CA2276467A1 - Methode de traitement de l'atherosclerose a l'aide d'un inhibiteur de mpt et de medicaments reduisant le cholesterol - Google Patents
Methode de traitement de l'atherosclerose a l'aide d'un inhibiteur de mpt et de medicaments reduisant le cholesterol Download PDFInfo
- Publication number
- CA2276467A1 CA2276467A1 CA002276467A CA2276467A CA2276467A1 CA 2276467 A1 CA2276467 A1 CA 2276467A1 CA 002276467 A CA002276467 A CA 002276467A CA 2276467 A CA2276467 A CA 2276467A CA 2276467 A1 CA2276467 A1 CA 2276467A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- aryl
- heteroaryl
- independently
- alkenyl
- 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
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- 239000003112 inhibitor Substances 0.000 title claims abstract description 72
- 238000000034 method Methods 0.000 title claims abstract description 57
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 title claims description 55
- 235000012000 cholesterol Nutrition 0.000 title claims description 15
- 229940079593 drug Drugs 0.000 title description 12
- 239000003814 drug Substances 0.000 title description 12
- 201000001320 Atherosclerosis Diseases 0.000 title description 11
- 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 claims abstract description 86
- 239000003529 anticholesteremic agent Substances 0.000 claims abstract description 21
- 208000035150 Hypercholesterolemia Diseases 0.000 claims abstract description 16
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229960002965 pravastatin Drugs 0.000 claims abstract description 15
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims abstract description 15
- 230000007211 cardiovascular event Effects 0.000 claims abstract description 9
- 230000007213 cerebrovascular event Effects 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 140
- 125000003118 aryl group Chemical group 0.000 claims description 126
- 125000001072 heteroaryl group Chemical group 0.000 claims description 94
- 108010038232 microsomal triglyceride transfer protein Proteins 0.000 claims description 85
- -1 diarylalkenyl Chemical group 0.000 claims description 65
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 60
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- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 125000005843 halogen group Chemical group 0.000 claims description 34
- 125000000304 alkynyl group Chemical group 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 33
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 33
- 125000001188 haloalkyl group Chemical group 0.000 claims description 31
- 125000001424 substituent group Chemical group 0.000 claims description 30
- 125000004414 alkyl thio group Chemical group 0.000 claims description 29
- 208000029078 coronary artery disease Diseases 0.000 claims description 26
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 24
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 23
- 208000010125 myocardial infarction Diseases 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 17
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- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
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- 125000005110 aryl thio group Chemical group 0.000 claims description 16
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 16
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- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 14
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- 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
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- 150000003839 salts Chemical class 0.000 claims description 12
- 125000004450 alkenylene group Chemical group 0.000 claims description 11
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- 125000004043 oxo group Chemical group O=* 0.000 claims description 10
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- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
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- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 8
- 125000005150 heteroarylsulfinyl group Chemical group 0.000 claims description 8
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical group C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 8
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- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 8
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 7
