DE10108752A1 - Neue Substituierte Imidazotriazinone - Google Patents
Neue Substituierte ImidazotriazinoneInfo
- Publication number
- DE10108752A1 DE10108752A1 DE10108752A DE10108752A DE10108752A1 DE 10108752 A1 DE10108752 A1 DE 10108752A1 DE 10108752 A DE10108752 A DE 10108752A DE 10108752 A DE10108752 A DE 10108752A DE 10108752 A1 DE10108752 A1 DE 10108752A1
- Authority
- DE
- Germany
- Prior art keywords
- mmol
- alkyl
- methyl
- compounds according
- general formula
- 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.)
- Withdrawn
Links
- IJYHVZICHKCLMQ-UHFFFAOYSA-N imidazo[4,5-d]triazin-4-one Chemical class O=C1N=NN=C2N=CN=C12 IJYHVZICHKCLMQ-UHFFFAOYSA-N 0.000 title abstract description 3
- 238000000034 method Methods 0.000 claims abstract description 13
- 230000008447 perception Effects 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 44
- -1 piperid-1-yl Chemical group 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 206010012289 Dementia Diseases 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 238000009833 condensation Methods 0.000 claims description 6
- 230000005494 condensation Effects 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 230000007786 learning performance Effects 0.000 claims description 5
- 230000007334 memory performance Effects 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 5
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical group 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 150000004677 hydrates Chemical class 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 229940126601 medicinal product Drugs 0.000 claims 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- 239000000203 mixture Substances 0.000 description 37
- 238000005160 1H NMR spectroscopy Methods 0.000 description 29
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 21
- 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 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 19
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 241000700159 Rattus Species 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 101100135858 Caenorhabditis elegans pde-2 gene Proteins 0.000 description 11
- PZPFXRQPPDCUQY-BJILWQEISA-M sodium;(e)-4-methoxy-4-oxobut-2-en-2-olate Chemical compound [Na+].COC(=O)\C=C(/C)[O-] PZPFXRQPPDCUQY-BJILWQEISA-M 0.000 description 10
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- HBVHDPSYAJZFEF-UHFFFAOYSA-N methyl 2-acetyloctanoate Chemical compound CCCCCCC(C(C)=O)C(=O)OC HBVHDPSYAJZFEF-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 8
- QRKJNEPQLYAHHR-UHFFFAOYSA-N 5-methyl-2-[(4-methylphenyl)methyl]-7-(2-oxoheptan-3-yl)-1h-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound CCCCC(C(C)=O)C1=NC(C)=C(C(N2)=O)N1N=C2CC1=CC=C(C)C=C1 QRKJNEPQLYAHHR-UHFFFAOYSA-N 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- 238000002821 scintillation proximity assay Methods 0.000 description 8
- 239000012279 sodium borohydride Substances 0.000 description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- YSRPMZSQKAQBPK-UHFFFAOYSA-N 5-methyl-2-[(4-methylphenyl)methyl]-7-(2-oxononan-3-yl)-1h-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound CCCCCCC(C(C)=O)C1=NC(C)=C(C(N2)=O)N1N=C2CC1=CC=C(C)C=C1 YSRPMZSQKAQBPK-UHFFFAOYSA-N 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- 239000012442 inert solvent Substances 0.000 description 7
- SIQGUWOXOTYXHP-UHFFFAOYSA-N methyl 2-acetylheptanoate Chemical compound CCCCCC(C(C)=O)C(=O)OC SIQGUWOXOTYXHP-UHFFFAOYSA-N 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- OOGDDCUZGDXEJJ-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methyl]-5-methyl-7-(2-oxononan-3-yl)-1h-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound CCCCCCC(C(C)=O)C1=NC(C)=C(C(N2)=O)N1N=C2CC1=CC=C(OC)C=C1 OOGDDCUZGDXEJJ-UHFFFAOYSA-N 0.000 description 6
