SK135699A3 - Pyrazolo[3,4-d]pyrimidinedione compounds, preparation method thereof, pharmaceutical composition containing them and their use - Google Patents

Pyrazolo[3,4-d]pyrimidinedione compounds, preparation method thereof, pharmaceutical composition containing them and their use Download PDF

Info

Publication number: SK135699A3
Authority: SK; Slovakia
Prior art keywords: formula; methyl; compound; pyrazolo; dione
Prior art date: 1997-04-15

Application number

SK1356-99A

Other languages

English (en)

Slovak (sk)

Inventor

David Cheshire

Martin Cooper

David Donald

Philip Thorne

Original Assignee

Astra Pharma Prod

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.)

1997-04-15

Filing date

1998-04-07

Publication date

2000-05-16

1998-04-07 Application filed by Astra Pharma Prod filed Critical Astra Pharma Prod

2000-05-16 Publication of SK135699A3 publication Critical patent/SK135699A3/sk

Links

-1 pyrimidinedione compounds Chemical class 0.000 title claims abstract description 56
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
238000002360 preparation method Methods 0.000 title claims description 8
238000000034 method Methods 0.000 claims abstract description 17
238000004519 manufacturing process Methods 0.000 claims abstract 3
150000001875 compounds Chemical class 0.000 claims description 105
125000000217 alkyl group Chemical group 0.000 claims description 35
229910052739 hydrogen Inorganic materials 0.000 claims description 32
150000003839 salts Chemical class 0.000 claims description 27
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 20
125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 20
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
238000006243 chemical reaction Methods 0.000 claims description 13
239000001257 hydrogen Substances 0.000 claims description 13
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
229910052717 sulfur Inorganic materials 0.000 claims description 12
239000011593 sulfur Substances 0.000 claims description 12
125000006022 2-methyl-2-propenyl group Chemical group 0.000 claims description 11
LOTBYPQQWICYBB-UHFFFAOYSA-N methyl n-hexyl-n-[2-(hexylamino)ethyl]carbamate Chemical compound CCCCCCNCCN(C(=O)OC)CCCCCC LOTBYPQQWICYBB-UHFFFAOYSA-N 0.000 claims description 11
229910002091 carbon monoxide Inorganic materials 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 10
125000005843 halogen group Chemical group 0.000 claims description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 10
125000003342 alkenyl group Chemical group 0.000 claims description 9
125000002947 alkylene group Chemical group 0.000 claims description 9
125000001624 naphthyl group Chemical group 0.000 claims description 7
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 6
125000004076 pyridyl group Chemical group 0.000 claims description 6
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 5
JQPPUDAFXKSBKZ-UHFFFAOYSA-N 3-(2-hydroxyethylsulfanyl)-5-methyl-7-(2-methylprop-2-enyl)-2-(naphthalen-1-ylmethyl)pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C1=CC=C2C(CN3N=C4N(C(N(C)C(=O)C4=C3SCCO)=O)CC(=C)C)=CC=CC2=C1 JQPPUDAFXKSBKZ-UHFFFAOYSA-N 0.000 claims description 4
CBKKPKLGJBZWKZ-UHFFFAOYSA-N 5-methyl-7-(2-methylpropyl)-2-(naphthalen-1-ylmethyl)-3-propylsulfanylpyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound N1=C2N(CC(C)C)C(=O)N(C)C(=O)C2=C(SCCC)N1CC1=CC=CC2=CC=CC=C12 CBKKPKLGJBZWKZ-UHFFFAOYSA-N 0.000 claims description 4
125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
239000002243 precursor Substances 0.000 claims description 4
238000002560 therapeutic procedure Methods 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
230000001506 immunosuppresive effect Effects 0.000 claims description 3
150000004702 methyl esters Chemical class 0.000 claims description 3
229910052757 nitrogen Inorganic materials 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
125000004430 oxygen atom Chemical group O* 0.000 claims description 3
150000008512 pyrimidinediones Chemical class 0.000 claims description 3
MRUJKRYZLRYJFH-UHFFFAOYSA-N 3-(4-hydroxybutyl)-5-methyl-7-(2-methylpropyl)-2-(naphthalen-1-ylmethyl)pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C1=CC=C2C(CN3N=C4N(C(N(C)C(=O)C4=C3CCCCO)=O)CC(C)C)=CC=CC2=C1 MRUJKRYZLRYJFH-UHFFFAOYSA-N 0.000 claims description 2
206010062016 Immunosuppression Diseases 0.000 claims description 2
239000001273 butane Substances 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
230000001939 inductive effect Effects 0.000 claims description 2
IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 claims description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 2
229910052698 phosphorus Inorganic materials 0.000 claims description 2
HOBJHRIVSVGHOI-UHFFFAOYSA-N 5-methyl-7-(2-methylprop-2-enyl)-2-(naphthalen-1-ylmethyl)-3-pyridin-2-ylsulfanylpyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C=12C(=O)N(C)C(=O)N(CC(=C)C)C2=NN(CC=2C3=CC=CC=C3C=CC=2)C=1SC1=CC=CC=N1 HOBJHRIVSVGHOI-UHFFFAOYSA-N 0.000 claims 1
125000000753 cycloalkyl group Chemical group 0.000 claims 1
201000010099 disease Diseases 0.000 abstract description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 8
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
239000000243 solution Substances 0.000 description 45
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 37
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 34
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
239000000203 mixture Substances 0.000 description 25
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 22
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 20
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
239000011541 reaction mixture Substances 0.000 description 16
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
239000007787 solid Substances 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
206010039083 rhinitis Diseases 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
238000002844 melting Methods 0.000 description 11
230000008018 melting Effects 0.000 description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 11
238000004440 column chromatography Methods 0.000 description 10
238000010992 reflux Methods 0.000 description 10
239000000377 silicon dioxide Substances 0.000 description 10
239000012267 brine Substances 0.000 description 9
229910052943 magnesium sulfate Inorganic materials 0.000 description 9
235000019341 magnesium sulphate Nutrition 0.000 description 9
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
150000002367 halogens Chemical group 0.000 description 8
239000002585 base Substances 0.000 description 7
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
206010047115 Vasculitis Diseases 0.000 description 6
239000002253 acid Substances 0.000 description 6
239000000460 chlorine Substances 0.000 description 6
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 6
239000000284 extract Substances 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
102000000588 Interleukin-2 Human genes 0.000 description 5
108010002350 Interleukin-2 Proteins 0.000 description 5
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
239000002904 solvent Substances 0.000 description 5
238000013518 transcription Methods 0.000 description 5
230000035897 transcription Effects 0.000 description 5
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
208000030507 AIDS Diseases 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
208000010668 atopic eczema Diseases 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
238000003756 stirring Methods 0.000 description 4
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
LGVSBMFKYTYNTE-UHFFFAOYSA-N 3-(3-hydroxypropylsulfanyl)-5-methyl-7-(2-methylpropyl)-1h-pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1C(SCCCO)=NN2 LGVSBMFKYTYNTE-UHFFFAOYSA-N 0.000 description 3
LYFRZKNYXCHJAA-UHFFFAOYSA-N 5-methyl-7-(2-methylpropyl)-2-(naphthalen-1-ylmethyl)pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C1=CC=C2C(CN3N=C4N(C(N(C)C(=O)C4=C3)=O)CC(C)C)=CC=CC2=C1 LYFRZKNYXCHJAA-UHFFFAOYSA-N 0.000 description 3
SGLXGFAZAARYJY-UHFFFAOYSA-N 6-Chloro-3-methyluracil Chemical compound CN1C(=O)C=C(Cl)NC1=O SGLXGFAZAARYJY-UHFFFAOYSA-N 0.000 description 3
PTXRYWYSWRFJJO-UHFFFAOYSA-N 6-hydrazinyl-3-methyl-1-(2-methylpropyl)pyrimidine-2,4-dione Chemical compound CC(C)CN1C(NN)=CC(=O)N(C)C1=O PTXRYWYSWRFJJO-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
108010018525 NFATC Transcription Factors Proteins 0.000 description 3
102000002673 NFATC Transcription Factors Human genes 0.000 description 3
210000001744 T-lymphocyte Anatomy 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
208000006673 asthma Diseases 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
SSBBQNOCGGHKJQ-UHFFFAOYSA-N hydroxy-(4-methylphenyl)-oxo-sulfanylidene-$l^{6}-sulfane Chemical compound CC1=CC=C(S(S)(=O)=O)C=C1 SSBBQNOCGGHKJQ-UHFFFAOYSA-N 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
210000004072 lung Anatomy 0.000 description 3
238000007799 mixed lymphocyte reaction assay Methods 0.000 description 3
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238000001953 recrystallisation Methods 0.000 description 3
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210000003491 skin Anatomy 0.000 description 3
239000000725 suspension Substances 0.000 description 3
208000011580 syndromic disease Diseases 0.000 description 3
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
BQNQEEJOUDSKHH-UHFFFAOYSA-N 3-(3-hydroxypropylsulfanyl)-5-methyl-7-(2-methylpropyl)-2-(naphthalen-1-ylmethyl)pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C1=CC=C2C(CN3N=C4N(C(N(C)C(=O)C4=C3SCCCO)=O)CC(C)C)=CC=CC2=C1 BQNQEEJOUDSKHH-UHFFFAOYSA-N 0.000 description 2
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
229960000549 4-dimethylaminophenol Drugs 0.000 description 2
SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 2
NSZSICWLXFCCRN-UHFFFAOYSA-N 6-chloro-3-methyl-1-(2-methylpropyl)pyrimidine-2,4-dione Chemical compound CC(C)CN1C(Cl)=CC(=O)N(C)C1=O NSZSICWLXFCCRN-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
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KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
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MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
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HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 2
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125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 2
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
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230000001404 mediated effect Effects 0.000 description 2
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239000000843 powder Substances 0.000 description 2
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208000023504 respiratory system disease Diseases 0.000 description 2
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229910000029 sodium carbonate Inorganic materials 0.000 description 2
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UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- 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
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Immunology (AREA)
Epidemiology (AREA)
Pulmonology (AREA)
Virology (AREA)
Tropical Medicine & Parasitology (AREA)
Transplantation (AREA)
Orthopedic Medicine & Surgery (AREA)
Molecular Biology (AREA)
Rheumatology (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
AIDS & HIV (AREA)
Physical Education & Sports Medicine (AREA)
Dermatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Use Of Switch Circuits For Exchanges And Methods Of Control Of Multiplex Exchanges (AREA)

