DE69709857T2 - Acridonderivate als antineoplastische-und antiretrovirale mittel - Google Patents
Acridonderivate als antineoplastische-und antiretrovirale mittelInfo
- Publication number
- DE69709857T2 DE69709857T2 DE69709857T DE69709857T DE69709857T2 DE 69709857 T2 DE69709857 T2 DE 69709857T2 DE 69709857 T DE69709857 T DE 69709857T DE 69709857 T DE69709857 T DE 69709857T DE 69709857 T2 DE69709857 T2 DE 69709857T2
- Authority
- DE
- Germany
- Prior art keywords
- compounds
- compound
- temacrazine
- hiv
- cells
- 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.)
- Expired - Lifetime
Links
- 239000002246 antineoplastic agent Substances 0.000 title claims abstract description 15
- 229940034982 antineoplastic agent Drugs 0.000 title claims abstract description 9
- 229940124522 antiretrovirals Drugs 0.000 title claims description 5
- 239000003903 antiretrovirus agent Substances 0.000 title claims description 5
- FZEYVTFCMJSGMP-UHFFFAOYSA-N acridone Chemical class C1=CC=C2C(=O)C3=CC=CC=C3NC2=C1 FZEYVTFCMJSGMP-UHFFFAOYSA-N 0.000 title abstract description 6
- 230000000118 anti-neoplastic effect Effects 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 99
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 11
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 6
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims description 29
- 238000004519 manufacturing process Methods 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 7
- 230000029812 viral genome replication Effects 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 238000011282 treatment Methods 0.000 abstract description 16
- 239000003443 antiviral agent Substances 0.000 abstract description 9
- 230000003612 virological effect Effects 0.000 abstract description 9
- 206010028980 Neoplasm Diseases 0.000 abstract description 7
- 230000003389 potentiating effect Effects 0.000 abstract description 7
- GDALETGZDYOOGB-UHFFFAOYSA-N Acridone Natural products C1=C(O)C=C2N(C)C3=CC=CC=C3C(=O)C2=C1O GDALETGZDYOOGB-UHFFFAOYSA-N 0.000 abstract description 4
- 241000725303 Human immunodeficiency virus Species 0.000 abstract description 4
- 201000011510 cancer Diseases 0.000 abstract description 4
- 125000000217 alkyl group Chemical group 0.000 abstract description 3
- 229910052736 halogen Inorganic materials 0.000 abstract description 3
- 150000002367 halogens Chemical class 0.000 abstract description 3
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- BESDYXOPYOAWRZ-UHFFFAOYSA-N temacrazine Chemical compound C12=C3C(=O)C4=CC=CC=C4N1N=NC2=CC=C3NCCCN(CC1)CCN1CCCNC1=CC=C2N=NN3C4=CC=CC=C4C(=O)C1=C32 BESDYXOPYOAWRZ-UHFFFAOYSA-N 0.000 description 62
- 210000004027 cell Anatomy 0.000 description 60
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 29
- 230000000694 effects Effects 0.000 description 28
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 19
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 19
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 19
- 229940079593 drug Drugs 0.000 description 19
- 239000000203 mixture Substances 0.000 description 18
- 241000700605 Viruses Species 0.000 description 15
- 230000000840 anti-viral effect Effects 0.000 description 14
- -1 alkyl radical Chemical class 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 13
- 101710205625 Capsid protein p24 Proteins 0.000 description 12
- 108020004414 DNA Proteins 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 101710177166 Phosphoprotein Proteins 0.000 description 12
- 101710149279 Small delta antigen Proteins 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000003556 assay Methods 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- 108020004999 messenger RNA Proteins 0.000 description 11
- 230000010076 replication Effects 0.000 description 11
- 208000015181 infectious disease Diseases 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 230000002458 infectious effect Effects 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000013518 transcription Methods 0.000 description 8
