NO333585B1 - Anvendelse av substituert cyanopyrrolidin til behandling av hyperlipidemi og assosierte sykdommer - Google Patents
Anvendelse av substituert cyanopyrrolidin til behandling av hyperlipidemi og assosierte sykdommer Download PDFInfo
- Publication number
- NO333585B1 NO333585B1 NO20045452A NO20045452A NO333585B1 NO 333585 B1 NO333585 B1 NO 333585B1 NO 20045452 A NO20045452 A NO 20045452A NO 20045452 A NO20045452 A NO 20045452A NO 333585 B1 NO333585 B1 NO 333585B1
- Authority
- NO
- Norway
- Prior art keywords
- compound
- formula
- hyperlipidemia
- pharmaceutically acceptable
- cholesterol
- Prior art date
Links
- 208000031226 Hyperlipidaemia Diseases 0.000 title claims abstract description 53
- 238000011282 treatment Methods 0.000 title abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 21
- 201000010099 disease Diseases 0.000 title description 15
- QJRYYOWARFCJQZ-UHFFFAOYSA-N pyrrolidine-1-carbonitrile Chemical class N#CN1CCCC1 QJRYYOWARFCJQZ-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 108
- 150000003839 salts Chemical group 0.000 claims abstract description 60
- 239000002253 acid Substances 0.000 claims abstract description 28
- 239000003814 drug Substances 0.000 claims description 28
- 229940079593 drug Drugs 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 239000004480 active ingredient Substances 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 14
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 6
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 4
- 230000002950 deficient Effects 0.000 claims description 3
- 206010020606 Hyperchylomicronaemia Diseases 0.000 claims description 2
- 208000029936 defective apolipoprotein b-100 Diseases 0.000 claims description 2
- 201000011110 familial lipoprotein lipase deficiency Diseases 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 13
- 239000003937 drug carrier Substances 0.000 abstract description 9
- 208000029078 coronary artery disease Diseases 0.000 abstract description 8
- 239000000203 mixture Substances 0.000 abstract description 8
- 238000002399 angioplasty Methods 0.000 abstract description 5
- 208000010125 myocardial infarction Diseases 0.000 abstract description 5
- 208000032928 Dyslipidaemia Diseases 0.000 abstract description 4
- 206010022562 Intermittent claudication Diseases 0.000 abstract description 4
- 208000032382 Ischaemic stroke Diseases 0.000 abstract description 4
- 208000018262 Peripheral vascular disease Diseases 0.000 abstract description 4
- 208000021156 intermittent vascular claudication Diseases 0.000 abstract description 4
- 230000000291 postprandial effect Effects 0.000 abstract description 4
- 208000037803 restenosis Diseases 0.000 abstract description 4
- 208000017170 Lipid metabolism disease Diseases 0.000 abstract description 3
- 206010028851 Necrosis Diseases 0.000 abstract description 3
- 230000017074 necrotic cell death Effects 0.000 abstract description 3
- 230000006907 apoptotic process Effects 0.000 abstract 1
- 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 52
- 108010007622 LDL Lipoproteins Proteins 0.000 description 24
- 102000007330 LDL Lipoproteins Human genes 0.000 description 24
- 239000000825 pharmaceutical preparation Substances 0.000 description 20
- 241000124008 Mammalia Species 0.000 description 19
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 19
- 235000012000 cholesterol Nutrition 0.000 description 19
- 102100040214 Apolipoprotein(a) Human genes 0.000 description 17
- 101710115418 Apolipoprotein(a) Proteins 0.000 description 17
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 17
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 15
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 15
- 238000012360 testing method Methods 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 12
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 12
- 239000013543 active substance Substances 0.000 description 11
- 239000003826 tablet Substances 0.000 description 11
- 108010010234 HDL Lipoproteins Proteins 0.000 description 10
- 102000015779 HDL Lipoproteins Human genes 0.000 description 10
- 229960003512 nicotinic acid Drugs 0.000 description 10
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 9
- 235000005152 nicotinamide Nutrition 0.000 description 9
- 239000011570 nicotinamide Substances 0.000 description 9
- 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 description 8
- 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 description 8
- 108010001831 LDL receptors Proteins 0.000 description 8
- 102000004895 Lipoproteins Human genes 0.000 description 8
- 108090001030 Lipoproteins Proteins 0.000 description 8
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 8
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 8
- 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 description 8
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 8
- 229960005370 atorvastatin Drugs 0.000 description 8
- 229960004844 lovastatin Drugs 0.000 description 8
- 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 description 8
- 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 description 8
- 229960002965 pravastatin Drugs 0.000 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 description 8
- 229960002855 simvastatin Drugs 0.000 description 8
- 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 description 8
- 230000000694 effects Effects 0.000 description 7
- 150000002632 lipids Chemical class 0.000 description 7
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 6
- 201000001320 Atherosclerosis Diseases 0.000 description 6
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 229960001138 acetylsalicylic acid Drugs 0.000 description 6
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 235000021152 breakfast Nutrition 0.000 description 6
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 229960003966 nicotinamide Drugs 0.000 description 6
- 239000004059 squalene synthase inhibitor Substances 0.000 description 6
- 229940011671 vitamin b6 Drugs 0.000 description 6
- 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 description 5
- 239000003529 anticholesteremic agent Substances 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 238000002648 combination therapy Methods 0.000 description 5
- 206010012601 diabetes mellitus Diseases 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 239000002319 fibrinogen receptor antagonist Substances 0.000 description 5
- 229960003765 fluvastatin Drugs 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 108050000824 Angiotensin II receptor Proteins 0.000 description 4
- 102000008873 Angiotensin II receptor Human genes 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 4
- 229920001268 Cholestyramine Polymers 0.000 description 4
- 229920002911 Colestipol Polymers 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 108010046315 IDL Lipoproteins Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 229920000080 bile acid sequestrant Polymers 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 4
- 229960002604 colestipol Drugs 0.000 description 4
- 230000007547 defect Effects 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- -1 hydrochloric Chemical class 0.000 description 4
- 235000012054 meals Nutrition 0.000 description 4
- 235000001968 nicotinic acid Nutrition 0.000 description 4
- 239000011664 nicotinic acid Substances 0.000 description 4
- 229960003912 probucol Drugs 0.000 description 4
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 229940088594 vitamin Drugs 0.000 description 4
- 229930003231 vitamin Natural products 0.000 description 4
- 235000013343 vitamin Nutrition 0.000 description 4
- 239000011782 vitamin Substances 0.000 description 4
- 235000019154 vitamin C Nutrition 0.000 description 4
- 239000011718 vitamin C Substances 0.000 description 4
- 235000019165 vitamin E Nutrition 0.000 description 4
- 239000011709 vitamin E Substances 0.000 description 4
- RWIUTHWKQHRQNP-ZDVGBALWSA-N (9e,12e)-n-(1-phenylethyl)octadeca-9,12-dienamide Chemical compound CCCCC\C=C\C\C=C\CCCCCCCC(=O)NC(C)C1=CC=CC=C1 RWIUTHWKQHRQNP-ZDVGBALWSA-N 0.000 description 3
- 239000005541 ACE inhibitor Substances 0.000 description 3
- 206010002383 Angina Pectoris Diseases 0.000 description 3
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 description 3
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 description 3
