CA2223574A1 - Biphenyl-2-carboxylic acid-tetrahydro-isoquinolin-6-yl amide derivatives, their preparation and their use as inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein b (apo b) secretion - Google Patents

Biphenyl-2-carboxylic acid-tetrahydro-isoquinolin-6-yl amide derivatives, their preparation and their use as inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein b (apo b) secretion

Info

Publication number
CA2223574A1
CA2223574A1 CA002223574A CA2223574A CA2223574A1 CA 2223574 A1 CA2223574 A1 CA 2223574A1 CA 002223574 A CA002223574 A CA 002223574A CA 2223574 A CA2223574 A CA 2223574A CA 2223574 A1 CA2223574 A1 CA 2223574A1
Authority
CA
Canada
Prior art keywords
alkylamino
alkoxy
aryl
radicals
compounds
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.)
Granted
Application number
CA002223574A
Other languages
French (fr)
Other versions
CA2223574C (en
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.
George Chang
Peter H. Dorff
George J. Quallich
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., George Chang, Peter H. Dorff, George J. Quallich filed Critical Pfizer Inc.
Priority claimed from PCT/IB1995/000448 external-priority patent/WO1996040640A1/en
Priority to PCT/IB1995/000448 priority Critical patent/WO1996040640A1/en
Priority to SK726-96A priority patent/SK283408B6/en
Priority to EP95918722A priority patent/EP0832069B1/en
Priority to APAP/P/1996/000804A priority patent/AP9600804A0/en
Priority to IL11848496A priority patent/IL118484A/en
Priority to BR9602628A priority patent/BR9602628A/en
Priority to PL96314636A priority patent/PL314636A1/en
Priority to SG1996009974A priority patent/SG44952A1/en
Priority to NZ286733A priority patent/NZ286733A/en
Priority to CZ19961644A priority patent/CZ289249B6/en
Priority to SI9600183A priority patent/SI9600183A/en
Priority to HRPCT/IB95/00448A priority patent/HRP960270A2/en
Priority to NO962385A priority patent/NO307826B1/en
Priority to HU9601566A priority patent/HUP9601566A3/en
Priority to LVP-96-176A priority patent/LV11615B/en
Priority to CN96108113A priority patent/CN1058709C/en
Publication of CA2223574A1 publication Critical patent/CA2223574A1/en
Priority to FI974440A priority patent/FI974440A/en
Publication of CA2223574C publication Critical patent/CA2223574C/en
Application granted granted Critical
Anticipated expiration legal-status Critical
Expired - Fee Related 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
    • C07D401/06—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

Abstract

Compounds of formula (I), wherein X is CH2, CO, CS or SO2;
Y is selected from: a direct link, aliphatic hydrocarbylene radicals having up to 20 carbon atoms, which radical may be mono-substituted by hydroxy, (C1-C10)alkoxy, (C1-C10)acyl, (C1-C10)acyloxy, or (C6-C10)aryl, NH, and O, provided that if X is CH2, Y
is a direct link; Z is selected from the following groups: (1) H, halo, cyano, (2) hydroxy, (C1-C10)alkoxy, (C1-C10)alkylthio, (C1-C10)acyl, thiophenylcarbonyl, (C1-C10)alkoxycarbonyl, (3) (C1-C10)alkylamino, di(C1-C10)alkylamino, (C6-C10)aryl(C1-C10)alkylamino, provided that Y is not O
or NH, (4) unsubstituted vinyl, (C6-C10)aryl, (C3-C8)cycloalkyl and fused bent derivatives thereof, (C7-C10)polycycloalkyl, (C4-C8)cycloalkenyl, (C7-C10)polycycloalkenyl, (5) (C6-C10)aryloxy, (C6-C10)arylthio, (C6-C10)aryl(C1-C10)alkoxy, (C6-C10)aryl(C1-C10)alkylthio, (C3-C8)cycloalkyloxy, (C4-C8)cycloalkenyloxy, (6) heterocyclyl selected from the group consisting of monocyclic radicals and fused polycyclic radicals, wherein said radicals contain a total of from 5 to 14 ring atoms, wherein said radicals contain a total of from 1 to 4 ring heteroatoms independently selected from oxygen, nitrogen, and sulfur, and wherein the individual rings of said radicals may be independently saturated, partially unsaturated, or aromatic, provided that if X is CH2, Z is H or is selected from groups (4) and (6), wherein, when Z contains one or more rings, said rings may each independently bear 0 to 4 substituents independently selected from halo, hydroxy, cyano, nitro, oxo, thioxo, aminosulfonyl, phenyl, phenoxy, phenylthio, halophenylthio, benzyl, benzyloxy, (C1-C10)alkyl, (C1-C10)alkoxy, (C1-C10)alkoxycarbonyl, (C1-C10)alkylthio, (C1-C10)alkylamino, (C1-C10)alkylaminocarbonyl, di(C1-C10)alkylamino, di(C1-C10)alkylaminocarbonyl, di(C1-C10)alkylamino(C1-C10)alkoxy, (C1-C3)perfluoroalkyl, (C1-C3)perfluoroalkoxy, (C1-C10)acyl, (C1-C10)acyloxy, (C1-C10)acyloxy(C1-C10)alkyl, and pyrrolidinyl; and pharmaceutically acceptable salts thereof. This invention relates to compounds which are inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein B (Apo B) secretion, and which are accordingly useful for the prevention and treatment of atherosclerosis and its clinical sequelae, for lowering serum lipids, and related diseases.
The invention further relates to compositions comprising the compounds and to methods of treating atherosclerosis, obesity, and related diseases and/or conditions with the compounds.
CA002223574A 1995-06-07 1995-06-07 Biphenyl-2-carboxylic acid-tetrahydro-isoquinolin-6-yl amide derivatives, their preparation and their use as inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein b (apo b) secretion Expired - Fee Related CA2223574C (en)

Priority Applications (17)

Application Number Priority Date Filing Date Title
PCT/IB1995/000448 WO1996040640A1 (en) 1995-06-07 1995-06-07 BIPHENYL-2-CARBOXYLIC ACID-TETRAHYDRO-ISOQUINOLIN-6-YL AMIDE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS INHIBITORS OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN AND/OR APOLIPOPROTEIN B (Apo B) SECRETION
SK726-96A SK283408B6 (en) 1995-06-07 1995-06-07 Amides and pharmaceutical preparations based on them
EP95918722A EP0832069B1 (en) 1995-06-07 1995-06-07 BIPHENYL-2-CARBOXYLIC ACID-TETRAHYDRO-ISOQUINOLIN-6-YL AMIDE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS INHIBITORS OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN AND/OR APOLIPOPROTEIN B (Apo B) SECRETION
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 (en) 1995-06-07 1996-06-04 Compound pharmaceutical composition method for treating a condition and method for decreasing apo b secretion in a mammal
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
SI9600183A SI9600183A (en) 1995-06-07 1996-06-06 Therapeutic amides
CZ19961644A CZ289249B6 (en) 1995-06-07 1996-06-06 Amides and pharmaceutical compositions based thereon
HRPCT/IB95/00448A HRP960270A2 (en) 1995-06-07 1996-06-06 Therapeutic amides
NO962385A NO307826B1 (en) 1995-06-07 1996-06-06 Therapeutic amides and pharmaceuticals
HU9601566A HUP9601566A3 (en) 1995-06-07 1996-06-06 Therapeutic tetrahydro-isoquinolin derivatives, their intermediates and pharmaceutical compositions containing the active component
LVP-96-176A LV11615B (en) 1995-06-07 1996-06-06 Therapeutic amides
CN96108113A CN1058709C (en) 1995-06-07 1996-06-07 Amide compounds for medical treatment
FI974440A FI974440A (en) 1995-06-07 1997-12-05 Biphenyl-2-carboxylic acid-tetrahydro-isoquinolin-6-yl-amide derivatives, their preparation and their use as inhibitors of microsomal statiglyceride transfer protein and / or apolipoprotein B (Apo B)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
PCT/IB1995/000448 WO1996040640A1 (en) 1995-06-07 1995-06-07 BIPHENYL-2-CARBOXYLIC ACID-TETRAHYDRO-ISOQUINOLIN-6-YL AMIDE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS INHIBITORS OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN AND/OR APOLIPOPROTEIN B (Apo B) SECRETION
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 true CA2223574A1 (en) 1996-12-19
CA2223574C CA2223574C (en) 2002-04-02

Family

ID=89994038

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002223574A Expired - Fee Related CA2223574C (en) 1995-06-07 1995-06-07 Biphenyl-2-carboxylic acid-tetrahydro-isoquinolin-6-yl amide derivatives, their preparation and their use as inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein b (apo b) secretion

Country Status (1)

Country Link
CA (1) CA2223574C (en)

Also Published As

Publication number Publication date
CA2223574C (en) 2002-04-02

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