JP2004524316A - 新規置換イミダゾトリアジノン類 - Google Patents
新規置換イミダゾトリアジノン類 Download PDFInfo
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- JP2004524316A JP2004524316A JP2002567934A JP2002567934A JP2004524316A JP 2004524316 A JP2004524316 A JP 2004524316A JP 2002567934 A JP2002567934 A JP 2002567934A JP 2002567934 A JP2002567934 A JP 2002567934A JP 2004524316 A JP2004524316 A JP 2004524316A
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- Prior art keywords
- mmol
- alkyl
- methyl
- compound according
- compound
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- 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 12
- 230000015654 memory Effects 0.000 claims abstract description 11
- 230000013016 learning Effects 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 8
- 230000008447 perception Effects 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 56
- -1 azepin-1-yl Chemical group 0.000 claims description 52
- 150000003839 salts Chemical class 0.000 claims description 19
- 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
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
- 206010012289 Dementia Diseases 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000000217 alkyl 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
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 238000009833 condensation Methods 0.000 claims description 4
- 230000005494 condensation Effects 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 3
- 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 3
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000005322 morpholin-1-yl group Chemical group 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
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 230000001953 sensory effect Effects 0.000 claims 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 230000008569 process Effects 0.000 abstract description 3
- 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 78
- 239000000203 mixture Substances 0.000 description 39
- 238000005160 1H NMR spectroscopy Methods 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 28
- QMNWYGTWTXOQTP-UHFFFAOYSA-N 1h-triazin-6-one Chemical compound O=C1C=CN=NN1 QMNWYGTWTXOQTP-UHFFFAOYSA-N 0.000 description 26
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-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
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 239000000243 solution Substances 0.000 description 17
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 14
- 241000700159 Rattus Species 0.000 description 13
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 10
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 9
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 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 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
- 239000000126 substance Substances 0.000 description 9
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 8
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 8
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 8
- 239000012442 inert solvent 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- OHUHHIUQRHRGQK-UHFFFAOYSA-N ethyl 3-acetamido-2-oxobutanoate Chemical compound CCOC(=O)C(=O)C(C)NC(C)=O OHUHHIUQRHRGQK-UHFFFAOYSA-N 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
- 239000012071 phase Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
- 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 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 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
- 239000002253 acid Substances 0.000 description 6
- 150000001411 amidrazones Chemical class 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 229910052751 metal Chemical class 0.000 description 6
- 239000002184 metal Chemical class 0.000 description 6
- 150000002825 nitriles Chemical class 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 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 5
- 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 5
- VZAUWENNCBLRET-UHFFFAOYSA-N 2-acetyloctanoic acid Chemical compound CCCCCCC(C(C)=O)C(O)=O VZAUWENNCBLRET-UHFFFAOYSA-N 0.000 description 5
- 101001117089 Drosophila melanogaster Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1 Proteins 0.000 description 5
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 150000001735 carboxylic acids Chemical class 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 5
- 230000002401 inhibitory effect Effects 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
- 229940049964 oleate Drugs 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 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 4
- 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 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
- IOLYZQRRQNMFQP-UHFFFAOYSA-N 2-acetylheptanoic acid Chemical compound CCCCCC(C(C)=O)C(O)=O IOLYZQRRQNMFQP-UHFFFAOYSA-N 0.000 description 4
- ZDDKTFIMZAORKT-UHFFFAOYSA-N 5-(aminomethyl)-1h-triazin-6-one Chemical compound NCC1=CN=NNC1=O ZDDKTFIMZAORKT-UHFFFAOYSA-N 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-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
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- KTHDTJVBEPMMGL-VKHMYHEASA-N N-acetyl-L-alanine Chemical compound OC(=O)[C@H](C)NC(C)=O KTHDTJVBEPMMGL-VKHMYHEASA-N 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
- 210000001367 artery Anatomy 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000012039 electrophile Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 150000004678 hydrides Chemical class 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 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
- ACJVDISWBNBFTJ-UHFFFAOYSA-N n-[1-[3-[(3,4-dimethoxyphenyl)methyl]-5-oxo-2h-1,2,4-triazin-6-yl]ethyl]-2-(1-hydroxyethyl)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 ACJVDISWBNBFTJ-UHFFFAOYSA-N 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
