HRP20211290T1 - Sinteza omekamtiv mekarbila - Google Patents
Sinteza omekamtiv mekarbila Download PDFInfo
- Publication number
- HRP20211290T1 HRP20211290T1 HRP20211290TT HRP20211290T HRP20211290T1 HR P20211290 T1 HRP20211290 T1 HR P20211290T1 HR P20211290T T HRP20211290T T HR P20211290TT HR P20211290 T HRP20211290 T HR P20211290T HR P20211290 T1 HRP20211290 T1 HR P20211290T1
- Authority
- HR
- Croatia
- Prior art keywords
- pmec
- fnb
- image
- mixing
- phosphate hydrate
- Prior art date
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- 230000015572 biosynthetic process Effects 0.000 title claims 3
- 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 title 1
- 229950001617 omecamtiv mecarbil Drugs 0.000 title 1
- 238000003786 synthesis reaction Methods 0.000 title 1
- 238000000034 method Methods 0.000 claims 15
- XXUKNWCJFNYLDP-UHFFFAOYSA-N 2-(4-amino-2-oxopyrimidin-1-yl)ethoxymethylphosphonic acid Chemical compound NC=1C=CN(CCOCP(O)(O)=O)C(=O)N=1 XXUKNWCJFNYLDP-UHFFFAOYSA-N 0.000 claims 13
- TWHXWYVOWJCXSI-UHFFFAOYSA-N phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O TWHXWYVOWJCXSI-UHFFFAOYSA-N 0.000 claims 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 6
- 239000002585 base Substances 0.000 claims 5
- 125000005270 trialkylamine group Chemical group 0.000 claims 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 4
- 239000007864 aqueous solution Substances 0.000 claims 4
- 239000000203 mixture Substances 0.000 claims 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- OSHVGUAPPIYWIS-UHFFFAOYSA-N piperazin-1-ium;acetate Chemical compound CC(O)=O.C1CNCCN1 OSHVGUAPPIYWIS-UHFFFAOYSA-N 0.000 claims 3
- 230000002194 synthesizing effect Effects 0.000 claims 3
- 238000005406 washing Methods 0.000 claims 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims 2
- MIESICVJNXXYKC-UHFFFAOYSA-N 1-(bromomethyl)-2-fluoro-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(CBr)=C1F MIESICVJNXXYKC-UHFFFAOYSA-N 0.000 claims 2
- NBCNUIXYBLFJMI-UHFFFAOYSA-N 2-fluoro-1-methyl-3-nitrobenzene Chemical compound CC1=CC=CC([N+]([O-])=O)=C1F NBCNUIXYBLFJMI-UHFFFAOYSA-N 0.000 claims 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 2
- QBSLBISOVGGPJO-UHFFFAOYSA-N methyl 4-[(2-fluoro-3-nitrophenyl)methyl]piperazine-1-carboxylate Chemical compound COC(=O)N1CCN(Cc2cccc(c2F)[N+]([O-])=O)CC1 QBSLBISOVGGPJO-UHFFFAOYSA-N 0.000 claims 2
- 239000011780 sodium chloride Substances 0.000 claims 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims 2
- 235000019345 sodium thiosulphate Nutrition 0.000 claims 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
- 239000004342 Benzoyl peroxide Substances 0.000 claims 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims 1
- -1 Piperazine methyl carboxylate phosphate hydrate Chemical compound 0.000 claims 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- 239000003637 basic solution Substances 0.000 claims 1
- 235000019400 benzoyl peroxide Nutrition 0.000 claims 1
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 claims 1
- 238000001914 filtration Methods 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims 1
- 229940011051 isopropyl acetate Drugs 0.000 claims 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 claims 1
- 239000003960 organic solvent Substances 0.000 claims 1
- XUXNAKZDHHEHPC-UHFFFAOYSA-M sodium bromate Chemical compound [Na+].[O-]Br(=O)=O XUXNAKZDHHEHPC-UHFFFAOYSA-M 0.000 claims 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pyridine Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Claims (14)
1. Piperazin metil karboksilat fosfat hidrat
[image]
(„PMEC“).
2. Postupak za sintetiziranje piperazin metil karboksilat
[image]
(„PMEC“) fosfat hidrata, naznačen time, da obuhvaća:
(a) miješanje piperazina i metil kloroformata u svrhu tvorbe PMEC;
(b) miješanje PMEC i 0,5 molarnih ekvivalenata fosforne kiseline u vodenoj otopini u svrhu tvorbe PMEC fosfat hidrata; i
(c) opcionalno filtriranje PMEC fosfat hidrata iz smjese u koraku (b).
