CA2261619C - Analogues de nucleotides - Google Patents

Analogues de nucleotides Download PDF

Info

Publication number: CA2261619C
Authority: CA; Canada
Prior art keywords: compound; alkyl; pmpa; aryl; compounds
Prior art date: 1996-07-26
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.): Expired - Lifetime

Application number

CA002261619A

Other languages

English (en)

Other versions

CA2261619A1 (fr

Inventor

Murty N. Arimilli

Kenneth C. Cundy

Joseph P. Dougherty

Choung U. Kim

Reza Oliyai

Valentino J. Stella

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Gilead Sciences Inc

Original Assignee

Gilead Sciences Inc

Priority date (The priority date 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 date listed.)

1996-07-26

Filing date

1997-07-25

Publication date

2006-05-23

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26696272&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2261619(C) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1997-07-25 Application filed by Gilead Sciences Inc filed Critical Gilead Sciences Inc

1998-02-05 Publication of CA2261619A1 publication Critical patent/CA2261619A1/fr

2006-05-23 Application granted granted Critical

2006-05-23 Publication of CA2261619C publication Critical patent/CA2261619C/fr

2017-07-25 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

125000003729 nucleotide group Chemical group 0.000 title description 7
150000001875 compounds Chemical class 0.000 claims abstract description 238
-1 alkyenylaryl Chemical group 0.000 claims abstract description 104
125000004400 (C1-C12) alkyl group Chemical group 0.000 claims abstract description 21
125000003118 aryl group Chemical group 0.000 claims abstract description 15
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 15
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims abstract description 13
230000000840 anti-viral effect Effects 0.000 claims abstract description 12
229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 10
150000002148 esters Chemical class 0.000 claims abstract description 9
125000003342 alkenyl group Chemical group 0.000 claims abstract description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 7
239000001301 oxygen Substances 0.000 claims abstract description 7
125000000304 alkynyl group Chemical group 0.000 claims abstract description 6
125000001475 halogen functional group Chemical group 0.000 claims abstract 7
125000002877 alkyl aryl group Chemical group 0.000 claims abstract 4
125000005025 alkynylaryl group Chemical group 0.000 claims abstract 4
125000005018 aryl alkenyl group Chemical group 0.000 claims abstract 4
125000003710 aryl alkyl group Chemical group 0.000 claims abstract 4
125000005015 aryl alkynyl group Chemical group 0.000 claims abstract 4
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims abstract 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 101
238000006243 chemical reaction Methods 0.000 claims description 43
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
238000000034 method Methods 0.000 claims description 22
229910052799 carbon Inorganic materials 0.000 claims description 21
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 20
150000003839 salts Chemical class 0.000 claims description 18
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 17
229910052757 nitrogen Inorganic materials 0.000 claims description 16
125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims description 13
125000006711 (C2-C12) alkynyl group Chemical group 0.000 claims description 13
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
239000001257 hydrogen Substances 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 11
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 10
125000000848 adenin-9-yl group Chemical group [H]N([H])C1=C2N=C([H])N(*)C2=NC([H])=N1 0.000 claims description 9
125000004093 cyano group Chemical group *C#N 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 8
MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical group NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
125000000847 cytosin-1-yl group Chemical group [*]N1C(=O)N=C(N([H])[H])C([H])=C1[H] 0.000 claims description 6
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 6
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
125000003738 guanin-9-yl group Chemical group O=C1N([H])C(N([H])[H])=NC2=C1N=C([H])N2[*] 0.000 claims description 5
208000015181 infectious disease Diseases 0.000 claims description 5
125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 5
239000012453 solvate Substances 0.000 claims description 5
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
150000004677 hydrates Chemical class 0.000 claims description 4
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
150000007530 organic bases Chemical class 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 3
241000700605 Viruses Species 0.000 claims description 3
229940059260 amidate Drugs 0.000 claims description 3
NPUKDXXFDDZOKR-LLVKDONJSA-N etomidate Chemical compound CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1 NPUKDXXFDDZOKR-LLVKDONJSA-N 0.000 claims description 3
239000003960 organic solvent Substances 0.000 claims description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
239000004310 lactic acid Substances 0.000 claims description 2
235000014655 lactic acid Nutrition 0.000 claims description 2
238000011282 treatment Methods 0.000 claims description 2
235000015165 citric acid Nutrition 0.000 claims 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
235000011007 phosphoric acid Nutrition 0.000 claims 1
230000001376 precipitating effect Effects 0.000 claims 1
239000001117 sulphuric acid Substances 0.000 claims 1
235000011149 sulphuric acid Nutrition 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 15
238000002360 preparation method Methods 0.000 abstract description 15
150000004649 carbonic acid derivatives Chemical class 0.000 abstract description 9
108091034117 Oligonucleotide Proteins 0.000 abstract description 7
150000004657 carbamic acid derivatives Chemical class 0.000 abstract description 5
238000002560 therapeutic procedure Methods 0.000 abstract description 3
238000011321 prophylaxis Methods 0.000 abstract description 2
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 abstract 1
239000000203 mixture Substances 0.000 description 68
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 description 68
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 61
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 53
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 44
239000000243 solution Substances 0.000 description 38
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 34
238000009472 formulation Methods 0.000 description 34
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
239000004480 active ingredient Substances 0.000 description 27
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
239000000047 product Substances 0.000 description 20
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
238000004128 high performance liquid chromatography Methods 0.000 description 17
239000007787 solid Substances 0.000 description 17
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
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229940002612 prodrug Drugs 0.000 description 14
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230000015572 biosynthetic process Effects 0.000 description 13
241000282472 Canis lupus familiaris Species 0.000 description 12
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
239000003921 oil Substances 0.000 description 12
238000003786 synthesis reaction Methods 0.000 description 12
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XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
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238000007792 addition Methods 0.000 description 9
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125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
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241001465754 Metazoa Species 0.000 description 7
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 description 7
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125000004122 cyclic group Chemical group 0.000 description 7
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125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
125000003072 pyrazolidinyl group Chemical group 0.000 description 1
DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical group C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
125000002755 pyrazolinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
125000004941 pyridazin-5-yl group Chemical group N1=NC=CC(=C1)* 0.000 description 1
125000004942 pyridazin-6-yl group Chemical group N1=NC=CC=C1* 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000001422 pyrrolinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
238000005185 salting out Methods 0.000 description 1
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238000007493 shaping process Methods 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
229940087562 sodium acetate trihydrate Drugs 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
239000012064 sodium phosphate buffer Substances 0.000 description 1
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HGHYERVLYRBRPJ-UHFFFAOYSA-N tert-butyl chloromethyl carbonate Chemical compound CC(C)(C)OC(=O)OCCl HGHYERVLYRBRPJ-UHFFFAOYSA-N 0.000 description 1
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000004927 thianaphthalenyl group Chemical group S1C(C=CC2=CC=CC=C12)* 0.000 description 1
125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
150000003568 thioethers Chemical group 0.000 description 1
229930192474 thiophene Chemical group 0.000 description 1
238000004448 titration Methods 0.000 description 1
229940100611 topical cream Drugs 0.000 description 1
229940100615 topical ointment Drugs 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
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239000000196 tragacanth Substances 0.000 description 1
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229940116362 tragacanth Drugs 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
LGQXXHMEBUOXRP-UHFFFAOYSA-N tributyl borate Chemical compound CCCCOB(OCCCC)OCCCC LGQXXHMEBUOXRP-UHFFFAOYSA-N 0.000 description 1
241000701161 unidentified adenovirus Species 0.000 description 1
241001529453 unidentified herpesvirus Species 0.000 description 1
241001430294 unidentified retrovirus Species 0.000 description 1
238000011870 unpaired t-test Methods 0.000 description 1
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AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical compound N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 description 1

Classifications

- 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
- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
- 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
- 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
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6509—Six-membered rings
- C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Virology (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Molecular Biology (AREA)
General Chemical & Material Sciences (AREA)
Public Health (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Biochemistry (AREA)
AIDS & HIV (AREA)
Tropical Medicine & Parasitology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA002261619A 1996-07-26 1997-07-25 Analogues de nucleotides Expired - Lifetime CA2261619C (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US68683896A	1996-07-26	1996-07-26
US2270896P	1996-07-26	1996-07-26
US08/686,838		1996-07-26
PCT/US1997/013244 WO1998004569A1 (fr)	1996-07-26	1997-07-25	Analogues de nucleotides

Publications (2)

Publication Number	Publication Date
CA2261619A1 CA2261619A1 (fr)	1998-02-05
CA2261619C true CA2261619C (fr)	2006-05-23

Family

ID=26696272

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002261619A Expired - Lifetime CA2261619C (fr)	1996-07-26	1997-07-25	Analogues de nucleotides

Country Status (4)

Country	Link
JP (6)	JP4033494B2 (fr)
CA (1)	CA2261619C (fr)
TW (2)	TW470748B (fr)
WO (1)	WO1998004569A1 (fr)

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EA015145B1 (ru)	2003-01-14	2011-06-30	Джилид Сайэнс, Инк.	Фармацевтическая композиция и пероральная фармацевтическая дозированная форма (варианты), проявляющие активность в отношении вич-инфекций, лечебный набор и таблетка и способ лечения или предотвращения симптомов или эффектов вич-инфекции
WO2005002626A2 (fr)	2003-04-25	2005-01-13	Gilead Sciences, Inc.	Composes de phosphonate therapeutiques
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AU2004247305B2 (en)	2003-06-16	2010-02-18	Institute Of Organic Chemistry And Biochemistry, Academy Of Sciences Of The Czech Republic	Pyrimidine compounds having phosphonate groups as antiviral nucleotide analogs
WO2005044308A1 (fr)	2003-10-24	2005-05-19	Gilead Sciences, Inc.	Analogues phosphonates d'antimetabolites
US7427624B2 (en)	2003-10-24	2008-09-23	Gilead Sciences, Inc.	Purine nucleoside phosphorylase inhibitory phosphonate compounds
AU2004286239A1 (en)	2003-10-24	2005-05-12	Gilead Sciences, Inc.	Methods and compositions for identifying therapeutic compounds
DE602004019815D1 (de)	2003-12-22	2009-04-16	Gilead Sciences Inc	4'-substituierte carbovir- und abacavir-derivate sowie verwandte verbindungen mit hiv- und hcv-antiviraler wirkung
WO2005063258A1 (fr) *	2003-12-22	2005-07-14	Gilead Sciences, Inc.	Conjugues de phosphonate inhibant la kinase
EP1778251B1 (fr)	2004-07-27	2011-04-13	Gilead Sciences, Inc.	Conjugues de phosphonate nucleosidique comme agents anti-vih
TWI375560B (en)	2005-06-13	2012-11-01	Gilead Sciences Inc	Composition comprising dry granulated emtricitabine and tenofovir df and method for making the same
CN102228463B (zh) *	2005-06-13	2012-12-19	博瑞生物医药技术(苏州)有限公司	泰诺福韦的晶体
TWI471145B (zh)	2005-06-13	2015-02-01	Bristol Myers Squibb & Gilead Sciences Llc	單一式藥學劑量型
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CN102093422B (zh) *	2009-12-10	2015-02-25	中国人民解放军军事医学科学院毒物药物研究所	无环核苷膦酸酯衍生物及其医药用途
WO2012152317A1 (fr) *	2011-05-10	2012-11-15	Okapi Sciences Nv	Composés destinés à être utilisés dans le traitement d'infections rétrovirales chez les félins
CN110343135A (zh)	2011-08-16	2019-10-18	吉利德科学公司	替诺福韦艾拉酚胺(tenofovir alafenamide)半反丁烯二酸盐
CN103626802A (zh) *	2012-08-23	2014-03-12	重庆药友制药有限责任公司	一种制备替诺福韦的新方法
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1997
- 1997-07-25 WO PCT/US1997/013244 patent/WO1998004569A1/fr not_active Ceased
- 1997-07-25 JP JP50831898A patent/JP4033494B2/ja not_active Expired - Lifetime
- 1997-07-25 CA CA002261619A patent/CA2261619C/fr not_active Expired - Lifetime
- 1997-08-21 TW TW089123708A patent/TW470748B/zh not_active IP Right Cessation
- 1997-08-21 TW TW086110757A patent/TW444020B/zh not_active IP Right Cessation
2007
- 2007-07-09 JP JP2007180398A patent/JP2007297406A/ja not_active Withdrawn
2010
- 2010-10-15 JP JP2010233086A patent/JP2011016847A/ja not_active Withdrawn
2014
- 2014-04-15 JP JP2014083387A patent/JP2014159450A/ja not_active Withdrawn
2015
- 2015-04-28 JP JP2015091141A patent/JP2015164934A/ja not_active Withdrawn
2016
- 2016-10-31 JP JP2016212748A patent/JP2017031212A/ja not_active Withdrawn

Also Published As

Publication number	Publication date
JP2000515866A (ja)	2000-11-28
JP2011016847A (ja)	2011-01-27
TW444020B (en)	2001-07-01
TW470748B (en)	2002-01-01
JP2017031212A (ja)	2017-02-09
JP2007297406A (ja)	2007-11-15
CA2261619A1 (fr)	1998-02-05
JP2014159450A (ja)	2014-09-04
WO1998004569A1 (fr)	1998-02-05
JP2015164934A (ja)	2015-09-17
JP4033494B2 (ja)	2008-01-16

Legal Events

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2002-06-26	EEER	Examination request
2017-09-26	MKEX	Expiry	Effective date: 20170725

Publication	Publication Date	Title
USRE38333E1 (en)	2003-11-25	Antiviral phosphonomethoxy nucleotide analogs having increased oral bioavailability
WO1998004569A1 (fr)	1998-02-05	Analogues de nucleotides
AU713374B2 (en)	1999-12-02	Nucleotide analogs
CA2298059C (fr)	2008-12-30	Composition d'analogues de nucleotides et procede de synthese
KR100358327B1 (ko)	2003-03-03	포스포네이트뉴클레오티드에스테르유도체
AU747163B2 (en)	2002-05-09	Nucleotide analog compositions
US6767900B2 (en)	2004-07-27	Phosphonate nucleotide compound
CA1340909C (fr)	2000-02-22	Derives d'une base purique, ainsi que leur utilisation therapeutique
HK1020964B (en)	2004-01-16	Nucleotide analogs
JP3580377B2 (ja)	2004-10-20	ホスホナートヌクレオチドエステル誘導体
HK1025334A (en)	2000-11-10	Nucleotide analogs
CA2605226C (fr)	2009-01-13	Composition d'analogues de nucleotides et procede de synthese
EP1243593A2 (fr)	2002-09-25	Composition d'analogues de nucléotides et procédé de synthèse
MXPA00000808A (en)	2001-03-05	Nucleotide analog composition and synthesis method