CA2632452A1 - Substituted o6-benzylguanines and use thereof - Google Patents
Substituted o6-benzylguanines and use thereof Download PDFInfo
- Publication number
- CA2632452A1 CA2632452A1 CA002632452A CA2632452A CA2632452A1 CA 2632452 A1 CA2632452 A1 CA 2632452A1 CA 002632452 A CA002632452 A CA 002632452A CA 2632452 A CA2632452 A CA 2632452A CA 2632452 A1 CA2632452 A1 CA 2632452A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- compound
- amino
- benzyl
- mammal
- 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.)
- Abandoned
Links
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical group O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims abstract description 83
- -1 5-substituted 2,4-diamino-6-benzyloxypyrimidines Chemical class 0.000 claims abstract description 71
- 238000000034 method Methods 0.000 claims abstract description 30
- 238000011282 treatment Methods 0.000 claims abstract description 30
- 241000124008 Mammalia Species 0.000 claims abstract description 28
- 231100000433 cytotoxic Toxicity 0.000 claims abstract description 22
- 230000001472 cytotoxic effect Effects 0.000 claims abstract description 22
- 230000003902 lesion Effects 0.000 claims abstract description 21
- 239000002295 alkylating antineoplastic agent Substances 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 18
- 230000002708 enhancing effect Effects 0.000 claims abstract description 16
- 239000003937 drug carrier Substances 0.000 claims abstract description 15
- 230000000973 chemotherapeutic effect Effects 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims description 117
- 229910052739 hydrogen Inorganic materials 0.000 claims description 76
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 29
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
- 125000001424 substituent group Chemical group 0.000 claims description 24
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000003282 alkyl amino group Chemical group 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 13
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 13
- DSIVLMKQNTVXOD-UHFFFAOYSA-N 5-nitro-4-phenylmethoxypyrimidin-2-amine Chemical compound NC1=NC=C([N+]([O-])=O)C(OCC=2C=CC=CC=2)=N1 DSIVLMKQNTVXOD-UHFFFAOYSA-N 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000001475 halogen functional group Chemical group 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 10
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 10
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 9
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 9
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 9
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 9
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 claims description 9
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 9
- 229920002554 vinyl polymer Polymers 0.000 claims description 9
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 7
- QRPFYXCKZRCRTD-UHFFFAOYSA-N 4-methyl-5-nitro-6-phenylmethoxypyrimidin-2-amine Chemical compound CC1=NC(N)=NC(OCC=2C=CC=CC=2)=C1[N+]([O-])=O QRPFYXCKZRCRTD-UHFFFAOYSA-N 0.000 claims description 7
- 239000002202 Polyethylene glycol Substances 0.000 claims description 7
- 125000003441 thioacyl group Chemical group 0.000 claims description 7
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims 2
- 230000000937 inactivator Effects 0.000 abstract description 19
- FXXUYUZEWHFQJZ-UHFFFAOYSA-N 6-phenylmethoxy-1,3,5-triazine-2,4-diamine Chemical compound NC1=NC(N)=NC(OCC=2C=CC=CC=2)=N1 FXXUYUZEWHFQJZ-UHFFFAOYSA-N 0.000 abstract description 10