- 230000035897 transcription Effects 0.000 description 8
- WAZBTRIRFDKNMU-UHFFFAOYSA-N 164672-54-2 Chemical compound C12=C3C(=O)C4=CC=CC=C4N1C=NC2=CC=C3NCCCN(C)CCCNC1=CC=C2C3=C1C(=O)C1=CC=CC=C1N3C=N2 WAZBTRIRFDKNMU-UHFFFAOYSA-N 0.000 description 7
- XUSNPFGLKGCWGN-UHFFFAOYSA-N 3-[4-(3-aminopropyl)piperazin-1-yl]propan-1-amine Chemical compound NCCCN1CCN(CCCN)CC1 XUSNPFGLKGCWGN-UHFFFAOYSA-N 0.000 description 6
- 230000001120 cytoprotective effect Effects 0.000 description 6
- 230000001566 pro-viral effect Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 108010016183 Human immunodeficiency virus 1 p16 protease Proteins 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000009826 neoplastic cell growth Effects 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- MQFWSJLJVULXGV-UHFFFAOYSA-N wmc-50 Chemical compound C12=C3C(=O)C4=CC=CC=C4N1N=NC2=CC=C3NCCCN(CC1)CCN1CCCNC1=CC=C2N=CN3C4=CC=CC=C4C(=O)C1=C32 MQFWSJLJVULXGV-UHFFFAOYSA-N 0.000 description 5
- NFEQWPGBULCHQJ-UHFFFAOYSA-N 10-[3-[4-[3-[(8-oxo-1,14-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-2,4,6,9,11,13(16),14-heptaen-10-yl)amino]propyl]piperazin-1-yl]propylamino]-1,14-diazatetracyclo[7.6.1.02,7.013,16]hexadeca-2,4,6,9,11,13(16),14-heptaen-8-one Chemical compound C12=C3C(=O)C4=CC=CC=C4N1C=NC2=CC=C3NCCCN(CC1)CCN1CCCNC1=CC=C2N=CN3C4=CC=CC=C4C(=O)C1=C32 NFEQWPGBULCHQJ-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 108700020129 Human immunodeficiency virus 1 p31 integrase Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 102100034391 Porphobilinogen deaminase Human genes 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- 206010038997 Retroviral infections Diseases 0.000 description 4
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 4
- 108010067390 Viral Proteins Proteins 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000001588 bifunctional effect Effects 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 210000005260 human cell Anatomy 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 230000010354 integration Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000010839 reverse transcription Methods 0.000 description 4
- 231100001274 therapeutic index Toxicity 0.000 description 4
- 241001430294 unidentified retrovirus Species 0.000 description 4
- 210000002845 virion Anatomy 0.000 description 4
- FGWARXSCGJFBCM-UHFFFAOYSA-N wmc-42 Chemical compound C12=C3C(=O)C4=CC=CC=C4N1N=NC2=CC=C3NCCCN(C)CCCNC1=CC=C2C3=C1C(=O)C1=CC=CC=C1N3C=N2 FGWARXSCGJFBCM-UHFFFAOYSA-N 0.000 description 4
- 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 4
- XNHLPMFRWXKIEY-UHFFFAOYSA-N 1-chloro-4-nitro-10h-acridin-9-one Chemical compound N1C2=CC=CC=C2C(=O)C2=C1C([N+](=O)[O-])=CC=C2Cl XNHLPMFRWXKIEY-UHFFFAOYSA-N 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 102100034343 Integrase Human genes 0.000 description 3
- 235000019759 Maize starch Nutrition 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 108010076039 Polyproteins Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 125000004103 aminoalkyl group Chemical group 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000002687 intercalation Effects 0.000 description 3
- 238000009830 intercalation Methods 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000010534 mechanism of action Effects 0.000 description 3
- 238000011580 nude mouse model Methods 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 229960002555 zidovudine Drugs 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- CZZQTPGFRJQMLZ-UHFFFAOYSA-N 8,10-dihydrotriazolo[4,5-a]acridin-9-one Chemical group N1=C2C=CC3=NN=NC3=C2C=C2C1=CCC(=O)C2 CZZQTPGFRJQMLZ-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- 208000037357 HIV infectious disease Diseases 0.000 description 2
- 101001067140 Homo sapiens Porphobilinogen deaminase Proteins 0.000 description 2
- 108010056651 Hydroxymethylbilane synthase Proteins 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 2
