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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- 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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- 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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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| CN107428792B (zh) * | 2014-12-15 | 2023-01-24 | 埃默里大学 | 用于治疗乙型肝炎病毒的磷酰胺 |
| AU2019207626B2 (en) | 2018-01-10 | 2023-10-05 | Nucorion Pharmaceuticals, Inc. | Phosphor(n)amidatacetal and phosph(on)atalcetal compounds |
| WO2019200340A1 (en) | 2018-04-12 | 2019-10-17 | Modis Therapeutics Inc. | Prodrugs of deoxynucleosides for treatment of diseases cased by unbalanced nucleotide pools |
| JP7496132B2 (ja) * | 2018-08-31 | 2024-06-06 | 国立大学法人 鹿児島大学 | 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 |
| MX2022000573A (es) | 2019-07-17 | 2022-02-10 | Nucorion Pharmaceuticals Inc | Compuestos ciclicos de desoxirribonucleotido. |
| 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 |
| WO2021202907A2 (en) * | 2020-04-02 | 2021-10-07 | 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 |
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| 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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| 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 |
| EP1827460A4 (en) | 2004-12-09 | 2012-03-14 | Univ Minnesota | NUCLEOSIDE WITH ANTIVIRAL AND ANTI-CANCER EFFECT |
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| WO2007056596A2 (en) | 2005-11-09 | 2007-05-18 | Wayne State University | Phosphoramidate derivatives of fau |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| AR071395A1 (es) | 2008-04-23 | 2010-06-16 | Gilead Sciences Inc | Analogos carba-nucleosidos 1'-sustituidos para tratamiento antiviral |
| JP2013527145A (ja) | 2010-03-31 | 2013-06-27 | ギリード・ファーマセット・エルエルシー | リン含有活性化剤の立体選択的合成 |
| CA2810928A1 (en) | 2010-09-22 | 2012-03-29 | Alios Biopharma, Inc. | Substituted nucleotide analogs |
| US20120142627A1 (en) | 2010-12-06 | 2012-06-07 | Emory University | Monophosphate prodrugs of dapd and analogs thereof |
| CN103987712B (zh) | 2011-07-19 | 2016-05-04 | 河南美泰宝生物制药有限公司 | 2’，3’-二脱氧-2’-α-氟-2’-β-C-甲基核苷和其前药 |
| US9809616B2 (en) * | 2012-10-29 | 2017-11-07 | Emory University | Pyrimidine nucleosides and their monophosphate prodrugs for the treatment of viral infections and cancer |
| US20140140951A1 (en) | 2012-11-14 | 2014-05-22 | Idenix Pharmaceuticals, Inc. | D-Alanine Ester of Rp-Nucleoside Analog |
| WO2014160484A1 (en) | 2013-03-13 | 2014-10-02 | Idenix Pharmaceuticals, Inc. | Amino acid phosphoramidate pronucleotides of 2'-cyano, azido and amino nucleosides for the treatment of hcv |
| CN105705511A (zh) | 2013-04-12 | 2016-06-22 | 艾其林医药公司 | 用于治疗hcv的氘化核苷前药 |
| CN107428792B (zh) * | 2014-12-15 | 2023-01-24 | 埃默里大学 | 用于治疗乙型肝炎病毒的磷酰胺 |
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