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
- 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.)
- Active
Links
- 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
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 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
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 101001072037 Homo sapiens cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 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
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 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
- 239000007983 Tris buffer Substances 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 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
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 2
- 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
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 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
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 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
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical group C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
- 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
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- JEHCUQDJKNBAQJ-ZCFIWIBFSA-N (4S)-1,4-dimethyl-4,5,6,7-tetrahydropyrazolo[3,4-c]pyridine Chemical compound C[C@@H]1CNCc2c1cnn2C JEHCUQDJKNBAQJ-ZCFIWIBFSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- RKOUFQLNMRAACI-UHFFFAOYSA-N 1,1,1-trifluoro-2-iodoethane Chemical compound FC(F)(F)CI RKOUFQLNMRAACI-UHFFFAOYSA-N 0.000 description 1
- OZTPQWRLHLQVBD-UHFFFAOYSA-N 1,2,3,4-tetrahydro-2,7-naphthyridine Chemical class C1=NC=C2CNCCC2=C1 OZTPQWRLHLQVBD-UHFFFAOYSA-N 0.000 description 1
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 description 1
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 1
- GZCJZOMIYUGQNY-UHFFFAOYSA-N 1,4-dimethylpyrazolo[3,4-c]pyridine Chemical compound CC1=CN=CC2=C1C=NN2C GZCJZOMIYUGQNY-UHFFFAOYSA-N 0.000 description 1
- FFFHDCDZHQWOKS-UHFFFAOYSA-N 1-(2,2,2-trifluoroethyl)-4,5,6,7-tetrahydropyrazolo[3,4-c]pyridine Chemical compound FC(F)(F)Cn1ncc2CCNCc12 FFFHDCDZHQWOKS-UHFFFAOYSA-N 0.000 description 1
- 125000001478 1-chloroethyl group Chemical group [H]C([H])([H])C([H])(Cl)* 0.000 description 1
- QMFQTLYMKDBOCK-UHFFFAOYSA-N 1-methoxy-2,7-naphthyridine Chemical compound COc1nccc2ccncc12 QMFQTLYMKDBOCK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- GBBSAMQTQCPOBF-UHFFFAOYSA-N 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane Chemical compound CB1OB(C)OB(C)O1 GBBSAMQTQCPOBF-UHFFFAOYSA-N 0.000 description 1
- BVZHUSQLXALJRA-UHFFFAOYSA-N 2-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-3-methyl-3,4-dihydro-1h-isoquinoline Chemical compound CC1CC2=CC=CC=C2CN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC=C1F BVZHUSQLXALJRA-UHFFFAOYSA-N 0.000 description 1
- MCLCOVRVGCRKDR-UHFFFAOYSA-N 2-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-6,7-dimethoxy-3,4-dihydro-1h-isoquinoline Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC=C1F MCLCOVRVGCRKDR-UHFFFAOYSA-N 0.000 description 1
- ATNKIZKOAYUJMJ-UHFFFAOYSA-N 2-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-6-methoxy-3,4-dihydro-1h-2,7-naphthyridine Chemical compound C1C=2C=NC(OC)=CC=2CCN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC=C1F ATNKIZKOAYUJMJ-UHFFFAOYSA-N 0.000 description 1
- NLCHXVUCIOYIME-UHFFFAOYSA-N 2-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-6-methyl-3,4-dihydro-1h-2,7-naphthyridine Chemical compound C=12C(N3CC4=CN=C(C)C=C4CC3)=NC=NN2C(C)=NC=1C1=CC=CC=C1F NLCHXVUCIOYIME-UHFFFAOYSA-N 0.000 description 1
- CBOPHBIFARVRRZ-UHFFFAOYSA-N 2-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-8-methoxy-3,4-dihydro-1h-2,7-naphthyridine Chemical compound C1C=2C(OC)=NC=CC=2CCN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC=C1F CBOPHBIFARVRRZ-UHFFFAOYSA-N 0.000 description 1
- GPPRXWUEJFPEDL-UHFFFAOYSA-N 2-bromo-1-(2-chloro-4-fluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CBr)C(Cl)=C1 GPPRXWUEJFPEDL-UHFFFAOYSA-N 0.000 description 1
- CGLYWDKTFBMSHI-UHFFFAOYSA-N 2-chloro-1,7-naphthyridine Chemical compound C1=CN=CC2=NC(Cl)=CC=C21 CGLYWDKTFBMSHI-UHFFFAOYSA-N 0.000 description 1
- XYINXVOXNQKIFQ-UHFFFAOYSA-N 2-cyclopropyl-5,6,7,8-tetrahydro-1,7-naphthyridine Chemical compound C1CC1c1ccc2CCNCc2n1 XYINXVOXNQKIFQ-UHFFFAOYSA-N 0.000 description 1
- SIKRYGNZEXFBTQ-UHFFFAOYSA-N 2-cyclopropyl-5-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-6,7-dihydro-4h-[1,3]oxazolo[5,4-c]pyridine Chemical compound C=12C(N3CC=4OC(=NC=4CC3)C3CC3)=NC=NN2C(C)=NC=1C1=CC=CC=C1F SIKRYGNZEXFBTQ-UHFFFAOYSA-N 0.000 description 1
- HFDPSIOPRFPKRB-UHFFFAOYSA-N 2-cyclopropyl-5-[7-methyl-5-(2-methylpropyl)imidazo[5,1-f][1,2,4]triazin-4-yl]-6,7-dihydro-4h-[1,3]oxazolo[5,4-c]pyridine Chemical compound C12=C(CC(C)C)N=C(C)N2N=CN=C1N(CC=1O2)CCC=1N=C2C1CC1 HFDPSIOPRFPKRB-UHFFFAOYSA-N 0.000 description 1