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 230000000719 anti-leukaemic effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229960005091 chloramphenicol Drugs 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 2
- 230000000120 cytopathologic effect Effects 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 108700004025 env Genes Proteins 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000012510 hollow fiber Substances 0.000 description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000011150 stannous chloride Nutrition 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 230000035899 viability Effects 0.000 description 2
- 230000006514 viral protein processing Effects 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 description 1
- YUIOPHXTILULQC-UHFFFAOYSA-N 1,4-Dithiane-2,5-diol Chemical compound OC1CSC(O)CS1 YUIOPHXTILULQC-UHFFFAOYSA-N 0.000 description 1
- 125000006083 1-bromoethyl group Chemical group 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- MALZYBOXBVXCSN-UHFFFAOYSA-N 11h-pyrido[3,2-a]carbazole Chemical class C1=CC2=NC=CC=C2C2=C1C1=CC=CC=C1N2 MALZYBOXBVXCSN-UHFFFAOYSA-N 0.000 description 1
- CUNDRHORZHFPLY-UHFFFAOYSA-N 138154-39-9 Chemical compound O=C1C2=CC(O)=CC=C2N2C=NC3=CC=C(NCCN(CC)CC)C1=C32 CUNDRHORZHFPLY-UHFFFAOYSA-N 0.000 description 1
- ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 1
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 1
- CQVKMVQRSNNAGO-UHFFFAOYSA-N 2-[4-formyl-3-methyl-n-(2-methylsulfonyloxyethyl)anilino]ethyl methanesulfonate Chemical compound CC1=CC(N(CCOS(C)(=O)=O)CCOS(C)(=O)=O)=CC=C1C=O CQVKMVQRSNNAGO-UHFFFAOYSA-N 0.000 description 1
- DIQMFLPWYOPHNQ-UHFFFAOYSA-N 2-chloro-1-nitro-10H-acridin-9-one Chemical compound N1C2=CC=CC=C2C(=O)C2=C1C=CC(Cl)=C2[N+](=O)[O-] DIQMFLPWYOPHNQ-UHFFFAOYSA-N 0.000 description 1
- ZRIMVGGATAJQIO-UHFFFAOYSA-N 5-[3-[3-[3-[(6-chloro-2-methoxyacridin-9-yl)amino]propylamino]propylamino]propyl]-6-phenylphenanthridin-5-ium-3,8-diamine;chloride;pentahydrochloride Chemical compound Cl.Cl.Cl.Cl.Cl.[Cl-].C12=CC(OC)=CC=C2N=C2C=C(Cl)C=CC2=C1NCCCNCCCNCCC[N+](C1=CC(N)=CC=C1C1=CC=C(N)C=C11)=C1C1=CC=CC=C1 ZRIMVGGATAJQIO-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- PBGBHMIOJCGLBT-UHFFFAOYSA-N 7h-pyrido[3,2-a]carbazole Chemical class C1=CN=C2C=CC3=C4CC=CC=C4N=C3C2=C1 PBGBHMIOJCGLBT-UHFFFAOYSA-N 0.000 description 1
- JPASRFGVACYSJG-UHFFFAOYSA-N 8,10-dihydroimidazo[4,5-a]acridin-9-one Chemical class N1=C2C=CC3=NC=NC3=C2C=C2C1=CCC(=O)C2 JPASRFGVACYSJG-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 241000714266 Bovine leukemia virus Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 101000966429 Chlamydomonas reinhardtii Dynein, 70 kDa intermediate chain, flagellar outer arm Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000713730 Equine infectious anemia virus Species 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 241000713800 Feline immunodeficiency virus Species 0.000 description 1
- 101710177291 Gag polyprotein Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010010369 HIV Protease Proteins 0.000 description 1
- 238000010268 HPLC based assay Methods 0.000 description 1
- 206010020460 Human T-cell lymphotropic virus type I infection Diseases 0.000 description 1
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 1
- 241000714259 Human T-lymphotropic virus 2 Species 0.000 description 1
- 101900297506 Human immunodeficiency virus type 1 group M subtype B Reverse transcriptase/ribonuclease H Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 241000764238 Isis Species 0.000 description 1
- NJBBLOIWMSYVCQ-VZTVMPNDSA-N Kynostatin 272 Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)COC=1C2=CC=NC=C2C=CC=1)CSC)[C@H](O)C(=O)N1[C@@H](CSC1)C(=O)NC(C)(C)C)C1=CC=CC=C1 NJBBLOIWMSYVCQ-VZTVMPNDSA-N 0.000 description 1
- 101710125418 Major capsid protein Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 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 description 1
