AU727615B2 - 1,5-dihydro-pyrazolo(3,4-d)-pyrimidinone derivatives - Google Patents
1,5-dihydro-pyrazolo(3,4-d)-pyrimidinone derivatives Download PDFInfo
- Publication number
- AU727615B2 AU727615B2 AU68240/98A AU6824098A AU727615B2 AU 727615 B2 AU727615 B2 AU 727615B2 AU 68240/98 A AU68240/98 A AU 68240/98A AU 6824098 A AU6824098 A AU 6824098A AU 727615 B2 AU727615 B2 AU 727615B2
- Authority
- AU
- Australia
- Prior art keywords
- chain
- carbon atoms
- straight
- formula
- phenyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Ceased
Links
- RAEVFJQVGBSKJO-UHFFFAOYSA-N 1,2,4,7-tetrahydropyrazolo[3,4-d]pyrimidin-3-one Chemical class N1=CNCC2=C1NNC2=O RAEVFJQVGBSKJO-UHFFFAOYSA-N 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 64
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 201000010099 disease Diseases 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 10
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 5
- 208000026106 cerebrovascular disease Diseases 0.000 claims abstract description 4
- 230000002526 effect on cardiovascular system Effects 0.000 claims abstract description 4
- 210000005259 peripheral blood Anatomy 0.000 claims abstract 3
- 239000011886 peripheral blood Substances 0.000 claims abstract 3
- 239000000203 mixture Substances 0.000 claims description 101
- 125000004432 carbon atom Chemical group C* 0.000 claims description 80
- -1 cyano, hydroxyl Chemical group 0.000 claims description 47
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 29
- 239000011734 sodium Substances 0.000 claims description 28
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 239000000460 chlorine Substances 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 125000002947 alkylene group Chemical group 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 239000011737 fluorine Substances 0.000 claims description 13
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 125000002541 furyl group Chemical group 0.000 claims description 12
- 125000001544 thienyl group Chemical group 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 239000012442 inert solvent Substances 0.000 claims description 11
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 238000007363 ring formation reaction Methods 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000001041 indolyl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000004450 alkenylene group Chemical group 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 238000009472 formulation Methods 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 239000007800 oxidant agent Substances 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 201000001881 impotence Diseases 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- MIQLKTPRUZLHFE-UHFFFAOYSA-N 1,5,6,7a-tetrahydropyrano[2,3-c]pyrazol-3-amine Chemical class N1NC(C=2C1OCCC=2)=N MIQLKTPRUZLHFE-UHFFFAOYSA-N 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 230000010933 acylation Effects 0.000 claims description 2
- 238000005917 acylation reaction Methods 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 230000009467 reduction Effects 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- 150000003217 pyrazoles Chemical class 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 228
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 210
- 239000000243 solution Substances 0.000 description 124
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 121
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 81
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 75
- 239000002904 solvent Substances 0.000 description 72
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- 239000012071 phase Substances 0.000 description 53
- 238000004587 chromatography analysis Methods 0.000 description 50
- 238000000746 purification Methods 0.000 description 45
- 239000007787 solid Substances 0.000 description 44
- 229920006395 saturated elastomer Polymers 0.000 description 43
- 239000003921 oil Substances 0.000 description 42
- 235000019439 ethyl acetate Nutrition 0.000 description 41
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 37
- 235000017557 sodium bicarbonate Nutrition 0.000 description 37
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 32
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 28
- 239000012074 organic phase Substances 0.000 description 28
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 25
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 21
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 20
- 150000003254 radicals Chemical class 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 17
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 14
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- 239000003125 aqueous solvent Substances 0.000 description 13
- 239000002585 base Substances 0.000 description 12
- HEMYXNDMAAOTCK-UHFFFAOYSA-N methyl 2-(1,3-benzodioxol-5-yl)acetate Chemical compound COC(=O)CC1=CC=C2OCOC2=C1 HEMYXNDMAAOTCK-UHFFFAOYSA-N 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 238000010626 work up procedure Methods 0.000 description 8
