JP2012533601A - 運動失調症の処置または予防のための、アザビシクロアルキル誘導体またはピロリジン−２−オン誘導体の使用 - Google Patents
運動失調症の処置または予防のための、アザビシクロアルキル誘導体またはピロリジン−２−オン誘導体の使用 Download PDFInfo
- Publication number
- JP2012533601A JP2012533601A JP2012521032A JP2012521032A JP2012533601A JP 2012533601 A JP2012533601 A JP 2012533601A JP 2012521032 A JP2012521032 A JP 2012521032A JP 2012521032 A JP2012521032 A JP 2012521032A JP 2012533601 A JP2012533601 A JP 2012533601A
- Authority
- JP
- Japan
- Prior art keywords
- ring system
- halogen
- alkyl
- formula
- nitrogen
- 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.)
- Pending
Links
- 206010003591 Ataxia Diseases 0.000 title claims abstract description 51
- 238000011282 treatment Methods 0.000 title claims abstract description 35
- 230000002265 prevention Effects 0.000 title claims abstract description 22
- HNJBEVLQSNELDL-YZRHJBSPSA-N pyrrolidin-2-one Chemical class O=C1CC[14CH2]N1 HNJBEVLQSNELDL-YZRHJBSPSA-N 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 112
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 55
- 229910052736 halogen Inorganic materials 0.000 claims description 41
- 150000002367 halogens Chemical class 0.000 claims description 41
- 125000000217 alkyl group Chemical group 0.000 claims description 40
- 229910052757 nitrogen Inorganic materials 0.000 claims description 36
- 125000004122 cyclic group Chemical group 0.000 claims description 23
- 125000005842 heteroatom Chemical group 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 125000001188 haloalkyl group Chemical group 0.000 claims description 19
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 239000001301 oxygen Chemical group 0.000 claims description 18
- 229910052717 sulfur Chemical group 0.000 claims description 18
- 239000011593 sulfur Chemical group 0.000 claims description 18
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 17
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 17
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 17
- 125000004434 sulfur atom Chemical group 0.000 claims description 17
- 125000002947 alkylene group Chemical group 0.000 claims description 14
- 125000002950 monocyclic group Chemical group 0.000 claims description 14
- 150000003839 salts Chemical group 0.000 claims description 14
- 125000003367 polycyclic group Chemical group 0.000 claims description 13
- -1 cyano, amino Chemical group 0.000 claims description 12
- 229920006395 saturated elastomer Polymers 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000006413 ring segment Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 7
- 239000012458 free base Substances 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 241000699670 Mus sp. Species 0.000 description 21
- 238000012360 testing method Methods 0.000 description 20
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 18
- 230000000694 effects Effects 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 206010008025 Cerebellar ataxia Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 102000014461 Ataxins Human genes 0.000 description 7
- 108010078286 Ataxins Proteins 0.000 description 7
- 201000004562 autosomal dominant cerebellar ataxia Diseases 0.000 description 7
- JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 7
- 229960004751 varenicline Drugs 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 208000024412 Friedreich ataxia Diseases 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 208000002569 Machado-Joseph Disease Diseases 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 230000007850 degeneration Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 208000010112 Spinocerebellar Degenerations Diseases 0.000 description 4