3. Postupak prema patentnom zahtjevu 2, naznačen time, da nadalje obuhvaća izoliranje PMEC stvorenog u koraku (a) kao otopine u metilen kloridu, dikloretanu, 2-metiltetrahidrofuranu, ili njihovoj mješavini.
4. Postupak prema patentnom zahtjevu 3, naznačen time, da se izoliranje provodi putem
(i) ispiranja dobivenog PMEC iz koraka (a) s organskim otapalom;
(ii) modificiranja pH vrijednosti na 8 do 14 dodavanjem baze u svrhu tvorbe bazične vodene otopine; i
(iii) ekstrahiranja PMEC iz bazične vodene otopine iz koraka (ii) s metilen kloridom, dikloretanom, 2-metil tetrahidrofuranom, ili njihovom mješavinom.
5. Postupak prema patentnom zahtjevu 2, naznačen time, da se korak (a) provodi u vodenoj otopini.
6. Postupak prema bilo kojem od patentnih zahtjeva 2 do 5, naznačen time, da se korak (a) provodi na temperaturi od 20 do 55 °C u vremenu od 1 do 12 sati.
7. Postupak za sintetiziranje metil 4-(2-fluoro-3-nitrobenzil)piperazin-1-karboksilata
[image]
(PIPN), naznačen time, da obuhvaća
(a) miješanje 2-fluoro-3-nitrotoluena, natrijevog bromata i natrijevog bisulfita u izopropilacetatu i vodi u svrhu tvorbe 1-(bromometil)-2-fluoro-3-nitrobenzena
[image]
(FNB);
(b) opcionalno ispiranje FNB s vodenim natrijevim tiosulfatom, s vodenim natrijevim kloridom, ili s oba; i
(c) miješanje FNB, trialkilaminske baze i piperazin metil karboksilat
[image]
(„PMEC“) fosfat hidrata u svrhu tvorbe PIPN.
8. Postupak prema patentnom zahtjevu 7, naznačen time, da se FNB ispire s vodenim natrijevim tiosulfatom i vodenim natrijevim kloridom.
9. Postupak za sintetiziranje metil 4-(2-fluoro-3-nitrobenzil)piperazin-1-karboksilata
[image]
(PIPN), naznačen time, da obuhvaća:
(a) miješanje 2-fluoro-3-nitrotoluena, benzoil peroksida, N-bromosukcinimida i octene kiseline na temperaturi od 70 do 95 °C u svrhu tvorbe 1-(bromometil)-2-fluoro-3-nitrobenzena
[image]
(FNB);
(b) opcionalno ekstrahiranje FNB s toluenom, ispiranje FNB s vodenom bazičnom otopinom, ili oboje;
(c) miješanje FNB, trialkilaminske baze i piperazin metil karboksilat
[image]
(„PMEC“) fosfatnog hidrata u svrhu tvorbe PIPN.
10. Postupak prema patentnom zahtjevu 9, naznačen time, da se FNB ekstrahira s toluenom i ispire s vodenim natrijevim hidroksidom.
11. Postupak prema bilo kojem od patentnih zahtjeva 7 do 10, naznačen time, da se PIPN tvori kao hidrokloridna sol.
12. Postupak prema bilo kojem od patentnih zahtjeva 7 do 11, naznačen time, da se PMEC fosfat hidrat pripravlja putem postupka prema bilo kojem od patentnih zahtjeva 2 do 6.
13. Postupak prema bilo kojem od patentnih zahtjeva 7 do 12, naznačen time, da trialkilaminska baza sadrži diizopropiletilamin ili trietilamin.
14. Postupak prema bilo kojem od patentnih zahtjeva 7 do 13, naznačen time, da prije miješanja FNB, trialkilaminske baze i PMEC fosfat hidrata, postupak nadalje obuhvaća dodavanje dietilfosfita i trialkilamina, i miješanje rezultirajuće smjese na temperaturi od 30 do 65 °C.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762527174P | 2017-06-30 | 2017-06-30 | |
| US201862664363P | 2018-04-30 | 2018-04-30 | |
| EP18743314.9A EP3645518B1 (en) | 2017-06-30 | 2018-06-29 | Synthesis of omecamtiv mecarbil |
| PCT/US2018/040176 WO2019006231A1 (en) | 2017-06-30 | 2018-06-29 | SYNTHESIS OF OMECAMTIV MECARBIL |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20211290T1 true HRP20211290T1 (hr) | 2021-11-12 |
Family
ID=62976317
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20211290TT HRP20211290T1 (hr) | 2017-06-30 | 2021-08-11 | Sinteza omekamtiv mekarbila |
Country Status (27)
| Country | Link |
|---|---|
| US (3) | US11040956B2 (hr) |
| EP (3) | EP3925950B1 (hr) |
| JP (2) | JP7181896B2 (hr) |
| KR (1) | KR102625774B1 (hr) |
| CN (1) | CN110799503B (hr) |
| AU (1) | AU2018294254C1 (hr) |
| BR (1) | BR112019028205A2 (hr) |
| CA (1) | CA3063102A1 (hr) |
| CL (2) | CL2019003898A1 (hr) |
| CY (1) | CY1124427T1 (hr) |
| DK (1) | DK3645518T3 (hr) |
| ES (1) | ES2882905T3 (hr) |
| GE (1) | GEP20227340B (hr) |
| HR (1) | HRP20211290T1 (hr) |
| HU (1) | HUE055242T2 (hr) |
| IL (2) | IL294834A (hr) |
| LT (1) | LT3645518T (hr) |
| MD (1) | MD3645518T2 (hr) |
| MX (2) | MX2021013326A (hr) |
| PL (1) | PL3645518T3 (hr) |
| PT (1) | PT3645518T (hr) |
| RS (1) | RS62328B1 (hr) |
| SG (1) | SG10202111790YA (hr) |
| SI (1) | SI3645518T1 (hr) |
| TW (2) | TWI769272B (hr) |
| UA (1) | UA127517C2 (hr) |
| WO (1) | WO2019006231A1 (hr) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2970123T3 (da) | 2013-03-14 | 2019-10-21 | Amgen Inc | Salt af omecamtiv mecarbil og fremgangsmåde til fremstilling heraf |
| AU2018290983B2 (en) | 2017-06-30 | 2023-11-23 | Amgen Inc. | Methods of treating heart failure with cardiac sarcomere activators |
| PT3645518T (pt) | 2017-06-30 | 2021-08-23 | Amgen Inc | Síntese de omecamtiv mecarbil |
| TWI790281B (zh) | 2017-09-13 | 2023-01-21 | 美商安進公司 | 雙醯胺肌節活化化合物及其用途 |
| US11465969B2 (en) | 2018-08-17 | 2022-10-11 | Cytokinetics, Inc. | Salts and crystal forms 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 |
| WO2021070124A1 (en) * | 2019-10-09 | 2021-04-15 | Dr. Reddy’S Laboratories Limited | Alternate processes for the preparation of omecamtiv mecarbil |
| CN117157274A (zh) | 2021-03-10 | 2023-12-01 | 安进股份有限公司 | 奥美卡替莫卡必尔的合成 |
| 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 |
| US11986474B1 (en) | 2023-06-27 | 2024-05-21 | Cytokinetics, Incorporated | Methods for treating heart failure by administering cardiac sarcomere activators |
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| US6492529B1 (en) * | 2000-01-18 | 2002-12-10 | Boehringer Ingelheim Pharmaceuticals, Inc. | Bis pyrazole-1H-pyrazole intermediates and their synthesis |
| JP5080970B2 (ja) | 2004-06-17 | 2012-11-21 | サイトキネティクス・インコーポレーテッド | 心疾患を治療するための置換尿素誘導体 |
| US20070208000A1 (en) | 2005-12-15 | 2007-09-06 | Morgan Bradley P | Certain chemical entities, compositions and methods |
| EP1959960B1 (en) | 2005-12-15 | 2013-04-10 | Cytokinetics, Inc. | Certain chemical entities, compositions and methods |
| JP5178526B2 (ja) | 2005-12-19 | 2013-04-10 | サイトキネティクス・インコーポレーテッド | 化合物、組成物および方法 |
| DE602007011793D1 (de) * | 2006-10-18 | 2011-02-17 | Pfizer Prod Inc | Biaryl-ether-harnstoffverbindungen |
| US20090192168A1 (en) | 2008-01-04 | 2009-07-30 | Alex Muci | Compounds, Compositions and Methods |
| US20120083476A1 (en) * | 2009-06-05 | 2012-04-05 | Janssen Pharmaceutica Nv | Heteroaryl-substituted spirocyclic diamine urea modulators of fatty acid amide hydrolase |
| US9895308B2 (en) | 2013-03-14 | 2018-02-20 | Amgen Inc. | Heterocyclic compounds and their uses |
| DK2970123T3 (da) | 2013-03-14 | 2019-10-21 | Amgen Inc | Salt af omecamtiv mecarbil og fremgangsmåde til fremstilling heraf |
| EP3127564B1 (en) | 2014-03-31 | 2018-12-26 | Med-tech Inc. | Blood purification device and priming method for blood purification device |
| TW201625568A (zh) * | 2014-11-24 | 2016-07-16 | 歌林達有限公司 | 作爲類香草素受體之配位體ｉｉ之經取代以噁唑及噻唑爲主之甲醯胺及脲衍生物 |
| CA2975260C (en) | 2015-01-29 | 2024-05-21 | Signal Pharmaceuticals Llc | Isotopologues of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide |
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