KR20230107282A - 오메캄티브 메카빌을 투여하여 심부전을 치료하는 방법 - Google Patents
오메캄티브 메카빌을 투여하여 심부전을 치료하는 방법 Download PDFInfo
- Publication number
- KR20230107282A KR20230107282A KR1020237019053A KR20237019053A KR20230107282A KR 20230107282 A KR20230107282 A KR 20230107282A KR 1020237019053 A KR1020237019053 A KR 1020237019053A KR 20237019053 A KR20237019053 A KR 20237019053A KR 20230107282 A KR20230107282 A KR 20230107282A
- Authority
- KR
- South Korea
- Prior art keywords
- patient
- omecamtib
- heart failure
- mecabil
- less
- 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.)
- Pending
Links
- 206010019280 Heart failures Diseases 0.000 title claims abstract description 375
- 238000000034 method Methods 0.000 title claims abstract description 226
- 150000003839 salts Chemical class 0.000 claims abstract description 73
- 230000001747 exhibiting effect Effects 0.000 claims abstract description 24
- 102400001263 NT-proBNP Human genes 0.000 claims description 180
- 238000011282 treatment Methods 0.000 claims description 174
- 230000034994 death Effects 0.000 claims description 93
- 231100000517 death Toxicity 0.000 claims description 93
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 89
- 206010003658 Atrial Fibrillation Diseases 0.000 claims description 57
- 230000002829 reductive effect Effects 0.000 claims description 55
- 206010003662 Atrial flutter Diseases 0.000 claims description 48
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 claims description 48
- 229960005156 digoxin Drugs 0.000 claims description 48
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 claims description 48
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 claims description 48
- 208000038002 heart failure with reduced ejection fraction Diseases 0.000 claims description 35
- 230000002861 ventricular Effects 0.000 claims description 33
- QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 claims description 29
- 230000000302 ischemic effect Effects 0.000 claims description 22
- 208000001953 Hypotension Diseases 0.000 claims description 19
- 208000019269 advanced heart failure Diseases 0.000 claims description 18
- 230000036543 hypotension Effects 0.000 claims description 18
- 229940083712 aldosterone antagonist Drugs 0.000 claims description 17
- 208000010125 myocardial infarction Diseases 0.000 claims description 16
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 14
- 239000002876 beta blocker Substances 0.000 claims description 13
- 229940097320 beta blocking agent Drugs 0.000 claims description 13
- 238000009125 cardiac resynchronization therapy Methods 0.000 claims description 12
- 239000005541 ACE inhibitor Substances 0.000 claims description 11
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 11
- 239000003826 tablet Substances 0.000 claims description 10
- 230000036471 bradycardia Effects 0.000 claims description 8
- 208000006218 bradycardia Diseases 0.000 claims description 8
- 239000002934 diuretic Substances 0.000 claims description 8
- 229940030606 diuretics Drugs 0.000 claims description 8
- 102000008873 Angiotensin II receptor Human genes 0.000 claims description 7
- 108050000824 Angiotensin II receptor Proteins 0.000 claims description 7
- 241000208011 Digitalis Species 0.000 claims description 7
- 239000002170 aldosterone antagonist Substances 0.000 claims description 7
- 239000002792 enkephalinase inhibitor Substances 0.000 claims description 7
- 230000002008 hemorrhagic effect Effects 0.000 claims description 6
- -1 inotropes Substances 0.000 claims description 6
- 239000013563 matrix tablet Substances 0.000 claims description 5
- 238000002203 pretreatment Methods 0.000 claims description 5
- 230000005713 exacerbation Effects 0.000 claims description 4
- 230000008085 renal dysfunction Effects 0.000 claims description 4
- 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 claims description 3
- 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 claims description 3
- 230000009466 transformation Effects 0.000 claims description 3
- 208000004880 Polyuria Diseases 0.000 claims description 2
- 230000035619 diuresis Effects 0.000 claims description 2
- 108010008064 pro-brain natriuretic peptide (1-76) Proteins 0.000 claims 1
- 101800001904 NT-proBNP Proteins 0.000 description 179
- 230000009467 reduction Effects 0.000 description 156
- 230000000694 effects Effects 0.000 description 113
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 78
- 239000000902 placebo Substances 0.000 description 78