- 208000036834 Spinocerebellar ataxia type 3 Diseases 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 201000003636 hereditary ataxia Diseases 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 241000282412 Homo Species 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 201000003577 Spinocerebellar ataxia type 14 Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 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 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 102000007368 Ataxin-7 Human genes 0.000 description 2
- 108010032953 Ataxin-7 Proteins 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- NLPRAJRHRHZCQQ-UHFFFAOYSA-N Epibatidine Natural products C1=NC(Cl)=CC=C1C1C(N2)CCC2C1 NLPRAJRHRHZCQQ-UHFFFAOYSA-N 0.000 description 2
- OUVXYXNWSVIOSJ-UHFFFAOYSA-N Fluo-4 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)N(CC(O)=O)CC(O)=O)=C1 OUVXYXNWSVIOSJ-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 108090000217 Frataxin Proteins 0.000 description 2
- 206010017577 Gait disturbance Diseases 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 208000023424 acquired ataxia Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 208000025434 cerebellar degeneration Diseases 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- NLPRAJRHRHZCQQ-IVZWLZJFSA-N epibatidine Chemical compound C1=NC(Cl)=CC=C1[C@@H]1[C@H](N2)CC[C@H]2C1 NLPRAJRHRHZCQQ-IVZWLZJFSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000004424 eye movement Effects 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 238000002825 functional assay Methods 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- UFBBWLWUIISIPW-UHFFFAOYSA-N imidazo[2,1-b][1,3]thiazole Chemical compound C1=CSC2=NC=CN21 UFBBWLWUIISIPW-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 210000002161 motor neuron Anatomy 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- CEJVXFKCWIIMGB-UHFFFAOYSA-N n-[6-(1h-indol-5-yl)pyridin-3-yl]-1-azabicyclo[3.3.1]nonan-4-amine Chemical compound C1=C2NC=CC2=CC(C2=CC=C(C=N2)NC2CCN3CC2CCC3)=C1 CEJVXFKCWIIMGB-UHFFFAOYSA-N 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 210000000287 oocyte Anatomy 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 210000000449 purkinje cell Anatomy 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000000391 smoking effect Effects 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- OAELZAVJUGTVJK-SJCJKPOMSA-N (2s,3r)-2-methyl-3-[6-(5-methylthiophen-2-yl)pyridazin-3-yl]oxy-1-azabicyclo[2.2.2]octane Chemical compound O([C@H]1[C@@H](N2CCC1CC2)C)C(N=N1)=CC=C1C1=CC=C(C)S1 OAELZAVJUGTVJK-SJCJKPOMSA-N 0.000 description 1
- BOOUVSNRSCUOIL-INIZCTEOSA-N (3r)-3-(5-phenylpyrimidin-2-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound O([C@@H]1C2CCN(C1)CC2)C(N=C1)=NC=C1C1=CC=CC=C1 BOOUVSNRSCUOIL-INIZCTEOSA-N 0.000 description 1
- UOXAHMAZBMSBFV-SFHVURJKSA-N (3r)-3-(6-phenylpyridin-3-yl)oxy-1-azabicyclo[2.2.2]octane Chemical compound O([C@@H]1C2CCN(C1)CC2)C(C=N1)=CC=C1C1=CC=CC=C1 UOXAHMAZBMSBFV-SFHVURJKSA-N 0.000 description 1
- IVSYTOZBFVMTEM-KRWDZBQOSA-N (3r)-3-[5-(2-fluoro-4-methylphenyl)pyrimidin-2-yl]oxy-1-azabicyclo[2.2.2]octane Chemical compound FC1=CC(C)=CC=C1C(C=N1)=CN=C1O[C@@H]1C(CC2)CCN2C1 IVSYTOZBFVMTEM-KRWDZBQOSA-N 0.000 description 1
- FJSAFINTVSTUNP-SFHVURJKSA-N (3r)-3-[5-(3,4-dimethylphenyl)pyrimidin-2-yl]oxy-1-azabicyclo[2.2.2]octane Chemical compound C1=C(C)C(C)=CC=C1C(C=N1)=CN=C1O[C@@H]1C(CC2)CCN2C1 FJSAFINTVSTUNP-SFHVURJKSA-N 0.000 description 1
- IADFRBKHIWFHFV-KRWDZBQOSA-N (3r)-3-[5-(4-methylphenyl)pyrimidin-2-yl]oxy-1-azabicyclo[2.2.2]octane Chemical compound C1=CC(C)=CC=C1C(C=N1)=CN=C1O[C@@H]1C(CC2)CCN2C1 IADFRBKHIWFHFV-KRWDZBQOSA-N 0.000 description 1
- QUVNZVHUMJPPGC-KRWDZBQOSA-N (3r)-3-[6-(2,5-difluoro-4-methylphenyl)pyridazin-3-yl]oxy-1-azabicyclo[2.2.2]octane Chemical compound C1=C(F)C(C)=CC(F)=C1C(N=N1)=CC=C1O[C@@H]1C(CC2)CCN2C1 QUVNZVHUMJPPGC-KRWDZBQOSA-N 0.000 description 1
- OWGWNCCDDZYCGR-SFHVURJKSA-N (3r)-3-[6-(2-fluoro-4,5-dimethylphenyl)pyridazin-3-yl]oxy-1-azabicyclo[2.2.2]octane Chemical compound C1=C(C)C(C)=CC(F)=C1C(N=N1)=CC=C1O[C@@H]1C(CC2)CCN2C1 OWGWNCCDDZYCGR-SFHVURJKSA-N 0.000 description 1
- GDJTWWGJXFJUTQ-KRWDZBQOSA-N (3r)-3-[6-(2-fluoro-4-methylphenyl)pyridazin-3-yl]oxy-1-azabicyclo[2.2.2]octane Chemical compound FC1=CC(C)=CC=C1C(N=N1)=CC=C1O[C@@H]1C(CC2)CCN2C1 GDJTWWGJXFJUTQ-KRWDZBQOSA-N 0.000 description 1
- RIZMSQYMRPTCFN-SFHVURJKSA-N (3r)-3-[6-(3,4-dimethylphenyl)pyridazin-3-yl]oxy-1-azabicyclo[2.2.2]octane Chemical compound C1=C(C)C(C)=CC=C1C(N=N1)=CC=C1O[C@@H]1C(CC2)CCN2C1 RIZMSQYMRPTCFN-SFHVURJKSA-N 0.000 description 1
- PLYXOZYCJHNCBB-FQEVSTJZSA-N (3r)-3-[6-(3,4-dimethylphenyl)pyridin-3-yl]oxy-1-azabicyclo[2.2.2]octane Chemical compound C1=C(C)C(C)=CC=C1C(N=C1)=CC=C1O[C@@H]1C(CC2)CCN2C1 PLYXOZYCJHNCBB-FQEVSTJZSA-N 0.000 description 1
- TYNXKNLHFFRJPQ-KRWDZBQOSA-N (3r)-3-[6-(4-methylphenyl)pyridazin-3-yl]oxy-1-azabicyclo[2.2.2]octane Chemical compound C1=CC(C)=CC=C1C(N=N1)=CC=C1O[C@@H]1C(CC2)CCN2C1 TYNXKNLHFFRJPQ-KRWDZBQOSA-N 0.000 description 1
- NPDLTEZXGWRMLQ-IBGZPJMESA-N (3r)-3-[6-(4-methylphenyl)pyridin-3-yl]oxy-1-azabicyclo[2.2.2]octane Chemical compound C1=CC(C)=CC=C1C(N=C1)=CC=C1O[C@@H]1C(CC2)CCN2C1 NPDLTEZXGWRMLQ-IBGZPJMESA-N 0.000 description 1
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 description 1
- UUZJJNBYJDFQHL-UHFFFAOYSA-N 1,2,3-triazolidine Chemical compound C1CNNN1 UUZJJNBYJDFQHL-UHFFFAOYSA-N 0.000 description 1
- CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 description 1
- CZSRXHJVZUBEGW-UHFFFAOYSA-N 1,2-thiazolidine Chemical compound C1CNSC1 CZSRXHJVZUBEGW-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 description 1
- VKXYLXZLODSKCD-UHFFFAOYSA-N 1-methyl-5-(2-phenylethynyl)-3-(piperidin-1-ylmethyl)pyrrolidin-2-one Chemical compound O=C1N(C)C(C#CC=2C=CC=CC=2)CC1CN1CCCCC1 VKXYLXZLODSKCD-UHFFFAOYSA-N 0.000 description 1
- NBYYGODJBZAJJF-UHFFFAOYSA-N 1-methyl-5-[2-(1-methylindol-5-yl)ethynyl]-3-(piperidin-1-ylmethyl)pyrrolidin-2-one Chemical compound O=C1N(C)C(C#CC=2C=C3C=CN(C)C3=CC=2)CC1CN1CCCCC1 NBYYGODJBZAJJF-UHFFFAOYSA-N 0.000 description 1
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
- HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 description 1
- OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical compound C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 description 1
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 1
- JXZOJYUTJFMJQV-UHFFFAOYSA-N 2,3-dimethyl-5-[6-[(2-methyl-1-azabicyclo[2.2.2]octan-3-yl)oxy]pyridazin-3-yl]-1h-indole Chemical compound C1CC2CCN1C(C)C2OC1=CC=C(C=2C=C3C(C)=C(C)NC3=CC=2)N=N1 JXZOJYUTJFMJQV-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
- GUUULVAMQJLDSY-UHFFFAOYSA-N 4,5-dihydro-1,2-thiazole Chemical compound C1CC=NS1 GUUULVAMQJLDSY-UHFFFAOYSA-N 0.000 description 1
- WEDKTMOIKOKBSH-UHFFFAOYSA-N 4,5-dihydrothiadiazole Chemical compound C1CN=NS1 WEDKTMOIKOKBSH-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- KNSUADXKFTZSIZ-UHFFFAOYSA-N 5-[2-(1-benzofuran-5-yl)ethynyl]-1-methyl-3-(piperidin-1-ylmethyl)pyrrolidin-2-one Chemical compound O=C1N(C)C(C#CC=2C=C3C=COC3=CC=2)CC1CN1CCCCC1 KNSUADXKFTZSIZ-UHFFFAOYSA-N 0.000 description 1
- SFLIOTDHINEOJN-UHFFFAOYSA-N 5-[2-(3-aminophenyl)ethynyl]-1-methyl-3-(piperidin-1-ylmethyl)pyrrolidin-2-one Chemical compound O=C1N(C)C(C#CC=2C=C(N)C=CC=2)CC1CN1CCCCC1 SFLIOTDHINEOJN-UHFFFAOYSA-N 0.000 description 1
- XHUPABDGSDCFMH-BFUOFWGJSA-N 5-[2-[[(2r,3s)-2-methyl-1-azabicyclo[2.2.2]octan-3-yl]oxy]pyrimidin-5-yl]-1h-indole Chemical compound C1CC2CCN1[C@H](C)[C@H]2OC1=NC=C(C=2C=C3C=CNC3=CC=2)C=N1 XHUPABDGSDCFMH-BFUOFWGJSA-N 0.000 description 1
- XHUPABDGSDCFMH-DJJJIMSYSA-N 5-[2-[[(2s,3r)-2-methyl-1-azabicyclo[2.2.2]octan-3-yl]oxy]pyrimidin-5-yl]-1h-indole Chemical compound C1CC2CCN1[C@@H](C)[C@@H]2OC1=NC=C(C=2C=C3C=CNC3=CC=2)C=N1 XHUPABDGSDCFMH-DJJJIMSYSA-N 0.000 description 1
- HEDDSROUHOVUPD-KDOFPFPSSA-N 5-[2-[[(4s,5r)-1-azabicyclo[3.3.1]nonan-4-yl]oxy]pyrimidin-5-yl]-1,3-dihydroindol-2-one Chemical compound C1=C2NC(=O)CC2=CC(C2=CN=C(N=C2)O[C@H]2CCN3CCC[C@@]2(C3)[H])=C1 HEDDSROUHOVUPD-KDOFPFPSSA-N 0.000 description 1
- LEUQBJWNAXGICB-APWZRJJASA-N 5-[2-[[(4s,5r)-1-azabicyclo[3.3.1]nonan-4-yl]oxy]pyrimidin-5-yl]-1h-indole Chemical compound C1=C2NC=CC2=CC(C2=CN=C(N=C2)O[C@H]2CCN3CCC[C@@]2(C3)[H])=C1 LEUQBJWNAXGICB-APWZRJJASA-N 0.000 description 1
- ZQXZZBNDHQVUEX-UHFFFAOYSA-N 5-[5-[(2-methyl-1-azabicyclo[2.2.2]octan-3-yl)oxy]pyridin-2-yl]-1h-indole Chemical compound C1CC2CCN1C(C)C2OC1=CC=C(C=2C=C3C=CNC3=CC=2)N=C1 ZQXZZBNDHQVUEX-UHFFFAOYSA-N 0.000 description 1
- MIMZWDOBVBBLPH-UTKZUKDTSA-N 5-[5-[[(4s,5r)-1-azabicyclo[3.3.1]nonan-4-yl]oxy]pyridin-2-yl]-1h-indole Chemical compound C1=C2NC=CC2=CC(C2=CC=C(C=N2)O[C@H]2CCN3CCC[C@@]2(C3)[H])=C1 MIMZWDOBVBBLPH-UTKZUKDTSA-N 0.000 description 1
- WFMNAESJUUOVOL-ZUOKHONESA-N 5-[6-[[(2r,3s)-2-methyl-1-azabicyclo[2.2.2]octan-3-yl]oxy]pyridazin-3-yl]-1h-indole Chemical compound C1CC2CCN1[C@H](C)[C@H]2OC1=CC=C(C=2C=C3C=CNC3=CC=2)N=N1 WFMNAESJUUOVOL-ZUOKHONESA-N 0.000 description 1
- WFMNAESJUUOVOL-RBZFPXEDSA-N 5-[6-[[(2s,3r)-2-methyl-1-azabicyclo[2.2.2]octan-3-yl]oxy]pyridazin-3-yl]-1h-indole Chemical compound C1CC2CCN1[C@@H](C)[C@@H]2OC1=CC=C(C=2C=C3C=CNC3=CC=2)N=N1 WFMNAESJUUOVOL-RBZFPXEDSA-N 0.000 description 1
- GGFORAABWCDWAK-KDOFPFPSSA-N 5-[6-[[(4s,5r)-1-azabicyclo[3.3.1]nonan-4-yl]oxy]pyridazin-3-yl]-1,3-dihydroindol-2-one Chemical compound C1=C2NC(=O)CC2=CC(C2=CC=C(N=N2)O[C@H]2CCN3CCC[C@@]2(C3)[H])=C1 GGFORAABWCDWAK-KDOFPFPSSA-N 0.000 description 1
- HAHGPGNZEBCTCN-APWZRJJASA-N 5-[6-[[(4s,5r)-1-azabicyclo[3.3.1]nonan-4-yl]oxy]pyridazin-3-yl]-1h-indole Chemical compound C1=C2NC=CC2=CC(C2=CC=C(N=N2)O[C@H]2CCN3CCC[C@@]2(C3)[H])=C1 HAHGPGNZEBCTCN-APWZRJJASA-N 0.000 description 1
- LFDMNNLPIWWHBW-QUCCMNQESA-N 5-[6-[[(4s,5r)-1-azabicyclo[3.3.1]nonan-4-yl]oxy]pyridin-3-yl]-1h-indole Chemical compound C1=C2NC=CC2=CC(C2=CC=C(N=C2)O[C@H]2CCN3CCC[C@@]2(C3)[H])=C1 LFDMNNLPIWWHBW-QUCCMNQESA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- 206010000125 Abnormal dreams Diseases 0.000 description 1
- 208000001827 Ataxia with vitamin E deficiency Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 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 1
- 240000002989 Euphorbia neriifolia Species 0.000 description 1
- TZXKOCQBRNJULO-UHFFFAOYSA-N Ferriprox Chemical compound CC1=C(O)C(=O)C=CN1C TZXKOCQBRNJULO-UHFFFAOYSA-N 0.000 description 1
- 102000003869 Frataxin Human genes 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 101001002508 Homo sapiens Immunoglobulin-binding protein 1 Proteins 0.000 description 1
- 101001026864 Homo sapiens Protein kinase C gamma type Proteins 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 102100021042 Immunoglobulin-binding protein 1 Human genes 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 101150109213 Nna1 gene Proteins 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- 206010048705 Paraneoplastic cerebellar degeneration Diseases 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100037314 Protein kinase C gamma type Human genes 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000005587 Refsum Disease Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 208000010340 Sleep Deprivation Diseases 0.000 description 1
- 201000003593 Spinocerebellar ataxia type 13 Diseases 0.000 description 1
- 201000003622 Spinocerebellar ataxia type 2 Diseases 0.000 description 1
- 201000003620 Spinocerebellar ataxia type 6 Diseases 0.000 description 1
- 201000003629 Spinocerebellar ataxia type 8 Diseases 0.000 description 1
- 206010043189 Telangiectasia Diseases 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 206010048214 Xanthoma Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- DAMMQJYGTSTKMD-ABAIWWIYSA-N [(1r)-1-(2-chlorophenyl)ethyl] n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]carbamate Chemical compound C1([C@H](OC(=O)N[C@@H]2C3CCN(CC3)C2)C)=CC=CC=C1Cl DAMMQJYGTSTKMD-ABAIWWIYSA-N 0.000 description 1
