NO324694B1 - Anvendelse av endotelinreseptor-antagonister for fremstilling av medikamenter for a kontrollere hyperlipidemi. - Google Patents
Anvendelse av endotelinreseptor-antagonister for fremstilling av medikamenter for a kontrollere hyperlipidemi. Download PDFInfo
- Publication number
- NO324694B1 NO324694B1 NO20002777A NO20002777A NO324694B1 NO 324694 B1 NO324694 B1 NO 324694B1 NO 20002777 A NO20002777 A NO 20002777A NO 20002777 A NO20002777 A NO 20002777A NO 324694 B1 NO324694 B1 NO 324694B1
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- Norway
- Prior art keywords
- receptor antagonists
- endothelin receptor
- medications
- manufacture
- endothelin
- Prior art date
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- 229940118365 Endothelin receptor antagonist Drugs 0.000 title abstract description 9
- 239000002308 endothelin receptor antagonist Substances 0.000 title abstract description 9
- 208000031226 Hyperlipidaemia Diseases 0.000 title abstract description 5
- 239000003814 drug Substances 0.000 title description 10
- 229940079593 drug Drugs 0.000 title description 10
- 238000004519 manufacturing process Methods 0.000 title description 3
- 238000002483 medication Methods 0.000 title 1
- 208000008589 Obesity Diseases 0.000 abstract description 6
- 235000020824 obesity Nutrition 0.000 abstract description 6
- 201000010099 disease Diseases 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 201000005569 Gout Diseases 0.000 abstract description 2
- 206010020772 Hypertension Diseases 0.000 abstract description 2
- 208000020832 chronic kidney disease Diseases 0.000 abstract description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 abstract description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 abstract description 2
- 206010003210 Arteriosclerosis Diseases 0.000 abstract 1
- 208000011775 arteriosclerosis disease Diseases 0.000 abstract 1
- 239000007903 gelatin capsule Substances 0.000 description 6
- 108050009340 Endothelin Proteins 0.000 description 5
- 102000002045 Endothelin Human genes 0.000 description 5
- 239000000654 additive Substances 0.000 description 5
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229940044551 receptor antagonist Drugs 0.000 description 3
- 239000002464 receptor antagonist Substances 0.000 description 3
- 239000007940 sugar coated tablet Substances 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 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 description 2
- 229940125833 compound 23 Drugs 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
- 101150037123 APOE gene Proteins 0.000 description 1
- 101710095339 Apolipoprotein E Proteins 0.000 description 1
- 102100029470 Apolipoprotein E Human genes 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 101100216294 Danio rerio apoeb gene Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010020710 Hyperphagia Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010038372 Renal arteriosclerosis Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 108010047918 TAK 044 Proteins 0.000 description 1
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003579 anti-obesity Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- MOTJMGVDPWRKOC-QPVYNBJUSA-N atrasentan Chemical compound C1([C@H]2[C@@H]([C@H](CN2CC(=O)N(CCCC)CCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 MOTJMGVDPWRKOC-QPVYNBJUSA-N 0.000 description 1
- LFYJSSARVMHQJB-QIXNEVBVSA-N bakuchiol Chemical compound CC(C)=CCC[C@@](C)(C=C)\C=C\C1=CC=C(O)C=C1 LFYJSSARVMHQJB-QIXNEVBVSA-N 0.000 description 1
- GJPICJJJRGTNOD-UHFFFAOYSA-N bosentan Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GJPICJJJRGTNOD-UHFFFAOYSA-N 0.000 description 1
- 229960003065 bosentan Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- UWHBIISPHYTOGL-PFSAEEMXSA-L disodium;2-[(2r,5s,8s,11s,14s,17r)-8-(carboxylatomethyl)-17-(1h-indol-3-ylmethyl)-14-(2-methylpropyl)-3,6,9,12,15,18-hexaoxo-5-[2-oxo-2-(4-phenylpiperazin-1-yl)ethyl]-11-thiophen-2-yl-1,4,7,10,13,16-hexazacyclooctadec-2-yl]acetate Chemical compound [Na+].[Na+].C([C@H]1C(=O)N[C@@H](CC([O-])=O)C(=O)N[C@@H](C(=O)N[C@H](C(N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@H](CC([O-])=O)C(=O)N1)=O)CC(C)C)C=1SC=CC=1)C(=O)N(CC1)CCN1C1=CC=CC=C1 UWHBIISPHYTOGL-PFSAEEMXSA-L 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- -1 invert sugar Substances 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- LJGUZUROJOJEMI-UHFFFAOYSA-N n-(3,4-dimethyl-1,2-oxazol-5-yl)-2-[4-(1,3-oxazol-2-yl)phenyl]benzenesulfonamide Chemical compound CC1=NOC(NS(=O)(=O)C=2C(=CC=CC=2)C=2C=CC(=CC=2)C=2OC=CN=2)=C1C LJGUZUROJOJEMI-UHFFFAOYSA-N 0.000 description 1
- ORJRYNKVKJAJPY-UHFFFAOYSA-N n-[[2-[2-[(4,5-dimethyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]-5-(1,3-oxazol-2-yl)phenyl]methyl]-n,3,3-trimethylbutanamide Chemical compound CC(C)(C)CC(=O)N(C)CC1=CC(C=2OC=CN=2)=CC=C1C1=CC=CC=C1S(=O)(=O)NC1=NOC(C)=C1C ORJRYNKVKJAJPY-UHFFFAOYSA-N 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
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000006259 organic additive Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000020830 overeating Nutrition 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229960002578 sitaxentan Drugs 0.000 description 1
- PHWXUGHIIBDVKD-UHFFFAOYSA-N sitaxentan Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3OCOC=3C=2)C)=C1Cl PHWXUGHIIBDVKD-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- COKFAUSKNMGISZ-BMGIYVBOSA-M sodium;(z)-2-(2,1,3-benzothiadiazol-5-yl)-4-(4-methoxyphenyl)-4-oxo-3-[(3,4,5-trimethoxyphenyl)methyl]but-2-enoate Chemical compound [Na+].C1=CC(OC)=CC=C1C(=O)C(\CC=1C=C(OC)C(OC)=C(OC)C=1)=C(/C([O-])=O)C1=CC2=NSN=C2C=C1 COKFAUSKNMGISZ-BMGIYVBOSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000002966 varnish Substances 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric 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
- A61P3/04—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
-
- 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
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (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)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Foreliggende oppfinnelse angår anvendelse av endotelinreseptor-antagonister for fremstilling av medikamenter for å kontrollere hyperlipidemi.
Peptidhormonet endotelin er kjent for sin sterke vasokonstriktoregenskap. Endotelin- reseptor-antagonister testes derfor hovedsakelig i kardiovaskulære patologier.
Endotelinreseptor-antagonister som kan anvendes er både endotelinA- og blandet endotelinA/B reseptor-antagonister.
Spesielt egnede endotelinreseptor-antagonister er:
1. TBC-11251 (J. Med. Chem., 40, No. 11, 1690-97, 1997), 2. BMS-193884 (EP 558,258)
3. BMS-207940 (Pharmaprojects (13,06,97)),
4. BQ-123 (Exp. Opin. Invest.Drugs, 1997, 6, No. 5, 475-487),
5. SB-209670 (Exp. Opin. Invest.Drugs, 1997, 6, No. 5, 475-487),
6. SB-217242 (Exp. Opin. Invest.Drugs, 1997, 6, No. 5, 475-487),
7. SB-209598 (Trends in Pharmacol. Sei., 17,177-81, 1996),
8. TAK-044 (Exp. Opin. Invest.Drugs, 1997, 6, No. 5, 475-487),
9. Bosentan (Trends in Pharmacol. Sei., 18, 408-12, 1997),
10. PD-156707 (J. Med. Chem., 40, No. 7,1063-74, 1997),
11. L-749329 (Bioorg. Med. Chem. Lett., 7, No. 3, 275-280,1997),
12. L-754142 (Exp. Opin. Invest.Drugs, 1997, 6, No. 5, 475-487),
13. ABT-627 (J. Med. Chem., 40, No. 20, 3217-27, 1997), 14. A-127772 (J. Med. Chem., 39, No. 5, 1039-1048, 1996), 15. A-206377 (213th American Chemical Society National Meeting, San Francisco,
California, USA, 13 - 17 April, 1997, Poster, MED1193),
16. A-182086 (J. Med. Chem., 40, No. 20, 3217-27, 1997), 17. EMD-93246 (211th American Chemical Society National Meeting, Ny Orleans,
USA, 1996, Poster, MED1143),
18. EMD-122801 (Bioorg. Med. Chem. Lett., 8, No. 1,17-22,1998),
19. ZD-1611 (Trends in Pharmacol. Sei., 18, 408-12,1997),
20. AC-610612 (R&D Focus Drugs News (18.05.98)),
21. T-0201 (70th Annual Meeting of the Japanese Pharmacological Society,
Chiba, Japan, 22-25 March 1997, Lecture, 0-133),
22. J-104132 (R&D Focus Drugs News (15,12,97)) og, spesielt,
Fedme er betegnelsen anvendt når kroppsvekten er minst 20% over normalvekten. Årsakene til fedme er overspising eller gal utnyttelse av maten, for eksempel familiær hyperkolesterolemi. Sykdommer forårsaket av eller ofte forbundet med fedme som kan nevnes er hypertensjon, type 2 diabetes, hyperlipidemi, kronisk nyresvikt og arteriosklerose og muligens også gikt.
