ES2140354B1 - Imidazo (1,2a) azinas sustituidas como inhibidores selectivos de la cox-2. - Google Patents

Imidazo (1,2a) azinas sustituidas como inhibidores selectivos de la cox-2.

Info

Publication number
ES2140354B1
ES2140354B1 ES009801652A ES9801652A ES2140354B1 ES 2140354 B1 ES2140354 B1 ES 2140354B1 ES 009801652 A ES009801652 A ES 009801652A ES 9801652 A ES9801652 A ES 9801652A ES 2140354 B1 ES2140354 B1 ES 2140354B1
Authority
ES
Spain
Prior art keywords
sup
sub
substituted
cox
imidazo
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.)
Expired - Lifetime
Application number
ES009801652A
Other languages
English (en)
Other versions
ES2140354A1 (es
Inventor
Gallemi Carles Farrerons
Bono Ignacio-Jose Miquel
Vidal Carlos Monserrat
Arnal Carmen Lagunas
Guasch Fernando Gimenez
Garcia Andres Fernandez
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Laboratorios Salvat SA
Original Assignee
Laboratorios Salvat SA
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority to ES009801652A priority Critical patent/ES2140354B1/es
Application filed by Laboratorios Salvat SA filed Critical Laboratorios Salvat SA
Priority to CN998116750A priority patent/CN1131865C/zh
Priority to NZ510196A priority patent/NZ510196A/xx
Priority to AU47824/99A priority patent/AU749770B2/en
Priority to OA1200100033A priority patent/OA11592A/en
Priority to PCT/ES1999/000235 priority patent/WO2000008024A1/es
Priority to AT99931266T priority patent/ATE224391T1/de
Priority to PL99345804A priority patent/PL345804A1/xx
Priority to BR9912968-0A priority patent/BR9912968A/pt
Priority to DE69903046T priority patent/DE69903046T2/de
Priority to SI9930061T priority patent/SI1104762T1/xx
Priority to APAP/P/2001/002082A priority patent/AP2001002082A0/en
Priority to IDW20010517A priority patent/ID28539A/id
Priority to TR2001/00359T priority patent/TR200100359T2/xx
Priority to HU0103004A priority patent/HUP0103004A3/hu
Priority to DK99931266T priority patent/DK1104762T3/da
Priority to CA002339187A priority patent/CA2339187A1/en
Priority to EA200100212A priority patent/EA003399B1/ru
Priority to ES99931266T priority patent/ES2182546T3/es
Priority to EP99931266A priority patent/EP1104762B1/en
Priority to IL14124299A priority patent/IL141242A0/xx
Priority to JP2000563657A priority patent/JP2002522438A/ja
Priority to SK166-2001A priority patent/SK1662001A3/sk
Priority to CZ2001433A priority patent/CZ291783B6/cs
Priority to YU7401A priority patent/YU7401A/sh
Priority to US09/762,146 priority patent/US6670365B1/en
Priority to PT99931266T priority patent/PT1104762E/pt
Priority to MXPA01001332A priority patent/MXPA01001332A/es
Priority to KR1020017001453A priority patent/KR20010079602A/ko
Publication of ES2140354A1 publication Critical patent/ES2140354A1/es
Publication of ES2140354B1 publication Critical patent/ES2140354B1/es
Application granted granted Critical
Priority to NO20010568A priority patent/NO20010568L/no
Priority to ZA200101632A priority patent/ZA200101632B/en
Priority to BG105299A priority patent/BG105299A/xx
Priority to HK01108500A priority patent/HK1037629A1/xx
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Imidazo[l,2a]azinas sustituidas como inhibidores selectivos de la COX-2. La presente invención hace referencia a nuevos productos de fórmula (I), donde A y B se seleccionan entre N y CH, con la condición de que cuando A es N, B es N; R{sup,1 se selecciona entre CH{sub,3 y NH{sub,2 ; R{sup,2 se selecciona entre H y CH{sub,3 , COCH{sub,3 y OCH{sub,3 ; y R{sup,3 y R{sup,4 , iguales o distintos entre sí, se seleccionan entre el grupo formado por H, F, Cl, Br, (C1-C3)-alquilo, trifluorometilo, (C1-C3)-alcoxilo y trifluorometoxilo, o forman un sustituyente {b -naftilo con el anillo bencénico. Los productos de fórmula (I) se preparan por condensación entre una aminoazina sustituida y una 2-bromo-2-(4-R{sup,1 -sulfonilfenil)-1-feniletanona sustituida, en un disolvente polar. Presentan una actividad inhibidora de la COX-2, con elevada selectividad frente a la COX-1. Son útiles para el tratamiento de la inflamación y/o de las enfermedades mediadas por las ciclooxigenasas, con la ventaja adicional de poseer un potencial ulcerogénico reducido.
ES009801652A 1998-08-03 1998-08-03 Imidazo (1,2a) azinas sustituidas como inhibidores selectivos de la cox-2. Expired - Lifetime ES2140354B1 (es)

