HRP20130918T1 - Derivati 4-aminopirimidina kao receptori antagonista histamina h4 - Google Patents
Derivati 4-aminopirimidina kao receptori antagonista histamina h4 Download PDFInfo
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- HRP20130918T1 HRP20130918T1 HRP20130918AT HRP20130918T HRP20130918T1 HR P20130918 T1 HRP20130918 T1 HR P20130918T1 HR P20130918A T HRP20130918A T HR P20130918AT HR P20130918 T HRP20130918 T HR P20130918T HR P20130918 T1 HRP20130918 T1 HR P20130918T1
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- cycloalkyl
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- 102000004187 Histamine H4 receptors Human genes 0.000 title claims 2
- 108090000796 Histamine H4 receptors Proteins 0.000 title claims 2
- 150000005007 4-aminopyrimidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 29
- 125000000217 alkyl group Chemical group 0.000 claims 23
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 16
- 125000003118 aryl group Chemical group 0.000 claims 8
- 229910052736 halogen Inorganic materials 0.000 claims 8
- 150000002367 halogens Chemical class 0.000 claims 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 8
- 125000001424 substituent group Chemical group 0.000 claims 7
- 125000005843 halogen group Chemical group 0.000 claims 6
- 125000000623 heterocyclic group Chemical group 0.000 claims 6
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 5
- 150000003839 salts Chemical class 0.000 claims 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 4
- 229910003827 NRaRb Inorganic materials 0.000 claims 3
- 125000004432 carbon atom Chemical group C* 0.000 claims 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 3
- 229910021529 ammonia Inorganic materials 0.000 claims 2
- 125000003725 azepanyl group Chemical group 0.000 claims 2
- 125000002393 azetidinyl group Chemical group 0.000 claims 2
- 125000002619 bicyclic group Chemical group 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 2
- 125000005842 heteroatom Chemical group 0.000 claims 2
- 125000002950 monocyclic group Chemical group 0.000 claims 2
- 125000003386 piperidinyl group Chemical group 0.000 claims 2
- 125000006239 protecting group Chemical group 0.000 claims 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 2
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims 1
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims 1
- 208000002193 Pain Diseases 0.000 claims 1
- 208000026935 allergic disease Diseases 0.000 claims 1
- 230000000172 allergic effect Effects 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 239000003638 chemical reducing agent Substances 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- -1 cyclopentyl cyclohexyl Chemical group 0.000 claims 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 230000001900 immune effect Effects 0.000 claims 1
- 208000026278 immune system disease Diseases 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation 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
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A61P11/00—Drugs for disorders of the respiratory system
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Claims (21)
1. Spoj formule I
[image]
naznačen time, da:
R1 predstavlja:
(1) C1-8 alkil;
(2) C3-8 cikloalkil-C0-6 alkil;
(3) aril-C1-6 alkil;
pri čemu u skupinama (1) do (3) bilo koja alkilna skupina po izboru može biti supstituirana s jednom ili više skupina halogena, a C3-8 cikloalkilna skupina po izboru može biti supstituirana s jednim ili više supstituenata neovisno odabranih od C1-4 alkila, halogena i arila;