- 229940068196 placebo Drugs 0.000 description 78
- 208000006011 Stroke Diseases 0.000 description 68
- 230000035488 systolic blood pressure Effects 0.000 description 56
- 238000004458 analytical method Methods 0.000 description 49
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 41
- 230000001965 increasing effect Effects 0.000 description 40
- 235000019359 magnesium stearate Nutrition 0.000 description 39
- 230000003993 interaction Effects 0.000 description 33
- 230000000747 cardiac effect Effects 0.000 description 32
- 208000024891 symptom Diseases 0.000 description 32
- 239000002131 composite material Substances 0.000 description 30
- 230000007423 decrease Effects 0.000 description 28
- 239000003814 drug Substances 0.000 description 28
- 235000019886 MethocelTM Nutrition 0.000 description 27
- 229940079593 drug Drugs 0.000 description 27
- 238000012360 testing method Methods 0.000 description 27
- 230000003247 decreasing effect Effects 0.000 description 23
- 239000008194 pharmaceutical composition Substances 0.000 description 23
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 23
- 238000002560 therapeutic procedure Methods 0.000 description 22
- 230000008901 benefit Effects 0.000 description 21
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 20
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 20
- 239000001530 fumaric acid Substances 0.000 description 20
- 229960001021 lactose monohydrate Drugs 0.000 description 20
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 20
- 239000008108 microcrystalline cellulose Substances 0.000 description 20
- 229940016286 microcrystalline cellulose Drugs 0.000 description 20
- 239000008187 granular material Substances 0.000 description 19
- 230000006870 function Effects 0.000 description 18
- 238000000634 powder X-ray diffraction Methods 0.000 description 18
- 108020001621 Natriuretic Peptide Proteins 0.000 description 17
- 102000004571 Natriuretic peptide Human genes 0.000 description 17
- 239000000692 natriuretic peptide Substances 0.000 description 17
- 230000001225 therapeutic effect Effects 0.000 description 14
- 230000036470 plasma concentration Effects 0.000 description 13
- 102000003505 Myosin Human genes 0.000 description 11
- 108060008487 Myosin Proteins 0.000 description 11
- 230000008859 change Effects 0.000 description 11
- 230000002411 adverse Effects 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 201000010099 disease Diseases 0.000 description 9
- 230000006872 improvement Effects 0.000 description 9
- 230000003907 kidney function Effects 0.000 description 9
- 238000005259 measurement Methods 0.000 description 9
- 230000005855 radiation Effects 0.000 description 9
- 102000013602 Cardiac Myosins Human genes 0.000 description 8
- 108010051609 Cardiac Myosins Proteins 0.000 description 8
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 8
- 102100039205 Cytochrome P450 3A4 Human genes 0.000 description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 8
- 239000011591 potassium Substances 0.000 description 8
- 229910052700 potassium Inorganic materials 0.000 description 8
- 206010047281 Ventricular arrhythmia Diseases 0.000 description 7
- 238000013459 approach Methods 0.000 description 7
- 230000036772 blood pressure Effects 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 230000037081 physical activity Effects 0.000 description 7
- 210000002235 sarcomere Anatomy 0.000 description 7
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 6
- 102000013394 Troponin I Human genes 0.000 description 6
- 108010065729 Troponin I Proteins 0.000 description 6
- 230000009286 beneficial effect Effects 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 229910052791 calcium Inorganic materials 0.000 description 6
- 208000029078 coronary artery disease Diseases 0.000 description 6
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 102100022595 Broad substrate specificity ATP-binding cassette transporter ABCG2 Human genes 0.000 description 5
- 101000823298 Homo sapiens Broad substrate specificity ATP-binding cassette transporter ABCG2 Proteins 0.000 description 5
- 206010062237 Renal impairment Diseases 0.000 description 5
- 210000004413 cardiac myocyte Anatomy 0.000 description 5
- 230000002802 cardiorespiratory effect Effects 0.000 description 5
- 230000009760 functional impairment Effects 0.000 description 5
- 230000000977 initiatory effect Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 208000031225 myocardial ischemia Diseases 0.000 description 5
- 231100000857 poor renal function Toxicity 0.000 description 5
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 description 4
- 208000031229 Cardiomyopathies Diseases 0.000 description 4
- 241000320892 Clerodendrum phlomidis Species 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- 239000012190 activator Substances 0.000 description 4
- 230000022900 cardiac muscle contraction Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 210000004351 coronary vessel Anatomy 0.000 description 4
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000000411 inducer Substances 0.000 description 4
- 238000013160 medical therapy Methods 0.000 description 4
- 230000002107 myocardial effect Effects 0.000 description 4
- 230000036454 renin-angiotensin system Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 238000007619 statistical method Methods 0.000 description 4
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 3
- 108010000561 Cytochrome P-450 CYP2C8 Proteins 0.000 description 3
- 108010001237 Cytochrome P-450 CYP2D6 Proteins 0.000 description 3
- 102100029359 Cytochrome P450 2C8 Human genes 0.000 description 3
- 102100021704 Cytochrome P450 2D6 Human genes 0.000 description 3
- 208000000059 Dyspnea Diseases 0.000 description 3
- 206010013975 Dyspnoeas Diseases 0.000 description 3
- 101001017818 Homo sapiens ATP-dependent translocase ABCB1 Proteins 0.000 description 3
- 229940098712 Myosin activator Drugs 0.000 description 3
- 206010033557 Palpitations Diseases 0.000 description 3
- 102000004903 Troponin Human genes 0.000 description 3
- 108090001027 Troponin Proteins 0.000 description 3
- 102100036859 Troponin I, cardiac muscle Human genes 0.000 description 3
- 101710128251 Troponin I, cardiac muscle Proteins 0.000 description 3
- 229940125364 angiotensin receptor blocker Drugs 0.000 description 3
- 239000000090 biomarker Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000013270 controlled release Methods 0.000 description 3
- 229940109239 creatinine Drugs 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 206010016256 fatigue Diseases 0.000 description 3
- 230000010247 heart contraction Effects 0.000 description 3
- 230000004217 heart function Effects 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 229960003943 hypromellose Drugs 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000012417 linear regression Methods 0.000 description 3
- 208000019423 liver disease Diseases 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 238000002483 medication Methods 0.000 description 3
- 210000003632 microfilament Anatomy 0.000 description 3
- 239000002394 mineralocorticoid antagonist Substances 0.000 description 3
- 230000002644 neurohormonal effect Effects 0.000 description 3
- 238000013146 percutaneous coronary intervention Methods 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 230000000250 revascularization Effects 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 208000013220 shortness of breath Diseases 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 206010002388 Angina unstable Diseases 0.000 description 2
- 206010013710 Drug interaction Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 206010049694 Left Ventricular Dysfunction Diseases 0.000 description 2
- 102100020888 Sodium/glucose cotransporter 2 Human genes 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 208000007814 Unstable Angina Diseases 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 238000011976 chest X-ray Methods 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000000306 component Substances 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 229960003624 creatine Drugs 0.000 description 2
- 239000006046 creatine Substances 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 230000003436 cytoskeletal effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 230000003205 diastolic effect Effects 0.000 description 2
- 230000009699 differential effect Effects 0.000 description 2
- 229940082657 digitalis glycosides Drugs 0.000 description 2
- 238000011863 diuretic therapy Methods 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 230000024924 glomerular filtration Effects 0.000 description 2
- 230000013632 homeostatic process Effects 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 229960003825 ivabradine Drugs 0.000 description 2
- ACRHBAYQBXXRTO-OAQYLSRUSA-N ivabradine Chemical compound C1CC2=CC(OC)=C(OC)C=C2CC(=O)N1CCCN(C)C[C@H]1CC2=C1C=C(OC)C(OC)=C2 ACRHBAYQBXXRTO-OAQYLSRUSA-N 0.000 description 2
