ES2637816T3 - Derivados de imidazo-triazina como inhibidores de PDE10 - Google Patents
Derivados de imidazo-triazina como inhibidores de PDE10 Download PDFInfo
- Publication number
- ES2637816T3 ES2637816T3 ES14727054.0T ES14727054T ES2637816T3 ES 2637816 T3 ES2637816 T3 ES 2637816T3 ES 14727054 T ES14727054 T ES 14727054T ES 2637816 T3 ES2637816 T3 ES 2637816T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- imidazo
- triazin
- tetrahydro
- tetrahydrofuran
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title description 7
- XZLIYCQRASOFQM-UHFFFAOYSA-N 5h-imidazo[4,5-d]triazine Chemical class N1=NC=C2NC=NC2=N1 XZLIYCQRASOFQM-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract description 27
- 229910052799 carbon Inorganic materials 0.000 abstract description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract description 8
- 125000001424 substituent group Chemical group 0.000 abstract description 8
- 125000000217 alkyl group Chemical group 0.000 abstract description 7
- 125000003118 aryl group Chemical group 0.000 abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 7
- 239000001257 hydrogen Substances 0.000 abstract description 7
- 125000001072 heteroaryl group Chemical group 0.000 abstract description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 abstract description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 5
- 229910052731 fluorine Inorganic materials 0.000 abstract description 5
- 239000011737 fluorine Substances 0.000 abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 5
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 4
- 150000003839 salts Chemical class 0.000 abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 3
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 abstract description 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 abstract description 2
- 150000002431 hydrogen Chemical class 0.000 abstract description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 1
- 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 abstract 1
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 abstract 1
- 125000004432 carbon atom Chemical group C* 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 238000000034 method Methods 0.000 description 80
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 47
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 45
- -1 11C Chemical compound 0.000 description 43
- 238000002360 preparation method Methods 0.000 description 40
- 239000007858 starting material Substances 0.000 description 38
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 23
- 239000000543 intermediate Substances 0.000 description 23
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- 238000003786 synthesis reaction Methods 0.000 description 19
- 125000006239 protecting group Chemical group 0.000 description 18
- 238000005481 NMR spectroscopy Methods 0.000 description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 13
- AZTMMFCJOROKMO-UHFFFAOYSA-N imidazo[5,1-f][1,2,4]triazine Chemical class N1=CN=CC2=CN=CN21 AZTMMFCJOROKMO-UHFFFAOYSA-N 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 150000001412 amines Chemical class 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 150000002500 ions Chemical class 0.000 description 11
- 230000014759 maintenance of location Effects 0.000 description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 11
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 210000004556 brain Anatomy 0.000 description 8
- 150000001721 carbon Chemical group 0.000 description 7
- 238000010828 elution Methods 0.000 description 7
- 238000011160 research Methods 0.000 description 7
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 208000028017 Psychotic disease Diseases 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 5
- 241000238631 Hexapoda Species 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 238000006069 Suzuki reaction reaction Methods 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 239000001569 carbon dioxide Substances 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 238000006073 displacement reaction Methods 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- IJYHVZICHKCLMQ-UHFFFAOYSA-N imidazo[4,5-d]triazin-4-one Chemical class O=C1N=NN=C2N=CN=C12 IJYHVZICHKCLMQ-UHFFFAOYSA-N 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 201000000980 schizophrenia Diseases 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- KNYHISBJRQVMAZ-UHFFFAOYSA-N 1h-pyrazolo[3,4-c]pyridine Chemical compound N1=CC=C2C=NNC2=C1 KNYHISBJRQVMAZ-UHFFFAOYSA-N 0.000 description 3
- 125000004791 2-fluoroethoxy group Chemical group FCCO* 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
- BPAUBEUYIXYWAV-UHFFFAOYSA-N 6-benzyl-2-chloro-7,8-dihydro-5h-1,6-naphthyridine Chemical compound C1CC2=NC(Cl)=CC=C2CN1CC1=CC=CC=C1 BPAUBEUYIXYWAV-UHFFFAOYSA-N 0.000 description 3
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 3
- 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 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 150000002545 isoxazoles Chemical class 0.000 description 3
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000004808 supercritical fluid chromatography Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical group C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 2
- QMNWYGTWTXOQTP-UHFFFAOYSA-N 1h-triazin-6-one Chemical compound O=C1C=CN=NN1 QMNWYGTWTXOQTP-UHFFFAOYSA-N 0.000 description 2
- FNRMMDCDHWCQTH-UHFFFAOYSA-N 2-chloropyridine;3-chloropyridine;4-chloropyridine Chemical compound ClC1=CC=NC=C1.ClC1=CC=CN=C1.ClC1=CC=CC=N1 FNRMMDCDHWCQTH-UHFFFAOYSA-N 0.000 description 2
- IFXGTTGFKFJPRP-UHFFFAOYSA-N 4,5-dihydropyrimidine-6-carboxylic acid Chemical compound OC(=O)C1=NC=NCC1 IFXGTTGFKFJPRP-UHFFFAOYSA-N 0.000 description 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
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- 101001072037 Homo sapiens cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Proteins 0.000 description 2
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- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
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- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
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- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 2
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- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
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- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
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- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
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- 238000004519 manufacturing process Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- UCFFGYASXIPWPD-UHFFFAOYSA-N methyl hypochlorite Chemical group COCl UCFFGYASXIPWPD-UHFFFAOYSA-N 0.000 description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 2
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 2
- 125000004043 oxo group Chemical group O=* 0.000 description 2
- 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 2
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
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- Health & Medical Sciences (AREA)
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- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Addiction (AREA)
- Dermatology (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361818650P | 2013-05-02 | 2013-05-02 | |
| US201361818650P | 2013-05-02 | ||
| PCT/IB2014/060945 WO2014177977A1 (en) | 2013-05-02 | 2014-04-23 | Imidazo-triazine derivatives as pde10 inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2637816T3 true ES2637816T3 (es) | 2017-10-17 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| ES14727054.0T Active ES2637816T3 (es) | 2013-05-02 | 2014-04-23 | Derivados de imidazo-triazina como inhibidores de PDE10 |
