ES2555167T3 - Nuevos derivados de indol sustituidos como moduladores de gamma secretasa - Google Patents
Nuevos derivados de indol sustituidos como moduladores de gamma secretasa Download PDFInfo
- Publication number
- ES2555167T3 ES2555167T3 ES12733754.1T ES12733754T ES2555167T3 ES 2555167 T3 ES2555167 T3 ES 2555167T3 ES 12733754 T ES12733754 T ES 12733754T ES 2555167 T3 ES2555167 T3 ES 2555167T3
- Authority
- ES
- Spain
- Prior art keywords
- substituents
- group
- hydrogen
- alkyloxy
- optionally substituted
- 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
- VHNYOQKVZQVBLC-RTCGXNAVSA-N (4r,7e,9as)-7-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]-4-(3,4,5-trifluorophenyl)-1,3,4,8,9,9a-hexahydropyrido[2,1-c][1,4]oxazin-6-one Chemical compound C1([C@@H]2COC[C@@H]3CC\C(C(N32)=O)=C/C=2C=C(C(=CC=2)N2C=C(C)N=C2)OC)=CC(F)=C(F)C(F)=C1 VHNYOQKVZQVBLC-RTCGXNAVSA-N 0.000 title 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 title 1
- 150000002475 indoles Chemical class 0.000 title 1
- 229940124648 γ-Secretase Modulator Drugs 0.000 title 1
- -1 NR7R8 Chemical group 0.000 abstract description 62
- 150000001875 compounds Chemical class 0.000 abstract description 58
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 45
- 239000001257 hydrogen Substances 0.000 abstract description 45
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 41
- 125000003545 alkoxy group Chemical group 0.000 abstract description 40
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 40
- 125000001424 substituent group Chemical group 0.000 abstract description 32
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 30
- 150000003839 salts Chemical class 0.000 abstract description 29
- 125000005843 halogen group Chemical group 0.000 abstract description 26
- 125000004076 pyridyl group Chemical group 0.000 abstract description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 17
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 abstract description 16
- 229910052731 fluorine Inorganic materials 0.000 abstract description 14
- 239000011737 fluorine Chemical group 0.000 abstract description 14
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 abstract description 13
- 125000004448 alkyl carbonyl group Chemical group 0.000 abstract description 13
- 125000003226 pyrazolyl group Chemical group 0.000 abstract description 12
- 239000012453 solvate Substances 0.000 abstract description 12
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 10
- 125000001153 fluoro group Chemical group F* 0.000 abstract description 10
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 abstract description 8
- 125000002883 imidazolyl group Chemical group 0.000 abstract description 8
- 125000002971 oxazolyl group Chemical group 0.000 abstract description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 6
- 125000002757 morpholinyl group Chemical group 0.000 abstract description 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 abstract description 4
- 102100024650 Carbonic anhydrase 3 Human genes 0.000 description 52
- 101000760630 Homo sapiens Carbonic anhydrase 3 Proteins 0.000 description 52
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 41
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 22
- 230000003287 optical effect Effects 0.000 description 20
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 230000002285 radioactive effect Effects 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 9
- 239000011324 bead Substances 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- YHWMFDLNZGIJSD-UHFFFAOYSA-N 2h-1,4-oxazine Chemical compound C1OC=CN=C1 YHWMFDLNZGIJSD-UHFFFAOYSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 229910052717 sulfur Inorganic materials 0.000 description 7
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-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