- 229960005524 O6-benzylguanine Drugs 0.000 abstract 2
- KRWMERLEINMZFT-UHFFFAOYSA-N O6-benzylguanine Chemical class C=12NC=NC2=NC(N)=NC=1OCC1=CC=CC=C1 KRWMERLEINMZFT-UHFFFAOYSA-N 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 79
- 239000000243 solution Substances 0.000 description 70
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 60
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- 239000007787 solid Substances 0.000 description 45
- 239000000203 mixture Substances 0.000 description 36
- 210000004027 cell Anatomy 0.000 description 34
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 28
- 206010028980 Neoplasm Diseases 0.000 description 25
- 229910052799 carbon Inorganic materials 0.000 description 25
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
- 239000002253 acid Substances 0.000 description 24
- 230000000694 effects Effects 0.000 description 24
- 229910052757 nitrogen Inorganic materials 0.000 description 24
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 23
- 238000005481 NMR spectroscopy Methods 0.000 description 21
- 235000019445 benzyl alcohol Nutrition 0.000 description 20
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 20
- 238000001914 filtration Methods 0.000 description 19
- 201000011510 cancer Diseases 0.000 description 18
- 150000002431 hydrogen Chemical group 0.000 description 18
- 230000002829 reductive effect Effects 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
- 238000009472 formulation Methods 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 16
- 102000002226 Alkyl and Aryl Transferases Human genes 0.000 description 15
- 108010014722 Alkyl and Aryl Transferases Proteins 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 239000002244 precipitate Substances 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 239000000284 extract Substances 0.000 description 14
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 14
- QGOLEGLENLEGAL-UHFFFAOYSA-N 6-phenylmethoxypyrimidine-2,4,5-triamine Chemical compound NC1=NC(N)=C(N)C(OCC=2C=CC=CC=2)=N1 QGOLEGLENLEGAL-UHFFFAOYSA-N 0.000 description 13
- 239000002502 liposome Substances 0.000 description 13
- MBQPVHNJEDDVCF-UHFFFAOYSA-N 5-nitroso-6-phenylmethoxypyrimidine-2,4-diamine Chemical compound NC1=NC(N)=C(N=O)C(OCC=2C=CC=CC=2)=N1 MBQPVHNJEDDVCF-UHFFFAOYSA-N 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- 230000000415 inactivating effect Effects 0.000 description 12
- 230000002779 inactivation Effects 0.000 description 12
- QHAPAKDNWZEJLZ-UHFFFAOYSA-N 5-nitro-6-phenylmethoxypyrimidin-4-amine Chemical compound NC1=NC=NC(OCC=2C=CC=CC=2)=C1[N+]([O-])=O QHAPAKDNWZEJLZ-UHFFFAOYSA-N 0.000 description 10
- VLVHHGNPHBVEIG-UHFFFAOYSA-N 5-nitro-6-phenylmethoxypyrimidine-2,4-diamine Chemical compound NC1=NC(N)=C([N+]([O-])=O)C(OCC=2C=CC=CC=2)=N1 VLVHHGNPHBVEIG-UHFFFAOYSA-N 0.000 description 10
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 10
- UUPZIHWWLWLUKS-UHFFFAOYSA-N [(6-oxo-3,7-dihydropurin-2-yl)amino]methyl 2,2-dimethylpropanoate Chemical compound N1C(NCOC(=O)C(C)(C)C)=NC(=O)C2=C1N=CN2 UUPZIHWWLWLUKS-UHFFFAOYSA-N 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 229910052708 sodium Inorganic materials 0.000 description 10
- 235000010288 sodium nitrite Nutrition 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- UFPIUYMVVMDAIY-UHFFFAOYSA-N 5-bromo-6-phenylmethoxypyrimidine-2,4-diamine Chemical compound NC1=NC(N)=C(Br)C(OCC=2C=CC=CC=2)=N1 UFPIUYMVVMDAIY-UHFFFAOYSA-N 0.000 description 9
- 208000029742 colonic neoplasm Diseases 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000546 pharmaceutical excipient Substances 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 229910052786 argon Inorganic materials 0.000 description 8
- 125000004181 carboxyalkyl group Chemical group 0.000 description 8
- 235000014113 dietary fatty acids Nutrition 0.000 description 8
- 239000000194 fatty acid Substances 0.000 description 8
- 229930195729 fatty acid Natural products 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 150000003230 pyrimidines Chemical class 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 159000000000 sodium salts Chemical class 0.000 description 8
- MVIHQMTVQZOYCE-UHFFFAOYSA-N 6-phenylmethoxypyrimidine-2,4-diamine Chemical compound NC1=NC(N)=CC(OCC=2C=CC=CC=2)=N1 MVIHQMTVQZOYCE-UHFFFAOYSA-N 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 229940100198 alkylating agent Drugs 0.000 description 7
- 239000002168 alkylating agent Substances 0.000 description 7
- 239000002246 antineoplastic agent Substances 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- 125000006575 electron-withdrawing group Chemical group 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
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- 239000012362 glacial acetic acid Substances 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 239000004094 surface-active agent Substances 0.000 description 7
- 208000026310 Breast neoplasm Diseases 0.000 description 6
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 6
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- LFQULJPVXNYWAG-UHFFFAOYSA-N sodium;phenylmethanolate Chemical compound [Na]OCC1=CC=CC=C1 LFQULJPVXNYWAG-UHFFFAOYSA-N 0.000 description 6
- XSQWTUFYGIMUNS-UHFFFAOYSA-N 6-chloro-8-methyl-7h-purin-2-amine Chemical compound NC1=NC(Cl)=C2NC(C)=NC2=N1 XSQWTUFYGIMUNS-UHFFFAOYSA-N 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 5
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- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 5
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- 102000049538 human AGT Human genes 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
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- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 5
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- SGSSKEDGVONRGC-UHFFFAOYSA-N N(2)-methylguanine Chemical compound O=C1NC(NC)=NC2=C1N=CN2 SGSSKEDGVONRGC-UHFFFAOYSA-N 0.000 description 4
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- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/50—Three nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/40—Nitrogen atoms
- C07D251/48—Two nitrogen atoms
- C07D251/52—Two nitrogen atoms with an oxygen or sulfur atom attached to the third ring carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/40—Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/283,953 US5525606A (en) | 1994-08-01 | 1994-08-01 | Substituted 06-benzylguanines and 6(4)-benzyloxypyrimidines |
| US08/283,953 | 1994-08-01 | ||
| CA002195856A CA2195856C (en) | 1994-08-01 | 1995-07-31 | Substituted o6-benzylguanines and use thereof |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002195856A Division CA2195856C (en) | 1994-08-01 | 1995-07-31 | Substituted o6-benzylguanines and use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2632452A1 true CA2632452A1 (en) | 1996-02-15 |
Family
ID=23088285
