HRP20100259T1 - Derivati 1,2,4,5-tetrahidro-3h-benzazepina, postupak za njihovu pripravu i farmaceutske smjese koje ih sadrže - Google Patents
Derivati 1,2,4,5-tetrahidro-3h-benzazepina, postupak za njihovu pripravu i farmaceutske smjese koje ih sadrže Download PDFInfo
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- HRP20100259T1 HRP20100259T1 HR20100259T HRP20100259T HRP20100259T1 HR P20100259 T1 HRP20100259 T1 HR P20100259T1 HR 20100259 T HR20100259 T HR 20100259T HR P20100259 T HRP20100259 T HR P20100259T HR P20100259 T1 HRP20100259 T1 HR P20100259T1
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- 238000000034 method Methods 0.000 title claims 2
- MZBVNYACSSGXID-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-1-benzazepine Chemical class N1CCCCC2=CC=CC=C21 MZBVNYACSSGXID-UHFFFAOYSA-N 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 33
- 239000002253 acid Substances 0.000 claims abstract 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 16
- 230000003287 optical effect Effects 0.000 claims abstract 16
- 150000003839 salts Chemical class 0.000 claims abstract 16
- 229920006395 saturated elastomer Polymers 0.000 claims abstract 10
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 8
- 229910052760 oxygen Inorganic materials 0.000 claims abstract 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract 7
- 125000005843 halogen group Chemical group 0.000 claims abstract 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract 5
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 4
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract 4
- 125000000217 alkyl group Chemical group 0.000 claims abstract 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract 2
- 125000002619 bicyclic group Chemical group 0.000 claims abstract 2
- 125000005842 heteroatom Chemical group 0.000 claims abstract 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract 2
- 125000002950 monocyclic group Chemical group 0.000 claims abstract 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 6
- 230000002265 prevention Effects 0.000 claims 4
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 230000001575 pathological effect Effects 0.000 claims 2
- 206010002388 Angina unstable Diseases 0.000 claims 1
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims 1
- 206010013774 Dry eye Diseases 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 claims 1
- 208000035150 Hypercholesterolemia Diseases 0.000 claims 1
- 206010061216 Infarction Diseases 0.000 claims 1
- 208000002193 Pain Diseases 0.000 claims 1
- 208000007718 Stable Angina Diseases 0.000 claims 1
- 208000007814 Unstable Angina Diseases 0.000 claims 1
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 208000037849 arterial hypertension Diseases 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 238000005859 coupling reaction Methods 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- 230000003205 diastolic effect Effects 0.000 claims 1
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 238000005984 hydrogenation reaction Methods 0.000 claims 1
- 208000013403 hyperactivity Diseases 0.000 claims 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 208000031225 myocardial ischemia Diseases 0.000 claims 1
- DWLVWMUCHSLGSU-UHFFFAOYSA-M n,n-dimethylcarbamate Chemical compound CN(C)C([O-])=O DWLVWMUCHSLGSU-UHFFFAOYSA-M 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000003449 preventive effect Effects 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 230000033764 rhythmic process Effects 0.000 claims 1
- 230000037390 scarring Effects 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 claims 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 claims 1
- 230000002861 ventricular Effects 0.000 claims 1
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- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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Abstract
Spoj formule (I): naznačen time da: - R1 predstavlja atom vodika ili skupinu odabranu od C3-C7cikloalkila, benzila i ravnog ili razgrananog C1-C6alkila, alkilne skupine zasićene ili nezasićene te po izboru supstituirane s hidroksi ili C3-C7cikloalkilnom skupinom ili s jednim ili više atoma halogena, - R2, R3, R4 i R5 koji mogu biti isti ili različiti, svaki predstavlja atom vodika ili hidroksi skupinu; metilnu skupinu; -OSO2R10 skupinu; -OCOR10 skupinu; ili ravnu ili razgrananu, zasićenu ili nezasićenu C1-C6alkoksi skupinu, po izboru supstituiranu s metoksi ili -(CO)-NR12R'12 skupinom, ili R2 i R3, ili R3 i R4, ili R4 i R5 zajedno tvore skupinu -O-(CH2)q-O-, -O-CH=CH-O ili -O-CH=CH-,- R6, R7, R8 i R9, koji mogu biti isti ili različiti, svaki predstavlja atom vodika ili ravnu ili razgrananu zasićenu ili nezasićenu C1-C6alkoksi skupinu, ili R6 i R7 ili R7 i R8, ili R8 i R9 zajedno tvore skupinu -O-(CH2)q-O-,- R10 predstavlja skupinu odabranu od ravnog ili razgrananog C1-C6alkoksi, NR11R'11 i ravnog ili razgrananog C1-C6alkila koji po izboru može biti supstituiran s jednim ili više atoma halogena, - R11 i R'11, koji mogu biti isti ili različiti, svaki predstavlja atom vodika ili ravnu ili razgrananu C1-C6alkilnu skupinu, ili R11 i R'11 zajedno s dušikovim atomom koji ih nosi tvore monociklički ili biciklički, 5-ero do 8-eročlani dušik koji sadrži heterocikl koji po izboru može imati drugi heteroatom odabran od O i N, rečeni heterocikl se može po izboru supstituirati s jednim ili više atoma halogena, - R12 i R'12, koji mogu biti isti ili različiti, svaki predstavljaju atom vodika ili ravnu ili razgrananu C1-C6alkilnu skupinu, - X predstavlja O, NH ili CH2,- m i p, koji mogu biti isti ili različiti, svaki predstavlja 0 ili 1, - n i q, koji mogu biti isti ili različiti, svaki predstavlja 1 ili 2, njihove optičke izomere kada isti postoje, i također njihove adicijske soli s farmaceutski prihvatljivom kiselinom. Patent sadrži još 17 patentnih zahtjeva.
Claims (18)
1. Spoj formule (I):
[image]
naznačen time da:
- R1 predstavlja atom vodika ili skupinu odabranu od C3-C7cikloalkila, benzila i ravnog ili razgrananog C1-C6alkila, alkilne skupine zasićene ili nezasićene te po izboru supstituirane s hidroksi ili C3-C7cikloalkilnom skupinom ili s jednim ili više atoma halogena,
- R2, R3, R4 i R5 koji mogu biti isti ili različiti, svaki predstavlja atom vodika ili hidroksi skupinu; metilnu skupinu; -OSO2R10 skupinu; -OCOR10 skupinu; ili ravnu ili razgrananu, zasićenu ili nezasićenu C1-C6alkoksi skupinu, po izboru supstituiranu s metoksi ili -(CO)-NR12R'12 skupinom, ili R2 i R3, ili R3 i R4, ili R4 i R5 zajedno tvore skupinu -O-(CH2)q-O-, -O-CH=CH-O ili -O-CH=CH-,
- R6, R7, R8 i R9, koji mogu biti isti ili različiti, svaki predstavlja atom vodika ili ravnu ili razgrananu zasićenu ili nezasićenu C1-C6alkoksi skupinu, ili R6 i R7 ili R7 i R8, ili R8 i R9 zajedno tvore skupinu -O-(CH2)q-O-,
- R10 predstavlja skupinu odabranu od ravnog ili razgrananog C1-C6alkoksi, NR11R'11 i ravnog ili razgrananog C1-C6alkila koji po izboru može biti supstituiran s jednim ili više atoma halogena,
- R11 i R'11, koji mogu biti isti ili različiti, svaki predstavlja atom vodika ili ravnu ili razgrananu C1-C6alkilnu skupinu, ili R11 i R'11 zajedno s dušikovim atomom koji ih nosi tvore monociklički ili biciklički, 5-ero do 8-eročlani dušik koji sadrži heterocikl koji po izboru može imati drugi heteroatom odabran od O i N, rečeni heterocikl se može po izboru supstituirati s jednim ili više atoma halogena,
- R12 i R'12, koji mogu biti isti ili različiti, svaki predstavljaju atom vodika ili ravnu ili razgrananu C1-C6alkilnu skupinu,
- X predstavlja O, NH ili CH2,
- m i p, koji mogu biti isti ili različiti, svaki predstavlja 0 ili 1,
- n i q, koji mogu biti isti ili različiti, svaki predstavlja 1 ili 2,
njihove optičke izomere kada isti postoje, i također njihove adicijske soli s farmaceutski prihvatljivom kiselinom.