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| US (3) | US8933224B2 (OSRAM) |
| EP (1) | EP2991989B1 (OSRAM) |
| JP (1) | JP6263606B2 (OSRAM) |
| KR (1) | KR101770905B1 (OSRAM) |
| CN (1) | CN105164134B (OSRAM) |
| AP (1) | AP2015008843A0 (OSRAM) |
| AR (1) | AR096161A1 (OSRAM) |
| AU (1) | AU2014261070A1 (OSRAM) |
| BR (1) | BR112015027760A8 (OSRAM) |
| CA (1) | CA2910759C (OSRAM) |
| CL (1) | CL2015003037A1 (OSRAM) |
| CR (1) | CR20150591A (OSRAM) |
| CU (1) | CU20150144A7 (OSRAM) |
| DK (1) | DK2991989T3 (OSRAM) |
| DO (1) | DOP2015000271A (OSRAM) |
| EA (1) | EA027936B1 (OSRAM) |
| EC (1) | ECSP15050110A (OSRAM) |
| ES (1) | ES2637816T3 (OSRAM) |
| GE (1) | GEP201706675B (OSRAM) |
| MA (1) | MA38559B1 (OSRAM) |
| MD (1) | MD20150103A2 (OSRAM) |
| MX (1) | MX2015015163A (OSRAM) |
| NI (1) | NI201500157A (OSRAM) |
| NZ (1) | NZ712949A (OSRAM) |
| PE (1) | PE20151940A1 (OSRAM) |
| PH (1) | PH12015502462A1 (OSRAM) |
| SG (1) | SG11201508201VA (OSRAM) |
| TN (1) | TN2015000490A1 (OSRAM) |
| TW (1) | TWI508966B (OSRAM) |
| UA (1) | UA111696C2 (OSRAM) |
| UY (1) | UY35547A (OSRAM) |
| WO (1) | WO2014177977A1 (OSRAM) |
| ZA (1) | ZA201508968B (OSRAM) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| NZ712949A (en) * | 2013-05-02 | 2017-04-28 | Pfizer | Imidazo-triazine derivatives as pde10 inhibitors |
| WO2018047081A1 (en) | 2016-09-09 | 2018-03-15 | Novartis Ag | Compounds and compositions as inhibitors of endosomal toll-like receptors |
| US12448374B2 (en) | 2018-06-07 | 2025-10-21 | Disarm Therapeutics, Inc. | Inhibitors of SARM1 |
| EP3897670A4 (en) | 2018-12-19 | 2022-09-07 | Disarm Therapeutics, Inc. | MRSA1 INHIBITORS IN COMBINATION WITH NEUROPROTECTIVE AGENTS |
| MX2022004741A (es) * | 2019-10-21 | 2022-05-16 | Sk Biopharmaceuticals Co Ltd | Uso de compuestos de imidazopirimidina o imidazotriazina para prevencion, alivio, o tratamiento de trastornos cognitivos, o para mejorar la funcion cognitiva. |
| CN117486878A (zh) * | 2023-10-27 | 2024-02-02 | 扬州市普林斯医药科技有限公司 | 一种恩那司他的制备方法 |
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| US20010007867A1 (en) | 1999-12-13 | 2001-07-12 | Yuhpyng L. Chen | Substituted 6,5-hetero-bicyclic derivatives |
| DE10130167A1 (de) | 2001-06-22 | 2003-01-02 | Bayer Ag | Imidazotriazine |
| US7220862B2 (en) | 2002-06-05 | 2007-05-22 | Bristol-Myers Squibb Company | Calcitonin gene related peptide receptor antagonists |
| DE10230604A1 (de) | 2002-07-08 | 2004-01-29 | Bayer Ag | Heterocyclisch substituierte Imidazotriazine |
| JP2007508241A (ja) | 2003-07-31 | 2007-04-05 | バイエル・フアーマシユーチカルズ・コーポレーシヨン | Ｐｄｅ１０ａ阻害剤を用いる糖尿病および関連障害の処置方法 |
| JP4559749B2 (ja) * | 2004-02-16 | 2010-10-13 | あすか製薬株式会社 | ピペラジニルピリジン誘導体 |
| EP1595881A1 (en) | 2004-05-12 | 2005-11-16 | Pfizer Limited | Tetrahydronaphthyridine derivates useful as histamine H3 receptor ligands |
| US20070167426A1 (en) | 2004-06-02 | 2007-07-19 | Schering Corporation | Compounds for the treatment of inflammatory disorders and microbial diseases |
| TW200716102A (en) | 2005-06-01 | 2007-05-01 | Wyeth Corp | Bicyclic 6-alkylidene-penems as class-D β -lactamases inhibitors |
| US20080051419A1 (en) | 2006-07-26 | 2008-02-28 | Pfizer Inc. | Amine derivatives useful as anticancer agents |
| WO2008041571A1 (en) | 2006-09-26 | 2008-04-10 | Kaneka Corporation | Process for producing optically active beta-hydroxy-alpha-aminocarboxylic acid ester |
| WO2008057402A2 (en) | 2006-11-02 | 2008-05-15 | Cytovia, Inc. | N-aryl-isoxazolopyrimidin-4-amines and related compounds as activators of caspases and inducers of apoptosis and the use thereof |
| EP2203171A2 (en) | 2007-08-21 | 2010-07-07 | Merck Sharp & Dohme Corp. | Cb2 receptor ligands for the treatment of pain |
| DE102007059723A1 (de) | 2007-12-12 | 2009-06-18 | Siemens Medical Instruments Pte. Ltd. | Hörvorrichtung mit Batterieklappenmodul |
| TWI431010B (zh) | 2007-12-19 | 2014-03-21 | Lilly Co Eli | 礦皮質素受體拮抗劑及使用方法 |
| MX2010010151A (es) | 2008-03-20 | 2010-10-25 | Amgen Inc | Moduladores de cinasa aurora y metodo de uso. |
| EP2493889B1 (en) * | 2009-10-30 | 2017-09-06 | Janssen Pharmaceutica, N.V. | IMIDAZO[1,2-b]PYRIDAZINE DERIVATIVES AND THEIR USE AS PDE10 INHIBITORS |
| EP2526102B1 (en) | 2010-01-22 | 2017-03-08 | Fundación Centro Nacional de Investigaciones Oncológicas Carlos III | Inhibitors of PI3 kinase |
| AR080754A1 (es) | 2010-03-09 | 2012-05-09 | Janssen Pharmaceutica Nv | Derivados de imidazo (1,2-a) pirazina y su uso como inhibidores de pde10 |
| TW201200518A (en) | 2010-03-10 | 2012-01-01 | Kalypsys Inc | Heterocyclic inhibitors of histamine receptors for the treatment of disease |
| US20130131057A1 (en) | 2010-05-13 | 2013-05-23 | Centro Nacional De Investigaciones Oncologicas (Cnio | New bicyclic compounds as pi3-k and mtor inhibitors |
| BR112012029994A2 (pt) | 2010-05-28 | 2019-09-24 | Biocryst Pharm Inc | composto heterocíclicos como inibidores de janus quinase |
| US20130085161A1 (en) | 2010-06-17 | 2013-04-04 | Novartis Ag | Piperidinyl substituted 1,3-dihydro-benzoimidazol-2-ylideneamine derivatives |
| AP2013007070A0 (en) * | 2011-02-23 | 2013-08-31 | Pfizer | Imidazo[5,1-f][1,2,4] triazines for the treatment of neurological disorders |
| NZ712949A (en) * | 2013-05-02 | 2017-04-28 | Pfizer | Imidazo-triazine derivatives as pde10 inhibitors |
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2014
- 2014-04-23 NZ NZ712949A patent/NZ712949A/en not_active IP Right Cessation
- 2014-04-23 EP EP14727054.0A patent/EP2991989B1/en active Active
- 2014-04-23 ES ES14727054.0T patent/ES2637816T3/es active Active
- 2014-04-23 SG SG11201508201VA patent/SG11201508201VA/en unknown
- 2014-04-23 MD MDA20150103A patent/MD20150103A2/ro not_active Application Discontinuation
- 2014-04-23 AU AU2014261070A patent/AU2014261070A1/en not_active Abandoned
- 2014-04-23 PE PE2015002303A patent/PE20151940A1/es not_active Application Discontinuation
- 2014-04-23 BR BR112015027760A patent/BR112015027760A8/pt not_active Application Discontinuation
- 2014-04-23 JP JP2016511150A patent/JP6263606B2/ja not_active Expired - Fee Related
- 2014-04-23 TN TN2015000490A patent/TN2015000490A1/fr unknown
- 2014-04-23 GE GEAP201413979A patent/GEP201706675B/en unknown
- 2014-04-23 CN CN201480024798.1A patent/CN105164134B/zh not_active Expired - Fee Related
- 2014-04-23 MX MX2015015163A patent/MX2015015163A/es unknown
- 2014-04-23 CA CA2910759A patent/CA2910759C/en not_active Expired - Fee Related
- 2014-04-23 EA EA201591819A patent/EA027936B1/ru not_active IP Right Cessation
- 2014-04-23 MA MA38559A patent/MA38559B1/fr unknown
- 2014-04-23 UA UAA201510060A patent/UA111696C2/uk unknown
- 2014-04-23 WO PCT/IB2014/060945 patent/WO2014177977A1/en not_active Ceased
- 2014-04-23 DK DK14727054.0T patent/DK2991989T3/en active
- 2014-04-23 AP AP2015008843A patent/AP2015008843A0/xx unknown
- 2014-04-23 KR KR1020157034216A patent/KR101770905B1/ko not_active Expired - Fee Related
- 2014-04-29 TW TW103115365A patent/TWI508966B/zh not_active IP Right Cessation
- 2014-04-30 US US14/265,458 patent/US8933224B2/en not_active Expired - Fee Related
- 2014-04-30 UY UY0001035547A patent/UY35547A/es not_active Application Discontinuation
- 2014-04-30 AR ARP140101792A patent/AR096161A1/es unknown
- 2014-11-21 US US14/549,871 patent/US9145427B2/en not_active Expired - Fee Related
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2015
- 2015-08-19 US US14/829,842 patent/US9296761B2/en not_active Expired - Fee Related
- 2015-10-13 CL CL2015003037A patent/CL2015003037A1/es unknown
- 2015-10-19 CU CUP2015000144A patent/CU20150144A7/es unknown
- 2015-10-23 PH PH12015502462A patent/PH12015502462A1/en unknown
- 2015-10-27 CR CR20150591A patent/CR20150591A/es unknown
- 2015-10-30 NI NI201500157A patent/NI201500157A/es unknown
- 2015-11-02 DO DO2015000271A patent/DOP2015000271A/es unknown
- 2015-11-30 EC ECIEPI201550110A patent/ECSP15050110A/es unknown
- 2015-12-01 ZA ZA2015/08968A patent/ZA201508968B/en unknown
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