- BUZFOTASUUCJBN-UHFFFAOYSA-N 6-(1-aminoethyl)-3-[(4-methylphenyl)methyl]-2h-1,2,4-triazin-5-one Chemical compound N1C(=O)C(C(N)C)=NN=C1CC1=CC=C(C)C=C1 BUZFOTASUUCJBN-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 101100243082 Caenorhabditis elegans pde-1 gene Proteins 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 150000001411 amidrazones Chemical class 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 150000001735 carboxylic acids Chemical class 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- NIKKPUQRMWDLJS-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)ethanimidamide;hydrochloride Chemical compound Cl.COC1=CC=C(CC(N)=N)C=C1OC NIKKPUQRMWDLJS-UHFFFAOYSA-N 0.000 description 5
- LOJFRHBZDMXJPA-UHFFFAOYSA-N 2-(4-methoxyphenyl)ethanimidamide;hydrochloride Chemical compound Cl.COC1=CC=C(CC(N)=N)C=C1 LOJFRHBZDMXJPA-UHFFFAOYSA-N 0.000 description 5
- IASLLBSBRCPNMN-UHFFFAOYSA-N 2-[(3,4-dimethoxyphenyl)methyl]-5-methyl-7-(2-oxooct-7-en-3-yl)-1h-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound C1=C(OC)C(OC)=CC=C1CC(NC1=O)=NN2C1=C(C)N=C2C(CCCC=C)C(C)=O IASLLBSBRCPNMN-UHFFFAOYSA-N 0.000 description 5
- VZAUWENNCBLRET-UHFFFAOYSA-N 2-acetyloctanoic acid Chemical compound CCCCCCC(C(C)=O)C(O)=O VZAUWENNCBLRET-UHFFFAOYSA-N 0.000 description 5
- ZDDKTFIMZAORKT-UHFFFAOYSA-N 5-(aminomethyl)-1h-triazin-6-one Chemical class NCC1=CN=NNC1=O ZDDKTFIMZAORKT-UHFFFAOYSA-N 0.000 description 5
- VLMURIOPGUSBEX-UHFFFAOYSA-N 5-methyl-2-[(4-methylphenyl)methyl]-7-(2-oxooctan-3-yl)-1h-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound CCCCCC(C(C)=O)C1=NC(C)=C(C(N2)=O)N1N=C2CC1=CC=C(C)C=C1 VLMURIOPGUSBEX-UHFFFAOYSA-N 0.000 description 5
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- SOWZJTHYGZXLQO-UHFFFAOYSA-N methyl 2-acetylhept-6-enoate Chemical compound COC(=O)C(C(C)=O)CCCC=C SOWZJTHYGZXLQO-UHFFFAOYSA-N 0.000 description 5
- MYLUDEMWIBXIKB-UHFFFAOYSA-N n-[1-[3-[(3,4-dimethoxyphenyl)methyl]-5-oxo-2h-1,2,4-triazin-6-yl]ethyl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NN=C(C(C)NC(C)=O)C(=O)N1 MYLUDEMWIBXIKB-UHFFFAOYSA-N 0.000 description 5
- SKBZPBWNXSQNNH-UHFFFAOYSA-N n-[1-[3-[(4-methoxyphenyl)methyl]-5-oxo-2h-1,2,4-triazin-6-yl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1CC1=NN=C(C(C)NC(C)=O)C(=O)N1 SKBZPBWNXSQNNH-UHFFFAOYSA-N 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 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 4
- GSRUYMAEMIDRFW-UHFFFAOYSA-N 2-(1-hydroxyethyl)hept-6-enoic acid Chemical compound CC(O)C(C(O)=O)CCCC=C GSRUYMAEMIDRFW-UHFFFAOYSA-N 0.000 description 4
- VJCXPEOOYUIMMA-UHFFFAOYSA-N 2-(4-methylphenyl)ethanimidamide;hydrochloride Chemical compound Cl.CC1=CC=C(CC(N)=N)C=C1 VJCXPEOOYUIMMA-UHFFFAOYSA-N 0.000 description 4
- QGJOKOQOBXMENN-UHFFFAOYSA-N 2-acetyl-n-[1-[3-[(3,4-dimethoxyphenyl)methyl]-5-oxo-2h-1,2,4-triazin-6-yl]ethyl]hept-6-enamide Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NN=C(C(C)NC(=O)C(CCCC=C)C(C)=O)C(=O)N1 QGJOKOQOBXMENN-UHFFFAOYSA-N 0.000 description 4
- IOLYZQRRQNMFQP-UHFFFAOYSA-N 2-acetylheptanoic acid Chemical compound CCCCCC(C(C)=O)C(O)=O IOLYZQRRQNMFQP-UHFFFAOYSA-N 0.000 description 4
- CYJZWMLWJBASOJ-UHFFFAOYSA-N 6-(1-aminoethyl)-3-[(4-methoxyphenyl)methyl]-2h-1,2,4-triazin-5-one Chemical compound C1=CC(OC)=CC=C1CC1=NN=C(C(C)N)C(=O)N1 CYJZWMLWJBASOJ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 101100296726 Caenorhabditis elegans pde-5 gene Proteins 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- 210000000709 aorta Anatomy 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical class B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
- 229910000085 borane Inorganic materials 0.000 description 4
- 239000012039 electrophile Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
- 150000004678 hydrides Chemical class 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- DXMKGNVBNJZQQH-UHFFFAOYSA-N methyl 2-(1-hydroxyethyl)hept-6-enoate Chemical compound COC(=O)C(C(C)O)CCCC=C DXMKGNVBNJZQQH-UHFFFAOYSA-N 0.000 description 4
- PYYFKCZKDCTZBH-UHFFFAOYSA-N methyl 2-acetylhexanoate Chemical compound CCCCC(C(C)=O)C(=O)OC PYYFKCZKDCTZBH-UHFFFAOYSA-N 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 3
- RELKLVHRYOAUBD-UHFFFAOYSA-N 6-(1-aminoethyl)-3-[(3,4-dimethoxyphenyl)methyl]-2h-1,2,4-triazin-5-one Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NN=C(C(C)N)C(=O)N1 RELKLVHRYOAUBD-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
- 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
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- 108010044467 Isoenzymes Proteins 0.000 description 3
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 3
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 3
- 235000011054 acetic acid Nutrition 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 150000001371 alpha-amino acids Chemical class 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000009835 boiling Methods 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
- 239000000872 buffer Substances 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
- C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
- C07D253/06—1,2,4-Triazines
- C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
- C07D253/07—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members with hetero atoms, or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- 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
-
- 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
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Priority Applications (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10108752A DE10108752A1 (de) | 2001-02-23 | 2001-02-23 | Neue Substituierte Imidazotriazinone |
| US10/468,511 US6998402B2 (en) | 2001-02-23 | 2002-02-11 | Substituted imidazotriazinones |
| DE50206892T DE50206892D1 (de) | 2001-02-23 | 2002-02-11 | Substituierte imidazotriazinone |
| PCT/EP2002/001392 WO2002068423A1 (de) | 2001-02-23 | 2002-02-11 | Neue substituierte imidazotriazinone |
| EP02704706A EP1363912B1 (de) | 2001-02-23 | 2002-02-11 | Substituierte imidazotriazinone |
| JP2002567934A JP2004524316A (ja) | 2001-02-23 | 2002-02-11 | 新規置換イミダゾトリアジノン類 |
| ES02704706T ES2265487T3 (es) | 2001-02-23 | 2002-02-11 | Nuevas imidazotriazinonas sustituidas. |
| CA002438890A CA2438890A1 (en) | 2001-02-23 | 2002-02-11 | Novel substituted imidazotriazinones |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10108752A DE10108752A1 (de) | 2001-02-23 | 2001-02-23 | Neue Substituierte Imidazotriazinone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE10108752A1 true DE10108752A1 (de) | 2002-09-05 |
Family
ID=7675248
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE10108752A Withdrawn DE10108752A1 (de) | 2001-02-23 | 2001-02-23 | Neue Substituierte Imidazotriazinone |
| DE50206892T Expired - Fee Related DE50206892D1 (de) | 2001-02-23 | 2002-02-11 | Substituierte imidazotriazinone |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE50206892T Expired - Fee Related DE50206892D1 (de) | 2001-02-23 | 2002-02-11 | Substituierte imidazotriazinone |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US6998402B2 (enExample) |
| EP (1) | EP1363912B1 (enExample) |
| JP (1) | JP2004524316A (enExample) |
| CA (1) | CA2438890A1 (enExample) |
| DE (2) | DE10108752A1 (enExample) |
| ES (1) | ES2265487T3 (enExample) |
| WO (1) | WO2002068423A1 (enExample) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10238722A1 (de) | 2002-08-23 | 2004-03-11 | Bayer Ag | Selektive Phosphodiesterase 9A-Inhibitoren als Arzneimittel zur Verbesserung kognitiver Prozesse |
| DE10238724A1 (de) | 2002-08-23 | 2004-03-04 | Bayer Ag | Alkyl-substituierte Pyrazolpyrimidine |
| DE10238723A1 (de) | 2002-08-23 | 2004-03-11 | Bayer Ag | Phenyl-substituierte Pyrazolyprimidine |
| HRP20050848A2 (en) * | 2003-03-04 | 2006-06-30 | Altana Pharma Ag | Purin-6-one-derivatives |
| 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 |
| US7226915B2 (en) | 2003-05-15 | 2007-06-05 | Hoffmann-La Roche Inc. | Diaminopyrroloquinazolines compounds as protein tyrosine phosphatase inhibitors |
| CN100334088C (zh) * | 2003-05-15 | 2007-08-29 | 霍夫曼-拉罗奇有限公司 | 作为蛋白质酪氨酸磷酸酶抑制剂的二氨基吡咯并喹唑啉化合物 |