- CLIUTCNDBPIRQJ-CYBMUJFWSA-N 2-cyclopropyl-5-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-6,7-dihydro-4h-[1,3]oxazolo[5,4-c]pyridine Chemical compound C=12C(N3CC=4OC(=NC=4CC3)C3CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 CLIUTCNDBPIRQJ-CYBMUJFWSA-N 0.000 description 1
- PVOYOTZJSORNQG-MRXNPFEDSA-N 2-cyclopropyl-6-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-7,8-dihydro-5h-1,6-naphthyridine Chemical compound C=12C(N3CC4=CC=C(N=C4CC3)C3CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 PVOYOTZJSORNQG-MRXNPFEDSA-N 0.000 description 1
- RTMBJAADFQTAQK-UHFFFAOYSA-N 2-cyclopropyl-7-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-6,8-dihydro-5h-1,7-naphthyridine Chemical compound C=12C(N3CC4=NC(=CC=C4CC3)C3CC3)=NC=NN2C(C)=NC=1C1=CC=CC=C1F RTMBJAADFQTAQK-UHFFFAOYSA-N 0.000 description 1
- WFXLUOKMXKHCQZ-MRXNPFEDSA-N 2-cyclopropyl-7-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-6,8-dihydro-5h-1,7-naphthyridine Chemical compound C=12C(N3CC4=NC(=CC=C4CC3)C3CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 WFXLUOKMXKHCQZ-MRXNPFEDSA-N 0.000 description 1
- AQNVNTKGWPBSID-CQSZACIVSA-N 2-methoxy-6-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-7,8-dihydro-5h-1,6-naphthyridine Chemical compound C1CC2=NC(OC)=CC=C2CN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 AQNVNTKGWPBSID-CQSZACIVSA-N 0.000 description 1
- HTQLKDIBCSAMAJ-CQSZACIVSA-N 2-methoxy-7-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-6,8-dihydro-5h-1,7-naphthyridine Chemical compound C1C2=NC(OC)=CC=C2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 HTQLKDIBCSAMAJ-CQSZACIVSA-N 0.000 description 1
- CPHDKMLWZMGOEN-CYBMUJFWSA-N 2-methyl-5-[7-methyl-5-[(2r)-oxolan-2-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine Chemical compound C1C=2SC(C)=NC=2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@H]1CCCO1 CPHDKMLWZMGOEN-CYBMUJFWSA-N 0.000 description 1
- DYXBYJQKNCXPPV-LBPRGKRZSA-N 2-methyl-5-[7-methyl-5-[(3r)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-6,7-dihydro-4h-[1,3]oxazolo[5,4-c]pyridine Chemical compound C1C=2OC(C)=NC=2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@H]1CCOC1 DYXBYJQKNCXPPV-LBPRGKRZSA-N 0.000 description 1
- OIJMEJHVROTLNO-LBPRGKRZSA-N 2-methyl-5-[7-methyl-5-[(3r)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine Chemical compound C1C=2SC(C)=NC=2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@H]1CCOC1 OIJMEJHVROTLNO-LBPRGKRZSA-N 0.000 description 1
- IKUXIHAPMKHTDP-OAHLLOKOSA-N 2-methyl-6-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-7,8-dihydro-5h-1,6-naphthyridine Chemical compound C=12C(N3CC4=CC=C(C)N=C4CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 IKUXIHAPMKHTDP-OAHLLOKOSA-N 0.000 description 1
- LCZKCVFUBQLRBY-OAHLLOKOSA-N 2-methyl-7-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-6,8-dihydro-5h-1,7-naphthyridine Chemical compound C=12C(N3CC4=NC(C)=CC=C4CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 LCZKCVFUBQLRBY-OAHLLOKOSA-N 0.000 description 1
- DHAJHNOEVAJJHI-UHFFFAOYSA-N 2-propan-2-yl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridine Chemical compound C1NCCC2=NN(C(C)C)C=C21 DHAJHNOEVAJJHI-UHFFFAOYSA-N 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- OKQIQXMDRFQMTE-UHFFFAOYSA-N 3-cyclopropyl-5-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-6,7-dihydro-4h-[1,2]oxazolo[4,3-c]pyridine Chemical compound C=12C(N3CC4=C(C5CC5)ON=C4CC3)=NC=NN2C(C)=NC=1C1=CC=CC=C1F OKQIQXMDRFQMTE-UHFFFAOYSA-N 0.000 description 1
- NTYHOWJEOSQNDJ-UHFFFAOYSA-N 3-cyclopropyl-5-[7-methyl-5-(2-methylpropyl)imidazo[5,1-f][1,2,4]triazin-4-yl]-6,7-dihydro-4h-[1,2]oxazolo[4,3-c]pyridine Chemical compound C12=C(CC(C)C)N=C(C)N2N=CN=C1N(CC1=2)CCC1=NOC=2C1CC1 NTYHOWJEOSQNDJ-UHFFFAOYSA-N 0.000 description 1
- FDOIPELBXCCADB-OAHLLOKOSA-N 3-cyclopropyl-5-[7-methyl-5-[(2r)-oxolan-2-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-6,7-dihydro-4h-[1,2]oxazolo[4,3-c]pyridine Chemical compound C=12C(N3CC4=C(C5CC5)ON=C4CC3)=NC=NN2C(C)=NC=1[C@H]1CCCO1 FDOIPELBXCCADB-OAHLLOKOSA-N 0.000 description 1
- DPACQUUZKODHSM-CYBMUJFWSA-N 3-cyclopropyl-5-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-6,7-dihydro-4h-[1,2]oxazolo[4,3-c]pyridine Chemical compound C=12C(N3CC4=C(C5CC5)ON=C4CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 DPACQUUZKODHSM-CYBMUJFWSA-N 0.000 description 1
- NRWKFLWHXLOQDQ-GFCCVEGCSA-N 3-ethyl-5-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-6,7-dihydro-4h-[1,2]oxazolo[4,3-c]pyridine Chemical compound C1C2=C(CC)ON=C2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 NRWKFLWHXLOQDQ-GFCCVEGCSA-N 0.000 description 1
- JPFBAMRNCUKWRT-GFCCVEGCSA-N 3-ethyl-5-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-6,7-dihydro-4h-[1,2]oxazolo[4,5-c]pyridine Chemical compound C1C=2C(CC)=NOC=2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 JPFBAMRNCUKWRT-GFCCVEGCSA-N 0.000 description 1