- 208000014882 Carotid artery disease Diseases 0.000 description 3
- 206010065559 Cerebral arteriosclerosis Diseases 0.000 description 3
- 101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 description 3
- 101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 description 3
- 229920002307 Dextran Polymers 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108010000775 Hydroxymethylglutaryl-CoA synthase Proteins 0.000 description 3
- 102100028889 Hydroxymethylglutaryl-CoA synthase, mitochondrial Human genes 0.000 description 3
- 229940123185 Squalene epoxidase inhibitor Drugs 0.000 description 3
- 229940123495 Squalene synthetase inhibitor Drugs 0.000 description 3
- 229930003537 Vitamin B3 Natural products 0.000 description 3
- 206010048214 Xanthoma Diseases 0.000 description 3
- 206010048215 Xanthomatosis Diseases 0.000 description 3
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 3
- 239000003957 anion exchange resin Substances 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 239000003524 antilipemic agent Substances 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 229940127218 antiplatelet drug Drugs 0.000 description 3
- 229960000516 bezafibrate Drugs 0.000 description 3
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229960001214 clofibrate Drugs 0.000 description 3
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 3
- 235000000639 cyanocobalamin Nutrition 0.000 description 3
- 239000011666 cyanocobalamin Substances 0.000 description 3
- 229960002104 cyanocobalamin Drugs 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 3
- 230000000378 dietary effect Effects 0.000 description 3
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 3
- 229960000815 ezetimibe Drugs 0.000 description 3
- 229960002297 fenofibrate Drugs 0.000 description 3
- 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 3
- 229940125753 fibrate Drugs 0.000 description 3
- 229960003627 gemfibrozil Drugs 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 229910052736 halogen Inorganic materials 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000000411 inducer Substances 0.000 description 3
- 201000005851 intracranial arteriosclerosis Diseases 0.000 description 3
- 229950008446 melinamide Drugs 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 3
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 3
- 235000008160 pyridoxine Nutrition 0.000 description 3
- 239000011677 pyridoxine Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000002461 renin inhibitor Substances 0.000 description 3
- 229940086526 renin-inhibitors Drugs 0.000 description 3
- 229950005143 sitosterol Drugs 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 150000003626 triacylglycerols Chemical class 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
- 235000019160 vitamin B3 Nutrition 0.000 description 3
- 239000011708 vitamin B3 Substances 0.000 description 3
- 235000019158 vitamin B6 Nutrition 0.000 description 3
- 239000011726 vitamin B6 Substances 0.000 description 3
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 102000015427 Angiotensins Human genes 0.000 description 2
- 108010064733 Angiotensins Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 108010004103 Chylomicrons Proteins 0.000 description 2
- 206010014476 Elevated cholesterol Diseases 0.000 description 2
- 206010014486 Elevated triglycerides Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 201000001376 Familial Combined Hyperlipidemia Diseases 0.000 description 2
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 description 2
- 208000026350 Inborn Genetic disease Diseases 0.000 description 2
- 108010028554 LDL Cholesterol Proteins 0.000 description 2
- 108090001060 Lipase Proteins 0.000 description 2
- 102000004882 Lipase Human genes 0.000 description 2
- 239000004367 Lipase Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 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
- 208000006011 Stroke Diseases 0.000 description 2
- 229930003779 Vitamin B12 Natural products 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 229940127226 anticholesterol agent Drugs 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000002876 beta blocker Substances 0.000 description 2
