HRP20171122T1 - Novi makrociklusi kao inhibitori faktora xia - Google Patents
Novi makrociklusi kao inhibitori faktora xia Download PDFInfo
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- HRP20171122T1 HRP20171122T1 HRP20171122TT HRP20171122T HRP20171122T1 HR P20171122 T1 HRP20171122 T1 HR P20171122T1 HR P20171122T T HRP20171122T T HR P20171122TT HR P20171122 T HRP20171122 T HR P20171122T HR P20171122 T1 HRP20171122 T1 HR P20171122T1
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- alkyl
- compound
- pharmaceutically acceptable
- independently
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- 108010080805 Factor XIa Proteins 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 150000002678 macrocyclic compounds Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 25
- 125000000217 alkyl group Chemical group 0.000 claims 18
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 15
- 229910052739 hydrogen Inorganic materials 0.000 claims 15
- 150000003839 salts Chemical class 0.000 claims 11
- 229910052799 carbon Inorganic materials 0.000 claims 9
- 229910052736 halogen Inorganic materials 0.000 claims 8
- 150000002367 halogens Chemical class 0.000 claims 8
- 125000000623 heterocyclic group Chemical group 0.000 claims 8
- 239000012453 solvate Substances 0.000 claims 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
- 208000035475 disorder Diseases 0.000 claims 6
- 229910052757 nitrogen Inorganic materials 0.000 claims 6
- 230000009424 thromboembolic effect Effects 0.000 claims 6
- 125000004432 carbon atom Chemical group C* 0.000 claims 5
- 125000005842 heteroatom Chemical group 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 125000003118 aryl group Chemical group 0.000 claims 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- 206010047249 Venous thrombosis Diseases 0.000 claims 2
- 125000004450 alkenylene group Chemical group 0.000 claims 2
- 125000002947 alkylene group Chemical group 0.000 claims 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 238000011282 treatment Methods 0.000 claims 2
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims 1
- 206010002388 Angina unstable Diseases 0.000 claims 1
- 200000000007 Arterial disease Diseases 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 206010003658 Atrial Fibrillation Diseases 0.000 claims 1
- 206010008088 Cerebral artery embolism Diseases 0.000 claims 1
- 206010008092 Cerebral artery thrombosis Diseases 0.000 claims 1
- 206010011091 Coronary artery thrombosis Diseases 0.000 claims 1
- 206010051055 Deep vein thrombosis Diseases 0.000 claims 1
- 206010014513 Embolism arterial Diseases 0.000 claims 1
- 206010061216 Infarction Diseases 0.000 claims 1
- 206010037379 Pulmonary embolism and thrombosis Diseases 0.000 claims 1
- 206010063544 Renal embolism Diseases 0.000 claims 1
- 208000007536 Thrombosis Diseases 0.000 claims 1
- 208000032109 Transient ischaemic attack Diseases 0.000 claims 1
- 208000007814 Unstable Angina Diseases 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
- 208000002528 coronary thrombosis Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 239000007943 implant Substances 0.000 claims 1
- 230000007574 infarction Effects 0.000 claims 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims 1
- 201000010849 intracranial embolism Diseases 0.000 claims 1
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical group O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 230000003836 peripheral circulation Effects 0.000 claims 1
- 230000002093 peripheral effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 201000005060 thrombophlebitis Diseases 0.000 claims 1
- 201000010875 transient cerebral ischemia Diseases 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/06—Peri-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/06—Peri-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (13)
1. Spoj sa formulom (I):
[image]
ili stereoizomer, tautomer, farmaceutski prihvatljiva sol, ili solvat tog spoja, gdje:
prsten A je odabran od arila i 5- do 6-članog heterociklusa koji sadrži: ugljikove atome i 1-4 heteroatoma koji su odabrani od N, NH, N(C1-4 alkil), S(O)p, i O, gdje su spomenuti aril i heterociklus po izboru supstituirani sa R1;
prsten B je 5- do 6-člani heterociklus koji sadrži: ugljikove atome i 1-4 heteroatoma koji su odabrani od N, NH, S(O)p, i O, gdje je spomenuti heterociklus po izboru supstituiran sa R10;
prsten C je 4- do 5-člani heterociklus koji sadrži: ugljikove atome i 1-4 heteroatoma koji su odabrani od N, NR9, S(O)p, i O, gdje je spomenuti heterociklus po izboru supstituiran sa R2;
X1 je odabran od C1-4 alkilena, i C2-4 alkenilena; po izboru jedan ili više ugljikovih atoma spomenutog alkilena i alkenilena može biti zamijenjeno sa O, S(O)p, NH, i N(C1-4 alkil);
R1 je, nezavisno u svakom slučaju, odabran od H, halogen, NO2, C1-6 alkil, OH, OMe, i CN;
R2 je odabran od H, =O, OH, NH2, CF3, halogena, i C1-4 alkila po izboru supstituiranog sa OH;
R3 je odabran od H i C1-4 alkila;
alternativno, R2 i R3, zajedno sa atomima za koje su direktno ili indirektno vezani, formiraju prsten pri čemu je spomenuti prsten po izboru supstituiran sa =O;
R4 je odabran od H, C1-4 alkila, hidroksila, i C3-6 cikloalkila;
R5 je odabran od H i C1-4 alkila;
R6 je odabran od H, halogena, C(O)OH, i C(O)O(C1-4 alkil);
R7 je odabran od H, C1-4 alkila, i CF3;
alternativno, R6 i R7 zajedno su =O;
R8 je, nezavisno u svakom slučaju, odabran od H, halogena, NHC(O)O-C1-4 alkila, CN, OH, O-C1-4 alkila; CF3, CO2H, CO2(C1-4 alkil), -CH2CO2H, -(CH2)2CO2H, -CH2CO2(C1-4 alkil), -(CH2)2CO2(C1-4 alkil), NH2, -CH2NH2, -NHCO(C1-4 alkil), -NHCO2(CH2)1-2O(C1-4 alkil), -NHCO2(CH2)1-30(C1-4 alkil), NHCO2CH2CH(C1-4 alkil)O(C1-4 alkil), -NHCO2(CH2)1-2OH, -NHCO2CH2CO2H, -CH2NHCO2(C1-4 alkil), -NHC(O)NH(C1-4 alkil), -NHC(O)N(C1-4 alkil)2, NHC(O)NH(C1-4 alkil)N[5- do 6-člani heterociklus)], -NHSO2(C1-4 alkil), -CONH2, -CONH(C1-4 alkil), -CON(C1-4 alkil)2, i -CH2CONH2;
R9 je odabran od H i C1-4 alkila;
R10 je, nezavisno u svakom slučaju, odabran od H, halogena, CN, =O, OH, NH2, C3-6 cikloalkila, C1-4 alkoksi, CF3, CH2OH, CO2H, CO2(C1-4 alkil), i CONH;i
p je, nezavisno u svakom slučaju, odabran od 0, 1, i 2;
pod uvjetom da su isključeni sljedeća spojevi
[image]
i
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2. Spoj patentnog zahtjeva 1 koje ima Formulu (II):
[image]
ili stereoizomer, tautomer, farmaceutski prihvatljiva sol, ili solvat tog spoja, gdje:
prsten A je odabran od arila i 6-članog heterociklusa koji sadrži: ugljikove atome i 1-3 heteroatoma koji su odabrani od N, NH, i N(C1-4 alkil);
prsten B je odabran od imidazola, piridina, piridona, i piridazina;
X1 je odabran od CH2 i CH=CH;
W i Q su svaki nezavisno odabrani od N, NR9, CR2, i CHR2; i
R2a je odabran od H, NH2, i C1-4 alkila.
3. Spoj patentnog zahtjeva 2, ili stereoizomer, tautomer, farmaceutski prihvatljiva sol, ili solvat tog spoja, gdje:
prsten A je odabran od fenila i piperidina;
[image]
je nezavisno odabran od
[image]
[image]
[image]
i
R10 je odabran od H, halogena, i CN.
4. Spoj patentnog zahtjeva 3 koje ima Formulu (III):
[image]
ili stereoizomer, tautomer, farmaceutski prihvatljiva sol, ili solvat tog spoja, gdje:
[image]
je nezavisno odabran od
[image]
W i Q su svaki nezavisno odabrani od N i CR2;
R1a i R1b su svaki nezavisno odabrani od H i halogena;
R2 je nezavisno u svakom slučaju, odabran od H i C1-4 alkila po izboru supstituiranog sa OH;
R2a je odabran od H, NH2, i Me;
R4 je odabran od H i C1-4 alkila;
R5 je odabran od H i C1-4 alkila;
R6 je nezavisno odabran od H, C(O)OH, i C(O)O(C1-4 alkil);
R7 je odabran od H, C1-4 alkila, i CF3;
alternativno, R6 i R7 zajedno su =O; i
R10 je odabran od H, halogen i CN.
5. Spoj patentnog zahtjeva 4 koje ima Formulu (IV):
[image]
ili stereoizomer, tautomer, farmaceutski prihvatljiva sol, ili solvat tog spoja, gdje:
W i Q su svaki nezavisno odabrani od N i CH;
R1a i R1b su svaki nezavisno odabrani od H, F, i Cl;
R4 je odabran od H, metil, etil, propil, izopropil, i butil;
R5 je H;
R8 je NHC(O)O-C1-4 alkil; i
R10 je odabran od H i CN.
6. Spoj patentnog zahtjeva 5 koje ima Formulu (V):
[image]
ili stereoizomer, tautomer, farmaceutski prihvatljiva sol, ili solvat tog spoja, gdje:
R1a je odabran od H i F;
R1b je Cl; i
R4 je odabran od H, metil, etil, i izopropil.
7. Spoj patentnog zahtjeva 4 koje ima Formulu (VI):
[image]
ili stereoizomer, tautomer, farmaceutski prihvatljiva sol, ili solvat tog spoja, gdje:
[image]
je nezavisno odabran od
[image]
W je odabran od N i CH;
Q je odabran od N i CH;
R1a i R1b su svaki nezavisno odabrani od F i Cl;
R4 je odabran od H, metil, i etil; i
R8 je NHC(O)OMe.
8. Spoj prema patentnom zahtjevu 1, odabrano iz grupe koja se sastoji od:
[image]
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gdje R je
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ili
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gdje R je
[image]
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ili
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gdje R je
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gdje R je
[image]
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i
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9. Farmaceutska kompozicija koja sadrži jedno ili više spoja u skladu sa bilo kojim od patentnih zahtjeva 1-8 i farmaceutski prihvatljiv nosač ili otapalo.
10. Spoj iz bilo kojeg od patentnih zahtjeva 1-8, ili stereoizomer, tautomer, ili farmaceutski prihvatljiva sol tog spoja, za primjenu u liječenju.
11. Terapijski efikasna količina spoja iz bilo kojeg od patentnih zahtjeva 1-8, ili stereoizomera, tautomera, ili farmaceutski prihvatljive soli tog spoja, za primjenu u liječenju i/ili profilaksi tromboembolijskog poremećaja.
12. Terapijski efikasna količina spoja bilo kojeg od patentnih zahtjeva 1-8, ili stereoizomera, tautomera, ili farmaceutski prihvatljive soli tog spoja, za primjenu prema patentnom zahtjevu 11, gdje tromboembolijski poremećaj je odabran iz grupe koja se sastoji od arterijskih kardiovaskularnih tromboembolijskih poremećaja, venskih kardiovaskularnih tromboembolijskih poremećaja i tromboembolijskih poremećaja u komorama srca ili u perifernoj cirkulaciji.
13. Terapijski efikasna količina spoja bilo kojeg od patentnih zahtjeva 1-8, ili stereoizomera, tautomera, ili farmaceutski prihvatljive soli tog spoja, za primjenu prema patentnom zahtjevu 12, gdje je tromboembolijski poremećaj odabran od nestabilne angine, akutnog koronarnog sindroma, atrijalne fibrilacije, infarkta miokarda, prolaznog ishemijskog napada, infarkta, ateroskleroze, periferne okluzivne arterijske bolesti, venske tromboze, duboke venske tromboze, tromboflebitisa, arterijske embolije, koronarne arterijske tromboze, cerebralne arterijske tromboze, cerebralne embolije, embolije bubrega, plućne embolije i tromboze koja nastaje od medicinskih implantata, uređaja ili procedura u kojima je krv izložena umjetnoj površini koja pospješuje trombozu.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161515401P | 2011-08-05 | 2011-08-05 | |
| EP12762427.8A EP2739628B1 (en) | 2011-08-05 | 2012-08-06 | Novel macrocycles as factor xia inhibitors |
| PCT/US2012/049706 WO2013022818A1 (en) | 2011-08-05 | 2012-08-06 | Novel macrocycles as factor xia inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20171122T1 true HRP20171122T1 (hr) | 2017-10-06 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20171122TT HRP20171122T1 (hr) | 2011-08-05 | 2017-07-21 | Novi makrociklusi kao inhibitori faktora xia |
Country Status (21)
| Country | Link |
|---|---|
| US (4) | US9221818B2 (hr) |
| EP (1) | EP2739628B1 (hr) |
| JP (1) | JP6158181B2 (hr) |
| CN (1) | CN103857681B (hr) |
| AR (1) | AR088748A1 (hr) |
| BR (1) | BR112014002202A2 (hr) |
| CA (1) | CA2844254A1 (hr) |
| CY (1) | CY1119281T1 (hr) |
| DK (1) | DK2739628T3 (hr) |
| EA (1) | EA024791B1 (hr) |
| ES (1) | ES2635088T3 (hr) |
| HR (1) | HRP20171122T1 (hr) |
| HU (1) | HUE034487T2 (hr) |
| LT (1) | LT2739628T (hr) |
| MX (1) | MX345763B (hr) |
| PL (1) | PL2739628T3 (hr) |
| PT (1) | PT2739628T (hr) |
| RS (1) | RS56244B1 (hr) |
| SI (1) | SI2739628T1 (hr) |
| TW (1) | TW201311689A (hr) |
| WO (1) | WO2013022818A1 (hr) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2011215898B2 (en) | 2010-02-11 | 2016-08-11 | Bristol-Myers Squibb Company | Macrocycles as Factor XIa inhibitors |
| TW201311689A (zh) | 2011-08-05 | 2013-03-16 | 必治妥美雅史谷比公司 | 作為因子ｘｉａ抑制劑之新穎巨環化合物 |
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| PT2739628T (pt) | 2017-08-02 |
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| SI2739628T1 (sl) | 2017-08-31 |
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| EP2739628B1 (en) | 2017-06-07 |
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| EA024791B1 (ru) | 2016-10-31 |
| JP6158181B2 (ja) | 2017-07-05 |
| US9221818B2 (en) | 2015-12-29 |
| EA201490418A1 (ru) | 2014-05-30 |
| US20180148461A1 (en) | 2018-05-31 |
| ES2635088T3 (es) | 2017-10-02 |
| EP2739628A1 (en) | 2014-06-11 |
| CN103857681B (zh) | 2017-07-14 |
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| CY1119281T1 (el) | 2018-02-14 |
| HUE034487T2 (en) | 2018-02-28 |
| BR112014002202A2 (pt) | 2017-03-07 |
| US20170158712A1 (en) | 2017-06-08 |
| CN103857681A (zh) | 2014-06-11 |
| US10208068B2 (en) | 2019-02-19 |
| MX345763B (es) | 2017-02-15 |
| RS56244B1 (sr) | 2017-11-30 |
| PL2739628T3 (pl) | 2017-11-30 |
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