- NXOHNTGMTMKBCO-CYBMUJFWSA-N 3-methoxy-6-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-7,8-dihydro-5h-1,6-naphthyridine Chemical compound C1C2=CC(OC)=CN=C2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 NXOHNTGMTMKBCO-CYBMUJFWSA-N 0.000 description 1
- UBSBMUMPRXIYFM-GFCCVEGCSA-N 3-methyl-5-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-6,7-dihydro-4h-[1,2]oxazolo[4,3-c]pyridine Chemical compound C=12C(N3CC4=C(C)ON=C4CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 UBSBMUMPRXIYFM-GFCCVEGCSA-N 0.000 description 1
- VUSZFJMBSGZDFE-GFCCVEGCSA-N 3-methyl-5-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-6,7-dihydro-4h-[1,2]oxazolo[4,5-c]pyridine Chemical compound C1C=2C(C)=NOC=2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 VUSZFJMBSGZDFE-GFCCVEGCSA-N 0.000 description 1
- KFOAQYYCEAGMEF-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1h-pyrazolo[3,4-c]pyridine Chemical compound C1NCCC2=C1NN=C2 KFOAQYYCEAGMEF-UHFFFAOYSA-N 0.000 description 1
- VGMJQHONPAXABH-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1h-pyrazolo[4,3-c]pyridine Chemical class C1NCCC2=C1C=NN2 VGMJQHONPAXABH-UHFFFAOYSA-N 0.000 description 1
- NMBOADHXCHYWOE-UHFFFAOYSA-N 4-(1,3-dimethyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazine Chemical compound C1C=2C(C)=NN(C)C=2CCN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC=C1F NMBOADHXCHYWOE-UHFFFAOYSA-N 0.000 description 1
- PLIXVEADZIEUNW-UHFFFAOYSA-N 4-(1,4-dimethyl-5,7-dihydro-4H-pyrazolo[3,4-c]pyridin-6-yl)-5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazine Chemical compound CN1N=CC2=C1CN(CC2C)C2=NC=NN1C2=C(N=C1C)C1=C(C=CC=C1)F PLIXVEADZIEUNW-UHFFFAOYSA-N 0.000 description 1
- MWXDJKXPANRHTQ-UHFFFAOYSA-N 4-(1-cyclopropyl-5,7-dihydro-4h-pyrazolo[3,4-c]pyridin-6-yl)-5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazine Chemical compound C=12C(N3CC=4N(C5CC5)N=CC=4CC3)=NC=NN2C(C)=NC=1C1=CC=CC=C1F MWXDJKXPANRHTQ-UHFFFAOYSA-N 0.000 description 1
- MOSXRSPLTNEPBR-CQSZACIVSA-N 4-(1-cyclopropyl-5,7-dihydro-4h-pyrazolo[3,4-c]pyridin-6-yl)-7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C=12C(N3CC=4N(C5CC5)N=CC=4CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 MOSXRSPLTNEPBR-CQSZACIVSA-N 0.000 description 1
- LUJSHNHCTJYGSI-ZDUSSCGKSA-N 4-(1-cyclopropyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-7-methyl-5-[(3r)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C=12C(N3CC4=C(N(N=C4)C4CC4)CC3)=NC=NN2C(C)=NC=1[C@H]1CCOC1 LUJSHNHCTJYGSI-ZDUSSCGKSA-N 0.000 description 1
- HRFFLJFPQHELPV-UHFFFAOYSA-N 4-(1-ethyl-5,7-dihydro-4h-pyrazolo[3,4-c]pyridin-6-yl)-5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazine Chemical compound C1C=2N(CC)N=CC=2CCN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC=C1F HRFFLJFPQHELPV-UHFFFAOYSA-N 0.000 description 1
- BVUSATBJYUTGJS-CQSZACIVSA-N 4-(1-ethyl-5,7-dihydro-4h-pyrazolo[3,4-c]pyridin-6-yl)-7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C1C=2N(CC)N=CC=2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 BVUSATBJYUTGJS-CQSZACIVSA-N 0.000 description 1
- VVBFRGXLQGJWRX-ZDUSSCGKSA-N 4-(2-cyclopropyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-7-methyl-5-[(3r)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C=12C(N3CC4=CN(N=C4CC3)C3CC3)=NC=NN2C(C)=NC=1[C@H]1CCOC1 VVBFRGXLQGJWRX-ZDUSSCGKSA-N 0.000 description 1
- VVBFRGXLQGJWRX-CYBMUJFWSA-N 4-(2-cyclopropyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C=12C(N3CC4=CN(N=C4CC3)C3CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 VVBFRGXLQGJWRX-CYBMUJFWSA-N 0.000 description 1
- SYRPJHKMGQGRQF-CQSZACIVSA-N 4-(3-cyclopropyl-2-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C=12C(N3CC4=C(C5CC5)N(C)N=C4CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 SYRPJHKMGQGRQF-CQSZACIVSA-N 0.000 description 1
- JDFBORTWMSETMR-UHFFFAOYSA-N 4-(3-ethyl-1-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazine Chemical compound C1C=2C(CC)=NN(C)C=2CCN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC=C1F JDFBORTWMSETMR-UHFFFAOYSA-N 0.000 description 1
- IPXAZSCBODCIAR-UHFFFAOYSA-N 4-(3-ethyl-1-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-5-(3-methoxyphenyl)-7-methylimidazo[5,1-f][1,2,4]triazine Chemical compound C1C=2C(CC)=NN(C)C=2CCN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC(OC)=C1 IPXAZSCBODCIAR-UHFFFAOYSA-N 0.000 description 1
- KVBNZPFJXCPAQS-UHFFFAOYSA-N 4-(3-ethyl-1-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-7-methyl-5-(2-methylpropyl)imidazo[5,1-f][1,2,4]triazine Chemical compound C1=NN2C(C)=NC(CC(C)C)=C2C(N2CCC=3N(C)N=C(C=3C2)CC)=N1 KVBNZPFJXCPAQS-UHFFFAOYSA-N 0.000 description 1
- CKAPKQAWQTZREY-UHFFFAOYSA-N 4-(3-ethyl-1-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-7-methyl-5-(oxan-4-yl)imidazo[5,1-f][1,2,4]triazine Chemical compound C1C=2C(CC)=NN(C)C=2CCN1C(C=12)=NC=NN2C(C)=NC=1C1CCOCC1 CKAPKQAWQTZREY-UHFFFAOYSA-N 0.000 description 1
- OOUJQFNVHVUXJQ-MRXNPFEDSA-N 4-(3-ethyl-1-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-7-methyl-5-[(2r)-oxolan-2-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C1C=2C(CC)=NN(C)C=2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@H]1CCCO1 OOUJQFNVHVUXJQ-MRXNPFEDSA-N 0.000 description 1
- VXPFYTLYXUNGJO-UHFFFAOYSA-N 4-(3-ethyl-2-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazine Chemical compound C1CC2=NN(C)C(CC)=C2CN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC=C1F VXPFYTLYXUNGJO-UHFFFAOYSA-N 0.000 description 1
- AABSVGIKIMJOKS-UHFFFAOYSA-N 4-(3-ethyl-2-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-7-methyl-5-(oxan-4-yl)imidazo[5,1-f][1,2,4]triazine Chemical compound C1CC2=NN(C)C(CC)=C2CN1C(C=12)=NC=NN2C(C)=NC=1C1CCOCC1 AABSVGIKIMJOKS-UHFFFAOYSA-N 0.000 description 1
- NIXRUMXIKZSSCT-CYBMUJFWSA-N 4-(3-ethyl-2-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C1CC2=NN(C)C(CC)=C2CN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 NIXRUMXIKZSSCT-CYBMUJFWSA-N 0.000 description 1
- PRFHFBOZKUMAMM-DGCLKSJQSA-N 4-[(4s)-1,4-dimethyl-5,7-dihydro-4h-pyrazolo[3,4-c]pyridin-6-yl]-7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C([C@H](C1=C(N(N=C1)C)C1)C)N1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 PRFHFBOZKUMAMM-DGCLKSJQSA-N 0.000 description 1
- FXOHIGKANXKTOR-UHFFFAOYSA-N 4-[1-(cyclobutylmethyl)-5,7-dihydro-4h-pyrazolo[3,4-c]pyridin-6-yl]-5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazine Chemical compound C=12C(N3CC=4N(CC5CCC5)N=CC=4CC3)=NC=NN2C(C)=NC=1C1=CC=CC=C1F FXOHIGKANXKTOR-UHFFFAOYSA-N 0.000 description 1
- RQMWVVBHJMUJNZ-UHFFFAOYSA-N 4-chloropyridin-2-amine Chemical group NC1=CC(Cl)=CC=N1 RQMWVVBHJMUJNZ-UHFFFAOYSA-N 0.000 description 1
- GNBKAOHTTIVAMT-UHFFFAOYSA-N 4-iodo-2-methoxypyridine-3-carbaldehyde Chemical compound COC1=NC=CC(I)=C1C=O GNBKAOHTTIVAMT-UHFFFAOYSA-N 0.000 description 1
- DTUBPCSMUKQAKJ-UHFFFAOYSA-N 4-phenylimidazol-1-amine Chemical class NN1C=NC(C=2C=CC=CC=2)=C1 DTUBPCSMUKQAKJ-UHFFFAOYSA-N 0.000 description 1
- IFXJKYPRCPDSHA-UHFFFAOYSA-N 5-(2-fluorophenyl)-7-methyl-4-(1-methyl-3-propan-2-yl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)imidazo[5,1-f][1,2,4]triazine Chemical compound C1C=2C(C(C)C)=NN(C)C=2CCN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC=C1F IFXJKYPRCPDSHA-UHFFFAOYSA-N 0.000 description 1
- JYRWHVPLBWTVEW-UHFFFAOYSA-N 5-(2-fluorophenyl)-7-methyl-4-(1-methyl-5,7-dihydro-4h-pyrazolo[3,4-c]pyridin-6-yl)imidazo[5,1-f][1,2,4]triazine Chemical compound C=12C(N3CC=4N(C)N=CC=4CC3)=NC=NN2C(C)=NC=1C1=CC=CC=C1F JYRWHVPLBWTVEW-UHFFFAOYSA-N 0.000 description 1
- UFJJAEIFRMPPHX-UHFFFAOYSA-N 5-(2-fluorophenyl)-7-methyl-4-[3-(trifluoromethyl)-6,7-dihydro-4h-pyrazolo[1,5-a]pyrazin-5-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C=12C(N3CC4=C(C=NN4CC3)C(F)(F)F)=NC=NN2C(C)=NC=1C1=CC=CC=C1F UFJJAEIFRMPPHX-UHFFFAOYSA-N 0.000 description 1
- YBPUQDFQSQUKRB-CYBMUJFWSA-N 5-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-3-propan-2-yl-6,7-dihydro-4h-[1,2]oxazolo[4,3-c]pyridine Chemical compound C1C2=C(C(C)C)ON=C2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 YBPUQDFQSQUKRB-CYBMUJFWSA-N 0.000 description 1
- UNHQCQWHTYOHHH-UHFFFAOYSA-N 6,7-dimethoxy-2-[7-methyl-5-(2-methylphenyl)imidazo[5,1-f][1,2,4]triazin-4-yl]-3,4-dihydro-1h-isoquinoline Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC=C1C UNHQCQWHTYOHHH-UHFFFAOYSA-N 0.000 description 1
- MFMZRZSKBPHDIL-UHFFFAOYSA-N 6,7-dimethoxy-2-[7-methyl-5-(2-methylpropyl)imidazo[5,1-f][1,2,4]triazin-4-yl]-3,4-dihydro-1h-isoquinoline Chemical compound C1=NN2C(C)=NC(CC(C)C)=C2C(N2CCC=3C=C(C(=CC=3C2)OC)OC)=N1 MFMZRZSKBPHDIL-UHFFFAOYSA-N 0.000 description 1
- DDOYQBCXQYGEBZ-UHFFFAOYSA-N 6,7-dimethoxy-2-[7-methyl-5-(oxolan-2-yl)imidazo[5,1-f][1,2,4]triazin-4-yl]-3,4-dihydro-1h-isoquinoline Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1C(C=12)=NC=NN2C(C)=NC=1C1CCCO1 DDOYQBCXQYGEBZ-UHFFFAOYSA-N 0.000 description 1
- DDOYQBCXQYGEBZ-MRXNPFEDSA-N 6,7-dimethoxy-2-[7-methyl-5-[(2r)-oxolan-2-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-3,4-dihydro-1h-isoquinoline Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@H]1CCCO1 DDOYQBCXQYGEBZ-MRXNPFEDSA-N 0.000 description 1
- DDOYQBCXQYGEBZ-INIZCTEOSA-N 6,7-dimethoxy-2-[7-methyl-5-[(2s)-oxolan-2-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-3,4-dihydro-1h-isoquinoline Chemical compound C1C=2C=C(OC)C(OC)=CC=2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCCO1 DDOYQBCXQYGEBZ-INIZCTEOSA-N 0.000 description 1
- GWOAUEMTLDKEIE-UHFFFAOYSA-N 6-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-2,3-dimethyl-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-one Chemical compound C=12C(N3CC=4C(=O)N(C)C(C)=NC=4CC3)=NC=NN2C(C)=NC=1C1=CC=CC=C1F GWOAUEMTLDKEIE-UHFFFAOYSA-N 0.000 description 1
- MVRUGMLWYASVEK-UHFFFAOYSA-N 6-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-2-methoxy-7,8-dihydro-5h-1,6-naphthyridine Chemical compound C1CC2=NC(OC)=CC=C2CN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC=C1F MVRUGMLWYASVEK-UHFFFAOYSA-N 0.000 description 1
- NRECROFMGVWREL-UHFFFAOYSA-N 6-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-2-methyl-7,8-dihydro-5h-1,6-naphthyridine Chemical compound C=12C(N3CC4=CC=C(C)N=C4CC3)=NC=NN2C(C)=NC=1C1=CC=CC=C1F NRECROFMGVWREL-UHFFFAOYSA-N 0.000 description 1
- HLTOBLLFSBKTLE-UHFFFAOYSA-N 6-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-3-methoxy-7,8-dihydro-5h-1,6-naphthyridine Chemical compound C1C2=CC(OC)=CN=C2CCN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC=C1F HLTOBLLFSBKTLE-UHFFFAOYSA-N 0.000 description 1
- IKBJWZVPIGLJJW-UHFFFAOYSA-N 6-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-7,8-dihydro-5h-1,6-naphthyridine Chemical compound C=12C(N3CC4=CC=CN=C4CC3)=NC=NN2C(C)=NC=1C1=CC=CC=C1F IKBJWZVPIGLJJW-UHFFFAOYSA-N 0.000 description 1
- DGVFBFRPVFJGKQ-UHFFFAOYSA-N 6-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-n,n-dimethyl-7,8-dihydro-5h-1,6-naphthyridin-2-amine Chemical compound C1CC2=NC(N(C)C)=CC=C2CN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC=C1F DGVFBFRPVFJGKQ-UHFFFAOYSA-N 0.000 description 1
- ONPZLGAKDLQTPK-UHFFFAOYSA-N 6-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-n-methyl-7,8-dihydro-5h-1,6-naphthyridin-2-amine Chemical compound C1CC2=NC(NC)=CC=C2CN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC=C1F ONPZLGAKDLQTPK-UHFFFAOYSA-N 0.000 description 1
- ACDIZGRFDLMEDE-UHFFFAOYSA-N 6-[7-methyl-5-(2-methylpropyl)imidazo[5,1-f][1,2,4]triazin-4-yl]-7,8-dihydro-5h-1,6-naphthyridine Chemical compound C1CC2=NC=CC=C2CN1C1=NC=NN2C(C)=NC(CC(C)C)=C12 ACDIZGRFDLMEDE-UHFFFAOYSA-N 0.000 description 1
- ZDBBZYINGXIHSY-UHFFFAOYSA-N 6-[7-methyl-5-(oxan-4-yl)imidazo[5,1-f][1,2,4]triazin-4-yl]-7,8-dihydro-5h-1,6-naphthyridine Chemical compound C=12C(N3CC4=CC=CN=C4CC3)=NC=NN2C(C)=NC=1C1CCOCC1 ZDBBZYINGXIHSY-UHFFFAOYSA-N 0.000 description 1
- HKXYKJZEBSIJSE-AWEZNQCLSA-N 6-[7-methyl-5-[(3r)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-7,8-dihydro-5h-1,6-naphthyridine Chemical compound C=12C(N3CC4=CC=CN=C4CC3)=NC=NN2C(C)=NC=1[C@H]1CCOC1 HKXYKJZEBSIJSE-AWEZNQCLSA-N 0.000 description 1
- HKXYKJZEBSIJSE-CQSZACIVSA-N 6-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-7,8-dihydro-5h-1,6-naphthyridine Chemical compound C=12C(N3CC4=CC=CN=C4CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 HKXYKJZEBSIJSE-CQSZACIVSA-N 0.000 description 1
- HOMAPWRCTZFIDF-UHFFFAOYSA-N 6-cyclopropyl-2-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-3,4-dihydro-1h-2,7-naphthyridine Chemical compound C=12C(N3CC4=CN=C(C=C4CC3)C3CC3)=NC=NN2C(C)=NC=1C1=CC=CC=C1F HOMAPWRCTZFIDF-UHFFFAOYSA-N 0.000 description 1
- PSRFQVGJFPAKQT-INIZCTEOSA-N 6-methoxy-2-[7-methyl-5-[(3r)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-3,4-dihydro-1h-isoquinoline Chemical compound C1CC2=CC(OC)=CC=C2CN1C(C=12)=NC=NN2C(C)=NC=1[C@H]1CCOC1 PSRFQVGJFPAKQT-INIZCTEOSA-N 0.000 description 1
- WZZBNSMKAJTTPV-CQSZACIVSA-N 6-methoxy-2-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-3,4-dihydro-1h-2,7-naphthyridine Chemical compound C1C=2C=NC(OC)=CC=2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 WZZBNSMKAJTTPV-CQSZACIVSA-N 0.000 description 1
- YZNASDMDYXCUPF-OAHLLOKOSA-N 6-methyl-2-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-3,4-dihydro-1h-2,7-naphthyridine Chemical compound C=12C(N3CC4=CN=C(C)C=C4CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 YZNASDMDYXCUPF-OAHLLOKOSA-N 0.000 description 1
- YZDIHSGBJQQLBO-OAHLLOKOSA-N 7,8-dimethoxy-2-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-3,4-dihydro-1h-isoquinoline Chemical compound C1C2=C(OC)C(OC)=CC=C2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 YZDIHSGBJQQLBO-OAHLLOKOSA-N 0.000 description 1
- GGOQKCIQOUZSDA-UHFFFAOYSA-N 7-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-2-(trifluoromethyl)-6,8-dihydro-5h-1,7-naphthyridine Chemical compound C=12C(N3CC4=NC(=CC=C4CC3)C(F)(F)F)=NC=NN2C(C)=NC=1C1=CC=CC=C1F GGOQKCIQOUZSDA-UHFFFAOYSA-N 0.000 description 1
- GLRQGQVBTJQILR-UHFFFAOYSA-N 7-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-2-methoxy-6,8-dihydro-5h-1,7-naphthyridine Chemical compound C1C2=NC(OC)=CC=C2CCN1C(C=12)=NC=NN2C(C)=NC=1C1=CC=CC=C1F GLRQGQVBTJQILR-UHFFFAOYSA-N 0.000 description 1
- LLSQKOVYIVFXNQ-UHFFFAOYSA-N 7-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-2-methyl-6,8-dihydro-5h-1,7-naphthyridine Chemical compound C=12C(N3CC4=NC(C)=CC=C4CC3)=NC=NN2C(C)=NC=1C1=CC=CC=C1F LLSQKOVYIVFXNQ-UHFFFAOYSA-N 0.000 description 1
- MXAJDDHMFYPJOE-UHFFFAOYSA-N 7-[5-(2-fluorophenyl)-7-methylimidazo[5,1-f][1,2,4]triazin-4-yl]-6,8-dihydro-5h-1,7-naphthyridine Chemical compound C=12C(N3CC4=NC=CC=C4CC3)=NC=NN2C(C)=NC=1C1=CC=CC=C1F MXAJDDHMFYPJOE-UHFFFAOYSA-N 0.000 description 1
- MYZJFYUDILCCEH-CYBMUJFWSA-N 7-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-2-(trifluoromethyl)-6,8-dihydro-5h-1,7-naphthyridine Chemical compound C=12C(N3CC4=NC(=CC=C4CC3)C(F)(F)F)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 MYZJFYUDILCCEH-CYBMUJFWSA-N 0.000 description 1
- DPZWYCQPJKWHLL-CQSZACIVSA-N 7-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-6,8-dihydro-5h-1,7-naphthyridine Chemical compound C=12C(N3CC4=NC=CC=C4CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 DPZWYCQPJKWHLL-CQSZACIVSA-N 0.000 description 1
- GQLCSOKIWUYAME-UHFFFAOYSA-N 7-benzyl-2-cyclopropyl-6,8-dihydro-5H-1,7-naphthyridine Chemical compound C(N1CCc2ccc(nc2C1)C1CC1)c1ccccc1 GQLCSOKIWUYAME-UHFFFAOYSA-N 0.000 description 1
- FDDXBJNULDNNPL-UHFFFAOYSA-N 7-methyl-1h-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound N1C=NC(=O)C=2N1C(C)=NC=2 FDDXBJNULDNNPL-UHFFFAOYSA-N 0.000 description 1
- LWTJSNAZZKYABX-UHFFFAOYSA-N 7-methyl-4-(1-methyl-3-propan-2-yl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-5-(oxan-4-yl)imidazo[5,1-f][1,2,4]triazine Chemical compound C1C=2C(C(C)C)=NN(C)C=2CCN1C(C=12)=NC=NN2C(C)=NC=1C1CCOCC1 LWTJSNAZZKYABX-UHFFFAOYSA-N 0.000 description 1
- JXGSWYKUIJTHLW-UHFFFAOYSA-N 7-methyl-4-(1-methyl-3-propan-2-yl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-5-(oxolan-2-yl)imidazo[5,1-f][1,2,4]triazine Chemical compound C1C=2C(C(C)C)=NN(C)C=2CCN1C(C=12)=NC=NN2C(C)=NC=1C1CCCO1 JXGSWYKUIJTHLW-UHFFFAOYSA-N 0.000 description 1
- JQNFABHCPGZYEE-AWEZNQCLSA-N 7-methyl-4-(1-methyl-3-propan-2-yl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-5-[(3r)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C1C=2C(C(C)C)=NN(C)C=2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@H]1CCOC1 JQNFABHCPGZYEE-AWEZNQCLSA-N 0.000 description 1
- JQNFABHCPGZYEE-CQSZACIVSA-N 7-methyl-4-(1-methyl-3-propan-2-yl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C1C=2C(C(C)C)=NN(C)C=2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 JQNFABHCPGZYEE-CQSZACIVSA-N 0.000 description 1
- QBCXBKWIHPOTLC-CYBMUJFWSA-N 7-methyl-4-(1-methyl-5,7-dihydro-4h-pyrazolo[3,4-c]pyridin-6-yl)-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C=12C(N3CC=4N(C)N=CC=4CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 QBCXBKWIHPOTLC-CYBMUJFWSA-N 0.000 description 1
- SNRPYULNMUXPPE-UHFFFAOYSA-N 7-methyl-4-(2-methyl-3-propan-2-yl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-5-(oxan-4-yl)imidazo[5,1-f][1,2,4]triazine Chemical compound C1CC2=NN(C)C(C(C)C)=C2CN1C(C=12)=NC=NN2C(C)=NC=1C1CCOCC1 SNRPYULNMUXPPE-UHFFFAOYSA-N 0.000 description 1
- IMVHNIZATAEPNF-LBPRGKRZSA-N 7-methyl-4-(2-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-5-[(3r)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C=12C(N3CC4=CN(C)N=C4CC3)=NC=NN2C(C)=NC=1[C@H]1CCOC1 IMVHNIZATAEPNF-LBPRGKRZSA-N 0.000 description 1
- MYKDJNAZONAFPX-MRXNPFEDSA-N 7-methyl-4-[1-(2-methylpropyl)-5,7-dihydro-4h-pyrazolo[3,4-c]pyridin-6-yl]-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C1C=2N(CC(C)C)N=CC=2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 MYKDJNAZONAFPX-MRXNPFEDSA-N 0.000 description 1
- DSBGOHSJTJJOHG-AWEZNQCLSA-N 7-methyl-5-[(3r)-oxolan-3-yl]-4-(2-propan-2-yl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)imidazo[5,1-f][1,2,4]triazine Chemical compound C1CC2=NN(C(C)C)C=C2CN1C(C=12)=NC=NN2C(C)=NC=1[C@H]1CCOC1 DSBGOHSJTJJOHG-AWEZNQCLSA-N 0.000 description 1
- LPYZVAAZANCDBC-OAHLLOKOSA-N 7-methyl-5-[(3s)-oxolan-3-yl]-4-(1-propan-2-yl-5,7-dihydro-4h-pyrazolo[3,4-c]pyridin-6-yl)imidazo[5,1-f][1,2,4]triazine Chemical compound C1C=2N(C(C)C)N=CC=2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 LPYZVAAZANCDBC-OAHLLOKOSA-N 0.000 description 1
- OCGGLSQFJOWXTE-CYBMUJFWSA-N 7-methyl-5-[(3s)-oxolan-3-yl]-4-[1-(2,2,2-trifluoroethyl)-5,7-dihydro-4h-pyrazolo[3,4-c]pyridin-6-yl]imidazo[5,1-f][1,2,4]triazine Chemical compound C=12C(N3CC=4N(CC(F)(F)F)N=CC=4CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 OCGGLSQFJOWXTE-CYBMUJFWSA-N 0.000 description 1
- ILOHWUYWJICLGI-UHFFFAOYSA-N 8-methoxy-1,2,3,4-tetrahydro-2,7-naphthyridine Chemical compound C1CNCC2=C1C=CN=C2OC ILOHWUYWJICLGI-UHFFFAOYSA-N 0.000 description 1
- KQIINWUTTOWGNK-CQSZACIVSA-N 8-methoxy-2-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-3,4-dihydro-1h-2,7-naphthyridine Chemical compound C1C=2C(OC)=NC=CC=2CCN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 KQIINWUTTOWGNK-CQSZACIVSA-N 0.000 description 1
- PHHNJEWGBIBZFN-MRXNPFEDSA-N 8-methyl-2-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-3,4-dihydro-1h-isoquinoline Chemical compound C=12C(N3CC4=C(C)C=CC=C4CC3)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 PHHNJEWGBIBZFN-MRXNPFEDSA-N 0.000 description 1
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Natural products CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010008748 Chorea Diseases 0.000 description 1
- USDIRSJFHPHMAS-UHFFFAOYSA-N ClC1=NC=C(C=2C1=NC=CN=2)F Chemical compound ClC1=NC=C(C=2C1=NC=CN=2)F USDIRSJFHPHMAS-UHFFFAOYSA-N 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 206010010219 Compulsions Diseases 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical class NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 101100049938 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) exr-1 gene Proteins 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 206010034719 Personality change Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 1
- 206010043118 Tardive Dyskinesia Diseases 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 208000012931 Urologic disease Diseases 0.000 description 1
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
- WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 1
- 150000008062 acetophenones Chemical class 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 150000001345 alkine derivatives Chemical group 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 150000001411 amidrazones Chemical class 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- XXXHSQBVHSJQKS-UHFFFAOYSA-N amino benzoate Chemical class NOC(=O)C1=CC=CC=C1 XXXHSQBVHSJQKS-UHFFFAOYSA-N 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 210000004227 basal ganglia Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
- ZOUWBWLDHBZPTM-UHFFFAOYSA-N benzyl 4-oxo-3-propanoylpiperidine-1-carboxylate Chemical compound CCC(=O)C1CN(CCC1=O)C(=O)OCc1ccccc1 ZOUWBWLDHBZPTM-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- YHNUDLCUIKMNSN-UHFFFAOYSA-N bis(1,2,4-triazol-1-yl)methanone Chemical compound C1=NC=NN1C(=O)N1C=NC=N1 YHNUDLCUIKMNSN-UHFFFAOYSA-N 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 102100036377 cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Human genes 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 208000012601 choreatic disease Diseases 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 231100000868 delusion Toxicity 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- XXECWTBMGGXMKP-UHFFFAOYSA-L dichloronickel;2-diphenylphosphanylethyl(diphenyl)phosphane Chemical compound Cl[Ni]Cl.C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 XXECWTBMGGXMKP-UHFFFAOYSA-L 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 238000009513 drug distribution Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 102000054918 human PDE10A Human genes 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 150000002466 imines Chemical group 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- KTMKRRPZPWUYKK-UHFFFAOYSA-N methylboronic acid Chemical compound CB(O)O KTMKRRPZPWUYKK-UHFFFAOYSA-N 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- CMGGVKKDMCBKBK-UHFFFAOYSA-N n,n-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-2-amine Chemical compound C1NCCC2=NC(N(C)C)=CC=C21 CMGGVKKDMCBKBK-UHFFFAOYSA-N 0.000 description 1
- GFTINWSUZXFYKT-UHFFFAOYSA-N n-methyl-5,6,7,8-tetrahydro-1,6-naphthyridin-2-amine Chemical compound C1NCCC2=NC(NC)=CC=C21 GFTINWSUZXFYKT-UHFFFAOYSA-N 0.000 description 1
- RYLBBLIIRSTMHF-CQSZACIVSA-N n-methyl-6-[7-methyl-5-[(3s)-oxolan-3-yl]imidazo[5,1-f][1,2,4]triazin-4-yl]-7,8-dihydro-5h-1,6-naphthyridin-2-amine Chemical compound C1CC2=NC(NC)=CC=C2CN1C(C=12)=NC=NN2C(C)=NC=1[C@@H]1CCOC1 RYLBBLIIRSTMHF-CQSZACIVSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical class [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000012587 nuclear overhauser effect experiment Methods 0.000 description 1
- SJECIYLGISUNRO-UHFFFAOYSA-N o-diphenylphosphorylhydroxylamine Chemical compound C=1C=CC=CC=1P(=O)(ON)C1=CC=CC=C1 SJECIYLGISUNRO-UHFFFAOYSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000011049 pearl Substances 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 210000002442 prefrontal cortex Anatomy 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- KJAQRHMKLVGSCG-UHFFFAOYSA-N propan-2-ylhydrazine Chemical compound CC(C)NN KJAQRHMKLVGSCG-UHFFFAOYSA-N 0.000 description 1
- 210000002637 putamen Anatomy 0.000 description 1
- 150000003216 pyrazines Chemical class 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 101150101384 rat1 gene Proteins 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- YUSMZDVTEOAHDL-CSKARUKUSA-N tert-butyl (3e)-3-(dimethylaminomethylidene)-4-oxopiperidine-1-carboxylate Chemical compound CN(C)\C=C1/CN(C(=O)OC(C)(C)C)CCC1=O YUSMZDVTEOAHDL-CSKARUKUSA-N 0.000 description 1
- SLHNDMPEIUPCNG-UHFFFAOYSA-N tert-butyl 4-oxo-3-(2,2,2-trifluoroacetyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)C(C(=O)C(F)(F)F)C1 SLHNDMPEIUPCNG-UHFFFAOYSA-N 0.000 description 1
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 208000014001 urinary system disease Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
- C07D471/02—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 two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- 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)
- Heart & Thoracic Surgery (AREA)
- Addiction (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (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
ID=50841902
