SK10142002A3 - Benzoanelované heterocyklylové deriváty nikotínamidu užitočné ako selektívne inhibítory izozymov PDE4 - Google Patents
Benzoanelované heterocyklylové deriváty nikotínamidu užitočné ako selektívne inhibítory izozymov PDE4 Download PDFInfo
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- SK10142002A3 SK10142002A3 SK1014-2002A SK10142002A SK10142002A3 SK 10142002 A3 SK10142002 A3 SK 10142002A3 SK 10142002 A SK10142002 A SK 10142002A SK 10142002 A3 SK10142002 A3 SK 10142002A3
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- nicotinamide
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US17928400P | 2000-01-31 | 2000-01-31 | |
PCT/IB2001/000124 WO2001057036A1 (fr) | 2000-01-31 | 2001-01-30 | Derives benzocondenses heterocycliques de nicotinamide utiles comme inhibiteurs selectifs d'isozymes pde4 |
Publications (1)
Publication Number | Publication Date |
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SK10142002A3 true SK10142002A3 (sk) | 2003-11-04 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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SK1014-2002A SK10142002A3 (sk) | 2000-01-31 | 2001-01-30 | Benzoanelované heterocyklylové deriváty nikotínamidu užitočné ako selektívne inhibítory izozymov PDE4 |
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US (1) | US7354941B2 (fr) |
EP (1) | EP1252158B1 (fr) |
JP (1) | JP3917863B2 (fr) |
KR (1) | KR20020072299A (fr) |
CN (1) | CN1404481A (fr) |
AP (1) | AP2002002589A0 (fr) |
AR (1) | AR027337A1 (fr) |
AT (1) | ATE293624T1 (fr) |
AU (1) | AU2700201A (fr) |
BG (1) | BG106852A (fr) |
BR (1) | BR0107964A (fr) |
CA (1) | CA2398182C (fr) |
CO (1) | CO5261634A1 (fr) |
CZ (1) | CZ20022410A3 (fr) |
DE (1) | DE60110205T2 (fr) |
EA (1) | EA004885B1 (fr) |
EE (1) | EE200200425A (fr) |
ES (1) | ES2238415T3 (fr) |
GE (1) | GEP20043302B (fr) |
GT (1) | GT200100022A (fr) |
HN (1) | HN2001000019A (fr) |
HU (1) | HUP0204262A2 (fr) |
IL (1) | IL150641A0 (fr) |
IS (1) | IS6421A (fr) |
MA (1) | MA26870A1 (fr) |
MX (1) | MXPA02007419A (fr) |
NO (1) | NO20023613L (fr) |
NZ (1) | NZ519547A (fr) |
OA (1) | OA12169A (fr) |
PA (1) | PA8511201A1 (fr) |
PE (1) | PE20011058A1 (fr) |
PL (1) | PL357995A1 (fr) |
PT (1) | PT1252158E (fr) |
SK (1) | SK10142002A3 (fr) |
SV (1) | SV2002000299A (fr) |
TN (1) | TNSN01020A1 (fr) |
TR (1) | TR200201880T2 (fr) |
UY (1) | UY26569A1 (fr) |
WO (1) | WO2001057036A1 (fr) |
ZA (1) | ZA200206033B (fr) |
Families Citing this family (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7417038B1 (en) * | 1998-10-15 | 2008-08-26 | Imperial Innovations Limited | Methods of treating cachexia |
KR100782891B1 (ko) * | 2000-01-28 | 2007-12-06 | 알자 코포레이션 | 과포화 용액으로 포획된 화합물을 포함하는 리포좀 |
WO2002022583A2 (fr) * | 2000-09-18 | 2002-03-21 | E. I. Du Pont De Nemours And Company | Pyridinyl-amides et pyridinyl-imides utilisés comme fongicides |
CA2436535A1 (fr) * | 2001-01-31 | 2002-08-08 | Prizer Products Inc. | Derives de biaryl nicotinamide utiles comme inhibiteurs d'isozymes de pde4 |
DE60113731T2 (de) * | 2001-01-31 | 2006-06-29 | Pfizer Products Inc., Groton | Als inhibitoren von pde4-isozymen geeignete etherderivate |
US7250518B2 (en) | 2001-01-31 | 2007-07-31 | Pfizer Inc. | Nicotinamide acids, amides, and their mimetics active as inhibitors of PDE4 isozymes |
KR20030072614A (ko) * | 2001-01-31 | 2003-09-15 | 화이자 프로덕츠 인크. | Pde4 이소자임 억제제로 유용한 티아졸릴-,옥사졸릴-, 피롤릴- 및 이미다졸릴-산 아미드 유도체 |
GB0118373D0 (en) * | 2001-07-27 | 2001-09-19 | Glaxo Group Ltd | Novel therapeutic method |
ATE349243T1 (de) * | 2001-09-19 | 2007-01-15 | Altana Pharma Ag | Kombination von einem pde-hemmer und eines leukotrien rezeptor antagonisten |
DK1429807T3 (da) * | 2001-09-19 | 2007-06-18 | Altana Pharma Ag | Kombination af et NSAID og en PDE4-inhibitor |
IS7221A (is) * | 2001-11-15 | 2004-04-15 | Memory Pharmaceuticals Corporation | Hringlaga adenosínmónófosfat fosfódíesterasa 4D7 ísóform og aðferðir til notkunar þeirra |
RS70104A (en) | 2002-02-11 | 2007-02-05 | Pfizer Limited, | Nicotinamide derivatives useful as pde4 inhibitors |
US6756392B2 (en) | 2002-02-11 | 2004-06-29 | Pfizer Inc | Nicotinamide derivatives useful as PDE4 inhibitors |
US6962940B2 (en) | 2002-03-20 | 2005-11-08 | Celgene Corporation | (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione: methods of using and compositions thereof |
CA2506949A1 (fr) * | 2002-11-27 | 2004-06-10 | Altana Pharma Ag | Inhibiteurs de pde4 et pde3/4 que l'on utilise dans le traitement de la cachexie |
JP2006516548A (ja) | 2002-12-30 | 2006-07-06 | アンジオテック インターナショナル アクツィエン ゲゼルシャフト | 迅速ゲル化ポリマー組成物からの薬物送達法 |
JPWO2004087150A1 (ja) * | 2003-03-31 | 2006-06-29 | 協和醗酵工業株式会社 | 医薬組成物 |
JPWO2004087151A1 (ja) * | 2003-03-31 | 2006-06-29 | 協和醗酵工業株式会社 | 医薬組成物 |
CA2520577A1 (fr) * | 2003-03-31 | 2004-10-14 | Kyowa Hakko Kogyo Co., Ltd. | Composition pharmaceutique |
WO2004090157A1 (fr) * | 2003-04-10 | 2004-10-21 | F. Hoffmann-La Roche Ag | Utilisation de pde4d dans le criblage de medicaments contre l'atherosclerose |
US20040265323A1 (en) * | 2003-05-16 | 2004-12-30 | Mccormick Beth A. | Compositions comprising pathogen elicited epithelial chemoattractant (eicosanoid hepoxilin A3), inhibitors thereof and methods of use thereof |
GB0317516D0 (en) | 2003-07-25 | 2003-08-27 | Pfizer Ltd | Nicotinamide derivatives useful as PDE4 inhibitors |
GB0317484D0 (en) | 2003-07-25 | 2003-08-27 | Pfizer Ltd | Nicotinamide derivatives useful as pde4 inhibitors |
GB0317471D0 (en) * | 2003-07-25 | 2003-08-27 | Pfizer Ltd | Novel compounds |
GB0317498D0 (en) * | 2003-07-25 | 2003-08-27 | Pfizer Ltd | Compounds |
US7132435B2 (en) | 2003-07-25 | 2006-11-07 | Pfizer Inc. | Compounds |
US7153870B2 (en) | 2003-07-25 | 2006-12-26 | Pfizer Inc. | Nicotinamide derivatives useful as PDE4 inhibitors |
AR049384A1 (es) | 2004-05-24 | 2006-07-26 | Glaxo Group Ltd | Derivados de purina |
EP1683795A1 (fr) * | 2005-01-21 | 2006-07-26 | Pfizer Limited | Formes crystallines de cis-5-fluoro-N-¬4-(2-hydroxy-4-methylbenzamido)cyclohexyl|-2-(tetrahydrothiopyran-4-yloxy)nicotinamide |
US20080194635A1 (en) * | 2005-01-21 | 2008-08-14 | Pfizer Inc. | Crystalline Forms of Cis-5-Fluoro-N-[4-(2-Hydroxy-4-Methylbenzamido) Cyclohexyl]-2-(Tetrahydrothiopyran-4-Yloxy) Nicotinamide |
GB0514809D0 (en) | 2005-07-19 | 2005-08-24 | Glaxo Group Ltd | Compounds |
GB0624282D0 (en) * | 2006-12-05 | 2007-01-10 | Cavalla David | Treatment of cachexia |
WO2008079328A2 (fr) * | 2006-12-22 | 2008-07-03 | Creighton University | Acides gras oméga-5 utiles dans l'inhibition de la 5-lipoxygénase et dans le traitement du cancer |
AR066016A1 (es) * | 2007-04-11 | 2009-07-15 | Alcon Res Ltd | Uso de un inhibidor del tnf alfa junto con una antihistamina para tratar la rinitis alergica y la conjuntivitis alergica |
EP2196465A1 (fr) | 2008-12-15 | 2010-06-16 | Almirall, S.A. | Dérivés de (3-oxo)pyridazin-4-ylurée comme inhibiteurs de PDE4 |
EP2226323A1 (fr) | 2009-02-27 | 2010-09-08 | Almirall, S.A. | Nouveaux dérivés de tétrahydropyrazolo [3,4-c]isoquinoléine-5-amine |
MY158504A (en) | 2009-09-01 | 2016-10-14 | Catabasis Pharmaceuticals Inc | Fatty acid niacin conjugates and their uses |
USRE46608E1 (en) | 2009-09-01 | 2017-11-14 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
EP2380890A1 (fr) | 2010-04-23 | 2011-10-26 | Almirall, S.A. | Nouveaux dérivés de 7,8-dihydro-1,6-naphthyridin-5(6h)-one comme PDE4 inhibiteurs |
EP2386555A1 (fr) * | 2010-05-13 | 2011-11-16 | Almirall, S.A. | Nouveaux dérivés de cyclohéxylamine dotés d'activités agoniste bêta 2 adrénergique et antagoniste muscarinique m3 |
EP2394998A1 (fr) | 2010-05-31 | 2011-12-14 | Almirall, S.A. | Dérivés de 3-(5-Amino-6-oxo-1,6-dihydropyridazin-3-yl)-biphenyl en tant qu'inhibiteurs de la PDE4 |
CN107635564B (zh) * | 2015-03-17 | 2020-07-24 | 理筱龙 | 人参皂苷m1用于预防或治疗硅肺病的用途 |
US11116737B1 (en) | 2020-04-10 | 2021-09-14 | University Of Georgia Research Foundation, Inc. | Methods of using probenecid for treatment of coronavirus infections |
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US4861891A (en) * | 1988-08-31 | 1989-08-29 | Pfizer Inc. | Antidepressant N-substituted nicotinamide compounds |
TW429148B (en) * | 1995-10-27 | 2001-04-11 | Pfizer | Pharmaceutical agents for the treatment of acute and chronic inflammatory diseases |
NZ337698A (en) * | 1997-04-04 | 2001-07-27 | Pfizer Prod Inc | Nicotinamide derivatives for selective inhibition of phosphodiesterase type 4 (PDE4) and the production of tumour necrosis factor (TNF) useful for the treatment of respiratory, rheumatoid and allergic diseases |
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