AU2002251140B2 - Chemical derivatives and their use as anti-telomerase agent - Google Patents
Chemical derivatives and their use as anti-telomerase agent Download PDFInfo
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- AU2002251140B2 AU2002251140B2 AU2002251140A AU2002251140A AU2002251140B2 AU 2002251140 B2 AU2002251140 B2 AU 2002251140B2 AU 2002251140 A AU2002251140 A AU 2002251140A AU 2002251140 A AU2002251140 A AU 2002251140A AU 2002251140 B2 AU2002251140 B2 AU 2002251140B2
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- Australia
- Prior art keywords
- radical
- alkyl
- optionally substituted
- amino
- group
- Prior art date
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- 239000000126 substance Substances 0.000 title description 8
- -1 C1-C4 alkyl radical Chemical class 0.000 claims description 577
- 125000000217 alkyl group Chemical group 0.000 claims description 278
- 150000003254 radicals Chemical class 0.000 claims description 196
- 150000001875 compounds Chemical class 0.000 claims description 147
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 138
- 229910052739 hydrogen Inorganic materials 0.000 claims description 115
- 239000001257 hydrogen Substances 0.000 claims description 109
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 101
- 229910052757 nitrogen Inorganic materials 0.000 claims description 91
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 91
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical group C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 75
- 125000003118 aryl group Chemical group 0.000 claims description 65
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 64
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 56
- 125000003282 alkyl amino group Chemical group 0.000 claims description 54
- 125000004076 pyridyl group Chemical group 0.000 claims description 52
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 49
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 49
- 125000003545 alkoxy group Chemical group 0.000 claims description 48
- 125000004193 piperazinyl group Chemical group 0.000 claims description 43
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 41
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 40
- 125000005936 piperidyl group Chemical group 0.000 claims description 40
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 39
- 125000005842 heteroatom Chemical group 0.000 claims description 37
- 125000002757 morpholinyl group Chemical group 0.000 claims description 37
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 34
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 32
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims description 25
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 21
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 19
- 125000004442 acylamino group Chemical group 0.000 claims description 19
- 229910052705 radium Inorganic materials 0.000 claims description 19
- 229910052701 rubidium Inorganic materials 0.000 claims description 19
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 229920006395 saturated elastomer Polymers 0.000 claims description 18
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 17
- 229910052786 argon Inorganic materials 0.000 claims description 16
- 125000004414 alkyl thio group Chemical group 0.000 claims description 15
- 125000003277 amino group Chemical group 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000004450 alkenylene group Chemical group 0.000 claims description 14
- 125000002947 alkylene group Chemical group 0.000 claims description 14
- 125000005237 alkyleneamino group Chemical group 0.000 claims description 14
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 14
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 claims description 13
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 13
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 13
- 239000001301 oxygen Substances 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- CWRYPZZKDGJXCA-UHFFFAOYSA-N acenaphthalene Natural products C1=CC(CC2)=C3C2=CC=CC3=C1 CWRYPZZKDGJXCA-UHFFFAOYSA-N 0.000 claims description 12
- HXGDTGSAIMULJN-UHFFFAOYSA-N acetnaphthylene Natural products C1=CC(C=C2)=C3C2=CC=CC3=C1 HXGDTGSAIMULJN-UHFFFAOYSA-N 0.000 claims description 12
- 239000012964 benzotriazole Substances 0.000 claims description 12
- 239000000460 chlorine Substances 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 125000002950 monocyclic group Chemical group 0.000 claims description 12
- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 12
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 10
- 108091081406 G-quadruplex Proteins 0.000 claims description 9
- 125000005331 diazinyl group Chemical group N1=NC(=CC=C1)* 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 125000005493 quinolyl group Chemical group 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 8
- 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 claims description 8
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 7
- ORTFAQDWJHRMNX-UHFFFAOYSA-M oxidooxomethyl Chemical compound [O-][C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-M 0.000 claims description 7
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims description 6
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 6
- 125000005191 hydroxyalkylamino group Chemical group 0.000 claims description 6
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 claims description 6
- 125000005184 naphthylamino group Chemical group C1(=CC=CC2=CC=CC=C12)N* 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 claims description 5
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical group C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 claims description 5
- CPEONABTMRSIKA-UHFFFAOYSA-N 1,4$l^{2}-oxazinane Chemical compound C1COCC[N]1 CPEONABTMRSIKA-UHFFFAOYSA-N 0.000 claims description 5
- 108020004414 DNA Proteins 0.000 claims description 5
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
- 239000007983 Tris buffer Substances 0.000 claims description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 4
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 3
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 3
- 230000005855 radiation Effects 0.000 claims description 3
- UWYZHKAOTLEWKK-UHFFFAOYSA-N tetrahydro-isoquinoline Natural products C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 3
- 125000005208 trialkylammonium group Chemical group 0.000 claims description 3
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 2
- KVNBKXXDKUNBKG-UHFFFAOYSA-N 3-N',4-N,4-N-trimethyl-2-methylsulfanylmorpholine-3,3,4-triamine Chemical compound CSC1C(N(CCO1)N(C)C)(NC)N KVNBKXXDKUNBKG-UHFFFAOYSA-N 0.000 claims description 2
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims 14
- 239000011593 sulfur Substances 0.000 claims 6
- 150000002431 hydrogen Chemical group 0.000 claims 5
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical group O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 3
- 125000004434 sulfur atom Chemical group 0.000 claims 3
- 239000004615 ingredient Substances 0.000 claims 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims 1
- DXFCQVSYYXDVTM-UHFFFAOYSA-N 2-n,4-n-bis(4-amino-2-methylquinolin-6-yl)-6-n-(4-chlorophenyl)-1,3,5-triazine-2,4,6-triamine Chemical compound C1=CC2=NC(C)=CC(N)=C2C=C1NC(N=C(NC=1C=C2C(N)=CC(C)=NC2=CC=1)N=1)=NC=1NC1=CC=C(Cl)C=C1 DXFCQVSYYXDVTM-UHFFFAOYSA-N 0.000 claims 1
- BFRBNFMXQSIQNB-UHFFFAOYSA-N 4-n-(4-amino-2-methylquinolin-6-yl)-2-n-(2-chlorophenyl)-6-n-[3-(dimethylamino)propyl]-1,3,5-triazine-2,4,6-triamine Chemical compound N=1C(NCCCN(C)C)=NC(NC=2C=C3C(N)=CC(C)=NC3=CC=2)=NC=1NC1=CC=CC=C1Cl BFRBNFMXQSIQNB-UHFFFAOYSA-N 0.000 claims 1
- SZTWFLXNHNQDIP-UHFFFAOYSA-N 6-n-[4-[[4-(dimethylamino)-2-methylquinolin-6-yl]amino]-6-(1-methylpiperidin-4-yl)-1,3,5-triazin-2-yl]-4-n,4-n,2-trimethylquinoline-4,6-diamine Chemical compound C1=C2C(N(C)C)=CC(C)=NC2=CC=C1NC(N=1)=NC(NC=2C=C3C(N(C)C)=CC(C)=NC3=CC=2)=NC=1C1CCN(C)CC1 SZTWFLXNHNQDIP-UHFFFAOYSA-N 0.000 claims 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims 1
- 125000004954 trialkylamino group Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
- 239000000203 mixture Substances 0.000 description 74
- 239000000243 solution Substances 0.000 description 61
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 58
- 239000002585 base Substances 0.000 description 58
- 238000001819 mass spectrum Methods 0.000 description 58
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
- 239000000047 product Substances 0.000 description 55
- 238000000034 method Methods 0.000 description 50
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 238000001914 filtration Methods 0.000 description 37
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 36
- 239000011541 reaction mixture Substances 0.000 description 36
- 239000008346 aqueous phase Substances 0.000 description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 30
- 239000002244 precipitate Substances 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000000843 powder Substances 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- 239000012074 organic phase Substances 0.000 description 25
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 24
- 235000019341 magnesium sulphate Nutrition 0.000 description 24
- 238000010992 reflux Methods 0.000 description 23
- 239000000377 silicon dioxide Substances 0.000 description 23
- 210000004027 cell Anatomy 0.000 description 22
- 239000007864 aqueous solution Substances 0.000 description 20
- 239000000706 filtrate Substances 0.000 description 20
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 19
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Chemical group C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 18
- 229910000027 potassium carbonate Inorganic materials 0.000 description 18
- 239000012429 reaction media Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 108010017842 Telomerase Proteins 0.000 description 17
- 239000002609 medium Substances 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000003480 eluent Substances 0.000 description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 14
- 230000000155 isotopic effect Effects 0.000 description 14
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
- 239000000908 ammonium hydroxide Substances 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 12
- 230000014759 maintenance of location Effects 0.000 description 12
- 108091034117 Oligonucleotide Proteins 0.000 description 11
- 239000012298 atmosphere Substances 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 9
- 206010028980 Neoplasm Diseases 0.000 description 9
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 9
- 125000004430 oxygen atom Chemical group O* 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 125000003386 piperidinyl group Chemical group 0.000 description 8
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 8
- YFRCFKDNLUHUPF-UHFFFAOYSA-N 4-n,4-n,2-trimethylquinoline-4,6-diamine Chemical compound C1=C(N)C=C2C(N(C)C)=CC(C)=NC2=C1 YFRCFKDNLUHUPF-UHFFFAOYSA-N 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
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- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0103916A FR2822468B1 (fr) | 2001-03-23 | 2001-03-23 | Derives chimiques et leur application comme agent anti-telomerase |
| FR01/03916 | 2001-03-23 | ||
| FR01/10370 | 2001-08-02 | ||
| FR0110370 | 2001-08-02 | ||
| PCT/FR2002/001005 WO2002076975A1 (fr) | 2001-03-23 | 2002-03-22 | Derives chimiques et leur application comme agent antitelomerase |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2002251140A1 AU2002251140A1 (en) | 2003-03-27 |
| AU2002251140B2 true AU2002251140B2 (en) | 2007-03-15 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002251140A Ceased AU2002251140B2 (en) | 2001-03-23 | 2002-03-22 | Chemical derivatives and their use as anti-telomerase agent |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP1373252A1 (https=) |
| JP (1) | JP2004524349A (https=) |
| AR (1) | AR034297A1 (https=) |
| AU (1) | AU2002251140B2 (https=) |
| CA (1) | CA2442012A1 (https=) |
| CO (1) | CO5380035A1 (https=) |
| IL (2) | IL158056A0 (https=) |
| MX (1) | MXPA03008269A (https=) |
| MY (1) | MY130957A (https=) |
| PE (1) | PE20020959A1 (https=) |
| WO (1) | WO2002076975A1 (https=) |
Families Citing this family (14)
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| WO2002096903A2 (fr) | 2001-05-28 | 2002-12-05 | Aventis Pharma S.A. | Derives chimiques et leur application comme agent antitelomerase |
| US7173032B2 (en) * | 2001-09-21 | 2007-02-06 | Reddy Us Therapeutics, Inc. | Methods and compositions of novel triazine compounds |
| AU2002361846A1 (en) * | 2001-12-21 | 2003-07-15 | Bayer Pharmaceuticals Corporation | Quinazoline and quinoline derivative compounds as inhibitors of prolylpeptidase, inducers of apoptosis and cancer treatment agents |
| AU2003253735A1 (en) * | 2002-06-25 | 2004-01-06 | The Center For Blood Research, Inc. | Vacuolins |
| FR2850970B1 (fr) * | 2003-02-07 | 2006-07-07 | Aventis Pharma Sa | Derives chimiques se liant de maniere tres specifique aux structures d'adn en g-quadruplexe et leur application comme agent anticancereux specifique |
| US8309562B2 (en) | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | Compounds and therapeutical use thereof |
| NZ544472A (en) | 2003-07-03 | 2009-04-30 | Myriad Genetics Inc | Compounds and therapeutical use thereof |
| US8258145B2 (en) | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
| CA2592900A1 (en) | 2005-01-03 | 2006-07-13 | Myriad Genetics Inc. | Nitrogen containing bicyclic compounds and therapeutical use thereof |
| JP2008540585A (ja) * | 2005-05-19 | 2008-11-20 | プロメティック・バイオサイエンスィズ・インコーポレーテッド | 転移性メラノーマ及び他の癌を治療するための化合物、そのような化合物を含有する組成物、および治療方法 |
| EP2046763A2 (en) * | 2006-07-31 | 2009-04-15 | Praecis Pharmaceuticals Incorporated | Aurora kinase inhibitors from an encoded small molecule library |
| KR20100038108A (ko) * | 2007-07-25 | 2010-04-12 | 브리스톨-마이어스 스큅 컴퍼니 | 트리아진 키나제 억제제 |
| FR2948686B1 (fr) * | 2009-07-30 | 2011-08-19 | Biomerieux Sa | Nouveaux substrats de peptidase |
| WO2019181714A1 (ja) * | 2018-03-20 | 2019-09-26 | 国立大学法人広島大学 | テロメア結合タンパク質を阻害する化合物、及びそれを含むテロメア結合タンパク質阻害剤 |
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|---|---|---|---|---|
| GB9206768D0 (en) * | 1992-03-27 | 1992-05-13 | Jarman Michael | New compounds for use in the treatment of cancer |
| JPH1160573A (ja) * | 1997-08-22 | 1999-03-02 | Nippon Kayaku Co Ltd | トリアジン誘導体及びテロメラーゼ阻害剤 |
| US6262053B1 (en) * | 1999-06-23 | 2001-07-17 | Parker Hughes Institute | Melamine derivatives as potent anti-cancer agents |
| SK7402002A3 (en) * | 1999-11-29 | 2002-11-06 | Aventis Pharma Sa | Arylamine derivatives and their use as anti-telomerase agent |
| KR100875362B1 (ko) * | 2002-02-05 | 2008-12-22 | 아스텔라스세이야쿠 가부시키가이샤 | 2,4,6-트리아미노-1,3,5-트리아진 유도체 |
-
2002
- 2002-03-21 CO CO02025874A patent/CO5380035A1/es not_active Application Discontinuation
- 2002-03-22 PE PE2002000227A patent/PE20020959A1/es not_active Application Discontinuation
- 2002-03-22 AR ARP020101060A patent/AR034297A1/es unknown
- 2002-03-22 EP EP02720068A patent/EP1373252A1/fr not_active Withdrawn
- 2002-03-22 MY MYPI20021036A patent/MY130957A/en unknown
- 2002-03-22 AU AU2002251140A patent/AU2002251140B2/en not_active Ceased
- 2002-03-22 MX MXPA03008269A patent/MXPA03008269A/es not_active Application Discontinuation
- 2002-03-22 IL IL15805602A patent/IL158056A0/xx unknown
- 2002-03-22 JP JP2002576233A patent/JP2004524349A/ja not_active Ceased
- 2002-03-22 WO PCT/FR2002/001005 patent/WO2002076975A1/fr not_active Ceased
- 2002-03-22 CA CA002442012A patent/CA2442012A1/fr not_active Abandoned
-
2003
- 2003-09-22 IL IL158056A patent/IL158056A/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1373252A1 (fr) | 2004-01-02 |
| WO2002076975A1 (fr) | 2002-10-03 |
| PE20020959A1 (es) | 2002-12-17 |
| MXPA03008269A (es) | 2004-10-15 |
| CA2442012A1 (fr) | 2002-10-03 |
| AR034297A1 (es) | 2004-02-18 |
| MY130957A (en) | 2007-07-31 |
| JP2004524349A (ja) | 2004-08-12 |
| IL158056A (en) | 2010-02-17 |
| CO5380035A1 (es) | 2004-03-31 |
| IL158056A0 (en) | 2004-03-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |