HRP20171044T1 - Kemijski i metabolički stabilni dipeptid s potentnom aktivnošću blokatora natrijevog kanala - Google Patents

Kemijski i metabolički stabilni dipeptid s potentnom aktivnošću blokatora natrijevog kanala Download PDF

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Publication number
HRP20171044T1
HRP20171044T1 HRP20171044TT HRP20171044T HRP20171044T1 HR P20171044 T1 HRP20171044 T1 HR P20171044T1 HR P20171044T T HRP20171044T T HR P20171044TT HR P20171044 T HRP20171044 T HR P20171044T HR P20171044 T1 HRP20171044 T1 HR P20171044T1
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Croatia
Prior art keywords
acid
treatment
compound
intended
compound according
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HRP20171044TT
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English (en)
Inventor
Michael Ross Johnson
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Parion Sciences, Inc.
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Publication of HRP20171044T1 publication Critical patent/HRP20171044T1/hr

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    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965—Non-condensed pyrazines
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
    • C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
    • C07D241/28—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
    • C07D241/30—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms in which said hetero-bound carbon atoms are part of a substructure —C(=X)—X—C(=X)—X— in which X is an oxygen or sulphur atom or an imino radical, e.g. imidoylguanidines
    • C07D241/32—(Amino-pyrazinoyl) guanidines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Claims (21)

1. Spoj, naznačen time što ga prikazuje formula (I): [image] , te njegovi racemati, enantiomeri, dijastereomeri, tautomeri, polimorfi, pseudopolimorfi i farmaceutski prihvatljive soli.
2. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je kisela adicijska sol anorganske kiseline ili organske kiseline koju se bira iz skupine koju čine klorovodična kiselina, bromovodična kiselina, sumporna kiselina, fosforna kiselina, dušična kiselina, octena kiselina, oksalna kiselina, vinska kiselina, jantarna kiselina, maleinska kiselina, furmarna kiselina, glukonska kiselina, limunska kiselina, jabučna kiselina, askorbinska kiselina, benzojeva kiselina, taninska kiselina, palmitinska kiselina, alginska kiselina, poliglutaminska kiselina, naftalensulfonska kiselina, metansulfonska kiselina, p-toluensulfonska kiselina, naftalendisulfonska kiselina, poligalakturonska kiselina, malonska kiselina, sulfosalicilna kiselina, glikolna kiselina, 2-hidroksi-3-naftoat, pamoat, salicilna kiselina, stearinska kiselina, ftalna kiselina, bademova kiselina, te mliječna kiselina.
3. Farmaceutski pripravak, naznačen time što sadrži spoj u skladu s patentnim zahtjevom 1 ili patentnim zahtjevom 2, kao i farmaceutski prihvatljivu podlogu.
4. Pripravak, naznačen time što sadrži: spoj u skladu s patentnim zahtjevom 1 ili patentnim zahtjevom 2; i agonist receptora P2Y2.
5. Pripravak, naznačen time što sadrži: spoj u skladu s patentnim zahtjevom 1 ili patentnim zahtjevom 2; i bronhodilator.
6. Spoj u skladu s patentnim zahtjevima 1 ili 2, naznačen time što je namijenjen upotrebi u poticanje vlaženja površine sluznice, gdje se djelotvornu količinu spoja u skladu s patentnim zahtjevima 1 ili 2 primjenjuje na površinu sluznice subjekta.
7. Spoj u skladu s patentnim zahtjevima 1 ili 2, naznačen time što je namijenjen upotrebi u liječenju kroničnog bronhitisa, liječenju bronhiektazije, liječenju cistične fibroze, liječenju sinusitisa, liječenju suhoće vagine, liječenju suhog oka, poticanju vlaženja oka, poticanju vlaženja rožnice, poticanju čišćenja sluzi na površinama sluznica, liječenju Sjögrenove bolesti, liječenju sindroma opstrukcije distalnog crijeva, liječenju suhe kože, liječenju ezofagitisa, liječenju suhih ustiju, liječenju dehidracije nosa, liječenju pneumonije uzrokovane respiratorom, liječenju astme, liječenju primarne cilijarne diskinezije, liječenju upale srednjeg uha, poticanju stvaranja ispljuvka u dijagnostičke svrhe, liječenju kronične opstruktivne plućne bolesti, liječenju emfizema, liječenju pneumonije, liječenju opstipacije, liječenju kroničnog divertikulitisa ili liječenje rinosinusitisa.
8. Pripravak koji sadrži osmolit i spoj u skladu s patentnim zahtjevima 1 ili 2, naznačen time što je namijenjen upotrebi u liječenju jednog ili više stanja koja se bira iz skupine koju čine kronični bronhitis, bronhiektazija, cistična fibroza, sinusitis, suhoća vagine, suho oko, Sjögrenova bolest, sindrom opstrukcije distalnog crijeva, suha koža, ezofagitis, suha usta (kserostomija), dehidracija nosa, astma, primarna cilijarna diskinezija, upala srednjeg uha, kronična opstruktivna plućna bolest, emfizem, pneumonija, divertikulitis, rinosinusitis, te kapljične infekcije.
9. Pripravak namijenjen upotrebi u skladu s patentnim zahtjevom 8, naznačen time što se spoj primjenjuje na subjektu prije primjene osmolita.
10. Pripravak namijenjen upotrebi u skladu s patentnim zahtjevom 8, naznačen time što se spoj primjenjuje na subjektu istodobno s primjenom osmolita.
11. Pripravak namijenjen upotrebi u skladu s patentnim zahtjevom 8, naznačen time što se spoj primjenjuje na subjektu nakon primjene osmolita.
12. Pripravak namijenjen upotrebi u skladu s patentnim zahtjevom 8, naznačen time što je osmolit hipertonična slana otopina ili manitol.
13. Pripravak namijenjen upotrebi u skladu s patentnim zahtjevom 8, naznačen time što je osmolit natrijev klorid, kojeg se unosi u subjekta kao mikronizirane čestice veličine pogodne za udisanje.
14. Pripravak namijenjen upotrebi u skladu s patentnim zahtjevom 8, naznačen time što se djelotvornu količinu osmolita i blokator natrijevog kanala primjenjuje na subjektu aerosoliziranjem uz pomoć uređaja koji može unijeti formulaciju u nosne prolaze ili plućne dišne puteve, gdje je aerosol veličine pogodne za udisanje.
15. Pripravak, naznačen time što sadrži: (a) spoj u skladu s patentnim zahtjevom 1 ili patentnim zahtjevom 2 i (b) osmotski aktivni spoj.
16. Spoj u skladu s patentnim zahtjevima 1 ili 2, naznačen time što je namijenjen upotrebi u poticanju stvaranja ispljuvka, gdje se djelotvornu količinu osmolita i spoj u skladu s patentnim zahtjevima 1 ili 2 primjenjuje na subjektu kojem je potrebno pojačano čišćenje mukocilijarnog epitela i vlaženje sluznice.
17. Spoj u skladu s patentnim zahtjevima 1 ili 2, naznačen time što je namijenjen upotrebi u profilaksi, profilaksi nakon izlaganja, preventivnom ili terapijskom liječenju protiv bolesti ili stanja koja uzrokuju patogeni, gdje se djelotvornu količinu spoja u skladu s patentnim zahtjevima 1 ili 2 primjenjuje na subjektu kojem je potrebno pojačano čišćenje mukocilijarnog epitela i vlaženje sluznice.
18. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 17, naznačen time što je patogen bedrenica ili kuga.
19. Pripravak koji sadrži osmolit i spoj u skladu s patentnim zahtjevima 1 ili 2, naznačen time što je namijenjen upotrebi u profilaksi, profilaksi nakon izlaganja, preventivnom ili terapijskom liječenju protiv bolesti ili stanja koja uzrokuju patogeni, gdje se djelotvornu količinu osmolita i spoja u skladu s patentnim zahtjevima 1 ili 2 primjenjuje na subjektu kojem je potrebno pojačano čišćenje mukocilijarnog epitela i vlaženje sluznice.
20. Pripravak namijenjen upotrebi u skladu s patentnim zahtjevom 19, naznačen time što je patogen bedrenica ili kuga.
21. Postupak priprave spoja formule I [image] , naznačen time što se sastoji u koraku reakcije spoja sljedeće formule: [image] sa spojem sljedeće formule: [image] u prisutnosti DIPEA, u EtOH, kako bi se dobio sljedeći spoj kao međuprodukt: [image] .
HRP20171044TT 2011-06-27 2017-07-10 Kemijski i metabolički stabilni dipeptid s potentnom aktivnošću blokatora natrijevog kanala HRP20171044T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161501524P 2011-06-27 2011-06-27
EP12803924.5A EP2723176B1 (en) 2011-06-27 2012-06-27 A chemically and metabolically stable dipeptide possessing potent sodium channel blocker activity
PCT/US2012/044372 WO2013003444A1 (en) 2011-06-27 2012-06-27 A chemically and metabolically stable dipeptide possessing potent sodium channel blocker activity

Publications (1)

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HRP20171044T1 true HRP20171044T1 (hr) 2017-10-06

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US (4) US9072738B2 (hr)
EP (1) EP2723176B1 (hr)
CN (1) CN103687488B (hr)
BR (1) BR112013032771B1 (hr)
CA (1) CA2839709C (hr)
DK (1) DK2723176T3 (hr)
ES (1) ES2633177T3 (hr)
HR (1) HRP20171044T1 (hr)
HU (1) HUE032851T2 (hr)
PL (1) PL2723176T3 (hr)
PT (1) PT2723176T (hr)
SI (1) SI2723176T1 (hr)
WO (1) WO2013003444A1 (hr)

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US9655896B2 (en) 2017-05-23
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US20150290189A1 (en) 2015-10-15
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