HRP20220278T1 - 2'-supstituirani-n6-supstituirani purinski nukleotidi za liječenje bolesti izazvanih rnk virusima - Google Patents
2'-supstituirani-n6-supstituirani purinski nukleotidi za liječenje bolesti izazvanih rnk virusima Download PDFInfo
- Publication number
- HRP20220278T1 HRP20220278T1 HRP20220278TT HRP20220278T HRP20220278T1 HR P20220278 T1 HRP20220278 T1 HR P20220278T1 HR P20220278T T HRP20220278T T HR P20220278TT HR P20220278 T HRP20220278 T HR P20220278T HR P20220278 T1 HRP20220278 T1 HR P20220278T1
- Authority
- HR
- Croatia
- Prior art keywords
- compound
- use according
- virus
- hydrogen
- aryl
- Prior art date
Links
- 241000700605 Viruses Species 0.000 title claims 10
- 239000002213 purine nucleotide Substances 0.000 title 1
- 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 34
- 229910052739 hydrogen Inorganic materials 0.000 claims 13
- 239000001257 hydrogen Substances 0.000 claims 13
- 125000003118 aryl group Chemical group 0.000 claims 9
- 125000000217 alkyl group Chemical group 0.000 claims 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 7
- -1 [image] Substances 0.000 claims 7
- 150000003839 salts Chemical class 0.000 claims 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims 6
- 125000001072 heteroaryl group Chemical group 0.000 claims 6
- 150000002431 hydrogen Chemical class 0.000 claims 4
- 239000002552 dosage form Substances 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 2
- 241000725619 Dengue virus Species 0.000 claims 2
- 241000710886 West Nile virus Species 0.000 claims 2
- 241000710772 Yellow fever virus Species 0.000 claims 2
- 241000907316 Zika virus Species 0.000 claims 2
- 125000002252 acyl group Chemical group 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 239000007909 solid dosage form Substances 0.000 claims 2
- 229940051021 yellow-fever virus Drugs 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 1
- 206010014596 Encephalitis Japanese B Diseases 0.000 claims 1
- 241000710781 Flaviviridae Species 0.000 claims 1
- 241000710831 Flavivirus Species 0.000 claims 1
- 201000005807 Japanese encephalitis Diseases 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims 1
- 235000001014 amino acid Nutrition 0.000 claims 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 1
- 239000002775 capsule Substances 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 239000001177 diphosphate Substances 0.000 claims 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims 1
- 235000011180 diphosphates Nutrition 0.000 claims 1
- 241001493065 dsRNA viruses Species 0.000 claims 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 239000001226 triphosphate Substances 0.000 claims 1
- 235000011178 triphosphate Nutrition 0.000 claims 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims 1
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
- C07H19/207—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine adenine dinucleotide or nicotinamide-adenine dinucleotide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H23/00—Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12
-
- 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 (24)
1. Spoj formule IIIe za uporabu u liječenju domaćina kojem je to potrebno inficiranog RNK virusom različitim od HCV:
[image]
ili njegova farmaceutski prihvatljiva sol;
naznačen time, što:
Y je NR1R2;
R1 je metil;
R2 je vodik;
R3 je vodik,
[image]
,
difosfat, trifosfat, aminokiselina vezana preko karbonilne grupe, ili -C(O)R3C;
R3A je odabran od O-, OH, -O-arila, -O-heteroarila i heterociklila;
R3B je odabran od O-, OH, N-vezane aminokiseline i N-vezanog estera aminokiseline;
R3C je alkil, alkenil, alkinil, -(C0-C2)(cikloalkil), -(C0-C2)(heterociklo), -(C0-C2)(aril), -(C0-C2)(heteroaril), -O-alkil, -O-alkenil, -O-alkinil, -O-(C0-C2)(cikloalkil), -O-(C0-C2)(heterociklo), -O-(C0-C2)(aril), -O-(C0-C2)(heteroaril), -S-alkil, -S-alkenil, -S-alkinil, -S-(C0-C2)(cikloalkil), -S-(C0-C2)(heterociklo), -S-(C0-C2)(aril), ili -S-(C0-C2)(heteroaril);
R7 je vodik, C1-6alkil, C3-7cikloalkil, heteroaril, heterociklil, ili aril;
R8 je vodik ili C1-6alkil;
R9a i R9b su neovisno odabrani od vodika, C1-6alkila, cikloalkila, -(CH2)c(NR9’)2, C1-6hidroksialkila, -CH2SH, -(CH2)2S(O)Me, -(CH2)3NHC(=NH)NH2, (1H-indol-3-il)metila, (1H-imidazol-4-il)metila, -(CH2)cCOR9", arila i aril(C1-3alkil)-;
R9’ je neovisno vodik ili C1-6 alkil;
R9" je -OR11 ili -N(R11’)2;
R10 je vodik, C1-6alkil, C1-6haloalkil, C3-7cikloalkil, heterocikloalkil, aminoacil, aril, heteroaril, aril, ili heteroaril;
R11 je C1-6alkil, cikloalkil, C2-6alkinil, C2-6alkenil, ili acil;
R11’ je vodik, C1-6alkil, cikloalkil, C2-6alkinil, C2-6alkenil, ili acil; i
c je 1 do 6;
pri čemu je virus iz obitelji Flaviviridae.
2. Spoj za uporabu prema patentnom zahtjevu 1,
naznačen time, što
R7 je aril;
R8 je vodik;
R9a i R9b su neovisno odabrani od metil grupe i vodika; i
R10 je alkil.
3. Spoj za uporabu prema patentnom zahtjevu 2,
naznačen time, što
R7 je fenil;
R8 je vodik;
R9a i R9b su neovisno odabrani od metil grupe i vodika; i
R10 je izopropil.
4. Spoj za uporabu prema patentnom zahtjevu 3, naznačen time, što je R3 vodik.
5. Spoj za uporabu prema patentnom zahtjevu 1, naznačen time, što je spoj odabran od:
[image]
ili njegova farmaceutski prihvatljiva sol.
6. Spoj za uporabu prema patentnom zahtjevu 1,
naznačen time, što je
aminokiselina fosforamidata u L-konfiguraciji.
7. Spoj za uporabu prema patentnom zahtjevu 5, naznačen time, što je spoj odabran od
[image]
ili njegova farmaceutski prihvatljiva sol.
8. Spoj za uporabu prema patentnom zahtjevu 5, naznačen time, što je spoj odabran od
[image]
ili njegova farmaceutski prihvatljiva sol.
9. Spoj za uporabu prema patentnom zahtjevu 1, naznačen time, što je spoj odabran od:
[image]
ili njegova farmaceutski prihvatljiva sol.
10. Spoj za uporabu prema patentnom zahtjevu 9, naznačen time, što je spoj odabran od
[image]
ili njegova farmaceutski prihvatljiva sol.
11. Spoj za uporabu prema patentnom zahtjevu 9, naznačen time, što je spoj odabran od
[image]
ili njegova farmaceutski prihvatljiva sol.
12. Spoj za uporabu prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, što je virus iz roda Flavivirus.
13. Spoj za uporabu prema patentnom zahtjevu 12, naznačen time, što je virus odabran od virusa denga groznice, virusa groznice zapadnog Nila, virusa žute groznice i virusa Zika.
14. Spoj za uporabu prema patentnom zahtjevu 13, naznačen time, što virus predstavlja virus denga groznice.
15. Spoj za uporabu prema patentnom zahtjevu 13, naznačen time, što virus predstavlja virus žute groznice.
16. Spoj za uporabu prema patentnom zahtjevu 13, naznačen time, što virus predstavlja virus groznice zapadnog Nila.
17. Spoj za uporabu prema patentnom zahtjevu 13, naznačen time, što virus predstavlja virus Zika.
18. Spoj za uporabu prema patentnom zahtjevu 12, naznačen time, što virus predstavlja virus japanskog B encefalitisa.
19. Spoj za uporabu prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, što je domaćin čovjek.
20. Spoj za uporabu prema bilo kojem od patentnih zahtjeva 1-19, naznačen time, što se spoj primjenjuje u doznom obliku pogodnom za oralnu primjenu.
21. Spoj za uporabu prema patentnom zahtjevu 20, naznačen time, što se spoj primjenjuje u čvrstom doznom obliku.
22. Spoj za uporabu prema patentnom zahtjevu 21, naznačen time, što je čvrsti dozni oblik tableta ili kapsula.
23. Spoj za uporabu prema bilo kojem od patentnih zahtjeva 1-19, naznačen time, što se spoj primjenjuje u doznom obliku pogodnom za intravensku primjenu.
24. Spoj za uporabu prema bilo kojem od patentnih zahtjeva 1-19, naznačen time, što se spoj primjenjuje u doznom obliku pogodnom za parenteralnu primjenu.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662384664P | 2016-09-07 | 2016-09-07 | |
EP17849474.6A EP3512863B1 (en) | 2016-09-07 | 2017-09-06 | 2'-substituted-n6-substituted purine nucleotides for rna virus treatment |
PCT/US2017/050323 WO2018048937A1 (en) | 2016-09-07 | 2017-09-06 | 2'-substituted-n6-substituted purine nucleotides for rna virus treatment |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20220278T1 true HRP20220278T1 (hr) | 2022-05-13 |
Family
ID=61562513
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20220278TT HRP20220278T1 (hr) | 2016-09-07 | 2017-09-06 | 2'-supstituirani-n6-supstituirani purinski nukleotidi za liječenje bolesti izazvanih rnk virusima |
Country Status (23)
Country | Link |
---|---|
US (2) | US10946033B2 (hr) |
EP (3) | EP3865136A1 (hr) |
JP (4) | JP2019526596A (hr) |
KR (3) | KR102456417B1 (hr) |
CN (2) | CN109689672B (hr) |
AU (3) | AU2017324939B2 (hr) |
BR (1) | BR112019004297A2 (hr) |
CA (2) | CA3187650A1 (hr) |
CY (1) | CY1125163T1 (hr) |
DK (1) | DK3512863T3 (hr) |
EA (2) | EA202190602A3 (hr) |
ES (1) | ES2907874T3 (hr) |
HR (1) | HRP20220278T1 (hr) |
HU (1) | HUE057743T2 (hr) |
LT (1) | LT3512863T (hr) |
MY (1) | MY197236A (hr) |
PL (1) | PL3512863T3 (hr) |
PT (1) | PT3512863T (hr) |
RS (1) | RS62943B1 (hr) |
SG (1) | SG11201901457TA (hr) |
SI (1) | SI3512863T1 (hr) |
WO (1) | WO2018048937A1 (hr) |
ZA (1) | ZA201901061B (hr) |
Families Citing this family (9)
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AU2016229966B2 (en) * | 2015-03-06 | 2018-09-27 | Atea Pharmaceuticals, Inc. | Beta-D-2'-deoxy-2'alpha-fluoro-2'-beta-C-substituted-2-modified-N6-substituted purine nucleotides for HCV treatment |
CN110248951B (zh) | 2017-02-01 | 2022-10-28 | 阿堤亚制药公司 | 用于治疗丙型肝炎病毒的核苷酸半硫酸盐 |
KR20200140865A (ko) | 2018-04-10 | 2020-12-16 | 아테아 파마슈티컬즈, 인크. | 간경변증을 갖는 hcv 감염 환자의 치료 |
CN111087421B (zh) * | 2019-12-24 | 2022-10-18 | 南京正大天晴制药有限公司 | 一种用于手性药物合成的磷酰胺化合物的制备方法 |
US10874687B1 (en) | 2020-02-27 | 2020-12-29 | Atea Pharmaceuticals, Inc. | Highly active compounds against COVID-19 |
WO2021173713A1 (en) | 2020-02-27 | 2021-09-02 | Atea Pharmaceuticals, Inc. | Highly active compounds against covid-19 |
WO2021253376A1 (zh) * | 2020-06-19 | 2021-12-23 | 南京正大天晴制药有限公司 | 一种用于手性药物合成的磷酰胺化合物的制备方法 |
EP4225282A1 (en) * | 2020-10-09 | 2023-08-16 | ATEA Pharmaceuticals, Inc. | Niran interfering drugs for sars-cov-2 mutant therapy |
WO2023034617A1 (en) * | 2021-09-03 | 2023-03-09 | Atea Pharmaceuticals, Inc. | 2'-chloro-2'-fluoro-n2-amino-n6-methylamino purine nucleotides for flavivirus treatment |
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