- 229940097320 beta blocking agent Drugs 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 235000019197 fats Nutrition 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
- 235000013305 food Nutrition 0.000 description 2
- 208000016361 genetic disease Diseases 0.000 description 2
- 235000019421 lipase Nutrition 0.000 description 2
- 230000037356 lipid metabolism Effects 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 235000021076 total caloric intake Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 235000019163 vitamin B12 Nutrition 0.000 description 2
- 239000011715 vitamin B12 Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 1
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 description 1
- KJTLQQUUPVSXIM-ZCFIWIBFSA-M (R)-mevalonate Chemical compound OCC[C@](O)(C)CC([O-])=O KJTLQQUUPVSXIM-ZCFIWIBFSA-M 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical class [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 208000000103 Anorexia Nervosa Diseases 0.000 description 1
- 102100029470 Apolipoprotein E Human genes 0.000 description 1
- 101710095339 Apolipoprotein E Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical class [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008635 Cholestasis Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000031288 Combined hyperlipidaemia Diseases 0.000 description 1
- 208000014311 Cushing syndrome Diseases 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 206010059183 Familial hypertriglyceridaemia Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 208000028782 Hereditary disease Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 208000001021 Hyperlipoproteinemia Type I Diseases 0.000 description 1
- 201000010252 Hyperlipoproteinemia Type III Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 238000008214 LDL Cholesterol Methods 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 108010033266 Lipoprotein(a) Proteins 0.000 description 1
- 102000057248 Lipoprotein(a) Human genes 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical class [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical class [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010035148 Plague Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 108090000783 Renin Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 208000035707 autosomal dominant type B hypercholesterolemia Diseases 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical class [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 229940076810 beta sitosterol Drugs 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- 235000013734 beta-carotene Nutrition 0.000 description 1
- 239000011648 beta-carotene Substances 0.000 description 1
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 1
- 229960002747 betacarotene Drugs 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Chemical class 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000007870 cholestasis Effects 0.000 description 1
- 231100000359 cholestasis Toxicity 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- 235000020974 cholesterol intake Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000013367 dietary fats Nutrition 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 201000001386 familial hypercholesterolemia Diseases 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000002308 glutamine derivatives Chemical class 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 208000020346 hyperlipoproteinemia Diseases 0.000 description 1
- 208000020887 hyperlipoproteinemia type 3 Diseases 0.000 description 1
- 208000000522 hyperlipoproteinemia type IV Diseases 0.000 description 1
- 208000003532 hypothyroidism Diseases 0.000 description 1
- 230000002989 hypothyroidism Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 108010022197 lipoprotein cholesterol Proteins 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000012792 lyophilization process Methods 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 210000003007 myelin sheath Anatomy 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 229940039748 oxalate Drugs 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Chemical class 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 108010000947 protamine zinc Chemical class 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000004141 reverse cholesterol transport Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 235000021003 saturated fats Nutrition 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol 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)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
