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 PDF

Info

Publication number: NO318788B1
Authority: NO; Norway
Prior art keywords: purin; diol; tetrahydrofuran; chloro; tetrahydro
Prior art date: 1998-06-23

Application number

NO20006520A

Other languages

English (en)

Norwegian (no)

Other versions

NO20006520L (no

NO20006520D0 (no

Inventor

David Edmund Bays

Brian David Judkins

Richard Peter Charles Cousins

Andrew Michael Kenneth Pennell

Martin Pass

Colin David Eldred

Hazel Joan Dyke

Original Assignee

Glaxo Group Ltd

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

1998-06-23

Filing date

2000-12-20

Publication date

2005-05-09

2000-12-20 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

2000-12-20 Publication of NO20006520D0 publication Critical patent/NO20006520D0/no

2001-02-14 Publication of NO20006520L publication Critical patent/NO20006520L/no

2005-05-09 Publication of NO318788B1 publication Critical patent/NO318788B1/no

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
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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
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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
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Classifications

- C—CHEMISTRY; METALLURGY
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- C07D473/00—Heterocyclic compounds containing purine ring systems
- A—HUMAN NECESSITIES
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- 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
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
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- 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
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- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/20—Hypnotics; Sedatives
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- 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
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- 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)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Molecular Biology (AREA)
Diabetes (AREA)
Genetics & Genomics (AREA)
Biotechnology (AREA)
Biochemistry (AREA)
Pain & Pain Management (AREA)
Hematology (AREA)
Epidemiology (AREA)
Obesity (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Anesthesiology (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pulmonology (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)

NO20006520A 1998-06-23 2000-12-20 Adenosinderivater, samt fremgangsmate for fremstilling og anvendels derav og farmasoytisk preparat. NO318788B1 (no)

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 (39)

Country	Link
US (2)	US6492348B1 (fr)
EP (2)	EP1447407A1 (fr)
JP (2)	JP3378240B2 (fr)
KR (1)	KR100612797B1 (fr)
CN (2)	CN1202118C (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)
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)

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HRP20120494T1 (hr)	2006-04-21	2012-08-31	Novartis Ag	Derivati purina za uporabu kao agonista adenozin a2a receptora
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GB0607944D0 (en) *	2006-04-21	2006-05-31	Novartis Ag	Organic compounds
GB0607948D0 (en) *	2006-04-21	2006-05-31	Novartis Ag	Organic compounds
GB0607954D0 (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
JP2010508835A (ja) *	2006-11-10	2010-03-25	ノバルティスアーゲー	シクロペンテンジオールモノアセテート誘導体
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
WO2013120078A1 (fr) *	2012-02-11	2013-08-15	Academia Sinica	Méthodes et compositions de traitement de la douleur
EA031895B1 (ru) *	2015-02-24	2019-03-29	Пфайзер Инк.	Замещенные нуклеозидные производные, полезные в качестве агентов против рака
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1998
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1999
- 1999-06-21 PE PE1999000547A patent/PE20000704A1/es not_active Application Discontinuation
- 1999-06-21 EP EP04076465A patent/EP1447407A1/fr not_active Withdrawn
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- 1999-06-21 EA EA200001222A patent/EA003828B1/ru not_active IP Right Cessation
- 1999-06-21 TR TR2001/00449T patent/TR200100449T2/xx unknown
- 1999-06-21 WO PCT/EP1999/004182 patent/WO1999067262A1/fr not_active Ceased
- 1999-06-21 AT AT99927999T patent/ATE277941T1/de not_active IP Right Cessation
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- 1999-06-21 HR HR20000896A patent/HRP20000896B1/xx not_active IP Right Cessation
- 1999-06-21 KR KR1020007014749A patent/KR100612797B1/ko not_active Expired - Fee Related
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- 1999-06-21 CN CNA2004100119394A patent/CN1616459A/zh active Pending
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2001
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Also Published As

Publication number	Publication date
PL345089A1 (en)	2001-12-03
PT1090019E (pt)	2005-01-31
HRP20000896B1 (en)	2006-03-31
MY122481A (en)	2006-04-29
DE69920697T2 (de)	2005-02-24
GB9813554D0 (en)	1998-08-19
SI1090019T1 (en)	2005-02-28
CA2335520C (fr)	2007-02-20
JP3378240B2 (ja)	2003-02-17
JP2003040891A (ja)	2003-02-13
HK1034978A1 (en)	2001-11-09
UA64794C2 (en)	2004-03-15
EP1090019A1 (fr)	2001-04-11
TW541312B (en)	2003-07-11
BR9911498A (pt)	2001-03-20
ZA200007514B (en)	2002-01-23
IL140284A0 (en)	2002-02-10
DE69920697D1 (de)	2004-11-04
EE04853B1 (et)	2007-06-15
CO5040216A1 (es)	2001-05-29
AU4514699A (en)	2000-01-10
NO20006520L (no)	2001-02-14
US20030096788A1 (en)	2003-05-22
EP1447407A1 (fr)	2004-08-18
PL194087B1 (pl)	2007-04-30
IS5773A (is)	2000-12-15
SK19582000A3 (sk)	2001-11-06
HUP0102453A3 (en)	2002-10-28
EA003828B1 (ru)	2003-10-30
ES2226399T3 (es)	2005-03-16
US6492348B1 (en)	2002-12-10
OA11574A (en)	2004-07-21
NO20006520D0 (no)	2000-12-20
RS50042B (sr)	2008-11-28
TR200100449T2 (tr)	2001-08-21
CN1314910A (zh)	2001-09-26
BG65064B1 (bg)	2007-01-31
EP1090019B1 (fr)	2004-09-29
GEP20032958B (en)	2003-04-25
KR20010083067A (ko)	2001-08-31
ATE277941T1 (de)	2004-10-15
JP2002518509A (ja)	2002-06-25
HRP20000896A2 (en)	2001-12-31
EE200000784A (et)	2002-04-15
BG105155A (en)	2001-09-28
CN1202118C (zh)	2005-05-18
AU758018B2 (en)	2003-03-13
US6677316B2 (en)	2004-01-13
KR100612797B1 (ko)	2006-08-17
AR018917A1 (es)	2001-12-12
WO1999067262A1 (fr)	1999-12-29
PE20000704A1 (es)	2000-08-03
IL140284A (en)	2006-04-10
YU82800A (sh)	2003-04-30
HUP0102453A2 (hu)	2002-04-29
EA200001222A1 (ru)	2001-08-27
AP2000002014A0 (en)	2000-12-31
NZ508915A (en)	2003-09-26
CA2335520A1 (fr)	1999-12-29
CN1616459A (zh)	2005-05-18
ID27484A (id)	2001-04-12

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AU7035200A (en)	2001-04-30	Compounds for the treatment of ischemia
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EP4339193A1 (fr)	2024-03-20	Composé ayant une activité antitumorale et son utilisation
MXPA00012915A (en)	2001-09-07	Adenosine derivatives
HK1034978B (en)	2005-04-08	Adenosine derivatives
HK1065047A (en)	2005-02-08	Adenosine derivatives
AU2002323990B2 (en)	2006-03-30	Adenosine derivatives
WO2004026890A1 (fr)	2004-04-01	Composes acetyleniques
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CA2999199A1 (fr)	2017-03-23	Acide nucleique reticule guna, procede de production de ce dernier, et compose intermediaire
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