HRP20170847T1 - Modulatori atp - vezujućih kasetnih transportera - Google Patents
Modulatori atp - vezujućih kasetnih transportera Download PDFInfo
- Publication number
- HRP20170847T1 HRP20170847T1 HRP20170847TT HRP20170847T HRP20170847T1 HR P20170847 T1 HRP20170847 T1 HR P20170847T1 HR P20170847T T HRP20170847T T HR P20170847TT HR P20170847 T HRP20170847 T HR P20170847T HR P20170847 T1 HRP20170847 T1 HR P20170847T1
- Authority
- HR
- Croatia
- Prior art keywords
- alkyl
- disease
- pharmaceutically acceptable
- acceptable salt
- nhc
- Prior art date
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- 108010006533 ATP-Binding Cassette Transporters Proteins 0.000 title 1
- 102000005416 ATP-Binding Cassette Transporters Human genes 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 26
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 19
- 150000003839 salts Chemical class 0.000 claims 18
- -1 heterocyclic radical Chemical class 0.000 claims 15
- 239000001257 hydrogen Substances 0.000 claims 14
- 229910052739 hydrogen Inorganic materials 0.000 claims 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 11
- 125000005843 halogen group Chemical group 0.000 claims 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 10
- 201000010099 disease Diseases 0.000 claims 9
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 claims 8
- 125000005842 heteroatom Chemical group 0.000 claims 8
- 229910052760 oxygen Inorganic materials 0.000 claims 8
- 229920006395 saturated elastomer Polymers 0.000 claims 8
- 125000000217 alkyl group Chemical group 0.000 claims 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 7
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims 6
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims 6
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 6
- 201000010064 diabetes insipidus Diseases 0.000 claims 6
- 150000002431 hydrogen Chemical class 0.000 claims 6
- 229910052757 nitrogen Inorganic materials 0.000 claims 6
- 239000001301 oxygen Chemical group 0.000 claims 6
- 229910052717 sulfur Inorganic materials 0.000 claims 6
- 125000002950 monocyclic group Chemical group 0.000 claims 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 5
- 125000001424 substituent group Chemical group 0.000 claims 5
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 4
- 201000003883 Cystic fibrosis Diseases 0.000 claims 4
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims 4
- 206010014561 Emphysema Diseases 0.000 claims 4
- 230000007812 deficiency Effects 0.000 claims 4
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims 4
- 239000011593 sulfur Chemical group 0.000 claims 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 4
- 206010013774 Dry eye Diseases 0.000 claims 3
- 229910006074 SO2NH2 Inorganic materials 0.000 claims 3
- 125000002619 bicyclic group Chemical group 0.000 claims 3
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 3
- 208000024827 Alzheimer disease Diseases 0.000 claims 2
- 206010003591 Ataxia Diseases 0.000 claims 2
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 2
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 claims 2
- 206010062264 Congenital hyperthyroidism Diseases 0.000 claims 2
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims 2
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims 2
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims 2
- 201000008163 Dentatorubral pallidoluysian atrophy Diseases 0.000 claims 2
- 206010013883 Dwarfism Diseases 0.000 claims 2
- 208000024720 Fabry Disease Diseases 0.000 claims 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims 2
- 201000011240 Frontotemporal dementia Diseases 0.000 claims 2
- 208000033981 Hereditary haemochromatosis Diseases 0.000 claims 2
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims 2
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 claims 2
