HRP20210469T1 - Valbenazin ditosilat i njegovi polimorfi - Google Patents

Valbenazin ditosilat i njegovi polimorfi Download PDF

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HRP20210469T1
HRP20210469T1 HRP20210469TT HRP20210469T HRP20210469T1 HR P20210469 T1 HRP20210469 T1 HR P20210469T1 HR P20210469T T HRP20210469T T HR P20210469TT HR P20210469 T HRP20210469 T HR P20210469T HR P20210469 T1 HRP20210469 T1 HR P20210469T1
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crystalline form
form according
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amorphous
increase
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HRP20210469TT
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Kevin MCGEE
Scott Zook
Andrew Carr
Thierry Bonnaud
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Neurocrine Biosciences, Inc.
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Application filed by Neurocrine Biosciences, Inc. filed Critical Neurocrine Biosciences, Inc.
Publication of HRP20210469T1 publication Critical patent/HRP20210469T1/hr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
    • C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
    • C07D455/04—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine
    • C07D455/06—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine containing benzo [a] quinolizine ring systems
    • 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
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/32—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of salts of sulfonic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/01—Sulfonic acids
    • C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C309/29—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton of non-condensed six-membered aromatic rings
    • C07C309/30—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton of non-condensed six-membered aromatic rings of six-membered aromatic rings substituted by alkyl groups
    • 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
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Psychology (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Claims (44)

1. Kristalni oblik, naznačen time, da je od spoja Formule I: [image]
2. Kristalni oblik prema patentnom zahtjevu 1, naznačen time, da ima uzorak rendgenske difrakcije na prahu koji sadrži maksimume na 6,3, 17,9 i 19,7 stupnjeva 2θ ± 0,2θ.
3. Kristalni oblik prema patentnom zahtjevu 2, naznačen time, da ima termogram diferencijalne pretražne kalorimetrije koji sadrži endotermički slučaj s početnom temperaturom od 240°C i maksimum na 243°C.
4. Kristalni oblik prema patentnom zahtjevu 2 ili 3, naznačen time, da ima dijagram termalne gravimetrijske analize koji sadrži gubitak mase manji od 0,4% kada se zagrijava od 25°C do 140°C.
5. Kristalni oblik prema bilo kojem od patentnih zahtjeva 2 do 4, naznačen time, da je stabilan nakon izlaganja na 25°C i 60% relativnoj vlažnosti za vrijeme od 3 mjeseca.
6. Kristalni oblik prema bilo kojem od patentnih zahtjeva 2 do 5, naznačen time, da pokazuje povećanje mase od 1% kada se podvrgne porastu u relativnoj vlažnosti od 0% do 95% relativne vlažnosti.
7. Kristalni oblik prema patentnom zahtjevu 1, naznačen time, da ima uzorak rendgenske difrakcije na prahu koji sadrži maksimume na 5,7, 15,3 i 22,5 stupnjeva 2θ ± 0,2θ.
8. Kristalni oblik prema patentnom zahtjevu 7, naznačen time, da ima termogram diferencijalne pretražne kalorimetrije koji sadrži endotermički slučaj s početnom temperaturom od 143°C i maksimum na 155°C i; i jedan drugi endotermički slučaj s početnom temperaturom od 232°C i maksimum na 235°C.
9. Kristalni oblik prema patentnom zahtjevu 7 ili 8, naznačen time, da ima dijagram termalne gravimetrijske analize koji sadrži gubitak mase od 2,2% kada se zagrijava od 25°C do 140°C.
10. Kristalni oblik prema bilo kojem od patentnih zahtjeva 7 do 9, naznačen time, da pokazuje povećanje mase od 0,5% kada se podvrgne porastu u relativnoj vlažnosti od 0% do 95% relativne vlažnosti.
11. Kristalni oblik prema patentnom zahtjevu 1, naznačen time, da ima uzorak rendgenske difrakcije na prahu koji sadrži maksimume na 6,3, 18,3, 18,9, 19,8 i 20,4 stupnjeva 2θ ± 0,2θ.
12. Kristalni oblik prema patentnom zahtjevu 11, naznačen time, da ima termogram diferencijalne pretražne kalorimetrije koji sadrži endotermičke slučajeve s temperaturama od 93°C, 158°C i 230°C.
13. Kristalni oblik prema patentnom zahtjevu 11 ili 12, naznačen time, da ima dijagram termalne gravimetrijske analize koji sadrži dva gubitka mase od 2,7% i 8,86% kada se zagrijava od 25°C do 140°C.
14. Kristalni oblik prema patentnom zahtjevu 1, naznačen time, da ima uzorak rendgenske difrakcije na prahu koji sadrži maksimume na 6,2, 10,4, 17,9, 19,2, 19,9 i 20,2 stupnjeva 2θ ± 0,2θ.
15. Kristalni oblik prema patentnom zahtjevu 14, naznačen time, da ima termogram diferencijalne pretražne kalorimetrije koji sadrži endotermičke slučajeve s temperaturama od 128°C, 159°C i 237°C.
16. Kristalni oblik prema patentnom zahtjevu 14 ili 15, naznačen time, da ima dijagram termalne gravimetrijske analize koji sadrži gubitak mase od 3,3% kada se zagrijava od 25°C do 140°C.
17. Kristalni oblik prema bilo kojem od patentnih zahtjeva 14 do 16, naznačen time, da pokazuje povećanje mase od 3,4% kada se podvrgne porastu u relativnoj vlažnosti od 0% do 95% relativne vlažnosti.
18. Kristalni oblik prema patentnom zahtjevu 1, naznačen time, da ima uzorak rendgenske difrakcije na prahu koji sadrži maksimume na 6,7, 7,9, 10,7, 12,8, 17,1 i 23,7 stupnjeva 2θ ± 0,2θ.
19. Kristalni oblik prema patentnom zahtjevu 18, naznačen time, da ima termogram diferencijalne pretražne kalorimetrije koji sadrži endotermičke slučajeve s temperaturama od 113°C i 181°C.
20. Kristalni oblik prema patentnom zahtjevu 18 ili 19, naznačen time, da ima dijagram termalne gravimetrijske analize koji sadrži gubitak mase od 4,1% kada se zagrijava od 25°C do 140°C.
21. Kristalni oblik prema bilo kojem od patentnih zahtjeva 18 do 20, naznačen time, da pokazuje povećanje mase od 1% kada se podvrgne porastu u relativnoj vlažnosti od 0% do 95% relativne vlažnosti.
22. Kristalni oblik prema patentnom zahtjevu 1, naznačen time, da ima uzorak rendgenske difrakcije na prahu koji sadrži maksimume na 6,8, 8,0, 16,3 i 17,5 stupnjeva 2θ ± 0,2θ.
23. Kristalni oblik prema patentnom zahtjevu 22, naznačen time, da ima termogram diferencijalne pretražne kalorimetrije koji sadrži endotermičke slučajeve s temperaturama od 175°C i 238°C.
24. Kristalni oblik prema patentnom zahtjevu 22 ili 23, naznačen time, da ima dijagram termalne gravimetrijske analize koji sadrži gubitak mase od 1% kada se zagrijava od 25°C do 140°C.
25. Kristalni oblik prema bilo kojem od patentnih zahtjeva 22 do 24, naznačen time, da pokazuje povećanje mase od 0,5% kada se podvrgne porastu u relativnoj vlažnosti od 40% do 80% relativne vlažnosti.
26. Amorfni oblik, naznačen time, da je od spoja Formule I: [image]
27. Farmaceutski pripravak, naznačen time, da sadrži kristalni oblik prema bilo kojem od patentnih zahtjeva 1 do 25 ili amorfni oblik prema patentnom zahtjevu 26, i farmaceutski prihvatljiv nosač.
28. Farmaceutski pripravak prema patentnom zahtjevu 27, naznačen time, da se pripravak formulira za oralnu primjenu.
29. Farmaceutski pripravak prema patentnom zahtjevu 27 ili 28, naznačen time, da se pripravak formulira kao jednostruki oblik za doziranje.
30. Kristalni oblik prema bilo kojem od patentnih zahtjeva 1 do 25 ili amorfni oblik prema patentnom zahtjevu 26, naznačen time, da je za uporabu u postupku inhibicije izooblika 2 vezikularnog monoaminskog transportera kod pojedinca.
31. Kristalni oblik prema bilo kojem od patentnih zahtjeva 1 do 25 ili amorfni oblik prema patentnom zahtjevu 26, naznačen time, da je za uporabu u postupku liječenja, prevencije, ili ublažavanja jednog ili više simptoma hiperkinetičkog poremećaja.
32. Kristalni oblik ili amorfni oblik za uporabu prema patentnom zahtjevu 31, naznačen time, da se kod hiperkinetičkog poremećaja radi o Huntingtonovoj bolesti, tardivnoj diskineziji, Touretteovom sindromu, distoniji, hemibalizmu, koreji, senilnoj koreji ili tikovima.
33. Kristalni oblik ili amorfni oblik za uporabu prema patentnom zahtjevu 31, naznačen time, da hiperkinetički poremećaj jest Huntingtonova bolest.
34. Kristalni oblik ili amorfni oblik za uporabu prema patentnom zahtjevu 31, naznačen time, da hiperkinetički poremećaj jest tardivna diskinezija.
35. Kristalni oblik ili amorfni oblik za uporabu prema patentnom zahtjevu 31, naznačen time, da hiperkinetički poremećaj jest Touretteov sindrom.
36. Kristalni oblik ili amorfni oblik za uporabu prema patentnom zahtjevu 31, naznačen time, da hiperkinetički poremećaj jesu tikovi.
37. Postupak za proizvodnju kristalnog oblika prema bilo kojem od patentnih zahtjeva 1 do 25 ili amorfnog oblika prema patentnom zahtjevu 26, naznačen time, da obuhvaća sljedeće korake: (a) pripravljanje kašaste smjese spoja Formule I u otapalu na prvoj temperaturi; i (b) generiranje kristalnog oblika ili amorfnog oblika pomoću hlađenja otopine na drugu temperaturu.
38. Postupak za proizvodnju kristalnog oblika prema bilo kojem od patentnih zahtjeva 1 do 25 ili amorfnog oblika prema patentnom zahtjevu 26, naznačen time, da obuhvaća sljedeće korake: (a) pripravljanje otopine spoja Formule I u otapalu na prvoj temperaturi; (b) formiranje kašaste smjese pomoću hlađenja otopine na drugu temperaturu; i (c) generiranje kristalnog oblika ili amorfnog oblika putem obrade kašaste smjese kroz jedan ili više ciklusa zagrijavanja i hlađenja.
39. Postupak prema patentnom zahtjevu 38, naznačen time, da se ciklus zagrijavanja i hlađenja izvodi na temperaturi u rasponu od -50 do 120°C.
40. Postupak prema bilo kojem od patentnih zahtjeva 37 do 39, naznačen time, da prva temperatura iznosi od 20 do 200°C.
41. Postupak prema bilo kojem od patentnih zahtjeva 37 do 40, naznačen time, da druga temperatura iznosi od -100 do 100°C.
42. Postupak prema bilo kojem od patentnih zahtjeva 37 do 41, naznačen time, da nadalje obuhvaća korak izolacije kristalnog oblika ili amorfnog oblika.
43. Postupak prema bilo kojem od patentnih zahtjeva 37 do 42, naznačen time, da se otapalo odabire od: ugljikovodika, kloriranog ugljikovodika, alkohola, etera, ketona, estera, karbonata, amida, nitrila, nitro spoja, heterocikla, vode, i njihovih mješavina.
44. Postupak prema bilo kojem od patentnih zahtjeva 37 do 42, naznačen time, da se otapalo odabire od: acetonitrila, 1,2-dikloroetana, DMF, 1,4-dioksana, metanola, 2-metoksietanola, MIBK, toluena, heptana, kumena, acetona, 1-butanola, MTBE, etanola, etil acetata, etil formijata, izobutil acetata, izopropil acetata, metil acetata, nitrometana, 1-propanola, IPA, MEK, THF, vode, i njihovih mješavina.
HRP20210469TT 2015-10-30 2016-10-28 Valbenazin ditosilat i njegovi polimorfi HRP20210469T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562249074P 2015-10-30 2015-10-30
EP16794479.2A EP3368534B1 (en) 2015-10-30 2016-10-28 Valbenazine ditosylate and polymorphs thereof
PCT/US2016/059306 WO2017075340A1 (en) 2015-10-30 2016-10-28 Valbenazine salts and polymorphs thereof

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HRP20210469T1 true HRP20210469T1 (hr) 2021-05-14

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HRP20240304TT HRP20240304T1 (hr) 2015-10-30 2016-10-28 Soli valbenazin dihidroklorida i njihovi polimorfi
HRP20210469TT HRP20210469T1 (hr) 2015-10-30 2016-10-28 Valbenazin ditosilat i njegovi polimorfi

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JP (3) JP7109360B2 (hr)
KR (2) KR102736973B1 (hr)
CN (3) CN115322188A (hr)
AU (1) AU2016343633B2 (hr)
CA (1) CA3002074A1 (hr)
CL (1) CL2018001089A1 (hr)
CO (1) CO2018004589A2 (hr)
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DK (2) DK3875459T3 (hr)
EA (1) EA201890852A1 (hr)
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HR (2) HRP20240304T1 (hr)
HU (2) HUE053872T2 (hr)
IL (2) IL284874B2 (hr)
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PH (1) PH12018500900A1 (hr)
PL (2) PL3368534T3 (hr)
PT (2) PT3368534T (hr)
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SA (1) SA518391477B1 (hr)
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SI (2) SI3368534T1 (hr)
SM (1) SMT202400177T1 (hr)
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HRP20240304T1 (hr) 2015-10-30 2024-05-10 Neurocrine Biosciences, Inc. Soli valbenazin dihidroklorida i njihovi polimorfi
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RU2019110048A (ru) 2016-10-06 2020-11-06 Ассиа Кемикал Индастрис Лтд. Твердые формы валбеназина
TW202345829A (zh) * 2016-12-02 2023-12-01 美商紐羅克里生物科學有限公司 戊苯那嗪（valbenazine）於治療精神分裂症或情感性精神分裂症之用途
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US10874648B2 (en) 2017-01-27 2020-12-29 Neurocrine Biosciences, Inc. Methods for the administration of certain VMAT2 inhibitors
EP3585787A1 (en) * 2017-02-27 2020-01-01 Sandoz AG Crystalline forms of valbenazine salts
US20200179352A1 (en) * 2017-04-26 2020-06-11 Neurocrine Biosciences, Inc. Use of valbenazine for treating levodopa-induced dyskinesia
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