NZ543864A - Pyrimidine compounds having phosphonate groups as antiviral nucleotide analogs - Google Patents
Pyrimidine compounds having phosphonate groups as antiviral nucleotide analogsInfo
- Publication number
- NZ543864A NZ543864A NZ543864A NZ54386404A NZ543864A NZ 543864 A NZ543864 A NZ 543864A NZ 543864 A NZ543864 A NZ 543864A NZ 54386404 A NZ54386404 A NZ 54386404A NZ 543864 A NZ543864 A NZ 543864A
- Authority
- NZ
- New Zealand
- Prior art keywords
- compound
- formula
- hydroxy
- independently
- amino
- Prior art date
Links
- 230000000840 anti-viral effect Effects 0.000 title abstract description 17
- 125000003729 nucleotide group Chemical group 0.000 title abstract description 6
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 title description 10
- 150000003230 pyrimidines Chemical class 0.000 title description 3
- -1 -N(R5)2 Chemical group 0.000 claims abstract description 102
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 67
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 51
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 48
- 150000002148 esters Chemical class 0.000 claims abstract description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 41
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 38
- 150000001408 amides Chemical class 0.000 claims abstract description 37
- 125000004970 halomethyl group Chemical group 0.000 claims abstract description 28
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 23
- 101100516572 Caenorhabditis elegans nhr-8 gene Proteins 0.000 claims abstract description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 20
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 19
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims abstract description 19
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 19
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 17
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 16
- 125000003118 aryl group Chemical group 0.000 claims abstract description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000001301 oxygen Substances 0.000 claims abstract description 14
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 11
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims abstract description 11
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000011593 sulfur Substances 0.000 claims abstract description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 10
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 155
- 229910052799 carbon Inorganic materials 0.000 claims description 50
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 42
- 239000000203 mixture Substances 0.000 claims description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 125000006239 protecting group Chemical group 0.000 claims description 22
- 238000002360 preparation method Methods 0.000 claims description 21
- 239000002585 base Substances 0.000 claims description 19
- 150000001721 carbon Chemical group 0.000 claims description 18
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 16
- 241000700605 Viruses Species 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 7
- 239000000010 aprotic solvent Substances 0.000 claims description 7
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 5
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 5
- 125000003368 amide group Chemical group 0.000 claims description 5
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 230000003301 hydrolyzing effect Effects 0.000 claims description 5
- 239000012453 solvate Substances 0.000 claims description 5
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- 239000003513 alkali Substances 0.000 claims description 4
- 229910001854 alkali hydroxide Inorganic materials 0.000 claims description 4
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims 2
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 abstract description 14
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- 229910052757 nitrogen Inorganic materials 0.000 description 22