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- DACWQSNZECJJGG-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyridine Chemical compound C1=CC=CN2N=CN=C21 DACWQSNZECJJGG-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- YHYLDEVWYOFIJK-UHFFFAOYSA-N 1h-indole-5-carbonitrile Chemical compound N#CC1=CC=C2NC=CC2=C1 YHYLDEVWYOFIJK-UHFFFAOYSA-N 0.000 description 2
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 2
- PIAWXNKEFFYUCD-UHFFFAOYSA-N 2-[8-(2-cyclopropylphenyl)-6,8-dihydro-5h-imidazo[2,1-c][1,4]oxazin-2-yl]-4-methoxy-1h-indole-5-carbonitrile Chemical compound C=1C=2C(OC)=C(C#N)C=CC=2NC=1C(N=C12)=CN1CCOC2C1=CC=CC=C1C1CC1 PIAWXNKEFFYUCD-UHFFFAOYSA-N 0.000 description 2
- UMAUKBQUICMSGM-UHFFFAOYSA-N 2-[8-(4-fluoro-2-methylphenyl)-6,8-dihydro-5H-[1,2,4]triazolo[5,1-c][1,4]oxazin-2-yl]-4-propan-2-yloxy-1H-indole-5-carbonitrile Chemical compound C=1C=2C(OC(C)C)=C(C#N)C=CC=2NC=1C(=NN1CCO2)N=C1C2C1=CC=C(F)C=C1C UMAUKBQUICMSGM-UHFFFAOYSA-N 0.000 description 2
- HVSDODQLRPYGML-UHFFFAOYSA-N 2-[8-(4-fluoro-2-methylphenyl)-6,8-dihydro-5h-imidazo[2,1-c][1,4]oxazin-2-yl]-4-methoxy-1h-indole-5-carbonitrile Chemical compound C=1C=2C(OC)=C(C#N)C=CC=2NC=1C(N=C12)=CN1CCOC2C1=CC=C(F)C=C1C HVSDODQLRPYGML-UHFFFAOYSA-N 0.000 description 2
- SWVQFTATJKGKJI-UHFFFAOYSA-N 4-methoxy-2-[8-[5-methyl-2-(2,2,2-trifluoroethyl)pyrazol-3-yl]-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-yl]-1h-indole-5-carbonitrile Chemical compound C=1C=2C(OC)=C(C#N)C=CC=2NC=1C(N=C12)=CN1CCCC2C1=CC(C)=NN1CC(F)(F)F SWVQFTATJKGKJI-UHFFFAOYSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 239000003797 essential amino acid Substances 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000006199 nebulizer Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- XWIYUCRMWCHYJR-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine Chemical compound C1=CC=C2NC=CC2=N1 XWIYUCRMWCHYJR-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- YNDHMPHNXKLPMA-UHFFFAOYSA-N 2-[5-[2-fluoro-5-(trifluoromethyl)phenyl]-5-methyl-6,8-dihydroimidazo[2,1-c][1,4]oxazin-2-yl]-4-methoxy-1h-indole-5-carbonitrile Chemical compound C=1C=2C(OC)=C(C#N)C=CC=2NC=1C(N=1)=CN2C=1COCC2(C)C1=CC(C(F)(F)F)=CC=C1F YNDHMPHNXKLPMA-UHFFFAOYSA-N 0.000 description 1
- GVCNSJONPNQBSI-UHFFFAOYSA-N 2-[8-(2-chloro-6-fluorophenyl)-6,8-dihydro-5H-[1,2,4]triazolo[5,1-c][1,4]oxazin-2-yl]-4-methoxy-1H-indole-5-carbonitrile Chemical compound C=1C=2C(OC)=C(C#N)C=CC=2NC=1C(=NN1CCO2)N=C1C2C1=C(F)C=CC=C1Cl GVCNSJONPNQBSI-UHFFFAOYSA-N 0.000 description 1
- PJTKIWAFRIDTBK-UHFFFAOYSA-N 2-[8-(2-chloro-6-fluorophenyl)-6,8-dihydro-5h-imidazo[2,1-c][1,4]oxazin-2-yl]-4-methoxy-1h-indole-5-carbonitrile Chemical compound C=1C=2C(OC)=C(C#N)C=CC=2NC=1C(N=C12)=CN1CCOC2C1=C(F)C=CC=C1Cl PJTKIWAFRIDTBK-UHFFFAOYSA-N 0.000 description 1
- CHLUUWQLDURKRV-UHFFFAOYSA-N 2-[8-(2-chlorophenyl)-6,8-dihydro-5h-imidazo[2,1-c][1,4]oxazin-2-yl]-4-methoxy-1h-indole-5-carbonitrile Chemical compound C=1C=2C(OC)=C(C#N)C=CC=2NC=1C(N=C12)=CN1CCOC2C1=CC=CC=C1Cl CHLUUWQLDURKRV-UHFFFAOYSA-N 0.000 description 1
- HKQJKTOVXPJOIC-UHFFFAOYSA-N 2-[8-(2-fluoro-6-methylphenyl)-6,8-dihydro-5h-imidazo[2,1-c][1,4]oxazin-2-yl]-4-methoxy-1h-indole-5-carbonitrile Chemical compound C=1C=2C(OC)=C(C#N)C=CC=2NC=1C(N=C12)=CN1CCOC2C1=C(C)C=CC=C1F HKQJKTOVXPJOIC-UHFFFAOYSA-N 0.000 description 1
- UBJJQXXWGRHIDV-UHFFFAOYSA-N 2-[8-(3-fluoro-2-methylphenyl)-6,8-dihydro-5h-imidazo[2,1-c][1,4]oxazin-2-yl]-4-methoxy-1h-indole-5-carbonitrile Chemical compound C=1C=2C(OC)=C(C#N)C=CC=2NC=1C(N=C12)=CN1CCOC2C1=CC=CC(F)=C1C UBJJQXXWGRHIDV-UHFFFAOYSA-N 0.000 description 1
- XYQDAYZDRBKPNR-UHFFFAOYSA-N 2-[8-(4-fluoro-2-methylphenyl)-6,8-dihydro-5H-[1,2,4]triazolo[5,1-c][1,4]oxazin-2-yl]-4-methoxy-1H-indole-5-carbonitrile Chemical compound C=1C=2C(OC)=C(C#N)C=CC=2NC=1C(=NN1CCO2)N=C1C2C1=CC=C(F)C=C1C XYQDAYZDRBKPNR-UHFFFAOYSA-N 0.000 description 1
- BMIBJCFFZPYJHF-UHFFFAOYSA-N 2-methoxy-5-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound COC1=NC=C(C)C=C1B1OC(C)(C)C(C)(C)O1 BMIBJCFFZPYJHF-UHFFFAOYSA-N 0.000 description 1
- FBKAGWTYLUGJDP-UHFFFAOYSA-N 4-(2,2-difluoroethoxy)-2-[8-(4-fluoro-2-methylphenyl)-6,8-dihydro-5H-[1,2,4]triazolo[5,1-c][1,4]oxazin-2-yl]-1H-indole-5-carbonitrile Chemical compound CC1=CC(F)=CC=C1C1C2=NC(C=3NC4=CC=C(C(OCC(F)F)=C4C=3)C#N)=NN2CCO1 FBKAGWTYLUGJDP-UHFFFAOYSA-N 0.000 description 1
- FOKVNBQSMNGHLL-UHFFFAOYSA-N 4-ethoxy-2-[8-(4-fluoro-2-methylphenyl)-6,8-dihydro-5H-[1,2,4]triazolo[5,1-c][1,4]oxazin-2-yl]-1H-indole-5-carbonitrile Chemical compound C=1C=2C(OCC)=C(C#N)C=CC=2NC=1C(=NN1CCO2)N=C1C2C1=CC=C(F)C=C1C FOKVNBQSMNGHLL-UHFFFAOYSA-N 0.000 description 1
- IHCUUUPUTSNNMH-UHFFFAOYSA-N 4-methoxy-2-(5-phenyl-6,8-dihydro-5h-imidazo[2,1-c][1,4]oxazin-2-yl)-1h-indole-5-carbonitrile Chemical compound C=1C=2C(OC)=C(C#N)C=CC=2NC=1C(N=C1COC2)=CN1C2C1=CC=CC=C1 IHCUUUPUTSNNMH-UHFFFAOYSA-N 0.000 description 1
- OTCNEYHBKYYZGC-UHFFFAOYSA-N 4-methoxy-2-[8-[2-(methoxymethyl)phenyl]-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-1H-indole-5-carbonitrile Chemical compound COCC1=CC=CC=C1C1C2=NC(C=3NC4=CC=C(C(OC)=C4C=3)C#N)=NN2CCC1 OTCNEYHBKYYZGC-UHFFFAOYSA-N 0.000 description 1
- PKLALEKIGAUIEA-UHFFFAOYSA-N 4-methoxy-2-[8-[2-(methoxymethyl)phenyl]-6,8-dihydro-5h-imidazo[2,1-c][1,4]oxazin-2-yl]-1h-indole-5-carbonitrile Chemical compound COCC1=CC=CC=C1C1C2=NC(C=3NC4=CC=C(C(OC)=C4C=3)C#N)=CN2CCO1 PKLALEKIGAUIEA-UHFFFAOYSA-N 0.000 description 1
- NFZWXCQYERVPEI-UHFFFAOYSA-N 4-methoxy-2-[8-[2-(trifluoromethyl)phenyl]-6,8-dihydro-5H-[1,2,4]triazolo[5,1-c][1,4]oxazin-2-yl]-1H-indole-5-carbonitrile Chemical compound C=1C=2C(OC)=C(C#N)C=CC=2NC=1C(=NN1CCO2)N=C1C2C1=CC=CC=C1C(F)(F)F NFZWXCQYERVPEI-UHFFFAOYSA-N 0.000 description 1
- ZOVFQRDNBWHWDZ-UHFFFAOYSA-N 4-methoxy-2-[8-[2-(trifluoromethyl)phenyl]-6,8-dihydro-5h-imidazo[2,1-c][1,4]oxazin-2-yl]-1h-indole-5-carbonitrile Chemical compound C=1C=2C(OC)=C(C#N)C=CC=2NC=1C(N=C12)=CN1CCOC2C1=CC=CC=C1C(F)(F)F ZOVFQRDNBWHWDZ-UHFFFAOYSA-N 0.000 description 1
- PBARAUJEVKQDKA-UHFFFAOYSA-N 8-(4-fluoro-2-methylphenyl)-2-[5-(1-methylpyrazol-4-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-6,8-dihydro-5H-[1,2,4]triazolo[5,1-c][1,4]oxazine Chemical compound CC1=CC(F)=CC=C1C1C2=NC(C=3NC4=CC=C(N=C4C=3)C3=CN(C)N=C3)=NN2CCO1 PBARAUJEVKQDKA-UHFFFAOYSA-N 0.000 description 1
- XQZDCTKOMDWSTA-UHFFFAOYSA-N 8-(4-fluoro-2-methylphenyl)-2-[5-(2-methylpyridin-4-yl)-1H-indol-2-yl]-6,8-dihydro-5H-[1,2,4]triazolo[5,1-c][1,4]oxazine Chemical compound C1=NC(C)=CC(C=2C=C3C=C(NC3=CC=2)C2=NN3CCOC(C3=N2)C=2C(=CC(F)=CC=2)C)=C1 XQZDCTKOMDWSTA-UHFFFAOYSA-N 0.000 description 1
- BPXHIQGWNMTLJM-UHFFFAOYSA-N 8-(4-fluoro-2-methylphenyl)-2-[5-(2-methylpyridin-4-yl)-1h-indol-2-yl]-6,8-dihydro-5h-imidazo[2,1-c][1,4]oxazine Chemical compound C1=NC(C)=CC(C=2C=C3C=C(NC3=CC=2)C=2N=C3C(OCCN3C=2)C=2C(=CC(F)=CC=2)C)=C1 BPXHIQGWNMTLJM-UHFFFAOYSA-N 0.000 description 1
- ADALGTFQPOYXOB-UHFFFAOYSA-N 8-(4-fluoro-2-methylphenyl)-2-[5-(4-methylimidazol-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine Chemical compound C1=NC(C)=CN1C1=CN=C(NC(=C2)C3=NN4CCCC(C4=N3)C=3C(=CC(F)=CC=3)C)C2=C1 ADALGTFQPOYXOB-UHFFFAOYSA-N 0.000 description 1
- HWWAJUFEKCOKSC-UHFFFAOYSA-N 8-(4-fluoro-2-methylphenyl)-2-[6-(4-methylimidazol-1-yl)-1H-benzimidazol-2-yl]-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine Chemical compound C1=NC(C)=CN1C1=CC=C(NC(=N2)C3=NN4CCCC(C4=N3)C=3C(=CC(F)=CC=3)C)C2=C1 HWWAJUFEKCOKSC-UHFFFAOYSA-N 0.000 description 1
- WVVJNLJORBXYPW-UHFFFAOYSA-N 8-(4-fluoro-2-methylphenyl)-2-[6-(5-methylimidazol-1-yl)-1H-benzimidazol-2-yl]-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridine Chemical compound CC1=CN=CN1C1=CC=C(NC(=N2)C3=NN4CCCC(C4=N3)C=3C(=CC(F)=CC=3)C)C2=C1 WVVJNLJORBXYPW-UHFFFAOYSA-N 0.000 description 1
- 238000006443 Buchwald-Hartwig cross coupling reaction Methods 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 240000004307 Citrus medica Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 238000005609 Rosenmund-von Braun cyanation reaction Methods 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 108010064397 amyloid beta-protein (1-40) Proteins 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000011049 pearl Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
-
- 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
- A61P25/28—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
-
- 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
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11174120 | 2011-07-15 | ||
| EP11174120 | 2011-07-15 | ||
| PCT/EP2012/063667 WO2013010904A1 (en) | 2011-07-15 | 2012-07-12 | Novel substituted indole derivatives as gamma secretase modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2555167T3 true ES2555167T3 (es) | 2015-12-29 |
Family
ID=46506432
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12733754.1T Active ES2555167T3 (es) | 2011-07-15 | 2012-07-12 | Nuevos derivados de indol sustituidos como moduladores de gamma secretasa |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US9115143B2 (enExample) |
| EP (1) | EP2731948B1 (enExample) |
| JP (1) | JP6068464B2 (enExample) |
| KR (1) | KR101913135B1 (enExample) |
| CN (1) | CN103874702B (enExample) |
| AR (1) | AR087182A1 (enExample) |
| AU (1) | AU2012285931B2 (enExample) |
| BR (1) | BR112014000713A2 (enExample) |
| CA (1) | CA2841102C (enExample) |
| EA (1) | EA023045B1 (enExample) |
| ES (1) | ES2555167T3 (enExample) |
| IL (1) | IL230422B (enExample) |
| IN (1) | IN2014MN00258A (enExample) |
| MX (1) | MX2014000626A (enExample) |
| TW (1) | TWI567079B (enExample) |
| WO (1) | WO2013010904A1 (enExample) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA106360C2 (ru) | 2009-02-06 | 2014-08-26 | Янссен Фармасьютікелз, Інк | Замещенные бициклические гетероциклические соединения как модуляторы гамма-секретазы |
| JP5559309B2 (ja) | 2009-05-07 | 2014-07-23 | ジヤンセン・フアーマシユーチカルズ・インコーポレーテツド | γ分泌酵素調節物質としての新規置換インダゾールおよびアザインダゾール誘導体 |
| BR112012000915A2 (pt) | 2009-07-15 | 2019-09-24 | Janssen Pharmaceuticals Inc | derivados de triazol e imidazol substituídos como moduladores de gama secretase. |
| NZ600648A (en) | 2010-01-15 | 2014-06-27 | Janssen Pharmaceuticals Inc | Novel substituted triazole derivatives as gamma secretase modulators |
| JP2014508794A (ja) | 2011-03-24 | 2014-04-10 | ジヤンセン・フアーマシユーチカルズ・インコーポレーテツド | γ−セクレターゼ調節剤としての新規な置換トリアゾリルピペラジンおよびトリアゾリルピペラジン誘導体 |
| AU2012285931B2 (en) | 2011-07-15 | 2017-01-12 | Cellzome Limited | Novel substituted indole derivatives as gamma secretase modulators |
| ES2585009T3 (es) | 2012-05-16 | 2016-10-03 | Janssen Pharmaceuticals, Inc. | Derivados de 3,4-dihidro-2H-pirido[1,2-a]pirazina-1,6-diona sustituidos útiles para el tratamiento de (inter alia) enfermedad de Alzheimer |
| EP2738172A1 (en) * | 2012-11-28 | 2014-06-04 | Almirall, S.A. | New bicyclic compounds as crac channel modulators |
| CN104918938B (zh) | 2012-12-20 | 2017-08-15 | 詹森药业有限公司 | 新颖的作为γ分泌酶调节剂的三环3，4‑二氢‑2H‑吡啶并[1，2‑a]吡嗪‑1，6‑二酮衍生物 |
| AU2014206834B2 (en) | 2013-01-17 | 2017-06-22 | Janssen Pharmaceutica Nv | Novel substituted pyrido-piperazinone derivatives as gamma secretase modulators |
| US10562897B2 (en) | 2014-01-16 | 2020-02-18 | Janssen Pharmaceutica Nv | Substituted 3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-diones as gamma secretase modulators |
| GB201506660D0 (en) | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| GB201506658D0 (en) | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| AU2017307208B2 (en) | 2016-07-30 | 2021-01-21 | Bristol-Myers Squibb Company | Dimethoxyphenyl substituted indole compounds as TLR7, TLR8 or TLR9 inhibitors |
| KR102519535B1 (ko) | 2016-09-09 | 2023-04-06 | 브리스톨-마이어스 스큅 컴퍼니 | 피리딜 치환된 인돌 화합물 |
| JOP20190060A1 (ar) | 2016-09-26 | 2019-03-26 | Chugai Pharmaceutical Co Ltd | مشتق بيرازولو بيريدين له تأثير مساعد لمستقبل glp-1 |
| KR102651947B1 (ko) | 2017-08-04 | 2024-03-26 | 브리스톨-마이어스 스큅 컴퍼니 | Tlr7/8/9의 억제제로서 유용한 치환된 인돌 화합물 |
| JP7266576B2 (ja) | 2017-08-04 | 2023-04-28 | ブリストル－マイヤーズ スクイブ カンパニー | ［１，２，４］トリアゾロ［４，３－ａ］ピリジニル置換のインドール化合物 |
| SG11202003283TA (en) * | 2017-10-11 | 2020-05-28 | Hoffmann La Roche | Bicyclic compounds for use as rip1 kinase inhibitors |
| US20210253593A1 (en) * | 2017-11-14 | 2021-08-19 | Bristol-Myers Squibb Company | Substituted indole compounds |
| MX2020006093A (es) | 2017-12-15 | 2020-08-24 | Bristol Myers Squibb Co | Compuestos de indol eter sustituidos. |
| JP7289301B2 (ja) | 2017-12-18 | 2023-06-09 | ブリストル－マイヤーズ スクイブ カンパニー | ４－アザインドール化合物 |
| WO2019126081A1 (en) | 2017-12-19 | 2019-06-27 | Bristol-Myers Squibb Company | Amide substituted indole compounds useful as tlr inhibitors |
| US11878975B2 (en) | 2017-12-19 | 2024-01-23 | Bristol-Myers Squibb Company | Substituted indole compounds useful as TLR inhibitors |
| MX2020005873A (es) | 2017-12-19 | 2020-08-13 | Bristol Myers Squibb Co | Compuestos de 6-azaindol. |
| CA3085942A1 (en) | 2017-12-20 | 2019-06-27 | Bristol-Myers Squibb Company | Aryl and heteroaryl substituted indole compounds |
| KR102722182B1 (ko) | 2017-12-20 | 2024-10-24 | 브리스톨-마이어스 스큅 컴퍼니 | 디아자인돌 화합물 |
| WO2019126242A1 (en) | 2017-12-20 | 2019-06-27 | Bristol-Myers Squibb Company | Amino indole compounds useful as tlr inhibitors |
| ES2966947T3 (es) * | 2018-09-03 | 2024-04-25 | Hoffmann La Roche | Derivados de heteroarilo bicíclicos |
| EP3628669A1 (en) * | 2018-09-28 | 2020-04-01 | GenKyoTex Suisse SA | Novel compounds as nadph oxidase inhibitors |
| EP3870589B1 (en) | 2018-10-24 | 2023-09-06 | Bristol-Myers Squibb Company | Substituted indole dimer compounds |
| US12172995B2 (en) | 2018-10-24 | 2024-12-24 | Bristol-Myers Squibb Company | Substituted indole and indazole compounds |
| MX2021006761A (es) | 2018-12-13 | 2021-07-15 | Hoffmann La Roche | Derivados de 7-fenoxi-n-(3-azabiciclo[3.2.1]octan-8-il)-6,7-dihidr o-5h-pirrolo[1,2-b][1,2,4]triazol-2-amina y compuestos relacionados como moduladores de gamma-secretasa para el tratamiento de la enfermedad de alzheimer. |
| ES2987832T3 (es) | 2019-05-09 | 2024-11-18 | Bristol Myers Squibb Co | Compuestos de benzimidazolona sustituidos |
| JP7629007B2 (ja) | 2019-10-01 | 2025-02-12 | ブリストル－マイヤーズ スクイブ カンパニー | 置換二環ヘテロアリール化合物 |
| ES2965164T3 (es) | 2019-10-04 | 2024-04-11 | Bristol Myers Squibb Co | Compuestos de carbazol sustituidos |
Family Cites Families (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0571253T3 (da) * | 1992-05-19 | 1999-07-19 | Adir | Benzimidazolderivater med antidiabetisk og antiblodpladekoagulerende virkning |
| US5767144A (en) | 1994-08-19 | 1998-06-16 | Abbott Laboratories | Endothelin antagonists |
| JP4108747B2 (ja) | 1995-07-13 | 2008-06-25 | アボット ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト | 治療薬としてのピペラジン誘導体 |
| CN1156445C (zh) | 1999-06-10 | 2004-07-07 | 沃尼尔·朗伯公司 | 采用二氢异吲哚衍生物抑制淀粉样蛋白聚集和使淀粉样蛋白沉积成像的方法 |
| AU5702201A (en) | 2000-04-13 | 2001-10-30 | Mayo Foundation | Abeta<sub>42</sub> lowering agents |
| US20030176454A1 (en) | 2000-05-15 | 2003-09-18 | Akira Yamada | N-coating heterocyclic compounds |
| DE10109867A1 (de) | 2001-03-01 | 2002-09-05 | Abbott Gmbh & Co Kg | Verwendung von Triazolverbindungen zur Prophylaxe und Therapie neurodegenerativer Erkrankungen, Hirntrauma und zerebraler Ischämie |
| DE10238002A1 (de) | 2002-08-20 | 2004-03-04 | Merck Patent Gmbh | Benzimidazolderivate |
| WO2004076448A1 (en) | 2003-02-27 | 2004-09-10 | F. Hoffmann-La Roche Ag | Ccr-3 receptor antagonists |
