JP2008526713A5 - - Google Patents
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- Publication number
- JP2008526713A5 JP2008526713A5 JP2007548823A JP2007548823A JP2008526713A5 JP 2008526713 A5 JP2008526713 A5 JP 2008526713A5 JP 2007548823 A JP2007548823 A JP 2007548823A JP 2007548823 A JP2007548823 A JP 2007548823A JP 2008526713 A5 JP2008526713 A5 JP 2008526713A5
- Authority
- JP
- Japan
- Prior art keywords
- dideoxy
- hiv
- cytidine
- use according
- mutation
- 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.)
- Granted
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- 230000035772 mutation Effects 0.000 claims description 130
- -1 nucleotide analogue phosphates Chemical class 0.000 claims description 95
- 150000001875 compounds Chemical class 0.000 claims description 88
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 84
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 claims description 72
- 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 63
- 229960002555 zidovudine Drugs 0.000 claims description 59
- 229940002612 prodrug Drugs 0.000 claims description 54
- 239000000651 prodrug Substances 0.000 claims description 54
- 108020004414 DNA Proteins 0.000 claims description 52
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- 235000011180 diphosphates Nutrition 0.000 claims description 36
- 239000002773 nucleotide Substances 0.000 claims description 36
- 125000003729 nucleotide group Chemical group 0.000 claims description 36
- 230000007246 mechanism Effects 0.000 claims description 35
- 229960004748 abacavir Drugs 0.000 claims description 33
- 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 32
- 238000004519 manufacturing process Methods 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 31
- 230000005764 inhibitory process Effects 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 25
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- 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 description 22
- 238000011282 treatment Methods 0.000 claims description 22
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- 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 19
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 claims description 18
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims description 18
- 102220500387 Neutral and basic amino acid transport protein rBAT_M41Y_mutation Human genes 0.000 claims description 18
- 229960004556 tenofovir Drugs 0.000 claims description 18
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 claims description 17
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- 229960001627 lamivudine Drugs 0.000 claims description 12
- 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 description 12
- 150000004712 monophosphates Chemical class 0.000 claims description 11
- 239000010452 phosphate Substances 0.000 claims description 11
- PFJBDCNEHIXTLU-VPCXQMTMSA-N 4-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@@]1(CO)[C@H](O)[C@H](O)[C@@H](CO)O1 PFJBDCNEHIXTLU-VPCXQMTMSA-N 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 238000001727 in vivo Methods 0.000 claims description 9
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- 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 8
- 239000004303 calcium sorbate Substances 0.000 claims description 8
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 8
- 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 7
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- UXCAQJAQSWSNPQ-XLPZGREQSA-N Alovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](F)C1 UXCAQJAQSWSNPQ-XLPZGREQSA-N 0.000 claims description 6
- 229960001997 adefovir Drugs 0.000 claims description 6
- 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 description 6
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- 108010078851 HIV Reverse Transcriptase Proteins 0.000 claims description 5
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- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000003580 L-valyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(C([H])([H])[H])(C([H])([H])[H])[H] 0.000 claims description 4
- 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 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
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- WZGBNAXNHRMYLG-ZXFLCMHBSA-N 4-amino-1-[(2r,4r,5s)-4,5-bis(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](CO)C1 WZGBNAXNHRMYLG-ZXFLCMHBSA-N 0.000 claims description 3
- RLAHNGKRJJEIJL-RFZPGFLSSA-N [(2r,4r)-4-(2,6-diaminopurin-9-yl)-1,3-dioxolan-2-yl]methanol Chemical compound C12=NC(N)=NC(N)=C2N=CN1[C@H]1CO[C@@H](CO)O1 RLAHNGKRJJEIJL-RFZPGFLSSA-N 0.000 claims description 3
- ATSMZGDYBPOXMZ-HTQZYQBOSA-N [(2r,4r)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]-1,3-dioxolan-2-yl]methanol Chemical compound C=12N=CN([C@@H]3O[C@H](CO)OC3)C2=NC(N)=NC=1NC1CC1 ATSMZGDYBPOXMZ-HTQZYQBOSA-N 0.000 claims description 3
- 229950004424 alovudine Drugs 0.000 claims description 3
- RYMCFYKJDVMSIR-RNFRBKRXSA-N apricitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1S[C@H](CO)OC1 RYMCFYKJDVMSIR-RNFRBKRXSA-N 0.000 claims description 3
- QDGZDCVAUDNJFG-FXQIFTODSA-N entecavir (anhydrous) Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)C1=C QDGZDCVAUDNJFG-FXQIFTODSA-N 0.000 claims description 3
- LDEKQSIMHVQZJK-CAQYMETFSA-N tenofovir alafenamide Chemical compound O([P@@](=O)(CO[C@H](C)CN1C2=NC=NC(N)=C2N=C1)N[C@@H](C)C(=O)OC(C)C)C1=CC=CC=C1 LDEKQSIMHVQZJK-CAQYMETFSA-N 0.000 claims description 3
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- ARLKCWCREKRROD-POYBYMJQSA-N [[(2s,5r)-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)CC1 ARLKCWCREKRROD-POYBYMJQSA-N 0.000 description 18
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|---|---|---|---|
| US71453604P | 2004-12-30 | 2004-12-30 | |
| US60/714,536 | 2004-12-30 | ||
| EP05100063A EP1679076A1 (en) | 2005-01-06 | 2005-01-06 | Compounds useful in the treatment of HIV |
| EP05100063.6 | 2005-01-06 | ||
| PCT/EP2005/057196 WO2006070004A1 (en) | 2004-12-30 | 2005-12-28 | Compounds useful in the treatment of hiv |
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| JP2008526713A JP2008526713A (ja) | 2008-07-24 |
| JP2008526713A5 true JP2008526713A5 (enExample) | 2009-04-09 |
| JP4887305B2 JP4887305B2 (ja) | 2012-02-29 |
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| EP (1) | EP1679076A1 (enExample) |
| JP (1) | JP4887305B2 (enExample) |
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|---|---|---|---|---|
| EP4119539A1 (en) * | 2015-09-23 | 2023-01-18 | XWPharma Ltd. | Prodrugs of gamma-hydroxybutyric acid, compositions and uses thereof |
| CN115244028A (zh) | 2019-12-20 | 2022-10-25 | 凯瑞康宁生物工程有限公司 | 4-缬氨酰氧基丁酸的合成方法 |
| US11357734B2 (en) | 2020-06-18 | 2022-06-14 | XWPharma Ltd. | Pharmaceutical granulations of water-soluble active pharmaceutical ingredients |
| AU2021292406B2 (en) | 2020-06-18 | 2024-03-14 | XWPharma Ltd. | Controlled release granulations of water-soluble active pharmaceutical ingredients |
| CN116261451A (zh) | 2020-07-24 | 2023-06-13 | 凯瑞康宁生物工程有限公司 | γ-羟基丁酸衍生物的药物组合物和药物动力学 |
| CA3194665A1 (en) | 2020-10-05 | 2022-04-14 | Jia-Ning Xiang | Modified release compositions of a gamma-hydroxybutyric acid derivative |
| CN117098533A (zh) | 2021-03-19 | 2023-11-21 | 凯瑞康宁公司 | γ-羟基丁酸衍生物的组合释放型制剂的药物动力学 |
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| EP0763048A1 (en) * | 1994-05-31 | 1997-03-19 | Medivir Aktiebolag | Post exposure prevention of hiv |
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- 2005-12-28 JP JP2007548823A patent/JP4887305B2/ja not_active Expired - Fee Related
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