- 239000004480 active ingredient Substances 0.000 description 21
- 238000009472 formulation Methods 0.000 description 20
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- 238000006243 chemical reaction Methods 0.000 description 17
- 238000001704 evaporation Methods 0.000 description 17
- 230000008020 evaporation Effects 0.000 description 17
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 17
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 16
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 125000000623 heterocyclic group Chemical group 0.000 description 14
- 239000000047 product Substances 0.000 description 13
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 229910000024 caesium carbonate Inorganic materials 0.000 description 9
- 238000010828 elution Methods 0.000 description 9
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 9
- 208000015181 infectious disease Diseases 0.000 description 9
- 229910052698 phosphorus Inorganic materials 0.000 description 9
- 241000725303 Human immunodeficiency virus Species 0.000 description 8
- 150000003863 ammonium salts Chemical class 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 8
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
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- 239000011541 reaction mixture Substances 0.000 description 8
- 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 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 238000002953 preparative HPLC Methods 0.000 description 7
- JSPYZDUIKDWUQG-UHFFFAOYSA-N 2-(2,6-diamino-5-methylpyrimidin-4-yl)oxyethoxymethylphosphonic acid Chemical compound CC1=C(N)N=C(N)N=C1OCCOCP(O)(O)=O JSPYZDUIKDWUQG-UHFFFAOYSA-N 0.000 description 6
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 6
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- PIFWODKWGYAHJA-UHFFFAOYSA-N 2-[di(propan-2-yloxy)phosphorylmethoxy]ethyl 4-methylbenzenesulfonate Chemical compound CC(C)OP(=O)(OC(C)C)COCCOS(=O)(=O)C1=CC=C(C)C=C1 PIFWODKWGYAHJA-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
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- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 239000000651 prodrug Chemical group 0.000 description 5
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- 210000001519 tissue Anatomy 0.000 description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- 208000031886 HIV Infections Diseases 0.000 description 4
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- 241001465754 Metazoa Species 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
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- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 230000000798 anti-retroviral effect Effects 0.000 description 4
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- 230000035772 mutation Effects 0.000 description 4
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- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 4
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- UQQHOWKTDKKTHO-ICQCTTRCSA-N (2r,3s,4s,5r)-2-(hydroxymethyl)-5-(6-methoxypurin-9-yl)oxolane-3,4-diol Chemical compound C1=NC=2C(OC)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O UQQHOWKTDKKTHO-ICQCTTRCSA-N 0.000 description 3
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
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- MAGFWTQIBVYZHP-UHFFFAOYSA-N 2-(2,6-diamino-5-cyanopyrimidin-4-yl)oxyethoxymethylphosphonic acid Chemical compound NC1=NC(N)=C(C#N)C(OCCOCP(O)(O)=O)=N1 MAGFWTQIBVYZHP-UHFFFAOYSA-N 0.000 description 2
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- 238000011785 NMRI mouse Methods 0.000 description 2
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- 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 description 2
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- 239000000376 reactant Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- 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 description 1
- 102220008319 rs199476307 Human genes 0.000 description 1
- 102220125879 rs199736749 Human genes 0.000 description 1
- 102220031036 rs3740912 Human genes 0.000 description 1
- 102220040539 rs587778365 Human genes 0.000 description 1
- 229960001852 saquinavir Drugs 0.000 description 1
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- YWFGPFUURZNKDW-UHFFFAOYSA-M sodium 2-amino-9-[(2-oxido-2-oxo-1,3,2lambda5-dioxaphosphinan-5-yl)oxymethyl]-1H-purin-6-one Chemical compound [Na+].Nc1nc(=O)c2ncn(COC3COP([O-])(=O)OC3)c2[nH]1 YWFGPFUURZNKDW-UHFFFAOYSA-M 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- JJICLMJFIKGAAU-UHFFFAOYSA-M sodium;2-amino-9-(1,3-dihydroxypropan-2-yloxymethyl)purin-6-olate Chemical compound [Na+].NC1=NC([O-])=C2N=CN(COC(CO)CO)C2=N1 JJICLMJFIKGAAU-UHFFFAOYSA-M 0.000 description 1
- 239000000600 sorbitol Chemical group 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 229960004556 tenofovir Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- NLDYACGHTUPAQU-UHFFFAOYSA-N tetracyanoethylene Chemical group N#CC(C#N)=C(C#N)C#N NLDYACGHTUPAQU-UHFFFAOYSA-N 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
- 125000005942 tetrahydropyridyl group Chemical group 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
- 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
- 229930192474 thiophene Chemical group 0.000 description 1
- 238000011200 topical administration 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
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- VSQQQLOSPVPRAZ-RRKCRQDMSA-N trifluridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C(F)(F)F)=C1 VSQQQLOSPVPRAZ-RRKCRQDMSA-N 0.000 description 1
- YFNGWGVTFYSJHE-UHFFFAOYSA-K trisodium;phosphonoformate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)C([O-])=O.OP(O)(=O)C([O-])=O.OP(O)(=O)C([O-])=O YFNGWGVTFYSJHE-UHFFFAOYSA-K 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- HDZZVAMISRMYHH-LITAXDCLSA-N tubercidin Chemical compound C1=CC=2C(N)=NC=NC=2N1[C@@H]1O[C@@H](CO)[C@H](O)[C@H]1O HDZZVAMISRMYHH-LITAXDCLSA-N 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- AUFUWRKPQLGTGF-FMKGYKFTSA-N uridine triacetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](COC(=O)C)O[C@H]1N1C(=O)NC(=O)C=C1 AUFUWRKPQLGTGF-FMKGYKFTSA-N 0.000 description 1
- 229940093257 valacyclovir Drugs 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- 229960003636 vidarabine Drugs 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
- 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 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
- C07F9/645—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
-
- 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
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- AIDS & HIV (AREA)
- Biotechnology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US47889303P | 2003-06-16 | 2003-06-16 | |
| PCT/CZ2004/000034 WO2004111064A1 (en) | 2003-06-16 | 2004-06-16 | Pyrimidine compounds having phosphonate groups as antiviral nucleotide analogs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ543864A true NZ543864A (en) | 2009-10-30 |
Family
ID=33551859
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ543864A NZ543864A (en) | 2003-06-16 | 2004-06-16 | Pyrimidine compounds having phosphonate groups as antiviral nucleotide analogs |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US7115592B2 (enExample) |
| EP (1) | EP1644389B1 (enExample) |
| JP (2) | JP5280631B2 (enExample) |
| KR (1) | KR101102815B1 (enExample) |
| CN (1) | CN1805966B (enExample) |
| AT (1) | ATE496056T1 (enExample) |
| AU (1) | AU2004247305B2 (enExample) |
| CA (1) | CA2527805C (enExample) |
| DE (1) | DE602004031115D1 (enExample) |
| DK (1) | DK1644389T3 (enExample) |
| EA (1) | EA011948B1 (enExample) |
| IL (1) | IL172015A (enExample) |
| NZ (1) | NZ543864A (enExample) |
| SI (1) | SI1644389T1 (enExample) |
| WO (1) | WO2004111064A1 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2616314A1 (en) * | 2005-07-27 | 2007-02-01 | Gilead Sciences, Inc. | Antiviral phosphonate conjugates for inhibition of hiv |
| FR2908133B1 (fr) * | 2006-11-08 | 2012-12-14 | Centre Nat Rech Scient | Nouveaux analogues de nucleotides comme molecules precurseurs d'antiviraux |
| ES2443952T3 (es) | 2009-09-02 | 2014-02-21 | Novartis Ag | Composiciones inmunógenas que incluyen moduladores de la actividad de TLR |
| CN102939291B (zh) | 2010-04-14 | 2016-09-07 | 加利福尼亚大学董事会 | 用于病毒感染治疗的具有降低的毒性的膦酸酯 |
| CN103209985B (zh) * | 2010-08-31 | 2016-08-24 | 奇默里克斯公司 | 膦酸酯衍生物及其合成方法 |
| CN105999275A (zh) | 2010-09-01 | 2016-10-12 | 诺华有限公司 | 免疫增强剂吸附不溶性金属离子 |
| FI2648701T3 (fi) | 2010-12-10 | 2023-06-12 | Sigmapharm Laboratories Llc | Hyvin stabiileja adefovirdipivoksiilin koostumuksia |
| US20140112950A1 (en) | 2011-03-02 | 2014-04-24 | Manmohan Singh | Combination vaccines with lower doses of antigen and/or adjuvant |
| US9593137B2 (en) | 2011-12-22 | 2017-03-14 | Geron Corporation | Guanine analogs as telomerase substrates and telomere length affectors |
| US9375471B2 (en) | 2012-03-08 | 2016-06-28 | Glaxosmithkline Biologicals Sa | Adjuvanted formulations of booster vaccines |
| 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 |
| CN102796138B (zh) * | 2012-09-07 | 2014-10-22 | 山东大学 | (2-(3-甲硫基-1,2,4-噻二嗪)乙氧基)甲基膦酸酯类衍生物及其制备与应用 |
| JP6462659B2 (ja) | 2013-03-15 | 2019-01-30 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 非環式ヌクレオシドホスホン酸ジエステル |
| CN112898345A (zh) | 2014-09-15 | 2021-06-04 | 加利福尼亚大学董事会 | 核苷酸类似物 |
| EP3350191B9 (en) | 2015-09-15 | 2021-12-22 | The Regents of the University of California | Nucleotide analogs |
| CA3262284A1 (en) | 2022-07-21 | 2024-01-25 | Antiva Biosciences Inc | Pharmaceutical compositions and forms for the treatment of human papillomavirus (HPV) infection and HPV-induced neoplasm |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CS233665B1 (en) | 1983-01-06 | 1985-03-14 | Antonin Holy | Processing of isomere o-phosphonylmethylderivative of anantiomere racemic vicinal diene |
| DE3580384D1 (de) | 1984-04-09 | 1990-12-13 | Toyo Boseki | Praeparat mit verzoegerter freigabe zum aufbringen auf die schleimhaeute der mundhoehle. |
| CS263951B1 (en) | 1985-04-25 | 1989-05-12 | Antonin Holy | 9-(phosponylmethoxyalkyl)adenines and method of their preparation |
| CS263952B1 (en) | 1985-04-25 | 1989-05-12 | Holy Antonin | Remedy with antiviral effect |
| JPS63501194A (ja) * | 1985-10-30 | 1988-05-12 | プラネルト・イエンス | 歯の残根から冠，ブリツジ等を除去するための装置 |
| US5141752A (en) | 1986-05-09 | 1992-08-25 | Alza Corporation | Delayed drug delivery device |
| CS264222B1 (en) | 1986-07-18 | 1989-06-13 | Holy Antonin | N-phosphonylmethoxyalkylderivatives of bases of pytimidine and purine and method of use them |
| NZ222553A (en) | 1986-11-18 | 1991-07-26 | Bristol Myers Co | Phosphonomethoxyalkylene purine and pyrimidine derivatives and pharmaceutical compositions |
| CA2001715C (en) | 1988-11-14 | 1999-12-28 | Muzammil M. Mansuri | Carbocyclic nucleosides and nucleotides |
| US5098443A (en) | 1989-03-23 | 1992-03-24 | University Of Miami | Method of implanting intraocular and intraorbital implantable devices for the controlled release of pharmacological agents |
| CA2297294C (en) | 1989-05-15 | 2005-11-08 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Phosphonomethoxymethylpurine/pyrimidine derivatives |
| MY104575A (en) | 1989-12-22 | 1994-04-30 | The Wellcome Foundation Ltd | Therapeutic nucleosides. |
| US5302585A (en) | 1990-04-20 | 1994-04-12 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Use of chiral 2-(phosphonomethoxy)propyl guanines as antiviral agents |
| CZ285420B6 (cs) | 1990-04-24 | 1999-08-11 | Ústav Organické Chemie A Biochemie Avčr | N-(3-Fluor-2-fosfonylmethoxypropyl)deriváty purinových a pyrimidinových heterocyklických bazí, způsoby jejich přípravy a použití |
| WO1992001698A1 (en) | 1990-07-19 | 1992-02-06 | Beecham Group Plc | Antiviral phosphono-alken derivatives of purines |
| EP0468119A1 (en) | 1990-07-24 | 1992-01-29 | Merrell Dow Pharmaceuticals Inc. | Novel carbocyclic analogs of certain nucleosides |
| DE10399025I2 (de) | 1990-09-14 | 2007-11-08 | Acad Of Science Czech Republic | Wirkstoffvorläufer von Phosphonaten |
| US5208221A (en) | 1990-11-29 | 1993-05-04 | Bristol-Myers Squibb Company | Antiviral (phosphonomethoxy) methoxy purine/pyrimidine derivatives |
| US5378475A (en) | 1991-02-21 | 1995-01-03 | University Of Kentucky Research Foundation | Sustained release drug delivery devices |
| CZ284678B6 (cs) | 1991-05-20 | 1999-01-13 | Ústav Organické Chemie A Biochemie Avčr | Di(2-propyl)estery 1-fluor-2-fosfonomethoxy-3-p -toluensulfonyloxypropanů, způsob jejich přípravy a použití |
| DE69218968T2 (de) | 1991-10-11 | 1997-10-09 | Inst Of Organic Chemistry And | Antivirale acyclische phosphonomethoxyalkyl substituierte, alkenyl und alkynyl purin und pyrimidin-derivate |
| US6057305A (en) | 1992-08-05 | 2000-05-02 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | Antiretroviral enantiomeric nucleotide analogs |
| EP0618214A1 (en) | 1993-04-01 | 1994-10-05 | Merrell Dow Pharmaceuticals Inc. | Unsaturated phosphonate derivatives of purines and pyrimidines |
| CA2171743C (en) | 1993-09-17 | 2007-11-20 | Norbert W. Bischofberger | Nucleotide analogs |
| SI9620042A (sl) | 1995-02-27 | 1998-12-31 | Gilead Sciences, Inc. | Novi selektivni inhibitorji virusnih ali bakterijskih neuraminidaz |
| US5977061A (en) | 1995-04-21 | 1999-11-02 | Institute Of Organic Chemistry And Biochemistry Of The Academy Of Sciences Of The Czech Republic | N6 - substituted nucleotide analagues and their use |
| JP4033494B2 (ja) | 1996-07-26 | 2008-01-16 | ギリヤド サイエンシーズ， インコーポレイテッド | ヌクレオチドアナログ |
| MXPA04000138A (es) * | 2001-06-29 | 2005-06-06 | Acad Of Science Czech Republic | Compuestos novedosos y metodos de trabajo. |
-
2004
- 2004-06-16 SI SI200431649T patent/SI1644389T1/sl unknown
- 2004-06-16 WO PCT/CZ2004/000034 patent/WO2004111064A1/en not_active Ceased
- 2004-06-16 NZ NZ543864A patent/NZ543864A/en not_active IP Right Cessation
- 2004-06-16 EP EP04738454A patent/EP1644389B1/en not_active Expired - Lifetime
- 2004-06-16 KR KR1020057024279A patent/KR101102815B1/ko not_active Expired - Lifetime
- 2004-06-16 DK DK04738454.0T patent/DK1644389T3/da active
- 2004-06-16 EA EA200600046A patent/EA011948B1/ru not_active IP Right Cessation
- 2004-06-16 AT AT04738454T patent/ATE496056T1/de not_active IP Right Cessation
- 2004-06-16 DE DE602004031115T patent/DE602004031115D1/de not_active Expired - Lifetime
- 2004-06-16 CN CN2004800168859A patent/CN1805966B/zh not_active Expired - Lifetime
- 2004-06-16 AU AU2004247305A patent/AU2004247305B2/en not_active Expired
- 2004-06-16 US US10/869,005 patent/US7115592B2/en not_active Expired - Lifetime
- 2004-06-16 JP JP2006515644A patent/JP5280631B2/ja not_active Expired - Lifetime
- 2004-06-16 CA CA2527805A patent/CA2527805C/en not_active Expired - Lifetime
-
2005
- 2005-11-17 IL IL172015A patent/IL172015A/en active IP Right Grant
-
2006
- 2006-06-23 US US11/473,924 patent/US20060241081A1/en not_active Abandoned
-
2012
- 2012-05-21 JP JP2012115602A patent/JP2012153731A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| KR20060041182A (ko) | 2006-05-11 |
| JP5280631B2 (ja) | 2013-09-04 |
| CA2527805C (en) | 2012-08-21 |
| CN1805966B (zh) | 2013-03-13 |
| US20050075318A1 (en) | 2005-04-07 |
| SI1644389T1 (sl) | 2011-06-30 |
| CN1805966A (zh) | 2006-07-19 |
| EP1644389A1 (en) | 2006-04-12 |
| US7115592B2 (en) | 2006-10-03 |
| AU2004247305A1 (en) | 2004-12-23 |
| IL172015A0 (en) | 2009-02-11 |
| DK1644389T3 (da) | 2011-05-09 |
| EP1644389B1 (en) | 2011-01-19 |
| DE602004031115D1 (de) | 2011-03-03 |
| EA200600046A1 (ru) | 2006-06-30 |
| KR101102815B1 (ko) | 2012-01-05 |
| JP2012153731A (ja) | 2012-08-16 |
| AU2004247305B2 (en) | 2010-02-18 |
| US20060241081A1 (en) | 2006-10-26 |
| WO2004111064A1 (en) | 2004-12-23 |
| JP2006527702A (ja) | 2006-12-07 |
| CA2527805A1 (en) | 2004-12-23 |
| IL172015A (en) | 2016-07-31 |
| EA011948B1 (ru) | 2009-06-30 |
| HK1088013A1 (en) | 2006-10-27 |
| ATE496056T1 (de) | 2011-02-15 |
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