CA2223574C - Derives de biphenyl-2-acide carboxylique-tetrahydro-isoquinoleine-6-yl amides, preparation de ces amides et utilisation en tant qu'inhibiteurs de la proteine de transfert de triglyceride microsomal et/ou de la secretion d'apolipoproteines b (apo b) - Google Patents

Derives de biphenyl-2-acide carboxylique-tetrahydro-isoquinoleine-6-yl amides, preparation de ces amides et utilisation en tant qu'inhibiteurs de la proteine de transfert de triglyceride microsomal et/ou de la secretion d'apolipoproteines b (apo b) Download PDF

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Publication number
CA2223574C
CA2223574C CA002223574A CA2223574A CA2223574C CA 2223574 C CA2223574 C CA 2223574C CA 002223574 A CA002223574 A CA 002223574A CA 2223574 A CA2223574 A CA 2223574A CA 2223574 C CA2223574 C CA 2223574C
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CA
Canada
Prior art keywords
biphenyl
trifluoromethyl
carboxylic acid
amide
compound
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 - Fee Related
Application number
CA002223574A
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English (en)
Other versions
CA2223574A1 (fr
Inventor
George Chang
Peter H. Dorff
George J. Quallich
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.)
Pfizer Inc
Original Assignee
Pfizer Inc
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 Pfizer Inc filed Critical Pfizer Inc
Priority claimed from PCT/IB1995/000448 external-priority patent/WO1996040640A1/fr
Priority to PCT/IB1995/000448 priority Critical patent/WO1996040640A1/fr
Priority to SK726-96A priority patent/SK283408B6/sk
Priority to EP95918722A priority patent/EP0832069B1/fr
Priority to APAP/P/1996/000804A priority patent/AP9600804A0/en
Priority to IL11848496A priority patent/IL118484A/en
Priority to BR9602628A priority patent/BR9602628A/pt
Priority to PL96314636A priority patent/PL314636A1/xx
Priority to SG1996009974A priority patent/SG44952A1/en
Priority to NZ286733A priority patent/NZ286733A/en
Priority to HRPCT/IB95/00448A priority patent/HRP960270A2/hr
Priority to CZ19961644A priority patent/CZ289249B6/cs
Priority to LVP-96-176A priority patent/LV11615B/en
Priority to SI9600183A priority patent/SI9600183A/sl
Priority to HU9601566A priority patent/HUP9601566A3/hu
Priority to NO962385A priority patent/NO307826B1/no
Priority to CN96108113A priority patent/CN1058709C/zh
Publication of CA2223574A1 publication Critical patent/CA2223574A1/fr
Priority to FI974440A priority patent/FI974440A7/fi
Publication of CA2223574C publication Critical patent/CA2223574C/fr
Application granted granted Critical
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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    • 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
    • C07D401/06—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 carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
    • C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
    • C07D217/06—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
    • 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
    • C07D401/10—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 carbon chain containing aromatic rings
    • 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
    • C07D405/06—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 only aliphatic carbon atoms
    • 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
    • C07D409/06—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 carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—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
    • 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
    • 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
    • C07D417/06—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 carbon chain containing only aliphatic carbon atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Cette invention concerne des composés représentés par la formule (I) ainsi que des sels pharmaceutiquement acceptables de ces composés. Dans la formule (I), X est CH2, CO, CS ou SO2, Y est sélectionné dans le groupe constitué par (a) une liaison directe, (b) des radicaux aliphatiques d'hydrocarbylène ayant jusqu'à 20 atome de carbone, ces radicaux pouvant être mono-substitués par hydroxy, (C1-C10)alkoxy, (C1-C10)acyle, (C1-C10)acyloxy ou (C6-C10)aryle, (c) NH, et O, à condition que lorsque X est CH2, Y soit une liaison directe; Z est sélectionné dans l'ensemble des groupes suivants: (1) H, halo, cyano, (2) hydroxy, (C1-C10)alkoxy, (C1-C10)alkylthio, (C1-C10)acyle, thiophénylcarbonyle, (C1-C10)alkoxycarbonyle, (3) (C1-C10)alkylamino, di(C1-C10)alkylamino, (C6-C10)aryle(C1-C10)alkylamino, à condition que Y ne soit ni O ni NH, (4) vinyle non substitué, (C6-C10)aryle, (C3-C8)cycloalkyle et ses dérivés benzo condensés, (C7-C10)polycycloalkyle, (C4-C8)cycloalkényle, (C7-C10)polycycloalkényle, (5) (C6-C10) aryloxy, (C6-C10)arylthio, (C6-C10)aryle(C1-C10)alkoxy, (C6-C10)aryle(C1-C10)alkylthio, (C3-C8)cycloalkyloxy, (C4-C8)cycloalkényloxy, (6) hétérocyclyle sélectionné dans le groupe constitué de radicaux monocycliques et de radicaux polycycliques condensés, lesdits radicaux contenant un total de 5 à 14 atomes cycliques, lesdits radicaux contenant un total de 1 à 4 hétéroatomes cycliques sélectionnés indépendamment parmi l'oxygène, l'azote et le soufre, et les noyaux individuels desdits radicaux pouvant être indépendamment saturés, partiellement insaturés ou aromatiques, à condition que si X est CH2, alors Z soit H ou soit choisi parmi les groupes (4) et (6), où, lorsque Z contient un ou plusieurs noyaux, lesdits noyaux peuvent porter chacun indépendamment de 0 à 4 substituants sélectionnés indépendamment parmi halo, hydroxy, cyano, nitro, oxo, thioxo, aminosulfonyle, phényle, phénoxy, phénylthio, halophénylthio, benzyle, benzyloxy, (C1-C10)alkyle, (C1-C10)alkoxy, (C1-C10)alkoxycarbonyle, (C1-C10)alkylthio, (C1-C10)alkylamino, (C1-C10)alkylaminocarbonyle, di(C1-C10)alkylamino, di(C1-C10)alkylaminocarbonyle, di(C1-C10)alkylamino(C1-C10)alkoxy, (C1-C3)perfluoroalkyle, (C1-C3)perfluoroalkoxy, (C1-C10)acyle, (C1-C10)acyloxy, (C1-C10)acyloxy(C1-C10)alkyle et pyrrolidinyle. Cette invention se rapporte à des composés qui sont des inhibiteurs de la protéine de transfert de triglycéride microsomal et/ou de la sécrétion d'apolipoprotéines B (Apo B), et qui de ce fait s'avèrent utiles s'agissant de la prévention et du traitement de l'athérosclérose et de ses séquelles cliniques, de la réduction des lipides sériques et du traitement des maladies associées. Cette invention se rapporte en outre à des compositions contenant lesdits composés ainsi qu'à des procédés de traitement, avec ces composés, de l'athérosclérose, de l'obésité, et de maladies et/ou de troubles associés.
CA002223574A 1995-06-07 1995-06-07 Derives de biphenyl-2-acide carboxylique-tetrahydro-isoquinoleine-6-yl amides, preparation de ces amides et utilisation en tant qu'inhibiteurs de la proteine de transfert de triglyceride microsomal et/ou de la secretion d'apolipoproteines b (apo b) Expired - Fee Related CA2223574C (fr)

Priority Applications (17)

Application Number Priority Date Filing Date Title
PCT/IB1995/000448 WO1996040640A1 (fr) 1995-06-07 1995-06-07 DERIVES DE BIPHENYL-2-ACIDE CARBOXYLIQUE-TETRAHYDRO-ISOQUINOLEINE-6-YL AMIDES, PREPARATION DE CES AMIDES ET UTILISATION EN TANT QU'INHIBITEURS DE LA PROTEINE DE TRANSFERT DE TRIGLYCERIDE MICROSOMAL ET/OU DE LA SECRETION D'APOLIPOPROTEINES B (Apo B)
SK726-96A SK283408B6 (sk) 1995-06-07 1995-06-07 Amidy a farmaceutické prostriedky na ich báze
EP95918722A EP0832069B1 (fr) 1995-06-07 1995-06-07 DERIVES DE BIPHENYL-2-ACIDE CARBOXYLIQUE-TETRAHYDRO-ISOQUINOLEINE-6-YL AMIDES, PREPARATION DE CES AMIDES ET UTILISATION EN TANT QU'INHIBITEURS DE LA PROTEINE DE TRANSFERT DE TRIGLYCERIDE MICROSOMAL ET/OU DE LA SECRETION D'APOLIPOPROTEINES B (Apo B)
APAP/P/1996/000804A AP9600804A0 (en) 1995-06-07 1996-05-09 Therapeutic amides.
IL11848496A IL118484A (en) 1995-06-07 1996-05-30 Trifluoromethyl-biphenyl carboxylic acid amides, uses thereof and pharmaceutical compositions containing them
BR9602628A BR9602628A (pt) 1995-06-07 1996-06-04 Composto composição farmacêutica método para o tratamento de uma condição e método para diminuir a secreção de apo b num mamífero
PL96314636A PL314636A1 (en) 1995-06-07 1996-06-05 Therapeutically actin amides
SG1996009974A SG44952A1 (en) 1995-06-07 1996-06-05 Therapeutic amides
NZ286733A NZ286733A (en) 1995-06-07 1996-06-05 6-(4'-trifluoromethylbiphenylcarbonylamino)-2-substituted isoquinoline derivatives; intermediates
CZ19961644A CZ289249B6 (cs) 1995-06-07 1996-06-06 Amidy a farmaceutické prostředky na jejich bázi
HRPCT/IB95/00448A HRP960270A2 (en) 1995-06-07 1996-06-06 Therapeutic amides
LVP-96-176A LV11615B (en) 1995-06-07 1996-06-06 Therapeutic amides
SI9600183A SI9600183A (en) 1995-06-07 1996-06-06 Therapeutic amides
HU9601566A HUP9601566A3 (en) 1995-06-07 1996-06-06 Therapeutic tetrahydro-isoquinolin derivatives, their intermediates and pharmaceutical compositions containing the active component
NO962385A NO307826B1 (no) 1995-06-07 1996-06-06 Terapeutiske amider og farmasøytisk preparat
CN96108113A CN1058709C (zh) 1995-06-07 1996-06-07 治疗用酰胺类化合物
FI974440A FI974440A7 (fi) 1995-06-07 1997-12-05 Bifenyyli-2-karboksyylihappo-tetrahydro-isokinolin-6-yyli-amidijohdannaisia, niiden valmistus ja niiden käyttö mikrosomaalistatriglyseridiä siirtävän proteiinin ja/tai apolipoproteiini B:n (Apo B) erittymiseen inhibiittoreina

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
PCT/IB1995/000448 WO1996040640A1 (fr) 1995-06-07 1995-06-07 DERIVES DE BIPHENYL-2-ACIDE CARBOXYLIQUE-TETRAHYDRO-ISOQUINOLEINE-6-YL AMIDES, PREPARATION DE CES AMIDES ET UTILISATION EN TANT QU'INHIBITEURS DE LA PROTEINE DE TRANSFERT DE TRIGLYCERIDE MICROSOMAL ET/OU DE LA SECRETION D'APOLIPOPROTEINES B (Apo B)
HU9601566A HUP9601566A3 (en) 1995-06-07 1996-06-06 Therapeutic tetrahydro-isoquinolin derivatives, their intermediates and pharmaceutical compositions containing the active component

Publications (2)

Publication Number Publication Date
CA2223574A1 CA2223574A1 (fr) 1996-12-19
CA2223574C true CA2223574C (fr) 2002-04-02

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Family Applications (1)

Application Number Title Priority Date Filing Date
CA002223574A Expired - Fee Related CA2223574C (fr) 1995-06-07 1995-06-07 Derives de biphenyl-2-acide carboxylique-tetrahydro-isoquinoleine-6-yl amides, preparation de ces amides et utilisation en tant qu'inhibiteurs de la proteine de transfert de triglyceride microsomal et/ou de la secretion d'apolipoproteines b (apo b)

Country Status (1)

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CA (1) CA2223574C (fr)

Also Published As

Publication number Publication date
CA2223574A1 (fr) 1996-12-19

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