CA3029315A1 - Phosphoramidates for the treatment of hepatitis b virus - Google Patents
Phosphoramidates for the treatment of hepatitis b virus Download PDFInfo
- Publication number
- CA3029315A1 CA3029315A1 CA3029315A CA3029315A CA3029315A1 CA 3029315 A1 CA3029315 A1 CA 3029315A1 CA 3029315 A CA3029315 A CA 3029315A CA 3029315 A CA3029315 A CA 3029315A CA 3029315 A1 CA3029315 A1 CA 3029315A1
- Authority
- CA
- Canada
- Prior art keywords
- substituted
- alkyl
- amino
- alkynyl
- alkenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 238000011282 treatment Methods 0.000 title claims abstract description 16
- 241000700721 Hepatitis B virus Species 0.000 title description 34
- 150000008298 phosphoramidates Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 141
- 239000000203 mixture Substances 0.000 claims abstract description 125
- 238000000034 method Methods 0.000 claims abstract description 66
- 239000003443 antiviral agent Substances 0.000 claims abstract description 42
- 229960001997 adefovir Drugs 0.000 claims abstract description 16
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 claims abstract description 16
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229960000980 entecavir Drugs 0.000 claims abstract description 16
- YXPVEXCTPGULBZ-WQYNNSOESA-N entecavir hydrate Chemical compound O.C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)C1=C YXPVEXCTPGULBZ-WQYNNSOESA-N 0.000 claims abstract description 16
- 229960001627 lamivudine Drugs 0.000 claims abstract description 16
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 claims abstract description 16
- 229960005311 telbivudine Drugs 0.000 claims abstract description 16
- IQFYYKKMVGJFEH-CSMHCCOUSA-N telbivudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1O[C@@H](CO)[C@H](O)C1 IQFYYKKMVGJFEH-CSMHCCOUSA-N 0.000 claims abstract description 16
- 229960004556 tenofovir Drugs 0.000 claims abstract description 16
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 claims abstract description 16
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims abstract description 9
- -1 4-substituted phenyl Chemical group 0.000 claims description 236
- 125000000217 alkyl group Chemical group 0.000 claims description 190
- 125000003118 aryl group Chemical group 0.000 claims description 144
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 120
- 229910052739 hydrogen Inorganic materials 0.000 claims description 105
- 125000000304 alkynyl group Chemical group 0.000 claims description 104
- 125000003342 alkenyl group Chemical group 0.000 claims description 100
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 87
- 239000001257 hydrogen Substances 0.000 claims description 86
- 125000003545 alkoxy group Chemical group 0.000 claims description 80
- 125000001072 heteroaryl group Chemical group 0.000 claims description 80
- 229910052805 deuterium Inorganic materials 0.000 claims description 76
- 150000003839 salts Chemical class 0.000 claims description 72
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 69
- 125000002252 acyl group Chemical group 0.000 claims description 67
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 65
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 65
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 59
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 58
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 54
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 53
- 239000002777 nucleoside Substances 0.000 claims description 49
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 44
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 43
- 150000002632 lipids Chemical class 0.000 claims description 43
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 43
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 43
- 241000700605 Viruses Species 0.000 claims description 42
- 125000003107 substituted aryl group Chemical group 0.000 claims description 42
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 39
- 150000003573 thiols Chemical class 0.000 claims description 37
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 35
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 34
- 230000015572 biosynthetic process Effects 0.000 claims description 34
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 34
- 208000015181 infectious disease Diseases 0.000 claims description 34
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 31
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 31
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 30
- 108020004414 DNA Proteins 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 239000003112 inhibitor Substances 0.000 claims description 25
- 125000001153 fluoro group Chemical group F* 0.000 claims description 24
- 125000005843 halogen group Chemical group 0.000 claims description 24
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 24
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 23
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 23
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 23
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 23
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 23
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 22
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 22
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 22
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 229940123066 Polymerase inhibitor Drugs 0.000 claims description 18
- 210000004185 liver Anatomy 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- XQSPYNMVSIKCOC-NTSWFWBYSA-N Emtricitabine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1 XQSPYNMVSIKCOC-NTSWFWBYSA-N 0.000 claims description 14
- 208000036142 Viral infection Diseases 0.000 claims description 14
- 230000009385 viral infection Effects 0.000 claims description 14
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 claims description 14
- WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine Chemical compound CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 claims description 12
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 claims description 12
- NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 claims description 12
- 239000000427 antigen Substances 0.000 claims description 11
- 102000036639 antigens Human genes 0.000 claims description 11
- 108091007433 antigens Proteins 0.000 claims description 11
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 229960004150 aciclovir Drugs 0.000 claims description 10
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 10
- ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 claims description 10
- 108091033409 CRISPR Proteins 0.000 claims description 8
- 238000010362 genome editing Methods 0.000 claims description 8
- 230000008685 targeting Effects 0.000 claims description 8
- YLDCUKJMEKGGFI-QCSRICIXSA-N 4-acetamidobenzoic acid;9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one;1-(dimethylamino)propan-2-ol Chemical compound CC(O)CN(C)C.CC(O)CN(C)C.CC(O)CN(C)C.CC(=O)NC1=CC=C(C(O)=O)C=C1.CC(=O)NC1=CC=C(C(O)=O)C=C1.CC(=O)NC1=CC=C(C(O)=O)C=C1.O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(NC=NC2=O)=C2N=C1 YLDCUKJMEKGGFI-QCSRICIXSA-N 0.000 claims description 7
- VWFCHDSQECPREK-LURJTMIESA-N Cidofovir Chemical compound NC=1C=CN(C[C@@H](CO)OCP(O)(O)=O)C(=O)N=1 VWFCHDSQECPREK-LURJTMIESA-N 0.000 claims description 7
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 claims description 7
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims description 7
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 claims description 7
- 229930010555 Inosine Natural products 0.000 claims description 7
- JNTOCHDNEULJHD-UHFFFAOYSA-N Penciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(CCC(CO)CO)C=N2 JNTOCHDNEULJHD-UHFFFAOYSA-N 0.000 claims description 7
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 7
- XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 claims description 7
- HDOVUKNUBWVHOX-QMMMGPOBSA-N Valacyclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCOC(=O)[C@@H](N)C(C)C)C=N2 HDOVUKNUBWVHOX-QMMMGPOBSA-N 0.000 claims description 7
- WPVFJKSGQUFQAP-GKAPJAKFSA-N Valcyte Chemical compound N1C(N)=NC(=O)C2=C1N(COC(CO)COC(=O)[C@@H](N)C(C)C)C=N2 WPVFJKSGQUFQAP-GKAPJAKFSA-N 0.000 claims description 7
- OIRDTQYFTABQOQ-UHTZMRCNSA-N Vidarabine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O OIRDTQYFTABQOQ-UHTZMRCNSA-N 0.000 claims description 7
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 claims description 7
- GLWHPRRGGYLLRV-XLPZGREQSA-N [[(2s,3s,5r)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](N=[N+]=[N-])C1 GLWHPRRGGYLLRV-XLPZGREQSA-N 0.000 claims description 7
- 229960004748 abacavir Drugs 0.000 claims description 7
- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 claims description 7
- 229940068561 atripla Drugs 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
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- XACKNLSZYYIACO-DJLDLDEBSA-N edoxudine Chemical compound O=C1NC(=O)C(CC)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XACKNLSZYYIACO-DJLDLDEBSA-N 0.000 claims description 7
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- 229960004396 famciclovir Drugs 0.000 claims description 7
- GGXKWVWZWMLJEH-UHFFFAOYSA-N famcyclovir Chemical compound N1=C(N)N=C2N(CCC(COC(=O)C)COC(C)=O)C=NC2=C1 GGXKWVWZWMLJEH-UHFFFAOYSA-N 0.000 claims description 7
- 229960002963 ganciclovir Drugs 0.000 claims description 7
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 claims description 7
- WEVJJMPVVFNAHZ-RRKCRQDMSA-N ibacitabine Chemical compound C1=C(I)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 WEVJJMPVVFNAHZ-RRKCRQDMSA-N 0.000 claims description 7
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- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 7
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- SGOIRFVFHAKUTI-ZCFIWIBFSA-N tenofovir (anhydrous) Chemical compound N1=CN=C2N(C[C@@H](C)OCP(O)(O)=O)C=NC2=C1N SGOIRFVFHAKUTI-ZCFIWIBFSA-N 0.000 claims description 7
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- 229940111527 trizivir Drugs 0.000 claims description 7
- 229940008349 truvada Drugs 0.000 claims description 7
- 229940093257 valacyclovir Drugs 0.000 claims description 7
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- DLGSOJOOYHWROO-WQLSENKSSA-N [(z)-(1-methyl-2-oxoindol-3-ylidene)amino]thiourea Chemical compound C1=CC=C2N(C)C(=O)\C(=N/NC(N)=S)C2=C1 DLGSOJOOYHWROO-WQLSENKSSA-N 0.000 claims description 6
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- 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
- A61K31/7068—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 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—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 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
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- 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
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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- 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
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- Biochemistry (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Dispersion Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| Application Number | Priority Date | Filing Date | Title |
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| US201662354471P | 2016-06-24 | 2016-06-24 | |
| US62/354,471 | 2016-06-24 | ||
| PCT/US2017/038963 WO2017223421A1 (en) | 2016-06-24 | 2017-06-23 | Phosphoramidates for the treatment of hepatitis b virus |
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| WO2016099982A2 (en) * | 2014-12-15 | 2016-06-23 | Emory University | Phosphoramidates for the treatment of hepatitis b virus |
| MX2020007393A (es) | 2018-01-10 | 2020-11-24 | Nucorion Pharmaceuticals Inc | Compuestos de fósforo(n)amidatacetal y fosf(on)atalcetal. |
| WO2019200340A1 (en) | 2018-04-12 | 2019-10-17 | Modis Therapeutics Inc. | Prodrugs of deoxynucleosides for treatment of diseases cased by unbalanced nucleotide pools |
| WO2020045628A1 (ja) * | 2018-08-31 | 2020-03-05 | ダイキン工業株式会社 | 核酸アナログ及び抗ｂ型肝炎ウイルス剤 |
| US11166976B2 (en) | 2018-11-08 | 2021-11-09 | Aligos Therapeutics, Inc. | S-antigen transport inhibiting oligonucleotide polymers and methods |
| CN113166190B (zh) * | 2018-11-23 | 2023-05-23 | 正大天晴药业集团股份有限公司 | 低聚核苷酸及前体药物 |
| AU2020315394A1 (en) | 2019-07-17 | 2022-02-17 | Nucorion Pharmaceuticals, Inc. | Cyclic deoxyribonucleotide compounds |
| CN110642910B (zh) * | 2019-09-02 | 2020-10-30 | 南开大学 | 胸苷衍生物及其制备方法和用途 |
| EP4037706A4 (en) * | 2019-10-02 | 2023-09-13 | University of Washington | Compositions and methods for treatment of hepatitis b virus infection |
| 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 |
| US20230183282A1 (en) * | 2020-04-02 | 2023-06-15 | The Regents Of The University Of Michigan | Remdesivir and remdesivir analogs, solutions, and nanoparticle, liposomal, and microparticle compositions for treating viral infections |
| CN113493481B (zh) * | 2020-04-08 | 2025-02-18 | 北京君科华元医药科技有限公司 | 单磷酸恩替卡韦丙氨酰胺酚酯及其医药用途 |
| 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 |
| WO2022251594A1 (en) * | 2021-05-27 | 2022-12-01 | Antios Therapeutics, Inc. | Pharmacokinetics and dose-related improvments in subjects treated with phosphoramidate clevudine prodrugs |
| WO2022256490A2 (en) * | 2021-06-03 | 2022-12-08 | Antios Therapeutics, Inc. | Improved synthesis of phosphoramidates for the treatment of hepatitis b virus |
| CN113501853B (zh) * | 2021-09-13 | 2021-12-07 | 南京颐媛生物医学研究院有限公司 | 4-硫代尿嘧啶脱氧核苷磷酸酯及其抗病毒药物用途 |
| US20250092401A1 (en) * | 2022-01-28 | 2025-03-20 | Glaxosmithkline Intellectual Property Development Limited | Combination therapy for treating hepatitis b virus infections |
| CN115260263B (zh) * | 2022-05-23 | 2025-02-21 | 浙江扬厉医药技术有限公司 | 烷基硫芳基克拉夫定磷酰胺类化合物及其应用 |
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| US3687931A (en) | 1970-03-19 | 1972-08-29 | Syntex Corp | Halogenated purine and pyrimidine nucleosides and process therefor |
| US5587362A (en) | 1994-01-28 | 1996-12-24 | Univ. Of Ga Research Foundation | L-nucleosides |
| US7462605B2 (en) | 1998-01-23 | 2008-12-09 | Celmed Oncology (Usa), Inc. | Phosphoramidate compounds and methods of use |
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| US20040229839A1 (en) | 2003-05-14 | 2004-11-18 | Biocryst Pharmaceuticals, Inc. | Substituted nucleosides, preparation thereof and use as inhibitors of RNA viral polymerases |
| GB0317009D0 (en) | 2003-07-21 | 2003-08-27 | Univ Cardiff | Chemical compounds |
| JP2008523082A (ja) | 2004-12-09 | 2008-07-03 | リージェンツ オブ ザ ユニバーシティ オブ ミネソタ | 抗菌活性および抗癌活性を有するヌクレオチド |
| CA2609343C (en) | 2005-06-07 | 2015-03-31 | Yale University | Methods of treating cancer and other conditions or disease states using lfmau and ldt |
| US7888330B2 (en) | 2005-11-09 | 2011-02-15 | Wayne State University | Phosphoramidate derivatives of FAU |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| HUE038946T2 (hu) | 2008-04-23 | 2018-12-28 | Gilead Sciences Inc | 1'-szubsztituált carba-nukleozid analógok antivirális kezelésre |
| SMT201700412T1 (it) | 2010-03-31 | 2017-11-15 | Gilead Pharmasset Llc | Procedimento per la cristallizzazione di (s)-isopropil 2-(((s)-(perfluorofenossi)(fenossi)fosforil)ammino)propanoato |
| EA025341B1 (ru) | 2010-09-22 | 2016-12-30 | Алиос Биофарма, Инк. | Замещенные аналоги нуклеотидов |
| WO2012078416A2 (en) | 2010-12-06 | 2012-06-14 | Rfs Pharma, Llc | Monophosphate prodrugs of dapd and analogs thereof |
| EP2734535A4 (en) | 2011-07-19 | 2014-10-22 | Nanjing Molecular Res Inc | 2 ', 3'-DIDEOXY-2'-ALPHA-FLUOR-2'-BETA-C-METHYL NUCLEOSIDE AND PRODRUGS THEREOF |
| EP2912050A4 (en) | 2012-10-29 | 2016-09-28 | Cocrystal Pharma Inc | PYRIMIDIN NUCLEOTIDES AND THEIR MONOPHOSPHATE PRODRUGS FOR THE TREATMENT OF VIRAL INFECTIONS AND CANCER |
| EP2920195A1 (en) | 2012-11-14 | 2015-09-23 | IDENIX Pharmaceuticals, Inc. | D-alanine ester of rp-nucleoside analog |
| US20140271547A1 (en) | 2013-03-13 | 2014-09-18 | Idenix Pharmaceuticals, Inc. | Amino acid phosphoramidate pronucleotides of 2'-cyano, azido and amino nucleosides for the treatment of hcv |
| CA2909270A1 (en) | 2013-04-12 | 2014-10-16 | Achillion Pharmaceuticals, Inc. | Highly active nucleoside derivative for the treatment of hcv |
| WO2016099982A2 (en) * | 2014-12-15 | 2016-06-23 | Emory University | Phosphoramidates for the treatment of hepatitis b virus |
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2017
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- 2017-06-23 SG SG11201811316YA patent/SG11201811316YA/en unknown
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2018
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2019
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| SG11201811316YA (en) | 2019-01-30 |
| KR20190057277A (ko) | 2019-05-28 |
| JP2019525905A (ja) | 2019-09-12 |
| IL263859B2 (en) | 2023-07-01 |
| BR112018076913A2 (pt) | 2019-04-02 |
| IL263859B1 (en) | 2023-03-01 |
| CN109689065A (zh) | 2019-04-26 |
| EP3474863A1 (en) | 2019-05-01 |
| US20190350954A1 (en) | 2019-11-21 |
| EP3474863A4 (en) | 2020-03-25 |
| AU2017281531A1 (en) | 2019-01-17 |
| PH12018550207A1 (en) | 2019-04-15 |
| US11364257B2 (en) | 2022-06-21 |
| JP2022116024A (ja) | 2022-08-09 |
| WO2017223421A1 (en) | 2017-12-28 |
| IL263859A (en) | 2019-01-31 |
| US20220280542A1 (en) | 2022-09-08 |
| ZA201900156B (en) | 2019-08-28 |
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