- 241001529934 Simian T-lymphotropic virus 3 Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 1
- 108010052104 Viral Regulatory and Accessory Proteins Proteins 0.000 description 1
- 241000713325 Visna/maedi virus Species 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 229960004150 aciclovir Drugs 0.000 description 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001251 acridines Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 238000002832 anti-viral assay Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 101150055766 cat gene Proteins 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 238000003398 chloramphenicol acetyltransferase induction Methods 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229960002656 didanosine Drugs 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- GTSMOYLSFUBTMV-UHFFFAOYSA-N ethidium homodimer Chemical compound [H+].[H+].[Cl-].[Cl-].[Cl-].[Cl-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2C(C)=[N+]1CCCNCCNCCC[N+](C1=CC(N)=CC=C1C1=CC=C(N)C=C11)=C1C1=CC=CC=C1 GTSMOYLSFUBTMV-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 1
- 229960002963 ganciclovir Drugs 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 1
- 238000001114 immunoprecipitation Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000005917 in vivo anti-tumor Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000013383 initial experiment Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229940124524 integrase inhibitor Drugs 0.000 description 1
- 239000002850 integrase inhibitor Substances 0.000 description 1
- 238000012739 integrated shape imaging system Methods 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 108010075606 kynostatin 272 Proteins 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- 229960000689 nevirapine Drugs 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- XDRYMKDFEDOLFX-UHFFFAOYSA-N pentamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 XDRYMKDFEDOLFX-UHFFFAOYSA-N 0.000 description 1
- 229960004448 pentamidine Drugs 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- SMUQFGGVLNAIOZ-UHFFFAOYSA-N quinaldine Chemical class C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 108010043277 recombinant soluble CD4 Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 229940064914 retrovir Drugs 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004467 single crystal X-ray diffraction Methods 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 230000035892 strand transfer Effects 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000012222 talc Nutrition 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
- 229960003433 thalidomide Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000723 toxicological property Toxicity 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000006656 viral protein synthesis Effects 0.000 description 1
- 210000000605 viral structure Anatomy 0.000 description 1
- 230000024058 virion binding Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 229960000523 zalcitabine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
-
- 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
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Oncology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Steroid Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1532696P | 1996-04-12 | 1996-04-12 | |
| US3505097P | 1997-01-22 | 1997-01-22 | |
| PCT/US1997/007070 WO1997038999A1 (en) | 1996-04-12 | 1997-04-09 | Acridone-derived compounds useful as antineoplastic and antiretroviral agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69709857D1 DE69709857D1 (de) | 2002-02-28 |
| DE69709857T2 true DE69709857T2 (de) | 2002-08-29 |
Family
ID=26687242
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69709857T Expired - Lifetime DE69709857T2 (de) | 1996-04-12 | 1997-04-09 | Acridonderivate als antineoplastische-und antiretrovirale mittel |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US6187775B1 (enExample) |
| EP (1) | EP0892801B1 (enExample) |