- HQYLURGLNKLOQJ-XHDPSFHLSA-N [(1s)-1-(2-fluorophenyl)ethyl] n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]carbamate Chemical compound C1([C@@H](OC(=O)N[C@H]2C3CCN(CC3)C2)C)=CC=CC=C1F HQYLURGLNKLOQJ-XHDPSFHLSA-N 0.000 description 1
- JHEJZTPMJZMAKF-SWLSCSKDSA-N [(1s)-1-phenylethyl] n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]carbamate Chemical compound C1([C@@H](OC(=O)N[C@H]2C3CCN(CC3)C2)C)=CC=CC=C1 JHEJZTPMJZMAKF-SWLSCSKDSA-N 0.000 description 1
- 208000004622 abetalipoproteinemia Diseases 0.000 description 1
- 108040006409 acetylcholine-gated cation-selective channel activity proteins Proteins 0.000 description 1
- 102000015296 acetylcholine-gated cation-selective channel activity proteins Human genes 0.000 description 1
- 208000030597 adult Refsum disease Diseases 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 208000037744 atactic disease Diseases 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 206010003882 axonal neuropathy Diseases 0.000 description 1
- 210000004227 basal ganglia Anatomy 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000003986 cell retinal photoreceptor Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000003198 cerebellar cortex Anatomy 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- OEUUFNIKLCFNLN-LLVKDONJSA-N chembl432481 Chemical compound OC(=O)[C@@]1(C)CSC(C=2C(=CC(O)=CC=2)O)=N1 OEUUFNIKLCFNLN-LLVKDONJSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical class COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229960003266 deferiprone Drugs 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 201000003264 familial isolated deficiency of vitamin E Diseases 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000009760 functional impairment Effects 0.000 description 1
- 150000002244 furazanes Chemical class 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000003370 grooming effect Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960004135 idebenone Drugs 0.000 description 1
- JGPMMRGNQUBGND-UHFFFAOYSA-N idebenone Chemical compound COC1=C(OC)C(=O)C(CCCCCCCCCCO)=C(C)C1=O JGPMMRGNQUBGND-UHFFFAOYSA-N 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000003695 memory enhancer Substances 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- PALRDUGMTRLJST-UHFFFAOYSA-N n-[5-(1h-indol-4-yl)pyrimidin-2-yl]-1-azabicyclo[3.3.1]nonan-4-amine Chemical compound C1CCC2CN1CCC2NC(N=C1)=NC=C1C1=CC=CC2=C1C=CN2 PALRDUGMTRLJST-UHFFFAOYSA-N 0.000 description 1
- BCHICSBYSWEUJF-UHFFFAOYSA-N n-[5-(1h-indol-5-yl)pyridin-2-yl]-1-azabicyclo[3.3.1]nonan-4-amine Chemical compound C1=C2NC=CC2=CC(C2=CC=C(N=C2)NC2CCN3CC2CCC3)=C1 BCHICSBYSWEUJF-UHFFFAOYSA-N 0.000 description 1
- PFVFVMVVRYVOQC-UHFFFAOYSA-N n-[5-(1h-indol-5-yl)pyrimidin-2-yl]-1-azabicyclo[3.3.1]nonan-4-amine Chemical compound C1=C2NC=CC2=CC(C2=CN=C(N=C2)NC2CCN3CC2CCC3)=C1 PFVFVMVVRYVOQC-UHFFFAOYSA-N 0.000 description 1
- AYSDPAWSPJSWSA-UHFFFAOYSA-N n-[6-(1h-indol-5-yl)pyridazin-3-yl]-1-azabicyclo[3.3.1]nonan-4-amine Chemical compound C1=C2NC=CC2=CC(C2=CC=C(N=N2)NC2CCN3CC2CCC3)=C1 AYSDPAWSPJSWSA-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 108010003410 nicotinic receptor beta2 Proteins 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 229960001227 oxiracetam Drugs 0.000 description 1
- IHLAQQPQKRMGSS-UHFFFAOYSA-N oxiracetam Chemical compound NC(=O)CN1CC(O)CC1=O IHLAQQPQKRMGSS-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 108091008695 photoreceptors Proteins 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
- 229960003081 probenecid Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 208000022925 sleep disturbance Diseases 0.000 description 1
- 230000003997 social interaction Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 201000003624 spinocerebellar ataxia type 1 Diseases 0.000 description 1
- 201000003598 spinocerebellar ataxia type 10 Diseases 0.000 description 1
- 201000003594 spinocerebellar ataxia type 12 Diseases 0.000 description 1
- 201000003570 spinocerebellar ataxia type 17 Diseases 0.000 description 1
- 201000003521 spinocerebellar ataxia type 27 Diseases 0.000 description 1
- 201000003393 spinocerebellar ataxia type 5 Diseases 0.000 description 1
- 201000003632 spinocerebellar ataxia type 7 Diseases 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000009056 telangiectasis Diseases 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- RLTPJVKHGBFGQA-UHFFFAOYSA-N thiadiazolidine Chemical compound C1CSNN1 RLTPJVKHGBFGQA-UHFFFAOYSA-N 0.000 description 1
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 230000021542 voluntary musculoskeletal movement Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- 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
- A61K31/439—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 the ring forming part of a bridged ring system, e.g. quinuclidine
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22795109P | 2009-07-23 | 2009-07-23 | |
| US61/227,951 | 2009-07-23 | ||
| PCT/EP2010/060571 WO2011009890A2 (en) | 2009-07-23 | 2010-07-21 | Use of azabicycloalkyl derivatives or pyrrolidine-2-one derivatives |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015117200A Division JP2015212277A (ja) | 2009-07-23 | 2015-06-10 | 運動失調症の処置または予防のための、アザビシクロアルキル誘導体またはピロリジン−２−オン誘導体の使用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2012533601A true JP2012533601A (ja) | 2012-12-27 |
| JP2012533601A5 JP2012533601A5 (enExample) | 2015-07-30 |
Family
ID=43127649
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012521032A Pending JP2012533601A (ja) | 2009-07-23 | 2010-07-21 | 運動失調症の処置または予防のための、アザビシクロアルキル誘導体またはピロリジン−２−オン誘導体の使用 |
| JP2015117200A Pending JP2015212277A (ja) | 2009-07-23 | 2015-06-10 | 運動失調症の処置または予防のための、アザビシクロアルキル誘導体またはピロリジン−２−オン誘導体の使用 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015117200A Pending JP2015212277A (ja) | 2009-07-23 | 2015-06-10 | 運動失調症の処置または予防のための、アザビシクロアルキル誘導体またはピロリジン−２−オン誘導体の使用 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20120157464A1 (enExample) |
| EP (2) | EP2456438A2 (enExample) |
| JP (2) | JP2012533601A (enExample) |
| CN (1) | CN102573842A (enExample) |
| WO (1) | WO2011009890A2 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6262265A (ja) * | 1985-09-13 | 1987-03-18 | Hitachi Ltd | 復水器自動検査補修システム |
| JO3250B1 (ar) | 2009-09-22 | 2018-09-16 | Novartis Ag | إستعمال منشطات مستقبل نيكوتينيك أسيتيل كولين ألفا 7 |
| JP6031458B2 (ja) * | 2011-03-18 | 2016-11-24 | ノバルティス アーゲー | パーキンソン病におけるドーパミン誘発ジスキネジアに使用するためのアルファ７ニコチン性アセチルコリン受容体アクティベーターとｍＧｌｕＲ５アンタゴニストの組み合わせ剤 |
| JP6263469B2 (ja) * | 2011-07-15 | 2018-01-17 | ノバルティス アーゲー | アザ二環式ジ−アリールエーテルの塩およびその製造方法またはその前駆体の製造方法 |
| MA37975B2 (fr) | 2012-09-11 | 2021-03-31 | Genzyme Corp | Inhibiteurs de synthase de glucosylcéramide |
| BR112015016994A8 (pt) * | 2013-01-15 | 2018-01-23 | Novartis Ag | uso de agonistas do receptor alfa 7 nicotínico de acetilcolina |
| US20150313884A1 (en) | 2013-01-15 | 2015-11-05 | Novartis Ag | Use of alpha 7 nicotinic acetylcholine receptor agonists |
| CA2898045C (en) * | 2013-01-15 | 2018-08-28 | Novartis Ag | Use of alpha 7 nicotinic acetylcholine receptor agonists |
| AU2014296255B2 (en) | 2013-07-31 | 2017-08-03 | Novartis Ag | 1,4-disubstituted pyridazine derivatives and their use for treating SMN-deficiency-related conditions |
| WO2021156769A1 (en) | 2020-02-03 | 2021-08-12 | Genzyme Corporation | Methods for treating neurological symptoms associated with lysosomal storage diseases |
| CA3186766A1 (en) | 2020-07-24 | 2022-01-27 | Danielle Combessis | Pharmaceutical compositions comprising venglustat |
Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001085727A1 (en) * | 2000-05-05 | 2001-11-15 | Novartis Ag | Azabicyclic carbamates and their use as alpha-7 nicotinic acetylcholine receptor agonists |
| WO2004016608A1 (en) * | 2002-08-14 | 2004-02-26 | Neurosearch A/S | Novel quinuclidine derivatives and their use |
| WO2004022556A1 (en) * | 2002-09-04 | 2004-03-18 | Novartis Ag | Aza-bicycloalkyl ethers and their use as alpha7-nachr agonist |
| US20040229868A1 (en) * | 2002-08-30 | 2004-11-18 | Memory Pharmaceuticals Corp. | Heterocyclic compounds, methods for the preparation thereof, and uses thereof |
| WO2005118535A1 (en) * | 2004-05-28 | 2005-12-15 | Novartis Ag | Substituted pyrrolidine-2-ones |
| WO2005123732A1 (en) * | 2004-06-18 | 2005-12-29 | Novartis Ag | 1-aza-bicyclo[3.3.1]nonanes |
| WO2006005608A1 (en) * | 2004-07-14 | 2006-01-19 | Novartis Ag | 3-(heteroaryl-oxy)-2-alkyl-1-aza-bicycloalkyl derivatives as alpha.7-nachr ligands for the treatment of cns diseases |
| US20070060588A1 (en) * | 2003-12-22 | 2007-03-15 | Jianguo Ji | Fused bicycloheterocycle substituted quinuclidine derivatives |
| WO2007045478A1 (en) * | 2005-10-21 | 2007-04-26 | Novartis Ag | Novel 1-aza bicycloalkyl derivatives for the treatment of psychotic and neurodegenerative disorders |
| WO2007068476A1 (en) * | 2005-12-16 | 2007-06-21 | Novartis Ag | [ (1h- indol- 5 -yl) -heteroaryloxy] - (1-aza-bicyclo [3.3.1] nonanes as cholinergic ligands of the n-achr for the treatment of psychotic and neurodegenrative disorders. |
| WO2007068475A1 (en) * | 2005-12-16 | 2007-06-21 | Novartis Ag | (1-aza-bicyclo[3.3.1] n0n-4-yl)-[5-(ih-indol-5-yl)-heteroaryl]-amines as cholinergic ligands of the n-achr for the treatment of psychotic and neurodegenerative disorders |
| WO2008087529A1 (en) * | 2007-01-16 | 2008-07-24 | Siena Biotech S.P.A. | Nicotinic acetylcholine receptor modulators |
| WO2009043780A1 (en) * | 2007-10-04 | 2009-04-09 | F. Hoffmann-La Roche Ag | Tetrazole-substituted aryl amide derivatives and uses thereof |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0128996D0 (en) | 2001-12-04 | 2002-01-23 | Novartis Ag | Organic compounds |
| SE0201943D0 (sv) | 2002-06-20 | 2002-06-20 | Astrazeneca Ab | New use |
| BR0203527A (pt) | 2002-09-03 | 2004-05-25 | Kluber Lubrication Lubrificant | Fluìdo transmissor de calor e seu respectivo processo de obtenção |
| CA2549969A1 (en) | 2003-10-31 | 2005-05-19 | Astrazeneca Ab | Alkynes ii |
| CN1870999A (zh) | 2003-10-31 | 2006-11-29 | 阿斯利康(瑞典)有限公司 | 炔烃ⅰ |
| EP1677788A1 (en) | 2003-10-31 | 2006-07-12 | AstraZeneca AB | Alkynes iii |
| US7071143B2 (en) | 2004-01-28 | 2006-07-04 | Eastman Kodak Company | Direct thermographic materials with improved protective layers |
| ATE441792T1 (de) | 2005-04-25 | 2009-09-15 | Hoerbiger & Co | Betätigungssteuereinrichtung für die lamellen einer hydraulischen doppelkupplung |
| KR20080076962A (ko) | 2005-12-20 | 2008-08-20 | 노파르티스 아게 | 대사성 글루타메이트 수용체 조절제로서의 니코틴산 유도체 |
| WO2007085036A1 (en) | 2006-01-26 | 2007-08-02 | Medizinische Universität Wien | Treatment of friedreich' s ataxia |
| JP5730466B2 (ja) | 2006-02-22 | 2015-06-10 | アポテックス テクノロジーズ インク．Ａｐｏｔｅｘ Ｔｅｃｈｎｏｌｏｇｉｅｓ Ｉｎｃ． | 鉄の細胞内不良処理からもたらされるフリードライヒ運動失調症の治療及び／又は予防のための方法およびデフェリプロンの使用 |
| US9463190B2 (en) * | 2008-03-31 | 2016-10-11 | University Of South Florida | Methods of treating disease-induced ataxia and non-ataxic imbalance |
-
2010
- 2010-07-21 CN CN2010800335791A patent/CN102573842A/zh active Pending
- 2010-07-21 EP EP10734744A patent/EP2456438A2/en not_active Ceased
- 2010-07-21 US US13/383,690 patent/US20120157464A1/en not_active Abandoned
- 2010-07-21 JP JP2012521032A patent/JP2012533601A/ja active Pending
- 2010-07-21 EP EP15176482.6A patent/EP2959902A1/en not_active Withdrawn
- 2010-07-21 WO PCT/EP2010/060571 patent/WO2011009890A2/en not_active Ceased
-
2015
- 2015-06-10 JP JP2015117200A patent/JP2015212277A/ja active Pending
Patent Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001085727A1 (en) * | 2000-05-05 | 2001-11-15 | Novartis Ag | Azabicyclic carbamates and their use as alpha-7 nicotinic acetylcholine receptor agonists |
| WO2004016608A1 (en) * | 2002-08-14 | 2004-02-26 | Neurosearch A/S | Novel quinuclidine derivatives and their use |
| US20040229868A1 (en) * | 2002-08-30 | 2004-11-18 | Memory Pharmaceuticals Corp. | Heterocyclic compounds, methods for the preparation thereof, and uses thereof |
| WO2004022556A1 (en) * | 2002-09-04 | 2004-03-18 | Novartis Ag | Aza-bicycloalkyl ethers and their use as alpha7-nachr agonist |
| US20070060588A1 (en) * | 2003-12-22 | 2007-03-15 | Jianguo Ji | Fused bicycloheterocycle substituted quinuclidine derivatives |
| WO2005118535A1 (en) * | 2004-05-28 | 2005-12-15 | Novartis Ag | Substituted pyrrolidine-2-ones |
| WO2005123732A1 (en) * | 2004-06-18 | 2005-12-29 | Novartis Ag | 1-aza-bicyclo[3.3.1]nonanes |
| WO2006005608A1 (en) * | 2004-07-14 | 2006-01-19 | Novartis Ag | 3-(heteroaryl-oxy)-2-alkyl-1-aza-bicycloalkyl derivatives as alpha.7-nachr ligands for the treatment of cns diseases |
| WO2007045478A1 (en) * | 2005-10-21 | 2007-04-26 | Novartis Ag | Novel 1-aza bicycloalkyl derivatives for the treatment of psychotic and neurodegenerative disorders |
| WO2007068476A1 (en) * | 2005-12-16 | 2007-06-21 | Novartis Ag | [ (1h- indol- 5 -yl) -heteroaryloxy] - (1-aza-bicyclo [3.3.1] nonanes as cholinergic ligands of the n-achr for the treatment of psychotic and neurodegenrative disorders. |
| WO2007068475A1 (en) * | 2005-12-16 | 2007-06-21 | Novartis Ag | (1-aza-bicyclo[3.3.1] n0n-4-yl)-[5-(ih-indol-5-yl)-heteroaryl]-amines as cholinergic ligands of the n-achr for the treatment of psychotic and neurodegenerative disorders |
| WO2008087529A1 (en) * | 2007-01-16 | 2008-07-24 | Siena Biotech S.P.A. | Nicotinic acetylcholine receptor modulators |
| WO2009043780A1 (en) * | 2007-10-04 | 2009-04-09 | F. Hoffmann-La Roche Ag | Tetrazole-substituted aryl amide derivatives and uses thereof |
Non-Patent Citations (2)
| Title |
|---|
| JPN5012015516; ＺＥＳＩＥＷＩＣＺ ＴＨＥＲＥＳＡ Ａ: 'ＳＵＢＪＥＣＴＩＶＥ ＩＭＰＲＯＶＥＭＥＮＴ ＩＮ ＰＲＯＰＲＩＯＣＥＰＴＩＯＮ ＩＮ ２ ＰＡＴＩＥＮＴＳ 以下備考' ＪＯＵＲＮＡＬ ＯＦ ＣＬＩＮＩＣＡＬ ＮＥＵＲＯＭＵＳＣＵＬＡＲ ＤＩＳＥＡＳＥ Ｖ１０ Ｎ４, 200906, Ｐ１９１-１９３ * |
| JPN6014034250; Ｄｏｍｉｎｉｋ Ｆｅｕｅｒｂａｃｈ ｅｔ ａｌ: Ｎｅｕｒｏｐｈａｒｍａｃｏｌｏｇｙ ５６, 2009, ２５４-２６３ * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2011009890A2 (en) | 2011-01-27 |
| EP2456438A2 (en) | 2012-05-30 |
| CN102573842A (zh) | 2012-07-11 |
| EP2959902A1 (en) | 2015-12-30 |
| WO2011009890A3 (en) | 2011-09-29 |
| JP2015212277A (ja) | 2015-11-26 |
| US20120157464A1 (en) | 2012-06-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2012533601A (ja) | 運動失調症の処置または予防のための、アザビシクロアルキル誘導体またはピロリジン−２−オン誘導体の使用 | |
| US11096916B2 (en) | Use of nicotinic acetylcholine receptor alpha 7 activators | |
| AU2012210652B2 (en) | Use of nicotinic acetylcholine receptor alpha 7 activators | |
| TWI659740B (zh) | 阿法７菸鹼性乙醯膽鹼受體促效劑之用途 | |
| AU2012232711B2 (en) | Combinations of alpha 7 nicotinic acetylcholine receptor activators and mGluR5 antagonists for use in dopamine induced dyskinesia in Parkinson's Disease | |
| HK1172557A (en) | Use of nicotinic acetylcholine receptor alpha 7 activators | |
| HK1167081B (en) | Use of nicotinic acetylcholine receptor alpha 7 activators | |
| HK1167081A (en) | Use of nicotinic acetylcholine receptor alpha 7 activators |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130704 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20140814 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140819 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20140822 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20140902 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150210 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20150610 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20150728 |
|
| A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20151002 |