HRP20191596T1 - Postupak za pripravu 2-{4-[2-({[2-(4-klorofenil)-1,3-tiazol-4-il]metil}sulfanil)-3,5-dicijan-6- (pirolidin-1-il)piridin-4-il]fenoksi}etil-l-alanil-l-alaninat hidroklorida - Google Patents
Postupak za pripravu 2-{4-[2-({[2-(4-klorofenil)-1,3-tiazol-4-il]metil}sulfanil)-3,5-dicijan-6- (pirolidin-1-il)piridin-4-il]fenoksi}etil-l-alanil-l-alaninat hidroklorida Download PDFInfo
- Publication number
- HRP20191596T1 HRP20191596T1 HRP20191596T HRP20191596T1 HR P20191596 T1 HRP20191596 T1 HR P20191596T1 HR P20191596 T HRP20191596 T HR P20191596T HR P20191596 T1 HRP20191596 T1 HR P20191596T1
- Authority
- HR
- Croatia
- Prior art keywords
- formula
- compound
- dicyano
- sulfanyl
- thiazol
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title claims 5
- 238000002360 preparation method Methods 0.000 title claims 3
- WESNEIGKOAXSGX-VXKWHMMOSA-N neladenoson bialanate Chemical compound C1=CC(OCCOC(=O)[C@H](C)NC(=O)[C@@H](N)C)=CC=C1C1=C(C#N)C(SCC=2N=C(SC=2)C=2C=CC(Cl)=CC=2)=NC(N2CCCC2)=C1C#N WESNEIGKOAXSGX-VXKWHMMOSA-N 0.000 title claims 2
- 150000001875 compounds Chemical class 0.000 claims 23
- -1 VIII Chemical class 0.000 claims 5
- 230000004048 modification Effects 0.000 claims 5
- 238000012986 modification Methods 0.000 claims 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 4
- 238000001237 Raman spectrum Methods 0.000 claims 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 4
- 239000002904 solvent Substances 0.000 claims 4
- QVHJQCGUWFKTSE-YFKPBYRVSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-YFKPBYRVSA-N 0.000 claims 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- 238000006243 chemical reaction Methods 0.000 claims 3
- 239000007787 solid Substances 0.000 claims 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 229910052802 copper Inorganic materials 0.000 claims 2
- 239000010949 copper Substances 0.000 claims 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 238000002955 isolation Methods 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 238000005580 one pot reaction Methods 0.000 claims 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 2
- 230000005855 radiation Effects 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 2
- QVHJQCGUWFKTSE-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)C(C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-UHFFFAOYSA-N 0.000 claims 1
- BHPYMZQTCPRLNR-UHFFFAOYSA-N 2-cyanoethanethioamide Chemical compound NC(=S)CC#N BHPYMZQTCPRLNR-UHFFFAOYSA-N 0.000 claims 1
- INWIFSBFLUSGMN-UHFFFAOYSA-N 4-chloro-5-(chloromethyl)-2-phenyl-1,3-thiazole Chemical compound ClCC1=C(N=C(S1)C1=CC=CC=C1)Cl INWIFSBFLUSGMN-UHFFFAOYSA-N 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 claims 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims 1
- 229960003767 alanine Drugs 0.000 claims 1
- 235000004279 alanine Nutrition 0.000 claims 1
- 239000003054 catalyst Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 238000001035 drying Methods 0.000 claims 1
- 208000017169 kidney disease Diseases 0.000 claims 1
- 201000006370 kidney failure Diseases 0.000 claims 1
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical class N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 claims 1
- 229940087646 methanolamine Drugs 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 230000007704 transition Effects 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 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
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P9/04—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Claims (17)
1. 2-(4-[2-(1[2-(4-klorofenil)-1,3-tiazol-4-il]metil}sulfanil)-3,5-dicijano-6-(pirolidin-1-il)piridin-4-il]fenoksi}etil-L-alanil L-alaninat monohidroklorid s formulom (I) u kristalnom obliku modifikacije I
naznačen time što difraktogram X-zraka spoja ima maksimalni vršak kuta 2-theta kod 6.5, 8.7 i 24.3, mjereno pomoću K alfa1 bakrovog zračenja (1.54060 Å).
