ZA200209966B - Sulfonyl-pyrrolidine derivatives useful for the treatment of neurological disorders. - Google Patents
Sulfonyl-pyrrolidine derivatives useful for the treatment of neurological disorders. Download PDFInfo
- Publication number
- ZA200209966B ZA200209966B ZA200209966A ZA200209966A ZA200209966B ZA 200209966 B ZA200209966 B ZA 200209966B ZA 200209966 A ZA200209966 A ZA 200209966A ZA 200209966 A ZA200209966 A ZA 200209966A ZA 200209966 B ZA200209966 B ZA 200209966B
- Authority
- ZA
- South Africa
- Prior art keywords
- sulfonyl
- phenyl
- toluene
- fluoro
- pyrrolidin
- Prior art date
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- 208000025966 Neurological disease Diseases 0.000 title claims description 10
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- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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ZA200209966A ZA200209966B (en) | 2000-06-30 | 2002-12-09 | Sulfonyl-pyrrolidine derivatives useful for the treatment of neurological disorders. |
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US (2) | US6589978B2 (fr) |
EP (1) | EP1299383B1 (fr) |
JP (1) | JP3994051B2 (fr) |
KR (1) | KR100529423B1 (fr) |
CN (1) | CN1178936C (fr) |
AR (1) | AR029288A1 (fr) |
AT (1) | ATE286895T1 (fr) |
AU (2) | AU2001281877B2 (fr) |
BR (1) | BR0112093A (fr) |
CA (1) | CA2413243A1 (fr) |
CZ (1) | CZ2003280A3 (fr) |
DE (1) | DE60108394T2 (fr) |
DK (1) | DK1299383T3 (fr) |
EC (1) | ECSP024403A (fr) |
ES (1) | ES2234869T3 (fr) |
HK (1) | HK1058358A1 (fr) |
HR (1) | HRP20021023B1 (fr) |
HU (1) | HUP0301167A3 (fr) |
IL (2) | IL153425A0 (fr) |
JO (1) | JO2384B1 (fr) |
MA (1) | MA26923A1 (fr) |
MX (1) | MXPA02012270A (fr) |
MY (1) | MY126903A (fr) |
NO (1) | NO324218B1 (fr) |
NZ (1) | NZ523025A (fr) |
PE (1) | PE20020103A1 (fr) |
PL (1) | PL360396A1 (fr) |
PT (1) | PT1299383E (fr) |
RU (1) | RU2272026C2 (fr) |
SI (1) | SI1299383T1 (fr) |
TW (1) | TWI265928B (fr) |
UY (1) | UY26812A1 (fr) |
WO (1) | WO2002002554A1 (fr) |
YU (1) | YU99702A (fr) |
ZA (1) | ZA200209966B (fr) |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040171614A1 (en) * | 2002-02-06 | 2004-09-02 | Schering-Plough Corporation | Novel gamma secretase inhibitors |
TW200302717A (en) * | 2002-02-06 | 2003-08-16 | Schering Corp | Novel gamma secretase inhibitors |
US7256186B2 (en) | 2002-02-06 | 2007-08-14 | Schering Corporation | Gamma secretase inhibitors |
DE10240818A1 (de) * | 2002-08-30 | 2004-05-13 | Grünenthal GmbH | Substituierte 2-Pyrrolidin-2-yl-[1,3,4]-oxadiazol-Derivate |
GB0225938D0 (en) * | 2002-11-06 | 2002-12-11 | Glaxo Group Ltd | Novel compounds |
JP2007531742A (ja) * | 2004-04-05 | 2007-11-08 | シェーリング コーポレイション | 新規のγセクレターゼインヒビター |
EP1758884A2 (fr) * | 2004-05-20 | 2007-03-07 | Elan Pharmaceuticals, Inc. | Inhibiteurs sulfonamido n-cycliques de gamma-secretase |
MX2007000040A (es) | 2004-06-30 | 2007-03-07 | Schering Corp | N-arilsulfonilaminas heterociclicas sustituidas como inhibidores de gamma-secretasas. |
US7803802B2 (en) * | 2004-07-22 | 2010-09-28 | Schering Corporation | Substituted amide beta secretase inhibitors |
CA2582777A1 (fr) | 2004-09-30 | 2006-04-06 | Takeda Pharmaceutical Company Limited | Inhibiteurs de pompe a protons |
EP1867641A4 (fr) * | 2005-04-04 | 2010-01-13 | Takeda Pharmaceutical | Médicament prophylactique ou thérapeutique contre la dépression ou la névrose d'angoisse |
JP2009506069A (ja) | 2005-08-26 | 2009-02-12 | ブレインセルス,インコーポレイティド | ムスカリン性受容体調節による神経発生 |
EP2258359A3 (fr) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenèse par modulation des récepteurs muscariniques avec sabcomeline |
ME00610B (fr) | 2005-08-30 | 2011-12-20 | Takeda Pharmaceuticals Co | Dérivés de 1-h-pyrrole substitués par un groupe 1-hétérocyclylsulfonyle, 2-aminométhyle, 5-(hétéro)aryle en tant qu'inhibiteurs des sécrétions acides |
CA2625153A1 (fr) | 2005-10-21 | 2007-04-26 | Braincells, Inc. | Modulation de la neurogenese par inhibition de la pde |