| JP4847868B2 (ja) | 2003-05-14 | 2011-12-28 | ニューロジェネティック ファーマシューティカルズ、 インコーポレイテッド | 化合物、及び、アミロイドベータの調節におけるその使用 |
| CA2535406A1 (en) | 2003-08-14 | 2005-02-24 | F. Hoffmann-La Roche Ag | Gabanergic modulators |
| ES2353309T3 (es) | 2004-03-08 | 2011-03-01 | Prosidion Ltd. | Hidrazidas del ácido pirrolopiridin-2-carboxílico como inhibidores de glucógeno fosforilasa. |
| JP4101852B2 (ja) | 2004-05-26 | 2008-06-18 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | シンナミド化合物 |
| US7923563B2 (en) | 2004-10-26 | 2011-04-12 | Eisai R&D Management Co., Ltd. | Amorphous object of cinnamide compound |
| ES2400287T3 (es) | 2005-03-14 | 2013-04-08 | High Point Pharmaceuticals, Llc | Derivados de benzazol, composiciones y procedimientos de uso como inhibidores de beta-secretasa |
| US7572807B2 (en) | 2005-06-09 | 2009-08-11 | Bristol-Myers Squibb Company | Heteroaryl 11-beta-hydroxysteroid dehydrogenase type I inhibitors |
| US20070078136A1 (en) | 2005-09-22 | 2007-04-05 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
| EP1931620A1 (en) | 2005-09-22 | 2008-06-18 | Sanofi-Aventis | Amino-alkyl-amide derivatives as ccr3 receptor liquids |
| WO2007043786A1 (en) | 2005-10-10 | 2007-04-19 | Seiyang Yang | Dynamic-based verification apparatus for verification from electronic system level to gate level, and verification method using the same |
| EP1937767B1 (en) | 2005-10-11 | 2013-05-22 | Chemtura Corporation | Diaromatic amines |
| PE20070805A1 (es) | 2005-11-10 | 2007-08-13 | Schering Corp | Imidazopirazinas como inhibidores de proteinquinasa |
| WO2007105053A2 (en) | 2006-03-13 | 2007-09-20 | Pfizer Products Inc. | Tetralines antagonists of the h-3 receptor |
| GB0606774D0 (en) | 2006-04-03 | 2006-05-10 | Novartis Ag | Organic compounds |
| US7893058B2 (en) | 2006-05-15 | 2011-02-22 | Janssen Pharmaceutica Nv | Imidazolopyrazine compounds useful for the treatment of degenerative and inflammatory diseases |
| US7951818B2 (en) | 2006-12-01 | 2011-05-31 | Galapagos Nv | Imidazolopyridine compounds useful for the treatment of degenerative and inflammatory diseases |
| AU2007332750A1 (en) | 2006-12-12 | 2008-06-19 | Schering Corporation | Aspartyl protease inhibitors containing a tricyclic ring system |
| CA2672960A1 (en) | 2006-12-20 | 2008-07-10 | Schering Corporation | Novel jnk inhibitors |
| JP2010518080A (ja) | 2007-02-08 | 2010-05-27 | メルク・シャープ・エンド・ドーム・コーポレイション | 治療薬 |
| EP2120573A4 (en) | 2007-02-12 | 2011-05-25 | Merck Sharp & Dohme | piperidine |
| US20100204230A1 (en) | 2007-02-12 | 2010-08-12 | Peter Blurton | Piperazine derivatives for treatment of ad and related conditions |
| MX2009012177A (es) | 2007-05-07 | 2009-11-23 | Schering Corp | Moduladores de gamma-secretasa. |
| ES2358863T3 (es) | 2007-05-11 | 2011-05-16 | F. Hoffmann-La Roche Ag | Hetarilanilinas como moduladores de beta-amiloide. |
| US8242150B2 (en) | 2007-06-13 | 2012-08-14 | Merck Sharp & Dohme Corp. | Triazole derivatives for treating alzheimer'S disease and related conditions |
| WO2009005729A1 (en) | 2007-06-29 | 2009-01-08 | Schering Corporation | Gamma secretase modulators |
| US7935815B2 (en) | 2007-08-31 | 2011-05-03 | Eisai R&D Management Co., Ltd. | Imidazoyl pyridine compounds and salts thereof |
| US8518975B2 (en) | 2007-09-06 | 2013-08-27 | Merck Sharp + Dohme Corp. | Gamma secretase modulators |
| GB0720444D0 (en) | 2007-10-18 | 2007-11-28 | Glaxo Group Ltd | Novel compounds |
| US8450343B2 (en) * | 2007-12-06 | 2013-05-28 | Xianhai Huang | Gamma secretase modulators |
| CN101945868A (zh) | 2007-12-11 | 2011-01-12 | 先灵公司 | γ分泌酶调节剂 |
| JP5328816B2 (ja) | 2008-02-22 | 2013-10-30 | エフ．ホフマン−ラ ロシュ アーゲー | アミロイドβの調節薬 |
| US20100137320A1 (en) | 2008-02-29 | 2010-06-03 | Schering Corporation | Gamma secretase modulators |
| WO2010010188A1 (en) | 2008-07-25 | 2010-01-28 | Galapagos Nv | Novel compounds useful for the treatment of degenerative and inflammatory diseases. |
| EP2340243B1 (en) | 2008-10-17 | 2014-10-08 | Boehringer Ingelheim International GmbH | Heteroaryl substituted indole compounds useful as mmp-13 inhibitors |
| WO2010054067A1 (en) | 2008-11-06 | 2010-05-14 | Schering Corporation | Gamma secretase modulators |
| MX2011004954A (es) | 2008-11-10 | 2011-05-30 | Hoffmann La Roche | Moduladores heterociclicos de gamma-secretasa. |
| AU2009322774A1 (en) | 2008-12-03 | 2011-06-30 | Via Pharmaceuticals, Inc | Inhibitors of diacylglycerol acyltransferase |
| PA8854101A1 (es) | 2008-12-18 | 2010-07-27 | Ortho Mcneil Janssen Pharm | Derivados de imidazol bicíclicos sustituidos como moduladores de gamma secretasa |
| TW201030002A (en) | 2009-01-16 | 2010-08-16 | Bristol Myers Squibb Co | Bicyclic compounds for the reduction of beta-amyloid production |
| UA106360C2 (ru) | 2009-02-06 | 2014-08-26 | Янссен Фармасьютікелз, Інк | Замещенные бициклические гетероциклические соединения как модуляторы гамма-секретазы |
| TWI461425B (zh) | 2009-02-19 | 2014-11-21 | Janssen Pharmaceuticals Inc | 作為伽瑪分泌酶調節劑之新穎經取代的苯并唑、苯并咪唑、唑并吡啶及咪唑并吡啶衍生物類 |
| JP2012051807A (ja) | 2009-02-26 | 2012-03-15 | Eisai R & D Management Co Ltd | アリールイミダゾール化合物 |
| CA2753696A1 (en) | 2009-02-26 | 2010-09-02 | Noritaka Kitazawa | Nitrogen-containing fused heterocyclic compounds and their use as beta amyloid production inhibitors |
| JP2012051806A (ja) * | 2009-02-26 | 2012-03-15 | Eisai R & D Management Co Ltd | イミダゾリルピラジン誘導体 |
| EP2403835A1 (en) | 2009-03-03 | 2012-01-11 | Pfizer Inc. | Novel phenyl imidazoles and phenyl triazoles as gamma-secretase modulators |
| US20110299830A1 (en) | 2009-03-16 | 2011-12-08 | Panasonic Corporation | Application running device |
| CA2756989A1 (en) * | 2009-04-03 | 2010-10-07 | Douglas Burdi | Compounds for treating disorders mediated by metabotropic glutamate receptor 5, and methods of use thereof |
| EA201171306A1 (ru) * | 2009-04-27 | 2012-05-30 | ХАЙ ПОЙНТ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи | ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ ИМИДАЗО[1,2-α]ПИРИДИНА, ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ И СПОСОБЫ ПРИМЕНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ β-СЕКРЕТАЗЫ |
| JP5559309B2 (ja) | 2009-05-07 | 2014-07-23 | ジヤンセン・フアーマシユーチカルズ・インコーポレーテツド | γ分泌酵素調節物質としての新規置換インダゾールおよびアザインダゾール誘導体 |
| JP2010274429A (ja) | 2009-05-26 | 2010-12-09 | Ihi Corp | アライメントステージ |
| BR112012000915A2 (pt) | 2009-07-15 | 2019-09-24 | Janssen Pharmaceuticals Inc | derivados de triazol e imidazol substituídos como moduladores de gama secretase. |
| NZ600648A (en) | 2010-01-15 | 2014-06-27 | Janssen Pharmaceuticals Inc | Novel substituted triazole derivatives as gamma secretase modulators |
| US8569331B2 (en) * | 2010-11-01 | 2013-10-29 | Arqule, Inc. | Substituted benzo[f]lmidazo[1,2-d]pyrido[2,3-b][1,4]diazepine compounds |
| JP2014508794A (ja) | 2011-03-24 | 2014-04-10 | ジヤンセン・フアーマシユーチカルズ・インコーポレーテツド | γ−セクレターゼ調節剤としての新規な置換トリアゾリルピペラジンおよびトリアゾリルピペラジン誘導体 |
| JP5767393B2 (ja) | 2011-03-31 | 2015-08-19 | ファイザー・インク | 新規二環式ピリジノン |
| AU2012285931B2 (en) | 2011-07-15 | 2017-01-12 | Cellzome Limited | Novel substituted indole derivatives as gamma secretase modulators |
-
2012
- 2012-07-12 AU AU2012285931A patent/AU2012285931B2/en not_active Ceased
- 2012-07-12 CA CA2841102A patent/CA2841102C/en not_active Expired - Fee Related
- 2012-07-12 CN CN201280034912.XA patent/CN103874702B/zh not_active Expired - Fee Related
- 2012-07-12 ES ES12733754.1T patent/ES2555167T3/es active Active
- 2012-07-12 EP EP12733754.1A patent/EP2731948B1/en active Active
- 2012-07-12 US US14/233,078 patent/US9115143B2/en not_active Expired - Fee Related
- 2012-07-12 WO PCT/EP2012/063667 patent/WO2013010904A1/en not_active Ceased
- 2012-07-12 MX MX2014000626A patent/MX2014000626A/es unknown
- 2012-07-12 EA EA201490287A patent/EA023045B1/ru not_active IP Right Cessation
- 2012-07-12 IN IN258MUN2014 patent/IN2014MN00258A/en unknown
- 2012-07-12 KR KR1020147003465A patent/KR101913135B1/ko not_active Expired - Fee Related
- 2012-07-12 BR BR112014000713A patent/BR112014000713A2/pt active Search and Examination
- 2012-07-12 TW TW101125035A patent/TWI567079B/zh not_active IP Right Cessation
- 2012-07-12 JP JP2014519557A patent/JP6068464B2/ja not_active Expired - Fee Related
- 2012-07-13 AR ARP120102548A patent/AR087182A1/es not_active Application Discontinuation
-
2014
- 2014-01-13 IL IL230422A patent/IL230422B/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| EP2731948B1 (en) | 2015-09-09 |
| EA201490287A1 (ru) | 2014-05-30 |
| CA2841102C (en) | 2019-08-13 |
| WO2013010904A1 (en) | 2013-01-24 |
| US9115143B2 (en) | 2015-08-25 |
| MX2014000626A (es) | 2014-04-30 |
| JP2014518286A (ja) | 2014-07-28 |
| TWI567079B (zh) | 2017-01-21 |
| AU2012285931B2 (en) | 2017-01-12 |
| AR087182A1 (es) | 2014-02-26 |
| TW201315736A (zh) | 2013-04-16 |
| IN2014MN00258A (enExample) | 2015-09-25 |
| KR20140063595A (ko) | 2014-05-27 |
| KR101913135B1 (ko) | 2018-10-30 |
| CN103874702B (zh) | 2015-12-09 |
| EP2731948A1 (en) | 2014-05-21 |
| US20140148450A1 (en) | 2014-05-29 |
| NZ619683A (en) | 2015-01-30 |
| EA023045B1 (ru) | 2016-04-29 |
| JP6068464B2 (ja) | 2017-01-25 |
| IL230422B (en) | 2018-03-29 |
| BR112014000713A2 (pt) | 2017-01-10 |
| CA2841102A1 (en) | 2013-01-24 |
| CN103874702A (zh) | 2014-06-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2555167T3 (es) | Nuevos derivados de indol sustituidos como moduladores de gamma secretasa | |
| US12152032B2 (en) | Heterocyclic compounds and uses thereof | |
| ES2983003T3 (es) | Compuestos heterocíclicos y heteroarílicos para el tratamiento de la enfermedad de Huntington | |
| JP6510068B2 (ja) | 新規なビフェニル化合物又はその塩 | |
| ES2805087T3 (es) | Compuestos de pirazolo[1,5-a]piridina sustituidos como inhibidores de la cinasa RET | |
| AU2023233205A1 (en) | SHP2 phosphatase inhibitors and methods of use thereof | |
| Campiani et al. | Pyrroloquinoxaline derivatives as high-affinity and selective 5-HT3 receptor agonists: synthesis, further structure− activity relationships, and biological studies | |
| ES2898965T3 (es) | Sondas de formación de imágenes de la proteína Huntingtina | |
| AU2025226693A1 (en) | Monoacylglycerol lipase modulators | |
| TW201827431A (zh) | Rip1激酶抑制劑及其使用方法 | |
| EA031601B1 (ru) | Ингибиторы syk | |
| EA037123B1 (ru) | Соединения для лечения спинальной мышечной атрофии | |
| US20170008877A1 (en) | Bicyclic lactams and methods of use thereof | |
| JP2020527174A (ja) | Ａｔｒキナーゼの複素環式阻害剤 | |
| US20230219965A1 (en) | Nitrogen-containing fused bicyclic compounds and their use as ubiquitin-specific-processing protease 1 (usp1) inhibitors | |
| KR20230107419A (ko) | 암 치료 방법 | |
| WO2025080946A2 (en) | Ras inhibitors | |
| WO2021074279A1 (en) | Spiro-fused tricyclic map4k1 inhibitors | |
| KR20230124665A (ko) | Cgas 관련 병태의 치료에 유용한 인돌 유도체 | |
| Perry et al. | Design and synthesis of soluble and cell-permeable PI3Kδ inhibitors for long-acting inhaled administration | |
| ES2793929T3 (es) | Antagonistas de V1a para tratar trastornos del sueño por desplazamiento de fase | |
| JP2025538097A (ja) | がんを処置するための方法 | |
| AR070073A1 (es) | Derivados de imidazo[1, 2 - a]piridin-2-carboxamidas, intermediarios para su preparacion, una composicion farmaceutica que los comprende y su uso en la fabricacion de medicamentos para el tratamiento de enfermedades que implican a los receptores not. | |
| EA035568B1 (ru) | ЗАМЕЩЕННЫЕ ПИРАЗОЛО[1,5-а]ПИРИДИНОВЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ RET КИНАЗЫ | |
| WO2025103502A1 (en) | Compounds and methods of treating cancers |