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002632452A Abandoned CA2632452A1 (en) | 1994-08-01 | 1995-07-31 | Substituted o6-benzylguanines and use thereof |
| CA002195856A Expired - Fee Related CA2195856C (en) | 1994-08-01 | 1995-07-31 | Substituted o6-benzylguanines and use thereof |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002195856A Expired - Fee Related CA2195856C (en) | 1994-08-01 | 1995-07-31 | Substituted o6-benzylguanines and use thereof |
Country Status (10)
| Country | Link |
|---|---|
| US (8) | US5525606A (enExample) |
| EP (3) | EP0775142B1 (enExample) |
| JP (2) | JP3981407B2 (enExample) |
| AT (2) | ATE286054T1 (enExample) |
| CA (2) | CA2632452A1 (enExample) |
| DE (2) | DE69523462T2 (enExample) |
| DK (2) | DK0775142T3 (enExample) |
| ES (2) | ES2167451T3 (enExample) |
| PT (2) | PT1142893E (enExample) |
| WO (1) | WO1996004281A1 (enExample) |
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| US6060458A (en) * | 1998-02-13 | 2000-05-09 | The United States Of America As Represented By The Department Of Health And Human Services | Oligodeoxyribonucleotides comprising O6 -benzylguanine and their use |
| GB9806739D0 (en) * | 1998-03-28 | 1998-05-27 | Univ Newcastle Ventures Ltd | Cyclin dependent kinase inhibitors |
| US6677345B1 (en) * | 1998-03-28 | 2004-01-13 | Cancer Research Campaign Technology Limited | Cyclin dependent kinase inhibitors |
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| KR100368515B1 (ko) * | 1999-02-03 | 2003-01-24 | 주식회사 엘지생명과학 | 싸이클린 의존 키나아제 저해제 및 그의 제조 방법 |
| US8791081B2 (en) * | 1999-08-13 | 2014-07-29 | Case Western Reserve University | MGMT inhibitor combination for the treatment of neoplastic disorders |
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| US6693099B2 (en) | 2000-10-17 | 2004-02-17 | The Procter & Gamble Company | Substituted piperazine compounds optionally containing a quinolyl moiety for treating multidrug resistance |
| AU2002216650A1 (en) * | 2000-10-31 | 2002-05-15 | Lynn Bonham | Triazine derivatives as lpaat-b inhibitors and uses thereof |
| GB0101686D0 (en) * | 2001-01-23 | 2001-03-07 | Cancer Res Campaign Tech | Cyclin dependent kinase inhibitors |
| CA2438099A1 (en) * | 2001-02-08 | 2002-12-12 | Memory Pharmaceuticals Corporation | Trifluoromethylpurines as phosphodiesterase 4 inhibitors |
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| US20070129334A1 (en) * | 2001-10-30 | 2007-06-07 | Conforma Therapeutics Corporation | Orally Active Purine-Based Inhibitors of Heat Shock Protein 90 |
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| AU2003261418B2 (en) * | 2002-08-08 | 2010-05-27 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors |
| GB0219746D0 (en) | 2002-08-23 | 2002-10-02 | Inst Of Ex Botany Ascr | Azapurine derivatives |
| DE10307928A1 (de) * | 2003-02-25 | 2004-09-16 | Faustus Forschungs Cie. Translational Cancer Research Gmbh | Verwendung von 1-(2-Chlorethyl)-1-nitroso-3-(2-hydroxyethyl)-urea zur Behandlung von Pankreaskarzinomen, Weichteilsarkomen, Hodentumoren, Lymphomen, Thymomen, Wilms Tumoren, Nierenkarzinomen, Melanomen, Lungentumoren, intracerebralen Metastasen, Tumoren im Kopf- und Halsbereich, und Mamma-Karzinomen |
| EP2145888A1 (en) * | 2003-09-18 | 2010-01-20 | Conforma Therapeutics Corporation | Deazapurine derivatives as HSP90-Inhibitors |
| EP1701957A1 (en) * | 2004-01-06 | 2006-09-20 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, represented by THE DEPARTMENT OF HEALTH & HUMAN SERVICES | 2-amino-o4-substituted pteridines and their use as inactivators of o6-alkylguanine-dna alkyltransferase |