- A61K31/401—Proline; Derivatives thereof, e.g. captopril
-
- 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
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biochemistry (AREA)
- Vascular Medicine (AREA)
- Toxicology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US38522002P | 2002-06-03 | 2002-06-03 | |
PCT/EP2003/005762 WO2003101448A1 (en) | 2002-06-03 | 2003-06-02 | The use of substituted cyanopyrrolidines and combination preparations containing them for treating hyperlipidemia and associated diseases |
Publications (2)
Publication Number | Publication Date |
---|---|
NO20045452L NO20045452L (no) | 2005-03-01 |
NO333585B1 true NO333585B1 (no) | 2013-07-15 |
Family
ID=29712145
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20045452A NO333585B1 (no) | 2002-06-03 | 2004-12-14 | Anvendelse av substituert cyanopyrrolidin til behandling av hyperlipidemi og assosierte sykdommer |
Country Status (26)
Country | Link |
---|---|
US (2) | US20050176806A1 (es) |
EP (1) | EP1513519B1 (es) |
JP (2) | JP2005532338A (es) |
KR (1) | KR20050012771A (es) |
CN (2) | CN101273987A (es) |
AT (1) | ATE422884T1 (es) |
AU (2) | AU2003245903B2 (es) |
BR (1) | BR0311535A (es) |
CA (1) | CA2487297C (es) |
CY (1) | CY1112800T1 (es) |
DE (1) | DE60326232D1 (es) |
DK (1) | DK1513519T3 (es) |
EC (1) | ECSP045469A (es) |
ES (1) | ES2321600T3 (es) |
HK (1) | HK1074794A1 (es) |
IL (1) | IL165181A (es) |
MX (1) | MXPA04012149A (es) |
NO (1) | NO333585B1 (es) |
NZ (1) | NZ536832A (es) |
PL (1) | PL210408B1 (es) |
PT (1) | PT1513519E (es) |
RU (1) | RU2362555C2 (es) |
SG (1) | SG154333A1 (es) |
SI (1) | SI1513519T1 (es) |
WO (1) | WO2003101448A1 (es) |
ZA (1) | ZA200409136B (es) |
Families Citing this family (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1513519B1 (en) * | 2002-06-03 | 2009-02-18 | Novartis AG | The use of substituted cyanopyrrolidines for treating hyperlipidemia |
AR041089A1 (es) * | 2003-05-15 | 2005-05-04 | Merck & Co Inc | Procedimiento y composiciones farmaceutiicas para tratar aterosclerosis, dislipidemias y afecciones relacionadas |
RS57561B1 (sr) | 2004-01-20 | 2018-10-31 | Novartis Ag | Formulacija dobijena direktnom kompresijom i proces za njeno dobijanje |
DOP2006000008A (es) | 2005-01-10 | 2006-08-31 | Arena Pharm Inc | Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1 |
WO2006083214A1 (en) * | 2005-02-02 | 2006-08-10 | Astrazeneca Ab | Pharmaceutical composition comprising a p2x7 receptor antagonist and a hmg-coa reductase inhibitor |
US7553861B2 (en) | 2005-04-22 | 2009-06-30 | Alantos Pharmaceuticals Holding, Inc. | Dipeptidyl peptidase-IV inhibitors |
PE20071221A1 (es) | 2006-04-11 | 2007-12-14 | Arena Pharm Inc | Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas |
WO2008097535A2 (en) * | 2007-02-08 | 2008-08-14 | Merck & Co., Inc. | Method of treating atherosclerosis, dyslipidemias and related conditions |
EP2146210A1 (en) | 2008-04-07 | 2010-01-20 | Arena Pharmaceuticals, Inc. | Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditions modulated by PYY |
AR077642A1 (es) | 2009-07-09 | 2011-09-14 | Arena Pharm Inc | Moduladores del metabolismo y el tratamiento de trastornos relacionados con el mismo |
BR112012025592A2 (pt) | 2010-04-06 | 2019-09-24 | Arena Pharm Inc | moduladores do receptor de gpr119 e o tratamento de distúrbios relacionados com os mesmos |
SG188548A1 (en) | 2010-09-22 | 2013-04-30 | Arena Pharm Inc | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
KR101298788B1 (ko) * | 2011-03-15 | 2013-08-22 | 보령제약 주식회사 | 안정성이 개선된 복합제제 |
US20140018371A1 (en) | 2011-04-01 | 2014-01-16 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
US20140066369A1 (en) | 2011-04-19 | 2014-03-06 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
WO2012145604A1 (en) | 2011-04-22 | 2012-10-26 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