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14727054.0T Active ES2637816T3 (es) | 2013-05-02 | 2014-04-23 | Derivados de imidazo-triazina como inhibidores de PDE10 |
Country Status (33)
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2910759C (en) * | 2013-05-02 | 2018-01-16 | Pfizer Inc. | Imidazo-triazine derivatives as pde10 inhibitors |
| CN115215886B (zh) | 2016-09-09 | 2024-10-11 | 诺华股份有限公司 | 作为内体Toll样受体抑制剂的化合物及组合物 |
| WO2019236884A1 (en) | 2018-06-07 | 2019-12-12 | Disarm Therapeutics, Inc. | Inhibitors of sarm1 |
| CA3123215C (en) | 2018-12-19 | 2024-04-02 | Disarm Therapeutics, Inc. | Inhibitors of sarm1 in combination with neuroprotective agents |
| CN114929230B (zh) * | 2019-10-21 | 2024-11-29 | 爱思开生物制药株式会社 | 咪唑并嘧啶或咪唑并三嗪化合物用于预防、减轻或治疗认知障碍或者用于改善认知功能的用途 |
| JP2025505163A (ja) * | 2022-02-02 | 2025-02-21 | ザ・カトリック・ユニヴェルシテイト・ルーバン | Ｙａｐ／ｔａｚ－ｔｅａｄを阻害するためのテトラヒドロピリドピリミジン及び関連類似体 |
| 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 |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| WO2005012485A2 (en) | 2003-07-31 | 2005-02-10 | Bayer Pharmaceuticals Corporation | Methods for treating diabetes and related disorders using pde10a inhibitors |
| 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 |
| US20120004222A1 (en) | 2007-08-21 | 2012-01-05 | Zhicai Wu | 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 |
| WO2009117157A1 (en) | 2008-03-20 | 2009-09-24 | Amgen Inc. | Aurora kinase modulators and method of use |
| JP5641664B2 (ja) * | 2009-10-30 | 2014-12-17 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプＪａｎｓｓｅｎ Ｐｈａｒｍａｃｅｕｔｉｃａ Ｎａａｍｌｏｚｅ Ｖｅｎｎｏｏｔｓｃｈａｐ | イミダゾ［１，２−ｂ］ピリダジン誘導体およびＰＤＥ１０阻害剤としてのそれらの使用 |
| 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 |
| WO2011141713A1 (en) | 2010-05-13 | 2011-11-17 | Centro Nacional De Investigaciones Oncologicas (Cnio) | New bicyclic compounds as pi3-k and mtor inhibitors |
| KR20130083389A (ko) | 2010-05-28 | 2013-07-22 | 바이오크리스트파마슈티컬즈,인코포레이티드 | 야누스 키나아제 억제제로서 헤테로사이클릭 화합물 |
| EP2582681A1 (en) | 2010-06-17 | 2013-04-24 | Novartis AG | Piperidinyl substituted 1,3-dihydro-benzoimidazol-2-ylideneamine derivatives |
| PE20140236A1 (es) | 2011-02-23 | 2014-03-14 | Pfizer | IMIDAZO[5,1-f][1,2,4]TRIAZINAS PARA EL TRATAMIENTO DE TRASTORNOS NEUROLOGICOS |
| CA2910759C (en) * | 2013-05-02 | 2018-01-16 | Pfizer Inc. | Imidazo-triazine derivatives as pde10 inhibitors |
-
2014
- 2014-04-23 CA CA2910759A patent/CA2910759C/en not_active Expired - Fee Related
- 2014-04-23 ES ES14727054.0T patent/ES2637816T3/es active Active
- 2014-04-23 NZ NZ712949A patent/NZ712949A/en not_active IP Right Cessation
- 2014-04-23 JP JP2016511150A patent/JP6263606B2/ja not_active Expired - Fee Related
- 2014-04-23 DK DK14727054.0T patent/DK2991989T3/en active
- 2014-04-23 EP EP14727054.0A patent/EP2991989B1/en active Active
- 2014-04-23 KR KR1020157034216A patent/KR101770905B1/ko not_active Expired - Fee Related
- 2014-04-23 GE GEAP201413979A patent/GEP201706675B/en unknown
- 2014-04-23 SG SG11201508201VA patent/SG11201508201VA/en unknown
- 2014-04-23 AU AU2014261070A patent/AU2014261070A1/en not_active Abandoned
- 2014-04-23 TN TN2015000490A patent/TN2015000490A1/fr unknown
- 2014-04-23 MA MA38559A patent/MA38559B1/fr unknown
- 2014-04-23 PE PE2015002303A patent/PE20151940A1/es not_active Application Discontinuation
- 2014-04-23 MD MDA20150103A patent/MD20150103A2/ro not_active Application Discontinuation
- 2014-04-23 WO PCT/IB2014/060945 patent/WO2014177977A1/en not_active Ceased
- 2014-04-23 CN CN201480024798.1A patent/CN105164134B/zh not_active Expired - Fee Related
- 2014-04-23 BR BR112015027760A patent/BR112015027760A8/pt not_active Application Discontinuation
- 2014-04-23 UA UAA201510060A patent/UA111696C2/uk unknown
- 2014-04-23 EA EA201591819A patent/EA027936B1/ru not_active IP Right Cessation
- 2014-04-23 MX MX2015015163A patent/MX2015015163A/es unknown
- 2014-04-23 AP AP2015008843A patent/AP2015008843A0/xx unknown
- 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
-
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
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2637816T3 (es) | Derivados de imidazo-triazina como inhibidores de PDE10 | |
| KR102165113B1 (ko) | Ａ2ａ 길항제 성질을 갖는 헤테로비시클로-치환된-[1,2,4]트리아졸로[1,5-ｃ]퀴나졸린-5-아민 화합물 | |
| AU2020293021B2 (en) | PRMT5 inhibitors | |
| AU2012301721B2 (en) | Heterocyclylamines as PI3K inhibitors | |
| ES2697174T3 (es) | Compuestos para tratar atrofia muscular espinal | |
| EP3038466B1 (en) | 2,2-difluorodioxolo a2a receptor antagonists | |
| AU2025226693A1 (en) | Monoacylglycerol lipase modulators | |
| KR20140059195A (ko) | 트리시클릭 헤테로시클릭 화합물 및 jak 저해제 | |
| EP4100381A1 (en) | Substituted 1,1'-biphenyl compounds and methods using same | |
| AU2021373162A1 (en) | Pyrazolopyridazinone compound, and pharmaceutical composition and use thereof | |
| JP6542900B2 (ja) | 抗肺結核症のニトロイミダゾール誘導体 | |
| OA17580A (en) | Imidazo-Triazine derivatives as PDE 10 inhibitors. |