AU2003299492B2 - Cyclic prodrugs of PMEA one of its analogues - Google Patents
Cyclic prodrugs of PMEA one of its analogues Download PDFInfo
- Publication number
- AU2003299492B2 AU2003299492B2 AU2003299492A AU2003299492A AU2003299492B2 AU 2003299492 B2 AU2003299492 B2 AU 2003299492B2 AU 2003299492 A AU2003299492 A AU 2003299492A AU 2003299492 A AU2003299492 A AU 2003299492A AU 2003299492 B2 AU2003299492 B2 AU 2003299492B2
- Authority
- AU
- Australia
- Prior art keywords
- compound
- pmea
- liver
- pharmaceutically acceptable
- acid
- 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.)
- Ceased
Links
- 239000000651 prodrug Substances 0.000 title description 187
- 229940002612 prodrug Drugs 0.000 title description 187
- 125000004122 cyclic group Chemical group 0.000 title description 34
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- 150000001875 compounds Chemical class 0.000 claims description 221
- 210000004185 liver Anatomy 0.000 claims description 99
- 239000003814 drug Substances 0.000 claims description 96
- 238000000034 method Methods 0.000 claims description 85
- -1 AM365 Chemical compound 0.000 claims description 64
- 150000003839 salts Chemical class 0.000 claims description 46
- 229930024421 Adenine Natural products 0.000 claims description 41
- 229960000643 adenine Drugs 0.000 claims description 41
- 239000003795 chemical substances by application Substances 0.000 claims description 34
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 32
- 238000002360 preparation method Methods 0.000 claims description 29
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 27
- 239000003443 antiviral agent Substances 0.000 claims description 24
- 230000001965 increasing effect Effects 0.000 claims description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 19
- ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 17
- 230000000174 oncolytic effect Effects 0.000 claims description 17
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- 125000000217 alkyl group Chemical group 0.000 claims description 16
- IVSXFFJGASXYCL-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=NC=N[C]21 IVSXFFJGASXYCL-UHFFFAOYSA-N 0.000 claims description 16
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- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 11
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- HSBKFSPNDWWPSL-VDTYLAMSSA-N 4-amino-5-fluoro-1-[(2s,5r)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]pyrimidin-2-one Chemical compound C1=C(F)C(N)=NC(=O)N1[C@@H]1C=C[C@H](CO)O1 HSBKFSPNDWWPSL-VDTYLAMSSA-N 0.000 claims description 9
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- GBBJCSTXCAQSSJ-XQXXSGGOSA-N clevudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1[C@H](F)[C@@H](O)[C@H](CO)O1 GBBJCSTXCAQSSJ-XQXXSGGOSA-N 0.000 claims description 9
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- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- CKTSBUTUHBMZGZ-CHKWXVPMSA-N 4-amino-1-[(2s,4r,5s)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)[C@H](O)C1 CKTSBUTUHBMZGZ-CHKWXVPMSA-N 0.000 claims description 8
- 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 8
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- 231100001274 therapeutic index Toxicity 0.000 claims description 8
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 7
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 claims description 7
- 208000002672 hepatitis B Diseases 0.000 claims description 7
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 claims description 7
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
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- 229960005277 gemcitabine Drugs 0.000 claims description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 6
- GWFOVSGRNGAGDL-FSDSQADBSA-N 2-amino-9-[(1r,2r,3s)-2,3-bis(hydroxymethyl)cyclobutyl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1C[C@H](CO)[C@H]1CO GWFOVSGRNGAGDL-FSDSQADBSA-N 0.000 claims description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 5
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 5
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 5
- 229960004316 cisplatin Drugs 0.000 claims description 5
- 229960004679 doxorubicin Drugs 0.000 claims description 5
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 5
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 5
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 5
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- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 4
- 108010092160 Dactinomycin Proteins 0.000 claims description 4
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims description 4
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- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 3
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- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 3
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- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
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- 229940083466 soybean lecithin Drugs 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
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- 229940032147 starch Drugs 0.000 description 1
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- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
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- 238000013269 sustained drug release Methods 0.000 description 1
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- 239000012730 sustained-release form Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
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- 229920002258 tannic acid Polymers 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
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- 238000012360 testing method Methods 0.000 description 1
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- GFFXZLZWLOBBLO-ASKVSEFXSA-N tezacitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(=C/F)/[C@H](O)[C@@H](CO)O1 GFFXZLZWLOBBLO-ASKVSEFXSA-N 0.000 description 1
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- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 230000007723 transport mechanism Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- QHUNJMXHQHHWQP-UHFFFAOYSA-N trimethylsilyl acetate Chemical compound CC(=O)O[Si](C)(C)C QHUNJMXHQHHWQP-UHFFFAOYSA-N 0.000 description 1
- JSPLKZUTYZBBKA-UHFFFAOYSA-N trioxidane Chemical compound OOO JSPLKZUTYZBBKA-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
- C07F9/6574—Esters of oxyacids of phosphorus
- C07F9/65742—Esters of oxyacids of phosphorus non-condensed with carbocyclic rings or heterocyclic rings or ring systems
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
-
- 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
-
- 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
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Biochemistry (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
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| US38054502P | 2002-05-13 | 2002-05-13 | |
| US60/380,545 | 2002-05-13 | ||
| PCT/US2003/014821 WO2004037161A2 (en) | 2002-05-13 | 2003-05-12 | Cyclic prodrugs of pmea one of its analogues |
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| AU2003299492A1 AU2003299492A1 (en) | 2004-05-13 |
| AU2003299492B2 true AU2003299492B2 (en) | 2010-06-10 |
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| JP (1) | JP4476811B2 (https=) |
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| CA (1) | CA2485702C (https=) |
| IL (2) | IL164809A0 (https=) |
| NZ (1) | NZ536328A (https=) |
| TW (1) | TWI347325B (https=) |
| WO (1) | WO2004037161A2 (https=) |
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| AU2003235501A1 (en) * | 2002-05-13 | 2003-11-11 | Metabasis Therapeutics, Inc. | PMEA and PMPA cyclic producing synthesis |
| JP5046219B2 (ja) * | 2002-10-31 | 2012-10-10 | リガンド・ファーマシューティカルズ・インコーポレイテッド | １，３−プロパン−１−アリールジオールの新規環状リン酸ジエステルおよびそのプロドラッグへの使用 |
| EP1732569B1 (en) * | 2004-01-21 | 2009-10-14 | Gilead Sciences, Inc. | Use of adefovir or tenofovir for inhibiting mmtv-like viruses involved in breast cancer and primary biliary cirrhosis |
| US20050182252A1 (en) * | 2004-02-13 | 2005-08-18 | Reddy K. R. | Novel 2'-C-methyl nucleoside derivatives |
| WO2005123729A1 (en) * | 2004-06-08 | 2005-12-29 | Metabasis Therapeutics, Inc. | Lewis acid mediated synthesis of cyclic esters |
| CN101094677A (zh) * | 2004-11-15 | 2007-12-26 | 塞普泰尔公司 | 蛋白酪氨酸磷酸酶抑制剂及其使用方法 |
| US7737273B2 (en) | 2005-07-26 | 2010-06-15 | Hetero Drugs Limited | Process for acyclic phosphonate nucleotide analogs |
| US20070042501A1 (en) * | 2005-08-20 | 2007-02-22 | Institute Of Nuclear Energy Research | A novel technology for the purity assay of TRODAT-1 raw material |
| EP2020996B1 (en) * | 2006-05-16 | 2011-11-23 | Gilead Sciences, Inc. | Method and compositions for treating hematological malignancies |
| CN101371841A (zh) * | 2007-08-23 | 2009-02-25 | 浙江医药股份有限公司新昌制药厂 | 结晶型恩替卡韦制剂及其制备方法和应用 |
| JP2009196959A (ja) * | 2008-02-25 | 2009-09-03 | Yamaguchi Univ | がん治療用医薬組成物 |
| CN101475594B (zh) * | 2009-02-06 | 2012-05-30 | 廖国超 | 肝靶向抗病毒前体药物环状磷酸酯及其应用 |
| CN101659676B (zh) * | 2009-09-07 | 2012-06-20 | 徐奎 | 一种硫代阿德福韦、替诺福韦肝靶向酯前体药物 |
| WO2011133963A2 (en) * | 2010-04-23 | 2011-10-27 | University Of Southern California | Tyrosine-based prodrugs of antiviral agents |
| US8884027B2 (en) | 2010-10-22 | 2014-11-11 | University Of Rochester | Melampomagnolide B derivatives as antileukemic and cytotoxic agents |
| WO2012062835A1 (en) * | 2010-11-12 | 2012-05-18 | Glaxo Wellcome Manufacturing Pte Ltd | Novel pharmaceutical compositions |
| RU2606845C2 (ru) | 2010-12-10 | 2017-01-10 | СИГМАФАРМ ЛЭБОРЭТОРИЗ, ЭлЭлСи | Высокостабильные композиции перорально активных аналогов нуклеотидов или перорально активных пролекарств аналогов нуклеотидов |
| US9550803B2 (en) | 2011-05-06 | 2017-01-24 | University Of Southern California | Method to improve antiviral activity of nucleotide analogue drugs |
| ES2874774T3 (es) | 2011-12-22 | 2021-11-05 | Geron Corp | Análogos de guanina como sustratos de telomerasa y afectores de la longitud de los telómeros |
| CN103665043B (zh) | 2012-08-30 | 2017-11-10 | 江苏豪森药业集团有限公司 | 一种替诺福韦前药及其在医药上的应用 |
| CN103333209B (zh) * | 2013-07-05 | 2015-09-30 | 西安新通药物研究有限公司 | 替诺福韦前药(hts)新晶体 |
| CN104710477A (zh) * | 2013-12-16 | 2015-06-17 | 安徽贝克联合制药有限公司 | 替诺福韦环膦酸酯化合物及其药学上可接受的盐和其制备方法及应用 |
| JP2017512183A (ja) | 2014-02-13 | 2017-05-18 | リガンド・ファーマシューティカルズ・インコーポレイテッド | プロドラッグ化合物およびそれらの使用 |
| RU2665135C2 (ru) | 2014-03-14 | 2018-08-28 | Олтек, Инк. | Композиции селеноорганических соединений и способы их применения |
| CN106687118A (zh) | 2014-07-02 | 2017-05-17 | 配体药物公司 | 前药化合物及其用途 |
| WO2017048252A1 (en) | 2015-09-15 | 2017-03-23 | Alltech, Inc. | Compositions of selenoorganic compounds and methods of use thereof |
| WO2017220028A1 (zh) | 2016-06-24 | 2017-12-28 | 浙江柏拉阿图医药科技有限公司 | 肝递送抗病毒前体药物核苷环磷酸酯化合物及应用 |
| CN107540710B (zh) * | 2016-06-24 | 2020-10-16 | 浙江柏拉阿图医药科技有限公司 | 肝递送抗病毒前体药物核苷环磷酸酯化合物及应用 |
| RU2020126177A (ru) | 2018-01-09 | 2022-02-10 | Лиганд Фармасьютикалз, Инк. | Ацетальные соединения и их терапевтическое применение |
| CN108863797B (zh) * | 2018-07-02 | 2021-01-15 | 吉首大学 | 一类3-(取代/非取代苯基)-3-羟基丙酰氧肟酸的制备方法 |
| CN116178440B (zh) * | 2022-12-23 | 2025-12-30 | 杏林中医药科技(广州)有限公司 | 一种肝脏靶向烷化剂及其应用 |
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| AU2003235501A1 (en) * | 2002-05-13 | 2003-11-11 | Metabasis Therapeutics, Inc. | PMEA and PMPA cyclic producing synthesis |
| NZ536328A (en) | 2002-05-13 | 2007-11-30 | Metabasis Therapeutics Inc | Novel phosphonic acid based prodrugs of PMEA and its analogues |
| JP5046219B2 (ja) * | 2002-10-31 | 2012-10-10 | リガンド・ファーマシューティカルズ・インコーポレイテッド | １，３−プロパン−１−アリールジオールの新規環状リン酸ジエステルおよびそのプロドラッグへの使用 |
| US7553825B2 (en) * | 2003-12-30 | 2009-06-30 | Gilead Sciences, Inc. | Anti-proliferative compounds, compositions, and methods of use thereof |
| WO2005123729A1 (en) * | 2004-06-08 | 2005-12-29 | Metabasis Therapeutics, Inc. | Lewis acid mediated synthesis of cyclic esters |
-
2003
- 2003-05-12 NZ NZ536328A patent/NZ536328A/en not_active IP Right Cessation
- 2003-05-12 EP EP10005037.6A patent/EP2223927B1/en not_active Expired - Lifetime
- 2003-05-12 JP JP2004546667A patent/JP4476811B2/ja not_active Expired - Fee Related
- 2003-05-12 IL IL16480903A patent/IL164809A0/xx unknown
- 2003-05-12 AU AU2003299492A patent/AU2003299492B2/en not_active Ceased
- 2003-05-12 US US10/436,922 patent/US7214668B2/en not_active Expired - Lifetime
- 2003-05-12 EP EP03799779A patent/EP1532157A4/en not_active Withdrawn
- 2003-05-12 CA CA2485702A patent/CA2485702C/en not_active Expired - Lifetime
- 2003-05-12 WO PCT/US2003/014821 patent/WO2004037161A2/en not_active Ceased
- 2003-11-18 TW TW092132408A patent/TWI347325B/zh not_active IP Right Cessation
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- 2004-10-25 IL IL164809A patent/IL164809A/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| EP1532157A2 (en) | 2005-05-25 |
| US20030229225A1 (en) | 2003-12-11 |
| EP2223927A2 (en) | 2010-09-01 |
| WO2004037161A2 (en) | 2004-05-06 |
| WO2004037161A3 (en) | 2005-03-31 |
| IL164809A0 (en) | 2005-12-18 |
| TW200426152A (en) | 2004-12-01 |
| US7214668B2 (en) | 2007-05-08 |
| EP2223927A3 (en) | 2010-09-15 |
| AU2003299492A1 (en) | 2004-05-13 |
| IL164809A (en) | 2012-08-30 |
| NZ536328A (en) | 2007-11-30 |
| EP1532157A4 (en) | 2009-02-25 |
| CA2485702C (en) | 2011-07-19 |
| JP4476811B2 (ja) | 2010-06-09 |
| CA2485702A1 (en) | 2004-05-06 |
| EP2223927B1 (en) | 2014-10-15 |
| TWI347325B (en) | 2011-08-21 |
| JP2006511490A (ja) | 2006-04-06 |
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