OA11574A - Adenosine derivatives. - Google Patents

Adenosine derivatives. Download PDF

Info

Publication number: OA11574A
Authority: OA; OAPI
Prior art keywords: purin; diol; tetrahydrofuran; chloro; tert
Prior art date: 1998-06-23

Application number

OA1200000352A

Other languages

English (en)

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 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

1999-06-21

Publication date

2004-07-21

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

2004-07-21 Publication of OA11574A publication Critical patent/OA11574A/en

Links

150000003835 adenosine derivatives Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 189
125000005842 heteroatom Chemical group 0.000 claims abstract description 25
150000003839 salts Chemical class 0.000 claims abstract description 17
239000000556 agonist Substances 0.000 claims abstract description 9
108010060263 Adenosine A1 Receptor Proteins 0.000 claims abstract description 7
102000030814 Adenosine A1 receptor Human genes 0.000 claims abstract description 7
SSYDTHANSGMJTP-UHFFFAOYSA-N oxolane-3,4-diol Chemical compound OC1COCC1O SSYDTHANSGMJTP-UHFFFAOYSA-N 0.000 claims description 113
229910052757 nitrogen Inorganic materials 0.000 claims description 76
125000000217 alkyl group Chemical group 0.000 claims description 75
229910052736 halogen Inorganic materials 0.000 claims description 57
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 54
150000002367 halogens Chemical class 0.000 claims description 51
125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims description 51
-1 n-propyl,isopropyl Chemical group 0.000 claims description 46
125000000753 cycloalkyl group Chemical group 0.000 claims description 40
229910052760 oxygen Inorganic materials 0.000 claims description 33
125000000623 heterocyclic group Chemical group 0.000 claims description 32
229910052717 sulfur Inorganic materials 0.000 claims description 32
229910052739 hydrogen Inorganic materials 0.000 claims description 27
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
239000001257 hydrogen Substances 0.000 claims description 25
125000001424 substituent group Chemical group 0.000 claims description 22
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
125000004433 nitrogen atom Chemical group N* 0.000 claims description 20
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 16
DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims description 15
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 12
208000002193 Pain Diseases 0.000 claims description 12
125000003545 alkoxy group Chemical group 0.000 claims description 12
125000004434 sulfur atom Chemical group 0.000 claims description 12
125000002619 bicyclic group Chemical group 0.000 claims description 11
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
125000001931 aliphatic group Chemical group 0.000 claims description 9
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 9
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
125000004432 carbon atom Chemical group C* 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
239000011593 sulfur Substances 0.000 claims description 8
125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
125000003342 alkenyl group Chemical group 0.000 claims description 7
125000002947 alkylene group Chemical group 0.000 claims description 7
125000003118 aryl group Chemical group 0.000 claims description 7
235000021588 free fatty acids Nutrition 0.000 claims description 7
208000031225 myocardial ischemia Diseases 0.000 claims description 7
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 6
229910003827 NRaRb Inorganic materials 0.000 claims description 6
208000018262 Peripheral vascular disease Diseases 0.000 claims description 6
229910006069 SO3H Inorganic materials 0.000 claims description 6
230000008901 benefit Effects 0.000 claims description 6
239000000460 chlorine Substances 0.000 claims description 6
125000004430 oxygen atom Chemical group O* 0.000 claims description 6
125000006413 ring segment Chemical group 0.000 claims description 6
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 5
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
208000015114 central nervous system disease Diseases 0.000 claims description 5
229910052801 chlorine Inorganic materials 0.000 claims description 5
230000003247 decreasing effect Effects 0.000 claims description 5
150000002009 diols Chemical class 0.000 claims description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
208000006011 Stroke Diseases 0.000 claims description 4
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
150000002545 isoxazoles Chemical class 0.000 claims description 4
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 4
125000004545 purin-9-yl group Chemical group N1=CN=C2N(C=NC2=C1)* 0.000 claims description 4
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125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
CIPWFJMFGUJABH-WFXMFSGNSA-N (2r,3r,4s,5s)-2-[2-chloro-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(Cl)=NC(NC=4C(=CC(F)=CC=4)Cl)=C3N=C2)O1 CIPWFJMFGUJABH-WFXMFSGNSA-N 0.000 claims description 2
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JYLKFUYLNFIYEE-ZOMKSWQUSA-N (2r,3r,4s,5s)-2-[2-chloro-6-(2-ethylsulfonylethylamino)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(NCCS(=O)(=O)CC)=C3N=C2)O1 JYLKFUYLNFIYEE-ZOMKSWQUSA-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
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 description 2
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 description 2
