HRP20170776T1 - Postupak za pripravu modulatora histaminskog h3 receptora - Google Patents
Postupak za pripravu modulatora histaminskog h3 receptora Download PDFInfo
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- HRP20170776T1 HRP20170776T1 HRP20170776TT HRP20170776T HRP20170776T1 HR P20170776 T1 HRP20170776 T1 HR P20170776T1 HR P20170776T T HRP20170776T T HR P20170776TT HR P20170776 T HRP20170776 T HR P20170776T HR P20170776 T1 HRP20170776 T1 HR P20170776T1
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- 238000000034 method Methods 0.000 title claims 38
- 238000002360 preparation method Methods 0.000 title claims 4
- 102000004384 Histamine H3 receptors Human genes 0.000 title 1
- 108090000981 Histamine H3 receptors Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 82
- 239000003960 organic solvent Substances 0.000 claims 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 10
- 239000003638 chemical reducing agent Substances 0.000 claims 9
- 239000002585 base Substances 0.000 claims 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical group [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 6
- 150000007529 inorganic bases Chemical class 0.000 claims 6
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 5
- -1 -CONRaRb Chemical group 0.000 claims 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims 3
- 239000002253 acid Substances 0.000 claims 3
- 150000003840 hydrochlorides Chemical class 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- 239000000203 mixture Substances 0.000 claims 3
- 229940002612 prodrug Drugs 0.000 claims 3
- 239000000651 prodrug Substances 0.000 claims 3
- 239000012279 sodium borohydride Substances 0.000 claims 3
- 229910000033 sodium borohydride Inorganic materials 0.000 claims 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 2
- 125000002252 acyl group Chemical group 0.000 claims 2
- 125000004423 acyloxy group Chemical group 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 150000001408 amides Chemical class 0.000 claims 2
- 150000001412 amines Chemical group 0.000 claims 2
- 125000000539 amino acid group Chemical group 0.000 claims 2
- 229910052799 carbon Inorganic materials 0.000 claims 2
- 239000000460 chlorine Substances 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 238000010992 reflux Methods 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical class CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 claims 1
- 125000005907 alkyl ester group Chemical group 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims 1
- 125000002843 carboxylic acid group Chemical group 0.000 claims 1
- 238000001212 derivatisation Methods 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 1
- 125000001033 ether group Chemical group 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 125000005541 phosphonamide group Chemical group 0.000 claims 1
- 150000003014 phosphoric acid esters Chemical class 0.000 claims 1
- 229920001184 polypeptide Chemical group 0.000 claims 1
- 108090000765 processed proteins & peptides Chemical group 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 claims 1
- 229940124530 sulfonamide Drugs 0.000 claims 1
- 150000003456 sulfonamides Chemical class 0.000 claims 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
Classifications
-
- 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Claims (36)
1. Postupak za pripravu spoja s formulom (I-E)
[image]
pri čemu
R1 je odabran iz skupine koju čine C1-4alkil i C3-10cikloalkil; m je 2
R2 je odabran iz skupine koju čine-OCHR3R4 i -Z-Ar;
R3 je vodik i R4 je a C3-10cikloalkil ili heterocikloalkil prsten; pri čemu C3-10cikloalkil ili heterocikloalkilni prsten je nesupstituiran ili supstituiran s -C1-4alkilom ili acetilom;
alternativno, R3 i R4 su uzeti zajedno s ugljikom na koji su spojeni da tvore a C3-10cikloalkil ili heterocikloalkil prsten; pri čemu C3-10cikloalkil ili heterocikloalkilni prsten je nesupstituiran ili supstituiran s -C1-4alkilom ili acetilom;
Z je odabran iz skupine koju čine S i O;
Ar je fenil ili heteroaril; pri čemu je fenil ili heteroaril nesupstituiran ili supstituiran s jednim, dva, ili tri R5 supstituenta; pri čemu je svaki R5 supstituent neovisno odabran iz skupine koja sadrži halogen, -C1-4alkil, -OH, -OC1-4alkil, -SC1-4alkil, -CN, -CONRaRb, i -NO2; i pri čemu Ra i Rb su svaki neovisno -H ili -C1-4alkil;
ili njegova farmaceutski prihvatljiva sol, ili farmaceutski prihvatljiv predlijek,
pri čemu se "predlijek " odnosi na spojeve koji imaju aminokiselinski ostatak, ili polipeptidni lanac od dva ili više aminokiselinskih ostataka, kovalentno povezan preko amidne ili esterske veze na slobodnu skupinu amino, hidroksi, ili skupinu karboksilne kiseline od spoja s formulom (I); spojeve pripravljene derivatiziranjem slobodnih hidroksi skupina upotrebom skupina koje uključuju hemisukcinate, fosfatne estere, dimetilaminoacetate, te fosforiloksimetiloksikarbonile; derivata karbamata hidroksi i amino skupina; karbonatne derivate, sulfonatne 89 estere, i sulfatne estere hidroksi skupina; spojeve pripravljene derivatiziranjem hidroksi skupina kao (aciloksi)metil i (aciloksi)etil eteri, pri čemu acil skupina može biti alkil ester, proizvoljno supstituirana s jednim ili više funkcionalnost etera, amina, ili karboksilne kiseline, ili gdje je acil skupina ester amino kiseline kako je gore opisano; i spojeve pripravljene derivatiziranjem slobodnih amina kao što su amidi, sulfonamidi ili fosfonamidi;
naznačen time da obuhvaća
[image]
reakciju spoja s formulom (V-S) s aldehidnim ili ketonskim derivatom željene R1 supstituirane skupine; čisto ili u organskom otapalu; da se dobije odgovarajući spoj s formulom (IX);
[image]
reakciju spoja s formulom (IX) sa sredstvom za redukciju; čisto, u vodi ili u vodenom organskom otapalu; da se dobije odgovarajući spoj s formulom (XI);
[image]
reakciju spoja s formulom (XI) sa spojem s formulom (VI), pri čemu LG1 je prva izlazna skupina i LG2 je druga izlazna skupina; u organskom otapalu;
alternativno reakciju spoja s formulom (XI) sa spojem s formulom (VI) pri čemu LG1 je prva izlazna skupina i LG2 je druga izlazna skupina; u prisutnosti baze; u smjesi vode i organskog otapala;
da se dobije odgovarajući spoj s formulom (X-E)
[image]
reakciju spoja s formulom (X-E) sa spojem s formulom (XII); u prisutnosti prve anorganske baze; u organskom otapalu; ili
reakciju spoja s formulom (X-E) sa spojem s formulom (XIII); u prisutnosti druge anorganske baze; u organskom otapalu; da se dobije odgovarajući spoj s formulom (I-E).
2. Postupak prema zahtjevu 1 za pripravu spoja (I-C)
[image]
ili njegove farmaceutski prihvatljive soli, ili farmaceutski prihvatljivog predlijeka; naznačen time da obuhvaća
[image]
reakciju spoja s formulom (V-S) sa spojem s formulom (VIII-S), čisto ili u organskom otapalu; da se dobije odgovarajući spoj s formulom (IX-S);
[image]
reakciju spoja s formulom (IX-S) sa sredstvom za redukciju; čisto, u vodi ili u organskom otapalu; da se dobije odgovarajući spoj s formulom (XI-S);
[image]
reakciju spoja s formulom (XI-S) sa spojem s formulom (VI-S), pri čemu LG1 je prva izlazna skupina i LG2 je druga izlazna skupina; u organskom otapalu;
alternativno, reakciju spoja s formulom (XI-S) sa spojem s formulom (VI-S), pri čemu LG1 je prva izlazna skupina i LG2 je druga izlazna skupina; u prisutnosti baze; u smjesi vode i organskog otapala;
da se dobije odgovarajući spoj s formulom (X-S);
[image]
reakciju spoja s formulom (X-S) sa spojem s formulom (XII-C); u prisutnosti druge anorganske baze; u organskom otapalu; da se dobije odgovarajući spoj (I-C).
3. Postupak prema zahtjevu 2, naznačen time da je spoj s formulom (VIII-S) prisutan u količini od 1.05 molarnih ekvivalenata.
4. Postupak prema zahtjevu 2, naznačen time da spoj s formulom (V-S) reagira sa spojem s formulom (VIII-S) u organskom otapalu i pri čemu organsko otapalo je toluen.
5. Postupak prema zahtjevu 2, naznačen time da spoj s formulom (V-S) reagira sa spojem s formulom (VIII-S) na temperaturi refluksa.
6. Postupak prema zahtjevu 2, naznačen time da spoj s formulom (IX-S) reagira sa sredstvom za redukciju u prisutnosti kiseline.
7. Postupak prema zahtjevu 2, naznačen time da se sredstvo za redukciju dodaje kao otopina u vodi, stabilizirana natrijevim hidroksidom u količini od 0.1 molarnih ekvivalenata.
8. Postupak prema zahtjevu 2, naznačen time da sredstvo za redukciju je natrijev borohidrid.
9. Postupak prema zahtjevu 8, naznačen time da je natrijev borohidrid prisutan u količini u rasponu od 0.5 do 1.5 molarnih ekvivalenata.
10. Postupak prema zahtjevu 2, naznačen time da u spoju s formulom (VI-S) LG1 i LG2 su svaki kloro.
11. Postupak prema zahtjevu 2, naznačen time da je spoj s formulom (VI-S) prisutan u količini u rasponu od 1.0 do 1.5 molarnih ekvivalenata.
12. Postupak prema zahtjevu 11, naznačen time da je spoj s formulom (VI-S) prisutan u količini od 1.05 molarnih ekvivalenata.
13. Postupak prema zahtjevu 2, naznačen time da spoj s formulom (XI-S) reagira sa spojem s formulom (VI-S) u organskom otapalu odabranom iz skupine koja sadrži metil t-butil eter, toluen i 2-metil-THF.
14. Postupak prema zahtjevu 2, naznačen time da spoj s formulom (XI-S) reagira sa spojem s formulom (VI-S) na temperaturi u rasponu od 0°C do 35°C.
15. Postupak prema zahtjevu 2, naznačen time da spoj s formulom (XI-S) reagira sa spojem s formulom (VI-S) u prisutnosti baze; pri čemu baza je natrijev hidroksid; i pri čemu je natrijev hidroksid prisutan u količini u rasponu od 1.05 do 1.2 molarnih ekvivalenata.
16. Postupak prema zahtjevu 2, naznačen time da spoj s formulom (VI-S) u MTBE reagira sa spojem s formulom (XI-S) u vodi, u prisutnosti 30% NaOH, na temperaturi u rasponu od 10°C do 15°C.
17. Postupak prema zahtjevu 2, naznačen time da je spoj s formulom (XII-C) prisutan u količini u rasponu od 1.1 do 1.5 molarnih ekvivalenata.
18. Postupak prema zahtjevu 2, naznačen time da druga anorganska baza je kalijev hidroksid.
19. Postupak prema zahtjevu 18, naznačen time da je kalijev hidroksid prisutan u količini u rasponu od 2.0 do 4.0 molarnih ekvivalenata.
20. Postupak prema zahtjevu 2, naznačen time da spoj s formulom (X-S) reagira sa spojem s formulom (XII-A) u organskom otapalu odabranom iz skupine koja sadrži toluen, acetonitril i smjesa toluena i vode.
21. Postupak prema zahtjevu 2, naznačen time da spoj s formulom (X-S) reagira sa spojem s formulom (XII-C) na temperaturi refluksa.
22. Postupak prema zahtjevu 2, naznačen time da LG2 je klor i pri čemu je spoj s formulom (X-S) pripremljen kao njegova odgovarajuća HCl sol.
23. Postupak prema zahtjevu 22, naznačen time da spoj s formulom (X-S) kao njegova odgovarajuća HCl sol reagira s prvom anorganskom bazom prije reakcije sa spojem formule (XII-C).
24. Postupak prema zahtjevu 23, naznačen time da prva anorganska baza je natrijev karbonat.
25. Postupak prema zahtjevu 24, naznačen time da je natrijev karbonat prisutan u količini dovoljnoj da oslobodi spoj s formulom (X-S) kao slobodnu bazu.
26. Postupak prema zahtjevu 24, naznačen time da je natrijev karbonat prisutan u količini od 1.5 molarnih ekvivalenata.
27. Postupak za pripravu spoja s formulom (X-S)
[image]
pri čemu LG1 je prva izlazna skupina; naznačen time da obuhvaća
[image]
reakciju spoja s formulom (V-S) sa spojem s formulom (VIII-S), čisto ili u organskom otapalu; da se dobije odgovarajući spoj s formulom (IX-S);
[image]
reakciju spoja s formulom (IX-S) sa sredstvom za redukciju; čisto, u vodi ili u organskom otapalu; da se dobije odgovarajući spoj s formulom (XI-S);
[image]
reakciju spoja s formulom (XI-S) sa spojem s formulom (VI-S), pri čemu LG2 je druga izlazna skupina; u organskom otapalu;
alternativno reakciju spoja s formulom (XI-S) sa spojem s formulom (VI-S), pri čemu LG2 je druga izlazna skupina; u prisutnosti baze; u smjesti i organskog otapala;
da se dobije odgovarajući spoj s formulom (X-S).
28. Postupak prema zahtjevu 27, naznačen time da LG1 je kloro.
29. Postupak prema zahtjevu 2 ili zahtjevu 27, naznačen time da je spoj s formulom (VIII-S) prisutan u količini u rasponu od 1.0 do 1.5 molarnih ekvivalenata.
30. Postupak prema zahtjevu 27, naznačen time da spoj s formulom (V-S) reagira sa spojem s formulom (VIII-S) u toluenu, na temperaturi većoj od 40°C.
31. Postupak prema zahtjevu 27, naznačen time da spoj s formulom (IX-S) reagira sa sredstvom za redukciju u prisutnosti kiseline ili postupak prema zahtjevu 6; pri čemu kiselina je klorovodična kiselina; i pri čemu je klorovodična kiselina prisutna u količini u rasponu od 3.0 do 5.0 molarnih ekvivalenata.
32. Postupak prema zahtjevu 27, naznačen time da sredstvo za redukciju je natrijev borohidrid i pri čemu se sredstvo za redukciju dodaje kao otopina u vodi, stabilizirana s 0.1 molarnih ekvivalenata natrijevog hidroksida.
33. Postupak prema zahtjevu 6 ili zahtjevu 27, naznačen time da spoj s formulom (IX-S) reagira na temperaturi u rasponu od -10°C do 0°C.
34. Postupak prema zahtjevu 27, pri čemu LG2 je klor; naznačen time da je spoj s formulom (VI-S) prisutan u količini u rasponu od 1.0 do 1.5 molarnih ekvivalenata; i pri čemu je spoj s formulom (X-S) pripremljen kao njegova odgovarajuća HCl sol.
35. Postupak prema zahtjevu 27, naznačen time da spoj s formulom (XI-S) reagira sa spojem s formulom (VI-S) u organskom otapalu odabranom iz skupine koja sadrži toluen i 2-metil-THF; i na temperaturi u rasponu od sobne temperature do 35°C.
36. Postupak prema zahtjevu 27, naznačen time da spoj s formulom (XI-S) u vodi reagira sa spojem s formulom (VI-S) u MTBE, u prisutnosti baze; pri čemu je baza 30% NaOH; na temperaturi u rasponu od 10°C do 15°C.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16117709P | 2009-03-18 | 2009-03-18 | |
| PCT/US2010/027638 WO2010107897A2 (en) | 2009-03-18 | 2010-03-17 | Process for the preparation of histamine h3 receptor modulators |
| EP10722449.5A EP2429996B1 (en) | 2009-03-18 | 2010-03-17 | Process for the preparation of histamine h3 receptor modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20170776T1 true HRP20170776T1 (hr) | 2017-08-11 |
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20170776TT HRP20170776T1 (hr) | 2009-03-18 | 2017-05-24 | Postupak za pripravu modulatora histaminskog h3 receptora |
| HRP20190476TT HRP20190476T1 (hr) | 2009-03-18 | 2019-03-11 | Postupak za pripravu modulatora histaminskog h3 receptora |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
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| HRP20190476TT HRP20190476T1 (hr) | 2009-03-18 | 2019-03-11 | Postupak za pripravu modulatora histaminskog h3 receptora |
Country Status (18)
| Country | Link |
|---|---|
| US (4) | US8748596B2 (hr) |
| EP (3) | EP3492451B1 (hr) |
| JP (1) | JP5642149B2 (hr) |
| CN (1) | CN102428070B (hr) |
| AU (1) | AU2010226711B2 (hr) |
| CA (2) | CA2965059C (hr) |
| CY (2) | CY1119437T1 (hr) |
| DK (2) | DK2429996T3 (hr) |
| ES (2) | ES2714852T3 (hr) |
| HR (2) | HRP20170776T1 (hr) |
| HU (2) | HUE044837T2 (hr) |
| LT (2) | LT3216784T (hr) |
| MX (3) | MX347775B (hr) |
| PL (2) | PL2429996T3 (hr) |
| PT (2) | PT2429996T (hr) |
| SI (2) | SI3216784T1 (hr) |
| TR (1) | TR201902858T4 (hr) |
| WO (1) | WO2010107897A2 (hr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL2429996T3 (pl) | 2009-03-18 | 2017-08-31 | Janssen Pharmaceutica Nv | Sposób wytwarzania modulatorów receptorów histaminowych H3 |
| KR101427221B1 (ko) * | 2012-08-29 | 2014-08-13 | 주식회사 에스텍파마 | 플루복사민 자유 염기의 정제방법 및 이를 이용한 고순도 플루복사민 말레이트의 제조방법 |
| CN104447867B (zh) * | 2013-09-17 | 2017-12-26 | 江苏天士力帝益药业有限公司 | 一种噻吩并哌啶衍生物、制备方法及其应用 |
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| JPS5724346B2 (hr) * | 1973-06-22 | 1982-05-24 | ||
| BRPI0315644B8 (pt) * | 2002-10-23 | 2021-05-25 | Janssen Pharmaceutica Nv | compostos de piperazinil e diazapanil benzamidas e benzotioamidas, suas composições e respectivos usos |
| WO2007143422A2 (en) * | 2006-05-30 | 2007-12-13 | Janssen Pharmaceutica N.V. | Substituted pyridyl amide compounds as modulators of the histamine h3 receptor |
| NZ584998A (en) * | 2007-11-20 | 2012-08-31 | Janssen Pharmaceutica Nv | Cycloalkyloxy-and heterocycloalkyloxypyridine compounds as modulators of the histamine h3 receptor |
| PL2429996T3 (pl) | 2009-03-18 | 2017-08-31 | Janssen Pharmaceutica Nv | Sposób wytwarzania modulatorów receptorów histaminowych H3 |
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