AP804A - APO-B-secretion/MTP inhibitory amides. - Google Patents

APO-B-secretion/MTP inhibitory amides. Download PDF

Info

Publication number
AP804A
AP804A APAP/P/1997/001145A AP9701145A AP804A AP 804 A AP804 A AP 804A AP 9701145 A AP9701145 A AP 9701145A AP 804 A AP804 A AP 804A
Authority
AP
ARIPO
Prior art keywords
inhibitors
compounds
crc10
alkyl
crc4
Prior art date
Application number
APAP/P/1997/001145A
Other versions
AP9701145A0 (en
Inventor
George Chang
George J Quallich
Original Assignee
Pfizer
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 filed Critical Pfizer
Publication of AP9701145A0 publication Critical patent/AP9701145A0/en
Application granted granted Critical
Publication of AP804A publication Critical patent/AP804A/en

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
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • 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
    • 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
    • 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
    • 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
    • C07D405/06—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
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Diabetes (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Indole Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

This invention is directed to compounds of the formula or the stereoisomers, pharmaceutically-acceptable salts and hydrates thereof. The compounds are Apo B/MTP inhibitors and are useful in the treatment of various disorders and conditions such as atherosclerosis, pancreatitis, obesity, hypercholesteremia, hypertriglyceridemia, hyperlipidemia, and diabetes. The compounds of this invention are also useful in combination with other pharmaceutical agents including cholesterol biosynthesis inhibitors and cholesterol absorption inhibitors, especially HMG-CoA reductase inhibitors and HMG-CoA synthase inhibitors; HMG-CoA reductase gene expression inhibitors; CETP inhibitors; bile acid sequestrants; fibrates; cholesterol absorption inhibitors; ACAT inhibitors, squalene synthetase inhibitors, ion-exchange resins, anti-oxidants and niacin. This invention is also directed to intermediates and processes useful in the preparation of compounds of formula (I).