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 claims description 2
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 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
150000005072 1,3,4-oxadiazoles Chemical class 0.000 claims description 2
IZPMNEDNPPWOJM-MEQWQQMJSA-N 2-[[9-[(2r,3r,4s,5s)-3,4-dihydroxy-5-(5-methyl-1,3-oxazol-2-yl)oxolan-2-yl]purin-6-yl]amino]-n-methylethanesulfonamide Chemical compound C1([C@H]2O[C@H]([C@@H]([C@@H]2O)O)N2C=3N=CN=C(C=3N=C2)NCCS(=O)(=O)NC)=NC=C(C)O1 IZPMNEDNPPWOJM-MEQWQQMJSA-N 0.000 claims description 2
HAWYWEUAHGSSCC-LUXYFRNMSA-N 2-[[9-[(2r,3r,4s,5s)-5-(3-tert-butyl-1,2-oxazol-5-yl)-3,4-dihydroxyoxolan-2-yl]-2-chloropurin-6-yl]amino]-n-ethylethanesulfonamide Chemical compound C1([C@H]2O[C@H]([C@@H]([C@@H]2O)O)N2C=3N=C(Cl)N=C(C=3N=C2)NCCS(=O)(=O)NCC)=CC(C(C)(C)C)=NO1 HAWYWEUAHGSSCC-LUXYFRNMSA-N 0.000 claims description 2
NRZNVVTZCZULLB-WFXMFSGNSA-N 2-[[9-[(2r,3r,4s,5s)-5-(3-tert-butyl-1,2-oxazol-5-yl)-3,4-dihydroxyoxolan-2-yl]-2-chloropurin-6-yl]amino]-n-propan-2-ylethanesulfonamide Chemical compound C1([C@H]2O[C@H]([C@@H]([C@@H]2O)O)N2C=3N=C(Cl)N=C(C=3N=C2)NCCS(=O)(=O)NC(C)C)=CC(C(C)(C)C)=NO1 NRZNVVTZCZULLB-WFXMFSGNSA-N 0.000 claims description 2
208000008784 apnea Diseases 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims description 2
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
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150000002916 oxazoles Chemical class 0.000 claims description 2
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150000003852 triazoles Chemical class 0.000 claims description 2
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 5
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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 claims 1
NCECMOPRCBXVOM-ZZHAAXSXSA-N (2s,3s,4r,5r)-2-(3-ethyl-1,2-oxazol-5-yl)-5-[6-[[(1s,2s)-2-hydroxycyclopentyl]amino]-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(N[C@@H]4[C@H](CCC4)O)=C3N=C2)O1 NCECMOPRCBXVOM-ZZHAAXSXSA-N 0.000 claims 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 claims 1
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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
125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims 1
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238000002560 therapeutic procedure Methods 0.000 abstract description 6
239000012453 solvate Substances 0.000 abstract 2
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239000002687 nonaqueous vehicle Substances 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
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ACFJLJIKQOJXQM-UHFFFAOYSA-N oxan-2-amine;hydrochloride Chemical compound Cl.NC1CCCCO1 ACFJLJIKQOJXQM-UHFFFAOYSA-N 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
CKXSVBRWQYXHGI-UHFFFAOYSA-N pent-1-yn-3-one Chemical compound CCC(=O)C#[C] CKXSVBRWQYXHGI-UHFFFAOYSA-N 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000008363 phosphate buffer Substances 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
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230000002335 preservative effect Effects 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
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 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
230000010410 reperfusion Effects 0.000 description 1
238000003571 reporter gene assay Methods 0.000 description 1
206010039073 rheumatoid arthritis Diseases 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
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
150000003385 sodium Chemical class 0.000 description 1
229910000029 sodium carbonate Inorganic materials 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
HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 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
229940080313 sodium starch Drugs 0.000 description 1
235000010265 sodium sulphite Nutrition 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
230000003019 stabilising effect Effects 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
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239000008117 stearic acid Substances 0.000 description 1
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150000003512 tertiary amines Chemical class 0.000 description 1
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239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
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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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
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- 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
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- C07—ORGANIC CHEMISTRY
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- 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
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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)
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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)
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OA1200000352A 1998-06-23 1999-06-21 Adenosine derivatives. OA11574A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GBGB9813554.4A GB9813554D0 (en)	1998-06-23	1998-06-23	Chemical compounds

Publications (1)

Publication Number	Publication Date
OA11574A true OA11574A (en)	2004-07-21

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ID=10834247

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OA1200000352A OA11574A (en)	1998-06-23	1999-06-21	Adenosine derivatives.