| JP2006219374A (ja) | 2003-06-13 | 2006-08-24 | Daiichi Asubio Pharma Co Ltd | Ｐｄｅ７阻害作用を有するイミダゾトリアジノン誘導体 |
| DE10328479A1 (de) | 2003-06-25 | 2005-01-13 | Bayer Ag | 6-Arylamino-5-cyano-4-pyrimidinone |
| DE102004001873A1 (de) | 2004-01-14 | 2005-09-29 | Bayer Healthcare Ag | Cyanopyrimidinone |
| US8648085B2 (en) | 2007-11-30 | 2014-02-11 | Boehringer Ingelheim International Gmbh | 1, 5-dihydro-pyrazolo (3, 4-D) pyrimidin-4-one derivatives and their use as PDE9A mudulators for the treatment of CNS disorders |
| 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 |
| CN102143965A (zh) | 2008-09-08 | 2011-08-03 | 贝林格尔.英格海姆国际有限公司 | 吡唑并嘧啶酮及其在治疗中枢神经系统疾病中的用途 |
| JP5503877B2 (ja) * | 2009-01-30 | 2014-05-28 | 住友化学株式会社 | ジベンゾオキセピン化合物の製造方法 |
| UY32531A (es) | 2009-03-31 | 2010-10-29 | Boehringer Ingelheim Int | Nuevos compuestos para el tratamiento de trastornos del snc |
| BR112013003097B1 (pt) | 2010-08-12 | 2021-03-16 | Boehringer Ingelheim International Gmbh | 6-cicloalquil-pirazolopirimidinonas e composição farmacêutica |
| US9540379B2 (en) | 2011-01-31 | 2017-01-10 | Boehringer Ingelheim International Gmbh | (1,2,4)triazolo[4,3-A]quinoxaline derivatives as inhibitors of phosphodiesterases |
| US8809345B2 (en) | 2011-02-15 | 2014-08-19 | Boehringer Ingelheim International Gmbh | 6-cycloalkyl-pyrazolopyrimidinones for the treatment of CNS disorders |
| US20140045856A1 (en) | 2012-07-31 | 2014-02-13 | Boehringer Ingelheim International Gmbh | 4-Methyl-2,3,5,9,9b-pentaaza-cyclopenta[a]naphthalenes |
| 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−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 製剤および医薬組成物 |
| EP3134413B1 (en) | 2014-04-23 | 2019-09-11 | Dart NeuroScience (Cayman) Ltd. | Substituted [1,2,4]triazolo[1,5-a]pyrimidin-7-yl compounds as pde2 inhibitors |
| TWI568737B (zh) | 2014-11-05 | 2017-02-01 | 達特神經科學（開曼）有限責任公司 | 作為ｐｄｅ２抑制劑之經取代的５－甲基－［１，２，４］三唑并［１，５－ａ］嘧啶－２－胺化合物 |
| BR112017012007B1 (pt) | 2014-12-06 | 2022-11-01 | Intra-Cellular Therapies, Inc | Compostos orgânicos inibitórios de pde2, composições farmacêuticas compreendendo os ditos compostos e uso dos mesmos no tratamento de um distúrbio mediado por pde2 |
| WO2016090382A1 (en) | 2014-12-06 | 2016-06-09 | Intra-Cellular Therapies, Inc. | Organic compounds |
| WO2017000276A1 (en) * | 2015-07-01 | 2017-01-05 | Merck Sharp & Dohme Corp. | Bicyclic heterocyclic compounds as pde2 inhibitors |
| EP3156405A1 (en) | 2015-10-13 | 2017-04-19 | Boehringer Ingelheim International GmbH | Spirocyclic ether derivatives of pyrazolo[1,5-a]pyrimidine-3-carboxamide |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU227841B1 (en) | 1997-11-12 | 2012-05-02 | Bayer Pharma AG | 2-phenyl substituted imidazotriazinones, process for their preparation and pharmaceutical compositions thereof |
-
2001
- 2001-02-23 DE DE10108752A patent/DE10108752A1/de not_active Withdrawn
-
2002
- 2002-02-11 JP JP2002567934A patent/JP2004524316A/ja active Pending
- 2002-02-11 DE DE50206892T patent/DE50206892D1/de not_active Expired - Fee Related
- 2002-02-11 EP EP02704706A patent/EP1363912B1/de not_active Expired - Lifetime
- 2002-02-11 WO PCT/EP2002/001392 patent/WO2002068423A1/de not_active Ceased
- 2002-02-11 CA CA002438890A patent/CA2438890A1/en not_active Abandoned
- 2002-02-11 ES ES02704706T patent/ES2265487T3/es not_active Expired - Lifetime
- 2002-02-11 US US10/468,511 patent/US6998402B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US6998402B2 (en) | 2006-02-14 |
| CA2438890A1 (en) | 2002-09-06 |
| EP1363912B1 (de) | 2006-05-24 |
| JP2004524316A (ja) | 2004-08-12 |
| DE50206892D1 (de) | 2006-06-29 |
| ES2265487T3 (es) | 2007-02-16 |
| WO2002068423A1 (de) | 2002-09-06 |
| US20050009822A1 (en) | 2005-01-13 |
| EP1363912A1 (de) | 2003-11-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8127 | New person/name/address of the applicant |
Owner name: BAYER HEALTHCARE AG, 51373 LEVERKUSEN, DE |
|
| 8139 | Disposal/non-payment of the annual fee |