| CA2566424A1 (en) * | 2004-05-12 | 2005-11-17 | Bayer Cropscience Gmbh | Plant growth regulation |
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| WO2006029065A1 (en) * | 2004-09-08 | 2006-03-16 | Goverment Of The United States Of America Represented By The Secretary, Department Of Health And Human Services | Beta-gluguronidase cleavable prodrugs of o6-alkylguanine-dna alkyltransferase inactivators |
| CN100386115C (zh) * | 2004-10-14 | 2008-05-07 | 孔庆忠 | 一种抗癌药物组合物 |
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| BRPI0609509A2 (pt) * | 2005-03-30 | 2010-04-13 | Conforma Therapeutics Corp | composto ou um polimorfo, solvato, tautÈmero, enanciÈmero, pró-droga ou sal farmaceuticamente aceitável do mesmo, composição farmacêutica, e, uso do composto, polimorfo, solvato, tautÈmero, enanciÈmero, pró-droga ou sal farmaceuticamente aceitável |
| WO2006114409A1 (en) * | 2005-04-27 | 2006-11-02 | Covalys Biosciences Ag | Pyrimidines reacting with o6-alkylguanine-dna alkyltransferase |
| DK1889198T3 (da) | 2005-04-28 | 2015-02-09 | Proteus Digital Health Inc | Farma-informatiksystem |
| ES2577514T3 (es) | 2005-08-22 | 2016-07-15 | The Regents Of The University Of California | Antagonistas de TLR |
| WO2007035963A2 (en) * | 2005-09-23 | 2007-03-29 | Conforma Therapeutics Corporation | Anti-tumor methods using multi drug resistance independent synthetic hsp90 inhibitors |
| WO2007142755A2 (en) * | 2006-05-31 | 2007-12-13 | The Regents Of The University Of California | Purine analogs |
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| EA019151B1 (ru) | 2007-02-07 | 2014-01-30 | Дзе Регентс Оф Дзе Юниверсити Оф Калифорния | Конъюгаты синтетических агонистов tlr и их применение |
| US8188055B2 (en) * | 2007-05-02 | 2012-05-29 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Inactivators of O6-alkylguanine-DNA alkyltransferase |
| EP1990661B1 (en) | 2007-05-07 | 2018-08-15 | CSEM Centre Suisse d'Electronique et de Microtechnique SA - Recherche et Développement | Isotropic zero-order diffractive filter |
| EP2259788A4 (en) * | 2008-02-07 | 2011-03-16 | Univ California | TREATMENT OF BLADDER DISEASES WITH A TLR7 ACTIVATOR |
| WO2010088924A1 (en) | 2009-02-06 | 2010-08-12 | Telormedix Sa | Pharmaceutical compositions comprising imidazoquinolin(amines) and derivatives thereof suitable for local administration |
| KR20110117705A (ko) * | 2009-02-11 | 2011-10-27 | 더 리전트 오브 더 유니버시티 오브 캘리포니아 | 톨-유사 수용체 조정제 및 질병의 치료 |
| WO2010095940A2 (en) | 2009-02-20 | 2010-08-26 | To-Bbb Holding B.V. | Glutathione-based drug delivery system |
| TWI556839B (zh) | 2009-05-06 | 2016-11-11 | 研究室護膚股份有限公司 | 包含活性劑－磷酸鈣粒子複合物之皮膚遞送組成物及其使用方法 |
| EP2470535A4 (en) * | 2009-08-24 | 2014-01-01 | Univ Duke | COMPOSITIONS, METHODS, AND KITS FOR DETERMINING AN ALKYL TRANSFERASE |
| CN101850504B (zh) * | 2010-05-06 | 2011-11-16 | 陕西理工学院 | 一种用两个步进电机控制主轴运动的振动制孔装置 |
| US20120077778A1 (en) | 2010-09-29 | 2012-03-29 | Andrea Bourdelais | Ladder-Frame Polyether Conjugates |
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| US20130236504A1 (en) * | 2012-03-06 | 2013-09-12 | Medical University Of South Carolina | Delivery System for Enhancing Drug Efficacy |
| WO2014025749A2 (en) * | 2012-08-06 | 2014-02-13 | Sirga Advanced Biopharma, Inc. | Small molecule inhibitors of viral protein interactions with human t-rna |
| ES2688194T3 (es) * | 2014-09-11 | 2018-10-31 | Bristol-Myers Squibb Company | Inhibidores de mieloperoxidasa de triazolopirimidina y triazolopiridina de tioéter |
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-
1994
- 1994-08-01 US US08/283,953 patent/US5525606A/en not_active Expired - Lifetime
-
1995
- 1995-07-31 EP EP95928237A patent/EP0775142B1/en not_active Expired - Lifetime
- 1995-07-31 PT PT01108585T patent/PT1142893E/pt unknown
- 1995-07-31 DE DE69523462T patent/DE69523462T2/de not_active Expired - Fee Related
- 1995-07-31 WO PCT/US1995/009702 patent/WO1996004281A1/en not_active Ceased
- 1995-07-31 CA CA002632452A patent/CA2632452A1/en not_active Abandoned
- 1995-07-31 CA CA002195856A patent/CA2195856C/en not_active Expired - Fee Related
- 1995-07-31 ES ES95928237T patent/ES2167451T3/es not_active Expired - Lifetime
- 1995-07-31 DK DK95928237T patent/DK0775142T3/da active
- 1995-07-31 AT AT01108585T patent/ATE286054T1/de not_active IP Right Cessation
- 1995-07-31 EP EP01108585A patent/EP1142893B1/en not_active Expired - Lifetime
- 1995-07-31 DK DK01108585T patent/DK1142893T3/da active
- 1995-07-31 JP JP50669496A patent/JP3981407B2/ja not_active Expired - Lifetime
- 1995-07-31 AT AT95928237T patent/ATE207490T1/de not_active IP Right Cessation
- 1995-07-31 EP EP04030121A patent/EP1518854A1/en not_active Withdrawn
- 1995-07-31 DE DE69533900T patent/DE69533900T2/de not_active Expired - Fee Related
- 1995-07-31 ES ES01108585T patent/ES2233513T3/es not_active Expired - Lifetime
- 1995-07-31 PT PT95928237T patent/PT775142E/pt unknown
- 1995-07-31 US US08/849,223 patent/US5958932A/en not_active Expired - Fee Related
-
1996
- 1996-06-11 US US08/661,923 patent/US5753668A/en not_active Expired - Lifetime
-
1997
- 1997-09-11 US US08/927,846 patent/US5916894A/en not_active Expired - Fee Related
-
1999
- 1999-05-25 US US09/318,238 patent/US6172070B1/en not_active Expired - Fee Related
- 1999-06-15 US US09/333,047 patent/US6333331B1/en not_active Expired - Fee Related
-
2000
- 2000-06-09 US US09/590,187 patent/US6303604B1/en not_active Expired - Fee Related
-
2001
- 2001-08-14 US US09/928,410 patent/US6436945B2/en not_active Expired - Fee Related
-
2006
- 2006-10-04 JP JP2006273447A patent/JP2007077157A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US5916894A (en) | 1999-06-29 |
| EP1518854A1 (en) | 2005-03-30 |
| ATE207490T1 (de) | 2001-11-15 |
| ES2233513T3 (es) | 2005-06-16 |
| EP0775142B1 (en) | 2001-10-24 |
| DK1142893T3 (da) | 2005-03-29 |
| PT775142E (pt) | 2002-04-29 |
| AU3207995A (en) | 1996-03-04 |
| DE69523462T2 (de) | 2002-07-11 |
| US20020013299A1 (en) | 2002-01-31 |
| JPH10508288A (ja) | 1998-08-18 |
| US6303604B1 (en) | 2001-10-16 |
| EP1142893A1 (en) | 2001-10-10 |
| DE69523462D1 (de) | 2001-11-29 |
| US6436945B2 (en) | 2002-08-20 |
| JP2007077157A (ja) | 2007-03-29 |
| CA2195856C (en) | 2008-09-30 |
| DE69533900T2 (de) | 2005-12-29 |
| DE69533900D1 (de) | 2005-02-03 |
| EP0775142A1 (en) | 1997-05-28 |
| JP3981407B2 (ja) | 2007-09-26 |
| AU702711B2 (en) | 1999-03-04 |
| US6172070B1 (en) | 2001-01-09 |
| US5753668A (en) | 1998-05-19 |
| US6333331B1 (en) | 2001-12-25 |
| CA2195856A1 (en) | 1996-02-15 |
| ES2167451T3 (es) | 2002-05-16 |
| PT1142893E (pt) | 2005-04-29 |
| EP1142893B1 (en) | 2004-12-29 |
| ATE286054T1 (de) | 2005-01-15 |
| US5525606A (en) | 1996-06-11 |
| DK0775142T3 (da) | 2002-02-18 |
| US5958932A (en) | 1999-09-28 |
| WO1996004281A1 (en) | 1996-02-15 |
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| EEER | Examination request | ||
| FZDE | Discontinued |