PE8998A1 - NEW Lp-PLA2 INHIBITOR COMPOUNDS - Google Patents

NEW Lp-PLA2 INHIBITOR COMPOUNDS

Info

Publication number
PE8998A1
PE8998A1 PE1996000496A PE00049696A PE8998A1 PE 8998 A1 PE8998 A1 PE 8998A1 PE 1996000496 A PE1996000496 A PE 1996000496A PE 00049696 A PE00049696 A PE 00049696A PE 8998 A1 PE8998 A1 PE 8998A1
Authority
PE
Peru
Prior art keywords
new
bencilsulfinilo
acetidone
conr6
aryl
Prior art date
Application number
PE1996000496A
Other languages
Spanish (es)
Inventor
Dashyant Dhanak
Robert John Ife
Deirdre Mary Bernadette Hickey
Colin Andrew Leach
David Graham Tew
Original Assignee
Smithkline Beecham Plc
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 claimed from GBGB9513442.5A external-priority patent/GB9513442D0/en
Priority claimed from GBGB9515056.1A external-priority patent/GB9515056D0/en
Priority claimed from GBGB9515206.2A external-priority patent/GB9515206D0/en
Priority claimed from GBGB9516985.0A external-priority patent/GB9516985D0/en
Priority claimed from GBGB9525132.8A external-priority patent/GB9525132D0/en
Priority claimed from GBGB9608650.9A external-priority patent/GB9608650D0/en
Priority claimed from GBGB9608651.7A external-priority patent/GB9608651D0/en
Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc
Publication of PE8998A1 publication Critical patent/PE8998A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
    • C07D205/085—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a nitrogen atom directly attached in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
    • C07D205/09—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a sulfur atom directly attached in position 4
    • C07D205/095—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a sulfur atom directly attached in position 4 and with a nitrogen atom directly attached in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Abstract

SE REFIERE A COMPUESTOS DE FORMULA (I), EN DONDE: R1 Y R2 SON PREFERENTEMENTE H; R4 Y R5 SON PREFERENTEMENTE H o METILO; "X" ES UN GRUPO ENLAZANTE, TAL COMO: CONH(CH2)6, CONR6(CH2)4C�C o (CH2)-O-(CH2)6; R6 ES H o ALQUILO C1-C6; "Y" ES 4-F o 4-Cl FENIL; "Z" ES O o S(O)n, EN DONDE n ES 0; 1 o 2; R3 ES ARIL O ARIL-ALQUIL(C1-C4), TAL COMO: 5-CARBOXIFURAN-2-METILSULFINILO, 4-CARBOXI-BENCILSULFINILO o BENCILSULFINILO. TAMBIEN SE REFIERE AL PROCEDIMIENTO DE PREPARACION DE (I), EN DONDE: a) PARA QUE "Z" SEA S, COMPRENDE: HACER REACCIONAR ACETIDONA (SUSTITUIDO EN LA POSICION 4 DE SAG) CON R3Z; b) PARA QUE "X" SEA CONR6(CH2)m o CONR6O(CH2)m, ENTRE OTROS (m ES 0; 1; 2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 12), COMPRENDE: HACER REACCIONAR ACETIDONA (SUSTITUIDO EN LA POSICION 1 DE CR4R5-COOH) CON NH-R6-X5-Y o NH2-0-X5-Y, EN DONDE X5 ES (CH2)m o ALQUILENO C1-C12, EN PRESENCIA DE UN AGENTE ACTIVADOR, A UNA TEMPERATURA DE -10�C A 20�C. SON INHIBIDORES DE LA FOSFOLIPASA A2 ASOCIADA A LIPOPROTEINAS (ENZIMA INHIBIDORA DE LA FORMACION DE LISOFOSFATIDILCOLINA Y ACIDOS GRASOS LIBRES OXIDADOS), UTILES EN CUALQUIER TRANSTORNO QUE IMPLIQUE PEROXIDACION DE LIPIDOS, TAL COMO EN EL TRATAMIENTO DE LA ATEROSCLEROSISIT REFERS TO COMPOUNDS OF FORMULA (I), WHERE: R1 AND R2 ARE PREFERABLY H; R4 AND R5 ARE PREFERABLY H or METHYL; "X" IS A LINKING GROUP, SUCH AS: CONH (CH2) 6, CONR6 (CH2) 4C�C or (CH2) -O- (CH2) 6; R6 IS H or C1-C6 ALKYL; "Y" IS 4-F or 4-Cl FENIL; "Z" IS O or S (O) n, WHERE n IS 0; 1 or 2; R3 IS ARYL OR ARYL-ALKYL (C1-C4), SUCH AS: 5-CARBOXIFURAN-2-METILSULFINILO, 4-CARBOXI-BENCILSULFINILO or BENCILSULFINILO. IT ALSO REFERS TO THE PREPARATION PROCEDURE FOR (I), WHERE: a) SO THAT "Z" IS S, IT INCLUDES: REACTION ACETIDONE (REPLACED IN POSITION 4 OF SAG) WITH R3Z; b) SO THAT "X" IS CONR6 (CH2) m or CONR6O (CH2) m, AMONG OTHERS (m IS 0; 1; 2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 12) , UNDERSTANDS: REACTION ACETIDONE (REPLACED IN POSITION 1 OF CR4R5-COOH) WITH NH-R6-X5-Y or NH2-0-X5-Y, WHERE X5 IS (CH2) m or ALKYLENE C1-C12, IN THE PRESENCE OF AN ACTIVATING AGENT, AT A TEMPERATURE OF -10�C to 20�C. THEY ARE INHIBITORS OF LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 (ENZYME INHIBITOR OF THE FORMATION OF FREE LYSOPHOSPHATYLCHOLINE AND FATTY AXIDES), USEFUL IN ANY DISORDERS THAT INVOLVE PERIPOID OF LIPOPROTEINS

PE1996000496A 1995-07-01 1996-06-28 NEW Lp-PLA2 INHIBITOR COMPOUNDS PE8998A1 (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
GBGB9513442.5A GB9513442D0 (en) 1995-07-01 1995-07-01 Novel compounds
GBGB9515056.1A GB9515056D0 (en) 1995-07-22 1995-07-22 Novel compounds
GBGB9515206.2A GB9515206D0 (en) 1995-07-25 1995-07-25 Novel compounds
GBGB9516985.0A GB9516985D0 (en) 1995-08-18 1995-08-18 Novel compounds
GBGB9525132.8A GB9525132D0 (en) 1995-12-08 1995-12-08 Novel compounds
GBGB9608650.9A GB9608650D0 (en) 1996-04-26 1996-04-26 Novel compounds
GBGB9608651.7A GB9608651D0 (en) 1996-04-26 1996-04-26 Novel compounds

Publications (1)

Publication Number Publication Date
PE8998A1 true PE8998A1 (en) 1998-03-20

Family

ID=27562921

Family Applications (1)

Application Number Title Priority Date Filing Date
PE1996000496A PE8998A1 (en) 1995-07-01 1996-06-28 NEW Lp-PLA2 INHIBITOR COMPOUNDS

Country Status (23)

Country Link
EP (1) EP0840725A1 (en)
JP (1) JP2002515852A (en)
KR (1) KR19990028630A (en)
CN (1) CN1197452A (en)
AP (1) AP728A (en)
AU (1) AU708032B2 (en)
BG (1) BG102214A (en)
BR (1) BR9609445A (en)
CA (1) CA2225627A1 (en)
CZ (1) CZ422197A3 (en)
EA (1) EA199800109A1 (en)
HU (1) HUP9901153A3 (en)
IL (1) IL122650A0 (en)
MA (1) MA23922A1 (en)
MX (1) MX9800186A (en)
NO (1) NO976158L (en)
NZ (1) NZ311684A (en)
OA (1) OA10648A (en)
PE (1) PE8998A1 (en)
PL (1) PL324240A1 (en)
SK (1) SK178497A3 (en)
TR (1) TR199701762T1 (en)
WO (1) WO1997002242A1 (en)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000502079A (en) * 1995-12-08 2000-02-22 スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー Monocyclic .BETA.-lactam derivatives for the treatment of atherosclerosis
GB9608649D0 (en) * 1996-04-26 1996-07-03 Smithkline Beecham Plc Novel compounds
EP0915843A1 (en) * 1996-04-26 1999-05-19 Smithkline Beecham Plc Azetidinone derivatives for the treatment of atheroscleroses
DE60139429D1 (en) * 2000-02-16 2009-09-10 Smithkline Beecham Plc Pyrimidine-5-onderivatives as LDL-PLA2 inhibitors
GB0024808D0 (en) 2000-10-10 2000-11-22 Smithkline Beecham Plc Novel compounds
US8962633B2 (en) 2007-05-11 2015-02-24 Thomas Jefferson University Methods of treatment and prevention of metabolic bone diseases and disorders
CN101687009A (en) 2007-05-11 2010-03-31 宾夕法尼亚大学理事会 Methods of treatment of skin ulcers
EA200971050A1 (en) 2007-05-11 2010-06-30 Томас Джефферсон Юниверсити METHODS OF TREATMENT AND PREVENTION OF NEURODEGENERATIVE DISEASES AND DISORDERS
TW201307324A (en) 2010-12-06 2013-02-16 Glaxo Group Ltd Compounds
EP2651403B1 (en) 2010-12-17 2020-12-02 Glaxo Group Limited Use of lp-pla2 inhibitors in the treatment and prevention of eye diseases
EP2725024A4 (en) 2011-06-27 2014-12-03 Shanghai Inst Materia Medica Azole heterocyclic compound, preparation method, pharmaceutical composition and use
BR112014001665A2 (en) 2011-07-27 2017-02-14 Glaxo Group Ltd 2,3-dihydroimidazo [1,2-c] pyrimidin-5 (1h) -one compounds used as lp-plaz inhibitors
TW201321382A (en) 2011-07-27 2013-06-01 Glaxo Group Ltd Compounds
CA2899143A1 (en) 2013-01-25 2014-07-31 Glaxosmithkline Intellectual Property Development Limited Bicyclic pyrimidone compounds as inhibitors of lp-pla2
WO2014114248A1 (en) 2013-01-25 2014-07-31 Glaxosmithkline Intellectual Property Development Limited Compounds
EP2948452B1 (en) 2013-01-25 2017-08-09 GlaxoSmithKline Intellectual Property Development Limited 2,3-dihydroimidazol[1,2-c]pyrimidin-5(1h)-one based lipoprotein-associated phospholipase a2 (lp-pla2) inhibitors
WO2016012917A1 (en) 2014-07-22 2016-01-28 Glaxosmithkline Intellectual Property Development Limited 1,2,3,5-tetrahydroimidazo[1,2-c]pyrimidine derivatives useful in the treatment of diseases and disorders mediated by lp-pla2
WO2016012916A1 (en) 2014-07-22 2016-01-28 Glaxosmithkline Intellectual Property Development Limited 1,2,3,5-tetrahydroimidazo[1,2-c]pyrimidine derivatives useful in the treatment of diseases and disorders mediated by lp-pla2
CN112778331B (en) 2019-11-09 2022-07-05 上海赛默罗生物科技有限公司 Tricyclic dihydroimidazopyrimidinone derivatives, preparation method, pharmaceutical composition and application thereof
CN115304620A (en) 2021-05-07 2022-11-08 上海赛默罗生物科技有限公司 Pyrimidone derivatives, preparation method, pharmaceutical composition and application thereof

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4680391A (en) * 1983-12-01 1987-07-14 Merck & Co., Inc. Substituted azetidinones as anti-inflammatory and antidegenerative agents
NZ228600A (en) * 1988-04-11 1992-02-25 Merck & Co Inc 1-(benzylaminocarbonyl)-4-phenoxy-azetidin-2-one derivatives
IL99658A0 (en) * 1990-10-15 1992-08-18 Merck & Co Inc Substituted azetidinones and pharmaceutical compositions containing them
GB9421816D0 (en) * 1994-10-29 1994-12-14 Smithkline Beecham Plc Novel compounds
SK80397A3 (en) * 1994-12-22 1998-01-14 Smithkline Beecham Plc Substituted azetidin-2-ones, preparation method thereof, farmaceutical compositions and their use

Also Published As

Publication number Publication date
AP9701161A0 (en) 1998-01-31
MX9800186A (en) 1998-07-31
EA199800109A1 (en) 1998-10-29
BG102214A (en) 1998-08-31
HUP9901153A3 (en) 1999-11-29
IL122650A0 (en) 1998-08-16
CN1197452A (en) 1998-10-28
SK178497A3 (en) 1998-07-08
NZ311684A (en) 2000-04-28
EP0840725A1 (en) 1998-05-13
WO1997002242A1 (en) 1997-01-23
TR199701762T1 (en) 1998-05-21
CZ422197A3 (en) 1998-06-17
AU708032B2 (en) 1999-07-29
NO976158L (en) 1998-02-25
OA10648A (en) 2002-09-25
JP2002515852A (en) 2002-05-28
KR19990028630A (en) 1999-04-15
BR9609445A (en) 1999-04-06
NO976158D0 (en) 1997-12-30
PL324240A1 (en) 1998-05-11
AP728A (en) 1999-01-29
HUP9901153A2 (en) 1999-08-30
AU6305096A (en) 1997-02-05
CA2225627A1 (en) 1997-01-23
MA23922A1 (en) 1996-12-31

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Legal Events

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FA Abandonment or withdrawal