ES2346969T3 - Uso de inhibidores de trombina de bajo peso molecular en terapia de disminucion de colesterol. - Google Patents
Uso de inhibidores de trombina de bajo peso molecular en terapia de disminucion de colesterol. Download PDFInfo
- Publication number
- ES2346969T3 ES2346969T3 ES04722129T ES04722129T ES2346969T3 ES 2346969 T3 ES2346969 T3 ES 2346969T3 ES 04722129 T ES04722129 T ES 04722129T ES 04722129 T ES04722129 T ES 04722129T ES 2346969 T3 ES2346969 T3 ES 2346969T3
- Authority
- ES
- Spain
- Prior art keywords
- pab
- formula
- aze
- compound
- alkyl
- 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.)
- Expired - Lifetime
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 86
- 235000012000 cholesterol Nutrition 0.000 title claims abstract description 37
- 229940122388 Thrombin inhibitor Drugs 0.000 title claims abstract description 33
- 239000003868 thrombin inhibitor Substances 0.000 title claims abstract description 33
- 238000002560 therapeutic procedure Methods 0.000 title claims abstract description 22
- 230000007423 decrease Effects 0.000 title claims description 13
- 101000712605 Theromyzon tessulatum Theromin Proteins 0.000 claims abstract description 20
- 150000002632 lipids Chemical class 0.000 claims abstract description 18
- 102000004895 Lipoproteins Human genes 0.000 claims abstract description 11
- 108090001030 Lipoproteins Proteins 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 33
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 23
- 150000003626 triacylglycerols Chemical class 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 15
- 108010010234 HDL Lipoproteins Proteins 0.000 claims description 14
- 102000015779 HDL Lipoproteins Human genes 0.000 claims description 14
- 239000013066 combination product Substances 0.000 claims description 14
- 229940127555 combination product Drugs 0.000 claims description 14
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 210000002966 serum Anatomy 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- -1 cyclohexyl glycol Chemical compound 0.000 claims description 10
- 239000012453 solvate Substances 0.000 claims description 10
- 229940124597 therapeutic agent Drugs 0.000 claims description 10
- 239000002671 adjuvant Substances 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 7
- 108010062497 VLDL Lipoproteins Proteins 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 6
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 102000005666 Apolipoprotein A-I Human genes 0.000 claims description 5
- 108010059886 Apolipoprotein A-I Proteins 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 208000020346 hyperlipoproteinemia Diseases 0.000 claims description 5
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 5
- 239000012634 fragment Substances 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 101710095342 Apolipoprotein B Proteins 0.000 claims description 3
- 102100040202 Apolipoprotein B-100 Human genes 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 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 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
- 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 2
- 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 2
- 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 2
- 229960005370 atorvastatin Drugs 0.000 claims description 2
- 229960003765 fluvastatin Drugs 0.000 claims description 2
- 229960004844 lovastatin Drugs 0.000 claims description 2
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound 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 2
- 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 2
- 229960002797 pitavastatin Drugs 0.000 claims description 2
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 claims description 2
- 229960002965 pravastatin Drugs 0.000 claims description 2
- 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 2
- 229960000672 rosuvastatin Drugs 0.000 claims description 2
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 2
- 229960002855 simvastatin Drugs 0.000 claims description 2
- 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 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims 3
- 230000003467 diminishing effect Effects 0.000 claims 1
- DKWNMCUOEDMMIN-PKOBYXMFSA-N melagatran Chemical compound C1=CC(C(=N)N)=CC=C1CNC(=O)[C@H]1N(C(=O)[C@H](NCC(O)=O)C2CCCCC2)CC1 DKWNMCUOEDMMIN-PKOBYXMFSA-N 0.000 claims 1
- 229960002137 melagatran Drugs 0.000 claims 1
- 108010071619 Apolipoproteins Proteins 0.000 abstract description 6
- 102000007592 Apolipoproteins Human genes 0.000 abstract description 6
- 238000000034 method Methods 0.000 abstract description 5
- 238000012986 modification Methods 0.000 abstract description 5
- 230000004048 modification Effects 0.000 abstract description 5
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 abstract description 3
- 230000002526 effect on cardiovascular system Effects 0.000 abstract description 2
- 229940002612 prodrug Drugs 0.000 description 16
- 239000000651 prodrug Substances 0.000 description 16
- 239000000203 mixture Substances 0.000 description 13
- 108010007622 LDL Lipoproteins Proteins 0.000 description 12
- 102000007330 LDL Lipoproteins Human genes 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- ZXIBCJHYVWYIKI-PZJWPPBQSA-N ximelagatran Chemical compound C1([C@@H](NCC(=O)OCC)C(=O)N2[C@@H](CC2)C(=O)NCC=2C=CC(=CC=2)C(\N)=N\O)CCCCC1 ZXIBCJHYVWYIKI-PZJWPPBQSA-N 0.000 description 8
- 229960001522 ximelagatran Drugs 0.000 description 8
- 238000009472 formulation Methods 0.000 description 7
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 7
- 229960005080 warfarin Drugs 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 108090000190 Thrombin Proteins 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 229960004072 thrombin Drugs 0.000 description 5
- 108010028554 LDL Cholesterol Proteins 0.000 description 4
- 208000006011 Stroke Diseases 0.000 description 4
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 4
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108010023302 HDL Cholesterol Proteins 0.000 description 3
- 238000008214 LDL Cholesterol Methods 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000003869 thrombin derivative Substances 0.000 description 3
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- 102000018616 Apolipoproteins B Human genes 0.000 description 2
- 108010027006 Apolipoproteins B Proteins 0.000 description 2
- 206010003658 Atrial Fibrillation Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 208000031481 Pathologic Constriction Diseases 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- 208000032109 Transient ischaemic attack Diseases 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000036262 stenosis Effects 0.000 description 2
- 208000037804 stenosis Diseases 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 201000010875 transient cerebral ischemia Diseases 0.000 description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- 229920002911 Colestipol Polymers 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 1
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
- 208000023768 LCAT deficiency Diseases 0.000 description 1
- 208000003465 Lecithin Cholesterol Acyltransferase Deficiency Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 229940061720 alpha hydroxy acid Drugs 0.000 description 1
- 150000001280 alpha hydroxy acids Chemical class 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000005800 cardiovascular problem Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
- 229960002604 colestipol Drugs 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 235000019688 fish Nutrition 0.000 description 1
- 125000004428 fluoroalkoxy group Chemical group 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 229960003627 gemfibrozil Drugs 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000009522 phase III clinical trial Methods 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960004796 rosuvastatin calcium Drugs 0.000 description 1
- LALFOYNTGMUKGG-BGRFNVSISA-L rosuvastatin calcium Chemical compound [Ca+2].CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O.CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O LALFOYNTGMUKGG-BGRFNVSISA-L 0.000 description 1
- 235000014102 seafood Nutrition 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- 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
- A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
-
- 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
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0306615 | 2003-03-22 | ||
| GBGB0306615.6A GB0306615D0 (en) | 2003-03-22 | 2003-03-22 | New use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2346969T3 true ES2346969T3 (es) | 2010-10-22 |
Family
ID=9955311
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES04722129T Expired - Lifetime ES2346969T3 (es) | 2003-03-22 | 2004-03-19 | Uso de inhibidores de trombina de bajo peso molecular en terapia de disminucion de colesterol. |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US20060183692A1 (https=) |
| EP (1) | EP1608311B1 (https=) |
| JP (1) | JP2006520813A (https=) |
| KR (1) | KR20050114237A (https=) |
| CN (1) | CN1761479A (https=) |
| AT (1) | ATE475417T1 (https=) |
| AU (1) | AU2004222409B2 (https=) |
| BR (1) | BRPI0408522A (https=) |
| CA (1) | CA2517191A1 (https=) |
| DE (1) | DE602004028348D1 (https=) |
| ES (1) | ES2346969T3 (https=) |
| GB (1) | GB0306615D0 (https=) |
| MX (1) | MXPA05010159A (https=) |
| NO (1) | NO20054285L (https=) |
| NZ (1) | NZ542505A (https=) |
| WO (1) | WO2004082702A1 (https=) |
| ZA (1) | ZA200507614B (https=) |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1237518B (it) * | 1989-11-24 | 1993-06-08 | Renato Conti | Eparine supersolfatate |
| JP3140790B2 (ja) * | 1996-04-23 | 2001-03-05 | メルク エンド カンパニー インコーポレーテッド | ピラジノン系トロンビン阻害薬 |
| WO1998011896A1 (en) * | 1996-09-18 | 1998-03-26 | Merck & Co., Inc. | Combination therapy for reducing the risks associated with cardiovascular disease |
| US20030077229A1 (en) * | 1997-10-01 | 2003-04-24 | Dugger Harry A. | Buccal, polar and non-polar spray or capsule containing cardiovascular or renal drugs |
| AR023510A1 (es) * | 1999-04-21 | 2002-09-04 | Astrazeneca Ab | Un equipo de partes, formulacion farmaceutica y uso de un inhibidor de trombina. |
| GB0014136D0 (en) * | 2000-06-10 | 2000-08-02 | Astrazeneca Ab | Combination therapy |
| US6462021B1 (en) * | 2000-11-06 | 2002-10-08 | Astrazeneca Ab | Use of low molecular weight thrombin inhibitor |
| AR035216A1 (es) * | 2000-12-01 | 2004-05-05 | Astrazeneca Ab | Derivados de acido mandelico ,derivados farmaceuticamente aceptables, uso de estos derivados para la fabricacion de medicamentos, metodos de tratamiento ,procesos para la preparacion de estos derivados, y compuestos intermediarios |
| AU2003270861A1 (en) * | 2002-10-02 | 2004-04-23 | Bristol-Myers Squibb Company | Novel combination of a factor xa inhibitor and clopidogrel |
| US7470538B2 (en) * | 2002-12-05 | 2008-12-30 | Case Western Reserve University | Cell-based therapies for ischemia |
| US7371759B2 (en) * | 2003-09-25 | 2008-05-13 | Bristol-Myers Squibb Company | HMG-CoA reductase inhibitors and method |
-
2003
- 2003-03-22 GB GBGB0306615.6A patent/GB0306615D0/en not_active Ceased
-
2004