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US (2)	US6492348B1 (no)
EP (2)	EP1447407A1 (no)
JP (2)	JP3378240B2 (no)
KR (1)	KR100612797B1 (no)
CN (2)	CN1202118C (no)
AP (1)	AP2000002014A0 (no)
AR (1)	AR018917A1 (no)
AT (1)	ATE277941T1 (no)
AU (1)	AU758018B2 (no)
BG (1)	BG65064B1 (no)
BR (1)	BR9911498A (no)
CA (1)	CA2335520C (no)
CO (1)	CO5040216A1 (no)
DE (1)	DE69920697T2 (no)
EA (1)	EA003828B1 (no)
EE (1)	EE04853B1 (no)
ES (1)	ES2226399T3 (no)
GB (1)	GB9813554D0 (no)
GE (1)	GEP20032958B (no)
HR (1)	HRP20000896B1 (no)
HU (1)	HUP0102453A3 (no)
ID (1)	ID27484A (no)
IL (2)	IL140284A0 (no)
IS (1)	IS5773A (no)
MY (1)	MY122481A (no)
NO (1)	NO318788B1 (no)
NZ (1)	NZ508915A (no)
OA (1)	OA11574A (no)
PE (1)	PE20000704A1 (no)
PL (1)	PL194087B1 (no)
PT (1)	PT1090019E (no)
RS (1)	RS50042B (no)
SI (1)	SI1090019T1 (no)
SK (1)	SK19582000A3 (no)
TR (1)	TR200100449T2 (no)
TW (1)	TW541312B (no)
UA (1)	UA64794C2 (no)
WO (1)	WO1999067262A1 (no)
ZA (1)	ZA200007514B (no)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9813554D0 (en) *	1998-06-23	1998-08-19	Glaxo Group Ltd	Chemical compounds
JP5042425B2 (ja) *	2000-03-01	2012-10-03	ユーロセルティックソシエテアノニム	機能性胃腸疾患治療用トラマドール
GB0106867D0 (en) *	2001-03-20	2001-05-09	Glaxo Group Ltd	Process
US20040162422A1 (en) *	2001-03-20	2004-08-19	Adrian Hall	Chemical compounds
GB0115178D0 (en) *	2001-06-20	2001-08-15	Glaxo Group Ltd	Compounds
GB0115182D0 (en) *	2001-06-20	2001-08-15	Glaxo Group Ltd	Medicaments
US7157440B2 (en)	2001-07-13	2007-01-02	Cv Therapeutics, Inc.	Partial and full agonists of A1 adenosine receptors
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
WO2003070739A1 (en) *	2002-02-19	2003-08-28	Cv Therapeutics, Inc.	Partial and full agonists of a1 adenosine receptors
JP2005533792A (ja) *	2002-06-17	2005-11-10	グラクソ　グループ　リミテッド	複素環置換アデノシン誘導体の製造方法
AU2003263846B2 (en) *	2002-08-15	2009-12-17	Gilead Palo Alto, Inc.	Partial and full agonists of A1 adenosine receptors
WO2004055033A1 (en) *	2002-12-18	2004-07-01	Glaxo Group Limited	Adenosine derivative in polymorph iv form
WO2004055034A1 (en) *	2002-12-18	2004-07-01	Glaxo Group Limited	Polymorph
WO2004055032A1 (en) *	2002-12-18	2004-07-01	Glaxo Group Limited	Adenosine derivative in polymorph v form
WO2004069185A2 (en)	2003-02-03	2004-08-19	Cv Therapeutics Inc.	Partial and full agonists of a1 adenosine receptors
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
GB0607950D0 (en) *	2006-04-21	2006-05-31	Novartis Ag	Organic compounds
HRP20120494T1 (hr)	2006-04-21	2012-08-31	Novartis Ag	Derivati purina za uporabu kao agonista adenozin a2a receptora
GB0607953D0 (en) *	2006-04-21	2006-05-31	Novartis Ag	Organic compounds
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 (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
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 (en) *	2012-02-11	2013-08-15	Academia Sinica	Methods and compositions for treating pain
EA031895B1 (ru) *	2015-02-24	2019-03-29	Пфайзер Инк.	Замещенные нуклеозидные производные, полезные в качестве агентов против рака
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
AR131380A1 (es)	2022-12-16	2025-03-12	Astrazeneca Ab	Purinas 2,6,9-trisustituidas

Family Cites Families (13)