- 210000005240 left ventricle Anatomy 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 238000002595 magnetic resonance imaging Methods 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 230000010016 myocardial function Effects 0.000 description 2
- 210000004165 myocardium Anatomy 0.000 description 2
- RFUBTTPMWSKEIW-UHFFFAOYSA-N omecamtiv mecarbil Chemical compound C1CN(C(=O)OC)CCN1CC1=CC=CC(NC(=O)NC=2C=NC(C)=CC=2)=C1F RFUBTTPMWSKEIW-UHFFFAOYSA-N 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 230000033764 rhythmic process Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000010206 sensitivity analysis Methods 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 239000007916 tablet composition Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 1
- BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 description 1
- IVHKZCSZELZKSJ-UHFFFAOYSA-N 2-hydroxyethyl sulfonate Chemical compound OCCOS(=O)=O IVHKZCSZELZKSJ-UHFFFAOYSA-N 0.000 description 1
- AVVVYDOYYJBULZ-UHFFFAOYSA-N 2-methyl-4-oxo-6-(pyridin-3-ylmethylamino)-1h-pyrimidine-5-carbonitrile;hydrochloride Chemical compound Cl.N1C(C)=NC(=O)C(C#N)=C1NCC1=CC=CN=C1 AVVVYDOYYJBULZ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010003130 Arrhythmia supraventricular Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
- 206010007556 Cardiac failure acute Diseases 0.000 description 1
- 208000024172 Cardiovascular disease 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
- 208000000130 Cytochrome P-450 CYP3A Inducers Diseases 0.000 description 1
- 208000009011 Cytochrome P-450 CYP3A Inhibitors Diseases 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
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 238000001134 F-test Methods 0.000 description 1
- 206010053172 Fatal outcomes Diseases 0.000 description 1
- 101000655467 Homo sapiens Multidrug and toxin extrusion protein 1 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010048858 Ischaemic cardiomyopathy Diseases 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 108010007859 Lisinopril Proteins 0.000 description 1
- 208000009378 Low Cardiac Output Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 206010027727 Mitral valve incompetence Diseases 0.000 description 1
- UWWDHYUMIORJTA-HSQYWUDLSA-N Moexipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC(OC)=C(OC)C=C2C1)C(O)=O)CC1=CC=CC=C1 UWWDHYUMIORJTA-HSQYWUDLSA-N 0.000 description 1
- 102100032877 Multidrug and toxin extrusion protein 1 Human genes 0.000 description 1
- 108091007573 Multidrug and toxin extrusion transporters Proteins 0.000 description 1
- 102100036836 Natriuretic peptides B Human genes 0.000 description 1
- 101710187802 Natriuretic peptides B Proteins 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
- 108091006269 SLC5A2 Proteins 0.000 description 1
- 101710103228 Sodium/glucose cotransporter 2 Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- VXFJYXUZANRPDJ-WTNASJBWSA-N Trandopril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@H]2CCCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 VXFJYXUZANRPDJ-WTNASJBWSA-N 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000035508 accumulation Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 238000011374 additional therapy Methods 0.000 description 1
- 239000000808 adrenergic beta-agonist Substances 0.000 description 1
- 230000036586 afterload Effects 0.000 description 1
- 229960002478 aldosterone Drugs 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940126905 angiotensin receptor-neprilysin inhibitor Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 206010002906 aortic stenosis Diseases 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 229960004530 benazepril Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000012503 blood component Substances 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 229960005057 canrenone Drugs 0.000 description 1
- UJVLDDZCTMKXJK-WNHSNXHDSA-N canrenone Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CCC(=O)C=C3C=C2)C)CC[C@@]11C)C[C@@]11CCC(=O)O1 UJVLDDZCTMKXJK-WNHSNXHDSA-N 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
- 229960000623 carbamazepine Drugs 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000013130 cardiovascular surgery Methods 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- ZCIGNRJZKPOIKD-CQXVEOKZSA-N cobicistat Chemical compound S1C(C(C)C)=NC(CN(C)C(=O)N[C@@H](CCN2CCOCC2)C(=O)N[C@H](CC[C@H](CC=2C=CC=CC=2)NC(=O)OCC=2SC=NC=2)CC=2C=CC=CC=2)=C1 ZCIGNRJZKPOIKD-CQXVEOKZSA-N 0.000 description 1