| JP (1) | JP4121151B2 (enExample) |
| AT (1) | ATE211471T1 (enExample) |
| AU (1) | AU725629B2 (enExample) |
| DE (1) | DE69709857T2 (enExample) |
| DK (1) | DK0892801T3 (enExample) |
| ES (1) | ES2171260T3 (enExample) |
| PT (1) | PT892801E (enExample) |
| WO (1) | WO1997038999A1 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1293525B1 (it) * | 1997-08-01 | 1999-03-01 | Uni Degli Studi Camerino | Bis-acridincarbossiammidi aventi attivita' antitumorale |
| WO2001066545A2 (en) * | 2000-03-07 | 2001-09-13 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | 1,8-NAPHTHALIMIDE IMIDAZO[4,5,1-de]ACRIDONES WITH ANTI-TUMOR ACTIVITY |
| US7144843B2 (en) * | 2001-01-31 | 2006-12-05 | Meiji Seika Kaisha, Ltd. | Pest controllers |
| US6670071B2 (en) * | 2002-01-15 | 2003-12-30 | Quallion Llc | Electric storage battery construction and method of manufacture |
| CA2470365C (en) | 2002-11-20 | 2011-05-17 | Japan Tobacco Inc. | 4-oxoquinoline compound and use thereof as hiv integrase inhibitor |
| RU2275361C3 (ru) * | 2002-11-20 | 2021-10-01 | Джапан Тобакко Инк. | Соединение 4-оксохинолина и его применение в качестве ингибитора вич интегразы |
| US8512144B2 (en) * | 2003-10-20 | 2013-08-20 | Tipping Point Group, Llc | Method and apparatus for providing secondary gaming machine functionality |
| MY134672A (en) | 2004-05-20 | 2007-12-31 | Japan Tobacco Inc | Stable crystal of 4-oxoquinoline compound |
| WO2005113509A1 (en) | 2004-05-20 | 2005-12-01 | Japan Tobacco Inc. | Novel 4-oxoquinoline compound and use thereof as hiv integrase inhibitor |
| ATE518866T1 (de) * | 2004-06-30 | 2011-08-15 | Council Scient Ind Res | Über die piperazineinheit gebundene pyrroloä2,1- cüä1,4übenzodiazepin-napthalimid-konjugate und verfahren zu deren herstellung |
| US8377586B2 (en) * | 2005-10-05 | 2013-02-19 | California Institute Of Technology | Fluoride ion electrochemical cell |
| US7829578B1 (en) | 2005-12-12 | 2010-11-09 | Oregon Health & Science University | Aromatic ketones and uses thereof |
| WO2007092436A2 (en) * | 2006-02-08 | 2007-08-16 | Xanthus Pharmaceuticals, Inc. | Compounds for treating inflammatory disorders, demyelinating disorders and cancers |
| IN2014CN00613A (enExample) | 2006-03-06 | 2015-08-21 | Japan Tobacco Inc | |
| WO2007136858A2 (en) | 2006-05-19 | 2007-11-29 | H. Lee Moffitt Cancer Center & Research Institute | Small molecule inhibitors of stat3 with anti-tumor activity |
| WO2008016661A2 (en) * | 2006-08-02 | 2008-02-07 | Xanthus Pharmaceuticals, Inc. | Morpholino compounds for treating inflammatory and demyelinating diseases and cancers |
| AU2007316416A1 (en) * | 2006-11-07 | 2008-05-15 | Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Self-assembling nanoparticles composed of transmembrane peptides and their application for specific intra-tumor delivery of anti-cancer drugs |
| WO2008064011A1 (en) | 2006-11-13 | 2008-05-29 | The Government Of The U.S. Of America As Represented By The Department Of Veterans Affairs | Acridone compounds |
| US8598354B2 (en) | 2008-12-05 | 2013-12-03 | University Of South Florida | Compounds having antiparasitic or anti-infectious activity |
| PL3070078T3 (pl) * | 2015-03-20 | 2018-02-28 | Politechnika Gdańska | Niesymetryczne bisakrydyny o działaniu przeciwnowotworowym i ich zastosowania |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9104548D0 (en) * | 1991-03-05 | 1991-04-17 | Cholody Wienlaw M | Antineoplastic modified imidazoacridines |
| US5508289A (en) * | 1994-03-14 | 1996-04-16 | The United States America As Represented By The Department Of Health And Human Services | Bis-acridone chemotherapeutic derivatives |
-
1997
- 1997-04-09 AU AU28157/97A patent/AU725629B2/en not_active Ceased
- 1997-04-09 AT AT97922508T patent/ATE211471T1/de active
- 1997-04-09 DE DE69709857T patent/DE69709857T2/de not_active Expired - Lifetime
- 1997-04-09 DK DK97922508T patent/DK0892801T3/da active
- 1997-04-09 ES ES97922508T patent/ES2171260T3/es not_active Expired - Lifetime