SK1356-99A 1997-04-15 1998-04-07 Pyrazolo[3,4-d]pyrimidinedione compounds, preparation method thereof, pharmaceutical composition containing them and their use SK135699A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
SE9701398A SE9701398D0 (sv)	1997-04-15	1997-04-15	Novel compounds
PCT/SE1998/000640 WO1998046606A1 (en)	1997-04-15	1998-04-07	Novel compounds

Publications (1)

Publication Number	Publication Date
SK135699A3 true SK135699A3 (en)	2000-05-16

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ID=20406576

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1356-99A SK135699A3 (en)	1997-04-15	1998-04-07	Pyrazolo[3,4-d]pyrimidinedione compounds, preparation method thereof, pharmaceutical composition containing them and their use

Country Status (21)

Country	Link
US (1)	US6028074A (is)
EP (1)	EP0975636B1 (is)
JP (1)	JP2001520645A (is)
KR (1)	KR20010006350A (is)
CN (1)	CN1259951A (is)
AT (1)	ATE245648T1 (is)
AU (1)	AU733066B2 (is)
BR (1)	BR9808540A (is)
CA (1)	CA2286078A1 (is)
DE (1)	DE69816608T2 (is)
EE (1)	EE9900465A (is)
HU (1)	HUP0002104A3 (is)
ID (1)	ID22746A (is)
IL (1)	IL132153A0 (is)
IS (1)	IS5198A (is)
NO (1)	NO995006L (is)
PL (1)	PL336230A1 (is)
SE (1)	SE9701398D0 (is)
SK (1)	SK135699A3 (is)
TR (1)	TR199902538T2 (is)
WO (1)	WO1998046606A1 (is)

Families Citing this family (52)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SE9801399D0 (sv)	1998-04-21	1998-04-21	Astra Pharma Prod	Method and apparatus for filling containers
GC0000177A (en)	1998-12-17	2006-03-29	Smithkline Beecham	Thrombopoietin mimetics
CY2010012I2 (el)	2000-05-25	2020-05-29	Novartis Ag	Μιμητικα θρομβοποιητινης
JP2004527541A (ja)	2001-03-01	2004-09-09	スミスクライン・ビーチャム・コーポレイション	トロンボポエチン模倣物
JP2005511500A (ja)	2001-08-31	2005-04-28	ザロックフェラーユニバーシティー	脳におけるホスホジエステラーゼ活性およびホスホジエステラーゼ１ｂ媒介シグナル伝達の調節
MY142390A (en)	2002-05-22	2010-11-30	Glaxosmithkline Llc	3' - [(2z)-[1-(3,4-dimethylphenyl)-1,5- dihydro-3- methyl-5-0xo-4h-pyrazol-4- ylidene]hydrazino]-2' -hydroxy -[1,1' -biphenyl]-3-carboxylic acid bis-(monoethanolamine)
TW200526638A (en)	2003-10-22	2005-08-16	Smithkline Beecham Corp	2-(3,4-dimethylphenyl)-4-{[2-hydroxy-3'-(1H-tetrazol-5-yl)biphenyl-3-yl]-hydrazono}-5-methyl-2,4-dihydropyrazol-3-one choline
EP1901701A4 (en) *	2005-05-24	2012-05-02	David M Ott	BODY CARE AND MEDICAL PRODUCTS WITH JOINED SULFUR ORGANIC GROUPS
WO2006133261A2 (en)	2005-06-06	2006-12-14	Intra-Cellular Therapies, Inc.	Organic compounds
EP2023729B1 (en) *	2006-06-06	2016-05-04	Intra-Cellular Therapies, Inc.	Organic compounds
WO2008063505A1 (en)	2006-11-13	2008-05-29	Intra-Cellular Therapies, Inc.	Organic compounds
EP2089034A4 (en)	2006-12-05	2010-07-28	Intra Cellular Therapies Inc	NEW USES
ECSP077628A (es)	2007-05-03	2008-12-30	Smithkline Beechman Corp	Nueva composición farmacéutica
KR20120012831A (ko)	2007-12-06	2012-02-10	인트라-셀룰라 써래피스, 인코퍼레이티드.	유기 화합물
AU2008331833A1 (en) *	2007-12-06	2009-06-11	Intra-Cellular Therapies, Inc	Organic compounds
EA201170769A1 (ru)	2008-12-06	2012-02-28	Интра-Селлулар Терапиз, Инк.	Органические соединения
GEP20146046B (en)	2008-12-06	2014-02-25	Intracellular Therapies Inc	Organic compounds
MX2011005933A (es)	2008-12-06	2011-12-16	Intra Cellular Therapies Inc	Compuestos organicos.
WO2010065147A1 (en)	2008-12-06	2010-06-10	Intra-Cellular Therapies, Inc.	Organic compounds
EA201170771A1 (ru)	2008-12-06	2012-01-30	Интра-Селлулар Терапиз, Инк.	Органические соединения
BRPI0922700A2 (pt)	2008-12-06	2015-08-11	Intracellular Therapies Inc	Compostos orgânicos
WO2010098839A1 (en)	2009-02-25	2010-09-02	Intra-Cellular Therapies, Inc.	Pde 1 inhibitors for ophthalmic disorders
EP2411397B1 (en)	2009-03-23	2013-05-29	Glenmark Pharmaceuticals S.A.	Isothiazolo-pyrimidinedione derivatives as trpa1 modulators
CA2756535A1 (en)	2009-03-23	2010-09-30	Glenmark Pharmaceuticals, S.A.	Furopyrimidinedione derivatives as trpa1 modulators
PE20120774A1 (es)	2009-03-23	2012-06-27	Glenmark Pharmaceuticals Sa	COMPUESTOS DERIVADOS DE PIRAZOLO[3,4-d]PIRIMIDINDIONA COMO MODULADORES DE TRPA1
US8623880B2 (en)	2009-03-23	2014-01-07	Glenmark Pharmaceuticals S.A.	Fused pyrimidine-dione derivatives as TRPA1 modulators
WO2010132127A1 (en)	2009-05-13	2010-11-18	Intra-Cellular Therapies, Inc.	Organic compounds
AU2010254046C1 (en)	2009-05-29	2014-03-06	Novartis Ag	Methods of administration of thrombopoietin agonist compounds
EP2461673A4 (en)	2009-08-05	2013-08-07	Intra Cellular Therapies Inc	NEW REGULATOR PROTEINS AND HEMMER
US9434730B2 (en)	2010-05-31	2016-09-06	Intra-Cellular Therapies, Inc.	PDE1 inhibitor compounds
WO2011153135A1 (en)	2010-05-31	2011-12-08	Intra-Cellular Therapies, Inc.	Organic compounds
EP2576551A4 (en)	2010-05-31	2014-04-16	Intra Cellular Therapies Inc	ORGANIC CONNECTIONS
TW201206937A (en)	2010-05-31	2012-02-16	Intra Cellular Therapies Inc	Organic compounds
EP2717877B1 (en)	2011-06-10	2017-11-08	Intra-Cellular Therapies, Inc.	Organic compounds
SG11201408093PA (en)	2012-06-08	2015-01-29	Glenmark Pharmaceuticals Sa	Amides of 2-amino-4-arylthiazole compounds and their salts
EP2956141A4 (en)	2013-02-17	2016-10-26	Intra Cellular Therapies Inc	NEW USES
AU2014234990B2 (en)	2013-03-15	2017-11-16	Intra-Cellular Therapies, Inc.	Organic compounds
EP3479825B1 (en)	2013-03-15	2021-02-17	Intra-Cellular Therapies, Inc.	Pde1 inhibitors for use in the treatment and/or prevention of cns or pns diseases or disorders
JP6696904B2 (ja)	2014-01-08	2020-05-20	イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−ＣｅｌｌｕｌａｒＴｈｅｒａｐｉｅｓ，Ｉｎｃ．	製剤および医薬組成物
WO2015196186A1 (en)	2014-06-20	2015-12-23	Intra-Cellular Therapies, Inc.	Organic compounds
US10131671B2 (en)	2014-08-07	2018-11-20	Intra-Cellular Therapies, Inc.	Organic compounds
US9546175B2 (en)	2014-08-07	2017-01-17	Intra-Cellular Therapies, Inc.	Organic compounds
US10285992B2 (en)	2014-08-07	2019-05-14	Intra-Cellular Therapies, Inc.	Combinations of PDE1 inhibitors and NEP inhibitors and associated methods
RU2711442C2 (ru)	2014-09-17	2020-01-17	Интра-Селлулар Терапиз, Инк.	Соединения и способы
WO2016090380A1 (en)	2014-12-06	2016-06-09	Intra-Cellular Therapies, Inc.	Organic compounds
HK1244427A1 (zh)	2014-12-06	2018-08-10	Intra-Cellular Therapies, Inc.	有机化合物
US10682354B2 (en)	2016-03-28	2020-06-16	Intra-Cellular Therapies, Inc.	Compositions and methods
WO2018015088A1 (en) *	2016-06-23	2018-01-25	F. Hoffmann-La Roche Ag	Novel [1,2,31triazolo[4,5-d]pyrimidine derivatives
US11291666B2 (en)	2016-09-12	2022-04-05	Intra-Cellular Therapies, Inc.	Uses
EP3746081A4 (en)	2018-01-31	2021-10-27	Intra-Cellular Therapies, Inc.	Novel uses
US12410175B2 (en)	2019-09-03	2025-09-09	Intra-Cellular Therapies, Inc.	Compounds
US12364695B2 (en)	2020-06-02	2025-07-22	Intra-Cellular Therapies, Inc.	Methods of treating inflammatory disease

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0063381A1 (de) *	1981-04-22	1982-10-27	Byk Gulden Lomberg Chemische Fabrik GmbH	Neue Pyrazolo(3,4-d)pyrimidine, Verfahren zu deren Herstellung und sie enthaltende Arzneimittel
US4603203A (en) *	1983-12-14	1986-07-29	Takeda Chemical Industries, Ltd.	3-aminopyrazolo[3,4-d]pyrimidine derivatives and production thereof
EP0237289A3 (en) *	1986-03-14	1988-07-27	Takeda Chemical Industries, Ltd.	Pyrazolo [3,4-d] pyrimidine derivatives, their production and use
TW444018B (en) *	1992-12-17	2001-07-01	Pfizer	Pyrazolopyrimidines
PL175831B1 (pl) *	1992-12-17	1999-02-26	Pfizer	Pochodna pirazolu

1997
- 1997-04-15 SE SE9701398A patent/SE9701398D0/xx unknown
1998
- 1998-04-07 HU HU0002104A patent/HUP0002104A3/hu unknown
- 1998-04-07 WO PCT/SE1998/000640 patent/WO1998046606A1/en not_active Ceased
- 1998-04-07 CA CA002286078A patent/CA2286078A1/en not_active Abandoned
- 1998-04-07 DE DE69816608T patent/DE69816608T2/de not_active Expired - Fee Related
- 1998-04-07 BR BR9808540-9A patent/BR9808540A/pt not_active IP Right Cessation
- 1998-04-07 ID IDW991207A patent/ID22746A/id unknown
- 1998-04-07 TR TR1999/02538T patent/TR199902538T2/xx unknown
- 1998-04-07 EE EEP199900465A patent/EE9900465A/xx unknown
- 1998-04-07 AU AU70909/98A patent/AU733066B2/en not_active Ceased
- 1998-04-07 CN CN98806075A patent/CN1259951A/zh active Pending
- 1998-04-07 KR KR1019997009435A patent/KR20010006350A/ko not_active Withdrawn
- 1998-04-07 EP EP98917859A patent/EP0975636B1/en not_active Expired - Lifetime
- 1998-04-07 JP JP54380398A patent/JP2001520645A/ja not_active Ceased
- 1998-04-07 PL PL98336230A patent/PL336230A1/xx unknown
- 1998-04-07 AT AT98917859T patent/ATE245648T1/de not_active IP Right Cessation
- 1998-04-07 SK SK1356-99A patent/SK135699A3/sk unknown
- 1998-04-07 IL IL13215398A patent/IL132153A0/xx unknown
- 1998-08-07 US US09/068,304 patent/US6028074A/en not_active Expired - Fee Related
1999
- 1999-09-27 IS IS5198A patent/IS5198A/is unknown
- 1999-10-14 NO NO995006A patent/NO995006L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
CA2286078A1 (en)	1998-10-22
DE69816608D1 (de)	2003-08-28
BR9808540A (pt)	2000-05-23
IL132153A0 (en)	2001-03-19
NO995006D0 (no)	1999-10-14
US6028074A (en)	2000-02-22
JP2001520645A (ja)	2001-10-30
ATE245648T1 (de)	2003-08-15
CN1259951A (zh)	2000-07-12
EP0975636A1 (en)	2000-02-02
AU7090998A (en)	1998-11-11
NO995006L (no)	1999-10-14
EP0975636B1 (en)	2003-07-23
DE69816608T2 (de)	2004-04-15
SE9701398D0 (sv)	1997-04-15
IS5198A (is)	1999-09-27
WO1998046606A1 (en)	1998-10-22
HUP0002104A2 (hu)	2001-01-29
KR20010006350A (ko)	2001-01-26
TR199902538T2 (xx)	2000-02-21
AU733066B2 (en)	2001-05-03
PL336230A1 (en)	2000-06-19
ID22746A (id)	1999-12-09
HUP0002104A3 (en)	2002-03-28
EE9900465A (et)	2000-04-17

Publication	Publication Date	Title
SK135699A3 (en)	2000-05-16	Pyrazolo[3,4-d]pyrimidinedione compounds, preparation method thereof, pharmaceutical composition containing them and their use
US8372854B2 (en)	2013-02-12	Pyrrolo[2,3-D]pyrimidine compounds
US8633206B2 (en)	2014-01-21	Pyrrolo[2,3-D]pyrimidine compounds
US8575336B2 (en)	2013-11-05	Indazoles
AU717429B2 (en)	2000-03-23	Pyrrolo(3,4-(D)pyrimidinone derivatives and their use as medicaments
WO1995028387A1 (en)	1995-10-26	Benzamide compound and medicinal use thereof
US5137890A (en)	1992-08-11	4-phenyl tetrahydropyrido(4,3-d)pyrimidines
EP1252163B1 (de)	2003-09-24	4-pyridyl- und 2,4-pyrimidinyl-substituierte pyrrolderivate und ihre anwendung in der pharmazie
PL158165B1 (pl)	1992-08-31	Sposób wytwarzania acylowych pochodnych hydroksypirymidyn PL PL PL PL
WO2014016789A1 (en)	2014-01-30	Pyrazolo[3,4-d]pyrimidin-4(5h)-one derivatives as pde9 inhibitors
CZ360599A3 (cs)	2000-04-12	Nové sloučeniny
NZ338008A (en)	2001-04-27	Pyrazolo[3,4-d]pyrimidinedione compounds