NZ542505A - Use of low molecular weight thrombin inhibitors in cholesterol-lowering therapy - Google Patents
Use of low molecular weight thrombin inhibitors in cholesterol-lowering therapyInfo
- Publication number
- NZ542505A NZ542505A NZ542505A NZ54250504A NZ542505A NZ 542505 A NZ542505 A NZ 542505A NZ 542505 A NZ542505 A NZ 542505A NZ 54250504 A NZ54250504 A NZ 54250504A NZ 542505 A NZ542505 A NZ 542505A
- Authority
- NZ
- New Zealand
- Prior art keywords
- substituents
- pab
- parts
- aze
- formula
- Prior art date
Links
- 229940122388 Thrombin inhibitor Drugs 0.000 title claims abstract description 63
- 239000003868 thrombin inhibitor Substances 0.000 title claims abstract description 63
- 238000002560 therapeutic procedure Methods 0.000 title claims abstract description 43
- 229940002612 prodrug Drugs 0.000 claims abstract description 43
- 239000000651 prodrug Substances 0.000 claims abstract description 43
- 101000712605 Theromyzon tessulatum Theromin Proteins 0.000 claims abstract description 42
- 239000003814 drug Substances 0.000 claims abstract description 36
- 238000004519 manufacturing process Methods 0.000 claims abstract description 12
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims abstract 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 claims description 58
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 39
- 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 description 37
- 229960002137 melagatran Drugs 0.000 claims description 33
- 125000001153 fluoro group Chemical group F* 0.000 claims description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims description 30
- 238000011282 treatment Methods 0.000 claims description 26
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 210000002966 serum Anatomy 0.000 claims description 20
- 239000012634 fragment Substances 0.000 claims description 19
- 150000003626 triacylglycerols Chemical class 0.000 claims description 19
- 108010010234 HDL Lipoproteins Proteins 0.000 claims description 18
- 102000015779 HDL Lipoproteins Human genes 0.000 claims description 18
- 229940124597 therapeutic agent Drugs 0.000 claims description 18
- 239000002671 adjuvant Substances 0.000 claims description 17
- 239000003085 diluting agent Substances 0.000 claims description 17
- 108010007622 LDL Lipoproteins Proteins 0.000 claims description 15
- 102000007330 LDL Lipoproteins Human genes 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 15
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 13
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 11
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 10
- 239000003112 inhibitor Substances 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 108010062497 VLDL Lipoproteins Proteins 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 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 8
- 229960002965 pravastatin Drugs 0.000 claims description 8
- 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 8
- 102000005666 Apolipoprotein A-I Human genes 0.000 claims description 7
- 108010059886 Apolipoprotein A-I Proteins 0.000 claims description 7
- FJLGEFLZQAZZCD-MCBHFWOFSA-N (3R,5S)-fluvastatin Chemical compound 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 FJLGEFLZQAZZCD-MCBHFWOFSA-N 0.000 claims description 5
- 101710095342 Apolipoprotein B Proteins 0.000 claims description 5
- 102100040202 Apolipoprotein B-100 Human genes 0.000 claims description 5
- 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 5
- 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 5
- 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 5
- 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 5
- 229960005370 atorvastatin Drugs 0.000 claims description 5
- 229960003765 fluvastatin Drugs 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 229960004844 lovastatin Drugs 0.000 claims description 5
- 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 5
- 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 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 229960000672 rosuvastatin Drugs 0.000 claims description 5
- 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 5
- 229960002855 simvastatin Drugs 0.000 claims description 5
- 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 5
- 229910052760 oxygen Inorganic materials 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
- 235000012000 cholesterol Nutrition 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 16
- 150000002632 lipids Chemical class 0.000 description 12
- 229960001522 ximelagatran Drugs 0.000 description 11
- 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 11
- 239000000203 mixture Substances 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 229940079593 drug Drugs 0.000 description 8
- 238000009472 formulation Methods 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 239000003869 thrombin derivative Substances 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
- 108010028554 LDL Cholesterol Proteins 0.000 description 6
- 102000004895 Lipoproteins Human genes 0.000 description 6
- 108090001030 Lipoproteins Proteins 0.000 description 6
- 208000006011 Stroke Diseases 0.000 description 6
- 108010071619 Apolipoproteins Proteins 0.000 description 5
- 102000007592 Apolipoproteins Human genes 0.000 description 5
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- -1 4-amidinobenzylamino Chemical group 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 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
- 108090000190 Thrombin Proteins 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 229960004072 thrombin Drugs 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
- 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
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 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
- 208000037265 diseases, disorders, signs and symptoms Diseases 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
- 238000001727 in vivo Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 208000037804 stenosis Diseases 0.000 description 2
- 230000036262 stenosis Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- WAMWSIDTKSNDCU-ZETCQYMHSA-N (2s)-2-azaniumyl-2-cyclohexylacetate Chemical group OC(=O)[C@@H](N)C1CCCCC1 WAMWSIDTKSNDCU-ZETCQYMHSA-N 0.000 description 1
- 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
- CDPROXZBMHOBTQ-SJORKVTESA-N 2-[[(2r)-3-cyclohexyl-1-[(2s)-2-[3-(diaminomethylideneamino)propylcarbamoyl]piperidin-1-yl]-1-oxopropan-2-yl]amino]acetic acid Chemical compound NC(N)=NCCCNC(=O)[C@@H]1CCCCN1C(=O)[C@H](NCC(O)=O)CC1CCCCC1 CDPROXZBMHOBTQ-SJORKVTESA-N 0.000 description 1
- IDWUSJOEYZAKSW-UHFFFAOYSA-N 3-(pyridin-1-ium-2-ylamino)propanoate Chemical compound OC(=O)CCNC1=CC=CC=N1 IDWUSJOEYZAKSW-UHFFFAOYSA-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
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 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
- 208000023768 LCAT deficiency Diseases 0.000 description 1
- 208000003465 Lecithin Cholesterol Acyltransferase Deficiency Diseases 0.000 description 1
- 206010067125 Liver injury 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
- 208000030831 Peripheral arterial occlusive disease Diseases 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
- 210000001367 artery Anatomy 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
- 230000004071 biological effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect 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
- 230000003915 cell function Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 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
- 239000013066 combination product Substances 0.000 description 1
- 229940127555 combination product Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- UITNIDFEANEWPC-UHFFFAOYSA-N ethyl 3-(pyridin-2-ylamino)propanoate Chemical compound CCOC(=O)CCNC1=CC=CC=N1 UITNIDFEANEWPC-UHFFFAOYSA-N 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
- 229950003499 fibrin Drugs 0.000 description 1
- 235000019688 fish Nutrition 0.000 description 1
- 125000004428 fluoroalkoxy group Chemical group 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 230000006870 function Effects 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
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 208000020346 hyperlipoproteinemia Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229950003291 inogatran Drugs 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012423 maintenance 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
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000009522 phase III clinical trial Methods 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 235000013594 poultry meat Nutrition 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 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
- 238000012552 review Methods 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
- 239000012453 solvate Substances 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
- 238000012360 testing method Methods 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 230000009424 thromboembolic 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 |
|---|---|---|---|
| GBGB0306615.6A GB0306615D0 (en) | 2003-03-22 | 2003-03-22 | New use |
| PCT/SE2004/000417 WO2004082702A1 (en) | 2003-03-22 | 2004-03-19 | Use of low molecular weight thrombin inhibitors in cholesterol-lowering therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ542505A true NZ542505A (en) | 2009-01-31 |
Family
ID=9955311
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ542505A NZ542505A (en) | 2003-03-22 | 2004-03-19 | Use of low molecular weight thrombin inhibitors in cholesterol-lowering therapy |
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 |
| ES2346969T3 (es) | 2010-10-22 |
| 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 |
|---|---|---|
| KR100815042B1 (ko) | 이형접합성 가족성 고콜레스테롤혈증 치료에 있어서로수바스타틴(zd-4522)의 용도 | |
| RU2765218C2 (ru) | Фиксированные комбинации и составы, содержащие етс1002 и один или более статинов, и способы лечения или уменьшения риска развития сердечно-сосудистого заболевания | |
| JPH04225916A (ja) | 脂血障害の治療用組成物 | |
| JP2005532338A5 (https=) | ||
| KR100539066B1 (ko) | 비정상적 지질대사-유래 질환치료에 유용한 스타틴과알카노일 l-카르니틴 함유 약제 조성물 | |
| AU2004222409B2 (en) | Use of low molecular weight thrombin inhibitors in cholesterol-lowering therapy | |
| RU2007149337A (ru) | Новый способ лечения гиперлипидемии | |
| WO2009100245A1 (en) | Low dose hmg-coa reductase inhibitor with reduced side effects | |
| HK1084329B (en) | Use of low molecular weight thrombin inhibitors in cholesterol-lowering therapy | |
| JP6227535B2 (ja) | 脂質異常症の予防又は治療薬 | |
| WO2012092103A1 (en) | Gemcabene and derivatives for treating pancreatitis | |
| AU2001282541B2 (en) | Medicinal compositions | |
| WO2010106135A1 (en) | Combined use for the treatment of ovarian carcinoma | |
| KR100983990B1 (ko) | Atp 시트르산 리아제의 발현 억제용 의약 조성물 | |
| AU2015202580B2 (en) | Gemcabene and derivatives for treating pancreatitis | |
| JP2002145774A (ja) | 医薬組成物 | |
| JP2001114682A (ja) | 没食子酸誘導体を含む医薬組成物 | |
| AU2017299587B2 (en) | Methods and compositions for alleviating myopathy | |
| US20090209613A1 (en) | Use of allymercaptocaptopril for treating or preventing obesity and obesity related diseases | |
| CN101057838A (zh) | 预防和/或治疗高脂血症的药物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RENW | Renewal (renewal fees accepted) | ||
| PSEA | Patent sealed |