- 1997-04-09 JP JP53745697A patent/JP4121151B2/ja not_active Expired - Fee Related
- 1997-04-09 WO PCT/US1997/007070 patent/WO1997038999A1/en not_active Ceased
- 1997-04-09 PT PT97922508T patent/PT892801E/pt unknown
- 1997-04-09 EP EP97922508A patent/EP0892801B1/en not_active Expired - Lifetime
- 1997-04-09 US US09/155,141 patent/US6187775B1/en not_active Expired - Lifetime
-
2001
- 2001-01-15 US US09/760,047 patent/US6541483B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO1997038999A1 (en) | 1997-10-23 |
| AU725629B2 (en) | 2000-10-19 |
| JP2000508662A (ja) | 2000-07-11 |
| ATE211471T1 (de) | 2002-01-15 |
| EP0892801A1 (en) | 1999-01-27 |
| PT892801E (pt) | 2002-06-28 |
| US20010009914A1 (en) | 2001-07-26 |
| US6541483B2 (en) | 2003-04-01 |
| AU2815797A (en) | 1997-11-07 |
| ES2171260T3 (es) | 2002-09-01 |
| DK0892801T3 (da) | 2002-04-22 |
| DE69709857D1 (de) | 2002-02-28 |
| EP0892801B1 (en) | 2002-01-02 |
| US6187775B1 (en) | 2001-02-13 |
| JP4121151B2 (ja) | 2008-07-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69709857T2 (de) | Acridonderivate als antineoplastische-und antiretrovirale mittel | |
| DE69412251T2 (de) | Aromatische nitro verbindungen und deren metabolite verwendbar als anti-virus-und anti-tumormittel | |
| Sriram et al. | Synthesis, anti-HIV and antitubercular activities of lamivudine prodrugs | |
| DE69122259T2 (de) | 5-iod-6-amino-1,2-benzopyrane und deren analoge | |
| EP1073653B1 (de) | Neue 2-heterocyclisch substituierte dihydropyrimidine | |
| DE69823344T2 (de) | Substituierte benzimidazol-derivate und ihre verwendung zur behandlung retroviraler infektionen | |
| DE69814049T2 (de) | Substituierte benzimidazole als nicht-nucleoside reverse transcriptase inhibitore | |
| DE60020820T2 (de) | Thiadiazolyl-harnstoffe oder -thioharnstoffe zur antiviralen behandlung | |
| WO1997038999A9 (en) | Acridone-derived compounds useful as antineoplastic and antiretroviral agents | |
| KR960000433B1 (ko) | 레트로비루스에 감염된 환자치료에 사용되는 3'-디옥시티미딘-2'-엔(3'-디옥시-2',3'-디디하이드로티미딘)의 항바이러스 조성물 | |
| DE69631158T2 (de) | Verbindungen und deren verwendung zur behandlung von infektiösen erkrankungen | |
| DE69534177T2 (de) | Naphtylisoquinolinalkaloiden, diese enthaltende pharmazeutische Zusammensetzungen und ihre Verwendung zur Behandlung von Malaria | |
| DE3781488T2 (de) | Pharmazeutische zusammensetzung, enthaltend 2',3'-dideoxycytidin-2'-en(2',3'-dideoxy-2',3'-didehydrocytidin) zur behandlung von mit retrovirus infizierten patienten. | |
| DE69302829T2 (de) | Bicyclische pyrimidinderivate, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische präparate | |
| DE69119700T2 (de) | Verwendung von Xanthinen zur Herstellung von Arzneimitteln zur Hemmung der Vermehrung menschlicher Retroviren | |
| US4093715A (en) | 5-Iodo-5'-amino-2',5'-dideoxycytidine and the pharmaceutically acceptable salts thereof | |
| DE69232417T2 (de) | Michellamine zur verwendung als antivirale wirkstoffe, zusammensetzung und behandlungsverfahren | |
| DE69513962T2 (de) | Acridonderivate von diinterkalatoren als chemotherapeutische wirkstoffe | |
| CN109369623A (zh) | 一种取代1,2,3三氮唑类二芳基嘧啶衍生物及其制备方法与应用 | |
| DE69627346T2 (de) | 4-aryl-thio-pyridin-2(1h)-onen, diese enthaltende arzneimittel und ihre anwendungen bei der behandlung von mit hiv zusammenhängenden krankheiten | |
| DE4014672A1 (de) | Verwendung von adamantan-derivaten zur zytoprotektion von nicht-infizierten und virus-infizierten lymphozyten als auch anderen zelltypen | |
| JPH10507446A (ja) | ビス−２−アミノピリジン類、その製造方法及び寄生虫感染を制御するためのその用途 | |
| WO2001074753A1 (de) | Synthetische derivate von lunularsäure, arzneimittel enthaltend diese verbindungen, verfahren zur herstellung der lunularsäurederivate sowie deren verwendung | |
| WO1992008457A1 (de) | Verwendung von thiazoloisoindolinon-derivaten als antivirale arzneimittel | |
| DE69506702T2 (de) | Verwendung einer naphtolsulfonsäure zur hemmung der retroviraler infektionen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |