ES2904938T3 - Derivados de [1,2,4]triazolo[4,3-a]pirazin-6(5H)-ona - Google Patents
Derivados de [1,2,4]triazolo[4,3-a]pirazin-6(5H)-ona Download PDFInfo
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- ES2904938T3 ES2904938T3 ES18752976T ES18752976T ES2904938T3 ES 2904938 T3 ES2904938 T3 ES 2904938T3 ES 18752976 T ES18752976 T ES 18752976T ES 18752976 T ES18752976 T ES 18752976T ES 2904938 T3 ES2904938 T3 ES 2904938T3
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- pyrido
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- 150000001875 compounds Chemical class 0.000 claims abstract description 99
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 23
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims abstract description 13
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 7
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 208000020832 chronic kidney disease Diseases 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000012458 free base Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 53
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 40
- 238000006243 chemical reaction Methods 0.000 description 40
- 239000000243 solution Substances 0.000 description 40
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 33
- 230000002829 reductive effect Effects 0.000 description 33
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- 238000002360 preparation method Methods 0.000 description 31
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- 238000003786 synthesis reaction Methods 0.000 description 28
- 230000015572 biosynthetic process Effects 0.000 description 27
- 235000019439 ethyl acetate Nutrition 0.000 description 23
- 238000000034 method Methods 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
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- 239000007787 solid Substances 0.000 description 19
- 238000003818 flash chromatography Methods 0.000 description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
- 235000019341 magnesium sulphate Nutrition 0.000 description 16
- 229910052757 nitrogen Inorganic materials 0.000 description 16
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- 239000000377 silicon dioxide Substances 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- -1 hexafluorophosphate Chemical compound 0.000 description 9
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 102100024317 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C Human genes 0.000 description 6
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- 101000609947 Homo sapiens Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha Proteins 0.000 description 6
- 101000988419 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4D Proteins 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- ZYOYYQRWXITKFF-UHFFFAOYSA-N pyrazine-2,3-dione Chemical compound O=C1N=CC=NC1=O ZYOYYQRWXITKFF-UHFFFAOYSA-N 0.000 description 6
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 5
- 101001098818 Homo sapiens cGMP-inhibited 3',5'-cyclic phosphodiesterase A Proteins 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 102100024316 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A Human genes 0.000 description 4
- 239000007821 HATU Substances 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 239000007832 Na2SO4 Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 239000013058 crude material Substances 0.000 description 4
- 102000048135 human PDE4D Human genes 0.000 description 4
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- 230000002441 reversible effect Effects 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 238000003828 vacuum filtration Methods 0.000 description 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- 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 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- PYLSAACWAQSKHB-UHFFFAOYSA-N CCC(Cn1c2cccnc2n2c(nnc2c1=O)C1(CC1)C1CC1)OC Chemical compound CCC(Cn1c2cccnc2n2c(nnc2c1=O)C1(CC1)C1CC1)OC PYLSAACWAQSKHB-UHFFFAOYSA-N 0.000 description 3
- QUCSZSARIRAUJK-UHFFFAOYSA-N CCCCn1c2cc(Br)cnc2n2c(nnc2c1=O)C1(C)CC1 Chemical compound CCCCn1c2cc(Br)cnc2n2c(nnc2c1=O)C1(C)CC1 QUCSZSARIRAUJK-UHFFFAOYSA-N 0.000 description 3
- WLYAPNZTYZDHRG-UHFFFAOYSA-N Cl.NNC(=O)C1(CC1)C1CC1 Chemical compound Cl.NNC(=O)C1(CC1)C1CC1 WLYAPNZTYZDHRG-UHFFFAOYSA-N 0.000 description 3
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- RFAXLXKIAKIUDT-UHFFFAOYSA-N IPA-3 Chemical compound C1=CC=C2C(SSC3=C4C=CC=CC4=CC=C3O)=C(O)C=CC2=C1 RFAXLXKIAKIUDT-UHFFFAOYSA-N 0.000 description 3
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- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
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- 241001649081 Dina Species 0.000 description 1
- 101100407341 Drosophila melanogaster Pde9 gene Proteins 0.000 description 1
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- 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 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102100039174 Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta Human genes 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- NVSPJDGXKBDYIZ-UHFFFAOYSA-N [1,2,4]triazolo[4,3-a]pyrazine Chemical compound C1=NC=CN2C=NN=C21 NVSPJDGXKBDYIZ-UHFFFAOYSA-N 0.000 description 1
- IKQCKJSWVAERRG-UHFFFAOYSA-M [Br-].CC(C)[Zn+] Chemical compound [Br-].CC(C)[Zn+] IKQCKJSWVAERRG-UHFFFAOYSA-M 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
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- 210000004369 blood Anatomy 0.000 description 1
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- 230000036772 blood pressure Effects 0.000 description 1
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- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
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- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
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- 229940124301 concurrent medication Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- MXFYYFVVIIWKFE-UHFFFAOYSA-N dicyclohexyl-[2-[2,6-di(propan-2-yloxy)phenyl]phenyl]phosphane Chemical group CC(C)OC1=CC=CC(OC(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 MXFYYFVVIIWKFE-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 206010013990 dysuria Diseases 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
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- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
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- 210000002216 heart Anatomy 0.000 description 1
- 102000055462 human PDE1B Human genes 0.000 description 1
- 102000054507 human PDE6B Human genes 0.000 description 1
- ATQYNBNTEXNNIK-UHFFFAOYSA-N imidazol-2-ylidene Chemical group [C]1NC=CN1 ATQYNBNTEXNNIK-UHFFFAOYSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- MGFYIUFZLHCRTH-UHFFFAOYSA-N nitrilotriacetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)=O MGFYIUFZLHCRTH-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
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- 238000005457 optimization Methods 0.000 description 1
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- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 101150037969 pde-6 gene Proteins 0.000 description 1
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- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- 125000001567 quinoxalinyl group Chemical class N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
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- 238000013341 scale-up Methods 0.000 description 1
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- VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical compound COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
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- 208000024891 symptom Diseases 0.000 description 1
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- NMLXKNNXODLJIN-UHFFFAOYSA-M zinc;carbanide;chloride Chemical compound [CH3-].[Zn+]Cl NMLXKNNXODLJIN-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (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 |
|---|---|---|---|
| US201762540122P | 2017-08-02 | 2017-08-02 | |
| PCT/US2018/043845 WO2019027783A1 (en) | 2017-08-02 | 2018-07-26 | DERIVATIVES OF [1,2,4] TRIAZOLO [4,3-A] PYRAZIN-6 (5H) -ONE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2904938T3 true ES2904938T3 (es) | 2022-04-06 |
Family
ID=63165529
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES18752976T Active ES2904938T3 (es) | 2017-08-02 | 2018-07-26 | Derivados de [1,2,4]triazolo[4,3-a]pirazin-6(5H)-ona |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US11180503B2 (https=) |
| EP (1) | EP3661936B1 (https=) |
| JP (1) | JP6850396B2 (https=) |
| CN (1) | CN110914268B (https=) |
| AR (1) | AR112457A1 (https=) |
| ES (1) | ES2904938T3 (https=) |
| TW (1) | TWI670271B (https=) |
| WO (1) | WO2019027783A1 (https=) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US11453673B2 (en) | 2018-02-06 | 2022-09-27 | Eli Lilly And Company | Substituted [1,2,4]triazolo[4,3-a]pyrazines as phosphodiesterase inhibitors |
| AU2024341364A1 (en) | 2023-09-14 | 2026-03-26 | Eli Lilly And Company | Pde1 inhibitors |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4354027A (en) | 1980-05-19 | 1982-10-12 | Usv Pharmaceutical Corporation | Triazoloquinoxalin-4-ones |
| WO2007150025A2 (en) * | 2006-06-23 | 2007-12-27 | Incyte Corporation | Purinone derivatives as hm74a agonists |
| CA2671980C (en) * | 2006-12-13 | 2015-05-05 | Aska Pharmaceutical Co., Ltd. | Quinoxaline derivatives |
| WO2008103357A1 (en) | 2007-02-21 | 2008-08-28 | E. I. Du Pont De Nemours And Company | Fungicidal tricyclic 1,2,4-triazoles |
| EP2509983B1 (en) * | 2009-11-16 | 2014-09-17 | Merck Sharp & Dohme Corp. | FUSED TRICYCLIC COMPOUNDS WITH ADENOSINE A2a RECEPTOR ANTAGONIST ACTIVITY |
| BR112013005439A2 (pt) | 2010-09-07 | 2017-09-19 | Astellas Pharma Inc | compostos de quinoxalina |
| CN103874701A (zh) * | 2011-09-09 | 2014-06-18 | H.隆德贝克有限公司 | 吡啶化合物和其用途 |
| MX357320B (es) | 2012-06-18 | 2018-07-04 | Dart Neuroscience Cayman Ltd | Compuestos de la azolopirimidina-5-(6h)-ona de piridina sustituida. |
| US20140045856A1 (en) * | 2012-07-31 | 2014-02-13 | Boehringer Ingelheim International Gmbh | 4-Methyl-2,3,5,9,9b-pentaaza-cyclopenta[a]naphthalenes |
| TW201629064A (zh) * | 2014-10-10 | 2016-08-16 | Ｈ 朗德貝克公司 | 作爲ｐｄｅ１抑制劑之三唑並吡酮 |
| TWI609870B (zh) * | 2016-02-12 | 2018-01-01 | 美國禮來大藥廠 | Pde1抑制劑 |
| JOP20170164A1 (ar) * | 2016-08-25 | 2019-01-30 | Lilly Co Eli | مشتق ترايازولو بيرازينون مفيد كمثبط لـ pde1 بشري |
-
2018
- 2018-07-17 AR ARP180101984 patent/AR112457A1/es unknown
- 2018-07-19 TW TW107124931A patent/TWI670271B/zh not_active IP Right Cessation
- 2018-07-26 WO PCT/US2018/043845 patent/WO2019027783A1/en not_active Ceased
- 2018-07-26 EP EP18752976.3A patent/EP3661936B1/en active Active
- 2018-07-26 ES ES18752976T patent/ES2904938T3/es active Active
- 2018-07-26 JP JP2020505232A patent/JP6850396B2/ja active Active
- 2018-07-26 CN CN201880050277.1A patent/CN110914268B/zh active Active
- 2018-07-26 US US16/624,545 patent/US11180503B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN110914268B (zh) | 2022-04-19 |
| US11180503B2 (en) | 2021-11-23 |
| EP3661936B1 (en) | 2021-12-22 |
| TW201920175A (zh) | 2019-06-01 |
| AR112457A1 (es) | 2019-10-30 |
| CN110914268A (zh) | 2020-03-24 |
| EP3661936A1 (en) | 2020-06-10 |
| JP2020529413A (ja) | 2020-10-08 |
| US20200123154A1 (en) | 2020-04-23 |
| JP6850396B2 (ja) | 2021-03-31 |
| TWI670271B (zh) | 2019-09-01 |
| WO2019027783A1 (en) | 2019-02-07 |
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