915A patent/NZ508915A/en unknown
- 1999-06-21 GE GEAP19995692A patent/GEP20032958B/en unknown
- 1999-06-21 JP JP2000555913A patent/JP3378240B2/ja not_active Expired - Lifetime
- 1999-06-21 AU AU45146/99A patent/AU758018B2/en not_active Ceased
- 1999-06-21 UA UA2000127404A patent/UA64794C2/uk unknown
- 1999-06-21 KR KR1020007014749A patent/KR100612797B1/ko not_active IP Right Cessation
- 1999-06-21 SI SI9930674T patent/SI1090019T1/xx unknown
- 1999-06-21 PL PL99345089A patent/PL194087B1/pl unknown
- 1999-06-21 IL IL14028499A patent/IL140284A0/xx active IP Right Grant
- 1999-06-21 OA OA1200000352A patent/OA11574A/en unknown
- 1999-06-21 PT PT99927999T patent/PT1090019E/pt unknown
- 1999-06-21 BR BR9911498-4A patent/BR9911498A/pt not_active Application Discontinuation
- 1999-06-21 SK SK1958-2000A patent/SK19582000A3/sk unknown
- 1999-06-21 CN CNA2004100119394A patent/CN1616459A/zh active Pending
- 1999-06-21 TR TR2001/00449T patent/TR200100449T2/xx unknown
- 1999-06-21 MY MYPI99002543A patent/MY122481A/en unknown
- 1999-06-21 EP EP99927999A patent/EP1090019B1/fr not_active Expired - Lifetime
- 1999-06-21 CN CNB998098957A patent/CN1202118C/zh not_active Expired - Fee Related
- 1999-06-21 ES ES99927999T patent/ES2226399T3/es not_active Expired - Lifetime
- 1999-06-21 US US09/736,018 patent/US6492348B1/en not_active Expired - Lifetime
- 1999-06-21 CO CO99038539A patent/CO5040216A1/es unknown
- 1999-06-21 AT AT99927999T patent/ATE277941T1/de not_active IP Right Cessation
- 1999-06-21 CA CA002335520A patent/CA2335520C/fr not_active Expired - Fee Related
- 1999-06-21 EA EA200001222A patent/EA003828B1/ru not_active IP Right Cessation
- 1999-06-22 AR ARP990102993A patent/AR018917A1/es unknown
- 1999-07-01 TW TW088111178A patent/TW541312B/zh not_active IP Right Cessation
-
2000
- 2000-12-13 IL IL140284A patent/IL140284A/en not_active IP Right Cessation
- 2000-12-14 ZA ZA200007514A patent/ZA200007514B/en unknown
- 2000-12-15 IS IS5773A patent/IS5773A/is unknown
- 2000-12-20 NO NO20006520A patent/NO318788B1/no unknown
- 2000-12-21 HR HR20000896A patent/HRP20000896B1/xx not_active IP Right Cessation
-
2001
- 2001-01-15 BG BG105155A patent/BG65064B1/bg unknown
- 2001-08-14 HK HK01105686A patent/HK1034978A1/xx not_active IP Right Cessation
-
2002
- 2002-06-11 JP JP2002170486A patent/JP2003040891A/ja active Pending
- 2002-08-13 US US10/217,107 patent/US6677316B2/en not_active Expired - Lifetime
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO318788B1 (no) | Adenosinderivater, samt fremgangsmate for fremstilling og anvendels derav og farmasoytisk preparat. | |
US6455510B1 (en) | Chemical Compounds | |
CA2470255C (fr) | Nucleosides n<sp>4</sp>-acylcytosines pour le traitement d'infections virales | |
JP2001522858A (ja) | 化合物 | |
JP2001522859A (ja) | 化合物 | |
BG107216A (bg) | 2-аминокарбонил-9н-пуринови производни | |
AU7035200A (en) | Compounds for the treatment of ischemia | |
TW201538517A (zh) | 作為流感病毒rna複製之抑制劑之經4’-二氟甲基取代之核苷衍生物 | |
CN113616659B (zh) | 含有腺苷衍生物的药物组合物 | |
CN101801970A (zh) | 腺苷衍生物、用于合成其的方法和包含其作为活性成分的用于预防和治疗炎症疾病的药物组合物 | |
EP2498774B1 (fr) | Composés à double action ciblant le récepteur d'adénosine a2a et un transporteur d'adénosine pour la prévention et le traitement de maladies neurodégénératives | |
EP4339193A1 (fr) | Composé ayant une activité antitumorale et son utilisation | |
CA3183668A1 (fr) | Urees cycliques d'azetidine | |
MXPA00012915A (en) | Adenosine derivatives | |
AU2002323990B2 (en) | Adenosine derivatives | |
WO2004026890A1 (fr) | Composes acetyleniques | |
CZ20004869A3 (cs) | Adenosinové deriváty | |
CA2999199A1 (fr) | Acide nucleique reticule guna, procede de production de ce dernier, et compose intermediaire | |
MXPA00004429A (en) | Adenosine a1 receptor agonists | |
MXPA00004428A (en) | Adensine a1 receptor agonists |