HRP20130154T1 - Postupak pripreme sinakalceta - Google Patents
Postupak pripreme sinakalceta Download PDFInfo
- Publication number
- HRP20130154T1 HRP20130154T1 HRP20130154AT HRP20130154T HRP20130154T1 HR P20130154 T1 HRP20130154 T1 HR P20130154T1 HR P20130154A T HRP20130154A T HR P20130154AT HR P20130154 T HRP20130154 T HR P20130154T HR P20130154 T1 HRP20130154 T1 HR P20130154T1
- Authority
- HR
- Croatia
- Prior art keywords
- formula
- compound
- image
- cinacalcet
- preparation
- Prior art date
Links
- VDHAWDNDOKGFTD-MRXNPFEDSA-N cinacalcet Chemical compound N([C@H](C)C=1C2=CC=CC=C2C=CC=1)CCCC1=CC=CC(C(F)(F)F)=C1 VDHAWDNDOKGFTD-MRXNPFEDSA-N 0.000 title claims 36
- 229960003315 cinacalcet Drugs 0.000 title claims 36
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 52
- 238000000034 method Methods 0.000 claims 17
- 238000006243 chemical reaction Methods 0.000 claims 13
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims 9
- 229910052739 hydrogen Inorganic materials 0.000 claims 9
- 239000001257 hydrogen Substances 0.000 claims 9
- ABXGMGUHGLQMAW-UHFFFAOYSA-N 1-[3-(trifluoromethyl)phenyl]ethanone Chemical compound CC(=O)C1=CC=CC(C(F)(F)F)=C1 ABXGMGUHGLQMAW-UHFFFAOYSA-N 0.000 claims 4
- 239000000203 mixture Substances 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- -1 N-methyl-N-methylenemethanaminium halide Chemical class 0.000 claims 3
- 239000002253 acid Substances 0.000 claims 3
- 239000002168 alkylating agent Substances 0.000 claims 3
- 229940100198 alkylating agent Drugs 0.000 claims 3
- 230000029936 alkylation Effects 0.000 claims 3
- 238000005804 alkylation reaction Methods 0.000 claims 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims 3
- 239000003638 chemical reducing agent Substances 0.000 claims 3
- 239000012024 dehydrating agents Substances 0.000 claims 3
- 230000018044 dehydration Effects 0.000 claims 3
- 238000006297 dehydration reaction Methods 0.000 claims 3
- 125000005843 halogen group Chemical group 0.000 claims 3
- 125000000623 heterocyclic group Chemical group 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- 238000003780 insertion Methods 0.000 claims 3
- 230000037431 insertion Effects 0.000 claims 3
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims 3
- 229910052757 nitrogen Inorganic materials 0.000 claims 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 3
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 claims 3
- 230000008878 coupling Effects 0.000 claims 2
- 238000010168 coupling process Methods 0.000 claims 2
- 238000005859 coupling reaction Methods 0.000 claims 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
- C07C225/02—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton
- C07C225/14—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated
- C07C225/16—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/30—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by two rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C215/22—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated
- C07C215/28—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
- C07C215/30—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton
-
- 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
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Claims (17)
1. Intermedijer sinakalceta sa sljedećom formulom (V)
[image]
2. Intermedijer sinakalceta sa sljedećom formulom (Va)
[image]
što je diastereomerna smjesa (R)- i (S)-3-((R)-1-(naftalen-1-il)etilamino-1-(3-(trifluorometil)fenil)propan-1-ol.
3. Intermedijer sinakalceta sa sljedećom formulom (Vb)
[image]
gdje je Bn benzil.
4. Postupak pripreme intermedijera sinakalceta formule (V) kako je definirano u zahtjevu 1, koji obuhvaća korak:
a) reakcija 3-(trifluorometil)acetofenona formule (II)
[image]
s (R)-(1-naftil)etilaminom formule (III)
[image]
u prisutnosti formaldehida, da se dobije spoj formule (V).
5. Postupak pripreme intermedijera sinakalceta formule (V) kako je definirano u zahtjevu 1, koji obuhvaća korake:
b) reakcija 3-(trifluorometil)acetofenona formule (II)
[image]
(i) sa spojem formule
HNR1R2
gdje R1 i R2 predstavljaju, nezavisno, vodik ili C1-C5 alkil, uz uvjet da kada je jedan od R1 i R2 vodik, drugi nije vodik; ili
gdje R1 i R2 zajedno formiraju C4-C7-alkilenski most, tako da s umetanjem atoma dušika s kojim su spojeni formiraju heterocikl, gdje jedna -CH2- skupina u C4-C7-alkilenskom mostu, može biti zamijenjena s - O-, u prisutnosti formaldehida; ili
(ii) s N-metil-N-metilenmetanaminijevim halidom formule
[image]
gdje Hal je atom halogena,
da se dobije spoj formule (IV)
[image]
gdje su R1 i R2 kako je gore definirano;
c) alkiliranje spoja formule (IV) sa sredstvom za alikiliranje izabranim iz grupe spojeva formule:
R3-X, (X)(OR3)2, SO2(OR3)2, PO(OR3)3, CH3PO(OR3)2 i (4-NO2C6H4O)PO(OR3)2, gdje R3 je C1-C4alkil i X je I, Br, OSO2CF3 ili OSO2F, da se dobije spoj formule (IVa)
[image]
gdje Y=X kako je gore definirano ili R3OCO2, R3OSO3, (R3O)2PO2. CH3PO2OR3, (4-NO2-C6H4O)PO2OR3; i
d) spajanje spoja formule (IVa) s (R)-(1-naftil)etilaminom formule (III)
[image]
da se dobije spoj formule (V).
6. Postupak pripreme sinakalceta formule (I)
[image]
koji obuhvaća pripremu intermedijera sinakalceta formule (V) prema zahtjevu 4 ili 5, i njegovu pretvorbu u sinakalcet formule (I).
7. Postupak pripreme intermedijera sinakalceta formule (Va) kako je definirano u zahtjevu 2, koji obuhvaća korak:
e) redukcija spoja formule (V) kako je definirano u zahtjevu 1, u prisutnosti reducensa ili pomoću procesa katalitičke hidrogenacije, da se dobije spoj formule (Va).
8. Postupak pripreme intermedijera sinakalceta formule (Va) prema zahtjevu 7, koji obuhvaća pripremu spoja formule (V) prema zahtjevu 4 ili 5.
9. Postupak pripreme sinakalceta formule (I)
[image]
koji obuhvaća pripremu intermedijera sinakalceta formule (Va) prema zahtjevu 7 ili 8, i njegovu pretvorbu u sinakalcet formule (I).
10. Postupak pripreme intermedijera sinakalceta formule (VI)
[image]
koji obuhvaća korak:
f) dehidracija spoja formule (Va) kako je definirano u zahtjevu 2, sa sredstvom za dehidraciju da se dobije spoj formule (VI); ili, alternativno,
g) redukcija spoja formule (V) kako je definirano u zahtjevu 1, sa Zn, u prisutnosti kiseline, da se tako dobije spoj formule (VI), u smjesi sa sinakalcetom formule (I).
11. Postupak pripreme intermedijera sinakalceta formule (VI) prema zahtjevu 10, koji obuhvaća pripremu spoja formule (Va) prema zahtjevu 7 ili 8.
12. Postupak pripreme intermedijera sinakalceta formule (VI) prema zahtjevu 10, koji obuhvaća pripremu spoja formule (V) prema zahtjevu 4 ili 5.
13. Postupak pripreme sinakalceta formule (I)
[image]
koji obuhvaća pripremu intermedijera sinakalceta formule (VI) prema zahtjevu 10, 11 ili 12, i njegovu pretvorbu u sinakalcet formule (I), preko redukcije dvostruke veze spoja formule (VI)
[image]
da se dobije sinakalcet formule (I).
14. Postupak pripreme sinakalceta formule (I)
[image]
koji obuhvaća korake:
a) reakcija 3-(trifluorometil)acetofenona formule (II)
[image]
s (R)-(1-naftil)etilaminom formule (III)
[image]
u prisutnosti formaldehida, da se dobije spoj formule (V)
[image]
e) redukcija spoja formule (V) u prisutnosti reducensa ili pomoću procesa katalitičke hidrogenacije da se dobije spoj formule (Va)
[image]
f) dehidracija spoja formule (Va) sa sredstvom za dehidraciju da se dobije spoj formule (VI)
[image]
h) redukcija spoja formule (VI), da se dobije sinakalcet formule (I) i, po želji, pretvorba sinakalceta u farmaceutski prihvatljivu sol.
15. Postupak pripreme sinakalceta formule (I)
[image]
koji obuhvaća korake:
a) reakcija 3-(trifluorometil)acetofenona formule (II)
[image]
s (R)-(1-naftil)etilaminom formule (III)
[image]
u prisutnosti formaldehida, da se dobije spoj formule (V)
[image]
g) redukcija spoja formule (V) kako je gore definirano sa Zn, u prisutnosti kiseline, da se tako dobije spoj formule (VI)
[image]
u zajedničkoj smjesi sa sinakalcetom formule (I);
h) redukcija spoja formule (VI), da se dobije sinakalcet formule (I) i, po želji, pretvorba sinakalceta u farmaceutski prihvatljivu sol.
16. Postupak pripreme sinakalceta formule (I)
[image]
koji obuhvaća korake:
b) reakcija spoja formule (II)
[image]
(i) sa spojem formule
HNR1R2
gdje R1 i R2 predstavljaju, nezavisno, vodik ili C1-C5 alkil, uz uvjet da kada je jedan od R1 i R2 vodik, drugi nije vodik; ili
gdje R1 i R2 zajedno formiraju C4-C7-alkilenski most, tako da s umetanjem atoma dušika s kojim su spojeni nastane heterocikl, gdje jedna -CH2- skupina u C4-C7-alkilenskom mostu, može biti zamijenjena s -O-, u prisutnosti formaldehida; ili
(ii) s N-metil-N-metilenmetanaminijevim halidom formule
[image]
gdje Hal je atom halogena,
da se dobije spoj formule (IV)
[image]
gdje su R1 i R2 kako je gore definirano;
c) alkiliranje spoja formule (IV) sa sredstvom za alikiliranje izabranim iz grupe spojeva formule:
R3-X, CO(OR3)2, SO2(OR3)2, PO(OR3)3, CH3PO(OR3)2 i (4-NO2C6H4O)PO(OR3)2, gdje R3 je C1-C4alkil i X je I, Br, OSO2CF3 ili OSO2F, da se dobije spoj formule (IVa)
[image]
gdje Y=X kako je gore definirano, R3OCO2, R3OSO3, (R3O)2PO2, CH3PO2OR3, ili (4-NO2-C6H4O)PO2OR3;
d) spajanje spoja formule (IVa) s (R)-(1-naftil)etilaminom formule (III) da se dobije spoj formule (V)
[image]
e) redukcija spoja formule (V) u prisutnosti reducensa ili pomoću procesa katalitičke hidrogenacije da se dobije spoj formule (Va)
[image]
f) dehidracija spoja formule (Va) sa sredstvom za dehidraciju da se dobije spoj formule (VI)
[image]
h) redukcija spoja formule (VI), da se dobije sinakalcet formule (I) i, po želji, pretvorba sinakalceta u farmaceutski prihvatljivu sol.
17. Postupak pripreme sinakalceta formule (I)
[image]
koji obuhvaća korake:
b) reakcija spoja formule (II) kako je gore definirano
(i) sa spojem formule
HNR1R2,
gdje R1 i R2 predstavljaju, nezavisno, vodik ili C1-C5 alkil, uz uvjet da kada je jedan od R1 i R2 vodik, drugi nije vodik; ili
gdje R1 i R2 zajedno formiraju C4-C7-alkilenski most, tako da s umetanjem atoma dušika s kojim su spojeni nastane heterocikl, gdje jedna -CH2- skupina u C4-C7-alkilenskom mostu, može biti zamijenjena s -O-, u prisutnosti formaldehida; ili
(ii) s N-metil-N-metilenmetanaminijevim halidom formule
[image]
gdje Hal je atom halogena,
da se dobije spoj formule (IV)
[image]
gdje su R1 i R2 kako je gore definirano;
c) alkiliranje spoja formule (IV) sa sredstvom za alikiliranje izabranim iz grupe spojeva formule:
R3-X, CO(OR3)2, SO2(OR3)2, PO(OR3)3, CH3PO(OR3)2 i (4-NO2C6H4O)PO(OR3)2, gdje R3 je C1-C4alkil i X je I, Br, OSO2CF3 ili OSO2F, da se dobije spoj formule (IVa)
[image]
gdje Y=X kako je gore definirano, R3OCO2, R3OSO3, (R3O)2PO2, CH3PO2OR3 ili (4-NO2-C6H4O)PO2OR3;
d) spajanje spoja formule (IVa) s (R)-(1-naftil)etilaminom formule (III) da se dobije spoj formule (V)
[image]
g) redukcija spoja formule (V) kako je gore definirano sa Zn, u prisutnosti kiseline, da se tako dobije spoj formule (VI)
[image]
u zajedničkoj smjesi sa sinakalcetom formule (I);
h) redukcija dvostruke veze u spoju formule (VI), da se dobije sinakalcet formule (I) i, po želji, pretvorba sinakalceta u farmaceutski prihvatljivu sol.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08167762 | 2008-10-28 | ||
| PCT/EP2009/063603 WO2010049293A2 (en) | 2008-10-28 | 2009-10-16 | Process for preparing cinacalcet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20130154T1 true HRP20130154T1 (hr) | 2013-03-31 |
Family
ID=42041800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20130154AT HRP20130154T1 (hr) | 2008-10-28 | 2013-02-25 | Postupak pripreme sinakalceta |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US8614353B2 (hr) |
| EP (1) | EP2358659B1 (hr) |
| JP (1) | JP5514218B2 (hr) |
| CN (1) | CN102159533B (hr) |
| AU (1) | AU2009309860B2 (hr) |
| BR (1) | BRPI0919635B8 (hr) |
| CA (1) | CA2734971C (hr) |
| CY (1) | CY1113722T1 (hr) |
| ES (1) | ES2401851T3 (hr) |
| HR (1) | HRP20130154T1 (hr) |
| IL (1) | IL211307A0 (hr) |
| PL (1) | PL2358659T3 (hr) |
| PT (1) | PT2358659E (hr) |
| SI (1) | SI2358659T1 (hr) |
| WO (1) | WO2010049293A2 (hr) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2010215520B2 (en) * | 2009-02-19 | 2016-07-21 | F.I.S. - Fabbrica Italiana Sintetici S.P.A. | Process for preparing Cinacalcet hydrochloride |
| WO2011029833A1 (en) | 2009-09-10 | 2011-03-17 | Zach System S.P.A. | Process for preparing cinacalcet |
| CZ303627B6 (cs) * | 2011-11-25 | 2013-01-16 | Zentiva, K.S. | Zpusob výroby Cinacalcetu |
| CN103664577B (zh) * | 2012-09-06 | 2015-04-08 | 北京万生药业有限责任公司 | 一种西那卡塞中间体的制备方法 |
| FR2995307A1 (fr) | 2012-09-07 | 2014-03-14 | Prod Chim Auxiliaires Et De Synthese | Procede de preparation du cinacalcet et de ses sels pharmaceutiquement acceptables |
| CN106810452B (zh) * | 2017-01-13 | 2018-12-28 | 华北水利水电大学 | 一种盐酸西那卡塞的制备方法 |
| CN106831441B (zh) * | 2017-01-23 | 2019-04-02 | 江苏康思尔医药科技有限公司 | 一种盐酸西那卡塞的制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7449603B2 (en) | 2006-04-27 | 2008-11-11 | Teva Pharmaceutical Industries Ltd. | Process for the preparation of cinacalcet base |
| US7393967B2 (en) * | 2006-04-27 | 2008-07-01 | Teva Pharmaceutical Industries Ltd. | Process for the preparation of cinacalcet base |
| WO2008035381A2 (en) * | 2006-09-22 | 2008-03-27 | Ind-Swift Laboratories Limited | Process for the preparation of amine derivatives as calcimimetics |
| WO2008117299A1 (en) * | 2007-03-26 | 2008-10-02 | Macleods Pharmaceuticals Limited | Process for preparing cinacalcet hydrochloride |
-
2009
- 2009-10-16 BR BRPI0919635A patent/BRPI0919635B8/pt active IP Right Grant
- 2009-10-16 PL PL09753056T patent/PL2358659T3/pl unknown
- 2009-10-16 CN CN200980136709.1A patent/CN102159533B/zh active Active
- 2009-10-16 EP EP09753056A patent/EP2358659B1/en active Active
- 2009-10-16 JP JP2011532599A patent/JP5514218B2/ja active Active
- 2009-10-16 SI SI200930541T patent/SI2358659T1/sl unknown
- 2009-10-16 CA CA2734971A patent/CA2734971C/en active Active
- 2009-10-16 ES ES09753056T patent/ES2401851T3/es active Active
- 2009-10-16 US US13/126,609 patent/US8614353B2/en active Active
- 2009-10-16 PT PT97530562T patent/PT2358659E/pt unknown
- 2009-10-16 AU AU2009309860A patent/AU2009309860B2/en active Active
- 2009-10-16 WO PCT/EP2009/063603 patent/WO2010049293A2/en active Application Filing
-
2011
- 2011-02-20 IL IL211307A patent/IL211307A0/en active IP Right Grant
-
2013
- 2013-02-25 HR HRP20130154AT patent/HRP20130154T1/hr unknown
- 2013-02-26 CY CY20131100175T patent/CY1113722T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PT2358659E (pt) | 2013-03-28 |
| CN102159533B (zh) | 2014-08-27 |
| CN102159533A (zh) | 2011-08-17 |
| IL211307A0 (en) | 2011-04-28 |
| SI2358659T1 (sl) | 2013-04-30 |
| BRPI0919635B1 (pt) | 2021-03-09 |
| BRPI0919635A8 (pt) | 2017-07-11 |
| WO2010049293A3 (en) | 2010-10-21 |
| BRPI0919635A2 (pt) | 2015-12-01 |
| PL2358659T3 (pl) | 2013-06-28 |
| JP5514218B2 (ja) | 2014-06-04 |
| AU2009309860B2 (en) | 2015-07-23 |
| BRPI0919635B8 (pt) | 2021-05-25 |
| CA2734971A1 (en) | 2010-05-06 |
| JP2012506847A (ja) | 2012-03-22 |
| US20110207965A1 (en) | 2011-08-25 |
| WO2010049293A2 (en) | 2010-05-06 |
| ES2401851T3 (es) | 2013-04-25 |
| EP2358659A2 (en) | 2011-08-24 |
| US8614353B2 (en) | 2013-12-24 |
| CY1113722T1 (el) | 2016-06-22 |
| CA2734971C (en) | 2017-01-31 |
| AU2009309860A1 (en) | 2010-05-06 |
| EP2358659B1 (en) | 2012-12-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP20130154T1 (hr) | Postupak pripreme sinakalceta | |
| RU2488582C2 (ru) | Бициклозамещенные азопроизводные пиразолона, способ их получения и фармацевтическое применение | |
| HRP20120129T1 (hr) | Hidroksimetil pirolidini kao agonisti beta 3 adrenergičkog receptora | |
| EA200900817A1 (ru) | Способ получения фторметилзамещённых гетероциклических соединений | |
| DE502006002659D1 (de) | Verfahren zur herstellung von 5-(4-ä4-(5-cyano-3-indolyl)-butylü-1-piperazinyl)-benzofuran-2-carboxamid | |
| DE602006008962D1 (de) | Verfahren zur herstellung von valsartan | |
| RS52872B (en) | PIRAL UNITS | |
| RS52542B (en) | NEW PROCEDURE FOR THE SYNTHESIS OF IVABRADINE AND ITS ADDITIONAL SALTS WITH PHARMACEUTICALLY ACCEPTABLE ACID | |
| WO2007107828A3 (en) | Amine derivatives | |
| HRP20150305T1 (hr) | Postupak za pripravu intermedijera spojeva korisnih kao modulatori opioid receptora | |
| MX2009003698A (es) | Preparacion de azoxistrobina. | |
| EA201100759A1 (ru) | Арилоазол-2-илцианоэтиламиносоединения противопаразитарного действия, обогащенные одним из энантиомеров | |
| RU2012105122A (ru) | Способ получения хиральных производных 3-триазолилсульфоксида | |
| HRP20130102T1 (hr) | Postupak dobivanja spojeva 4-amino-2-(2,6-dioksopiperidin-3-il)izoindolin-1,3-diona | |
| DE602006011482D1 (de) | Regioselektives verfahren zur zubereitung von benzimidazol-thiophenen | |
| WO2008107502A8 (es) | Composicion para el tratamiento de enfermedades infecciosas | |
| WO2009023844A3 (en) | 3' substituted compounds having 5-ht6 receptor affinity | |
| WO2009134995A3 (en) | Tetrazole compounds for reducing uric acid | |
| CN102869644B (zh) | 用于制备他喷他多及其中间体的方法 | |
| WO2009145590A3 (en) | Phenyl piperazine compounds, pharmaceutical composition comprising the same, and use thereof | |
| HRP20131133T1 (hr) | Postupak za dobivanje 4-[(1,6-dihidro-6-okso-2-pirimidinil)amino benzonitrila | |
| WO2011016052A3 (en) | Process for preparing pregabalin | |
| HRP20150554T1 (hr) | Postupak za pripravu nebivolola | |
| ATE528295T1 (de) | Trisubstituierte 3,4-dihydro-1h-isochinolin- verbindung, verfahren zu ihrer herstellung und ihre anwendung | |
| ATE517086T1 (de) | Verfahren zur synthese von 3-amino-1- arylpropylindolen |