Priority Applications (33)

Application Number Priority Date Filing Date Title
ES009801652A ES2140354B1 (es) 1998-08-03 1998-08-03 Imidazo (1,2a) azinas sustituidas como inhibidores selectivos de la cox-2.
IL14124299A IL141242A0 (en) 1998-08-03 1999-07-23 Substituted imidazo [1,2a] azines as selective inhibitors of cox-2
AU47824/99A AU749770B2 (en) 1998-08-03 1999-07-23 Substituted imidazo(1,2A)azines as selective inhibitors of COX-2
EP99931266A EP1104762B1 (en) 1998-08-03 1999-07-23 Substituted imidazo[1,2a]azines as selective inhibitors of cox-2
PCT/ES1999/000235 WO2000008024A1 (es) 1998-08-03 1999-07-23 IMIDAZO[1,2a]AZINAS SUSTITUIDAS COMO INHIBIDORES SELECTIVOS DE LA COX-2
AT99931266T ATE224391T1 (de) 1998-08-03 1999-07-23 Substituierte imidazo(1,2a)azine als selective inhibitoren der cox-2
PL99345804A PL345804A1 (en) 1998-08-03 1999-07-23 Substituted imidazo[1,2a]azines as selective inhibotors of cox-2
BR9912968-0A BR9912968A (pt) 1998-08-03 1999-07-23 Imidazo[1,2a]azinas substituìdas como inibidores de cox-2 seletivos
DE69903046T DE69903046T2 (de) 1998-08-03 1999-07-23 Substituierte imidazo[1,2a]azine als selective inhibitoren der cox-2
SI9930061T SI1104762T1 (en) 1998-08-03 1999-07-23 Substituted imidazo(1,2a)azines as selective inhibitors of cox-2
APAP/P/2001/002082A AP2001002082A0 (en) 1998-08-03 1999-07-23 Substituted imidazo(1,2alizines as selective inhibitors of cox-2.
IDW20010517A ID28539A (id) 1998-08-03 1999-07-23 Imidazo (1,2a) azina bersubstitusi sebagai penghambat selektif cox-2
TR2001/00359T TR200100359T2 (tr) 1998-08-03 1999-07-23 COX-2 Selektif inhibitörleri olarak ikameli imidazo[1,2a] azinler.
HU0103004A HUP0103004A3 (en) 1998-08-03 1999-07-23 Substituted imidazo[1,2a]azines as selective inhibitors of cox-2, process for their preparation and pharmaceutical compositions containing them
DK99931266T DK1104762T3 (da) 1998-08-03 1999-07-23 Substituerede imidazo[1,2a]aziner som selektive COX-2-inhibitorer
CA002339187A CA2339187A1 (en) 1998-08-03 1999-07-23 Substituted imidazo¬1,2a|azines as selective inhibitors of cox-2
CN998116750A CN1131865C (zh) 1998-08-03 1999-07-23 作为选择性COX－2抑制剂的取代的咪唑并[1,2a]吖嗪
ES99931266T ES2182546T3 (es) 1998-08-03 1999-07-23 Imidazo(1,2a)azinas sustituidas como inhibidores selectivos de la cox-2.
OA1200100033A OA11592A (en) 1998-08-03 1999-07-23 Substituted imidazo!1,2aÜazines as selective inhibitors of cox-2.
EA200100212A EA003399B1 (ru) 1998-08-03 1999-07-23 ЗАМЕЩЕННЫЕ АМИДАЗО[1, 2a]АЗИНЫ КАК СЕЛЕКТИВНЫЕ COX-2 ИНГИБИТОРЫ
SK166-2001A SK1662001A3 (en) 1998-08-03 1999-07-23 Substituted imidazo[1,2a]azines as selective inhibotors of cox-2
JP2000563657A JP2002522438A (ja) 1998-08-03 1999-07-23 選択的ＣＯＸ−２阻害剤としての置換イミダゾ［１，２ａ］アジン類
CZ2001433A CZ291783B6 (cs) 1998-08-03 1999-07-23 Substituované imidazo[1,2-a]aziny jako selektivní inhibitory COX-2
YU7401A YU7401A (sh) 1998-08-03 1999-07-23 Supstituisani imidazo(1,2a)azini kao selektivni cox-2 inhibitori
US09/762,146 US6670365B1 (en) 1998-08-03 1999-07-23 Substituted imidazo 1,2a}azines as selective inhibitors of cox-2
PT99931266T PT1104762E (pt) 1998-08-03 1999-07-23 Imidazo¬1,2a|azinas substituidas como inibidoras selectivas de cox 2
MXPA01001332A MXPA01001332A (es) 1998-08-03 1999-07-23 Imidazo(1,2a)azinas sustituidas como inhibidores selectivos de la coclooxigenasa-2.
KR1020017001453A KR20010079602A (ko) 1998-08-03 1999-07-23 선택적인 ｃｏｘ-2 저해제인 치환된 이미다조[1,2ａ]아진
NZ510196A NZ510196A (en) 1998-08-03 1999-07-23 Substituted imidazo[1,2-a]pyridines, pyrimidines or triazines useful as selective inhibitors of cox-2
NO20010568A NO20010568L (no) 1998-08-03 2001-02-02 Substituerte imidazo[1,2a]aziner som selektive COX-2- inhibitorer
ZA200101632A ZA200101632B (en) 1998-08-03 2001-02-27 Substituted imidazo[1,2A]azines as selective inhibitors of cox-2.
BG105299A BG105299A (en) 1998-08-03 2001-02-28 Substituted amidazo[1,2a]azines as selective inhibitors of cox-2
HK01108500A HK1037629A1 (en) 1998-08-03 2001-12-04 Substituted imidazo [1,2a]azines as selective inhibitors of cox-2

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
ES009801652A ES2140354B1 (es) 1998-08-03 1998-08-03 Imidazo (1,2a) azinas sustituidas como inhibidores selectivos de la cox-2.

Publications (2)

Publication Number Publication Date
ES2140354A1 ES2140354A1 (es) 2000-02-16
ES2140354B1 true ES2140354B1 (es) 2000-11-01

Family

ID=8304755

Family Applications (2)

Application Number Title Priority Date Filing Date
ES009801652A Expired - Lifetime ES2140354B1 (es) 1998-08-03 1998-08-03 Imidazo (1,2a) azinas sustituidas como inhibidores selectivos de la cox-2.
ES99931266T Expired - Lifetime ES2182546T3 (es) 1998-08-03 1999-07-23 Imidazo(1,2a)azinas sustituidas como inhibidores selectivos de la cox-2.

Family Applications After (1)

Application Number Title Priority Date Filing Date
ES99931266T Expired - Lifetime ES2182546T3 (es) 1998-08-03 1999-07-23 Imidazo(1,2a)azinas sustituidas como inhibidores selectivos de la cox-2.

Country Status (31)

Country Link
US (1) US6670365B1 (es)
EP (1) EP1104762B1 (es)
JP (1) JP2002522438A (es)
KR (1) KR20010079602A (es)
CN (1) CN1131865C (es)
AP (1) AP2001002082A0 (es)
AT (1) ATE224391T1 (es)
AU (1) AU749770B2 (es)
BG (1) BG105299A (es)
BR (1) BR9912968A (es)
CA (1) CA2339187A1 (es)
CZ (1) CZ291783B6 (es)
DE (1) DE69903046T2 (es)
DK (1) DK1104762T3 (es)
EA (1) EA003399B1 (es)
ES (2) ES2140354B1 (es)
HK (1) HK1037629A1 (es)
HU (1) HUP0103004A3 (es)
ID (1) ID28539A (es)
IL (1) IL141242A0 (es)
MX (1) MXPA01001332A (es)
NO (1) NO20010568L (es)
NZ (1) NZ510196A (es)
OA (1) OA11592A (es)
PL (1) PL345804A1 (es)
PT (1) PT1104762E (es)
SK (1) SK1662001A3 (es)
TR (1) TR200100359T2 (es)
WO (1) WO2000008024A1 (es)
YU (1) YU7401A (es)
ZA (1) ZA200101632B (es)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8241622B2 (en) * 2001-07-13 2012-08-14 University Of Iowa Research Foundation Adeno-associated virus vectors with intravector heterologous terminal palindromic sequences
US20030100594A1 (en) * 2001-08-10 2003-05-29 Pharmacia Corporation Carbonic anhydrase inhibitor
DE10247271A1 (de) * 2002-10-10 2004-08-26 Grünenthal GmbH Substituierte C-Imidazo[1,2-a]pyridin-3-yle
DE10256881A1 (de) * 2002-12-05 2004-06-24 Beiersdorf Ag Neue topische Verwendung von Bis-Arylimidazo[1,2-a]thiolanderivaten
DK1534305T3 (da) 2003-05-07 2007-02-05 Osteologix As Behandling af brusk-/knoglelidelser med vandoplöselige strontiumsalte
BRPI0412636A (pt) * 2003-07-30 2006-09-26 S A L V A T Lab Sa imidazopirimidinas substituìdas para a prevenção e tratamento de cáncer
WO2007034278A2 (en) * 2005-09-19 2007-03-29 Pfizer Products Inc. Fused imidazole derivatives as c3a receptor antagonists
JP2009521928A (ja) * 2005-12-30 2009-06-11 ユニバーシテイ・オブ・アイオワ・リサーチ・フアウンデーシヨン 神経細胞変性疾患の治療に有用な化合物を特定する方法
WO2007096764A2 (en) * 2006-02-27 2007-08-30 Glenmark Pharmaceuticals S.A. Bicyclic heteroaryl derivatives as cannabinoid receptor modulators
EP2220083B1 (en) * 2007-11-14 2017-07-19 Janssen Pharmaceuticals, Inc. Imidazo[1,2-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors
US20100130522A1 (en) * 2008-10-01 2010-05-27 Synta Pharmaceuticals Corp. Compounds for inflammation and immune-related uses
GB201321732D0 (en) * 2013-12-09 2014-01-22 Ucb Pharma Sa Therapeutic agents
WO2017139381A1 (en) 2016-02-08 2017-08-17 University Of Iowa Research Foundation Methods to produce chimeric adeno-associated virus/bocavirus parvovirus
AU2017229347A1 (en) 2016-03-07 2018-11-01 University Of Iowa Research Foundation AAV-mediated expression using a synthetic promoter and enhancer
WO2022195579A1 (en) 2021-03-15 2022-09-22 Saul Yedgar Hyaluronic acid-conjugated dipalmitoyl phosphatidyl ethanolamine in combination with non-steroidal anti-inflammatory drugs (nsaids) for treating or alleviating inflammatory diseases