- 229960002402 cobicistat Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000008828 contractile function Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000002586 coronary angiography Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- METQSPRSQINEEU-UHFFFAOYSA-N dihydrospirorenone Natural products CC12CCC(C3(CCC(=O)C=C3C3CC33)C)C3C1C1CC1C21CCC(=O)O1 METQSPRSQINEEU-UHFFFAOYSA-N 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229960004845 drospirenone Drugs 0.000 description 1
- METQSPRSQINEEU-HXCATZOESA-N drospirenone Chemical compound C([C@]12[C@H]3C[C@H]3[C@H]3[C@H]4[C@@H]([C@]5(CCC(=O)C=C5[C@@H]5C[C@@H]54)C)CC[C@@]31C)CC(=O)O2 METQSPRSQINEEU-HXCATZOESA-N 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000008406 drug-drug interaction Effects 0.000 description 1
- 238000002592 echocardiography Methods 0.000 description 1
- 238000011984 electrochemiluminescence immunoassay Methods 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 229960001208 eplerenone Drugs 0.000 description 1
- JUKPWJGBANNWMW-VWBFHTRKSA-N eplerenone Chemical compound C([C@@H]1[C@]2(C)C[C@H]3O[C@]33[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)C(=O)OC)C[C@@]21CCC(=O)O1 JUKPWJGBANNWMW-VWBFHTRKSA-N 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000009246 food effect Effects 0.000 description 1
- 235000021471 food effect Nutrition 0.000 description 1
- 229960002490 fosinopril Drugs 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004041 inotropic agent Substances 0.000 description 1
- 238000002642 intravenous therapy Methods 0.000 description 1
- 229960004125 ketoconazole Drugs 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 229960002394 lisinopril Drugs 0.000 description 1
- CZRQXSDBMCMPNJ-ZUIPZQNBSA-N lisinopril dihydrate Chemical compound O.O.C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 CZRQXSDBMCMPNJ-ZUIPZQNBSA-N 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 208000012866 low blood pressure Diseases 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 238000005399 mechanical ventilation Methods 0.000 description 1
- 238000010197 meta-analysis Methods 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 208000019266 moderate heart failure Diseases 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 229960005170 moexipril Drugs 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 201000000585 muscular atrophy Diseases 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
- 235000005985 organic acids Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 229960002582 perindopril Drugs 0.000 description 1
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000011422 pharmacological therapy Methods 0.000 description 1
- 238000011458 pharmacological treatment Methods 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
- 230000000704 physical effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000007406 plaque accumulation Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 230000036316 preload Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 229960001455 quinapril Drugs 0.000 description 1
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 1
- 229960003401 ramipril Drugs 0.000 description 1
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
- 229960000311 ritonavir Drugs 0.000 description 1
- 229940100334 sacubitril / valsartan Drugs 0.000 description 1
- 231100000279 safety data Toxicity 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 229960002256 spironolactone Drugs 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000013517 stratification 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
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229960002051 trandolapril Drugs 0.000 description 1
- 238000013175 transesophageal echocardiography Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229960004699 valsartan Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 206010047302 ventricular tachycardia Diseases 0.000 description 1
- 229950005018 vericiguat Drugs 0.000 description 1
- QZFHIXARHDBPBY-UHFFFAOYSA-N vericiguat Chemical compound N1=C(N)C(NC(=O)OC)=C(N)N=C1C(C1=CC(F)=CN=C11)=NN1CC1=CC=CC=C1F QZFHIXARHDBPBY-UHFFFAOYSA-N 0.000 description 1
- 206010047470 viral myocarditis Diseases 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical class [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
- A61N1/38—Applying electric currents by contact electrodes alternating or intermittent currents for producing shock effects
- A61N1/39—Heart defibrillators
- A61N1/3956—Implantable devices for applying electric shocks to the heart, e.g. for cardioversion
-
- 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
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Radiology & Medical Imaging (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063112995P | 2020-11-12 | 2020-11-12 | |
| US63/112,995 | 2020-11-12 | ||
| US202163154077P | 2021-02-26 | 2021-02-26 | |
| US63/154,077 | 2021-02-26 | ||
| US202163187084P | 2021-05-11 | 2021-05-11 | |
| US63/187,084 | 2021-05-11 | ||
| US202163202873P | 2021-06-28 | 2021-06-28 | |
| US63/202,873 | 2021-06-28 | ||
| US202163203436P | 2021-07-22 | 2021-07-22 | |
| US63/203,436 | 2021-07-22 | ||
| PCT/US2021/058988 WO2022103966A1 (en) | 2020-11-12 | 2021-11-11 | Methods of treating heart failure by administering omecamtiv mecarbil |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20230107282A true KR20230107282A (ko) | 2023-07-14 |
Family
ID=78822539
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020237019053A Pending KR20230107282A (ko) | 2020-11-12 | 2021-11-11 | 오메캄티브 메카빌을 투여하여 심부전을 치료하는 방법 |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US12194039B2 (https=) |
| EP (2) | EP4243825B1 (https=) |
| JP (1) | JP2024500616A (https=) |
| KR (1) | KR20230107282A (https=) |
| AU (1) | AU2021380754A1 (https=) |
| CA (1) | CA3200673A1 (https=) |
| CL (2) | CL2023001351A1 (https=) |
| DK (1) | DK4243825T3 (https=) |
| ES (1) | ES3060408T3 (https=) |
| FI (1) | FI4243825T3 (https=) |
| HR (1) | HRP20251568T1 (https=) |
| IL (1) | IL302850A (https=) |
| LT (1) | LT4243825T (https=) |
| MX (1) | MX2023005455A (https=) |
| NZ (1) | NZ800220A (https=) |
| PL (1) | PL4243825T3 (https=) |
| PT (1) | PT4243825T (https=) |
| RS (1) | RS67558B1 (https=) |
| SI (1) | SI4243825T1 (https=) |
| SM (1) | SMT202600073T1 (https=) |
| TW (1) | TW202233189A (https=) |
| WO (1) | WO2022103966A1 (https=) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2522579T3 (es) | 2004-06-17 | 2014-11-17 | Cytokinetics, Inc. | Compuestos, composiciones y métodos |
| SG11201507258PA (en) | 2013-03-14 | 2015-10-29 | Amgen Inc | Heterocyclic compounds and their uses |
| AU2018294254C1 (en) | 2017-06-30 | 2022-10-13 | Amgen Inc. | Synthesis of omecamtiv mecarbil |
| DK3645002T3 (da) | 2017-06-30 | 2024-12-16 | Amgen Inc | Fremgangsmåder til behandling af hjertesvigt med hjerte-sarkomer-aktivatorer |
| PT3594199T (pt) | 2018-07-09 | 2020-09-04 | Amgen Inc | 2-fluoro-3-nitrotolueno cristalino e processo para a sua preparação |
| MA53226A (fr) | 2018-08-17 | 2021-11-24 | Amgen Inc | Sel et formes cristallines d'omecamtiv mecarbil |
| WO2020131574A1 (en) | 2018-12-18 | 2020-06-25 | Amgen Inc. | Method of reducing aromatic nitro compounds |
| DK4243825T3 (da) | 2020-11-12 | 2025-12-01 | Amgen Inc | Omecamtiv mecarbil til behandling af hjerteinsattsvigt hos udvalgte patientgrupper |
| IL305751A (en) | 2021-03-10 | 2023-11-01 | Amgen Inc | SYNTHESIS OF OMECAMTIV MECARBIL |
| US20250161298A1 (en) * | 2022-02-22 | 2025-05-22 | Yale University | Methods of treating, ameliorating, or preventing heart failure, and methods of promoting heart muscle growth |
| WO2024081611A1 (en) * | 2022-10-11 | 2024-04-18 | Cytokinetics, Incorporated | Methods for treating heart failure by administering cardiac sarcomere activators |
| US11986474B1 (en) | 2023-06-27 | 2024-05-21 | Cytokinetics, Incorporated | Methods for treating heart failure by administering cardiac sarcomere activators |
| WO2026050494A1 (en) * | 2024-08-29 | 2026-03-05 | Cytokinetics, Incorporated | Omecamtiv mecarbil for use in treating heart failure by activating cardiac sarcomere |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4450150A (en) | 1973-05-17 | 1984-05-22 | Arthur D. Little, Inc. | Biodegradable, implantable drug delivery depots, and method for preparing and using the same |
| EP1053752A1 (en) | 1998-02-10 | 2000-11-22 | Yoshitomi Pharmaceutical Industries, Ltd. | Preparations with controlled release |
| GB2344287A (en) | 1998-12-03 | 2000-06-07 | Ferring Bv | Controlled release pharmaceutical formulation |
| AU2003279842A1 (en) | 2002-10-04 | 2004-05-04 | Microchips, Inc. | Medical device for controlled drug delivery and cardiac monitoring and/or stimulation |
| ES2522579T3 (es) | 2004-06-17 | 2014-11-17 | Cytokinetics, Inc. | Compuestos, composiciones y métodos |
| ES2419007T3 (es) | 2005-12-15 | 2013-08-19 | Cytokinetics, Inc. | Ciertas entidades químicas, composiciones y procedimientos |
