NO311325B1 - Anvendelse av en kombinasjon av en kolesterolbiosynteseinhibitor og en <beta>-laktam-kolesterolabsorpsjonsinhibitor for fremstilling av et medikament;og farmasöytisk preparat inneholdende disse inhibitorer - Google Patents
Anvendelse av en kombinasjon av en kolesterolbiosynteseinhibitor og en <beta>-laktam-kolesterolabsorpsjonsinhibitor for fremstilling av et medikament;og farmasöytisk preparat inneholdende disse inhibitorer Download PDFInfo
- Publication number
- NO311325B1 NO311325B1 NO19952529A NO952529A NO311325B1 NO 311325 B1 NO311325 B1 NO 311325B1 NO 19952529 A NO19952529 A NO 19952529A NO 952529 A NO952529 A NO 952529A NO 311325 B1 NO311325 B1 NO 311325B1
- Authority
- NO
- Norway
- Prior art keywords
- cholesterol
- inhibitor
- lactam
- cholesterol absorption
- alkoxy
- Prior art date
Links
- 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 abstract description 144
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 title claims abstract description 23
- 229940079593 drug Drugs 0.000 title claims description 4
- 239000003814 drug Substances 0.000 title claims description 4
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 235000012000 cholesterol Nutrition 0.000 title abstract description 37
- 239000003112 inhibitor Substances 0.000 title abstract description 20
- 230000015572 biosynthetic process Effects 0.000 title abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 title abstract 2
- 150000003952 β-lactams Chemical class 0.000 claims abstract description 24
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 8
- 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 32
- 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 32
- 229960004844 lovastatin Drugs 0.000 claims description 31
- 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 31
- 230000009467 reduction Effects 0.000 claims description 19
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 16
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 16
- 239000003937 drug carrier Substances 0.000 claims description 9
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- 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 description 4
- 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 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 229960002965 pravastatin Drugs 0.000 claims description 4
- 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 description 4
- IMNTVVOUWFPRSB-JWQCQUIFSA-N sch-48461 Chemical group C1=CC(OC)=CC=C1[C@H]1N(C=2C=CC(OC)=CC=2)C(=O)[C@@H]1CCCC1=CC=CC=C1 IMNTVVOUWFPRSB-JWQCQUIFSA-N 0.000 claims description 4
- 229960002855 simvastatin Drugs 0.000 claims description 4
- 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 4
- 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 3
- 229960003765 fluvastatin Drugs 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- -1 3-phenyl-1-propenyl Chemical group 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 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 2
- 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 2
- 125000005336 allyloxy group Chemical group 0.000 claims description 2
- 229960005370 atorvastatin Drugs 0.000 claims description 2
- 125000004980 cyclopropylene group Chemical group 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 8
- 229940126062 Compound A Drugs 0.000 description 24
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 24
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- 108010007622 LDL Lipoproteins Proteins 0.000 description 5
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- 108010062497 VLDL Lipoproteins Proteins 0.000 description 4
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- 150000001875 compounds Chemical class 0.000 description 4
- 239000002285 corn oil Substances 0.000 description 4
- 235000005687 corn oil Nutrition 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 210000000936 intestine Anatomy 0.000 description 4
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 4
- 241000282560 Macaca mulatta Species 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 235000019483 Peanut oil Nutrition 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000001906 cholesterol absorption Effects 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 235000013861 fat-free Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000312 peanut oil Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- RLFWWDJHLFCNIJ-UHFFFAOYSA-N 4-aminoantipyrine Chemical compound CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 2
- 108010089254 Cholesterol oxidase Proteins 0.000 description 2
- 108010004103 Chylomicrons Proteins 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 210000000941 bile Anatomy 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
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- 230000037396 body weight Effects 0.000 description 2