2. Spoj prema patentnom zahtjevu 1, naznačen time što difraktogram X-zraka spoja ima maksimalni vršak kuta 2-theta kod 6.5, 8.7, 18.3, 19.9, 20.7, 23.5 i 24.3, mjereno pomoću K alfa1 bakrovog zračenja (1.54060 Å).
3. 2-{4-[2-({[2-(4-Klorofenil)-1,3-tiazol-4-il]metil}sulfanil)-3,5-dicijano-6-(pirolidin-1-il)piridin-4-il]fenoksi}etil-L-alanil L-alaninat monohidroklorid s formulom (I) u kristalnom obliku modifikacije I
naznačen time što Ramanov spektar spoja ima maksimum linija kod 2907, 1004 i 598 cm-1.
4. Spoj prema patentnom zahtjevu 3, naznačen time što Ramanov spektar spoja ima maksimum linija kod 2907, 1539, 1515, 1182, 1004 i 598 cm-1.
5. Spoj prema patentnom zahtjevu 3 ili 4, naznačen time što Ramanov spektar spoja ima maksimum linija kod 2907, 1539, 1515, 1394, 1245, 1182, 1004 i 598 cm-1.
6. Lijek naznačen time što sadrži spoj prema bilo kojem od patentnih zahtjeva 1 do 5 i nema većih udjela bilo kojeg drugog oblika spoja s formulom (I).
7. Lijek naznačen time što sadrži spoj prema bilo kojem od patentnih zahtjeva 1 do 5 u količini više od 90 masenih postotaka na temelju ukupne količine prisutnog spoja formule (I).
8. Spoj prema bilo kojem od patentnih zahtjeva 1 do 5 naznačen time što je za uporabu u postupku liječenja kardiovaskularnih poremećaja ili poremećaja bubrega.
9. Postupak pripreme 2-{4-[2-({[2-(4-klorofenil)-1,3-tiazol-4-il]metil}sulfanil)-3,5-dicijano-6-(pirolidin-1-il)piridin-4-il]fenoksi}etil-L-alanil L-alaninat monohidroklorida s formulom (I) u kristalnom obliku modifikacije I, koji ima maksimalni vršak difraktograma X-zraka i maksimum linija Ramanovog spektra naveden z patentnim zahtjevima 1 do 5, naznačen time što se dialaninat dihidroklorid s formulom (IX)
miješa u suvišku izopropanola ili smjese n-propanola/vode (98:2) kod sobne temperature, dajući, nakon sušenja, spoj s formulom (I) u kristalnoj modifikaciji I.
10. Postupak prema zahtjevu 9 za pripravu spoja (I)
naznačen time što
[A] u koraku 1 u reakciji u jednoj posudi spoj s formulom (II)
reagira u prisutnosti otapala, katalizatora faznog prijelaza, nitrita i bakrovog (II) klorida i dobiva se intermedijer formule (III)
koji reagira bez izolacije, tj. u otopini, s pirolidinom kako bi se dobilo spoj s formulom (IV)
[B] spoj s formulom (IV) dobiven na ovaj način, u koraku 2, pretvara se i u reakciji u jednoj posudi s Boc-L-alaninom u prisutnosti kondenzacijskog sredstva dicikloheksilkarbodiimida (DCC) u kombinaciji s 4-(dimetilamino)piridinom i u prisutnosti otapala u zaštićeni Boc-alaninat (V)
koji se, bez izolacije, tj. u otopini, prevodi s klorovodičnom kiselinom u alaninat dihidroklorid s formulom (VIII)
i
[C] spoj s formulom (VIII) dobiven na ovaj način, u koraku 3, u kombinaciji s 4-(dimetilamino)piridinom i u prisutnosti otapala, reagira s Boc-L-alaninom u prisutnosti kondenzacijskog sredstva dicikloheksilkarbodiimida (DCC) da se dobije zaštićeni Boc-dialaninat (VII)
i
[D] spoj s formulom (VII) dobiven na ovaj način, u koraku 4, u prisutnosti otapala, reagira s klorovodičnom kiselinom da bi se dobio dialaninat dihidroklorid s formulom (IX)
i
[E] spoj s formulom (IX) dobiven na ovaj način, u koraku 5, miješa se u suvišku izopropanola ili smjese n-propanola/vode (98:2) kod sobne temperature, dajući spoj s formulom (I) u kristalnoj modifikaciji I.