| US20080031957A1 (en) | 2006-05-15 | 2008-02-07 | Deluca Hector F | Pulmonary delivery of 1alpha,25-dihydroxyvitamin D3 and co-administration of parathyroid hormone or calcitonin |
| FR2902092B1 (fr) | 2006-06-07 | 2008-09-05 | Sapelem Soc Par Actions Simpli | Appareil de manutention de charge |
| WO2008130158A1 (en) | 2007-04-19 | 2008-10-30 | Dong-A Pharmaceutical. Co., Ltd | A biodegradable microsphere composition suitable for the controlled release of glucose controlling peptide and formulation thereof |
| US9895308B2 (en) | 2013-03-14 | 2018-02-20 | Amgen Inc. | Heterocyclic compounds and their uses |
| SG11201507258PA (en) | 2013-03-14 | 2015-10-29 | Amgen Inc | Heterocyclic compounds and their uses |
| EP3250557B1 (en) | 2015-01-29 | 2024-11-20 | Signal Pharmaceuticals, LLC | Isotopologues of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide |
| US10543215B2 (en) | 2015-06-26 | 2020-01-28 | Amgen Inc. | Combination therapy of cardiac myosin activator and sinus node if current inhibitor |
| CA3052625A1 (en) | 2017-02-06 | 2018-08-09 | Acceleron Pharma Inc. | Compositions and methods for treating heart failure |
| AU2018294254C1 (en) | 2017-06-30 | 2022-10-13 | Amgen Inc. | Synthesis of omecamtiv mecarbil |
| DK3645002T3 (da) | 2017-06-30 | 2024-12-16 | Amgen Inc | Fremgangsmåder til behandling af hjertesvigt med hjerte-sarkomer-aktivatorer |
| PT3594199T (pt) | 2018-07-09 | 2020-09-04 | Amgen Inc | 2-fluoro-3-nitrotolueno cristalino e processo para a sua preparação |
| EP3820851A1 (en) | 2018-07-12 | 2021-05-19 | Assia Chemical Industries Ltd | Solid state forms of omecamtiv mecarbil & omecamtiv mecarbil dihcl |
| FI3599243T3 (fi) | 2018-07-26 | 2023-06-22 | Cvie Therapeutics Ltd | 17beeta-heterosyklyylidigitaliksen kaltaisia yhdisteitä sydämen vajaatoiminnan hoitoon |
| MA53226A (fr) | 2018-08-17 | 2021-11-24 | Amgen Inc | Sel et formes cristallines d'omecamtiv mecarbil |
| WO2020131574A1 (en) | 2018-12-18 | 2020-06-25 | Amgen Inc. | Method of reducing aromatic nitro compounds |
| MX2021010483A (es) | 2019-03-05 | 2021-10-01 | Windtree Therapeutics Inc | Formulacion intravenosa que contiene istaroxima para el tratamiento de insuficiencia cardiaca aguda (ahf). |
| WO2021053175A1 (en) | 2019-09-19 | 2021-03-25 | Synthon B.V. | Salts of omecamtiv mecarbil and solid forms thereof |
| EP4031541A1 (en) | 2019-09-19 | 2022-07-27 | Synthon B.V. | Salts of omecamtiv mecarbil and solid forms thereof |
| EP4041710A1 (en) | 2019-10-09 | 2022-08-17 | Dr. Reddy's Laboratories Limited | Alternate processes for the preparation of omecamtiv mecarbil |
| WO2021070123A1 (en) | 2019-10-09 | 2021-04-15 | Dr. Reddy’S Laboratories Limited | Solid forms of omecamtiv mecarbil dihydrochloride and processes thereof |
| EP4054588A4 (en) | 2019-11-10 | 2023-12-13 | MyoKardia, Inc. | Methods of treatment with myosin modulator |
| GB201918853D0 (en) | 2019-12-19 | 2020-02-05 | Lund Lars H | Methods of treatment |
| CN114929671B (zh) | 2020-01-03 | 2024-04-16 | 苏州科睿思制药有限公司 | 化合物i二盐酸盐的共晶及其制备方法和用途 |
| US20230090391A1 (en) | 2020-02-10 | 2023-03-23 | Amgen Inc. | Omecamtiv mecarbil tablet |
| DK4243825T3 (da) | 2020-11-12 | 2025-12-01 | Amgen Inc | Omecamtiv mecarbil til behandling af hjerteinsattsvigt hos udvalgte patientgrupper |
| IL305751A (en) | 2021-03-10 | 2023-11-01 | Amgen Inc | SYNTHESIS OF OMECAMTIV MECARBIL |
| WO2023205291A2 (en) | 2022-04-21 | 2023-10-26 | The Board Of Regents Of The University Of Oklahoma | Targeting myocardial tissue for delivery of therapeutic and imaging agents |
| WO2024081611A1 (en) | 2022-10-11 | 2024-04-18 | Cytokinetics, Incorporated | Methods for treating heart failure by administering cardiac sarcomere activators |
| US11986474B1 (en) | 2023-06-27 | 2024-05-21 | Cytokinetics, Incorporated | Methods for treating heart failure by administering cardiac sarcomere activators |
-
2021
- 2021-11-11 DK DK21820408.9T patent/DK4243825T3/da active
- 2021-11-11 PL PL21820408.9T patent/PL4243825T3/pl unknown
- 2021-11-11 WO PCT/US2021/058988 patent/WO2022103966A1/en not_active Ceased
- 2021-11-11 SM SM20260073T patent/SMT202600073T1/it unknown
- 2021-11-11 FI FIEP21820408.9T patent/FI4243825T3/fi active
- 2021-11-11 MX MX2023005455A patent/MX2023005455A/es unknown
- 2021-11-11 ES ES21820408T patent/ES3060408T3/es active Active
- 2021-11-11 LT LTEPPCT/US2021/058988T patent/LT4243825T/lt unknown
- 2021-11-11 AU AU2021380754A patent/AU2021380754A1/en active Pending
- 2021-11-11 EP EP21820408.9A patent/EP4243825B1/en active Active
- 2021-11-11 PT PT218204089T patent/PT4243825T/pt unknown
- 2021-11-11 US US17/454,592 patent/US12194039B2/en active Active
- 2021-11-11 EP EP25214250.0A patent/EP4706638A3/en active Pending
- 2021-11-11 JP JP2023528276A patent/JP2024500616A/ja active Pending
- 2021-11-11 HR HRP20251568TT patent/HRP20251568T1/hr unknown
- 2021-11-11 IL IL302850A patent/IL302850A/en unknown
- 2021-11-11 TW TW110142070A patent/TW202233189A/zh unknown
- 2021-11-11 SI SI202130373T patent/SI4243825T1/sl unknown
- 2021-11-11 KR KR1020237019053A patent/KR20230107282A/ko active Pending
- 2021-11-11 CA CA3200673A patent/CA3200673A1/en active Pending
- 2021-11-11 NZ NZ800220A patent/NZ800220A/en unknown
- 2021-11-11 RS RS20251248A patent/RS67558B1/sr unknown
-
2023
- 2023-05-10 CL CL2023001351A patent/CL2023001351A1/es unknown
-
2024
- 2024-02-15 CL CL2024000466A patent/CL2024000466A1/es unknown
- 2024-12-03 US US18/967,331 patent/US20250205228A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| LT4243825T (lt) | 2026-01-12 |
| WO2022103966A1 (en) | 2022-05-19 |
| WO2022103966A9 (en) | 2022-08-18 |
| US12194039B2 (en) | 2025-01-14 |
| SI4243825T1 (sl) | 2026-01-30 |
| EP4706638A3 (en) | 2026-04-22 |
| JP2024500616A (ja) | 2024-01-10 |
| AU2021380754A9 (en) | 2024-10-24 |
| PT4243825T (pt) | 2026-01-30 |
| CL2023001351A1 (es) | 2023-10-20 |
| DK4243825T3 (da) | 2025-12-01 |
| MX2023005455A (es) | 2023-07-27 |
| EP4706638A2 (en) | 2026-03-11 |
| SMT202600073T1 (it) | 2026-03-09 |
| PL4243825T3 (pl) | 2026-03-23 |
| CA3200673A1 (en) | 2022-05-19 |
| HRP20251568T1 (hr) | 2026-03-13 |
| EP4243825B1 (en) | 2025-11-12 |
| RS67558B1 (sr) | 2026-01-30 |
| IL302850A (en) | 2023-07-01 |
| NZ800220A (en) | 2026-02-27 |
| FI4243825T3 (fi) | 2025-12-15 |
| US20250205228A1 (en) | 2025-06-26 |
| ES3060408T3 (en) | 2026-03-26 |
| TW202233189A (zh) | 2022-09-01 |
| US20220184068A1 (en) | 2022-06-16 |
| AU2021380754A1 (en) | 2023-06-22 |
| EP4243825A1 (en) | 2023-09-20 |
| CL2024000466A1 (es) | 2024-08-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20230107282A (ko) | 오메캄티브 메카빌을 투여하여 심부전을 치료하는 방법 | |
| von Haehling et al. | Muscle wasting as an independent predictor of survival in patients with chronic heart failure | |
| AU2024200991B2 (en) | Methods of treating heart failure with cardiac sarcomere activators | |
| Upadhya et al. | Heart failure with preserved ejection fraction in older adults | |
| Gibson et al. | Reduction of stent thrombosis in patients with acute coronary syndromes treated with rivaroxaban in ATLAS-ACS 2 TIMI 51 | |
| WO2024081611A1 (en) | Methods for treating heart failure by administering cardiac sarcomere activators | |
| Gerbaud et al. | Effect of ivabradine on left ventricular remodelling after reperfused myocardial infarction: a pilot study | |
| Farsky et al. | Optimal medical therapy with or without surgical revascularization and long-term outcomes in ischemic cardiomyopathy | |
| SHIMOYAMA et al. | Docetaxel induced cardiotoxicity | |
| Savage et al. | Advances in clinical cardiology 2024: a summary of key clinical trials | |
| Ural et al. | Effect of oral nitrates on all-cause mortality and hospitalization in heart failure patients with reduced ejection fraction: a propensity-matched analysis | |
| Gabara et al. | Ischaemic heart disease: stable angina | |
| HK40101740A (zh) | 通过施用奥美卡替莫卡必尔治疗心力衰竭的方法 | |
| CN116710139A (zh) | 通过施用奥美卡替莫卡必尔治疗心力衰竭的方法 | |
| Heras | Ischemic Heart Disease in Women: Clinical Presentation, Non-Invasive Testing, and Management of Acute Coronary Syndromes | |
| Nardi et al. | ANMCO Position Paper: direct oral anticoagulants for stroke prevention in atrial fibrillation: clinical scenarios and future perspectives | |
| Di Monaco et al. | The patient with chronic ischemic heart disease. Role of ranolazine in the management of stable angina. | |
| Gabara et al. | Ischaemic heart disease: stable angina | |
| Fox et al. | Management of acute coronary syndrome | |
| Williford et al. | Ischemic Heart Disease | |
| Pop et al. | Benefits and Risks of Anticoagulation in Acute Coronary Syndrome | |
| Wereski et al. | A practical guide to chronic heart failure management | |
| TW202602436A (zh) | 用於治療心臟衰竭之醛固酮合成酶抑制劑 | |
| WO2026050494A1 (en) | Omecamtiv mecarbil for use in treating heart failure by activating cardiac sarcomere | |
| Usman et al. | Stable Coronary Artery Disease |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20230605 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20241111 Comment text: Request for Examination of Application |