Description

Apo B-SECRETION/MTP INHIBITORY AMIDES
Field Of The Invention
This invention relates to compounds which are inhibitors of microsomal triglyceride transfer protein (MTP) 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 in the prevention and treatment of related diseases. The invention further relates to pharmaceutical compositions comprising these compounds and to methods of treating atherosclerosis, obesity, and related diseases and/or conditions with said compounds, either alone or in combination with other medicaments, including lipid lowering agents. Further still, the invention relates to certain processes and intermediates related thereto which are useful in the preparation of the compounds of the instant invention.
Background Of The Invention
Microsomal triglyceride transfer protein catalyzes the transport of triglyceride, cholesteryl ester, and phospholipids and has been implicated as a putative mediator in the assembly of Apo B-containing lipoproteins, biomolecules which contribute to the formation of atherosclerotic lesions. Specifically, the subcellular (lumen of the microsomal fraction) and tissue distribution (liver and intestine) of MTP have led to speculation that it plays a role in the assembly of plasma lipoproteins, as these are the sites of plasma lipoprotein assembly. The ability of MTP to catalyze the transport of triglyceride between membranes is consistent with this speculation, and suggests that MTP may catalyze the transport of triglyceride from its site of synthesis in the endoplasmic reticulum membrane to nascent lipoprotein particles within the lumen of the endoplasmic reticulum.
Compounds which inhibit MTP and/or otherwise inhibit Apo B secretion are accordingly useful in the treatment of atherosclerosis and other conditions related thereto. Such compounds are also useful in the treatment of other diseases or conditions in which, by inhibiting MTP and/or Apo B secretion, serum cholesterol and triglyceride levels may be reduced. Such conditions may include, for example, hypercholesterolemia, hypertriglyceridemia, pancreatitis, and obesity; and hypercholesterolemia, hypertriglyceridemia, and hyperlipidemia associated with pancreatitis, obesity, and diabetes. For a detailed discussion, see for example, Wetterau et al„ Science, 258, 999-1001, (1992), Wetterau et al., Biochem. Biophys. Acta., 875, 610-617 (1986), European patent application publication No. 0 584 446 A2, and European patent application publication No. 0 643 057 A1 the latter of which discloses certain compounds of the generic formulae
which have utility as inhibitors of MTP.
Summary Of The Invention
The instant invention relates to compounds which are Apo B-secretion/MTP inhibitors represented by the structural formula (I), including the stereoisomers and the pharmaceutically acceptable salts and hydrates thereof,
wherein G is selected from:
(a) a phenyl or heterocyclic ring wherein said heterocyclic ring contains a total of from 3 to 14 ring atoms, wherein said heterocyclic ring incorporates a total of from 1 to 4 ring heteroatoms selected independently from oxygen, nitrogen, and sulfur, wherein the individual rings of said heterocyclic ring may be independently saturated, partially saturated or aromatic, and wherein each of said phenyl or heterocyclic rings may have optionally from 1 to 4 substituents selected independently from halogen, hydroxy, cyano, nitro, oxo, thioxo, aminosulfonyl, phenyl, phenoxy, phenylthio, benzyl, benzoyl, benzyloxy, (CrC10)alkyl, (Cr C4)perfluoroalkyl, (C1-C10)alkoxy, (Ci-C4)perfluoroalkoxy, {C1-C50)alkoxycarbonyl, (Ct-CuOalkylthio, (Ci-C10)alkylamino, di(C1-Ci0)alkylamino, (Cr C10)alkylaminocarbonyl, di(CrC10)alkylaminocarbonyl, diiCrCioJalkylaminoiCr C10)alkoxy, (CrC10)acyl, (C^-C^perfluoroacyl, (CrCi0)acyloxy, (CrC-ioJacyloxyiCr C10)alkyl, (C-rCeJacylamino and (CrCeJperfluoroacylamino; (b) -CH2CN,
(d) (C2-C12)alkyl or (C2-C12)perfluoroalkyl wherein each of said (C2-Ci2)alkyl and (C2-C12)perfluoroalkyl is substituted optionally with from 1-3 substituents selected independently from: (1) phenyl, halogen, nitro, cyano, hydroxy, -NR1R2, -OCOR3, (Ci-C4)alkoxy, (CrC4)perfluoroalkoxy, (CrC4)thioalkoxy or (CrC^perfluorothioalkoxy, where R1 and R2 in the definition of -NR1R2 are each selected independently from hydrogen, formyl, phenyl, benzyl, benzoyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkenyl, (CrC4)alkyl, (C1-C4)perfluoroalkyl, (CrC10)alkoxycarbonyl, (Cr C6)acyl, (C-|-C6)perfluoroacyl, aminocarbonyl, (CrC10)alkylaminocarbonyl, di(Cr C10)alkylaminocartx3nyl, aminosulfonyl, (CrC^alkylaminosulfonyl, di(Cr C4)alkylaminosulfonyl, (CrCJperfluoroalkylaminosuIfonyl, (Cr