- 206010051125 Hypofibrinogenaemia Diseases 0.000 claims 2
- 208000000038 Hypoparathyroidism Diseases 0.000 claims 2
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 claims 2
- 208000015439 Lysosomal storage disease Diseases 0.000 claims 2
- 208000002678 Mucopolysaccharidoses Diseases 0.000 claims 2
- 102100026784 Myelin proteolipid protein Human genes 0.000 claims 2
- 206010068871 Myotonic dystrophy Diseases 0.000 claims 2
- 208000012902 Nervous system disease Diseases 0.000 claims 2
- 208000025966 Neurological disease Diseases 0.000 claims 2
- 206010031243 Osteogenesis imperfecta Diseases 0.000 claims 2
- 208000018737 Parkinson disease Diseases 0.000 claims 2
- 208000017493 Pelizaeus-Merzbacher disease Diseases 0.000 claims 2
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims 2
- 208000025237 Polyendocrinopathy Diseases 0.000 claims 2
- 108091000054 Prion Proteins 0.000 claims 2
- 208000024777 Prion disease Diseases 0.000 claims 2
- 201000005660 Protein C Deficiency Diseases 0.000 claims 2
- 239000005864 Sulphur Substances 0.000 claims 2
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 claims 2
- 208000004622 abetalipoproteinemia Diseases 0.000 claims 2
- 125000001931 aliphatic group Chemical group 0.000 claims 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 230000015271 coagulation Effects 0.000 claims 2
- 238000005345 coagulation Methods 0.000 claims 2
- 206010012601 diabetes mellitus Diseases 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- 201000001386 familial hypercholesterolemia Diseases 0.000 claims 2
- 230000020764 fibrinolysis Effects 0.000 claims 2
- 235000019256 formaldehyde Nutrition 0.000 claims 2
- 208000013746 hereditary thrombophilia due to congenital protein C deficiency Diseases 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims 2
- 201000008980 hyperinsulinism Diseases 0.000 claims 2
- PURKAOJPTOLRMP-UHFFFAOYSA-N ivacaftor Chemical compound C1=C(O)C(C(C)(C)C)=CC(C(C)(C)C)=C1NC(=O)C1=CNC2=CC=CC=C2C1=O PURKAOJPTOLRMP-UHFFFAOYSA-N 0.000 claims 2
- 150000002632 lipids Chemical class 0.000 claims 2
- 201000001441 melanoma Diseases 0.000 claims 2
- 206010028093 mucopolysaccharidosis Diseases 0.000 claims 2
- 201000000585 muscular atrophy Diseases 0.000 claims 2
- 208000000638 myeloperoxidase deficiency Diseases 0.000 claims 2
- 230000002988 nephrogenic effect Effects 0.000 claims 2
- 230000004770 neurodegeneration Effects 0.000 claims 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims 2
- 108010040003 polyglutamine Proteins 0.000 claims 2
- 229920000155 polyglutamine Polymers 0.000 claims 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims 2
- 150000003254 radicals Chemical class 0.000 claims 2
- 208000011580 syndromic disease Diseases 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims 1
- 102100034452 Alternative prion protein Human genes 0.000 claims 1
- 208000005139 Hereditary Angioedema Types I and II Diseases 0.000 claims 1
- 206010019860 Hereditary angioedema Diseases 0.000 claims 1
- 208000015178 Hurler syndrome Diseases 0.000 claims 1
- 208000006302 Laron syndrome Diseases 0.000 claims 1
- 208000008955 Mucolipidoses Diseases 0.000 claims 1
- 206010072928 Mucolipidosis type II Diseases 0.000 claims 1
- 206010056886 Mucopolysaccharidosis I Diseases 0.000 claims 1
- XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 claims 1
- 102000029797 Prion Human genes 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 239000003242 anti bacterial agent Substances 0.000 claims 1
- 239000002260 anti-inflammatory agent Substances 0.000 claims 1
- 229940121363 anti-inflammatory agent Drugs 0.000 claims 1
- 229960005475 antiinfective agent Drugs 0.000 claims 1
- 239000004599 antimicrobial Substances 0.000 claims 1
- 230000003115 biocidal effect Effects 0.000 claims 1
- 229940124630 bronchodilator Drugs 0.000 claims 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000003172 expectorant agent Substances 0.000 claims 1
- 208000012770 hereditary angioedema type 1 Diseases 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 208000020460 mucolipidosis II alpha/beta Diseases 0.000 claims 1
- 229940066491 mucolytics Drugs 0.000 claims 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 235000016709 nutrition Nutrition 0.000 claims 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 230000020978 protein processing Effects 0.000 claims 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
Classifications
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- 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
- C07D471/10—Spiro-condensed systems
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- A61K31/265—Esters, e.g. nitroglycerine, selenocyanates of carbonic, thiocarbonic, or thiocarboxylic acids, e.g. thioacetic acid, xanthogenic acid, trithiocarbonic acid
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Claims (21)
1. Spoj formule VA-1:
[image]
ili njegova farmaceutski prihvatljiva sol,
naznačen time da je svaki od WRW2 i WRW4 neovisno odabran od vodika, CN, CF3, halo, C1-C6 ravnog ili razgranatog alkila, 3-12-članog cikloalifatskog ostatka, fenila, C5-C10 heteroarila ili C3-C7 heterocikličkog ostatka, pri čemu navedeni heteroaril ili heterociklil, imaju do 3 heteroatoma odabrana od O, S, ili N, pri čemu su navedeni WRW2 i WRW4 neovisno i proizvoljno supstituirani s do tri supstituenta odabrana od -OR’, -CF3, -OCF3, SR’, S(O)R’, SO2R’, -SCF3, halo, CN, -COOR’, -COR’, -O(CH2)2N(R’)(R’), -O(CH2)N(R’)(R’), -CON(R’)(R’), -(CH2)OR’,-(CH2)OR’, CH2CN, proizvoljno supstituiran fenil ili fenoksi, -N(R’)(R’), -NR’C(O)OR’, -NR’C(O)R’, -(CH2)2N(R’)(R’), ili-(CH2)N(R’)(R’); i
WRW5 je odabran od vodika, -OH, NH2, CN, CHF2, NHR’ , N(R’)2, -NHC(O)R’, -NHC(O)OR’, NHSO2R’, -OR’, CH2OH, CH2N(R’)2, C(O)OR’, SO2NHR’, SO2N(R’)2, CH2O(C1-C6 alkil), -CH2C(O)(C1-C6) alkila), ili CH2NHC(O)OR’; i
X je veza:
RX je vodik;
R’ je neovisno odabran od vodika ili proizvoljno supstituirane skupine odabrane od C1-C8 alifatske skupine, 3-8-članog zasićenog, djelomično zasićenog, ili potpuno nezasićenog monocikličkog prstena koji ima 0-3 heteroatoma neovisno odabrana od dušika, kisika, ili sumpora, ili 8-12-članog zasićenog, djelomično nezasićenog, ili potpuno nezasićenog bicikličkog sustava prstenova koji ima 0-5 heteroatoma neovisno odabranih od dušika, kisika ili sumpora; ili dva R’ kad su uzeti zajedno s atom(ima) za koje su vezani tvore proizvoljno supstituirani 3-12-člani zasićen, djelomično nezasićeni, ili potpuno nezasićeni monociklički ili biciklički prsten koji ima 0-4 heteroatoma neovisno odabrana od dušika, kisika, ili sumpora; uz uvjet da:
i)
[image]
formula VA-1 nije fenil, 2-metilfenil, 2,4-diklorofenil, 2-bromofenil, 4-bromofenil, 2,4dimetilfenil, 2-etilfenil, 3-karboksilna kiselina fenil, 2-fluorofenil, 3-etoksifenil, 4-klorofenil, ili 3-metoksifenil; i
ii)
[image]
formula VA-1 nije fenil supstituiran s -OCH2CH2Ph, -OCH2CH2(2-trifluorometil-fenil, -OCH2CH2-(6,7-dimetoksi-1,2,3,4-tetrahidroizokinolin-2-il), ili supstituirani 1H-pirazol-3-il.
2. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time da:
svaki od WRW2 i WRW4 je neovisno odabran od vodika, CN, CF3, halo, C1-C6 ravnolančanog ili razgranatog alkila, 3-12-člani cikloalifatski, ili fenil, pri čemu navedeni WRW2 i WRW4 su neovisno i proizvoljno supstituirani s do tri supstituenta odabrana od -OR’, -CF3, -OCF3, -SCF3, halo, -COOR’, -COR’, -O(CH2)2N(R’)(R’), -O(CH2)N(R’)(R’), -CON(R’)(R’), -(CH2)2OR’, -(CH2)OR’, proizvoljno supstituirani fenil, -N(R’)(R’), -NR’C(O)OR’, -NR’C(O)R’, -(CH2)2N(R’)(R’), ili -(CH2)N(R’)(R’); i
WRW5 je odabran od vodika, -OH, NH2, CN, NHR’, N(R’)2, -NHC(O)R’, -NHC(O)OR’, NHSO2R’, -OR’, CH2OH, C(O)OR’, SO2NHR’, ili CH2NHC(O)OR’.
3. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time da:
WRW2 je fenilni prsten proizvoljno supstituiran s do tri supstituenta odabrana od -OR’, -CF3, -OCF3, SR’, S(O)R’, SO2R’, -SCF3, halo, CN, -COOR’, -COR’, -O(CH2)2N(R’) (R’), -O(CH2)N(R’)(R’), -CON(R’)(R’), -(CH2)2OR’, -(CH2)OR’, CH2CN, proizvoljno supstituirani fenil ili fenoksi, -N(R’)(R’), -NR’C(O)OR’, -NR’C(O)R’, -(CH2)2N(R’) (R’), ili -(CH2)N(R’) (R’);
WRW4 je C1-C6 ravnolančani ili razgranati alkil; i
WRW5 je OH.
4. Spoj prema zahtjevu 2, ili njegova farmaceutski prihvatljiva sol, naznačen time da je svaki od WRW2 i WRW4 neovisno odabran od CF3, halo, CN, ili C1-C6 ravnolančanog ili razgranatog alkila.
5. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time da je svaki od WRW2 i WRW4 neovisno odabran od proizvoljno supstituiranog n-propila, izopropila, n-butila, sek-butila, t-butila, 1,1-dimetil-2hidroksietila, 1,1-dimetil-2-(etoksikarbonil)-etila, 1,1-dimetil-3-(t-butoksikarbonil-amino) propila, ili n-pentila.
6. Spoj prema zahtjevu 4, ili njegova farmaceutski prihvatljiva sol, naznačen time da je svaki od WRW2 i WRW4 C1-C6 ravnolančani ili razgranati alkil.
7. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time da je WRW5 odabran od vodika, CHF2, NH2, CN, NHR’, N(R’)2, CH2N(R’)2, -NHC(O)R’, -NHC(O)OR’, -OR’, C(O)OR’, ili SO2NHR’.
8. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time da je WRW5 odabran od vodika, NH2, CN, CHF2, NH(C1-C6 alkil), N(C1-C6 alkil)2, -NHC(O) (C1-C6 alkil), -CH2NHC(O)O(C1-C6 alkil), -NHC(O)O(C1-C6 alkil), -OH, -O(C1-C6 alkil), C(O)O(C1-C6 alkil), CH2OC1-C6 alkil), ili SO2NH2.
9. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time da je WRW5 odabran od -OH, OMe, NH2, -NHMe, -N(Me)2, -CH2NH2, CH2OH, NHC(O)OMe, NHC(O)OEt, CN, CHF2, -CH2NHC(O)O(t-butil), -O-(etoksietil), -O-(hidroksietil), -C(O)OMe, ili -SO2NH2.
10. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time da navedeni spoj ima jednu ili više od slijedećih karakteristika:
a. WRW2 je vodik;
b. WRW4 je C1-C6 ravan ili razgranati alkil ili monociklički ili biciklički alifatski ostatak; i
c. WRW5 je odabran od vodika, CN, CHF2, NH2, NH(C1-C6 alkil), N(C1-C6 alkil)2, -NHC(O) (C1-C6 alkil), -NHC(O)O(C1-C6 alkil), -CH2C(O)O(C1-C6 alkil), -OH, - O(C1-C6 alkil), C(O)O(C1-C6 alkil), ili SO2NH2.
11. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time da navedeni spoj ima jednu ili više od slijedećih karakteristika:
a. WRW2 je halo, C1-C6 alkil, CF3, CN, ili fenil proizvoljno supstituiran s do 3 supstituenta odabrana od -O(C1-C4 alkil), ili halo;
b. WRW4 je CF3, halo, C1-C6 alkil, ili C6-C10 cikloalifatski ostatak; i
c. WRW5 je OH, NH2, NH(C1-C6 alkil), ili N(C1-C6) alkil).
12. Spoj prema zahtjevu 1, naznačen time da je spoj odabran od:
[image]
[image]
[image]
[image]
[image]
[image]
ili farmaceutski prihvatljiva sol bilo kojeg od gore navedenih spojeva.
13. Spoj prema zahtjevu 10, naznačen time da je spoj odabran od:
[image]
ili farmaceutski prihvatljiva sol bilo kojeg od gore navedenih spojeva.
14. Spoj prema zahtjevu 11, naznačen time da je spoj odabran od:
[image]
ili farmaceutski prihvatljiva sol bilo kojeg od gore navedenih spojeva
15. Farmaceutski pripravak naznačen time da sadrži spoj prema bilo kojem od zahtjeva 1 do 14, ili njegovu farmaceutski prihvatljivu sol i farmaceutski prihvatljiv nosač ili adjuvant.
16. Pripravak prema zahtjevu 15, naznačen time da navedeni pripravak sadrži dodatno sredstvo odabrano od mukolitičkog sredstva, bronhodilatatora, antibiotika, antiinfektivnog sredstva i protuupalnog sredstva, CFTR modulatora ili prehrambenog sredstva.
17. Spoj formule VA-1:
[image]
ili njegova farmaceutski prihvatljiva sol
naznačen time da je svaki od WRW2 i WRW4 neovisno odabran od vodika, CN, CF3, halo, C1-C6 ravnolančanog ili razgranatog alkila, 3-12-članog cikloalifatskog ostatka, fenila, C5-C10 heteroarila ili C3-C7 heterocikličkog ostatka, pri čemu navedeni heteroaril ili heterociklički ostatak imaju do 3 heteroatoma odabrana od O, S, ili N, pri čemu je navedeni WRW2 i WRW4 neovisno i proizvoljno supstituiran s do tri supstituenta odabrana od -OR’, -CF3, -OCF3, SR’, S(O)R’, SO2R’, -SCF3, halo, CN, -COOR’, -COR’,-O(CH2)2N(R’)(R’), -O(CH2)N(R’)(R’), -CON(R’)(R’), (CH2)2OR’,-(CH2)OR’, CH2CN, proizvoljno supstituirani fenil ili fenoksi, -N(R’)(R’), -NR’C(O)OR’, -NR’C(O)R’, -(CH2)2N(R’)(R’), ili-(CH2)N(R’)(R’); i
WRW5 je odabran od vodika, -OH, NH2, CN, CHF2, NHR’, N(R’)2, -NHC(O)R’, -NHC(O)OR’, NHSO2R’, -OR’, CH2OH, CH2N(R’)2, C(O)OR’, SO2NHR’, SO2N(R’)2, CH2O(C1-C6 alkil), -CH2C(O)O(C1-C6 alkil), ili CH2NHC(O)OR’; i
X je veza:
RX je vodik;
R’ je neovisno odabran od vodika ili proizvoljno supstituirane skupine odabrane od C1-C8 alifatske skupine, 3-8-člane zasićene, djelomično nezasićenog, ili potpuno nezasićenog monocikličkog prstena koji ima 0-3 heteroatoma,
neovisno odabranih od dušika, kisika ili sumpora, ili 8-12-člani zasićeni, djelomično zasićeni ili potpuno nezasićen biciklički prsten koji ima 0-5 heteroatoma neovisno odabranih od dušika, kisika ili sumpora; ili dva R’ uzeta zajedno s atomima za koje su vezani tvore proizvoljno supstituirani 3-12-člani zasićeni, djelomično nezasićeni, ili potpuno zasićeni monociklički ili biciklički prsten koji ima 0-4 heteroatoma neovisno odabrana od dušika, kisika ili sumpora;
ili pripravak prema bilo kojem od zahtjeva 15 do 16, za upotrebu liječenju ili ublažavanju ozbiljnosti bolesti kod pacijenta, pri čemu je navedena bolest odabrana od cistične fibroze, nasljednog emfizema, nasljedne hemokromatoze, fibrinolize (koagulacija), kao što je nedostatak proteina C, nasljednog angioedema tipa 1, nedostatak procesnih lipida, kao što je obiteljska hiperkolesterolemija, hilomikronemija tip 1, abetalipoproteinemija, lizosomska bolest nakupljanja, kao što je bolest I-stanica/pseudo-Hurler, mukopolisaharidoza, Sandhof/Tay-Sachs, Crigler-Najjar tip II, poliendokrinopatija/hiperinzulinemija, dijabetes melitus, Laronov sindrom patuljastog rasta, nedostatak mijeloperoksidaze, primarni hipoparatiroidizam, melanom, glikanoza CDG tip 1, kogenitalni hipertiroidizam, osteogeneza imperfekta, nasljedna hipofibrinogenemija, nedostatak ACT, dijabetes insipidus (DI), neurohipofizealni DI, nefrogeni DI, Charcot-Marie-Tooth sindrom, Pelizaeus-Merzbacherova bolest, neurodegenerativne bolesti kao što su Alzheimerova bolest, Parkinsonova bolest, amiotrofna lateralna skleroza, progresivna supranuklearna paraliza, Pikova bolest, nekoliko poliglutaminskih neuroloških poremećaja kao što su Huntingtonov poremećaj, spinocerebralna ataksija tip I, kičmena ili bulbarna mišićna atrofija, dentato-rubro-palido-Luysiana atrofija i miotonična distrofija, kao i spongiformne encefalopatije kao što je nasljedna Creutzfeldt-Jakobova bolest (zbog nedostatka obrade prionskih proteina), Fabrijeva bolest, Gerstmann-Sträussler-Scheinker-ov sindrom, KOPB, sindrom suhog oka ili Sjögrenova bolest.
18. Spoj ili pripravak za upotrebu prema zahtjevu 17, naznačen time da je bolest cistična fibroza, nasljedni emfizem, KOPB ili bolest suhog oka.
19. Spoj ili pripravak za upotrebu prema zahtjevu 18, naznačen time da je bolest cistična fibroza.
20. N-(5-hidroksi-2,4-diterc-butil-fenil)-4-okso-1H-kinolin-3-karboksamid ili njegova farmaceutski prihvatljiva sol za liječenje ili ublažavanje ozbiljnosti bolesti kod pacijenta, naznačen time da je bolest odabrana od cistične fibroze, nasljednog emfizema, nasljedne hemokromatoze, fibrinolize (koagulacija), kao što je nedostatak proteina C, tipa 1 nasljednog angioedema, nedostatak procesnih lipida, kao što je obiteljska hiperkolesterolemija, Tip 1 hilomikronemija, abetalipoproteinemija, bolest pohrane lizozoma, kao što je bolest I-stanica/pseudo-Hurler, mukopolisaharidoza, Sandhof/Tay-Sachs, Crigler-Najjar tip II, poliendokrinopatija/hiperinzulinemija, dijabetes melitus, Laronov sindrom patuljastog rasta, nedostatak mijeloperoksidaze, primarni hipoparatiroidizam, melanom, glikanoza CDG tip 1, kogenitalni hipertiroidizam, osteogeneza imperfekta, nasljedna hipofibrinogenemija, nedostatak ACT, dijabetes insipidus (DI), neurohipofizealni DI, nefrogeni DI, Charcot-Marie-Tooth sindrom, Pelizaeus-Merzbacherova bolest, neurodegenerativne bolesti kao što su Alzheimerova bolest, Parkinsonova bolest, amiotrofna lateralna skleroza, progresivna supranuklearna paraliza, Pickova bolest, nekoliko poliglutaminskih neuroloških poremećaja kao što su Huntingtonov poremećaj, spinocerebralna ataksija tip I, kičmena ili bulbarna mišićna atrofija, dentato-rubro-palido-Luysiana atrofija i miotonična distrofija, kao i spongiformne encefalopatije kao što je nasljedna Creutzfeldt-Jakobova bolest (zbog nedostatka obrade prionskih proteina), Fabrijeva bolest, Gerstmann-Sträussler-Scheinker-ov sindrom, KOPB, sindrom suhog oka ili Sjögrenova bolest.
21. N-(5-hidroksi-2,4-diterc-butil-fenil)-4-okso-1H-kinolin-3-karboksamid ili njegova farmaceutski prihvatljiva sol za upotrebu prema zahtjevu 20, naznačen time da je bolest odabrana od nasljednog emfizema, KOPB ili sindroma suhog oka.
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