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2785133A (en) * 1954-03-26 1957-03-12 Gen Aniline & Film Corp Compositions for a method of whitening fine fabrics
US3455924A (en) * 1967-02-08 1969-07-15 Upjohn Co Dianisylimidazoles
WO1992010190A1 (en) 1990-12-13 1992-06-25 Smithkline Beecham Corporation Novel csaids
WO1993019066A1 (en) * 1992-03-17 1993-09-30 Nippon Shinyaku Co., Ltd. Imidazopyridine derivative and medicine
US5620999A (en) 1994-07-28 1997-04-15 Weier; Richard M. Benzenesulfonamide subtituted imidazolyl compounds for the treatment of inflammation
SK133297A3 (en) * 1995-04-04 1998-07-08 Glaxo Group Ltd Imidazo[1,2-a]pyridine derivatives, pharmaceutical composition containing same and their use
UA57002C2 (uk) * 1995-10-13 2003-06-16 Мерк Фросст Кенада Енд Ко./Мерк Фросст Кенада Енд Сі. Похідне (метилсульфоніл)феніл-2-(5н)-фуранону, фармацевтична композиція та спосіб лікування

Also Published As

Publication number Publication date
US6670365B1 (en) 2003-12-30
ES2182546T3 (es) 2003-03-01
NO20010568D0 (no) 2001-02-02
EA003399B1 (ru) 2003-04-24
NO20010568L (no) 2001-04-02
ATE224391T1 (de) 2002-10-15
CN1131865C (zh) 2003-12-24
IL141242A0 (en) 2002-03-10
KR20010079602A (ko) 2001-08-22
CN1321157A (zh) 2001-11-07
HUP0103004A2 (hu) 2002-01-28
DE69903046D1 (de) 2002-10-24
EP1104762A1 (en) 2001-06-06
EA200100212A1 (ru) 2001-08-27
SK1662001A3 (en) 2001-08-06
ES2140354A1 (es) 2000-02-16
MXPA01001332A (es) 2002-11-29
DE69903046T2 (de) 2003-05-22
CZ291783B6 (cs) 2003-05-14
JP2002522438A (ja) 2002-07-23
DK1104762T3 (da) 2002-10-21
BR9912968A (pt) 2001-05-08
HK1037629A1 (en) 2002-02-15
EP1104762B1 (en) 2002-09-18
HUP0103004A3 (en) 2003-03-28
WO2000008024A1 (es) 2000-02-17
YU7401A (sh) 2003-10-31
OA11592A (en) 2004-07-30
AU749770B2 (en) 2002-07-04
BG105299A (en) 2001-11-30
AU4782499A (en) 2000-02-28
CZ2001433A3 (cs) 2001-08-15
ID28539A (id) 2001-05-31
PL345804A1 (en) 2002-01-02
CA2339187A1 (en) 2000-02-17
PT1104762E (pt) 2002-11-29
ZA200101632B (en) 2001-08-30
TR200100359T2 (tr) 2001-06-21
NZ510196A (en) 2002-09-27
AP2001002082A0 (en) 2001-03-31

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