C4)perfluoroalkylaminosulfonyl, difCrC^alkylsulfonyl, and (C-|- C4)perfluoroalky!sulfonyl, or where R1 and R2, taken together with the nitrogen atom to which they are attached, form a saturated, partially-saturated or aromatic heterocyclic ring, wherein said heterocyclic ring contains a total of from 3 to 14 ring atoms and incorporates optionally an additional 1 to 4 ring heteroatoms selected independently from oxygen, nitrogen and sulfur, wherein said heterocyclic ring may have optionally from 1 to 4 substituents selected independently from halogen, hydroxy, cyano, nitro, oxo, thioxo, aminosulfonyl, phenyl, phenoxy, phenylthio, benzyl, benzoyl, benzyloxy, (Ci-C10)alkyl, (CvCJperfluoroalkyl, (CrCio)alkoxy, (Cr C4)perfluoroalkoxy, (CrCi0)alkoxycarbonyl, (CrCio)alkylthio, (CrC10)alkylamino, di(CrCio)alkylamino, (CrC10)alkylaminocarbonyl, di(Ci-Ci0)alkylaminocarbonyl, diiCrC^alkylaminoiC-j-CicOalkoxy, (CrC10)acyl, (Ci-C10)perfluoroacyl, (Cr C10)acylamino, (CrC10)acyloxy, and (C1-Ci0)acyloxy(C1-C10)alkyl, where R3 is selected from -NR1R2, phenyl, (CrC10)alkyl, (Cr C4)perfluoroalkyl, (CrC6)alkoxy and (CrC^perfluoroalkoxy, f (2) (C3-C8)cycloalkyl or (C3-C8)cycloalkenyl wherein each of said (C3-C8)cycloalkyl and (C3-C8)cycloalkenyl may have optionally from 1 to 4 substituents selected independently from halogen, hydroxy, cyano, nitro, oxo, thioxo, aminosulfonyl, phenyl, phenoxy, phenylthio, benzyl, benzoyl, benzyloxy, (C-i-Ci0)alkyl, (CrC4)perfluoroalkyl, (C1-C10)alkoxy, (CrC4)perfluoroalkoxy, (Cr Ci0)alkoxycarbonyl, (C1-C10)alkylthio, (CrC10)alkylamino, di(C1-C10)alkylamino, (Cr C10)alkylaminocarbonyl, di(CrC10)alkylaminocarbonyl, diiCrCioJalkylaminofCr C10)alkoxy, (CrCi0)acyl, (C-,-C10)perfluoroacyl, (C1-C10)acylamino, (Cr Cio)perfluoroacylamino, (CrC10)acyloxy, and (CrC^JacyloxyCC-i-CioJalkyl, and (3) a saturated, partially-saturated or aromatic heterocyclic ring containing a total of from 3 to 14 ring atoms, wherein said heterocyclic ring incorporates a total of from 1 to 4 ring heteroatoms selected independently from oxygen, nitrogen and sulfur, wherein said heterocyclic ring may have optionally from 1 to 4 substituents selected independently from halogen, hydroxy, cyano, nitro, oxo, thioxo, aminosulfonyl, phenyl, phenoxy, phenylthio, benzyl, benzoyl, benzyloxy, (C-,-C10)alkyl, (CrC4)perfluoroalkyl, (CrCio)alkoxy, (CrC4)perfluoroalkoxy, (Cr C10)alkoxycarbonyl, (Ci-C10)alkylthio, (CrC10)alkylamino, di(Ci-C10)alkylamino, (Cr C10)alkylaminocarbonyl, di(CrC10)alkylaminocarbonyl, di(Ci-C10)alkylamino(C-i-C10)alkoxy, (CrCi0)acyl, (CrC^perfluoroacyl, (Οι·Όιο)3εΥΐθπιϊηο, (Cr C10)perfluoroacylamino, (CrC10)acyloxy, and (C1-C10)acyloxy(C1-C10)alkyl, provided that (C2-C12)alkyl does not include unsubstituted allyl; (e) (C3-C8)cycloalkyl or (C3-C8)cycloalkenyl wherein each of said (C3-C8)cycloalkyl and (C3-C8)cycloalkenyl may have optionally from 1 to 4 substituents selected independently from halogen, hydroxy, cyano, nitro, oxo, thioxo, aminosulfonyl, phenyl, phenoxy, phenylthio, benzyl, benzoyl, benzyloxy, (Ci-C10)alkyl, (Cr C4)perfluoroalkyl, (C1-C10)alkoxy, (C^C^perfluoroalkoxy, (CrC10)alkoxycart)onyl, (CrC10)alkylthio, (CrC^Jalkylamino, di(CrC10)alkylamino, (Cr
Cio)alkylaminocarbonyl, di(Ci-C10)alkylaminocarbonyl, di(C1-C50)alkylamino(C1-Ci0)alkoxy, (CrC10)acyl, (CrC10)perfluoroacyl, (CrC10)acylamino, (Cr C10)perfluoroacylamino, (CrC10)acyloxy, and (C1-C10)acyloxy(C1-C10)alkyl; and (f) -(CH2)nCOR4, where R4 is selected from hydroxy, phenyl, -NR1R2, (CrC4)alkyl, (Ci-C4)perfluoroalkyl, (CrC4)alkoxy, (C^-C^perfluoroalkoxy, (C3-C8)cycloalkyl, and (C3-C8)cycloalkenyl, where n is an integer from 1 to 4. A preferred subgroup of the compounds of formula (I) and the stereoisomers, pharmaceutically acceptable salts and hydrates thereof, includes those compounds wherein G is selected from: (a) a phenyl or heterocyclic ring wherein said heterocyclic ring contains a total of from 3 to 7 ring atoms, wherein said heterocyclic ring incorporates a total of from 1 to 4 ring heteroatoms selected independently from oxygen, nitrogen, and sulfur, wherein said heterocyclic ring may be saturated, partially saturated or aromatic, and wherein each of said phenyl or heterocyclic rings may each have optionally from 1 to 4 substituents selected independently from halogen, hydroxy, phenyl, benzyl, benzoyl, benzyloxy, (CrCio)alkyl. (CrC4)perfluoroalkyl, (CrC-t0)alkoxy, (Cr C4)perfluoroalkoxy, (C-|-e10)alkoxycarbonyl, (CrC10)alkylthio, (CrC10)alkylamino, di(CrCi0)alkylamino, (CrC10)alkylaminocarbonyl, di(CrC10)alkylaminocarbonyl, dKCrC^alkylaminoCCrC^alkoxy, (CrC10)acyl, (Ci-C10)perfluoroacyi, (C-r Ce)acylamino, (CrCe)perfiuoroacylamino, (C1-C10)acyloxy, and (CrCioJacyloxyiCr Cio)alkyl; (b) (C2-C12)alkyl wherein said (C2-Ci2)alkyl is substituted optionally with from 1-3 substituents selected from: (1) phenyl, halogen, cyano, hydroxy, -NR1R2, -OCOR3, (Ci-C4)alkoxy, or (Ci-C4)perfluoroalkoxy, where R3 is selected from -NR1R2, (CrC4)alkyl and (C1-C4)perfluoroalkyl, (2) (C3-C6)cycloalkyl or (C3-C6)cycloalkenyl wherein each of said (C3-C6)cycloalkyl and (C3-C6)cycloalkenyl may optionally have from 1 to 4 substituents selected independently from hydroxy, (CrC4)alkyl, (CrC4)alkoxy, and (C-|-C4)alkoxycarbonyl, and (3) a saturated, partially-saturated or aromatic heterocyclic ring containing a total of from 3 to 6 ring atoms, wherein said heterocyclic ring incorporates a total of from 1 to 4 ring heteroatoms selected independently from oxygen, nitrogen and sulfur, wherein said heterocyclic ring may have optionally from 1 to 4 substituents selected independently from halogen, hydroxy, phenyl, benzyl, benzoyl, benzyloxy, (Cf-C10)alkyl, (CrC4)perfluoroalkyl, (C1-C10)alkoxy, (CrCioJalkoxycarbonyl, (Cr C10)alkylthio, (Ci-Cio)alkylamino, di(CrC10)alkylamino, (C1-C10)alkylaminoci3rbonyl, di(C-,-Cio)alkylaminocarbonyl, di(Ci-C1o)alkylamino(C1-C10)alkoxy, (Cr C4)perfluoroalkoxy, (C-i-Cio)acyl, (CrC10)acylamino, (C1-C10)perfluoroacylamino, (Cr C10)acyloxy, and (C1-C10)acyloxy(C1-C10)alkyl; provided that (C2-C12)alkyl does not include unsubstituted allyl, (c) (C3-C6)cycloalkyl or (C3-C6)cycloalkenyl wherein each of said (C3-C6)cycloalkyl and (C3-C6)cycloalkenyl may have optionally from 1 to 4 substituents selected independently from hydroxy, (CrC4)alkyl, (CrC4)alkoxy, (CrCwJacylamino, (Cr C10)perfluoroacylamino and (CrC4)alkoxycarbonyl; and (d) -(CH2)nCOR4, where R4 is selected from hydroxy, phenyl, -NR1R2, (CrC4)alkyl, (CrC^perfluoroalkyl, (CrC4)alkoxy, (C-,-C4)perfIuoroalkoxy, (C3-C6)cycloalkyl, and (C3-C6)cycloalkenyl, where n is an integer from 1 to 4.
More particularly preferred of the compounds of formula (I) including the stereoisomers, pharmaceutically acceptable salts and hydrates thereof, are those compounds of the subgroup wherein G is selected from: (a) (C2-C12)alkyl, wherein said (C2-C12)alkyl is substituted optionally with a group selected from phenyl, halogen, cyano, hydroxy, (CrC4)alkoxy, or a saturated, partially-saturated or aromatic heterocyclic ring selected from thienyl, pyrazolyl, pyrrolidinyl, pyrrolyl, furanyl, thiazolyl, isoxazolyl, imidazolyl, triazolyl, tetrahydropyranyl, pyridyl, and pyrimidyl, wherein each of said heterocyclic rings may have optionally from 1 to 3 substitutents selected independently from halogen, (CrC4)acyl, (CrC4)perfIuoroacyl, (CrC4)alkyl, (CrCJperfluoroalkyl, (CrC4)alkoxy, (Ci-C4)alkylaminocarbonyl, and (C1-C4)acylamino; provided that (C^-C^Jalkyl does not include unsubstituted allyl; (b) -(CH2)nNR1R2, where n is an integer from 2 to 4; and (c) -(CH2)nCOR4, where n is 1 or 2.
The following compounds of formula (I), including the stereoisomers and the pharmaceutically acceptable salts and hydrates thereof, listed hereinbelow together with their corresponding IUPAC chemical names, are especially preferred wherein G is selected from: -CH2COOH, (6-i(4’-Trifiuoromethvlbiphenvl-2-carbonvn-amino]-3.4-dihvdro-1H-isoauinolin-2-viy-acetic acid: -(CH2)4CH3, 4,-Irifluoromethylbiphenyl-2-carboxylic acid-(n-pentyl-1.2.3.4-tetrahydroisoauinolin-g-yl)-amide; -(CH2)3OCH3, 4,-Trifluoromethylbiphenyl-2-carboxylic acid-r2-f3-methoxypropyl)-1.2.3.4-tetrahvdroisoquinolin-6-yi]-amide: -(CH2)2OCH3, 4’-Trifluoromethylbipheny[-2-carboxylic acid-[2-(2-methoxvethvl)-1.2.3.4-tetrahvdroisoquinolin-6-yQ-amide: -(CH2)2OCH2CH3, 4’-TrifluoromethylbiDhenyl-2-carboxylic acid-r2-I2-ethoxyethvl)-1.2.3.4-tetrahydroisoquinolin-6-yl]-aro!de: -(CH2)2CN, 4’-Trifluoromethylbiphenyl-2-carboxylic acid-[2-(2-cvanoethyl)-1.2.3.4-tetrahydroisoauinolin-6-yll-amide: -(CH2)2OCOCH3,
Acetic acid 2-(6-[f4’-trifluoromethylbiphenyl-2-carbonyl)-amino]-3.4-dihydro-1 H-isoquinolin-2-yl}-ethyl ester: -(CH2}2OCON(CH3)2,
Dimethvlcarbamic acid 2-{6-[(4’-trifluoromethylbiphenyl-2-carbonvl)-amino]-3jL· dihvdro-1 H-isoauinolin-2-yl}-ethyl ester; -(CH2)2NH2, t 4’-Trifluoromethylbiphenyl-2-carboxylic acid-[2-(2-aminoethyn-1.2.3.4-tetrahydroisioquinolin-6-yl]-amide: -(CH2)2NHCOCH3, 4.’-Trifluoromethylbiphenyl-2-carboxylic acid-[2-(2-acetylaminoethyl)-1.2.3,4-tetrahydroisoauinolin-6-yn-amide; -(CH2)2CON(CH3)2, 4’-Trif1uoromethvlbiphenvl-2-carboxviic acid-[2-(2-dimethytcarbamoylethyl)-1.2.3.4-tetrahydroisoquinolin-6-yQ-amide: -CH2CON(CH3)2, 4’-TrifluorQmethylbiphenyl-2-carboxylic acid-f 2-dimethylcarbamoylmethvl-1.2.3.4-te.trahvdroisoauinolin-6-yl)-amide: -CH2CON(CH2CH3)2,

Claims (1)

  1. Original document published without claims.
APAP/P/1997/001145A 1996-11-27 1997-11-20 APO-B-secretion/MTP inhibitory amides. AP804A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US3230796P 1996-11-27 1996-11-27
PCT/IB1997/001368 WO1998023593A1 (en) 1996-11-27 1997-11-03 Apo b-secretion/mtp inhibitory amides

Publications (2)

Publication Number Publication Date
AP9701145A0 AP9701145A0 (en) 1998-01-31
AP804A true AP804A (en) 2000-01-28

Family

ID=21864233

Family Applications (1)

Application Number Title Priority Date Filing Date
APAP/P/1997/001145A AP804A (en) 1996-11-27 1997-11-20 APO-B-secretion/MTP inhibitory amides.

Country Status (34)

Country Link
US (1) US6121283A (en)
EP (1) EP0944602A1 (en)
JP (1) JP3270764B2 (en)
KR (1) KR100334567B1 (en)
CN (2) CN1238764A (en)
AP (1) AP804A (en)
AR (1) AR010309A1 (en)
AU (1) AU716151B2 (en)
BG (2) BG103434A (en)
BR (1) BR9714364A (en)
CA (1) CA2272719C (en)
CZ (1) CZ292160B6 (en)
DZ (1) DZ2358A1 (en)
EA (1) EA001539B1 (en)
GT (1) GT199700122A (en)
HN (1) HN1997000144A (en)
HR (1) HRP970642A2 (en)
ID (1) ID18995A (en)
IL (1) IL129744A0 (en)
IS (1) IS5040A (en)
MA (1) MA26451A1 (en)
NO (1) NO312760B1 (en)
NZ (1) NZ335162A (en)
OA (1) OA11050A (en)
PA (1) PA8441601A1 (en)
PE (1) PE17199A1 (en)
SK (1) SK65499A3 (en)
TN (1) TNSN97193A1 (en)
TR (1) TR199901180T2 (en)
TW (1) TW502023B (en)
UY (1) UY24789A1 (en)
WO (1) WO1998023593A1 (en)
YU (1) YU23499A (en)
ZA (1) ZA9710641B (en)

Families Citing this family (98)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6262277B1 (en) 1994-09-13 2001-07-17 G.D. Searle And Company Intermediates and processes for the preparation of benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake
US6642268B2 (en) 1994-09-13 2003-11-04 G.D. Searle & Co. Combination therapy employing ileal bile acid transport inhibiting benzothipines and HMG Co-A reductase inhibitors
DK0832069T3 (en) * 1995-06-07 2003-04-22 Pfizer Biphenyl-2-carboxylic acid tetrahydroisoquinolin-6-ylamide derivatives, their preparation and their use as inhibitors of secretion of microsomal triglyceride transfer protein and / or apolipoprotein B (Apo B)
GB9708805D0 (en) 1997-05-01 1997-06-25 Smithkline Beecham Plc Compounds
US5968950A (en) * 1997-06-23 1999-10-19 Pfizer Inc Apo B-secretion/MTP inhibitor hydrochloride salt
GB9810876D0 (en) 1998-05-20 1998-07-22 Smithkline Beecham Plc Compounds
AU4543899A (en) 1998-06-08 1999-12-30 Advanced Medicine, Inc. Multibinding inhibitors of microsomal triglyceride transferase protein
SK4782001A3 (en) 1998-10-08 2001-11-06 Smithkline Beecham Plc Tetrahydrobenzazepine derivatives useful as modulators of dopamine d3 receptors (antipsychotic agents)
GB9826412D0 (en) * 1998-12-03 1999-01-27 Glaxo Group Ltd Chemical compounds
DK1140184T3 (en) 1998-12-23 2003-09-29 Searle Llc Combinations of cholesterol ester transfer protein inhibitors and nicotinic acid derivatives for cardiovascular indications
EP1342475A1 (en) * 1998-12-23 2003-09-10 G.D. Searle LLC. Combinations of ileal bile acid transport inhibitors and cholesteryl ester transfer protein inhibitors for cardiovascular indications
CN1342091A (en) * 1998-12-23 2002-03-27 G.D.瑟尔有限公司 Combinations of cardiovascular indications
DE19929065A1 (en) * 1999-06-25 2000-12-28 Bayer Ag Synergistic drug combination, especially for treating cardiovascular diseases associated with metabolic disorders, comprising bi- or tricyclic aza-heterocyclic MTP inhibitor and HMG-CoA reductase inhibitor
DE19929012A1 (en) * 1999-06-25 2000-12-28 Bayer Ag Synergistic drug combination, especially for treating cardiovascular diseases associated with metabolic disorders, comprising bi- or tricyclic aza-heterocyclic MTP inhibitor and metabolically active drug
DE19929031A1 (en) * 1999-06-25 2000-12-28 Bayer Ag Synergistic drug combination, especially for treating cardiovascular diseases associated with metabolic disorders, comprising bi- or tricyclic aza-heterocyclic MTP inhibitor and lipid metabolism regulator or vitamin
WO2001005767A1 (en) * 1999-07-20 2001-01-25 Novartis Ag Organic compounds
CA2324800A1 (en) * 1999-11-10 2001-05-10 Mary Anne Hickman Use of apo b secretion/mtp inhibitors
CA2324801A1 (en) * 1999-11-10 2001-05-10 Andrew Gordon Swick Use of apo b secretion/mtp inhibitors and anti-obesity agents
CO5271688A1 (en) * 1999-11-10 2003-04-30 Pfizer Prod Inc USE OF APOLIPROTEIN B AND / OR SECRETION INHIBITOR OF MICROSMAL TRIGLICERID TRANSFER PROTEIN
IL139450A0 (en) * 1999-11-10 2001-11-25 Pfizer Prod Inc Methods of administering apo b-secretion/mtp inhibitors
US6878707B2 (en) 2000-01-18 2005-04-12 Novartis Ag Carboxamides useful as inhibitors of microsomal triglyceride transfer protein and of apolipoprotein b secretion
AU6011301A (en) * 2000-03-14 2001-09-24 Actelion Pharmaceuticals Ltd 1,2,3,4-tetrahydroisoquinoline derivatives
AU2001262185A1 (en) * 2000-04-10 2001-10-23 Novartis Ag Substituted (hetero)aryl carboxamide derivatives as microsomal triglyceride transfer protein (mtp) and apolipoprotein b (apo b) secretion
GB0013383D0 (en) * 2000-06-01 2000-07-26 Glaxo Group Ltd Therapeutic benzamide derivatives
GB0013346D0 (en) * 2000-06-01 2000-07-26 Glaxo Group Ltd Therapeutic benzamide derivatives
AU2001277727A1 (en) * 2000-08-10 2002-02-25 Tanabe Seiyaku Co., Ltd. Benzoylaminoisoindoline compounds, processes for the preparation of the same andintermediates for the synthesis thereof
AU2001277728A1 (en) * 2000-08-10 2002-02-25 Tanabe Seiyaku Co., Ltd. Biphenylcarboxamidoisoindoline compounds, processes for the preparation of the same and intermediates for the synthesis thereof
HUP0301728A3 (en) * 2000-09-01 2004-05-28 Sankyo Co Hmg-coa reductase inhibiting pharmaceutical compositions and their use
JO2654B1 (en) 2000-09-04 2012-06-17 شركة جانسين فارماسوتيكا ان. في Polyarylcarboxamides useful as lipid lowering agents
RU2003112691A (en) * 2000-10-05 2004-09-20 Фудзисава Фармасьютикал Ко.,Лтд. (Jp) BENZAMIDE COMPOUNDS AS ACO SECRETION INHIBITORS
JO2409B1 (en) 2000-11-21 2007-06-17 شركة جانسين فارماسوتيكا ان. في Biphenylcarboxamides useful as lipid lowering agents
US20040157866A1 (en) * 2001-04-30 2004-08-12 Hisashi Takasugi Amide compounds
MXPA03011784A (en) 2001-06-22 2004-04-02 Pfizer Prod Inc Pharmaceutical compositions of dispersions of drugs and neutral polymers.
CN1880304B (en) * 2001-06-28 2010-11-24 辉瑞产品公司 Triamide substituted indoles, benzofurans and benzothiophenes
AU2002322585A1 (en) * 2001-07-20 2003-03-03 Adipogenix, Inc. Fat accumulation-modulating compounds
US20030130343A1 (en) * 2001-08-10 2003-07-10 Adipogenix, Inc. Fat accumulation-modulating compounds
US20050038035A1 (en) * 2001-11-28 2005-02-17 Hisashi Takasugi Heterocyclic amide compounds as apolipoprotein b inhibitors
AU2003207431A1 (en) 2002-01-17 2003-09-02 Pharmacia Corporation Novel alkyl/aryl hydroxy or keto thiepines.
KR100664822B1 (en) 2002-02-01 2007-01-04 화이자 프로덕츠 인코포레이티드 Process for preparing homogeneous spray-dried solid amorphous drug dispersions using a modified spray-drying apparatus
CN1630629B (en) 2002-02-28 2010-05-05 日本烟草产业株式会社 Ester compound and medical use thereof
US7241774B2 (en) * 2002-03-13 2007-07-10 University Of Tennessee Research Foundation Substituted tetrahydroisoquinoline compounds, methods of making, and their use
WO2004039795A2 (en) * 2002-10-29 2004-05-13 Fujisawa Pharmaceutical Co., Ltd. Amide compounds for the treatment of hyperlipidemia
EP1578725A1 (en) * 2002-12-20 2005-09-28 Pfizer Products Inc. Microsomal triglyceride transfer protein inhibitors
CA2510815A1 (en) * 2002-12-20 2004-07-08 Pfizer Products Inc. Microsomal triglyceride transfer protein inhibitors
AU2004222436A1 (en) 2003-03-17 2004-09-30 Japan Tobacco Inc. Method for increasing the oral bioavailability of S-(2-(((1- (2-ethylbutyl) cyclohexyl)carbonyl) amino) phenyl)-2-methylpropanethioate
JP4832897B2 (en) 2003-08-29 2011-12-07 日本たばこ産業株式会社 Ester derivatives and their pharmaceutical uses
JP4094050B2 (en) 2004-03-01 2008-06-04 アクテリオン ファーマシューティカルズ リミテッド Substituted 1,2,3,4-tetrahydroisoquinoline derivatives
NZ549721A (en) 2004-03-05 2010-08-27 Univ Pennsylvania Methods for treating disorders or diseases associated with hyperlipidemia and hypercholesterolemia while minimizing side-effects
US7262318B2 (en) * 2004-03-10 2007-08-28 Pfizer, Inc. Substituted heteroaryl- and phenylsulfamoyl compounds