US20140038889A1 (en) | 2011-04-22 | 2014-02-06 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
WO2012170702A1 (en) | 2011-06-08 | 2012-12-13 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
WO2013055910A1 (en) | 2011-10-12 | 2013-04-18 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
EA021236B1 (ru) * | 2012-10-03 | 2015-05-29 | Дафот Энтерпраизес Лимитед | Nα-АЦИЛЬНЫЕ ПРОИЗВОДНЫЕ АМИНОАЦИЛ-2-ЦИАНОПИРРОЛИДИНА - ИНГИБИТОРЫ ПРОЛИЛЭНДОПЕПТИДАЗЫ И ДИПЕПТИДИЛПЕПТИДАЗЫ-IV, ОБЛАДАЮЩИЕ ГИПОГЛИКЕМИЧЕСКИМ, ПРОТИВОГИПОКСИЧЕСКИМ, НЕЙРОПРОТЕКТОРНЫМ И УЛУЧШАЮЩИМ КОГНИТИВНЫЕ ФУНКЦИИ ДЕЙСТВИЕМ |
WO2014074668A1 (en) | 2012-11-08 | 2014-05-15 | Arena Pharmaceuticals, Inc. | Modulators of gpr119 and the treatment of disorders related thereto |
EA201791982A1 (ru) | 2015-03-09 | 2020-02-17 | Интекрин Терапьютикс, Инк. | Способы лечения неалкогольной жировой болезни печени и/или липодистрофии |
CA3058806A1 (en) | 2017-04-03 | 2018-10-11 | Coherus Biosciences Inc. | Ppar.gamma. agonist for treatment of progressive supranuclear palsy |
AU2020245415A1 (en) * | 2019-03-22 | 2021-09-16 | Rush University Medical Center | Combination of nasal gene delivery and oral cinnamic acid, oleamide or gemfibrozil for lysosomal stoarge disorders |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2572399B1 (fr) * | 1984-10-31 | 1987-01-16 | Panmedica Sa | Nouveaux derives de l'adamantanamine, leurs procedes de preparation et medicaments les contenant |
DE122010000020I1 (de) * | 1996-04-25 | 2010-07-08 | Prosidion Ltd | Verfahren zur Senkung des Blutglukosespiegels in Säugern |
US6011155A (en) * | 1996-11-07 | 2000-01-04 | Novartis Ag | N-(substituted glycyl)-2-cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
EP1052994A2 (en) * | 1998-02-02 | 2000-11-22 | Trustees Of Tufts College | Use of dipeptidylpetidase inhibitors to regulate glucose metabolism |
DE19828114A1 (de) * | 1998-06-24 | 2000-01-27 | Probiodrug Ges Fuer Arzneim | Produgs instabiler Inhibitoren der Dipeptidyl Peptidase IV |
DE19828113A1 (de) * | 1998-06-24 | 2000-01-05 | Probiodrug Ges Fuer Arzneim | Prodrugs von Inhibitoren der Dipeptidyl Peptidase IV |
AU6367399A (en) * | 1998-11-02 | 2000-05-22 | Welfide Corporation | Pyrrolidine compounds and medicinal utilization thereof |
CO5150173A1 (es) * | 1998-12-10 | 2002-04-29 | Novartis Ag | Compuestos n-(glicilo sustituido)-2-cianopirrolidinas inhibidores de peptidasa de dipeptidilo-iv (dpp-iv) los cuales son efectivos en el tratamiento de condiciones mediadas por la inhibicion de dpp-iv |
US6262118B1 (en) * | 1999-06-04 | 2001-07-17 | Metabolex, Inc. | Use of (-) (3-trihalomethylphenoxy) (4-halophenyl) acetic acid derivatives for treatment of insulin resistance, type 2 diabetes and hyperlipidemia |
JP4232332B2 (ja) * | 1999-11-10 | 2009-03-04 | 末藏 岩田 | タンク付電動床磨機用ブラシ台 |
JP2003520226A (ja) * | 2000-01-21 | 2003-07-02 | ノバルティス アクチエンゲゼルシャフト | ジペプチジルペプチダーゼ−iv阻害剤および抗糖尿病薬剤を含む組合せ物 |
EP1470246A2 (en) * | 2001-10-31 | 2004-10-27 | Novartis AG | Methods to treat diabetes and related conditions based on polymorphisms in the tcf1 gene |
AR039090A1 (es) * | 2002-03-22 | 2005-02-09 | Novartis Ag | Combinacion de compuestos organicos |
GB0212412D0 (en) * | 2002-05-29 | 2002-07-10 | Novartis Ag | Combination of organic compounds |
EP1513519B1 (en) * | 2002-06-03 | 2009-02-18 | Novartis AG | The use of substituted cyanopyrrolidines for treating hyperlipidemia |
US7935723B2 (en) * | 2004-06-04 | 2011-05-03 | Novartis Pharma Ag | Use of organic compounds |
PT1928499E (pt) * | 2005-09-20 | 2011-09-09 | Novartis Ag | Utilização de um inibidor da dpp-iv para reduzir eventos hipoglicémicos |
-
2003
- 2003-06-02 EP EP03737984A patent/EP1513519B1/en not_active Expired - Lifetime
- 2003-06-02 BR BR0311535-6A patent/BR0311535A/pt not_active IP Right Cessation
- 2003-06-02 CA CA2487297A patent/CA2487297C/en not_active Expired - Fee Related
- 2003-06-02 ES ES03737984T patent/ES2321600T3/es not_active Expired - Lifetime
- 2003-06-02 CN CNA2008100965659A patent/CN101273987A/zh active Pending
- 2003-06-02 PL PL374016A patent/PL210408B1/pl not_active IP Right Cessation
- 2003-06-02 KR KR10-2004-7019595A patent/KR20050012771A/ko active Search and Examination