Det har hittil vært mulig bare med store vanskeligheter å simulere patologisk tilstand av fedme i dyreforsøk (administrering av ekstremt høye kolesteroldoser). Imidlertid, har nylig, "knockout" mus som mangler genet for apolipoprotein E blitt avlet og kan anvendes for testing av forbindelser mot fedme.
Effekten av endotelinreseptor-antagonistsubstans 23 ble undersøkt i dyremodellen av apoE "knockout" mus. I kontrollrotter, som forventet, økte kroppsvekten til dyrene på en høy-fettdiett sterkt. Dette ble forbundet med en økning i størrelsen av leveren med samtidig fettdegenerasjon av leveren. I en parallel gruppe, ble dyrene behandlet med substans 23 (50 mg/kg/d). I denne gruppen, ble økningen i kropps- og levervekt fullstendig forhindret. Leveren var også histologisk uforandret.
EndotelinA- og endotelinA/B reseptor-antagonister må administreres hele livet. Deres dose er fra 50 til 500 mg pr. pasient og dag.
EndotelinA- og endotelinA/B reseptor-antagonister blir generelt administrert oralt, for eksempel i form av ubelagte, lakkerte og sukker-belagte tabletter, harde og myke gelatinkapsler, løsninger, emulsjoner eller suspensjoner. Imidlertid, kan administrering også finne sted rektalt, for eksempel i form av suppositorier eller parenteralt, for eksempel i form av injeksjonsløsninger.
For å produsere ubelagte, lakkerte og sukker-belagte tabletter, harde og myke gelatinkapsler, kan endotelinreseptor-antagonister prosesseres med farmasøytisk inerte, uorganiske eller organiske tilsetningsmidler. Tilsetningsmidler av disse typer som kan anvendes for ubelagte og sukker-belagte tabletter og harde gelatinkapsler er laktose, maisstivelse eller derivater derav, talk, stearinsyre eller dens salter. Tilsetningsmidler egnet for myke gelatinkapsler er vegetabilske oljer, vokser, fett, semifaste- og væskepolyoler.
Tilsetningsmidler egnet for å produsere løsninger og siruper er, for eksempel vann, polyoler, sukrose, invertsukker, glukose og lignende. Tilsetningsmidler egnet for injeksjonsløsninger er vann, alkoholer, polyoler, glycerol, vegetabilske oljer. Tilsetningsmidler egnet for suppositorier er naturlige eller herdede oljer, vokser, fett, semivæske eller væskepolyoler og lignende.
De farmasøytiske preparater kan dessuten inneholde konserveringsmidler, solubiliseringsmidler, stabiliseringsmidler, fuktemidler, emulgeringsmidler, søtningsmidler, farger, aromatiseringsmidler, salter for å endre det osmotiske trykket, buffere, belegningsmidler og/eller antioksydasjonsmidler.
De følgende eksempler illustrerer oppfinnelsen.
Eksempel 1
Lakkerte tabletter av de følgende preparater ble produsert:
Forbindelse 23, laktosen, cellulosen og polyvinylpyrrolidonet er våt-granulert og tørket. De siktede granuler blir blandet med magnesiumstearatet og blandingen er kompressert til ovale tablettkjerner som hver veier 390,0 mg. Kjernene blir deretter lakk-belagt inntil de lakkerte tabletter har nådd en endelig vekt på 400 mg.
Eksempel 2
Lakkerte tabletter ble produsert i analogi med Eksempel 1, men inneholdt 300 mg Forbindelse 26 istedenfor 300 mg Forbindelse 23.
Eksempel 3
Produksjon av harde gelatinkapsler av de følgende preparater:
De første fem bestanddeler er våt-granulert og tørket. Granulene blir blandet med natriumkarboksymetylstivelsen, talket og magnesiumstearatet og blandingen pakkes i størrelse 0 harde gelatinkapsler.
1. Anvendelse av endotelinreseptor-antagonister med følgende formler:
for å fremstille medikamenter for å kontrollere hyperlipidemi.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19754082A DE19754082A1 (de) | 1997-12-05 | 1997-12-05 | Methode zur Bekämpfung der Fettleibigkeit |
| PCT/EP1998/007501 WO1999029308A2 (de) | 1997-12-05 | 1998-11-21 | Methode zur bekämpfung der fettleibigkeit |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20002777D0 NO20002777D0 (no) | 2000-05-30 |
| NO20002777L NO20002777L (no) | 2000-06-02 |
| NO324694B1 true NO324694B1 (no) | 2007-12-03 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20002777A NO324694B1 (no) | 1997-12-05 | 2000-05-30 | Anvendelse av endotelinreseptor-antagonister for fremstilling av medikamenter for a kontrollere hyperlipidemi. |
| NO20074419A NO20074419L (no) | 1997-12-05 | 2007-08-30 | Anvendelse av endotelinreseptorantagonister for fremstilling av medikamenter for a bekjempe sykdom |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20074419A NO20074419L (no) | 1997-12-05 | 2007-08-30 | Anvendelse av endotelinreseptorantagonister for fremstilling av medikamenter for a bekjempe sykdom |
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| Country | Link |
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| US (1) | US6197780B1 (no) |
| EP (1) | EP1035851B1 (no) |
| JP (1) | JP2002512173A (no) |
| KR (1) | KR20010032779A (no) |
| CN (1) | CN1152685C (no) |
| AT (1) | ATE204172T1 (no) |
| AU (1) | AU751053B2 (no) |
| BR (1) | BR9815335A (no) |
| CA (1) | CA2311423C (no) |
| CZ (1) | CZ300442B6 (no) |
| DE (2) | DE19754082A1 (no) |
| ES (1) | ES2162493T3 (no) |
| HK (1) | HK1037141A1 (no) |
| HU (1) | HUP0100171A3 (no) |
| NO (2) | NO324694B1 (no) |
| RU (1) | RU2292891C2 (no) |
| WO (1) | WO1999029308A2 (no) |
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| DE19533023B4 (de) | 1994-10-14 | 2007-05-16 | Basf Ag | Neue Carbonsäurederivate, ihre Herstellung und Verwendung |
| EP1130027A1 (de) * | 2000-02-29 | 2001-09-05 | Aventis Pharma Deutschland GmbH | Memno-Peptide, Verfahren zu ihrer Herstellung und Verwendung derselben |
| US20050175667A1 (en) * | 2004-02-10 | 2005-08-11 | Wenda Carlyle | Use of endothelin antagonists to prevent restenosis |
| EP2190433A2 (en) | 2007-08-22 | 2010-06-02 | Gilead Colorado, Inc. | Therapy for complications of diabetes |
| PL3628320T3 (pl) | 2011-11-11 | 2022-07-25 | Gilead Apollo, Llc | Inhibitory acc i ich zastosowania |
| WO2016099233A2 (ru) * | 2014-10-20 | 2016-06-23 | Товарищество С Ограниченной Ответственностью "Фармацевтическая Компания "Ромат" | Фармацевтическая композиция для лечения туберкулеза |
| AR106472A1 (es) | 2015-10-26 | 2018-01-17 | Gilead Apollo Llc | Inhibidores de acc y usos de los mismos |
| SI3380479T1 (sl) | 2015-11-25 | 2023-04-28 | Gilead Apollo, Llc | Triazolni inhibitorji ACC in uporabe le-teh |
| CA3004796C (en) | 2015-11-25 | 2023-11-14 | Gilead Apollo, Llc | Pyrazole acc inhibitors and uses thereof |
| CA3004798C (en) | 2015-11-25 | 2023-10-31 | Gilead Apollo, Llc | Ester acc inhibitors and uses thereof |
| EP3379933B1 (en) | 2015-11-25 | 2023-02-15 | Gilead Apollo, LLC | Fungicidal compositions containing derivatives of 2,4-dioxo-1,4-dihydrothieno[2,3-d]pyrimidine |
| EP4364795A3 (en) | 2016-03-02 | 2024-08-14 | Gilead Apollo, LLC | Solid forms of a thienopyrimidinedione acc inhibitor and methods for production thereof |
| US20180280394A1 (en) | 2017-03-28 | 2018-10-04 | Gilead Sciences, Inc. | Methods of treating liver disease |
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| WO1994012499A1 (en) * | 1992-12-01 | 1994-06-09 | The Green Cross Corporation | 1,8-naphthyridin-2-one derivative and use thereof_ |
| WO1997008169A1 (en) | 1995-08-24 | 1997-03-06 | Warner-Lambert Company | Furanone endothelin antagonists |
| JP3116347B2 (ja) * | 1996-11-13 | 2000-12-11 | 田辺製薬株式会社 | 医薬組成物 |
-
1997
- 1997-12-05 DE DE19754082A patent/DE19754082A1/de not_active Withdrawn
-
1998
- 1998-11-21 JP JP2000523980A patent/JP2002512173A/ja active Pending
- 1998-11-21 DE DE59801230T patent/DE59801230D1/de not_active Expired - Lifetime
- 1998-11-21 US US09/530,131 patent/US6197780B1/en not_active Expired - Lifetime
- 1998-11-21 BR BR9815335-8A patent/BR9815335A/pt not_active Application Discontinuation
- 1998-11-21 KR KR1020007006075A patent/KR20010032779A/ko not_active Application Discontinuation
- 1998-11-21 EP EP98965685A patent/EP1035851B1/de not_active Expired - Lifetime
- 1998-11-21 WO PCT/EP1998/007501 patent/WO1999029308A2/de not_active Application Discontinuation
- 1998-11-21 AU AU21535/99A patent/AU751053B2/en not_active Ceased
- 1998-11-21 AT AT98965685T patent/ATE204172T1/de active
- 1998-11-21 HU HU0100171A patent/HUP0100171A3/hu unknown
- 1998-11-21 CN CNB988118327A patent/CN1152685C/zh not_active Expired - Fee Related
- 1998-11-21 CZ CZ20002006A patent/CZ300442B6/cs not_active IP Right Cessation
- 1998-11-21 CA CA002311423A patent/CA2311423C/en not_active Expired - Fee Related
- 1998-11-21 ES ES98965685T patent/ES2162493T3/es not_active Expired - Lifetime
-
2000
- 2000-05-30 NO NO20002777A patent/NO324694B1/no not_active IP Right Cessation
-
2001
- 2001-11-09 HK HK01107896A patent/HK1037141A1/xx not_active IP Right Cessation
-
2003
- 2003-12-29 RU RU2003138080/15A patent/RU2292891C2/ru not_active IP Right Cessation
-
2007
- 2007-08-30 NO NO20074419A patent/NO20074419L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| RU2292891C2 (ru) | 2007-02-10 |
| US6197780B1 (en) | 2001-03-06 |
| KR20010032779A (ko) | 2001-04-25 |
| HK1037141A1 (en) | 2002-02-01 |
| WO1999029308A3 (de) | 1999-09-30 |
| CZ300442B6 (cs) | 2009-05-20 |
| WO1999029308A2 (de) | 1999-06-17 |
| AU2153599A (en) | 1999-06-28 |
| DE19754082A1 (de) | 1999-06-10 |
| ATE204172T1 (de) | 2001-09-15 |
| EP1035851A2 (de) | 2000-09-20 |
| ES2162493T3 (es) | 2001-12-16 |
| CA2311423A1 (en) | 1999-06-17 |
| BR9815335A (pt) | 2000-10-17 |
| CN1152685C (zh) | 2004-06-09 |
| DE59801230D1 (de) | 2001-09-20 |
| HUP0100171A2 (hu) | 2003-02-28 |
| JP2002512173A (ja) | 2002-04-23 |
| CN1301162A (zh) | 2001-06-27 |
| NO20002777D0 (no) | 2000-05-30 |
| HUP0100171A3 (en) | 2003-10-28 |
| EP1035851B1 (de) | 2001-08-16 |
| AU751053B2 (en) | 2002-08-08 |
| NO20002777L (no) | 2000-06-02 |
| CA2311423C (en) | 2008-01-29 |
| NO20074419L (no) | 2000-06-02 |
| RU2003138080A (ru) | 2005-06-10 |
| CZ20002006A3 (cs) | 2000-11-15 |
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