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- 230000015556 catabolic process Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 210000001842 enterocyte Anatomy 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 230000000871 hypocholesterolemic effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000033227 intestinal cholesterol absorption Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- 102100029077 3-hydroxy-3-methylglutaryl-coenzyme A reductase Human genes 0.000 description 1
- 101710158485 3-hydroxy-3-methylglutaryl-coenzyme A reductase Proteins 0.000 description 1
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
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- 102000001494 Sterol O-Acyltransferase Human genes 0.000 description 1
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- XKXHCNPAFAXVRZ-UHFFFAOYSA-N benzylazanium;chloride Chemical compound [Cl-].[NH3+]CC1=CC=CC=C1 XKXHCNPAFAXVRZ-UHFFFAOYSA-N 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
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- 230000031154 cholesterol homeostasis Effects 0.000 description 1
- 150000001841 cholesterols Chemical class 0.000 description 1
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- 150000003626 triacylglycerols Chemical class 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- DFKDOZMCHOGOBR-UHFFFAOYSA-N zaragozic acid A Natural products O1C(C(O)(C(O2)C(O)=O)C(O)=O)(C(O)=O)C(OC(=O)C=CC(C)CC(C)CC)C(O)C21CCC(=C)C(OC(C)=O)C(C)CC1=CC=CC=C1 DFKDOZMCHOGOBR-UHFFFAOYSA-N 0.000 description 1
- DFKDOZMCHOGOBR-NCSQYGPNSA-N zaragozic acid A Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CC[C@]12[C@H](O)[C@H]([C@](O2)(C(O)=O)[C@@](O)([C@H](O1)C(O)=O)C(O)=O)OC(=O)/C=C/[C@@H](C)C[C@@H](C)CC)C1=CC=CC=C1 DFKDOZMCHOGOBR-NCSQYGPNSA-N 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
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Cosmetics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US99548892A | 1992-12-23 | 1992-12-23 | |
| PCT/US1993/012291 WO1994014433A1 (fr) | 1992-12-23 | 1993-12-21 | Combinaison d'un inhibiteur de biosynthese du cholesterol et d'un inhibiteur d'absorption du cholesterol beta-lactame |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO952529D0 NO952529D0 (no) | 1995-06-23 |
| NO952529L NO952529L (no) | 1995-06-23 |
| NO311325B1 true NO311325B1 (no) | 2001-11-19 |
Family
ID=25541876
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19952529A NO311325B1 (no) | 1992-12-23 | 1995-06-23 | Anvendelse av en kombinasjon av en kolesterolbiosynteseinhibitor og en <beta>-laktam-kolesterolabsorpsjonsinhibitor for fremstilling av et medikament;og farmasöytisk preparat inneholdende disse inhibitorer |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US5661145A (fr) |
| EP (1) | EP0675714B1 (fr) |
| JP (1) | JP3992728B2 (fr) |
| KR (1) | KR100306936B1 (fr) |
| CN (1) | CN1090479C (fr) |
| AT (1) | ATE175872T1 (fr) |
| AU (1) | AU680864B2 (fr) |
| CA (1) | CA2152351C (fr) |
| CZ (1) | CZ287125B6 (fr) |
| DE (1) | DE69323213T2 (fr) |
| DK (1) | DK0675714T3 (fr) |
| EE (1) | EE03383B1 (fr) |
| ES (1) | ES2128552T3 (fr) |
| FI (1) | FI952916A0 (fr) |
| GR (1) | GR3029405T3 (fr) |
| HR (1) | HRP931515B1 (fr) |
| HU (1) | HU221724B1 (fr) |
| IL (1) | IL108112A (fr) |
| LT (1) | LT3300B (fr) |
| LV (1) | LV10919B (fr) |
| MX (1) | MX9308053A (fr) |
| MY (1) | MY109538A (fr) |
| NO (1) | NO311325B1 (fr) |
| NZ (1) | NZ259790A (fr) |
| PL (1) | PL174128B1 (fr) |
| SG (1) | SG45147A1 (fr) |
| SI (1) | SI9300677A (fr) |
| SK (1) | SK281173B6 (fr) |
| TW (1) | TW319698B (fr) |
| WO (1) | WO1994014433A1 (fr) |
| YU (1) | YU49060B (fr) |
| ZA (1) | ZA939552B (fr) |
Families Citing this family (81)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5631365A (en) * | 1993-09-21 | 1997-05-20 | Schering Corporation | Hydroxy-substituted azetidinone compounds useful as hypocholesterolemic agents |
| AU2453295A (en) * | 1994-09-20 | 1996-04-19 | Pfizer Inc. | Combination of a cholesterol absorption inhibitor and a cholesterol synthesis inhibitor |
| US5624920A (en) * | 1994-11-18 | 1997-04-29 | Schering Corporation | Sulfur-substituted azetidinone compounds useful as hypocholesterolemic agents |
| US5633246A (en) * | 1994-11-18 | 1997-05-27 | Schering Corporation | Sulfur-substituted azetidinone compounds useful as hypocholesterolemic agents |
| US5656624A (en) * | 1994-12-21 | 1997-08-12 | Schering Corporation | 4-[(heterocycloalkyl or heteroaromatic)-substituted phenyl]-2-azetidinones useful as hypolipidemic agents |
| KR20040029459A (ko) | 1995-11-02 | 2004-04-06 | 워너-램버트 캄파니 엘엘씨 | 지질 농도를 조절하는 제약 조성물 및 방법 |
| US20030153541A1 (en) * | 1997-10-31 | 2003-08-14 | Robert Dudley | Novel anticholesterol compositions and method for using same |
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| US4680391A (en) * | 1983-12-01 | 1987-07-14 | Merck & Co., Inc. | Substituted azetidinones as anti-inflammatory and antidegenerative agents |
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