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 7
- TYNSUEXNGLNQSS-UHFFFAOYSA-N 6-carbamoyl-5-hydroxy-4-methoxy-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylic acid Chemical compound C1=2C=C(C(O)=O)NC=2C(OC)=C(O)C2=C1CCN2C(N)=O TYNSUEXNGLNQSS-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 229910052786 argon Inorganic materials 0.000 description 7
- 235000015165 citric acid Nutrition 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 239000003208 petroleum Substances 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- GXMOSBIOUZALPM-UHFFFAOYSA-N 2-(1-ethoxypropylidene)propanedinitrile Chemical compound CCOC(CC)=C(C#N)C#N GXMOSBIOUZALPM-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- IUYQIJQHYDZUDF-UHFFFAOYSA-N pyrazolo[3,4-d]pyrimidin-4-one Chemical compound O=C1N=CN=C2N=NC=C12 IUYQIJQHYDZUDF-UHFFFAOYSA-N 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- BOSVWXDDFBSSIZ-UHFFFAOYSA-N 2-(1-ethoxyethylidene)propanedinitrile Chemical compound CCOC(C)=C(C#N)C#N BOSVWXDDFBSSIZ-UHFFFAOYSA-N 0.000 description 5
- ICXAYWYCLCNIBP-UHFFFAOYSA-N 5-amino-1-decan-4-yl-3-methylpyrazole-4-carboxamide Chemical compound CCCCCCC(CCC)N1N=C(C)C(C(N)=O)=C1N ICXAYWYCLCNIBP-UHFFFAOYSA-N 0.000 description 5
- FKNWZDVPYBLRKY-UHFFFAOYSA-N 5-amino-3-methoxy-1-(5-phenylpentan-2-yl)pyrazole-4-carbonitrile Chemical compound NC1=C(C#N)C(OC)=NN1C(C)CCCC1=CC=CC=C1 FKNWZDVPYBLRKY-UHFFFAOYSA-N 0.000 description 5
- QAXDVKBGZRMSHF-UHFFFAOYSA-N 6-acetyl-5-hydroxy-4-methoxy-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylic acid Chemical compound C1=2C=C(C(O)=O)NC=2C(OC)=C(O)C2=C1CCN2C(C)=O QAXDVKBGZRMSHF-UHFFFAOYSA-N 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- DILOFCBIBDMHAY-UHFFFAOYSA-N methyl 2-(3,4-dimethoxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(OC)C(OC)=C1 DILOFCBIBDMHAY-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
- GEDSOQMESIYDQX-UHFFFAOYSA-N 5-phenylpentan-2-ylhydrazine Chemical compound NNC(C)CCCC1=CC=CC=C1 GEDSOQMESIYDQX-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 210000000709 aorta Anatomy 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- MWNQUUNHAXFIDV-UHFFFAOYSA-N decan-4-ylhydrazine Chemical compound CCCCCCC(NN)CCC MWNQUUNHAXFIDV-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- IGXAJUPIDFDTTR-UHFFFAOYSA-N methyl 2-(3,4,5-trimethoxyphenyl)acetate Chemical compound COC(=O)CC1=CC(OC)=C(OC)C(OC)=C1 IGXAJUPIDFDTTR-UHFFFAOYSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- JDAADONCQPUNRY-UHFFFAOYSA-N tert-butyl n-(5-phenylpentan-2-ylideneamino)carbamate Chemical compound CC(C)(C)OC(=O)NN=C(C)CCCC1=CC=CC=C1 JDAADONCQPUNRY-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- VQVBNWUUKLBHGI-UHFFFAOYSA-N 2-(4-bromophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=C(Br)C=C1 VQVBNWUUKLBHGI-UHFFFAOYSA-N 0.000 description 3
- XIHOVMBYUMTLNJ-UHFFFAOYSA-N 2-(dimethoxymethylidene)propanedinitrile Chemical group COC(OC)=C(C#N)C#N XIHOVMBYUMTLNJ-UHFFFAOYSA-N 0.000 description 3
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 3
- DZHPZBOEIHHVDM-UHFFFAOYSA-N 5-amino-1-(2-hydroxy-6-phenylhexan-3-yl)-3-methoxypyrazole-4-carbonitrile Chemical compound NC1=C(C#N)C(OC)=NN1C(C(C)O)CCCC1=CC=CC=C1 DZHPZBOEIHHVDM-UHFFFAOYSA-N 0.000 description 3
- SAJMNAAPHDISPS-UHFFFAOYSA-N 5-amino-1-decan-4-yl-3-ethylpyrazole-4-carboxamide Chemical compound CCCCCCC(CCC)N1N=C(CC)C(C(N)=O)=C1N SAJMNAAPHDISPS-UHFFFAOYSA-N 0.000 description 3
- LUQFHUKHDKTFNX-UHFFFAOYSA-N 5-amino-1-decan-4-yl-3-propylpyrazole-4-carboxamide Chemical compound CCCCCCC(CCC)N1N=C(CCC)C(C(N)=O)=C1N LUQFHUKHDKTFNX-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 108010044467 Isoenzymes Proteins 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 3
- LJMHFESNTLDPNK-UHFFFAOYSA-N methyl 2-(3-chloro-4-methoxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(OC)C(Cl)=C1 LJMHFESNTLDPNK-UHFFFAOYSA-N 0.000 description 3
- PJVUOWPNGGCOSE-UHFFFAOYSA-N methyl 2-(4-methylpiperazin-1-yl)sulfonyl-2-phenylacetate Chemical compound C1CN(C)CCN1S(=O)(=O)C(C(=O)OC)C1=CC=CC=C1 PJVUOWPNGGCOSE-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- GLJGNZFOPZFERF-UHFFFAOYSA-N nonan-3-ylhydrazine Chemical compound CCCCCCC(CC)NN GLJGNZFOPZFERF-UHFFFAOYSA-N 0.000 description 3
- FODQIVGFADUBKE-UHFFFAOYSA-N octamoxin Chemical compound CCCCCCC(C)NN FODQIVGFADUBKE-UHFFFAOYSA-N 0.000 description 3
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000005051 trimethylchlorosilane Substances 0.000 description 3
- ZVXKYWHJBYIYNI-UHFFFAOYSA-N 1h-pyrazole-4-carboxamide Chemical compound NC(=O)C=1C=NNC=1 ZVXKYWHJBYIYNI-UHFFFAOYSA-N 0.000 description 2
- RQUBFCKHWLKLRV-UHFFFAOYSA-N 2-(1-ethoxybutylidene)propanedinitrile Chemical compound CCCC(OCC)=C(C#N)C#N RQUBFCKHWLKLRV-UHFFFAOYSA-N 0.000 description 2
- QBJIMTPENIGDOG-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)acetyl chloride Chemical compound COC1=CC=C(CC(Cl)=O)C=C1OC QBJIMTPENIGDOG-UHFFFAOYSA-N 0.000 description 2
- OEICGMPRFOJHKO-UHFFFAOYSA-N 2-(ethoxymethylidene)propanedinitrile Chemical compound CCOC=C(C#N)C#N OEICGMPRFOJHKO-UHFFFAOYSA-N 0.000 description 2
- CYZQHZJORZIETF-UHFFFAOYSA-N 2-hydroxy-6-phenylhexan-3-one Chemical compound CC(O)C(=O)CCCC1=CC=CC=C1 CYZQHZJORZIETF-UHFFFAOYSA-N 0.000 description 2
- ZPVFWPFBNIEHGJ-UHFFFAOYSA-N 2-octanone Chemical compound CCCCCCC(C)=O ZPVFWPFBNIEHGJ-UHFFFAOYSA-N 0.000 description 2
- XMZQWZJMTBCUFT-UHFFFAOYSA-N 3-bromopropylbenzene Chemical compound BrCCCC1=CC=CC=C1 XMZQWZJMTBCUFT-UHFFFAOYSA-N 0.000 description 2
- DTRQOKJQNZVPMZ-UHFFFAOYSA-N 5-amino-1-(2-hydroxy-6-phenylhexan-3-yl)-3-methylpyrazole-4-carboxamide Chemical compound N1=C(C)C(C(N)=O)=C(N)N1C(C(O)C)CCCC1=CC=CC=C1 DTRQOKJQNZVPMZ-UHFFFAOYSA-N 0.000 description 2
- LKXHGCAQFYIOOO-UHFFFAOYSA-N 5-amino-1-(2-hydroxy-6-phenylhexan-3-yl)pyrazole-4-carboxamide Chemical compound N1=CC(C(N)=O)=C(N)N1C(C(O)C)CCCC1=CC=CC=C1 LKXHGCAQFYIOOO-UHFFFAOYSA-N 0.000 description 2
- VQZNHJYFUCKLOM-UHFFFAOYSA-N 5-amino-1-(5-phenylpentan-2-yl)pyrazole-4-carboxamide Chemical compound N1=CC(C(N)=O)=C(N)N1C(C)CCCC1=CC=CC=C1 VQZNHJYFUCKLOM-UHFFFAOYSA-N 0.000 description 2
- WHQIUITUQMWVAW-UHFFFAOYSA-N 5-amino-3-ethyl-1-(5-phenylpentan-2-yl)pyrazole-4-carboxamide Chemical compound NC1=C(C(N)=O)C(CC)=NN1C(C)CCCC1=CC=CC=C1 WHQIUITUQMWVAW-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- IYTXKIXETAELAV-UHFFFAOYSA-N Aethyl-n-hexyl-keton Natural products CCCCCCC(=O)CC IYTXKIXETAELAV-UHFFFAOYSA-N 0.000 description 2
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- 102000002723 Atrial Natriuretic Factor Human genes 0.000 description 2
- 101800001288 Atrial natriuretic factor Proteins 0.000 description 2
- 101800001890 Atrial natriuretic peptide Proteins 0.000 description 2
- 102000000584 Calmodulin Human genes 0.000 description 2
- 108010041952 Calmodulin Proteins 0.000 description 2
- 101001098806 Dictyostelium discoideum cGMP-specific 3',5'-cGMP phosphodiesterase 3 Proteins 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 238000002399 angioplasty Methods 0.000 description 2
- 230000003288 anthiarrhythmic effect Effects 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- OJKBCQOJVMAHDX-UHFFFAOYSA-N diethyl(pyridin-3-yl)borane Chemical compound CCB(CC)C1=CC=CN=C1 OJKBCQOJVMAHDX-UHFFFAOYSA-N 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000000066 endothelium dependent relaxing factor Substances 0.000 description 2
- 238000001952 enzyme assay Methods 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- QHJOWSXZDCTNQX-UHFFFAOYSA-N methyl 2-(4-bromophenyl)acetate Chemical compound COC(=O)CC1=CC=C(Br)C=C1 QHJOWSXZDCTNQX-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- FDFKDGDRVTYEBX-UHFFFAOYSA-N n-[5-amino-3-ethyl-1-(2-hydroxy-6-phenylhexan-3-yl)pyrazol-4-yl]acetamide Chemical compound NC1=C(NC(C)=O)C(CC)=NN1C(C(C)O)CCCC1=CC=CC=C1 FDFKDGDRVTYEBX-UHFFFAOYSA-N 0.000 description 2
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- WPEJAMNVWNRRKN-UHFFFAOYSA-N tert-butyl n-(nonan-3-ylideneamino)carbamate Chemical compound CCCCCCC(CC)=NNC(=O)OC(C)(C)C WPEJAMNVWNRRKN-UHFFFAOYSA-N 0.000 description 2
- HAKJMZSVOFUMHF-UHFFFAOYSA-N tert-butyl n-(octan-2-ylideneamino)carbamate Chemical compound CCCCCCC(C)=NNC(=O)OC(C)(C)C HAKJMZSVOFUMHF-UHFFFAOYSA-N 0.000 description 2
- DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 210000002229 urogenital system Anatomy 0.000 description 2
- 230000000304 vasodilatating effect Effects 0.000 description 2
- XAEOVQODHLLNKX-UHFFFAOYSA-N (3-aminophenyl)boronic acid;hydrate Chemical compound O.NC1=CC=CC(B(O)O)=C1 XAEOVQODHLLNKX-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- KOPMZTKUZCNGFY-UHFFFAOYSA-N 1,1,1-triethoxybutane Chemical compound CCCC(OCC)(OCC)OCC KOPMZTKUZCNGFY-UHFFFAOYSA-N 0.000 description 1
- NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 1
- FGWYWKIOMUZSQF-UHFFFAOYSA-N 1,1,1-triethoxypropane Chemical compound CCOC(CC)(OCC)OCC FGWYWKIOMUZSQF-UHFFFAOYSA-N 0.000 description 1
- UNEBVOHBARDSCT-UHFFFAOYSA-N 1-decan-4-yl-3-ethyl-6-[(3,4,5-trimethoxyphenyl)methyl]-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound CCCCCCC(CCC)N1N=C(CC)C(C(N2)=O)=C1N=C2CC1=CC(OC)=C(OC)C(OC)=C1 UNEBVOHBARDSCT-UHFFFAOYSA-N 0.000 description 1
- CKCVJTFTDPLYLC-UHFFFAOYSA-N 1-decan-4-yl-3-methyl-6-[(3,4,5-trimethoxyphenyl)methyl]-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound CCCCCCC(CCC)N1N=C(C)C(C(N2)=O)=C1N=C2CC1=CC(OC)=C(OC)C(OC)=C1 CKCVJTFTDPLYLC-UHFFFAOYSA-N 0.000 description 1
- IBOCASWDGMPZJG-UHFFFAOYSA-N 1-decan-4-yl-3-propyl-6-[(3,4,5-trimethoxyphenyl)methyl]-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound CCCCCCC(CCC)N1N=C(CCC)C(C(N2)=O)=C1N=C2CC1=CC(OC)=C(OC)C(OC)=C1 IBOCASWDGMPZJG-UHFFFAOYSA-N 0.000 description 1
- YKIRBNPGXSPXDC-UHFFFAOYSA-N 1-decan-4-yl-6-[(3,4-dichlorophenyl)methyl]-3-ethyl-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound CCCCCCC(CCC)N1N=C(CC)C(C(N2)=O)=C1N=C2CC1=CC=C(Cl)C(Cl)=C1 YKIRBNPGXSPXDC-UHFFFAOYSA-N 0.000 description 1
- DPTSLFSIQSJLOT-UHFFFAOYSA-N 1-decan-4-yl-6-[(3,4-dichlorophenyl)methyl]-3-propyl-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound CCCCCCC(CCC)N1N=C(CCC)C(C(N2)=O)=C1N=C2CC1=CC=C(Cl)C(Cl)=C1 DPTSLFSIQSJLOT-UHFFFAOYSA-N 0.000 description 1
- PKEZKXRYHHUNML-UHFFFAOYSA-N 1-decan-4-yl-6-[(3,4-dimethoxyphenyl)methyl]-3-ethyl-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound CCCCCCC(CCC)N1N=C(CC)C(C(N2)=O)=C1N=C2CC1=CC=C(OC)C(OC)=C1 PKEZKXRYHHUNML-UHFFFAOYSA-N 0.000 description 1
- IWIRWHHXYVBIFR-UHFFFAOYSA-N 1-decan-4-yl-6-[(3,4-dimethoxyphenyl)methyl]-3-propyl-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound CCCCCCC(CCC)N1N=C(CCC)C(C(N2)=O)=C1N=C2CC1=CC=C(OC)C(OC)=C1 IWIRWHHXYVBIFR-UHFFFAOYSA-N 0.000 description 1
- UZUYKYNVSJTWEH-UHFFFAOYSA-N 2-(3-methoxyphenyl)acetyl chloride Chemical compound COC1=CC=CC(CC(Cl)=O)=C1 UZUYKYNVSJTWEH-UHFFFAOYSA-N 0.000 description 1
- UMQUIRYNOVNYPA-UHFFFAOYSA-N 2-(4-chlorophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=C(Cl)C=C1 UMQUIRYNOVNYPA-UHFFFAOYSA-N 0.000 description 1
- SIOJFYRPBYGHOO-UHFFFAOYSA-N 2-(4-fluorophenyl)acetyl chloride Chemical compound FC1=CC=C(CC(Cl)=O)C=C1 SIOJFYRPBYGHOO-UHFFFAOYSA-N 0.000 description 1
- QDZAWVLWIMOXJT-UHFFFAOYSA-N 2-(4-methylphenyl)acetyl chloride Chemical compound CC1=CC=C(CC(Cl)=O)C=C1 QDZAWVLWIMOXJT-UHFFFAOYSA-N 0.000 description 1
- HWTMLSYLXGLSDF-UHFFFAOYSA-N 2-(4-phenylphenyl)acetyl chloride Chemical compound C1=CC(CC(=O)Cl)=CC=C1C1=CC=CC=C1 HWTMLSYLXGLSDF-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- BQBQAOOVQWPQQQ-UHFFFAOYSA-N 3-ethyl-1-(2-hydroxy-6-phenylhexan-3-yl)-6-[(4-morpholin-4-ylsulfonylphenyl)methyl]-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C1=2N=C(CC=3C=CC(=CC=3)S(=O)(=O)N3CCOCC3)NC(=O)C=2C(CC)=NN1C(C(C)O)CCCC1=CC=CC=C1 BQBQAOOVQWPQQQ-UHFFFAOYSA-N 0.000 description 1
- MBLJYHVNCODWSR-UHFFFAOYSA-N 3-hydrazinyl-6-phenylhexan-2-ol Chemical compound CC(O)C(NN)CCCC1=CC=CC=C1 MBLJYHVNCODWSR-UHFFFAOYSA-N 0.000 description 1
- KJTRXVXWSSPHRV-UHFFFAOYSA-N 4-benzoyl-5-methyl-2-phenyl-1h-pyrazol-3-one Chemical compound O=C1C(C(=O)C=2C=CC=CC=2)=C(C)NN1C1=CC=CC=C1 KJTRXVXWSSPHRV-UHFFFAOYSA-N 0.000 description 1
- LOMJTXMKRKBHCY-UHFFFAOYSA-N 5-amino-1-(2-hydroxy-6-phenylhexan-3-yl)-3-methylpyrazole-4-carbonitrile Chemical compound N1=C(C)C(C#N)=C(N)N1C(C(O)C)CCCC1=CC=CC=C1 LOMJTXMKRKBHCY-UHFFFAOYSA-N 0.000 description 1
- WFPFSBOONBJQNX-UHFFFAOYSA-N 5-amino-1-(5-phenylpentan-2-yl)pyrazole-4-carbonitrile Chemical compound N1=CC(C#N)=C(N)N1C(C)CCCC1=CC=CC=C1 WFPFSBOONBJQNX-UHFFFAOYSA-N 0.000 description 1
- GOLGJOUGRCECQK-UHFFFAOYSA-N 5-amino-3-ethyl-1-(5-phenylpentan-2-yl)pyrazole-4-carbonitrile Chemical compound NC1=C(C#N)C(CC)=NN1C(C)CCCC1=CC=CC=C1 GOLGJOUGRCECQK-UHFFFAOYSA-N 0.000 description 1
- HFEVEIJAYFFEBH-UHFFFAOYSA-N 5-amino-3-methyl-1-nonan-3-ylpyrazole-4-carboxamide Chemical compound CCCCCCC(CC)N1N=C(C)C(C(N)=O)=C1N HFEVEIJAYFFEBH-UHFFFAOYSA-N 0.000 description 1
- DGMYRPFYNFQCHM-UHFFFAOYSA-N 5-phenylpentan-2-one Chemical compound CC(=O)CCCC1=CC=CC=C1 DGMYRPFYNFQCHM-UHFFFAOYSA-N 0.000 description 1
- TZYQTWHRLVDYPL-UHFFFAOYSA-N 5h-pyrimidin-4-one Chemical compound O=C1CC=NC=N1 TZYQTWHRLVDYPL-UHFFFAOYSA-N 0.000 description 1
- WEDRAIDNDMACQP-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-ylmethyl)-1-(2-hydroxy-6-phenylhexan-3-yl)-3-methyl-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound CC(O)C(CCCC1=CC=CC=C1)N1N=C(C)C2=C1N=C(CC1=CC3=C(OCO3)C=C1)NC2=O WEDRAIDNDMACQP-UHFFFAOYSA-N 0.000 description 1
- CMVYTXGJNCHQCY-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-ylmethyl)-1-(2-hydroxy-6-phenylhexan-3-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound N1=CC(C(NC(CC=2C=C3OCOC3=CC=2)=N2)=O)=C2N1C(C(O)C)CCCC1=CC=CC=C1 CMVYTXGJNCHQCY-UHFFFAOYSA-N 0.000 description 1
- FAFZKTYYPRIXOR-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-ylmethyl)-1-(5-phenylpentan-2-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound N1=CC(C(NC(CC=2C=C3OCOC3=CC=2)=N2)=O)=C2N1C(C)CCCC1=CC=CC=C1 FAFZKTYYPRIXOR-UHFFFAOYSA-N 0.000 description 1
- HDPMLFIGFKDLMI-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-ylmethyl)-1-decan-4-yl-3-ethyl-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C1=C2OCOC2=CC(CC2=NC3=C(C(N2)=O)C(CC)=NN3C(CCC)CCCCCC)=C1 HDPMLFIGFKDLMI-UHFFFAOYSA-N 0.000 description 1
- JVKCTDZUFTWBSZ-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-ylmethyl)-1-decan-4-yl-3-methyl-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C1=C2OCOC2=CC(CC2=NC3=C(C(N2)=O)C(C)=NN3C(CCC)CCCCCC)=C1 JVKCTDZUFTWBSZ-UHFFFAOYSA-N 0.000 description 1
- PQCWAZAHOSTUOA-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-ylmethyl)-1-decan-4-yl-3-propyl-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C1=C2OCOC2=CC(CC2=NC3=C(C(N2)=O)C(CCC)=NN3C(CCC)CCCCCC)=C1 PQCWAZAHOSTUOA-UHFFFAOYSA-N 0.000 description 1
- APQRJFPUALILDP-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-ylmethyl)-3-methyl-1-octan-2-yl-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C1=C2OCOC2=CC(CC2=NC3=C(C(N2)=O)C(C)=NN3C(C)CCCCCC)=C1 APQRJFPUALILDP-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- RTASJNVULHVBRT-UHFFFAOYSA-N 6-[(3,4-dimethoxyphenyl)methyl]-3-methyl-1-nonan-3-yl-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound CCCCCCC(CC)N1N=C(C)C(C(N2)=O)=C1N=C2CC1=CC=C(OC)C(OC)=C1 RTASJNVULHVBRT-UHFFFAOYSA-N 0.000 description 1
- FZRUJNJBLGXBAQ-UHFFFAOYSA-N 6-[(4-aminophenyl)methyl]-3-methyl-1-nonan-3-yl-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound CCCCCCC(CC)N1N=C(C)C(C(N2)=O)=C1N=C2CC1=CC=C(N)C=C1 FZRUJNJBLGXBAQ-UHFFFAOYSA-N 0.000 description 1
- LSVGWZFTVDTNLU-UHFFFAOYSA-N 6-[(4-bromophenyl)methyl]-1-decan-4-yl-3-ethyl-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound CCCCCCC(CCC)N1N=C(CC)C(C(N2)=O)=C1N=C2CC1=CC=C(Br)C=C1 LSVGWZFTVDTNLU-UHFFFAOYSA-N 0.000 description 1
- HQZWIIFJXZHVBQ-UHFFFAOYSA-N 6-[(4-bromophenyl)methyl]-1-decan-4-yl-3-propyl-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound CCCCCCC(CCC)N1N=C(CCC)C(C(N2)=O)=C1N=C2CC1=CC=C(Br)C=C1 HQZWIIFJXZHVBQ-UHFFFAOYSA-N 0.000 description 1
- SQOLYTHLCWGKGL-UHFFFAOYSA-N 6-benzyl-1-(2-hydroxy-6-phenylhexan-3-yl)-3-methoxy-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C1=2N=C(CC=3C=CC=CC=3)NC(=O)C=2C(OC)=NN1C(C(C)O)CCCC1=CC=CC=C1 SQOLYTHLCWGKGL-UHFFFAOYSA-N 0.000 description 1
- HZKANFARSFHPEL-UHFFFAOYSA-N 6-benzyl-1-(5-phenylpentan-2-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical class N1=CC(C(NC(CC=2C=CC=CC=2)=N2)=O)=C2N1C(C)CCCC1=CC=CC=C1 HZKANFARSFHPEL-UHFFFAOYSA-N 0.000 description 1
- ZZNMARICFYRSPB-UHFFFAOYSA-N 6-benzyl-3-methoxy-1-(5-phenylpentan-2-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C1=2N=C(CC=3C=CC=CC=3)NC(=O)C=2C(OC)=NN1C(C)CCCC1=CC=CC=C1 ZZNMARICFYRSPB-UHFFFAOYSA-N 0.000 description 1
- HNFYMDFKPYEHFR-UHFFFAOYSA-N 6-benzyl-3-methoxy-5,6-dihydropyrazolo[3,4-d]pyrimidin-4-one Chemical compound N1=NC(OC)=C(C(N2)=O)C1=NC2CC1=CC=CC=C1 HNFYMDFKPYEHFR-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- YNMZZHPSYMOGCI-UHFFFAOYSA-N Aethyl-octyl-keton Natural products CCCCCCCCC(=O)CC YNMZZHPSYMOGCI-UHFFFAOYSA-N 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 101100135859 Dictyostelium discoideum regA gene Proteins 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 101001117089 Drosophila melanogaster Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1 Proteins 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 206010021639 Incontinence Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- 101000986989 Naja kaouthia Acidic phospholipase A2 CM-II Proteins 0.000 description 1
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101100082606 Plasmodium falciparum (isolate 3D7) PDEbeta gene Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 101100135860 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PDE2 gene Proteins 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000004133 Sodium thiosulphate Substances 0.000 description 1
- 208000007718 Stable Angina Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000006859 Swern oxidation reaction Methods 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- GBFVXQIHCDNOBW-UHFFFAOYSA-N acetyl 2-(4-aminophenyl)acetate Chemical compound CC(=O)OC(=O)CC1=CC=C(N)C=C1 GBFVXQIHCDNOBW-UHFFFAOYSA-N 0.000 description 1
- LODDPGLMHYAGKZ-UHFFFAOYSA-N acetyl 2-(4-morpholin-4-ylsulfonylphenyl)acetate Chemical compound C1=CC(CC(=O)OC(=O)C)=CC=C1S(=O)(=O)N1CCOCC1 LODDPGLMHYAGKZ-UHFFFAOYSA-N 0.000 description 1
- DJLHTCITHARYHW-UHFFFAOYSA-N acetyl 2-phenylacetate Chemical compound CC(=O)OC(=O)CC1=CC=CC=C1 DJLHTCITHARYHW-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 230000002744 anti-aggregatory effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000001663 anti-spastic effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 229950005499 carbon tetrachloride Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 229960001701 chloroform Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 229960002887 deanol Drugs 0.000 description 1
- MKJDUHZPLQYUCB-UHFFFAOYSA-N decan-4-one Chemical compound CCCCCCC(=O)CCC MKJDUHZPLQYUCB-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- WZKCZNJTDZCNMH-UHFFFAOYSA-N ethyl 2-(3,4-dimethoxyphenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(OC)C(OC)=C1 WZKCZNJTDZCNMH-UHFFFAOYSA-N 0.000 description 1
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- TVIVLENJTXGRAM-UHFFFAOYSA-N methyl 2-(4-aminophenyl)acetate Chemical compound COC(=O)CC1=CC=C(N)C=C1 TVIVLENJTXGRAM-UHFFFAOYSA-N 0.000 description 1
- NYZOHVGGRFFBEH-UHFFFAOYSA-N methyl 2-(4-morpholin-4-ylsulfonylphenyl)acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1S(=O)(=O)N1CCOCC1 NYZOHVGGRFFBEH-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000003836 peripheral circulation Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 201000004240 prostatic hypertrophy Diseases 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- WBQTXTBONIWRGK-UHFFFAOYSA-N sodium;propan-2-olate Chemical compound [Na+].CC(C)[O-] WBQTXTBONIWRGK-UHFFFAOYSA-N 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- HHXGKZZSFJCVAF-UHFFFAOYSA-N tert-butyl n-(decan-4-ylideneamino)carbamate Chemical compound CCCCCCC(CCC)=NNC(=O)OC(C)(C)C HHXGKZZSFJCVAF-UHFFFAOYSA-N 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- DUAJIKVIRGATIW-UHFFFAOYSA-N trinitrogen(.) Chemical compound [N]=[N+]=[N-] DUAJIKVIRGATIW-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- JLYXXMFPNIAWKQ-UHFFFAOYSA-N γ Benzene hexachloride Chemical compound ClC1C(Cl)C(Cl)C(Cl)C(Cl)C1Cl JLYXXMFPNIAWKQ-UHFFFAOYSA-N 0.000 description 1
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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Gynecology & Obstetrics (AREA)
- Vascular Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19709877A DE19709877A1 (de) | 1997-03-11 | 1997-03-11 | 1,5-Dihydro-pyrazolo[3,4-d]-pyrimidinon-derivate |
| DE19709877 | 1997-03-11 | ||
| PCT/EP1998/001086 WO1998040384A1 (de) | 1997-03-11 | 1998-02-26 | 1,5-dihydro-pyrazolo[3,4-d]-pyrimidinon-derivate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU6824098A AU6824098A (en) | 1998-09-29 |
| AU727615B2 true AU727615B2 (en) | 2000-12-14 |
Family
ID=7822900
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU68240/98A Ceased AU727615B2 (en) | 1997-03-11 | 1998-02-26 | 1,5-dihydro-pyrazolo(3,4-d)-pyrimidinone derivatives |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US6174884B1 (https=) |
| EP (1) | EP0973774B1 (https=) |
| JP (1) | JP2001514638A (https=) |
| KR (1) | KR20000076124A (https=) |
| CN (1) | CN1151155C (https=) |
| AT (1) | ATE231509T1 (https=) |
| AU (1) | AU727615B2 (https=) |
| BR (1) | BR9807995A (https=) |
| CA (1) | CA2283211A1 (https=) |
| DE (2) | DE19709877A1 (https=) |
| DK (1) | DK0973774T3 (https=) |
| ES (1) | ES2191294T3 (https=) |
| HU (1) | HUP0001805A3 (https=) |
| IL (1) | IL131450A0 (https=) |
| NZ (1) | NZ337724A (https=) |
| RU (1) | RU2219180C2 (https=) |
| WO (1) | WO1998040384A1 (https=) |
Families Citing this family (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9823103D0 (en) * | 1998-10-23 | 1998-12-16 | Pfizer Ltd | Pharmaceutically active compounds |
| EP1307201B1 (de) | 2000-08-01 | 2004-11-24 | Bayer HealthCare AG | Selektive pde 2-inhibitoren als arzneimittel zur verbesserung der wahrnehmung |
| EP1343506A1 (de) * | 2000-12-19 | 2003-09-17 | MERCK PATENT GmbH | Pharmazeutische formulierung enthaltend pyrazolo 4,3-d]pyrimidine und antithrombotica, calcium-antagonisten, prostaglandine oder prostaglandinderivate |
| DE10064105A1 (de) | 2000-12-21 | 2002-06-27 | Bayer Ag | Neue Substituierte Imidazotriazinone |
| JP2004525890A (ja) * | 2001-02-02 | 2004-08-26 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | ピラゾロ［４，３−ｄ］ピリミジンおよびエンドセリンレセプターアンタゴニストまたはチエノピリミジンおよびエンドセリンレセプターアンタゴニストを含む医薬製剤 |
| KR100393160B1 (ko) * | 2001-06-14 | 2003-07-31 | 한국과학기술연구원 | 신규한 피라졸로피리미딘티온 유도체, 그의 제법 및발기부전 치료제로서의 용도 |
| US6479493B1 (en) | 2001-08-23 | 2002-11-12 | Cell Pathways, Inc. | Methods for treatment of type I diabetes |
| EP1436265A4 (en) * | 2001-09-27 | 2004-12-15 | Smithkline Beecham Corp | CHEMICALS |
| FR2842809A1 (fr) * | 2002-07-26 | 2004-01-30 | Greenpharma Sas | NOUVELLES PYRAZOLO[1,5-a]-1,3,5-TRIAZINES SUBSTITUEES ET LEURS ANALOGUES, COMPOSITIONS PHARMACEUTIQUES LES CONTENANT, UTILISATION A TITRE DE MEDICAMENT ET PROCEDES POUR LEUR PREPARATION |
| DE10238723A1 (de) | 2002-08-23 | 2004-03-11 | Bayer Ag | Phenyl-substituierte Pyrazolyprimidine |
| DE10238724A1 (de) | 2002-08-23 | 2004-03-04 | Bayer Ag | Alkyl-substituierte Pyrazolpyrimidine |
| DE10238722A1 (de) | 2002-08-23 | 2004-03-11 | Bayer Ag | Selektive Phosphodiesterase 9A-Inhibitoren als Arzneimittel zur Verbesserung kognitiver Prozesse |
| CN100397023C (zh) * | 2003-01-04 | 2008-06-25 | 胡云北 | 黄磷废渣载热量及反应尾气发热量的回收与综合利用方法 |
| HRP20050848A2 (en) * | 2003-03-04 | 2006-06-30 | Altana Pharma Ag | Purin-6-one-derivatives |
| DE102004004142A1 (de) | 2003-05-09 | 2004-11-25 | Bayer Healthcare Ag | 6-Cyclylmethyl- und 6-Alkylmethyl-substituierte Pyrazolopyrimidine |
| DE10320785A1 (de) * | 2003-05-09 | 2004-11-25 | Bayer Healthcare Ag | 6-Arylmethyl-substituierte Pyrazolopyrimidine |
| US8044060B2 (en) | 2003-05-09 | 2011-10-25 | Boehringer Ingelheim International Gmbh | 6-cyclylmethyl- and 6-alkylmethyl pyrazolo[3,4-D]pyrimidines, methods for their preparation and methods for their use to treat impairments of perception, concentration learning and/or memory |
| DE10328479A1 (de) | 2003-06-25 | 2005-01-13 | Bayer Ag | 6-Arylamino-5-cyano-4-pyrimidinone |
| CA2536458A1 (en) * | 2003-08-28 | 2005-03-10 | Altana Pharma Ag | Composition comprising a pulmonary surfactant and a pde2 inhibitor |
| DE102004001873A1 (de) | 2004-01-14 | 2005-09-29 | Bayer Healthcare Ag | Cyanopyrimidinone |
| CN1934111A (zh) | 2004-02-27 | 2007-03-21 | 霍夫曼-拉罗奇有限公司 | 杂芳基稠合的吡唑并衍生物 |
| CN101397299B (zh) * | 2007-09-29 | 2011-11-16 | 温州大学 | 一种吡唑[3,4-d]嘧啶酮的合成方法 |
| JP5498392B2 (ja) | 2007-11-30 | 2014-05-21 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | １，５−ジヒドロ−ピラゾロ［３，４−ｄ］ピリミジン−４−オン誘導体及びｃｎｓ障害の治療のためのｐｄｅ９ａモジュレーターとしてのそれらの使用 |
| UA105362C2 (en) | 2008-04-02 | 2014-05-12 | Бьорингер Ингельхайм Интернациональ Гмбх | 1-heterocyclyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a modulators |
| KR20110063447A (ko) | 2008-09-08 | 2011-06-10 | 베링거 인겔하임 인터내셔날 게엠베하 | 피라졸로피리미딘 및 ｃｎｓ 장애의 치료를 위한 이들의 용도 |
| PT2414363E (pt) | 2009-03-31 | 2014-02-26 | Boehringer Ingelheim Int | Derivados de 1-heterociclil-1,5-di-hidro-pirazolo[3,4- d]pirimidin-4-ona e sua utilização como moduladores de pde9a |
| AU2010232729A1 (en) | 2009-03-31 | 2011-10-20 | Arqule, Inc. | Substituted indolo-pyridinone compounds |
| TW201118099A (en) * | 2009-08-12 | 2011-06-01 | Boehringer Ingelheim Int | New compounds for the treatment of CNS disorders |
| EP2603511B1 (en) | 2010-08-12 | 2017-03-15 | Boehringer Ingelheim International GmbH | 6-cycloalkyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a inhibitors |
| US20130040971A1 (en) | 2011-02-14 | 2013-02-14 | Boehringer Ingelheim International Gmbh | 6-cycloalkyl-pyrazolopyrimidinones for the treatment of cns disorders |
| US8809345B2 (en) | 2011-02-15 | 2014-08-19 | Boehringer Ingelheim International Gmbh | 6-cycloalkyl-pyrazolopyrimidinones for the treatment of CNS disorders |
| CA2830027C (en) | 2011-03-31 | 2016-04-26 | Pfizer Inc. | Novel bicyclic pyridinones |
| WO2012172449A1 (en) | 2011-06-13 | 2012-12-20 | Pfizer Inc. | Lactams as beta secretase inhibitors |
| JP6043355B2 (ja) | 2011-08-31 | 2016-12-14 | ファイザー・インク | ヘキサヒドロピラノ［３，４−ｄ］［１，３］チアジン−２−アミン化合物 |
| JO3407B1 (ar) | 2012-05-31 | 2019-10-20 | Eisai R&D Man Co Ltd | مركبات رباعي هيدرو بيرازولو بيريميدين |
| UA110688C2 (uk) | 2012-09-21 | 2016-01-25 | Пфайзер Інк. | Біциклічні піридинони |
| BR112015019276A2 (pt) | 2013-02-19 | 2017-07-18 | Pfizer | compostos de azabenzimidazol como inibidores de isoenzimas de pde4 para o tratamento de distúrbios do snc e outros distúrbios |
| JP6425717B2 (ja) | 2013-10-04 | 2018-11-21 | ファイザー・インク | ガンマセクレターゼモジュレーターとしての新規二環式ピリジノン |
| AP2016009465A0 (en) | 2014-04-01 | 2016-09-30 | Pfizer | Chromene and 1,1 a,2,7b-tetrahydrocyclopropa[c]chromene pyridopyrazinediones as gamma-secretase modulators |
| WO2016012896A1 (en) | 2014-07-24 | 2016-01-28 | Pfizer Inc. | Pyrazolopyrimidine compounds |
| MD20170011A2 (ro) | 2014-08-06 | 2017-08-31 | Pfizer Inc. | Compuşi imidazopiridazinici |
| MX368391B (es) | 2015-02-03 | 2019-09-30 | Pfizer | Ciclopropabenzofuranil-piridopirazindionas novedosas. |
| JO3627B1 (ar) | 2015-04-30 | 2020-08-27 | H Lundbeck As | إيميدازو بيرازينونات على هيئة مثبطات pde1 |
| WO2016179059A1 (en) * | 2015-05-05 | 2016-11-10 | Merck Sharp & Dohme Corp. | Heteroaryl-pyrimidinone compounds as pde2 inhibitors |
| CN107787322B (zh) | 2015-06-17 | 2023-07-07 | 辉瑞大药厂 | 三环化合物以及它们作为磷酸二酯酶抑制剂的用途 |
| CN113332292A (zh) | 2016-02-23 | 2021-09-03 | 辉瑞公司 | 6,7-二氢-5H-吡唑并[5,1-b][1,3]噁嗪-2-甲酰胺化合物 |
| TWI729109B (zh) | 2016-04-12 | 2021-06-01 | 丹麥商Ｈ 朗德貝克公司 | 作爲PDE1抑制劑的1,5-二氫-4H-吡唑并[3,4-d]嘧啶-4-酮和1,5-二氫-4H-吡唑并[4,3-c]吡啶-4-酮 |
| PT3478679T (pt) | 2016-07-01 | 2021-06-30 | Pfizer | Derivados de 5,7-dihidro-pirrolo-piridina para o tratamento de doenças neurológicas e neurodegenerativas |
| WO2018073251A1 (en) * | 2016-10-18 | 2018-04-26 | H. Lundbeck A/S | Imidazopyrazinones, pyrazolopyrimidinones and pyrazolopyridinones as pde1 inhibitors |
| AU2017350473A1 (en) | 2016-10-28 | 2019-04-18 | H. Lundbeck A/S | Combination treatments comprising imidazopyrazinones for the treatment of psychiatric and/or cognitive disorders |
| WO2018078042A1 (en) | 2016-10-28 | 2018-05-03 | H. Lundbeck A/S | Combination treatments comprising administration of imidazopyrazinones |
| KR102590848B1 (ko) | 2016-12-28 | 2023-10-19 | 다트 뉴로사이언스, 엘엘씨 | Pde2 억제제로서 치환된 피라졸로피리미디논 화합물 |
| AU2018281131B2 (en) | 2017-06-08 | 2022-01-20 | Merck Sharp & Dohme Corp. | Pyrazolopyrimidine PDE9 inhibitors |
| IL271290B2 (en) | 2017-06-22 | 2023-11-01 | Pfizer | Dihydro-pyrrolo-pyridine derivatives |
| DK3717488T3 (da) | 2017-11-27 | 2021-12-13 | Dart Neuroscience Llc | Substituerede furanopyrimidinforbindelser som pde1-inhibitorer |
| PT3768669T (pt) | 2018-03-23 | 2023-04-24 | Pfizer | Derivados de piperazina azaspiro |
| USD1021287S1 (en) * | 2021-01-19 | 2024-04-02 | Averia Electronics, Inc. | Wearable light emitting module with a removable band |
| USD1029414S1 (en) * | 2021-01-19 | 2024-05-28 | Averia Electronics, Inc. | Wearable light emitting module with a removable band |
| US12144815B2 (en) | 2021-02-23 | 2024-11-19 | Hoth Therapeutics, Inc. | Use of aprepitant for treating Alzheimer's disease |
| WO2024118524A1 (en) | 2022-11-28 | 2024-06-06 | Cerevel Therapeutics, Llc | Azaindole compounds and their use as phosphodiesterase inhibitors |
| WO2025145091A1 (en) | 2023-12-29 | 2025-07-03 | Pfizer Inc. | Crystalline forms of a muscarinic m4 receptor modulator and methods of treating diseases |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3211732A (en) | 1965-10-12 | Pyrazolob:x-d]pyrlil/hdines | ||
| US3165520A (en) * | 1965-01-12 | Certificate of correction | ||
| CH398626A (de) * | 1960-05-11 | 1966-03-15 | Ciba Geigy | Verfahren zur Herstellung neuer Pyrazolopyrimidine |
| DE1153023B (de) | 1960-05-11 | 1963-08-22 | Ciba Geigy | Verfahren zur Herstellung von 4-Hydroxy-pyrazolo[3,4-d] pyrimidinen |
| CH633297A5 (de) | 1977-09-16 | 1982-11-30 | Sandoz Ag | Verfahren zur herstellung von fluorenphosphoniten. |
| GB9121028D0 (en) | 1991-10-03 | 1991-11-13 | Pfizer Ltd | Therapeutic agents |
| US5294612A (en) * | 1992-03-30 | 1994-03-15 | Sterling Winthrop Inc. | 6-heterocyclyl pyrazolo [3,4-d]pyrimidin-4-ones and compositions and method of use thereof |
| FI944933A7 (fi) * | 1992-04-21 | 1994-10-20 | Biocryst Pharm Inc | 7-disubstitoitu metyyli-4-okso-3H,5H-pyrrolo(3,2-d) pyrimidiini ja sit ä sisältäviä farmaseuttisia käyttöjä ja koostumuksia |
| PL322452A1 (en) * | 1995-03-10 | 1998-02-02 | Sanofi Pharmaceuticals | 6-arylpyrasole [3,4-d]pyrimidin-4-ones, preparations containing such compounds and methods of mking use of them |
| US5656629A (en) | 1995-03-10 | 1997-08-12 | Sanofi Winthrop, Inc. | 6-substituted pyrazolo (3,4-d)pyrimidin-4-ones and compositions and methods of use thereof |
-
1997
- 1997-03-11 DE DE19709877A patent/DE19709877A1/de not_active Withdrawn
-
1998
- 1998-02-26 RU RU99121518/04A patent/RU2219180C2/ru not_active IP Right Cessation
- 1998-02-26 CA CA002283211A patent/CA2283211A1/en not_active Abandoned
- 1998-02-26 US US09/367,538 patent/US6174884B1/en not_active Expired - Fee Related
- 1998-02-26 AU AU68240/98A patent/AU727615B2/en not_active Ceased
- 1998-02-26 DK DK98913595T patent/DK0973774T3/da active
- 1998-02-26 CN CNB988049872A patent/CN1151155C/zh not_active Expired - Fee Related
- 1998-02-26 EP EP98913595A patent/EP0973774B1/de not_active Expired - Lifetime
- 1998-02-26 HU HU0001805A patent/HUP0001805A3/hu unknown
- 1998-02-26 KR KR1019997008213A patent/KR20000076124A/ko not_active Ceased
- 1998-02-26 BR BR9807995-6A patent/BR9807995A/pt not_active IP Right Cessation
- 1998-02-26 AT AT98913595T patent/ATE231509T1/de not_active IP Right Cessation
- 1998-02-26 DE DE59807011T patent/DE59807011D1/de not_active Expired - Fee Related
- 1998-02-26 WO PCT/EP1998/001086 patent/WO1998040384A1/de not_active Ceased
- 1998-02-26 NZ NZ337724A patent/NZ337724A/xx unknown
- 1998-02-26 ES ES98913595T patent/ES2191294T3/es not_active Expired - Lifetime
- 1998-02-26 IL IL13145098A patent/IL131450A0/xx not_active IP Right Cessation
- 1998-02-26 JP JP53913598A patent/JP2001514638A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| IL131450A0 (en) | 2001-01-28 |
| CN1151155C (zh) | 2004-05-26 |
| NZ337724A (en) | 2000-08-25 |
| HK1028035A1 (en) | 2001-02-02 |
| KR20000076124A (ko) | 2000-12-26 |
| CN1255133A (zh) | 2000-05-31 |
| AU6824098A (en) | 1998-09-29 |
| RU2219180C2 (ru) | 2003-12-20 |
| ATE231509T1 (de) | 2003-02-15 |
| DE19709877A1 (de) | 1998-09-17 |
| US6174884B1 (en) | 2001-01-16 |
| HUP0001805A2 (hu) | 2000-11-28 |
| HUP0001805A3 (en) | 2002-09-30 |
| JP2001514638A (ja) | 2001-09-11 |
| EP0973774A1 (de) | 2000-01-26 |
| BR9807995A (pt) | 2000-03-08 |
| ES2191294T3 (es) | 2003-09-01 |
| CA2283211A1 (en) | 1998-09-17 |
| EP0973774B1 (de) | 2003-01-22 |
| WO1998040384A1 (de) | 1998-09-17 |
| DE59807011D1 (de) | 2003-02-27 |
| DK0973774T3 (da) | 2003-05-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU727615B2 (en) | 1,5-dihydro-pyrazolo(3,4-d)-pyrimidinone derivatives | |
| US6235742B1 (en) | 5-substituted pyrazolo[4,3-D]pyrimidin-7-ones | |
| ES2232202T3 (es) | Heterobiciclos que contienen nitrogeno como inhibidores del factor xa. | |
| AU2002339268B2 (en) | Novel pyrrole derivatives as pharmaceutical agents | |
| KR102449652B1 (ko) | Rock의 억제제로서의 스피로-융합 시클릭 우레아 | |
| AU2002248151B2 (en) | Compounds specific to adenosine A1, A2A, and A3 receptor and uses thereof | |
| US6506771B2 (en) | Heteroaryl-phenyl heterobicyclic factor Xa inhibitors | |
| JP4056015B2 (ja) | ＰＤＥ−５抑制活性を有する５，７−ジアミノピラゾロ［４，３−ｄ］ピリミジン | |
| US6458796B1 (en) | Dihydro-[1,2,3]triazolo-[4,5-d]pyrimidin-7-one | |
| US6818646B2 (en) | Substituted pyrrolopyridinone derivatives useful as phosphodiesterase inhibitors | |
| US7723347B2 (en) | Substituted phenylamino-pyrimidines | |
| KR20020038941A (ko) | 포스포디에스테라아제 억제제로서의5-(2-치환된-5-헤테로사이클릴설포닐피리드-3-일)-디하이드로피라졸로[4,3-ｄ]피리미딘-7-온 | |
| SK67699A3 (en) | Novel substituted pyrazole derivatives for the treatment of cardiocirculatory diseases | |
| US6498176B1 (en) | 3-(anilinomethylene) oxindoles as protein tyrosine kinase and protein serine/threonine kinase inhibitors | |
| TW200305412A (en) | Chemical compounds | |
| TWI472530B (zh) | 蛋白質激酶抑制劑 | |
| NZ280830A (en) | 2,9-disubstituted purin-6-one derivatives, preparation and medicaments | |
| FR2960876A1 (fr) | Derives de 3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1h)-dicarboxamide leur preparation et leur application en therapeutique. | |
| CZ281810B6 (cs) | Nové hetaryloxy-beta-karboliny, způsob jejich výroby a použití ve farmaceutických prostředcích | |
| US6858616B2 (en) | Nitrogen containing heterobicycles as factor Xa inhibitors | |
| WO1999018104A1 (en) | Naphtho-imidazo[1,2-a]pyridine derivatives, their preparation and their use in treating central nervous system disorders | |
| AU2006326247A1 (en) | Tricyclic lactam derivatives, their manufacture and use as pharmaceutical agents | |
| AU7395098A (en) | 5-((Heteroaryl)Alkyl)-3-Oxo-Pyrido(1,2-a) Benzimidazole-4- carboxamide derivatives useful in treating central nervous system disorders | |
| FR2845995A1 (fr) | Nouveaux derives de pyrrolo[3,4-c]carbazole et de pyrido[2,3-b]pyrrolo[3,4-e]indole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent | |
| KR20250138136A (ko) | 신규한 화합물, 및 이를 포함하는 암의 예방 또는 치료용 약학적 조성물 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) |