- 239000000758 substrate Substances 0.000 description 4
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 4
- 0 *C(C1=NN=C(C(*)(*)*)NC1=O)NC(C(*)(*)C(*)=O)=O Chemical compound *C(C1=NN=C(C(*)(*)*)NC1=O)NC(C(*)(*)C(*)=O)=O 0.000 description 3
- 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
- LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 description 3
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 3
- 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 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
- 102000000584 Calmodulin Human genes 0.000 description 3
- 108010041952 Calmodulin Proteins 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
- 108010044467 Isoenzymes Proteins 0.000 description 3
- 235000011054 acetic acid Nutrition 0.000 description 3
- 150000001371 alpha-amino acids Chemical class 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 229910000085 borane Inorganic materials 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
- 239000002775 capsule Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000007850 degeneration Effects 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 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 3
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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Classifications
-
- 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
-
- 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
-
- 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
Landscapes
- 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)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10108752A DE10108752A1 (de) | 2001-02-23 | 2001-02-23 | Neue Substituierte Imidazotriazinone |
| PCT/EP2002/001392 WO2002068423A1 (de) | 2001-02-23 | 2002-02-11 | Neue substituierte imidazotriazinone |
Publications (2)
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| JP2004524316A true JP2004524316A (ja) | 2004-08-12 |
| JP2004524316A5 JP2004524316A5 (enExample) | 2005-12-22 |
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| JP2002567934A Pending JP2004524316A (ja) | 2001-02-23 | 2002-02-11 | 新規置換イミダゾトリアジノン類 |
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| EP (1) | EP1363912B1 (enExample) |
| JP (1) | JP2004524316A (enExample) |
| CA (1) | CA2438890A1 (enExample) |
| DE (2) | DE10108752A1 (enExample) |
| ES (1) | ES2265487T3 (enExample) |
| WO (1) | WO2002068423A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010087381A1 (ja) * | 2009-01-30 | 2010-08-05 | 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 |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10238723A1 (de) | 2002-08-23 | 2004-03-11 | Bayer Ag | Phenyl-substituierte Pyrazolyprimidine |
| 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 |
| WO2004089953A1 (en) * | 2003-03-04 | 2004-10-21 | Altana Pharma Ag | Purin-6-one-derivatives |
| 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 |
| DE10320785A1 (de) | 2003-05-09 | 2004-11-25 | Bayer Healthcare Ag | 6-Arylmethyl-substituierte Pyrazolopyrimidine |
| 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 |
| US7226915B2 (en) * | 2003-05-15 | 2007-06-05 | Hoffmann-La Roche Inc. | Diaminopyrroloquinazolines compounds as protein tyrosine phosphatase inhibitors |
| 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 |
| JP5453431B2 (ja) | 2008-09-08 | 2014-03-26 | 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 | ピラゾロピリミジン及びｃｎｓ障害の治療のためのそれらの使用 |
| 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 |
| NZ603725A (en) | 2010-08-12 | 2015-04-24 | Boehringer Ingelheim Int | 6-cycloalkyl-1,5-dihydro-pyrazolo [3,4-d] pyrimidin-4-one derivatives and their use as pde9a inhibitors |
| 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 |
| MA50375A (fr) | 2014-04-23 | 2021-05-26 | Dart Neuroscience Cayman Ltd | Compositions contenant des composés substitués de [1,2,4]triazolo[1,5-a]pyrimidine-7-yl utilisés en tant qu'inhibiteurs pde2 |
| WO2016073424A1 (en) | 2014-11-05 | 2016-05-12 | Dart Neuroscience, Llc | Substituted 5-methyl-[1, 2, 4] triazolo [1,5-a) pyrimidin-2-amine compounds as pde2 inhibitors |
| AU2015357496B2 (en) | 2014-12-06 | 2019-09-19 | Intra-Cellular Therapies, Inc. | Organic compounds |
| KR102562576B1 (ko) | 2014-12-06 | 2023-08-01 | 인트라-셀룰라 써래피스, 인코퍼레이티드. | 유기 화합물 |
| 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 |
|---|---|---|---|---|
| PT1049695E (pt) * | 1997-11-12 | 2002-07-31 | Bayer Ag | Imidazotriazinonas 2-fenil substituidas enquanto inibidores de fosfodiesterase |
-
2001
- 2001-02-23 DE DE10108752A patent/DE10108752A1/de not_active Withdrawn
-
2002
- 2002-02-11 CA CA002438890A patent/CA2438890A1/en not_active Abandoned
- 2002-02-11 EP EP02704706A patent/EP1363912B1/de not_active Expired - Lifetime
- 2002-02-11 DE DE50206892T patent/DE50206892D1/de not_active Expired - Fee Related
- 2002-02-11 JP JP2002567934A patent/JP2004524316A/ja active Pending
- 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
- 2002-02-11 WO PCT/EP2002/001392 patent/WO2002068423A1/de not_active Ceased
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010087381A1 (ja) * | 2009-01-30 | 2010-08-05 | 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 |
| JP2010173983A (ja) * | 2009-01-30 | 2010-08-12 | Sumitomo Chemical Co Ltd | ジベンゾオキセピン化合物の製造方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002068423A1 (de) | 2002-09-06 |
| DE50206892D1 (de) | 2006-06-29 |
| CA2438890A1 (en) | 2002-09-06 |
| DE10108752A1 (de) | 2002-09-05 |
| EP1363912B1 (de) | 2006-05-24 |
| US20050009822A1 (en) | 2005-01-13 |
| ES2265487T3 (es) | 2007-02-16 |
| EP1363912A1 (de) | 2003-11-26 |
| US6998402B2 (en) | 2006-02-14 |
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