- 2004-03-19 KR KR1020057017258A patent/KR20050114237A/ko not_active Ceased
- 2004-03-19 MX MXPA05010159A patent/MXPA05010159A/es not_active Application Discontinuation
- 2004-03-19 US US10/550,154 patent/US20060183692A1/en not_active Abandoned
- 2004-03-19 DE DE602004028348T patent/DE602004028348D1/de not_active Expired - Lifetime
- 2004-03-19 JP JP2006507972A patent/JP2006520813A/ja active Pending
- 2004-03-19 ES ES04722129T patent/ES2346969T3/es not_active Expired - Lifetime
- 2004-03-19 CN CNA2004800072860A patent/CN1761479A/zh active Pending
- 2004-03-19 AT AT04722129T patent/ATE475417T1/de not_active IP Right Cessation
- 2004-03-19 BR BRPI0408522-1A patent/BRPI0408522A/pt not_active IP Right Cessation
- 2004-03-19 CA CA002517191A patent/CA2517191A1/en not_active Abandoned
- 2004-03-19 NZ NZ542505A patent/NZ542505A/en unknown
- 2004-03-19 AU AU2004222409A patent/AU2004222409B2/en not_active Ceased
- 2004-03-19 WO PCT/SE2004/000417 patent/WO2004082702A1/en not_active Ceased
- 2004-03-19 EP EP04722129A patent/EP1608311B1/en not_active Expired - Lifetime
-
2005
- 2005-09-16 NO NO20054285A patent/NO20054285L/no not_active Application Discontinuation
- 2005-09-20 ZA ZA200507614A patent/ZA200507614B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2004222409A1 (en) | 2004-09-30 |
| CA2517191A1 (en) | 2004-09-30 |
| MXPA05010159A (es) | 2005-11-16 |
| HK1084329A1 (en) | 2006-07-28 |
| EP1608311A1 (en) | 2005-12-28 |
| JP2006520813A (ja) | 2006-09-14 |
| ZA200507614B (en) | 2006-06-28 |
| GB0306615D0 (en) | 2003-04-30 |
| NO20054285L (no) | 2005-10-20 |
| CN1761479A (zh) | 2006-04-19 |
| NO20054285D0 (no) | 2005-09-16 |
| KR20050114237A (ko) | 2005-12-05 |
| BRPI0408522A (pt) | 2006-03-07 |
| EP1608311B1 (en) | 2010-07-28 |
| DE602004028348D1 (de) | 2010-09-09 |
| US20060183692A1 (en) | 2006-08-17 |
| NZ542505A (en) | 2009-01-31 |
| ATE475417T1 (de) | 2010-08-15 |
| WO2004082702A8 (en) | 2005-03-24 |
| WO2004082702A1 (en) | 2004-09-30 |
| AU2004222409B2 (en) | 2007-03-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6295205B2 (ja) | 心血管疾患のリスクを低減する方法 | |
| US20180133177A1 (en) | Treatment of NASH with Gemcabene | |
| ES2305118T3 (es) | Uso de rosuvastatina (zd-4522) en el tratamiento de hipercolesteremia familiar heterocigota. | |
| RU2765218C2 (ru) | Фиксированные комбинации и составы, содержащие етс1002 и один или более статинов, и способы лечения или уменьшения риска развития сердечно-сосудистого заболевания | |
| ES2321600T3 (es) | El uso cianopirrolidinas sustituidas para tratar hiperlipidemia. | |
| JP2005533810A (ja) | 新規な抗コレステロール組成物及びその使用方法 | |
| JP2012232995A (ja) | 高脂血症および高コレステロール血症に関連する障害または疾患を、副作用を最小限にしつつ処置するための方法 | |
| JP2005532338A5 (https=) | ||
| JP2007527433A5 (https=) | ||
| ES2346969T3 (es) | Uso de inhibidores de trombina de bajo peso molecular en terapia de disminucion de colesterol. | |
| US20060173067A1 (en) | Small molecules for the treatment of atherosclerosis | |
| JP2018027953A (ja) | 膵炎を治療するためのゲムカベンおよび誘導体 | |
| JP2021534208A (ja) | 高コレステロール関連疾患について処置されている患者において糖尿病のリスクを低減させる方法 | |
| RU2007149337A (ru) | Новый способ лечения гиперлипидемии | |
| JP6227535B2 (ja) | 脂質異常症の予防又は治療薬 | |
| HK1084329B (en) | Use of low molecular weight thrombin inhibitors in cholesterol-lowering therapy | |
| AU2015202580B2 (en) | Gemcabene and derivatives for treating pancreatitis | |
| CN1473042A (zh) | 药物组合物 | |
| WO2025093129A1 (en) | Treatment and prevention of age-related macular degeneration using a cetp inhibitor | |
| Ferrario | ARBITER 6-HALTS. Does it have the power to settle all matters? | |
| Park et al. | KOREAN ROSUVASTATIN EFFECTIVENESS STUDY IN NONDIABETIC METABOLIC SYNDROME (KREST) | |
| WO2015191179A1 (en) | Ttp inhibitiors of low density lipprotein secretion for the management of diseases associated with elevated blood ldl levels |