SK19582000A3 - Adenozínové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie - Google Patents

Adenozínové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie Download PDF

Info

Publication number: SK19582000A3
Authority: SK; Slovakia
Prior art keywords: purin; diol; tetrahydrofuran; alkyl; alk
Prior art date: 1998-06-23

Application number

SK1958-2000A

Other languages

English (en)

Slovak (sk)

Inventor

David Edmund Bays

Richard Peter Charles Cousins

Hazel Joan Dyke

Colin David Eldred

Brian David Judkins

Martin Pass

Andrew Michael Kenneth Pennell

Original Assignee

Glaxo Group Limited

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

1999-06-21

Publication date

2001-11-06

1999-06-21 Application filed by Glaxo Group Limited filed Critical Glaxo Group Limited

2001-11-06 Publication of SK19582000A3 publication Critical patent/SK19582000A3/sk

Links

150000003835 adenosine derivatives Chemical class 0.000 title claims description 31
239000008194 pharmaceutical composition Substances 0.000 title claims description 11
150000001875 compounds Chemical class 0.000 claims abstract description 215
125000005842 heteroatom Chemical group 0.000 claims abstract description 33
150000003839 salts Chemical class 0.000 claims abstract description 28
239000012453 solvate Substances 0.000 claims abstract description 23
239000000556 agonist Substances 0.000 claims abstract description 11
-1 oxadiazol-5-yl Chemical group 0.000 claims description 294
125000000217 alkyl group Chemical group 0.000 claims description 106
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 98
229910052757 nitrogen Inorganic materials 0.000 claims description 88
SSYDTHANSGMJTP-UHFFFAOYSA-N oxolane-3,4-diol Chemical compound OC1COCC1O SSYDTHANSGMJTP-UHFFFAOYSA-N 0.000 claims description 70
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 70
125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims description 65
229910052736 halogen Inorganic materials 0.000 claims description 54
150000002367 halogens Chemical class 0.000 claims description 50
125000000623 heterocyclic group Chemical group 0.000 claims description 47
125000004433 nitrogen atom Chemical group N* 0.000 claims description 45
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 43
125000001424 substituent group Chemical group 0.000 claims description 43
229910052739 hydrogen Inorganic materials 0.000 claims description 41
229910052760 oxygen Inorganic materials 0.000 claims description 41
229910052717 sulfur Inorganic materials 0.000 claims description 40
125000000753 cycloalkyl group Chemical group 0.000 claims description 38
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
239000001257 hydrogen Substances 0.000 claims description 35
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 34
CSFDTBRRIBJILD-UHFFFAOYSA-N 4-chloro-2-fluoroaniline Chemical compound NC1=CC=C(Cl)C=C1F CSFDTBRRIBJILD-UHFFFAOYSA-N 0.000 claims description 31
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
125000005843 halogen group Chemical group 0.000 claims description 27
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
125000004434 sulfur atom Chemical group 0.000 claims description 24
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 23
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 23
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 18
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
125000003545 alkoxy group Chemical group 0.000 claims description 16
125000002619 bicyclic group Chemical group 0.000 claims description 16
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
125000004430 oxygen atom Chemical group O* 0.000 claims description 16
208000002193 Pain Diseases 0.000 claims description 14
125000001931 aliphatic group Chemical group 0.000 claims description 13
239000000460 chlorine Substances 0.000 claims description 12
150000002431 hydrogen Chemical class 0.000 claims description 11
125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 11
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 10
125000004545 purin-9-yl group Chemical group N1=CN=C2N(C=NC2=C1)* 0.000 claims description 10
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 9
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
XRAKCYJTJGTSMM-UHFFFAOYSA-N 2-chloro-4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1Cl XRAKCYJTJGTSMM-UHFFFAOYSA-N 0.000 claims description 9
125000002947 alkylene group Chemical group 0.000 claims description 9
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 9
125000003118 aryl group Chemical group 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 9
AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical compound NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 claims description 8
125000004093 cyano group Chemical group *C#N 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 8
125000006413 ring segment Chemical group 0.000 claims description 8
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
230000000694 effects Effects 0.000 claims description 7
235000021588 free fatty acids Nutrition 0.000 claims description 7
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 6
125000004429 atom Chemical group 0.000 claims description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
125000006125 ethylsulfonyl group Chemical group 0.000 claims description 6
208000031225 myocardial ischemia Diseases 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
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 claims description 6
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 5
208000018262 Peripheral vascular disease Diseases 0.000 claims description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
229910052731 fluorine Inorganic materials 0.000 claims description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
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 claims description 4
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 claims description 4
FTZQXOJYPFINKJ-UHFFFAOYSA-N 2-fluoroaniline Chemical compound NC1=CC=CC=C1F FTZQXOJYPFINKJ-UHFFFAOYSA-N 0.000 claims description 4
125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 4
208000015114 central nervous system disease Diseases 0.000 claims description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
208000035475 disorder Diseases 0.000 claims description 4
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 4
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 4
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 claims description 4
PLMTYOYCKOUDRJ-MEQWQQMJSA-N (2s,3s,4r,5r)-2-(5-ethyl-1,3,4-oxadiazol-2-yl)-5-[6-(propan-2-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O1C(CC)=NN=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC(C)C)=C3N=C2)O1 PLMTYOYCKOUDRJ-MEQWQQMJSA-N 0.000 claims description 3
125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 claims description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
208000006011 Stroke Diseases 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
239000011737 fluorine Substances 0.000 claims description 3
125000000842 isoxazolyl group Chemical group 0.000 claims description 3
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
229940124597 therapeutic agent Drugs 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
ZFSROZQCHFPVRW-ZZHAAXSXSA-N (2s,3s,4r,5r)-2-(3-ethyl-1,2-oxazol-5-yl)-5-[6-[[(1s,2s)-2-hydroxycyclopentyl]amino]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(N[C@@H]4[C@H](CCC4)O)=C3N=C2)O1 ZFSROZQCHFPVRW-ZZHAAXSXSA-N 0.000 claims description 2
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 description 2
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 description 2
ZQYJPMPXQLNTPQ-QCUYGVNKSA-N (2s,3s,4r,5r)-2-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-[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=NC(NC=4C(=CC(Cl)=CC=4)F)=C3N=C2)O1 ZQYJPMPXQLNTPQ-QCUYGVNKSA-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
FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical group C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims description 2
125000004899 1-ethylpropylamino group Chemical group C(C)C(CC)N* 0.000 claims description 2
UXDDTJSRLPDVPH-UHFFFAOYSA-N 2-(3-ethyl-1,2-oxazol-5-yl)oxolane-3,4-diol Chemical compound O1N=C(CC)C=C1C1C(O)C(O)CO1 UXDDTJSRLPDVPH-UHFFFAOYSA-N 0.000 claims description 2
FWPKIGQRXMCRDN-FBHSLPMESA-N C(C)(C)(C)C1=NOC(=C1)[C@H]1O[C@H]([C@@H]([C@@H]1O)O)N1C2=NC=NC(=C2N=C1)NC1CCN(CC1)CCCC Chemical compound C(C)(C)(C)C1=NOC(=C1)[C@H]1O[C@H]([C@@H]([C@@H]1O)O)N1C2=NC=NC(=C2N=C1)NC1CCN(CC1)CCCC FWPKIGQRXMCRDN-FBHSLPMESA-N 0.000 claims description 2
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 2
125000006317 cyclopropyl amino group Chemical group 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
ULYSABNRLLVZCE-UHFFFAOYSA-N furan-3,4-diol Chemical compound OC1=COC=C1O ULYSABNRLLVZCE-UHFFFAOYSA-N 0.000 claims description 2
125000001072 heteroaryl group Chemical group 0.000 claims description 2
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 2
108020003175 receptors Proteins 0.000 claims description 2
102000005962 receptors Human genes 0.000 claims description 2
230000002829 reductive effect Effects 0.000 claims description 2
208000019116 sleep disease Diseases 0.000 claims description 2
150000003852 triazoles Chemical class 0.000 claims description 2
125000006164 6-membered heteroaryl group Chemical group 0.000 claims 2
208000003417 Central Sleep Apnea Diseases 0.000 claims 2
239000002582 adenosine A1 receptor agonist Substances 0.000 claims 2
125000000304 alkynyl group Chemical group 0.000 claims 2
210000002381 plasma Anatomy 0.000 claims 2
FAWDJJZJAHUDJZ-LUXYFRNMSA-N (2r,3r,4s,5s)-2-[2-chloro-6-(oxan-4-ylamino)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(NC4CCOCC4)=C3N=C2)O1 FAWDJJZJAHUDJZ-LUXYFRNMSA-N 0.000 claims 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 claims 1
BHXZUHBHHITIMG-MOROJQBDSA-N (2r,3s,4r,5r)-2-(3-tert-butyl-1h-1,2,4-triazol-5-yl)-5-[6-(oxan-4-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound N1C(C(C)(C)C)=NN=C1[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCOCC4)=C3N=C2)O1 BHXZUHBHHITIMG-MOROJQBDSA-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
VCIAOYUBXZDXAQ-JZJXAQOMSA-N (2s,3s,4r,5r)-2-(3-tert-butyl-1,2-oxazol-5-yl)-5-[6-[(1-ethylsulfonylpiperidin-4-yl)amino]purin-9-yl]oxolane-3,4-diol Chemical compound C1CN(S(=O)(=O)CC)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 VCIAOYUBXZDXAQ-JZJXAQOMSA-N 0.000 claims 1
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 1
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 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical group C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 claims 1
VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 claims 1
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims 1
VYGKAFKGJUWLMV-TVKQPGBESA-N ethyl 4-[[9-[(2r,3r,4s,5s)-3,4-dihydroxy-5-[3-(hydroxymethyl)-1,2-oxazol-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(CO)C=2)O1 VYGKAFKGJUWLMV-TVKQPGBESA-N 0.000 claims 1
125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
108010060263 Adenosine A1 Receptor Proteins 0.000 abstract description 5
102000030814 Adenosine A1 receptor Human genes 0.000 abstract description 5
238000002560 therapeutic procedure Methods 0.000 abstract description 2
238000000034 method Methods 0.000 description 479
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 366
239000000543 intermediate Substances 0.000 description 195
238000002360 preparation method Methods 0.000 description 181
238000001819 mass spectrum Methods 0.000 description 173
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 169
239000011541 reaction mixture Substances 0.000 description 158
239000000243 solution Substances 0.000 description 155
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 147
239000000203 mixture Substances 0.000 description 126
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 102
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 75
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 75
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 74
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 74
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 72
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 57
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239000002904 solvent Substances 0.000 description 53
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 52
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 52
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
239000007787 solid Substances 0.000 description 49
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
239000003480 eluent Substances 0.000 description 48
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
239000000741 silica gel Substances 0.000 description 46
229910002027 silica gel Inorganic materials 0.000 description 46
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 45
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 45
238000010992 reflux Methods 0.000 description 42
238000002156 mixing Methods 0.000 description 38
235000015165 citric acid Nutrition 0.000 description 37
229910052943 magnesium sulfate Inorganic materials 0.000 description 37
235000019341 magnesium sulphate Nutrition 0.000 description 37
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 36
239000008346 aqueous phase Substances 0.000 description 36
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LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
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Classifications

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- 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
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- 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
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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
- 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

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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)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Neurosurgery (AREA)
Molecular Biology (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Diabetes (AREA)
Biochemistry (AREA)
Pain & Pain Management (AREA)
Genetics & Genomics (AREA)
Biotechnology (AREA)
Obesity (AREA)
Epidemiology (AREA)
Hematology (AREA)
Rheumatology (AREA)
Pulmonology (AREA)
Endocrinology (AREA)
Emergency Medicine (AREA)
Anesthesiology (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)

SK1958-2000A 1998-06-23 1999-06-21 Adenozínové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie SK19582000A3 (sk)

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 (en)	1998-06-23	1999-06-21	Adenosine derivatives

Publications (1)

Publication Number	Publication Date
SK19582000A3 true SK19582000A3 (sk)	2001-11-06

Family

ID=10834247

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1958-2000A SK19582000A3 (sk)	1998-06-23	1999-06-21	Adenozínové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie

Country Status (39)

Country	Link
US (2)	US6492348B1 (id)
EP (2)	EP1447407A1 (id)
JP (2)	JP3378240B2 (id)
KR (1)	KR100612797B1 (id)
CN (2)	CN1616459A (id)
AP (1)	AP2000002014A0 (id)
AR (1)	AR018917A1 (id)
AT (1)	ATE277941T1 (id)
AU (1)	AU758018B2 (id)
BG (1)	BG65064B1 (id)
BR (1)	BR9911498A (id)
CA (1)	CA2335520C (id)
CO (1)	CO5040216A1 (id)
DE (1)	DE69920697T2 (id)
EA (1)	EA003828B1 (id)
EE (1)	EE04853B1 (id)
ES (1)	ES2226399T3 (id)
GB (1)	GB9813554D0 (id)
GE (1)	GEP20032958B (id)
HR (1)	HRP20000896B1 (id)
HU (1)	HUP0102453A3 (id)
ID (1)	ID27484A (id)
IL (2)	IL140284A0 (id)
IS (1)	IS5773A (id)
MY (1)	MY122481A (id)
NO (1)	NO318788B1 (id)
NZ (1)	NZ508915A (id)
OA (1)	OA11574A (id)
PE (1)	PE20000704A1 (id)
PL (1)	PL194087B1 (id)
PT (1)	PT1090019E (id)
RS (1)	RS50042B (id)
SI (1)	SI1090019T1 (id)
SK (1)	SK19582000A3 (id)
TR (1)	TR200100449T2 (id)
TW (1)	TW541312B (id)
UA (1)	UA64794C2 (id)
WO (1)	WO1999067262A1 (id)
ZA (1)	ZA200007514B (id)

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GB0115178D0 (en) *	2001-06-20	2001-08-15	Glaxo Group Ltd	Compounds
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WO2004055033A1 (en) *	2002-12-18	2004-07-01	Glaxo Group Limited	Adenosine derivative in polymorph iv form
AU2003292255A1 (en) *	2002-12-18	2004-07-09	Glaxo Group Limited	Polymorph
KR20050097971A (ko)	2003-02-03	2005-10-10	씨브이 쎄러퓨틱스, 인코포레이티드	Ａ₁아데노신 수용체의 부분 및 전 작용제
WO2005053712A1 (en) *	2003-12-02	2005-06-16	Glaxo Group Limited	Use of adenonsine derivatives for treating dyslipidemia, obesity, cardiovascular risk factors, metabolic syndrome, polycystic ovary syndrome, 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
EP2322525B1 (en) *	2006-04-21	2013-09-18	Novartis AG	Purine derivatives for use as adenosin A2A receptor agonists
GB0607954D0 (en) *	2006-04-21	2006-05-31	Novartis Ag	Organic compounds
GB0607950D0 (en) *	2006-04-21	2006-05-31	Novartis Ag	Organic compounds
GB0607944D0 (en) *	2006-04-21	2006-05-31	Novartis Ag	Organic compounds
GB0607953D0 (en) *	2006-04-21	2006-05-31	Novartis Ag	Organic compounds
GB0607948D0 (en) *	2006-04-21	2006-05-31	Novartis Ag	Organic compounds
EP1889846A1 (en)	2006-07-13	2008-02-20	Novartis AG	Purine derivatives as A2a agonists
EP1903044A1 (en) *	2006-09-14	2008-03-26	Novartis AG	Adenosine Derivatives as A2A Receptor Agonists
CA2669108A1 (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
US20150038445A1 (en) *	2012-02-11	2015-02-05	Academia Sinica	Methods and compositions for treating pain
JP6584521B2 (ja) *	2015-02-24	2019-10-02	ファイザー・インク	抗がん剤として有用な置換ヌクレオシド誘導体
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
JP2026500305A (ja)	2022-12-16	2026-01-06	アストラゼネカ・アクチエボラーグ	２，６，９三置換プリン

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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 HR HR20000896A patent/HRP20000896B1/xx not_active IP Right Cessation
- 1999-06-21 WO PCT/EP1999/004182 patent/WO1999067262A1/en not_active Ceased
- 1999-06-21 ID IDW20010186A patent/ID27484A/id unknown
- 1999-06-21 CA CA002335520A patent/CA2335520C/en not_active Expired - Fee Related
- 1999-06-21 NZ NZ508915A patent/NZ508915A/en unknown
- 1999-06-21 PE PE1999000547A patent/PE20000704A1/es not_active Application Discontinuation
- 1999-06-21 ES ES99927999T patent/ES2226399T3/es not_active Expired - Lifetime
- 1999-06-21 GE GEAP19995692A patent/GEP20032958B/en unknown
- 1999-06-21 AU AU45146/99A patent/AU758018B2/en not_active Ceased
- 1999-06-21 CN CNA2004100119394A patent/CN1616459A/zh active Pending
- 1999-06-21 PT PT99927999T patent/PT1090019E/pt unknown
- 1999-06-21 US US09/736,018 patent/US6492348B1/en not_active Expired - Lifetime
- 1999-06-21 HU HU0102453A patent/HUP0102453A3/hu unknown
- 1999-06-21 DE DE69920697T patent/DE69920697T2/de not_active Expired - Lifetime
- 1999-06-21 OA OA1200000352A patent/OA11574A/en unknown
- 1999-06-21 JP JP2000555913A patent/JP3378240B2/ja not_active Expired - Lifetime
- 1999-06-21 SI SI9930674T patent/SI1090019T1/xx unknown
- 1999-06-21 KR KR1020007014749A patent/KR100612797B1/ko not_active Expired - Fee Related
- 1999-06-21 PL PL99345089A patent/PL194087B1/pl unknown
- 1999-06-21 EP EP04076465A patent/EP1447407A1/en not_active Withdrawn
- 1999-06-21 UA UA2000127404A patent/UA64794C2/uk unknown
- 1999-06-21 EP EP99927999A patent/EP1090019B1/en not_active Expired - Lifetime
- 1999-06-21 CO CO99038539A patent/CO5040216A1/es unknown
- 1999-06-21 AP APAP/P/2000/002014A patent/AP2000002014A0/en unknown
- 1999-06-21 CN CNB998098957A patent/CN1202118C/zh not_active Expired - Fee Related
- 1999-06-21 RS YUP-828/00A patent/RS50042B/sr unknown
- 1999-06-21 IL IL14028499A patent/IL140284A0/xx active IP Right Grant
- 1999-06-21 MY MYPI99002543A patent/MY122481A/en unknown
- 1999-06-21 EE EEP200000784A patent/EE04853B1/xx not_active IP Right Cessation
- 1999-06-21 EA EA200001222A patent/EA003828B1/ru not_active IP Right Cessation
- 1999-06-21 BR BR9911498-4A patent/BR9911498A/pt not_active Application Discontinuation
- 1999-06-21 AT AT99927999T patent/ATE277941T1/de not_active IP Right Cessation
- 1999-06-21 TR TR2001/00449T patent/TR200100449T2/xx unknown
- 1999-06-21 SK SK1958-2000A patent/SK19582000A3/sk unknown
- 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
2001
- 2001-01-15 BG BG105155A patent/BG65064B1/bg unknown
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

Publication number	Publication date
HUP0102453A2 (hu)	2002-04-29
US6677316B2 (en)	2004-01-13
EA003828B1 (ru)	2003-10-30
CN1202118C (zh)	2005-05-18
YU82800A (sh)	2003-04-30
HK1034978A1 (en)	2001-11-09
NZ508915A (en)	2003-09-26
US20030096788A1 (en)	2003-05-22
IS5773A (is)	2000-12-15
HRP20000896A2 (en)	2001-12-31
ID27484A (id)	2001-04-12
JP2002518509A (ja)	2002-06-25
BG65064B1 (bg)	2007-01-31
EE200000784A (et)	2002-04-15
EA200001222A1 (ru)	2001-08-27
IL140284A (en)	2006-04-10
BR9911498A (pt)	2001-03-20
US6492348B1 (en)	2002-12-10
BG105155A (en)	2001-09-28
GEP20032958B (en)	2003-04-25
KR100612797B1 (ko)	2006-08-17
EE04853B1 (et)	2007-06-15
CA2335520C (en)	2007-02-20
PE20000704A1 (es)	2000-08-03
AU758018B2 (en)	2003-03-13
NO20006520D0 (no)	2000-12-20
AR018917A1 (es)	2001-12-12
CN1616459A (zh)	2005-05-18
OA11574A (en)	2004-07-21
UA64794C2 (en)	2004-03-15
JP2003040891A (ja)	2003-02-13
PT1090019E (pt)	2005-01-31
EP1090019A1 (en)	2001-04-11
TW541312B (en)	2003-07-11
AU4514699A (en)	2000-01-10
AP2000002014A0 (en)	2000-12-31
CO5040216A1 (es)	2001-05-29
HUP0102453A3 (en)	2002-10-28
EP1090019B1 (en)	2004-09-29
HRP20000896B1 (en)	2006-03-31
RS50042B (sr)	2008-11-28
TR200100449T2 (tr)	2001-08-21
PL194087B1 (pl)	2007-04-30
PL345089A1 (en)	2001-12-03
NO20006520L (no)	2001-02-14
MY122481A (en)	2006-04-29
NO318788B1 (no)	2005-05-09
ZA200007514B (en)	2002-01-23
SI1090019T1 (en)	2005-02-28
CN1314910A (zh)	2001-09-26
ATE277941T1 (de)	2004-10-15
DE69920697T2 (de)	2005-02-24
EP1447407A1 (en)	2004-08-18
DE69920697D1 (de)	2004-11-04
WO1999067262A1 (en)	1999-12-29
CA2335520A1 (en)	1999-12-29
GB9813554D0 (en)	1998-08-19
KR20010083067A (ko)	2001-08-31
JP3378240B2 (ja)	2003-02-17
IL140284A0 (en)	2002-02-10
ES2226399T3 (es)	2005-03-16

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