2. Spoj formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da R1 predstavlja atom vodika ili ravnu ili razgrananu C1-C6alkilnu skupinu, njihove optičke izomere ako isti postoje, te njihove adicijske soli s farmaceutski prihvatljivom kiselinom.
3. Spoj formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da R1 predstavlja C3-C7cikloalkilnu skupinu ili cikloalkilnu skupinu pri čemu polovica cikloalkila sadrži od 3 do 7 atoma ugljika a polovica alkila sadrži od 1 do 6 atoma ugljika i jeste ravna ili razgranana, njihove optičke izomere kada isti postoje, te također njihove adicijske soli s farmaceutski prihvatljivom kiselinom.
4. Spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačen time, da R2, R3, R4 i R5, koji mogu biti isti ili različiti, svaki predstavlja atom vodika ili ravnu ili razgrananu, zasićenu ili nezasićenu C1-C6alkoksi skupinu ili -OCOR10 gdje R10 predstavlja skupinu NR11R'11 kako je definirano u patentnom zahtjevu 1, njihove optičke izomere ako isti postoje, te također njihove adicijske soli s farmaceutski prihvatljivom kiselinom.
5. Spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačen time, da su R6, R7, R8 i R9, koji mogu biti isti ili različiti, svaki predstavlja atom vodika ili ravnu ili razgrananu, zasićenu ili nezasićenu C1-C6alkoksi skupinu, njihove optičke izomere ako isti postoje, te također njihove adicijske soli s farmaceutski prihvatljivom kiselinom.
6. Spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačen time, da m predstavlja 0, njihove optičke izomere kada isti postoje, te također njihove adicijske soli s farmaceutski prihvatljivom kiselinom.
7. Spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačen time, da m predstavlja 1, a X predstavlja CH2, njihove optičke izomere kada isti postoje, te također njihove adicijske soli s farmaceutski prihvatljivom kiselinom.
8. Spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 7, naznačen time, da p predstavlja 1, njihove optičke izomere, te također njihove adicijske soli s farmaceutski prihvatljivom kiselinom.
9. Spoj formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 7, naznačen time, da p predstavlja 1, njihove optičke izomere kada oni postoje, te također njihove adicijske soli s farmaceutski prihvatljivom kiselinom.
10. Spoj formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da R1 predstavlja atom vodika ili ravnu ili razgrananu C1-C6alkilnu skupinu, R2, R3, R4 i R5, koji mogu biti isti ili različiti, svaki predstavlja atom vodika ili ravnu ili razgrananu, zasićenu ili nezasićenu C1-C6alkoksi skupinu, R6, R7, R8 i R9, koji mogu biti isti ili različiti, svaki predstavlja atom vodika ili ravnu ili razgrananu, zasićenu ili nezasićenu C1-C6alkoksi skupinu, m predstavlja 0, n predstavlja 1 a p predstavlja 0, njihove optičke izomere, te također njihove adicijske soli s farmaceutski prihvatljivom kiselinom.
11. Spoj formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da je odabran od:
- N-{[3,4-dimetoksibiciklo[4.2.0]okta-1,3,5-trien-7-il]metil}-3-(7,8-dimetoksi-1,2,4,5-tetrahidro-3H-3-benazepin-3-il)-N-metil-3-oksopropan-1-amina, njegovih optičkih izomera te također njegovih adicijskih soli s farmaceutski prihvatljivom kiselinom;
- N-{[3,4-dimetoksibiciklo[4.2.0]okta-1,3,5-trien-7-il]metil}-3-(7,8-dimetoksi-1,2,4,5-tetrahidro-3H-3-benazepin-3-il)-3-oksopropan-1-amina, njegovih optičkih izomera te također njegovih adicijskih soli s farmaceutski prihvatljivom kiselinom;
- N-[2-(5,6-dimetoksi-2,3-dihidro-1H-inden-2-il)metil]-3-(7,8-dimetoksi-1,2,4,5-tetrahidro-3H-3-benazepin-3-il)-N-metil-4-oksobutan-1-amina, njegovih optičkih izomera te također njegovih adicijskih soli s farmaceutski prihvatljivom kiselinom;
- N-{[3,4-dimetoksibiciklo[4.2.0]okta-1,3,5-trien-7-il]metil}-3-(7,8-dimetoksi-1,2,4,5-tetrahidro-3H-3-benazepin-3-il)-4-oksobutan-1-amina, njegovih optičkih izomera te također njegovih adicijskih soli s farmaceutski prihvatljivom kiselinom; i
- 7-{[[3-(7,8-dimetoksi-1,2,4,5-tetrahidro-3H-3-benazepin-3-il)-3-oksopropil]-(metil)amino]metil}-biciklo[4.2.0]okta-1,3,5-trien-3-il dimetilkarbamata, njegovih optičkih izomera te također njegovih adicijskih soli s farmaceutski prihvatljivom kiselinom.
12. Postupak za sintezu spojeva formule (I) u skladu s patentnim zahtjevom 1, naznačen time da počinje od spoja formule (II):
[image]
gdje su R6, R7, R8 i R9 definirani u patentnom zahtjevu 1,
koji se podvrgava reakciji hidrogenacije kako bi se dobio spoj formule (III):
[image]
gdje su R6, R7, R8 i R9 definirani u patentnom zahtjevu 1, koji se reducira kako bi se dobio spoj formule (IV):
[image]
gdje su R6, R7, R8 i R9 definirani u patentnom zahtjevu 1, koji reagira
- ili, kada je poželjno da se dobiju spojevi formule (I) gdje m predstavlja nulu, s akriloil kloridom kako bi se dobio spoj formule (V):
[image]
gdje su R6, R7, R8 i R9 definirani u patentnom zahtjevu 1, koji se podvrgava reakciji sparivanja sa spojem formule (VI):
[image]
gdje su n, p, R1, R2, R3, R4 i R5 definirani u patentnom zahtjevu 1,
kako bi se dobili spojevi formule (Ia), posebno stanje spojeva formule (I) gdje
m predstavlja nulu:
[image]
pri čemu su n, p, R1, R2, R3, R4, R5, R6, R7, R8 i R9 definirani u patentnom zahtjevu 1,
- ili, kada je poželjno da se dobiju spojevi formule (I) kada (X)m predstavlja O ili NH, s difosgenom kako bi se dobio spoj formule (VII):
[image]
gdje su R6, R7, R8 i R9 definirani u patentnom zahtjevu 1, koji reagira sa spojem formule (VIII):
[image]
pri čemu n, p, R1, R2, R3, R4 i R5 su definirani u patentnom zahtjevu 1 a X1 predstavlja O ili NH,
kako bi se dobili spojevi formule (Ib), posebno stanje spojeva formule (I) gdje m predstavlja 1, a X predstavlja O ili NH:
[image]
gdje su n, p, R1, R2, R3, R4, R5, R6, R7, R8 i R9 definirani u patentnom zahtjevu 1 a X1 predstavlja O ili NH,
- ili kada je poželjno da se dobiju spojevi formule (I) kada (X)m predstavlja CH2, s gama-butirolaktonom kako bi se dobio spoj formule (IX):
[image]
pri čemu su R6, R7, R8 i R9 definirani u patentnom zahtjevu 1, koji oksidira kako bi se dobio spoj formule (X):
[image]
gdje su R6, R7, R8 i R9 definirani u patentnom zahtjevu 1,
koji reagira sa spojem formule (VI) kako bi se dobili spojevi formule (Ic),
poseban slučaj spojeva formule (I) kada m predstavlja CH2:
[image]
gdje su n, p, R1, R2, R3, R4, R5, R6, R7, R8 i R9 definirani u patentnom zahtjevu 1.
13. Farmaceutski pripravak koji sadrži djelatnu tvar spoja formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 11, naznačen time, da je u kombinaciji s jednim ili više farmaceutski prihvatljivih, inertnih, netoksičnih ekscipijenasa ili nosača.
14. Farmaceutski pripravak u skladu s patentnim zahtjevom 13, naznačen time, da se koristi u liječenju ili prevenciji patoloških stanja u kojima broj otkucaja srca djeluju kao okidač ili imaju otegotnu ulogu.
15. Farmaceutski pripravak u skladu s patentnim zahtjevom 14, naznačen time, da se koristi za liječenje ili prevenciju ishemijske bolesti srca, zatajenja srca bilo sistoličko ili dijastoličko i bilo kod njihovih kroničnih ili akutnih oblika, poremećaji ventrikularnog ili supraventrikularnog ritma, ili patoloških stanja koji je čimbenik rizika za ožilje.
16. Farmaceutski pripravak u skladu s patentnim zahtjevom 15, naznačen time, da se koristi za liječenje i prevenciju stabilne angine, nestabilne angine, prijetećih sindroma, infarkta miokarda ili post infarktnog stanja.
17. Farmaceutski pripravak u skladu s patentnim zahtjevom 15, naznačen time, da se koristi za liječenje ili prevenciju arterijske hipertenzije, dijabetesa ili hiperkolesterolemije.
18. Farmaceutski pripravak u skladu s patentnim zahtjevom 13, naznačen time, da se koristi u kurativno ili preventivno liječenje boli, hiperaktivnosti mjehura ili suhoće oka.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0706346A FR2920773B1 (fr) | 2007-09-11 | 2007-09-11 | Derives de 1,2,4,5-tetrahydro-3h-benzazepines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
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| Publication Number | Publication Date |
|---|---|
| HRP20100259T1 true HRP20100259T1 (hr) | 2010-06-30 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20100259T HRP20100259T1 (hr) | 2007-09-11 | 2010-05-11 | Derivati 1,2,4,5-tetrahidro-3h-benzazepina, postupak za njihovu pripravu i farmaceutske smjese koje ih sadrže |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| FR2961105B1 (fr) * | 2010-06-15 | 2013-02-08 | Servier Lab | Utilisation de l'association d'un inhibiteur du courant if sinusal et d'un inhibiteur de l'enzyme de conversion de l'angiotensine pour le traitement de l'insuffisance cardiaque |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| FR2984319B1 (fr) * | 2011-12-20 | 2013-12-27 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| FR2984320B1 (fr) * | 2011-12-20 | 2013-11-29 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| FR2988720B1 (fr) * | 2012-03-27 | 2014-03-14 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
| TWI654180B (zh) | 2012-06-29 | 2019-03-21 | 美商艾佛艾姆希公司 | 殺真菌之雜環羧醯胺 |
| FR3003859B1 (fr) * | 2013-03-26 | 2015-03-13 | Servier Lab | "procede de synthese de derives de la 7,8-dimethoxy-1,3-dihydro-2h-3-benzazepin-2-one et application a la synthese de l'ivabradine" |
| US9333208B2 (en) | 2013-07-16 | 2016-05-10 | Movses H. Karakossian | HCN inhibitors affecting ganglion cell function and visual function |
| FR3020810B1 (fr) * | 2014-05-06 | 2016-05-06 | Servier Lab | Nouveau sel de l'ivabradine et son procede de preparation. |
| FR3046793B1 (fr) * | 2016-01-14 | 2018-01-05 | Les Laboratoires Servier | Nouveaux derives de phosphinanes et azaphosphinanes, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| EP3615052B1 (en) * | 2017-04-27 | 2023-01-25 | The University of Hong Kong | Use of hcn inhibitors for treatment of cancer |
| CN112724001B (zh) * | 2019-10-28 | 2022-12-13 | 鲁南制药集团股份有限公司 | 一种伊伐布雷定手性中间体化合物 |
| CN113372273B (zh) * | 2020-03-10 | 2023-05-09 | 鲁南制药集团股份有限公司 | 一种伊伐布雷定中间体化合物iv |
| CN113372274B (zh) * | 2020-03-10 | 2023-03-24 | 鲁南制药集团股份有限公司 | 一种伊伐布雷定的制备方法 |
| JP7315806B1 (ja) | 2021-08-31 | 2023-07-26 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 単環ピリジン誘導体の製造方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3119874A1 (de) * | 1981-05-19 | 1982-12-09 | Dr. Karl Thomae Gmbh, 7950 Biberach | "benzazepinderivate, ihre herstellung und ihre verwendung als arzneimittel" |
| DE3418270A1 (de) | 1984-05-17 | 1985-11-21 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue aminotetralinderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| GB8707120D0 (en) * | 1987-03-25 | 1987-04-29 | Pfizer Ltd | Antiarrhythmic agents |
| JPH02193971A (ja) * | 1989-01-20 | 1990-07-31 | Yamanouchi Pharmaceut Co Ltd | トリ置換―２，３，４，５―テトラヒドロベンズアゼピン誘導体とその中間体 |
| FR2681862B1 (fr) * | 1991-09-27 | 1993-11-12 | Adir Cie | Nouvelles (benzocycloalkyl)alkylamines, leur procede de preparation, et les compositions pharmaceutiques qui les contiennent. |
| EP0700389A1 (en) * | 1993-05-27 | 1996-03-13 | Smithkline Beecham Laboratoires Pharmaceutiques | Anti-arrhythmic n-substituted 3-benzazepines or isoquinolines |
| TW527355B (en) * | 1997-07-02 | 2003-04-11 | Bristol Myers Squibb Co | Inhibitors of farnesyl protein transferase |
| US6514964B1 (en) * | 1999-09-27 | 2003-02-04 | Amgen Inc. | Fused cycloheptane and fused azacycloheptane compounds and their methods of use |
| FR2882554B1 (fr) * | 2005-02-28 | 2007-05-04 | Servier Lab | Forme critalline beta d du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
| FR2894826B1 (fr) | 2005-12-21 | 2010-10-22 | Servier Lab | Nouvelle association d'un inhibiteur du courant if sinusal et d'un inhibiteur calcique et les compositions pharmaceutiques qui la contiennent |
-
2007
- 2007-09-11 FR FR0706346A patent/FR2920773B1/fr not_active Expired - Fee Related
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2008
- 2008-08-19 PE PE2008001405A patent/PE20090620A1/es active IP Right Grant
- 2008-08-20 SG SG200806160-8A patent/SG151172A1/en unknown
- 2008-08-20 CR CR10229A patent/CR10229A/es unknown
- 2008-08-21 UY UY31305A patent/UY31305A1/es active IP Right Grant
- 2008-08-26 AP AP2008004589A patent/AP2384A/xx active
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- 2008-09-02 TW TW097133661A patent/TWI374029B/zh not_active IP Right Cessation
- 2008-09-02 CA CA2639349A patent/CA2639349C/fr active Active
- 2008-09-03 ZA ZA2008/07586A patent/ZA200807586B/en unknown
- 2008-09-04 UA UAA200810902A patent/UA100003C2/ru unknown
- 2008-09-05 JP JP2008227956A patent/JP4932805B2/ja not_active Expired - Fee Related
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- 2008-09-09 PA PA20088795301A patent/PA8795301A1/es unknown
- 2008-09-09 US US12/283,110 patent/US8076325B2/en not_active Expired - Fee Related
- 2008-09-09 AR ARP080103906A patent/AR068386A1/es active IP Right Grant
- 2008-09-10 SA SA08290567A patent/SA08290567B1/ar unknown
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- 2008-09-10 EA EA200801828A patent/EA014756B1/ru unknown
- 2008-09-10 JO JO2008404A patent/JO2652B1/en active
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- 2008-09-11 WO PCT/FR2008/001268 patent/WO2009066041A2/fr active Application Filing
- 2008-09-11 AT AT08290851T patent/ATE460401T1/de active
- 2008-09-11 EP EP08290851A patent/EP2036892B1/fr active Active
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- 2008-09-11 DE DE602008000786T patent/DE602008000786D1/de active Active
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