11. Postupak prema zahtjevu 10, naznačen time što se spoj s formulom (II)
dobiva najprije u prisutnosti metanola i trietilamina, reagirajući sa supstituiranim malononitrilom s formulom (XI)
s cijanotioacetamidom s formulom (XII)
i zatim reakcijom intermedijera dobivenog s klorometilklorefeniltiazolom s formulom (XIV)
12. Postupak prema zahtjevu 10, naznačen time što je u koraku 1, prije daljnje reakcije, izoliran intermedijer s formulom, koji je dobiven kao krutina.
13. Postupak prema zahtjevu 10, naznačen time što se u koraku 2, prije daljnje reakcije, izolira zaštićeni Boc-alaninat s formulom (V), koji je dobiven kao kruta tvar.
14. Postupak prema zahtjevu 10, naznačen time što zaštićeni Boc-dialaninat s formulom (VII) dobiven u koraku 3 nije izoliran, već je izravno dalje reagira.
15. Postupak prema zahtjevu 10, naznačen time što je u koraku 1, prije daljnje reakcije, izoliran intermedijer s formulom (III), koji je dobiven kao krutina.
16. Spoj 2-{4-[2-({[2-(4-klorofenil)-1,3-tiazol-4-il]metil}sulfanil)-3,5-dicijano-6-(pirolidin-1-il)piridin-4-il]fenoksi}etil-L-alanil L-alaninat dihidroklorid s formulom (IX)
17. Spoj 2-{4-[2-({[2-(4-klorofenil)-1,3-tiazol-4-il]metil}sulfanil)-3,5-dicijano-6-(pirolidin-1-il)piridin-4-il]fenoksi}etil L-alaninat dihidroklorid (VIII)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15166606 | 2015-05-06 | ||
| EP15192030 | 2015-10-29 | ||
| PCT/EP2016/059779 WO2016188711A1 (de) | 2015-05-06 | 2016-05-02 | Verfahren zur herstellung von 2-{4-[2-({[2-(4-chlorphenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)-3,5-dicyan-6-(pyrrolidin-1-yl)pyridin-4-yl]phenoxy}ethyl-l-alanyl-l-alaninat-monohydrochlorid |
| EP16722584.6A EP3292133B1 (de) | 2015-05-06 | 2016-05-02 | Verfahren zur herstellung von 2-{4-[2-({[2-(4-chlorphenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)-3,5-dicyan-6-(pyrrolidin-1-yl)pyridin-4-yl]phenoxy}ethyl-l-alanyl-l-alaninat-monohydrochlorid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20191596T1 true HRP20191596T1 (hr) | 2019-11-29 |
Family
ID=55969107
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20191596 HRP20191596T1 (hr) | 2015-05-06 | 2019-09-04 | Postupak za pripravu 2-{4-[2-({[2-(4-klorofenil)-1,3-tiazol-4-il]metil}sulfanil)-3,5-dicijan-6- (pirolidin-1-il)piridin-4-il]fenoksi}etil-l-alanil-l-alaninat hidroklorida |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US20180155336A1 (hr) |
| EP (1) | EP3292133B1 (hr) |
| JP (1) | JP2018516882A (hr) |
| KR (1) | KR20180002698A (hr) |
| CN (1) | CN107531688A (hr) |
| AU (1) | AU2016268920A1 (hr) |
| BR (1) | BR112017023852A2 (hr) |
| CA (1) | CA2984984A1 (hr) |
| CL (1) | CL2017002764A1 (hr) |
| CO (1) | CO2017011294A2 (hr) |
| CU (1) | CU20170136A7 (hr) |
| DK (1) | DK3292133T3 (hr) |
| EA (1) | EA201792422A1 (hr) |
| EC (1) | ECSP17072780A (hr) |
| ES (1) | ES2744227T3 (hr) |
| HK (1) | HK1246290A1 (hr) |
| HR (1) | HRP20191596T1 (hr) |
| HU (1) | HUE044787T2 (hr) |
| IL (1) | IL255208A0 (hr) |
| LT (1) | LT3292133T (hr) |
| MA (1) | MA42039A (hr) |
| MX (1) | MX2017014134A (hr) |
| PE (1) | PE20180204A1 (hr) |
| PH (1) | PH12017502010A1 (hr) |
| PL (1) | PL3292133T3 (hr) |
| PT (1) | PT3292133T (hr) |
| SG (1) | SG11201708747PA (hr) |
| SI (1) | SI3292133T1 (hr) |
| TN (1) | TN2017000466A1 (hr) |
| TW (1) | TW201713651A (hr) |
| UY (1) | UY36664A (hr) |
| WO (1) | WO2016188711A1 (hr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2018108884A1 (de) | 2016-12-16 | 2018-06-21 | Bayer Pharma Aktiengesellschaft | Pharmazeutische tablettenformulierung |
| WO2019180072A1 (en) | 2018-03-22 | 2019-09-26 | Bayer Pharma Aktiengesellschaft | Parenteral pharmaceutical composition comprising neladenoson bialanate |
| TWI721449B (zh) * | 2019-06-11 | 2021-03-11 | 行政院原子能委員會核能研究所 | 2-[[2-[[[3-(4-氯苯基)-8-甲基-8-氮雜雙環[3.2.1]-辛-2-基]-甲基](2-巰基乙基)胺基]乙基]胺基]乙硫醇-[1r(外向-外向)]三鹽酸化物之純化方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10238113A1 (de) * | 2001-12-11 | 2003-06-18 | Bayer Ag | Substituierte 2-Thio-3,5-dicyano-4-phenyl-6-aminopyridine und ihre Verwendung |
| DE102009006602A1 (de) * | 2009-01-29 | 2010-08-05 | Bayer Schering Pharma Aktiengesellschaft | Alkylamino-substituierte Dicyanopyridine und deren Aminosäureester-Prodrugs |
| US20120058983A1 (en) * | 2010-09-02 | 2012-03-08 | Bayer Pharma Aktiengesellschaft | Adenosine A1 agonists for the treatment of glaucoma and ocular hypertension |
-
2016
- 2016-05-02 ES ES16722584T patent/ES2744227T3/es active Active
- 2016-05-02 MA MA042039A patent/MA42039A/fr unknown
- 2016-05-02 MX MX2017014134A patent/MX2017014134A/es unknown
- 2016-05-02 BR BR112017023852-7A patent/BR112017023852A2/pt not_active Application Discontinuation
- 2016-05-02 WO PCT/EP2016/059779 patent/WO2016188711A1/de active Application Filing
- 2016-05-02 DK DK16722584.6T patent/DK3292133T3/da active
- 2016-05-02 JP JP2017557439A patent/JP2018516882A/ja active Pending
- 2016-05-02 HU HUE16722584 patent/HUE044787T2/hu unknown
- 2016-05-02 CU CUP2017000136A patent/CU20170136A7/xx unknown
- 2016-05-02 PT PT16722584T patent/PT3292133T/pt unknown
- 2016-05-02 US US15/568,575 patent/US20180155336A1/en not_active Abandoned
- 2016-05-02 SG SG11201708747PA patent/SG11201708747PA/en unknown
- 2016-05-02 EP EP16722584.6A patent/EP3292133B1/de active Active
- 2016-05-02 UY UY0001036664A patent/UY36664A/es not_active Application Discontinuation
- 2016-05-02 SI SI201630320T patent/SI3292133T1/sl unknown
- 2016-05-02 CN CN201680026200.1A patent/CN107531688A/zh active Pending
- 2016-05-02 PE PE2017002369A patent/PE20180204A1/es unknown
- 2016-05-02 AU AU2016268920A patent/AU2016268920A1/en not_active Abandoned
- 2016-05-02 EA EA201792422A patent/EA201792422A1/ru unknown
- 2016-05-02 LT LTEP16722584.6T patent/LT3292133T/lt unknown
- 2016-05-02 TN TNP/2017/000466A patent/TN2017000466A1/en unknown
- 2016-05-02 CA CA2984984A patent/CA2984984A1/en not_active Abandoned
- 2016-05-02 KR KR1020177033435A patent/KR20180002698A/ko unknown
- 2016-05-02 PL PL16722584T patent/PL3292133T3/pl unknown
- 2016-05-04 TW TW105113790A patent/TW201713651A/zh unknown
-
2017
- 2017-10-23 IL IL255208A patent/IL255208A0/en unknown
- 2017-10-31 EC ECIEPI201772780A patent/ECSP17072780A/es unknown
- 2017-11-02 CL CL2017002764A patent/CL2017002764A1/es unknown
- 2017-11-02 CO CONC2017/0011294A patent/CO2017011294A2/es unknown
- 2017-11-03 PH PH12017502010A patent/PH12017502010A1/en unknown
-
2018
- 2018-05-07 HK HK18105816.1A patent/HK1246290A1/zh unknown
-
2019
- 2019-09-04 HR HRP20191596 patent/HRP20191596T1/hr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PE20180204A1 (es) | 2018-01-31 |
| HK1246290A1 (zh) | 2018-09-07 |
| UY36664A (es) | 2016-11-30 |
| CO2017011294A2 (es) | 2018-01-16 |
| WO2016188711A1 (de) | 2016-12-01 |
| EP3292133B1 (de) | 2019-06-26 |
| US20180155336A1 (en) | 2018-06-07 |
| EA201792422A1 (ru) | 2018-02-28 |
| SI3292133T1 (sl) | 2019-08-30 |
| HUE044787T2 (hu) | 2019-11-28 |
| DK3292133T3 (da) | 2019-09-23 |
| ES2744227T3 (es) | 2020-02-24 |
| EP3292133A1 (de) | 2018-03-14 |
| TW201713651A (zh) | 2017-04-16 |
| CL2017002764A1 (es) | 2018-05-25 |
| BR112017023852A2 (pt) | 2018-07-17 |
| ECSP17072780A (es) | 2017-12-01 |
| MX2017014134A (es) | 2018-03-15 |
| KR20180002698A (ko) | 2018-01-08 |
| CA2984984A1 (en) | 2016-12-01 |
| TN2017000466A1 (en) | 2019-04-12 |
| CU20170136A7 (es) | 2018-02-08 |
| PL3292133T3 (pl) | 2019-12-31 |
| JP2018516882A (ja) | 2018-06-28 |
| CN107531688A (zh) | 2018-01-02 |
| AU2016268920A1 (en) | 2017-11-09 |
| SG11201708747PA (en) | 2017-11-29 |
| IL255208A0 (en) | 2017-12-31 |
| MA42039A (fr) | 2018-03-14 |
| LT3292133T (lt) | 2019-08-26 |
| PH12017502010A1 (en) | 2018-03-26 |
| PT3292133T (pt) | 2019-09-18 |
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