US20050288340A1 (en) * 2004-06-29 2005-12-29 Pfizer Inc Substituted heteroaryl- and phenylsulfamoyl compounds
US20060030623A1 (en) * 2004-07-16 2006-02-09 Noboru Furukawa Agent for the treatment or prevention of diabetes, obesity or arteriosclerosis
US8101774B2 (en) 2004-10-18 2012-01-24 Japan Tobacco Inc. Ester derivatives and medicinal use thereof
BRPI0516772A (en) * 2004-10-25 2008-09-23 Japan Tobacco Inc solid formulation with improved solubility and stability and method for producing said formulation
EP1843819A2 (en) * 2004-11-15 2007-10-17 Obe Therapy Biotechnology S.A.S. Methods of reducing body fat
AU2005308575A1 (en) 2004-11-23 2006-06-01 Warner-Lambert Company Llc 7-(2h-pyrazol-3-yl)-3, 5-dihyroxy-heptanoic acid derivatives as HMG Co-A reductase inhibitors for the treatment of lipidemia
JP2006249022A (en) 2005-03-11 2006-09-21 Sumitomo Chemical Co Ltd Process for producing 4- (2-methylphenyl) benzotrifluoride
EA024768B1 (en) 2005-04-19 2016-10-31 Сюрфэйс Лоджикс, Инк. Inhibitors of microsomal triglyceride transfer protein and apo-b secretion
JP2008542255A (en) * 2005-05-27 2008-11-27 ファイザー・プロダクツ・インク Combination of cannabinoid-1 receptor antagonist and microsomal triglyceride transfer protein inhibitor for the treatment of obesity or maintenance of weight loss
US7741317B2 (en) 2005-10-21 2010-06-22 Bristol-Myers Squibb Company LXR modulators
US7888376B2 (en) 2005-11-23 2011-02-15 Bristol-Myers Squibb Company Heterocyclic CETP inhibitors
US8383660B2 (en) 2006-03-10 2013-02-26 Pfizer Inc. Dibenzyl amine compounds and derivatives
US7919506B2 (en) 2006-03-10 2011-04-05 Pfizer Inc. Dibenzyl amine compounds and derivatives
JP2009531314A (en) * 2006-03-10 2009-09-03 ニューロジェン・コーポレーション Piperazinyloxoalkyltetrahydroisoquinolines and related analogs
EP2261333B1 (en) * 2006-04-03 2016-03-30 Roche Innovation Center Copenhagen A/S Pharmaceutical composition comprising anti-miRNA antisense oligonucleotides
DK2666859T3 (en) 2006-04-03 2019-04-08 Roche Innovation Ct Copenhagen As PHARMACEUTICAL COMPOSITION CONTAINING ANTI-miRNA ANTISENSE OLIGONUCLEOTIDES
US20090042835A1 (en) * 2006-06-02 2009-02-12 Davis Roger A Compositions and methods for ameliorating hyperlipidemia
EP2037929A4 (en) * 2006-06-02 2010-02-17 Univ San Diego State Res Found COMPOSITIONS AND METHODS FOR IMPROVING HYPERLIPIDEMIA
EP2076597A2 (en) * 2006-10-09 2009-07-08 Santaris Pharma A/S Rna antagonist compounds for the modulation of pcsk9
CL2007002958A1 (en) * 2006-10-12 2008-05-09 Epix Delaware Inc COMPOUNDS DERIVED FROM HETEROARIL-CARBOXAMIDA, ANTAGONISTS OF THE CHEMIOQUINE RECEPTOR; PHARMACEUTICAL COMPOSITION; AND USE FOR THE TREATMENT OR PREVENTION OF SUCH DISEASES AS REJECTION OF ORGAN TRANSPLANTS, Rheumatoid Arthritis, LUPUS, ENTR
JP5525261B2 (en) * 2006-10-24 2014-06-18 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ MTP-inhibiting tetrahydro-naphthalene-1-carboxylic acid derivative
JO2653B1 (en) 2006-10-24 2012-06-17 شركة جانسين فارماسوتيكا ان. في Piperidine Or Piperazine Substituted Tetrahydro-Naphthalene-1-Carboxylic Acid Mtp Inhibiting Compounds.apoB
JP5498168B2 (en) 2006-12-01 2014-05-21 ブリストル−マイヤーズ スクイブ カンパニー N-((3-Benzyl) -2,2- (bis-phenyl) -propan-1-amine derivatives as CETP inhibitors for the treatment of atherosclerosis and cardiovascular disease
WO2008075949A1 (en) * 2006-12-20 2008-06-26 Friesland Brands B.V. Modulation of human microsomal triglyceride transfer protein (mtp or mttp) gene expression by food-grade/ingested dietary microorganisms
US20080161279A1 (en) * 2006-12-21 2008-07-03 Wisler Gerald L Methods of Treating Obesity
DK2149605T3 (en) * 2007-03-22 2013-09-30 Santaris Pharma As Short RNA antagonist compounds to modulate the desired mRNA
AU2008228243B2 (en) * 2007-03-22 2014-05-15 Santaris Pharma A/S RNA antagonist compounds for the inhibition of Apo-B100 expression
AU2008268442A1 (en) * 2007-06-25 2008-12-31 Neurogen Corporation Piperazinyl oxoalkyl tetrahydro-beta-carbolines and related analogues
WO2009027527A2 (en) * 2007-08-30 2009-03-05 Santaris Pharma A/S Rna antagonist compounds for the modulation of fabp4/ap2
ES2463665T3 (en) 2007-10-04 2014-05-28 Stella Aps Combination treatment for the treatment of hepatitis C virus infection
CA2707549A1 (en) 2007-12-03 2009-06-11 Itzik Harosh Boropeptide inhibitors of enteropeptidase and their uses in treatment of obesity, overweight and/or diseases associated with an abnormal fat metabolism
KR20100102646A (en) 2007-12-11 2010-09-24 가부시키가이샤 사이토파스파인더 Carboxamide compounds and their use as chemokine receptor agonists
US20090197947A1 (en) * 2008-02-01 2009-08-06 The Research Foundation Of State University Of New York Medicaments and methods for lowering plasma lipid levels and screening drugs
EP2268811A1 (en) * 2008-03-07 2011-01-05 Santaris Pharma A/S Pharmaceutical compositions for treatment of microrna related diseases
US8492357B2 (en) 2008-08-01 2013-07-23 Santaris Pharma A/S Micro-RNA mediated modulation of colony stimulating factors
JP5773535B2 (en) * 2009-04-24 2015-09-02 ロシュ・イノベーション・センター・コペンハーゲン・アクティーゼルスカブＲｏｃｈｅ Ｉｎｎｏｖａｔｉｏｎ Ｃｅｎｔｅｒ Ｃｏｐｅｎｈａｇｅｎ Ａ／Ｓ Pharmaceutical composition for the treatment of HCV patients unresponsive to interferon
US8563528B2 (en) 2009-07-21 2013-10-22 Santaris Pharma A/S Antisense oligomers targeting PCSK9
SG11201507496UA (en) 2013-04-17 2015-11-27 Pfizer N-piperidin-3-ylbenzamide derivatives for treating cardiovascular diseases
AU2014300981B2 (en) 2013-06-27 2017-08-10 Ricc A/S Antisense oligomers and conjugates targeting PCSK9
US9856478B2 (en) 2013-10-30 2018-01-02 Trustees Of Dartmouth College Method for selectively inhibiting ACAT1 in the treatment of obesity, metabolic syndrome, and atherosclerosis
WO2016055901A1 (en) 2014-10-08 2016-04-14 Pfizer Inc. Substituted amide compounds
EP3209299A4 (en) 2014-10-22 2018-04-04 The Board of Regents of The University of Texas System Small-molecule inhibitors targeting discoidin domain receptor 1 and uses thereof
US11248001B2 (en) 2019-01-18 2022-02-15 Astrazeneca Ab PCSK9 inhibitors and methods of use thereof
EP4188372A1 (en) 2020-07-29 2023-06-07 Amryt Pharmaceuticals Inc. Lomitapide for use in methods of treating hyperlipidemia and hypercholesterolemia in pediatric patients
CA3212863A1 (en) * 2021-03-26 2022-09-29 Laura Carzaniga Indoline derivatives as ddr1 and ddr2 inhibitors
EP4313972B1 (en) * 2021-03-26 2025-01-29 Chiesi Farmaceutici S.p.A. Indoline derivatives as ddrs inhibitors
CN113292493A (en) * 2021-06-23 2021-08-24 上海立科化学科技有限公司 Preparation method of 5, 7-dichloro-1, 2,3, 4-tetrahydroisoquinoline
WO2024216197A2 (en) * 2023-04-13 2024-10-17 Acelot, Inc. Compounds and methods for treating protein aggregation diseases
US12453728B1 (en) 2024-08-08 2025-10-28 Redux Therapeutics, Llc Compositions comprising inhibitors of microsomal triglyceride transfer protein and Apo-B secretion

