CA2191455A1 - Composes d'azetidinone substitues utilises comme agent hypercholesterolemiant - Google Patents

Composes d'azetidinone substitues utilises comme agent hypercholesterolemiant

Info

Publication number
CA2191455A1
CA2191455A1 CA002191455A CA2191455A CA2191455A1 CA 2191455 A1 CA2191455 A1 CA 2191455A1 CA 002191455 A CA002191455 A CA 002191455A CA 2191455 A CA2191455 A CA 2191455A CA 2191455 A1 CA2191455 A1 CA 2191455A1
Authority
CA
Canada
Prior art keywords
phenyl
oxo
aryl
trans
lower alkyl
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.)
Abandoned
Application number
CA002191455A
Other languages
English (en)
Inventor
Wayne Vaccaro
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.)
Merck Sharp and Dohme Corp
Original Assignee
Individual
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
Application filed by Individual filed Critical Individual
Publication of CA2191455A1 publication Critical patent/CA2191455A1/fr
Abandoned legal-status Critical Current

Links

Classifications

    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • 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
    • 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
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D405/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D405/10—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 carbon chain containing aromatic rings
    • 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
    • C07D409/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804—Compounds having Si-O-C linkages

Abstract

Agent hypercholestérolémiant d'azétidinone substitué de formule (I) ou d'un sel pharmaceutiquement acceptable où : Ar?1¿ représente aryle ou R?3¿-aryle; Ar?2¿ représente aryl ou R?4¿-aryle; R?1¿ est sélectionné dans le groupe composé de -(CH¿2?)¿q?-, où q est compris entre 2-6; -(CH¿2?)¿e?-Z-(CH¿2?)¿r?-, où Z représente -O-, -C(O)-, phénylène, -NR?10¿- ou -S(O)¿0-2?-, e est compris entre 0-5 et r est compris entre 0-5, à condition que la somme de e et de r soit comprise entre 1-6; -(C¿2?-C¿6? alcénylène)-; et -(CH¿2?)¿f?-V-(CH¿2?)¿g?-, où V représente C¿3?-C¿6? cycloalkylène, f est compris entre 1-5 et g est compris entre 0-5, à condition que la somme de f et g soit comprise entre 1-6; R?2¿ représente -(alkylène inférieur)-COR?5¿ ou -(CH=CH)-COR?5¿; R?3¿ et R?4¿ représentent séparément des substituants en position 1-3 sélectionnés à partir d'alkyle inférieur, -OR?6¿, -O(CO)R?6¿, -O(CO)OR?9¿, -O(CH¿2?)¿1-5?OR?6¿, -O(CO)NR?6¿R?7¿, -NR?6¿R?7¿, -NR?6¿(CO)R?7¿, -NR?6¿(CO)OR?9¿, -NR?6¿(CO)NR?7¿R?8¿, -NR?6¿SO¿2?R?9¿, -COOR?6¿, -CONR?6¿R?7¿, -COR?6¿, -SO¿2?NR?6¿R?7¿, S(O)¿0-2?R?9¿, -O(CH¿2?)¿1-10?-COOR?6¿, -O(CH¿2?)¿1-10?CONR?6¿R?7¿, -(alkylène inférieur)-COOR?6¿, -CH=CH-COOR?6¿, -CF¿3?, -CN, -NO¿2? et halogène; R?5¿ représente -OR ou -NRR?12¿; R, R?6¿, R?7¿, R?8¿ et R?12¿ sont sélectionnés séparément à partir d'hydrogène, alkyle inférieur, et alkyle inférieur à substitution aryle; R?9¿ représente alkyle inférieur, ou alkyle inférieur à substitution aryle; et R?10¿ représente alkyle inférieur, alkyle inférieur aryle ou -C(O)R?6¿; l'invention concerne également une méthode permettant d'abaisser le taux de cholestérol sérique en appliquant un composé, seul ou en combinaison avec un inhibiteur de biosynthèse du cholestérol, ainsi que les compositions pharmaceutiques les contenant.
CA002191455A 1994-06-20 1995-06-15 Composes d'azetidinone substitues utilises comme agent hypercholesterolemiant Abandoned CA2191455A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US26178594A 1994-06-20 1994-06-20
US08/261,785 1994-06-20

Publications (1)

Publication Number Publication Date
CA2191455A1 true CA2191455A1 (fr) 1995-12-28

Family

ID=22994864

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002191455A Abandoned CA2191455A1 (fr) 1994-06-20 1995-06-15 Composes d'azetidinone substitues utilises comme agent hypercholesterolemiant

Country Status (6)

Country Link
EP (1) EP0766667A1 (fr)
JP (1) JPH10501811A (fr)
AU (1) AU2943095A (fr)
CA (1) CA2191455A1 (fr)
MX (1) MX9606319A (fr)
WO (1) WO1995035277A1 (fr)

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5633246A (en) * 1994-11-18 1997-05-27 Schering Corporation Sulfur-substituted azetidinone compounds useful as hypocholesterolemic agents
IL156552A0 (en) 2000-12-21 2004-01-04 Aventis Pharma Gmbh Diphenyl azetidinone derivatives, method for the production thereof, medicaments containing these compounds, and their use
CZ20031733A3 (cs) 2000-12-21 2003-09-17 Aventis Pharma Deutschland Gmbh Difenylazetidinonové deriváty a farmaceutické prostředky s jejich obsahem
WO2002058685A2 (fr) * 2001-01-26 2002-08-01 Schering Corporation Combinaisons d'acide nicotinique et de derives de ce dernier, inhibiteur(s) d'absorption de sterols et traitements de conditions vasculaires
AU2007201970B2 (en) * 2001-01-26 2008-04-17 Organon Llc Combinations of peroxisome proliferator-activated receptor (PPAR) activator(s) and sterol absorption inhibitor(s) and treatments for vascular indications
SI1385548T1 (sl) * 2001-01-26 2007-10-31 Schering Corp Kombinacije zaviralca(-ev) absorpcije sterola s kardiovaskularnim(-i) sredstvom(-i) za zdravljenje vaskularnih obolenj
AU2006203175B2 (en) * 2001-01-26 2008-07-24 Organon Llc Combinations of peroxisome proliferator-activated receptor (PPAR) activators(s) and sterol absorption inhibitors(s) and treatments for vascular indications
AU2006202618B2 (en) * 2001-01-26 2007-04-19 Organon Llc Combinations of peroxisome proliferator-activated receptor (PPAR) activator(s) and sterol absorption inhibitor(s) and treatments for vascular indications
EP1864680A3 (fr) * 2001-01-26 2012-03-28 Schering Corporation Combinaisons d'activateur(s) du récepteur activé de la prolifération des peroxysomes (PPAR) et inhibiteur(s) d'absorption de stérol, et traitements pour les indications vasculaires
EP1353694B1 (fr) * 2001-01-26 2007-12-19 Schering Corporation Combinaisons du ezetimibe et de l'aspirine pour le traitement des troubles vasculaires
EP1911462A3 (fr) * 2001-01-26 2011-11-30 Schering Corporation Combinaisons comprenant un inhibiteur d'absorption de stérol
EP1785144A3 (fr) * 2001-01-26 2007-05-23 Shering Corporation Combinaisons de séquestrant(s) d'acides biliaires, et inhibiteur(s) d'absorption de stérol, et traitements pour les indications vasculaires
CN101297969B (zh) * 2001-01-26 2011-03-09 先灵公司 过氧化物酶体增殖物激活受体(ppar)活化剂和甾醇吸收抑制剂的组合药
AU2008201609B8 (en) * 2001-01-26 2009-01-08 Organon Llc Combinations of peroxisome proliferator-activated receptor (ppar) activator(s) and sterol absorption inhibitors(s) and treatments for vascular indications
ATE374641T1 (de) * 2001-01-26 2007-10-15 Schering Corp Kombinationen vom ppar-aktivator fenofibrat mit dem hemmer der sterol-absorption ezetimibe zur behandlung von kardiovaskulären indikationen
GB0215579D0 (en) 2002-07-05 2002-08-14 Astrazeneca Ab Chemical compounds
AR040588A1 (es) 2002-07-26 2005-04-13 Schering Corp Formulacion farmaceutica que comprende un inhibidor de la absorcion del colesterol y un inhibidor de una hmg- co a reductasa
US7871998B2 (en) 2003-12-23 2011-01-18 Astrazeneca Ab Diphenylazetidinone derivatives possessing cholesterol absorption inhibitory activity
SA06270191B1 (ar) 2005-06-22 2010-03-29 استرازينيكا ايه بي مشتقات من 2- أزيتيدينون جديدة باعتبارها مثبطات لامتصاص الكوليسترول لعلاج حالات فرط نسبة الدهون في الدم
TW200806623A (en) * 2005-10-05 2008-02-01 Merck & Co Inc Anti-hypercholesterolemic compounds
AR060623A1 (es) 2006-04-27 2008-07-02 Astrazeneca Ab Compuestos derivados de 2-azetidinona y un metodo de preparacion
JPWO2008108486A1 (ja) 2007-03-06 2010-06-17 帝人ファーマ株式会社 １−ビアリールアゼチジノン誘導体
CA2708159C (fr) 2007-12-10 2016-01-26 Ratiopharm Gmbh Formulation pharmaceutique comprenant de l'ezetimibe
EP2403848A1 (fr) 2009-03-06 2012-01-11 Lipideon Biotechnology AG Compositions pharmaceutiques hypocholestérolémiques
CN101993403B (zh) 2009-08-11 2012-07-11 浙江海正药业股份有限公司 氮杂环丁酮类化合物及医药应用
WO2015092448A1 (fr) * 2013-12-18 2015-06-25 Rudjer Boskovic Institute Inhibiteurs de l'absorption du cholestérol de type bêta-lactamines

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0524595A1 (fr) * 1991-07-23 1993-01-27 Schering Corporation Dérivés de bêta-lactame substitués comme agents hypocholestérolémiques et leurs procédés de préparation
US5631365A (en) * 1993-09-21 1997-05-20 Schering Corporation Hydroxy-substituted azetidinone compounds useful as hypocholesterolemic agents

Also Published As

Publication number Publication date
AU2943095A (en) 1996-01-15
EP0766667A1 (fr) 1997-04-09
WO1995035277A1 (fr) 1995-12-28
JPH10501811A (ja) 1998-02-17
MX9606319A (es) 1997-05-31

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Legal Events

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