- 2003-06-02 AU AU2003245903A patent/AU2003245903B2/en not_active Ceased
- 2003-06-02 PT PT03737984T patent/PT1513519E/pt unknown
- 2003-06-02 CN CNB038128446A patent/CN100402026C/zh not_active Expired - Fee Related
- 2003-06-02 SG SG200608456-0A patent/SG154333A1/en unknown
- 2003-06-02 DK DK03737984T patent/DK1513519T3/da active
- 2003-06-02 AT AT03737984T patent/ATE422884T1/de active
- 2003-06-02 MX MXPA04012149A patent/MXPA04012149A/es active IP Right Grant
- 2003-06-02 WO PCT/EP2003/005762 patent/WO2003101448A1/en active IP Right Grant
- 2003-06-02 US US10/516,633 patent/US20050176806A1/en not_active Abandoned
- 2003-06-02 JP JP2004508806A patent/JP2005532338A/ja not_active Withdrawn
- 2003-06-02 SI SI200331571T patent/SI1513519T1/sl unknown
- 2003-06-02 DE DE60326232T patent/DE60326232D1/de not_active Expired - Lifetime
- 2003-06-02 RU RU2004139029/14A patent/RU2362555C2/ru not_active IP Right Cessation
- 2003-06-02 NZ NZ536832A patent/NZ536832A/en not_active IP Right Cessation
-
2004
- 2004-11-11 IL IL165181A patent/IL165181A/en not_active IP Right Cessation
- 2004-11-11 ZA ZA2004/09136A patent/ZA200409136B/en unknown
- 2004-12-01 EC EC2004005469A patent/ECSP045469A/es unknown
- 2004-12-14 NO NO20045452A patent/NO333585B1/no not_active IP Right Cessation
-
2005
- 2005-08-18 HK HK05107206.0A patent/HK1074794A1/xx not_active IP Right Cessation
-
2006
- 2006-11-30 AU AU2006246483A patent/AU2006246483B9/en not_active Ceased
-
2009
- 2009-05-11 CY CY20091100499T patent/CY1112800T1/el unknown
-
2010
- 2010-04-05 JP JP2010087181A patent/JP2010155866A/ja active Pending
-
2011
- 2011-09-26 US US13/245,226 patent/US20120014907A1/en not_active Abandoned
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2006246483B9 (en) | The use of substituted cyanopyrrolidines and combination preparations containing them for treating hyperlipidemia and associated diseases | |
Haria et al. | Pravastatin: a reappraisal of its pharmacological properties and clinical effectiveness in the management of coronary heart disease | |
KR101494067B1 (ko) | 부작용을 최소화하면서 과지질혈증 및 과콜레스테롤혈증과 연관된 질환 또는 질병의 치료 방법 | |
JP2005532338A5 (es) | ||
NO326245B1 (no) | Anvendelse av et statin for fremstilling av et medikament ved behandling av heterozygot familiaer hyperkolesterolemi | |
JP2001514224A (ja) | アムロジピンとスタチン化合物を含む併用療法 | |
Basak et al. | An overview on management of diabetic dyslipidemia | |
KR20010101790A (ko) | (e)-7-[4-(4-플루오로페닐)-6-이소프로필-2-[메틸(메틸술포닐)아미노]피리미딘-5-일](3r,5s)-3,5-디히드록시헵트-6-엔산 및 p450 이소효소 3a4의 억제제, 유도제 또는기질을 함유하는 약물 조합물 | |
CA2679416A1 (en) | Combination therapy, composition and methods for the treatment of cardiovascular disorders | |
Alzahrani et al. | Evaluative role of family physician in diagnosis and management of gout in primary health care centers: A simple literature review | |
TWI302457B (en) | A pharmaceutical composition for improving blood lipid or reducing blood homocysteine | |
JP6227535B2 (ja) | 脂質異常症の予防又は治療薬 | |
NZ548902A (en) | The use of substituted cyanopyrrolidines and combination preparations containing them for treating hyperlipidemia and associated diseases | |
Shimpi et al. | Bempedoic acid a novel drug used for the treatment of Hyperlipidaemia: A Review | |
Dujovne et al. | Clinical pharmacologic concepts for the rational selection and use of drugs for the management of dyslipidemia | |
Marks | Control of lipid disorders in patients with atherosclerotic vascular disease | |
Rajput | Lipid-modifying therapy | |
US20090275551A1 (en) | Fluvastatin for the treatment of patients with a history of muscle related side effects with other statins | |
Behl et al. | Dyslipidemia in Diabetes Mellitus | |
Van der Westhuizen | Evidence based pharmacy practice (EBPP): dyslipidaemia | |
SK11092001A3 (sk) | Kombinácia vzájomne nereagujúcich liečiv obsahujúca inhibítor hmg-coa reduktázy a inhibítor, induktor alebo substrát p450 izoenzýmu 3a4 | |
HU226062B1 (en) | Drug combinations comprising (e)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl-(methylsulfonyl)-amino]pyrimidin-5-yl](3r,5s)-3,5-dihydroxyhept-6-enoic acid and an inhibitor, inducer or substrate of p450 isoenzyme 3a4 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |