AU2006218704A1 - Tricyclic-nucleoside prodrugs for treating viral infections - Google Patents
Tricyclic-nucleoside prodrugs for treating viral infections Download PDFInfo
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- AU2006218704A1 AU2006218704A1 AU2006218704A AU2006218704A AU2006218704A1 AU 2006218704 A1 AU2006218704 A1 AU 2006218704A1 AU 2006218704 A AU2006218704 A AU 2006218704A AU 2006218704 A AU2006218704 A AU 2006218704A AU 2006218704 A1 AU2006218704 A1 AU 2006218704A1
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- Prior art keywords
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- hydrogen
- Prior art date
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- 229940002612 prodrug Drugs 0.000 title claims description 33
- 239000000651 prodrug Substances 0.000 title claims description 33
- 208000036142 Viral infection Diseases 0.000 title claims description 14
- 230000009385 viral infection Effects 0.000 title claims description 13
- HOGVTUZUJGHKPL-HTVVRFAVSA-N triciribine Chemical compound C=12C3=NC=NC=1N(C)N=C(N)C2=CN3[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HOGVTUZUJGHKPL-HTVVRFAVSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 197
- 229910052739 hydrogen Inorganic materials 0.000 claims description 129
- 239000001257 hydrogen Substances 0.000 claims description 117
- 125000000217 alkyl group Chemical group 0.000 claims description 102
- -1 cyano, azido, amino Chemical group 0.000 claims description 96
- 125000000623 heterocyclic group Chemical group 0.000 claims description 80
- 125000001072 heteroaryl group Chemical group 0.000 claims description 65
- 229910052721 tungsten Inorganic materials 0.000 claims description 64
- 150000002431 hydrogen Chemical group 0.000 claims description 55
- 150000003839 salts Chemical class 0.000 claims description 53
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 52
- 239000000203 mixture Substances 0.000 claims description 48
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 47
- 125000005843 halogen group Chemical group 0.000 claims description 44
- 241000711549 Hepacivirus C Species 0.000 claims description 40
- 125000003118 aryl group Chemical group 0.000 claims description 38
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 38
- 238000000034 method Methods 0.000 claims description 38
- 229910052757 nitrogen Inorganic materials 0.000 claims description 36
- 125000003107 substituted aryl group Chemical group 0.000 claims description 34
- 150000001413 amino acids Chemical class 0.000 claims description 33
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 33
- 229910052799 carbon Inorganic materials 0.000 claims description 31
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- 125000004122 cyclic group Chemical group 0.000 claims description 24
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- 230000036961 partial effect Effects 0.000 claims description 23
- 125000002252 acyl group Chemical group 0.000 claims description 22
- ANCLJVISBRWUTR-UHFFFAOYSA-N diaminophosphinic acid Chemical compound NP(N)(O)=O ANCLJVISBRWUTR-UHFFFAOYSA-N 0.000 claims description 22
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims description 22
- 241000700605 Viruses Species 0.000 claims description 21
- 102000006992 Interferon-alpha Human genes 0.000 claims description 20
- 108010047761 Interferon-alpha Proteins 0.000 claims description 20
- 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 20
- 229960000329 ribavirin Drugs 0.000 claims description 20
- 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 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 17
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
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- 125000004442 acylamino group Chemical group 0.000 claims description 15
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- IWUCXVSUMQZMFG-RGDLXGNYSA-N 1-[(2s,3s,4r,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,4-triazole-3-carboxamide Chemical compound N1=C(C(=O)N)N=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 IWUCXVSUMQZMFG-RGDLXGNYSA-N 0.000 claims description 12
- 125000005012 alkyl thioether group Chemical group 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000005254 oxyacyl group Chemical group 0.000 claims description 12
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 11
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- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 11
- BVMWIXWOIGJRGE-UHFFFAOYSA-N NP(O)=O Chemical compound NP(O)=O BVMWIXWOIGJRGE-UHFFFAOYSA-N 0.000 claims description 10
- 125000004423 acyloxy group Chemical group 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 10
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 10
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 10
- 150000003573 thiols Chemical class 0.000 claims description 10
- 241000710781 Flaviviridae Species 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 208000015181 infectious disease Diseases 0.000 claims description 9
- NHKZSTHOYNWEEZ-AFCXAGJDSA-N taribavirin Chemical compound N1=C(C(=N)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NHKZSTHOYNWEEZ-AFCXAGJDSA-N 0.000 claims description 9
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- 230000002401 inhibitory effect Effects 0.000 claims description 7
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- 125000000033 alkoxyamino group Chemical group 0.000 claims description 5
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 5
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 5
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 5
- 235000013902 inosinic acid Nutrition 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- 229910052720 vanadium Inorganic materials 0.000 claims description 5
- 208000005176 Hepatitis C Diseases 0.000 claims description 4
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- 108010078233 Thymalfasin Proteins 0.000 claims description 4
- 102400000800 Thymosin alpha-1 Human genes 0.000 claims description 4
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 claims description 4
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- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/16—Peri-condensed 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
- C07H19/22—Pteridine 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
- C07H19/23—Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US65746305P | 2005-02-28 | 2005-02-28 | |
| US60/657,463 | 2005-02-28 | ||
| PCT/US2006/007131 WO2006093986A1 (en) | 2005-02-28 | 2006-02-28 | Tricyclic-nucleoside prodrugs for treating viral infections |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2006218704A1 true AU2006218704A1 (en) | 2006-09-08 |
Family
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Family Applications (2)
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-
2006
- 2006-02-28 WO PCT/US2006/007132 patent/WO2006093987A1/en not_active Ceased
- 2006-02-28 JP JP2007558141A patent/JP2008531703A/ja not_active Withdrawn
- 2006-02-28 AP AP2007004118A patent/AP2007004118A0/xx unknown
- 2006-02-28 CA CA002597685A patent/CA2597685A1/en not_active Abandoned
- 2006-02-28 CA CA002597683A patent/CA2597683A1/en not_active Abandoned
- 2006-02-28 US US11/365,321 patent/US7524825B2/en not_active Expired - Fee Related
- 2006-02-28 AP AP2007004128A patent/AP2007004128A0/xx unknown
- 2006-02-28 KR KR1020077020680A patent/KR20070106767A/ko not_active Withdrawn
- 2006-02-28 BR BRPI0607769-2A patent/BRPI0607769A2/pt not_active IP Right Cessation
- 2006-02-28 AU AU2006218704A patent/AU2006218704A1/en not_active Abandoned
- 2006-02-28 AU AU2006218705A patent/AU2006218705A1/en not_active Abandoned
- 2006-02-28 EA EA200701849A patent/EA200701849A1/ru unknown
- 2006-02-28 US US11/365,170 patent/US7534771B2/en not_active Expired - Fee Related
- 2006-02-28 KR KR1020077021265A patent/KR20070106781A/ko not_active Withdrawn
- 2006-02-28 AR ARP060100751A patent/AR058419A1/es unknown
- 2006-02-28 MX MX2007010460A patent/MX2007010460A/es not_active Application Discontinuation
- 2006-02-28 ZA ZA200707410A patent/ZA200707410B/xx unknown
- 2006-02-28 EP EP06736450A patent/EP1853617A1/en not_active Withdrawn
- 2006-02-28 EA EA200701850A patent/EA200701850A1/ru unknown
- 2006-02-28 MX MX2007010463A patent/MX2007010463A/es not_active Application Discontinuation
- 2006-02-28 CN CNA2006800063907A patent/CN101128474A/zh active Pending
- 2006-02-28 WO PCT/US2006/007131 patent/WO2006093986A1/en not_active Ceased
- 2006-02-28 CN CNA2006800063894A patent/CN101142226A/zh active Pending
- 2006-02-28 BR BRPI0607770-6A patent/BRPI0607770A2/pt not_active IP Right Cessation
- 2006-02-28 HR HR20070436A patent/HRP20070436A2/xx not_active Application Discontinuation
- 2006-02-28 EP EP06736451A patent/EP1853618A1/en not_active Withdrawn
- 2006-02-28 JP JP2007558142A patent/JP2008531704A/ja not_active Withdrawn
- 2006-02-28 HR HR20070435A patent/HRP20070435A9/xx not_active Application Discontinuation
- 2006-03-01 TW TW095106861A patent/TW200640474A/zh unknown
-
2007
- 2007-07-31 IL IL184954A patent/IL184954A0/en unknown
- 2007-07-31 IL IL184955A patent/IL184955A0/en unknown
- 2007-09-11 NO NO20074613A patent/NO20074613L/no not_active Application Discontinuation
- 2007-09-27 NO NO20074915A patent/NO20074915L/no not_active Application Discontinuation
-
2009
- 2009-03-31 US US12/415,286 patent/US20090208457A1/en not_active Abandoned
- 2009-03-31 US US12/415,335 patent/US20090253648A1/en not_active Abandoned
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| MK1 | Application lapsed section 142(2)(a) - no request for examination in relevant period |