* Cited by examiner, † Cited by third party
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 (no) *	1992-05-14	1992-05-14	Novo Nordisk As
GB9301000D0 (en) *	1993-01-20	1993-03-10	Glaxo Group Ltd	Chemical compounds
WO1995003304A1 (en) *	1993-07-23	1995-02-02	Merrell Pharmaceuticals Inc.	Novel 9-n-bicyclic nucleoside agents useful as selective inhibitors of proinflammatory cytokines
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 EP EP04076465A patent/EP1447407A1/en not_active Withdrawn
- 1999-06-21 GE GEAP19995692A patent/GEP20032958B/en unknown
- 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/en not_active Ceased
- 1999-06-21 AT AT99927999T patent/ATE277941T1/de not_active IP Right Cessation
- 1999-06-21 ID IDW20010186A patent/ID27484A/id unknown
- 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
- 1999-06-21 JP JP2000555913A patent/JP3378240B2/ja not_active Expired - Lifetime
- 1999-06-21 CO CO99038539A patent/CO5040216A1/es unknown
- 1999-06-21 AU AU45146/99A patent/AU758018B2/en not_active Ceased
- 1999-06-21 DE DE69920697T patent/DE69920697T2/de not_active Expired - Lifetime
- 1999-06-21 AP APAP/P/2000/002014A patent/AP2000002014A0/en unknown
- 1999-06-21 UA UA2000127404A patent/UA64794C2/uk unknown
- 1999-06-21 MY MYPI99002543A patent/MY122481A/en unknown
- 1999-06-21 SI SI9930674T patent/SI1090019T1/xx 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 CN CNB998098957A patent/CN1202118C/zh not_active Expired - Fee Related
- 1999-06-21 NZ NZ508915A patent/NZ508915A/en unknown
- 1999-06-21 PL PL99345089A patent/PL194087B1/pl unknown
- 1999-06-21 CA CA002335520A patent/CA2335520C/en not_active Expired - Fee Related
- 1999-06-21 EE EEP200000784A patent/EE04853B1/xx not_active IP Right Cessation
- 1999-06-21 EP EP99927999A patent/EP1090019B1/en not_active Expired - Lifetime
- 1999-06-21 SK SK1958-2000A patent/SK19582000A3/sk unknown
- 1999-06-21 ES ES99927999T patent/ES2226399T3/es not_active Expired - Lifetime
- 1999-06-21 PT PT99927999T patent/PT1090019E/pt unknown
- 1999-06-21 CN CNA2004100119394A patent/CN1616459A/zh active Pending
- 1999-06-21 BR BR9911498-4A patent/BR9911498A/pt not_active Application Discontinuation
- 1999-06-21 OA OA1200000352A patent/OA11574A/en unknown
- 1999-06-21 RS YUP-828/00A patent/RS50042B/sr unknown
- 1999-06-21 IL IL14028499A patent/IL140284A0/xx active IP Right Grant
- 1999-06-22 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
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 (en)	2007-02-20
JP3378240B2 (ja)	2003-02-17
JP2003040891A (ja)	2003-02-13
HK1034978A1 (en)	2001-11-09
UA64794C2 (en)	2004-03-15
EP1090019A1 (en)	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 (en)	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
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 (en)	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 (en)	1999-12-29
PE20000704A1 (es)	2000-08-03
IL140284A (en)	2006-04-10
NO318788B1 (no)	2005-05-09
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 (en)	1999-12-29
CN1616459A (zh)	2005-05-18
ID27484A (id)	2001-04-12

Publication	Publication Date	Title
AU758018B2 (en)	2003-03-13	Adenosine derivatives
EP1030857B1 (en)	2004-08-18	Adenosine a1 receptor agonists
JP2009532448A (ja)	2009-09-10	置換アデニンおよびそれらの使用
EP3807290B1 (en)	2022-03-30	Tetrahydropyran-based thiodisaccharide mimics as galectin-3 inhibitors
AU2002323990B2 (en)	2006-03-30	Adenosine derivatives
HK1065047A (en)	2005-02-08	Adenosine derivatives
HK1034978B (en)	2005-04-08	Adenosine derivatives
MXPA00012915A (en)	2001-09-07	Adenosine derivatives
WO2004026890A1 (en)	2004-04-01	Acetylene compounds
CZ20004869A3 (cs)	2001-06-13	Adenosinové deriváty
WO2002074781A1 (en)	2002-09-26	Process for preparing n6-substituted aminopurine ribofuranose nucleosides
MXPA00004428A (en)	2001-05-17	Adensine a1 receptor agonists