(4) skupina formule (i)
[image]
ili
(5) skupina formule (ii):
[image]
R2 i R3 tvore, zajedno s N atomom za kojeg su vezani, zasićenu heterocikličku skupinu koja može biti 4- do 7-meročlana monociklička, 7- do 8-meročlana premoštena biciklička ili 8- do 12-teročlana spojena biciklička, pri čemu rečena heterociklička skupina može sadržati do dva N atoma i ne sadrži bilo koje druge heteroatome, te po izboru može biti supstituirana s jednim ili više supstituenata neovisno odabranih od C1-4 alkil i NRaRb, pod uvjetom da heterociklička skupina ili sadrži 2 N atoma i nije supstituirana s NRaRb skupinom ili sadrži 1 N atom i supstituirana je s jednom NRaRb skupinom; ili
R2 predstavlja H ili C1-4 alkil, a R3 predstavlja azetidinil, pirolidinil, piperidinil ili azepanil, koji po izboru mogu biti supstituirani s jednom ili više C1-4 alkilnih skupina;
Ra predstavlja H ili C1-4 alkil;
Rb predstavlja H ili C1-4 alkil;
ili Ra i Rb tvore, zajedno s N atomom za kojeg su vezani azetidinil, pirolidinil, piperidinil ili azepanil skupinu koja po izboru može biti supstituirana s jednom ili više C1-4 alkilnih skupina;
R4 i R5 su neovisno odabrani od H i C1-4 alkila te dodatno jedne od R4 ili R5 skupina mogu predstavljati aril ili C3-8 cikloalkil-C0-6 alkila, i dodatno dvije R4 i R5 skupina na istom C atomu mogu biti vezane zajedno tvoreći s rečenim C atomom C3-8 cikloalkilnu skupinu;
R6 predstavlja skupinu odabranu od C1-8 alkil, C3-8 cikloalkil-C0-6 alkila i aril-C0-4 alkila, pri čemu bilo koja alkilna skupina po izboru može biti supstituirana s jednom ili više skupina halogena a C3-8 cikloalkilna skupina po izboru može biti supstituirana s jednim ili više supstituenata neovisno odabranih od C1-4 alkila, halogena i arila;
R7 predstavlja zasićeni monociklički 4- do 7-meročlani heterociklički prsten koji se sastoji od O atoma te ne sadrži bilo koje druge dodatne heteroatome, pri čemu rečeni prsten može biti vezan za ostatak molekule preko bilo kojeg dostupnog C atoma te pri čemu R7 po izboru može biti supstituiran s jednom ili više skupina neovisno odabranih od C1-4 alkila i halogena; n predstavlja 1, 2 ili 3; p predstavlja o, 1 ili 2; i
aril predstavlja fenilnu skupinu po izboru supstituiranu s jednom ili više skupina neovisno odabranih od C1-4 alkila, halogena, C1-4 alkoksi, C1-4 haloalkila, C1-4 haloalkoksi, cijano i amino;
ili njihove soli.
2. Spoj u skladu s patentnim zahtjevom 1, naznačen time, da
R1 predstavlja:
(1) C4-6alkil;
(2) C3-8 cikloalkil-C0-1 alkil; ili
(3) aril-C1-2 alkil.
3. Spoj u skladu s patentnim zahtjevom 1, naznačen time, da R1 predstavlja C1-8 alkil ili C3-8 cikloalkil-C0-6 alkil, pri čemu bilo koja alkilna skupina po izboru može biti supstituirana s jednom ili više skupina halogena i C3-8 cikloalkilna skupina po izboru može biti supstituirana s jednim ili više supstituenata neovisno odabranih od C1-4 alkila, halogena i arila; poželjno je da R1 predstavlja C1-8 alkil ili C3-8 cikloalkil-C0-6 alkil; još poželjnije da R1 predstavlja C4-6 alkil ili C3-8 cikloalkil-C0-1 alkil; a još je više poželjno da R1 predstavlja izobutil, 2,2-dimetilpropil, ciklobutil, ciklopentil cikloheksil, cikloheksilmetil ili ciklopropilmetil.
4. Spoj u skladu s patentnim zahtjevom 1, naznačen time, da R1 predstavlja C1-8 alkil po izboru supstituiran s jednim ili više skupina halogena.
5. Spoj u skladu s patentnim zahtjevom 4, naznačen time, da R1 predstavlja C4-6 alkil.
6. Spoj u skladu s patentnim zahtjevom 5, naznačen time, da R1 predstavlja izobutil ili 2,2-dimetilpropil.
7. Spoj u skladu s patentnim zahtjevom 6, naznačen time, da R1 predstavlja izobutil.
8. Spoj u skladu s patentnim zahtjevom 6, naznačen time, da R1 predstavlja 2,2-dimetilpropil.
9. Spoj u skladu s patentnim zahtjevom 1, naznačen time, da R1 predstavlja C3-8 cikloalkil-C0-6 alkil, gdje alkilna skupina po izboru može biti supstituirana s jednom ili više skupina halogena a C3-8 cikloalkilna skupina po izboru može biti supstituirana s jednim ili više supstituenata neovisno odabranih od C1-4 alkila, halogena i arila; poželjno je da R1 predstavlja C3-8 cikloalkil-C1 alkil; još poželjnije je da R1 predstavlja ciklopropilmetil ili cikloheksilmetil.
10. Spoj u skladu s patentnim zahtjevom 1, naznačen time, da R1 predstavlja C3-8 cikloalkil po izboru supstituiran s jednim ili više supstituenata neovisno odabranih od C1-4 alkila, halogena i arila.
11. Spoj u skladu s patentnim zahtjevom 10, naznačen time, da R1 predstavlja ciklobutil, ciklopentil ili cikloheksil.
12. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 11, naznačen time, da R2 i R3 tvore, zajedno s N atomom za kojeg su vezani, zasićenu heterocikličku skupinu odabranu od:
[image]
gdje RC predstavlja H ili C1-4alkil, poželjno je da RC predstavlja H.
13. Spoj u skladu s patentnim zahtjevom 12, naznačen time, da R2 i R3 tvore, zajedno s N atomom za kojeg su vezani, zasićenu heterocikličku skupinu odabranu od (a) i (b).
14. Spoj u skladu s patentnim zahtjevom 12, naznačen time, da R2 i R3 tvore, zajedno s N atomom za kojeg su vezani, zasićenu heterocikličku skupinu od formule (a).
15. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 14, naznačen time, da Ra i Rb neovisno predstavljaju H ili C1-4 alkil; poželjno je da Ra i Rb neovisno predstavljaju H ili metil; i još poželjnije da Ra predstavlja H, a Rb predstavlja H ili metil.
16. Spoj u skladu s patentnim zahtjevom 15, naznačen time, da Ra predstavlja H, a Rb predstavlja metil.
17. Farmaceutski pripravak, naznačen time, da sadrži spoj formule I u skladu s bilo kojim od patentnih zahtjeva 1 do 16 ili njegove farmaceutski prihvatljive soli te jedan ili više prihvatljivih farmaceutski prihvatljivih ekscipijensa.
18. Spoj formule I u skladu s bilo kojim od patentnih zahtjeva 1 do 16 ili njegove farmaceutski prihvatljive soli, naznačen time, da se koristi u terapiji.
19. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 16 ili njegove farmaceutski prihvatljive soli, naznačen time, da se koristi u liječenju bolesti povezanih s receptorom histamina H4.
20. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 16 ili njegove farmaceutski prihvatljive soli, naznačen time, da se koristi u liječenju alergijskih, imunoloških ili upalnih bolesti ili bolova.
21. Postupak priprave spoja formule I u skladu s patentnim zahtjevom 1, naznačen time, da se isti sastoji od:
(a) reagiranja spoja formule II s amonijakom ili ekvivalentom amonijaka
[image]
pri čemu R1, R2 i R3 imaju značenje kako je opisano u patentnom zahtjevu 1; ili
(b) reagiranja spoja formule VII sa spojem formule IV (ili njihovog amino- zaštitnog oblika)
[image]
pri čemu R1, R2 i R3 imaju značenje kako je opisano u patentnom zahtjevu 1, nakon čega po potrebi slijedi uklanjanje bilo koje zaštitne skupine koja može biti nazočna; ili
(c) reagiranja spoja formule VIIB sa spojem formule IV (ili njihovog amino-zaštitnog oblika)
[image]
pri čemu Ra predstavlja skupinu koja odlazi, a R1, R2 i R3 imaju značenje kako je opisano u patentnom zahtjevu 1, nakon čega po potrebi slijedi uklanjanje bilo koje zaštitne skupine koja može biti nazočna; ili
(d) kada u spoju formule I, R1 predstavlja R1,-CH2-CH2-, tretiranja spoja formule IX s redukcijskim sredstvom
[image]
pri čemu Rr predstavlja C1-6 alkil ili C3-a cikloalkil-C0-4 alkil ili aril-C0-4 alkil, gdje bilo koja alkilna skupina po izboru može biti supstituirana s jednim ili više skupina halogena i C3-a cikloalkilna skupina po izboru može biti supstituirana s jednim ili više supstituenata neovisno odabranih od C1-4 alkila, halogena i arila, ili R1' predstavlja skupinu formule (i) gdje n predstavlja 2, a R4 i R5 predstavljaju H ili skupinu formule (ii) gdje p predstavlja 2, a R4 i R5 predstavljaju H; i R2 i R3 imaju značenje opisano u patentnom zahtjevu 1; ili
(e) preinačenja spoja formule I u drugi spoj formule I u jednom ili nekoliko koraka.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07382006 | 2007-12-21 | ||
| US3153408P | 2008-02-26 | 2008-02-26 | |
| PCT/EP2008/067950 WO2009080721A2 (en) | 2007-12-21 | 2008-12-18 | 4 -aminopyrimidine derivatives as histamine h4 receptor antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20130918T1 true HRP20130918T1 (hr) | 2013-11-08 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20130918AT HRP20130918T1 (hr) | 2007-12-21 | 2013-09-27 | Derivati 4-aminopirimidina kao receptori antagonista histamina h4 |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US8431580B2 (hr) |
| EP (1) | EP2235012B1 (hr) |
| JP (1) | JP5498396B2 (hr) |
| KR (1) | KR101639819B1 (hr) |
| CN (1) | CN101903385B (hr) |
| AR (1) | AR069814A1 (hr) |
| AU (1) | AU2008341678B2 (hr) |
| BR (1) | BRPI0820779B8 (hr) |
| CA (1) | CA2709650C (hr) |
| CL (1) | CL2008003811A1 (hr) |
| CY (1) | CY1114427T1 (hr) |
| DK (1) | DK2235012T3 (hr) |
| ES (1) | ES2430210T3 (hr) |
| HK (1) | HK1149003A1 (hr) |
| HR (1) | HRP20130918T1 (hr) |
| IL (1) | IL206413A (hr) |
| PE (1) | PE20091330A1 (hr) |
| PL (1) | PL2235012T3 (hr) |
| PT (1) | PT2235012E (hr) |
| RU (1) | RU2489430C2 (hr) |
| SI (1) | SI2235012T1 (hr) |
| TW (1) | TWI429440B (hr) |
| UA (1) | UA101963C2 (hr) |
| WO (1) | WO2009080721A2 (hr) |
| ZA (1) | ZA201005179B (hr) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102007026341A1 (de) | 2007-06-06 | 2008-12-11 | Merck Patent Gmbh | Benzoxazolonderivate |
| DE102007032507A1 (de) | 2007-07-12 | 2009-04-02 | Merck Patent Gmbh | Pyridazinonderivate |
| DE102007061963A1 (de) | 2007-12-21 | 2009-06-25 | Merck Patent Gmbh | Pyridazinonderivate |
| DE102008019907A1 (de) | 2008-04-21 | 2009-10-22 | Merck Patent Gmbh | Pyridazinonderivate |
| DE102008028905A1 (de) | 2008-06-18 | 2009-12-24 | Merck Patent Gmbh | 3-(3-Pyrimidin-2-yl-benzyl)-[1,2,4]triazolo[4,3-b]pyridazinderivate |
| MX2011006682A (es) | 2008-12-22 | 2011-07-13 | Merck Patent Gmbh | Nuevas formas polimorficas de dihidrogeno-fosfato de 6-(1-metil-1h-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoxi)-pirim idin-2-il]-bencil}-2h-piridazin-3-ona y procesos para su preparacion. |
| EP2201982A1 (en) | 2008-12-24 | 2010-06-30 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Histamine H4 receptor antagonists for the treatment of vestibular disorders |
| KR101675614B1 (ko) | 2009-10-29 | 2016-11-11 | 벡투라 리미티드 | Ｊａｋ３ 키나아제 저해제로서의 ｎ―함유 헤테로아릴 유도체 |
| CA2785353C (en) * | 2009-12-23 | 2017-10-31 | Palau Pharma, S.A. | Aminoalkylpyrimidine derivatives as histamine h4 receptor antagonists |
| EP2858647B1 (en) | 2012-06-08 | 2018-05-23 | Sensorion | H4 receptor inhibitors for treating tinnitus |
| EP3697776B1 (en) * | 2017-10-17 | 2023-04-19 | Palau Pharma, S.L.U. | Synthesis of 4-aminopyrimidine compounds |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2361869C2 (ru) * | 2002-02-05 | 2009-07-20 | ХАЙ ПОЙНТ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи | Новые арил- и гетероарилпиперазины |
| EP1505064A1 (en) * | 2003-08-05 | 2005-02-09 | Bayer HealthCare AG | 2-Aminopyrimidine derivatives |
| WO2005054239A1 (en) * | 2003-12-05 | 2005-06-16 | Bayer Healthcare Ag | 2-aminopyrimidine derivatives |
| US20080058356A1 (en) * | 2003-12-15 | 2008-03-06 | Neurocrine Biosciences, Inc. | 2,6 Bisheteroaryl-4-Aminopyrimidines as Adenosine Receptor Antagonists |
| EP1888565B1 (en) * | 2005-04-11 | 2011-03-23 | Almirall, S.A. | 2, 6-di (hetero) aryl -4-amido-pyrimidines as adenosine receptor antagonists |
| KR20080043840A (ko) * | 2005-09-13 | 2008-05-19 | 팔라우 파르마 에스에이 | 히스타민 ｈ4 수용체 활성의 조정자로서 2-아미노피리미딘유도체 |
| EP1976851A2 (en) * | 2006-01-17 | 2008-10-08 | Neurocrine Biosciences, Inc. | Phenoxy-substituted pyrimidines as adenosine receptor antagonists |
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2008
- 2008-12-18 JP JP2010538738A patent/JP5498396B2/ja active Active
- 2008-12-18 TW TW097149462A patent/TWI429440B/zh active
- 2008-12-18 CN CN200880121970XA patent/CN101903385B/zh active Active
- 2008-12-18 BR BRPI0820779A patent/BRPI0820779B8/pt active IP Right Grant
- 2008-12-18 UA UAA201007805A patent/UA101963C2/ru unknown
- 2008-12-18 CA CA2709650A patent/CA2709650C/en active Active
- 2008-12-18 PL PL08865603T patent/PL2235012T3/pl unknown
- 2008-12-18 CL CL2008003811A patent/CL2008003811A1/es unknown
- 2008-12-18 KR KR1020107013477A patent/KR101639819B1/ko active IP Right Grant
- 2008-12-18 WO PCT/EP2008/067950 patent/WO2009080721A2/en active Application Filing
- 2008-12-18 AU AU2008341678A patent/AU2008341678B2/en active Active
- 2008-12-18 AR ARP080105539A patent/AR069814A1/es unknown
- 2008-12-18 US US12/809,371 patent/US8431580B2/en active Active
- 2008-12-18 PT PT88656038T patent/PT2235012E/pt unknown
- 2008-12-18 RU RU2010130418/04A patent/RU2489430C2/ru active
- 2008-12-18 SI SI200831056T patent/SI2235012T1/sl unknown
- 2008-12-18 ES ES08865603T patent/ES2430210T3/es active Active
- 2008-12-18 EP EP08865603.8A patent/EP2235012B1/en active Active
- 2008-12-18 DK DK08865603.8T patent/DK2235012T3/da active
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- 2010-06-16 IL IL206413A patent/IL206413A/en active IP Right Grant
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