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4022900A (en) * 1970-09-09 1977-05-10 Marion Laboratories, Inc. Compositions containing 1,2,3,4-tetrahydroisoquinolines used as hypotensive agents
EP0643057A1 (en) * 1993-09-03 1995-03-15 Bristol-Myers Squibb Company Inhibitors of microsomal triglyceride transfer protein
WO1996026205A1 (en) * 1995-02-21 1996-08-29 Bristol-Myers Squibb Company Inhibitors of microsomal triglyceride transfer protein and method

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996040640A1 (en) * 1995-06-07 1996-12-19 Pfizer Inc. 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

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4022900A (en) * 1970-09-09 1977-05-10 Marion Laboratories, Inc. Compositions containing 1,2,3,4-tetrahydroisoquinolines used as hypotensive agents
EP0643057A1 (en) * 1993-09-03 1995-03-15 Bristol-Myers Squibb Company Inhibitors of microsomal triglyceride transfer protein
WO1996026205A1 (en) * 1995-02-21 1996-08-29 Bristol-Myers Squibb Company Inhibitors of microsomal triglyceride transfer protein and method

Also Published As

Publication number Publication date
EA001539B1 (en) 2001-04-23
KR20000057269A (en) 2000-09-15
IS5040A (en) 1999-04-30
NO992525D0 (en) 1999-05-26
BG103434A (en) 2000-07-31
TW502023B (en) 2002-09-11
OA11050A (en) 2002-03-07
US6121283A (en) 2000-09-19
NO312760B1 (en) 2002-07-01
BR9714364A (en) 2000-03-21
ID18995A (en) 1998-05-28
HN1997000144A (en) 1997-12-16
CZ292160B6 (en) 2003-08-13
TR199901180T2 (en) 1999-08-23
JP2000505810A (en) 2000-05-16
JP3270764B2 (en) 2002-04-02
KR100334567B1 (en) 2002-05-03
IL129744A0 (en) 2000-02-29
PA8441601A1 (en) 2000-05-24
CA2272719C (en) 2002-10-01
AU4634797A (en) 1998-06-22
EA199900416A1 (en) 1999-12-29
HRP970642A2 (en) 1998-10-31
UY24789A1 (en) 2000-09-29
PE17199A1 (en) 1999-02-19
GT199700122A (en) 1999-05-19
CN1238764A (en) 1999-12-15
TNSN97193A1 (en) 2005-03-15
SK65499A3 (en) 2001-05-10
DZ2358A1 (en) 2002-12-28
ZA9710641B (en) 1999-05-26
AU716151B2 (en) 2000-02-17
NZ335162A (en) 2000-01-28
CA2272719A1 (en) 1998-06-04
CN1380289A (en) 2002-11-20
MA26451A1 (en) 2004-12-20
AR010309A1 (en) 2000-06-07
NO992525L (en) 1999-05-26
EP0944602A1 (en) 1999-09-29
WO1998023593A1 (en) 1998-06-04
YU23499A (en) 2001-07-10
BG108830A (en) 2005-10-31
AP9701145A0 (en) 1998-01-31

Similar Documents

Publication Publication Date Title
US6121304A (en) Pentafluorobenzenesulfonamides and analogs
ES2754221T3 (en) Compound capable of binding the S1P receptor and pharmaceutical use thereof
RU2618628C1 (en) N-piperidin-3-yl-benzamide derivatives for cardiovascular diseases treatment
US7291644B2 (en) Indole derivatives
EP2593428B1 (en) N-sulfonylbenzamides as inhibitors of voltage-gated sodium channels
JP5989923B2 (en) Methyl group-modifying enzyme regulator, composition and use thereof
AU2015219920B2 (en) Triazine compound and use thereof for medical purposes
PT2004607E (en) (4-(4-[6-(trifluoromethyl-pyridin-3-ylamino)-n-containing-heteroaryl]-phenyl)-cyclohexyl)-acetic acid derivatives and pharmaceutical uses thereof
EP1852433A4 (en) CARBAZOLE DERIVATIVE, SOLVATE DERIVED THEREFROM, OR PHARMACEUTICAL QUALITY SALT OF SAID DERIVATIVE
WO2010125831A1 (en) Sulfamoyl benzoic acid derivatives as trpm8 antagonists
KR20200015888A (en) Amide Derivatives Used as Nav1.7 and Nav1.8 Blockers
NZ532080A (en) Heterocyclic compounds and methods of use
JP2009513523A (en) Benzenesulfonylamino compounds and pharmaceutical compositions containing them
UY24789A1 (en) INHIBITING AMIDES OF THE APO B / MTP SECRETION
EA016345B1 (en) Novel sulphonylpyrroles as inhibitors of hdac s novel sulphonylpyrroles
US12258308B2 (en) Benzene derivative
US7135495B2 (en) Indole derivatives
Gribble et al. ATP-citrate lyase as a target for hypolipidemic intervention. Design and synthesis of 2-substituted butanedioic acids as novel, potent inhibitors of the enzyme
US20160102074A1 (en) Substituted amide compounds
CN1227008C (en) Method for converting a COX-inhibiting compound that is not a COX-2 selective inhibitor into a derivative of a COX-2 selective inhibitor
Takahashi et al. Novel indoline-based acyl-CoA: cholesterol acyltransferase inhibitor with antiperoxidative activity: improvement of physicochemical properties and biological activities by introduction of carboxylic acid
US6762182B1 (en) Converting cox inhibition compounds that are not COX-2 selective inhibitors to derivatives that are COX-2 selective inhibitors
Wang et al. Synthesis and biological evaluation of ezetimibe analogs as possible cholesterol absorption inhibitors
AU2024314133A1 (en) Combination therapies of fasn inhibitors with thyroid hormone receptor agonists
JP2010090078A (en) Tricyclic heteroaryl derivative