US20070112017A1 (en) | 2005-10-31 | 2007-05-17 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
US7678808B2 (en) | 2006-05-09 | 2010-03-16 | Braincells, Inc. | 5 HT receptor mediated neurogenesis |
EP2377531A2 (fr) | 2006-05-09 | 2011-10-19 | Braincells, Inc. | Neurogénèse par modulation de l'angiotensine |
WO2008030651A1 (fr) | 2006-09-08 | 2008-03-13 | Braincells, Inc. | Combinaisons contenant un dérivé de 4-acylaminopyridine |
US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
DK2066659T3 (da) * | 2006-09-29 | 2013-12-09 | Gruenenthal Gmbh | Substitueret sulfonamid-derivat |
US8933105B2 (en) | 2007-02-28 | 2015-01-13 | Takeda Pharmaceutical Company Limited | Pyrrole compounds |
SI2318006T1 (sl) * | 2008-08-15 | 2017-01-31 | Nivalis Therapeutics, Inc. | Novi pirolni inhibitorji S-nitrozoglutation reduktaze kot terapevtska sredstva |
MY152008A (en) | 2008-08-27 | 2014-08-15 | Takeda Pharmaceutical | Pyrrole compounds |
US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
ES2351323B1 (es) * | 2009-06-26 | 2011-10-05 | Institut Univ. De Ciència I Tecnologia, S.A. | Bibliotecas de n-fenil-1-sulfonil-2-pirrolidinacarboxamidas para el descubrimiento de farmacos. |
ES2351452B1 (es) * | 2009-07-01 | 2011-10-05 | Institut Univ. De Ciència I Tecnologia, S.A. | Bibliotecas de n-fenil-1-sulfonil-2-pirrolidinacarboxamidas para la identificacion de actividad biologica y farmacologica. |
AU2022296214A1 (en) * | 2021-06-25 | 2024-01-25 | Albius Sciences Alpha Private Limited | Heterocycloalkyl-substituted polyheteroazole derivative as medical drug for treatment and/or prevention of rs virus infectious disease |
Family Cites Families (15)
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US3905979A (en) * | 1974-05-09 | 1975-09-16 | Stanford Research Inst | Diazabicyclooctanes and diazabicycloheptanes |
US4539411A (en) * | 1982-02-05 | 1985-09-03 | Hoffmann-La Roche Inc. | Rhodium complexes of chiral phosphines |
US5036153A (en) * | 1989-05-11 | 1991-07-30 | Braish Tamim F | Preparation of 2,5-diazabicyclo[2.2.1]heptanes and intermediates |
GB9612884D0 (en) | 1996-06-20 | 1996-08-21 | Smithkline Beecham Plc | Novel compounds |
US5721256A (en) | 1997-02-12 | 1998-02-24 | Gpi Nil Holdings, Inc. | Method of using neurotrophic sulfonamide compounds |
US6645939B1 (en) * | 1997-11-24 | 2003-11-11 | Merck & Co., Inc. | Substituted β-alanine derivatives as cell adhesion inhibitors |
CA2309338A1 (fr) | 1997-11-24 | 1999-06-03 | Merck & Co., Inc. | Derives d'acide amine cycliques utilises comme inhibiteurs de l'adhesion cellulaire |
GB9804426D0 (en) | 1998-03-02 | 1998-04-29 | Pfizer Ltd | Heterocycles |
AT411339B (de) | 1998-05-13 | 2003-12-29 | Fronius Schweissmasch Prod | Verfahren zum steuern eines schweissgerätes und steuervorrichtung hierfür |
HUP0102532A3 (en) | 1998-06-03 | 2002-06-28 | Gpi Nil Holdings Inc Wilmingto | Aza-heterocyclic compounds used to treat neurological disorders and hair loss and process for their preparation and pharmaceutical compositions containing them |
BR9916328A (pt) | 1998-12-18 | 2001-10-02 | Schering Corp | Inibidores de transferase de farnesila |
EA200100815A1 (ru) * | 1999-01-27 | 2002-08-29 | Орто-Макнейл Фармасьютикал, Инк. | Пептидильные гетероциклические кетоны, применимые в качестве ингибиторов триптазы |
TW575561B (en) | 1999-03-25 | 2004-02-11 | Hoffmann La Roche | 1-arenesulfonyl-2-aryl-pyrrolidine and piperidine derivatives |
WO2000071541A1 (fr) * | 1999-05-20 | 2000-11-30 | Dong Wha Pharm. Ind. Co., Ltd. | Derives d'acide quinoleine-carboxylique actifs optiquement presentant des substituts 7-pyrrolidines amenant une activite optique et leur procede de preparation |
US6143776A (en) * | 2000-02-02 | 2000-11-07 | Sunesis Pharmaceuticals, Inc. | Tosylproline analogs as thymidylate synthase inhibitors |
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