- 125000004419 alkynylene group Chemical group 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
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- 229960002855 simvastatin Drugs 0.000 claims description 7
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 6
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 6
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 claims description 6
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 6
- 125000005164 aryl thioalkyl group Chemical group 0.000 claims description 6
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- 229960005110 cerivastatin Drugs 0.000 claims description 6
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 claims description 6
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 6
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- 125000005419 heteroarylsulfonylamino group Chemical group 0.000 claims description 6
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- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical group C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims description 5
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- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 claims description 5
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- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 description 1
- 229950009116 mevastatin Drugs 0.000 description 1
- BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- WGESLFUSXZBFQF-UHFFFAOYSA-N n-methyl-n-prop-2-enylprop-2-en-1-amine Chemical class C=CCN(C)CC=C WGESLFUSXZBFQF-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002814 niacins Chemical class 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- HEGSGKPQLMEBJL-RKQHYHRCSA-N octyl beta-D-glucopyranoside Chemical compound CCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HEGSGKPQLMEBJL-RKQHYHRCSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical class O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920000371 poly(diallyldimethylammonium chloride) polymer Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 1
- 229910001488 sodium perchlorate Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- 150000005691 triesters Chemical class 0.000 description 1
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical class [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 1
- 239000002691 unilamellar liposome Substances 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
L'invention concerne une méthode de prévention ou de réduction du risque d'apparition de maladies cardio-vasculaires par l'administration d'un inhibiteur de protéine de transfert microsomale (MTP) seul ou en combinaison avec un autre médicament réduisant le cholestérol tel qu'un inhibiteur de la HMG CoA-réductase, dont la pravastatine, à un patient qui peut présenter ou non un ou plusieurs facteurs de risque pour un accident coronaire et/ou cérébro-vasculaire tel que l'hypercholestérolémie.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3559297P | 1997-01-17 | 1997-01-17 | |
| US60/035,592 | 1997-01-17 | ||
| PCT/US1998/000524 WO1998031366A1 (fr) | 1997-01-17 | 1998-01-12 | Methode de traitement de l'atherosclerose a l'aide d'un inhibiteur de mpt et de medicaments reduisant le cholesterol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2276467A1 true CA2276467A1 (fr) | 1998-07-23 |
Family
ID=21883624
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002276467A Abandoned CA2276467A1 (fr) | 1997-01-17 | 1998-01-12 | Methode de traitement de l'atherosclerose a l'aide d'un inhibiteur de mpt et de medicaments reduisant le cholesterol |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0989852A4 (fr) |
| JP (1) | JP2001508795A (fr) |
| AU (1) | AU727895B2 (fr) |
| CA (1) | CA2276467A1 (fr) |
| WO (1) | WO1998031366A1 (fr) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2304505A1 (fr) * | 1997-09-24 | 1999-04-01 | Nova Molecular, Inc. | Methodes permettant d'augmenter les taux d'apolipoproteine dans le traitement de maladies neurodegeneratives |
| WO1999063929A2 (fr) | 1998-06-08 | 1999-12-16 | Advanced Medicine, Inc. | Inhibiteurs multiliaison de proteine triglyceride transferase microsomique |
| SE9902987D0 (sv) | 1999-08-24 | 1999-08-24 | Astra Pharma Prod | Novel compounds |
| DE10030375A1 (de) * | 2000-06-21 | 2002-01-03 | Bayer Ag | Verwendung von MTP-Inhibitoren zur Senkung von ppTRL |
| US6982251B2 (en) | 2000-12-20 | 2006-01-03 | Schering Corporation | Substituted 2-azetidinones useful as hypocholesterolemic agents |
| US7071181B2 (en) | 2001-01-26 | 2006-07-04 | Schering Corporation | Methods and therapeutic combinations for the treatment of diabetes using sterol absorption inhibitors |
| AR035533A1 (es) | 2001-01-26 | 2004-06-02 | Schering Corp | Uso de por lo menos un inhibidor de la absorcion de los esteroles o sus sales, solvatos, prodrogas farmaceuticamente aceptables o mezclas de los mismos para la preparacion de un medicamento para el tratamiento de la sitosterolemia, composiciones farmaceuticas, el uso de dichas composiciones para la |
| IL156445A0 (en) | 2001-01-26 | 2004-01-04 | Schering Corp | Combinations of peroxisome proliferator-activated receptor (ppar) activator(s) and sterol absorption inhibitor(s) and treatments for vascular indications |
| GB0104050D0 (en) | 2001-02-19 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
| GB0107228D0 (en) | 2001-03-22 | 2001-05-16 | Astrazeneca Ab | Chemical compounds |
| US7056906B2 (en) | 2001-09-21 | 2006-06-06 | Schering Corporation | Combinations of hormone replacement therapy composition(s) and sterol absorption inhibitor(s) and treatments for vascular conditions in post-menopausal women |
| US7053080B2 (en) | 2001-09-21 | 2006-05-30 | Schering Corporation | Methods and therapeutic combinations for the treatment of obesity using sterol absorption inhibitors |
| MXPA04002573A (es) | 2001-09-21 | 2004-06-18 | Schering Corp | Tratamiento de xantoma con derivados de azetidinona como inhibidores de la absorcion de esterol. |
| SE0103818D0 (sv) | 2001-11-15 | 2001-11-15 | Astrazeneca Ab | Chemical compounds |
| WO2004043457A1 (fr) | 2002-11-06 | 2004-05-27 | Schering Corporation | Inhibiteurs d'absorption de cholesterol pour le traitement de troubles auto-immuns |
| EP1601668B1 (fr) | 2003-03-07 | 2008-08-27 | Schering Corporation | Composes d'azetidinone substitues, leurs formulations et utilisations en vue du traitement de l'hypercholesterolemie |
| US7459442B2 (en) | 2003-03-07 | 2008-12-02 | Schering Corporation | Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof |
| JP2006519869A (ja) | 2003-03-07 | 2006-08-31 | シェーリング コーポレイション | 置換アゼチジノン化合物、置換アゼチジノン化合物を調製するためのプロセス、それらの処方物および使用 |
| CA2517572C (fr) | 2003-03-07 | 2011-12-13 | Schering Corporation | Composes d'azetidinone substitues, leurs formulations et leur utilisation pour traiter l'hypercholesterolemie |
| SE0301369D0 (sv) | 2003-05-09 | 2003-05-09 | Astrazeneca Ab | Chemical compounds |
| US7932268B2 (en) | 2004-03-05 | 2011-04-26 | The Trustees Of The University Of Pennsylvania | Methods for treating disorders or diseases associated with hyperlipidemia and hypercholesterolemia while minimizing side effects |
| EP1951220A2 (fr) * | 2005-10-18 | 2008-08-06 | Aegerion Pharmaceuticals | Compositions destinees a l'abbaissement du cholesterol serique et/ou des triglycerides |
| CN111187200A (zh) * | 2020-04-09 | 2020-05-22 | 南京昊绿生物科技有限公司 | 一种洛美他派-d8的合成方法 |
| US20230285376A1 (en) | 2020-07-29 | 2023-09-14 | Amryt Pharmaceuticals Inc. | Lomitapide for use in methods of treating hyperlipidemia and hypercholesterolemia in pediatric patients |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3674836A (en) * | 1968-05-21 | 1972-07-04 | Parke Davis & Co | 2,2-dimethyl-{11 -aryloxy-alkanoic acids and salts and esters thereof |
| MX7065E (es) * | 1980-06-06 | 1987-04-10 | Sankyo Co | Un procedimiento microbiologico para preparar derivados de ml-236b |
| CA2091102C (fr) * | 1992-03-06 | 2009-05-26 | John R. Ii Wetterau | Proteine de transfert de triglycerides microsomaux |
| US5595872A (en) * | 1992-03-06 | 1997-01-21 | Bristol-Myers Squibb Company | Nucleic acids encoding microsomal trigyceride transfer protein |
-
1998
- 1998-01-12 AU AU62397/98A patent/AU727895B2/en not_active Ceased
- 1998-01-12 JP JP53446098A patent/JP2001508795A/ja not_active Withdrawn
- 1998-01-12 EP EP98904548A patent/EP0989852A4/fr not_active Withdrawn
- 1998-01-12 CA CA002276467A patent/CA2276467A1/fr not_active Abandoned
- 1998-01-12 WO PCT/US1998/000524 patent/WO1998031366A1/fr not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| AU727895B2 (en) | 2001-01-04 |
| WO1998031366A1 (fr) | 1998-07-23 |
| JP2001508795A (ja) | 2001-07-03 |
| EP0989852A4 (fr) | 2002-11-13 |
| EP0989852A1 (fr) | 2000-04-05 |
| AU6239798A (en) | 1998-08-07 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |