AU767599B2 - Novel prodrugs for phosphorus-containing compounds - Google Patents
Novel prodrugs for phosphorus-containing compounds Download PDFInfo
- Publication number
- AU767599B2 AU767599B2 AU30699/99A AU3069999A AU767599B2 AU 767599 B2 AU767599 B2 AU 767599B2 AU 30699/99 A AU30699/99 A AU 30699/99A AU 3069999 A AU3069999 A AU 3069999A AU 767599 B2 AU767599 B2 AU 767599B2
- Authority
- AU
- Australia
- Prior art keywords
- group
- aryl
- alkyl
- substituted
- attached
- 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.)
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- 229940002612 prodrug Drugs 0.000 title claims description 257
- 239000000651 prodrug Substances 0.000 title claims description 257
- 229910052698 phosphorus Inorganic materials 0.000 title claims description 247
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 title claims description 227
- 239000011574 phosphorus Substances 0.000 title claims description 227
- 150000001875 compounds Chemical class 0.000 title claims description 184
- 125000003118 aryl group Chemical group 0.000 claims description 487
- 125000000217 alkyl group Chemical group 0.000 claims description 472
- 125000002723 alicyclic group Chemical group 0.000 claims description 307
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 305
- 125000001072 heteroaryl group Chemical group 0.000 claims description 266
- 229910052721 tungsten Inorganic materials 0.000 claims description 261
- 125000004429 atom Chemical group 0.000 claims description 241
- 229910052760 oxygen Inorganic materials 0.000 claims description 240
- 239000001301 oxygen Substances 0.000 claims description 235
- 125000004122 cyclic group Chemical group 0.000 claims description 230
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 191
- -1 alkylthiocarbonyloxy Chemical group 0.000 claims description 162
- 229910052799 carbon Inorganic materials 0.000 claims description 156
- 238000000034 method Methods 0.000 claims description 154
- 229910052739 hydrogen Inorganic materials 0.000 claims description 148
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 148
- 125000005842 heteroatom Chemical group 0.000 claims description 133
- 125000003107 substituted aryl group Chemical group 0.000 claims description 133
- 125000004432 carbon atom Chemical group C* 0.000 claims description 125
- 229910052720 vanadium Inorganic materials 0.000 claims description 120
- 125000004423 acyloxy group Chemical group 0.000 claims description 119
- 239000003814 drug Substances 0.000 claims description 118
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 116
- 125000005200 aryloxy carbonyloxy group Chemical group 0.000 claims description 110
- 150000001721 carbon Chemical group 0.000 claims description 110
- 229940079593 drug Drugs 0.000 claims description 91
- 150000003839 salts Chemical class 0.000 claims description 76
- 125000001424 substituent group Chemical group 0.000 claims description 64
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 55
- 229910052757 nitrogen Inorganic materials 0.000 claims description 51
- 125000005750 substituted cyclic group Chemical group 0.000 claims description 51
- 238000001727 in vivo Methods 0.000 claims description 50
- 125000000304 alkynyl group Chemical group 0.000 claims description 49
- 125000003342 alkenyl group Chemical group 0.000 claims description 47
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 46
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 46
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 43
- 241001465754 Metazoa Species 0.000 claims description 38
- 210000004185 liver Anatomy 0.000 claims description 38
- 125000000623 heterocyclic group Chemical group 0.000 claims description 36
- 238000004519 manufacturing process Methods 0.000 claims description 32
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 28
- OIRDTQYFTABQOQ-UHTZMRCNSA-N Vidarabine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O OIRDTQYFTABQOQ-UHTZMRCNSA-N 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 26
- 150000002367 halogens Chemical class 0.000 claims description 25
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 22
- 125000004414 alkyl thio group Chemical group 0.000 claims description 22
- OIRDTQYFTABQOQ-UHFFFAOYSA-N ara-adenosine Natural products Nc1ncnc2n(cnc12)C1OC(CO)C(O)C1O OIRDTQYFTABQOQ-UHFFFAOYSA-N 0.000 claims description 22
- 101150035354 araA gene Proteins 0.000 claims description 22
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 claims description 21
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 21
- 208000006454 hepatitis Diseases 0.000 claims description 21
- 231100000283 hepatitis Toxicity 0.000 claims description 21
- 101100002068 Bacillus subtilis (strain 168) araR gene Proteins 0.000 claims description 20
- 101150044616 araC gene Proteins 0.000 claims description 20
- 239000003112 inhibitor Substances 0.000 claims description 20
- 125000004437 phosphorous atom Chemical group 0.000 claims description 20
- 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 19
- 239000002253 acid Substances 0.000 claims description 18
- 239000003443 antiviral agent Substances 0.000 claims description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
- 230000008569 process Effects 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 16
- 230000000694 effects Effects 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 229910019142 PO4 Inorganic materials 0.000 claims description 14
- 239000002246 antineoplastic agent Substances 0.000 claims description 14
- 150000002148 esters Chemical class 0.000 claims description 14
- 125000005843 halogen group Chemical group 0.000 claims description 14
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 241000282414 Homo sapiens Species 0.000 claims description 12
- 208000036142 Viral infection Diseases 0.000 claims description 12
- 210000001853 liver microsome Anatomy 0.000 claims description 12
- ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 claims description 12
- 230000009385 viral infection Effects 0.000 claims description 12
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 108091000080 Phosphotransferase Proteins 0.000 claims description 11
- 201000011510 cancer Diseases 0.000 claims description 11
- 239000010452 phosphate Substances 0.000 claims description 11
- 102000020233 phosphotransferase Human genes 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 10
- 230000002708 enhancing effect Effects 0.000 claims description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 10
- 235000011178 triphosphate Nutrition 0.000 claims description 10
- 239000001226 triphosphate Substances 0.000 claims description 10
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims description 10
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 9
- 230000000840 anti-viral effect Effects 0.000 claims description 9
- 239000004059 squalene synthase inhibitor Substances 0.000 claims description 9
- 230000003612 virological effect Effects 0.000 claims description 9
- HBUBKKRHXORPQB-FJFJXFQQSA-N (2R,3S,4S,5R)-2-(6-amino-2-fluoro-9-purinyl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O HBUBKKRHXORPQB-FJFJXFQQSA-N 0.000 claims description 8
- 150000007513 acids Chemical class 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 8
- 231100000419 toxicity Toxicity 0.000 claims description 8
- 230000001988 toxicity Effects 0.000 claims description 8
- 208000030852 Parasitic disease Diseases 0.000 claims description 7
- 241000700605 Viruses Species 0.000 claims description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 239000007795 chemical reaction product Substances 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 7
- 230000001965 increasing effect Effects 0.000 claims description 7
- 208000030159 metabolic disease Diseases 0.000 claims description 7
- 150000004712 monophosphates Chemical class 0.000 claims description 7
- 239000002777 nucleoside Substances 0.000 claims description 7
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 7
- 230000003285 pharmacodynamic effect Effects 0.000 claims description 7
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
- 230000001093 anti-cancer Effects 0.000 claims description 6
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 6
- 238000002059 diagnostic imaging Methods 0.000 claims description 6
- 229960005102 foscarnet Drugs 0.000 claims description 6
- 210000003494 hepatocyte Anatomy 0.000 claims description 6
- 239000012216 imaging agent Substances 0.000 claims description 6
- 230000002459 sustained effect Effects 0.000 claims description 6
- 231100001274 therapeutic index Toxicity 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 210000003169 central nervous system Anatomy 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- RCGCZPXSRLLKCK-INIZCTEOSA-N (1s)-4-(3-phenoxyphenyl)-1-phosphonobutane-1-sulfonic acid Chemical compound OP(O)(=O)[C@@H](S(O)(=O)=O)CCCC1=CC=CC(OC=2C=CC=CC=2)=C1 RCGCZPXSRLLKCK-INIZCTEOSA-N 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 206010059866 Drug resistance Diseases 0.000 claims description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 102000006601 Thymidine Kinase Human genes 0.000 claims description 4
- 108020004440 Thymidine kinase Proteins 0.000 claims description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 4
- 235000012000 cholesterol Nutrition 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 4
- 150000002009 diols Chemical class 0.000 claims description 4
- 229930195729 fatty acid Natural products 0.000 claims description 4
- 239000000194 fatty acid Substances 0.000 claims description 4
- 150000004665 fatty acids Chemical class 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
- 201000004792 malaria Diseases 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 238000012261 overproduction Methods 0.000 claims description 4
- 238000011282 treatment Methods 0.000 claims description 4
- 150000003626 triacylglycerols Chemical class 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 230000001131 transforming effect Effects 0.000 claims description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 2
- 239000003524 antilipemic agent Substances 0.000 claims description 2
- 229960002949 fluorouracil Drugs 0.000 claims description 2
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims 27
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims 24
- JNTOCHDNEULJHD-UHFFFAOYSA-N Penciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(CCC(CO)CO)C=N2 JNTOCHDNEULJHD-UHFFFAOYSA-N 0.000 claims 23
- XUYJLQHKOGNDPB-UHFFFAOYSA-N phosphonoacetic acid Chemical compound OC(=O)CP(O)(O)=O XUYJLQHKOGNDPB-UHFFFAOYSA-N 0.000 claims 20
- 150000002431 hydrogen Chemical class 0.000 claims 16
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 15
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims 15
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims 15
- 125000005243 carbonyl alkyl group Chemical group 0.000 claims 15
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims 15
- BYEIJZFKOAXBBV-ATZCPNFKSA-N N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine Chemical compound CC(C)[C@H](C(O)=O)NC(=O)[C@H](CS)NC(=O)CCC[C@H](N)C(O)=O BYEIJZFKOAXBBV-ATZCPNFKSA-N 0.000 claims 14
- 101710099475 3'-phosphoadenosine 5'-phosphate phosphatase Proteins 0.000 claims 13
- 101710196411 Fructose-1,6-bisphosphatase Proteins 0.000 claims 13
- 101710186733 Fructose-1,6-bisphosphatase, chloroplastic Proteins 0.000 claims 13
- 101710109119 Fructose-1,6-bisphosphatase, cytosolic Proteins 0.000 claims 13
- 101710198902 Fructose-1,6-bisphosphate aldolase/phosphatase Proteins 0.000 claims 13
- FRPXSOOHWNMLPH-LURJTMIESA-N [(2s)-1-(6-aminopurin-9-yl)-3-hydroxypropan-2-yl]oxymethylphosphonic acid Chemical compound NC1=NC=NC2=C1N=CN2C[C@@H](CO)OCP(O)(O)=O FRPXSOOHWNMLPH-LURJTMIESA-N 0.000 claims 13
- BFZJTDBFUROXJA-UHFFFAOYSA-N [1-(6-aminopurin-9-yl)-3-fluoropropan-2-yl]oxymethylphosphonic acid Chemical compound NC1=NC=NC2=C1N=CN2CC(CF)OCP(O)(O)=O BFZJTDBFUROXJA-UHFFFAOYSA-N 0.000 claims 13
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 claims 13
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims 12
- 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 12
- 150000001409 amidines Chemical class 0.000 claims 12
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims 12
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims 12
- 150000003462 sulfoxides Chemical class 0.000 claims 12
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 claims 11
- 229960001179 penciclovir Drugs 0.000 claims 10
- 229960000329 ribavirin Drugs 0.000 claims 10
- 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 10
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 9
- UYTPUPDQBNUYGX-UHFFFAOYSA-N Guanine Natural products O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims 9
- IVSXFFJGASXYCL-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=NC=N[C]21 IVSXFFJGASXYCL-UHFFFAOYSA-N 0.000 claims 9
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims 8
- GHTIVOZHSNRAAW-JZXVYGCJSA-N (1E)-1-(4-hydroxybut-2-enylidene)-4-iminopyrimidin-1-ium-2-olate Chemical compound OCC=C\C=[N+]1/C=CC(=N)N=C1[O-] GHTIVOZHSNRAAW-JZXVYGCJSA-N 0.000 claims 7
- IPVFGAYTKQKGBM-BYPJNBLXSA-N 1-[(2r,3s,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-iodopyrimidine-2,4-dione Chemical compound F[C@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 IPVFGAYTKQKGBM-BYPJNBLXSA-N 0.000 claims 7
- XHXFQGAZAVKMFF-UHFFFAOYSA-N 2-(2,6-diaminopurin-9-yl)ethoxymethylphosphonic acid Chemical compound NC1=NC(N)=C2N=CN(CCOCP(O)(O)=O)C2=N1 XHXFQGAZAVKMFF-UHFFFAOYSA-N 0.000 claims 7
- BCSLVBZWCFTDPK-UDJQAZALSA-N 2-amino-9-[(2r,3r,4s)-3,4-bis(hydroxymethyl)oxetan-2-yl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](CO)[C@H]1CO BCSLVBZWCFTDPK-UDJQAZALSA-N 0.000 claims 7
- 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 7
- QBEIABZPRBJOFU-VDTYLAMSSA-N 4-amino-5-fluoro-1-[(2s,5r)-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)CC1 QBEIABZPRBJOFU-VDTYLAMSSA-N 0.000 claims 7
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 claims 7
- SWFJAJRDLUUIOA-IBCQBUCCSA-N 5-ethyl-1-[(2r,3s,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(CC)=CN1[C@H]1[C@@H](F)[C@H](O)[C@@H](CO)O1 SWFJAJRDLUUIOA-IBCQBUCCSA-N 0.000 claims 7
- GSDZMZKDKWSUOV-OEJXEDHQSA-N 5-prop-1-ynyl-1-[(3S,4R,5R)-3,4,5-trihydroxyoxan-2-yl]pyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C#CC)=CN1C1[C@@H](O)[C@H](O)[C@H](O)CO1 GSDZMZKDKWSUOV-OEJXEDHQSA-N 0.000 claims 7
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 claims 7
- VWFCHDSQECPREK-LURJTMIESA-N Cidofovir Chemical compound NC=1C=CN(C[C@@H](CO)OCP(O)(O)=O)C(=O)N=1 VWFCHDSQECPREK-LURJTMIESA-N 0.000 claims 7
- YOOVTUPUBVHMPG-UHFFFAOYSA-N Coformycin Natural products OC1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 YOOVTUPUBVHMPG-UHFFFAOYSA-N 0.000 claims 7
- VZKXOWRNJDEGLZ-WHFBIAKZSA-N Cys-Asp-Gly Chemical compound SC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O VZKXOWRNJDEGLZ-WHFBIAKZSA-N 0.000 claims 7
- PYJIWOQTJHPDAK-PRJMDXOYSA-N [(1s,2r,3s)-3-(6-aminopurin-9-yl)-2-(hydroxymethyl)cyclobutyl]methanol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](CO)[C@H]1CO PYJIWOQTJHPDAK-PRJMDXOYSA-N 0.000 claims 7
- 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 7
- 229950004398 broxuridine Drugs 0.000 claims 7
- YOOVTUPUBVHMPG-LODYRLCVSA-O coformycin(1+) Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C([NH+]=CNC[C@H]2O)=C2N=C1 YOOVTUPUBVHMPG-LODYRLCVSA-O 0.000 claims 7
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- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
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- C—CHEMISTRY; METALLURGY
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
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- 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
- C07F9/657163—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 the ring phosphorus atom being bound to at least one carbon atom
- C07F9/657181—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 the ring phosphorus atom being bound to at least one carbon atom the ring phosphorus atom and, at least, one ring oxygen atom being part of a (thio)phosphonic acid derivative
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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
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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
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- 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
- C07F9/65744—Esters of oxyacids of phosphorus condensed with carbocyclic or heterocyclic rings or ring systems
-
- 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
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- 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
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- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
- C07H19/207—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine adenine dinucleotide or nicotinamide-adenine dinucleotide
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Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2004200670A AU2004200670B2 (en) | 1998-03-06 | 2004-02-20 | Novel Prodrugs for Phosphorous-containing Compounds |
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| US7716498P | 1998-03-06 | 1998-03-06 | |
| US7716598P | 1998-03-06 | 1998-03-06 | |
| US60/077165 | 1998-03-06 | ||
| US60/077164 | 1998-03-06 | ||
| PCT/US1999/004908 WO1999045016A2 (en) | 1998-03-06 | 1999-03-05 | Novel prodrugs for phosphorus-containing compounds |
Related Child Applications (1)
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| AU2004200670A Division AU2004200670B2 (en) | 1998-03-06 | 2004-02-20 | Novel Prodrugs for Phosphorous-containing Compounds |
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| AU3069999A AU3069999A (en) | 1999-09-20 |
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| ES (1) | ES2401070T3 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AU6452098A (en) | 1997-03-07 | 1998-09-22 | Metabasis Therapeutics, Inc. | Novel purine inhibitors of fructose-1,6-bisphosphatase |
| DE69910045T2 (de) | 1998-09-09 | 2004-04-22 | Metabasis Therapeutics Inc., San Diego | Neue heteroaromatische fructose 1,6-bisphosphatase inhibitoren |
| US7205404B1 (en) | 1999-03-05 | 2007-04-17 | Metabasis Therapeutics, Inc. | Phosphorus-containing prodrugs |
| US6831069B2 (en) | 1999-08-27 | 2004-12-14 | Ribapharm Inc. | Pyrrolo[2,3-d]pyrimidine nucleoside analogs |
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Also Published As
| Publication number | Publication date |
|---|---|
| EP1060182B1 (en) | 2012-12-19 |
| CA2322487C (en) | 2010-07-20 |
| WO1999045016A9 (en) | 2000-03-02 |
| JP4741725B2 (ja) | 2011-08-10 |
| EP1060182A2 (en) | 2000-12-20 |
| AU3069999A (en) | 1999-09-20 |
| ES2401070T3 (es) | 2013-04-16 |
| WO1999045016A2 (en) | 1999-09-10 |
| WO1999045016A3 (en) | 2000-06-15 |
| CA2322487A1 (en) | 1999-09-10 |
| JP2002505333A (ja) | 2002-02-19 |
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