HRP20000794A2 - Bioreductive cytotoxic agents - Google Patents
Bioreductive cytotoxic agents Download PDFInfo
- Publication number
- HRP20000794A2 HRP20000794A2 HR20000794A HRP20000794A HRP20000794A2 HR P20000794 A2 HRP20000794 A2 HR P20000794A2 HR 20000794 A HR20000794 A HR 20000794A HR P20000794 A HRP20000794 A HR P20000794A HR P20000794 A2 HRP20000794 A2 HR P20000794A2
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- Prior art keywords
- group
- salt
- alkyl
- quinone
- substituted
- Prior art date
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- 229940127089 cytotoxic agent Drugs 0.000 title description 2
- 239000002254 cytotoxic agent Substances 0.000 title description 2
- 231100000599 cytotoxic agent Toxicity 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 60
- 150000003839 salts Chemical class 0.000 claims description 49
- 125000003118 aryl group Chemical group 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- -1 bis(chloroethyl) amino group Chemical group 0.000 claims description 35
- AZQWKYJCGOJGHM-UHFFFAOYSA-N para-benzoquinone Natural products O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 33
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 32
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 30
- 125000004151 quinonyl group Chemical group 0.000 claims description 29
- 230000002152 alkylating effect Effects 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 27
- 125000003342 alkenyl group Chemical group 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 125000003277 amino group Chemical group 0.000 claims description 20
- 150000002148 esters Chemical class 0.000 claims description 20
- 125000005647 linker group Chemical group 0.000 claims description 19
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 125000004104 aryloxy group Chemical group 0.000 claims description 13
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 13
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 13
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 11
- 125000003368 amide group Chemical group 0.000 claims description 10
- 125000005041 acyloxyalkyl group Chemical group 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 239000002168 alkylating agent Substances 0.000 claims description 8
- 125000005110 aryl thio group Chemical group 0.000 claims description 8
- 150000007942 carboxylates Chemical class 0.000 claims description 8
- 125000004969 haloethyl group Chemical group 0.000 claims description 8
- 230000002829 reductive effect Effects 0.000 claims description 8
- 125000004149 thio group Chemical group *S* 0.000 claims description 8
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000005368 heteroarylthio group Chemical group 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 125000004185 ester group Chemical group 0.000 claims description 6
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 6
- 230000009467 reduction Effects 0.000 claims description 6
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 4
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 4
- 125000005126 aryl alkyl carbonyl amino group Chemical group 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000004059 quinone derivatives Chemical class 0.000 claims 24
- 125000001309 chloro group Chemical group Cl* 0.000 claims 5
- 125000004429 atom Chemical group 0.000 claims 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- 125000005055 alkyl alkoxy group Chemical group 0.000 claims 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 40
- 238000005160 1H NMR spectroscopy Methods 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 36
- 230000015572 biosynthetic process Effects 0.000 description 29
- 238000003786 synthesis reaction Methods 0.000 description 29
- 239000000243 solution Substances 0.000 description 28
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- 231100000433 cytotoxic Toxicity 0.000 description 22
- 230000001472 cytotoxic effect Effects 0.000 description 22
- 206010028980 Neoplasm Diseases 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 13
- 239000001301 oxygen Substances 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 11
- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- 210000004881 tumor cell Anatomy 0.000 description 9
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 125000005842 heteroatom Chemical group 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- WLYDZHCJSPHCFM-UHFFFAOYSA-N 2-(chloromethyl)-3,5,6-trimethylcyclohexa-2,5-diene-1,4-dione Chemical compound CC1=C(C)C(=O)C(CCl)=C(C)C1=O WLYDZHCJSPHCFM-UHFFFAOYSA-N 0.000 description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 229910052717 sulfur Chemical group 0.000 description 6
- 239000011593 sulfur Chemical group 0.000 description 6
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 5
- 229940100198 alkylating agent Drugs 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- XLHUBROMZOAQMV-UHFFFAOYSA-N 1,4-benzosemiquinone Chemical compound [O]C1=CC=C(O)C=C1 XLHUBROMZOAQMV-UHFFFAOYSA-N 0.000 description 3
- PKFSXBZXFYABSS-UHFFFAOYSA-N 3-[bis(2-chloroethyl)amino]-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1N(CCCl)CCCl PKFSXBZXFYABSS-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000219198 Brassica Species 0.000 description 3
- 235000003351 Brassica cretica Nutrition 0.000 description 3
- 235000003343 Brassica rupestris Nutrition 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 235000010460 mustard Nutrition 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 235000009518 sodium iodide Nutrition 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 150000002367 halogens Chemical group 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 230000001146 hypoxic effect Effects 0.000 description 2
- UEGCRFNWTGYVKX-UHFFFAOYSA-N methyl 3-hydroxy-4-nitrobenzoate Chemical compound COC(=O)C1=CC=C([N+]([O-])=O)C(O)=C1 UEGCRFNWTGYVKX-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 239000012038 nucleophile Substances 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
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- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
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- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- UVNPEUJXKZFWSJ-LMTQTHQJSA-N (R)-N-[(4S)-8-[6-amino-5-[(3,3-difluoro-2-oxo-1H-pyrrolo[2,3-b]pyridin-4-yl)sulfanyl]pyrazin-2-yl]-2-oxa-8-azaspiro[4.5]decan-4-yl]-2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@@](=O)N[C@@H]1COCC11CCN(CC1)c1cnc(Sc2ccnc3NC(=O)C(F)(F)c23)c(N)n1 UVNPEUJXKZFWSJ-LMTQTHQJSA-N 0.000 description 1
- WOAHJDHKFWSLKE-UHFFFAOYSA-N 1,2-benzoquinone Chemical compound O=C1C=CC=CC1=O WOAHJDHKFWSLKE-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 229940005561 1,4-benzoquinone Drugs 0.000 description 1
- GZZYDSKWJOBDHZ-UHFFFAOYSA-N 1,4-dimethoxy-2,3,5-trimethylbenzene Chemical compound COC1=CC(C)=C(OC)C(C)=C1C GZZYDSKWJOBDHZ-UHFFFAOYSA-N 0.000 description 1
- HUXJXNSHCKHFIL-UHFFFAOYSA-N 1-(2-bromoethoxy)-2-methoxyethane Chemical compound COCCOCCBr HUXJXNSHCKHFIL-UHFFFAOYSA-N 0.000 description 1
- SMLUDDUGVGGKKX-UHFFFAOYSA-N 1-(chloromethyl)-2,5-dimethoxy-3,4,6-trimethylbenzene Chemical compound COC1=C(C)C(C)=C(OC)C(CCl)=C1C SMLUDDUGVGGKKX-UHFFFAOYSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 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
- 201000010982 kidney cancer Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 229940096405 magnesium cation Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- LGRLWUINFJPLSH-UHFFFAOYSA-N methanide Chemical compound [CH3-] LGRLWUINFJPLSH-UHFFFAOYSA-N 0.000 description 1
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- LRCWQOFZJPOTBG-UHFFFAOYSA-N methyl 2-[bis(2-chloroethyl)amino]-3,5-dimethylbenzoate Chemical compound COC(=O)C1=CC(C)=CC(C)=C1N(CCCl)CCCl LRCWQOFZJPOTBG-UHFFFAOYSA-N 0.000 description 1
- PLYICQTXEFHVJY-UHFFFAOYSA-N methyl 2-[bis(2-hydroxyethyl)amino]-3,5-dimethylbenzoate Chemical compound COC(=O)C1=CC(C)=CC(C)=C1N(CCO)CCO PLYICQTXEFHVJY-UHFFFAOYSA-N 0.000 description 1
- XRCRCNXSQYQLAQ-UHFFFAOYSA-N methyl 2-amino-3,5-dimethylbenzoate Chemical compound COC(=O)C1=CC(C)=CC(C)=C1N XRCRCNXSQYQLAQ-UHFFFAOYSA-N 0.000 description 1
- BXOZUEZYGQJCGL-UHFFFAOYSA-N methyl 3-[2-(2-methoxyethoxy)ethoxy]-4-nitrobenzoate Chemical compound COCCOCCOC1=CC(C(=O)OC)=CC=C1[N+]([O-])=O BXOZUEZYGQJCGL-UHFFFAOYSA-N 0.000 description 1
- QVDWKLDUBSJEOG-UHFFFAOYSA-N methyl 3-amino-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(N)=C1 QVDWKLDUBSJEOG-UHFFFAOYSA-N 0.000 description 1
- XKIXKSODRXNORK-UHFFFAOYSA-N methyl 4-[bis(2-hydroxyethyl)amino]-3-[2-(2-methoxyethoxy)ethoxy]benzoate Chemical compound COCCOCCOC1=CC(C(=O)OC)=CC=C1N(CCO)CCO XKIXKSODRXNORK-UHFFFAOYSA-N 0.000 description 1
- TYGGZGYFSCZOTQ-UHFFFAOYSA-N methyl 4-[bis(2-hydroxyethyl)amino]-3-octoxybenzoate Chemical compound CCCCCCCCOC1=CC(C(=O)OC)=CC=C1N(CCO)CCO TYGGZGYFSCZOTQ-UHFFFAOYSA-N 0.000 description 1
- WGJSUIMJONMGJU-UHFFFAOYSA-N methyl 4-amino-3-[2-(2-methoxyethoxy)ethoxy]benzoate Chemical compound COCCOCCOC1=CC(C(=O)OC)=CC=C1N WGJSUIMJONMGJU-UHFFFAOYSA-N 0.000 description 1
- VJUUTZBYIOHGJJ-UHFFFAOYSA-N methyl 4-amino-3-octoxybenzoate Chemical compound CCCCCCCCOC1=CC(C(=O)OC)=CC=C1N VJUUTZBYIOHGJJ-UHFFFAOYSA-N 0.000 description 1
- DQTKZPXZGLAHMM-UHFFFAOYSA-N methyl 4-nitro-3-octoxybenzoate Chemical compound CCCCCCCCOC1=CC(C(=O)OC)=CC=C1[N+]([O-])=O DQTKZPXZGLAHMM-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 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
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 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
- 238000011275 oncology therapy Methods 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000004053 quinones Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 150000005838 radical anions Chemical class 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 239000012066 reaction slurry Substances 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
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001356 surgical procedure Methods 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
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical group C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/64—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring the carbon skeleton being further substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C50/00—Quinones
- C07C50/24—Quinones containing halogen
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/56—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/60—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in meta- or para- positions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/53—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
- C07C233/54—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
- C07C271/28—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/112—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- C07D295/116—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings with the doubly bound oxygen or sulfur atoms directly attached to a carbocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Furan Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US8642998P | 1998-05-22 | 1998-05-22 | |
US09/083,652 US5969133A (en) | 1998-05-22 | 1998-05-22 | Bioreductive cytotoxic agents |
PCT/US1999/011199 WO1999061409A1 (en) | 1998-05-22 | 1999-05-20 | Bioreductive cytotoxic agents |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20000794A2 true HRP20000794A2 (en) | 2001-10-31 |
Family
ID=26769555
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20000794A HRP20000794A2 (en) | 1998-05-22 | 2000-11-20 | Bioreductive cytotoxic agents |
Country Status (12)
Country | Link |
---|---|
EP (1) | EP1080066A4 (zh) |
JP (1) | JP2002516304A (zh) |
KR (1) | KR20010074498A (zh) |
CN (1) | CN1302287A (zh) |
AU (1) | AU750381B2 (zh) |
BR (1) | BR9911066A (zh) |
CA (1) | CA2332806A1 (zh) |
HR (1) | HRP20000794A2 (zh) |
HU (1) | HUP0102932A3 (zh) |
NO (1) | NO20005880L (zh) |
PL (1) | PL344257A1 (zh) |
WO (1) | WO1999061409A1 (zh) |
Families Citing this family (8)
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US6137003A (en) * | 1998-10-28 | 2000-10-24 | Shionogi Bioresearch | Bis (haloethyl) aminobenzene derivatives |
GB0517957D0 (en) | 2005-09-03 | 2005-10-12 | Morvus Technology Ltd | Method of combating infection |
GB0526552D0 (en) | 2005-12-29 | 2006-02-08 | Morvus Technology Ltd | New use |
GB2442202A (en) | 2006-09-30 | 2008-04-02 | Morvus Technology Ltd | Vermin poison |
BR112013030370A2 (pt) * | 2011-05-26 | 2017-08-08 | Apex Therapeutics Inc | compostos de quinona para tratamento de doenças mediadas por ape1 |
CN111039764A (zh) * | 2018-10-12 | 2020-04-21 | 山东大学 | 一种双亲乙烯衍生物及制备方法 |
PL3866772T3 (pl) | 2018-10-17 | 2024-04-08 | Ptc Therapeutics, Inc. | 2,3,5-trimetylo-6-nonylocykloheksa-2,5-dieno-1,4-dion do hamowania i leczenia alfa-synukleinopatii, tauopatii i innych zaburzeń |
WO2023283466A1 (en) | 2021-07-08 | 2023-01-12 | Ptc Therapeutics, Inc. | Pharmaceutical compositions comprising 2,3,5-trimethyl-6-nonylcyclohexa-2,5-diene-1,4-dione |
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GB9501052D0 (en) * | 1995-01-19 | 1995-03-08 | Cancer Res Campaign Tech | Improvements relating to prodrugs |
US5786488A (en) * | 1996-11-13 | 1998-07-28 | Sugen, Inc. | Synthetic methods for the preparation of indolyquinones |
AU1166097A (en) * | 1995-12-21 | 1997-07-17 | British Technology Group Limited | Indoloquinone derivatives as bioreductive agents |
-
1999
- 1999-05-20 CA CA002332806A patent/CA2332806A1/en not_active Abandoned
- 1999-05-20 CN CN99806490A patent/CN1302287A/zh active Pending
- 1999-05-20 KR KR1020007013155A patent/KR20010074498A/ko not_active Application Discontinuation
- 1999-05-20 EP EP99924405A patent/EP1080066A4/en not_active Withdrawn
- 1999-05-20 PL PL99344257A patent/PL344257A1/xx unknown
- 1999-05-20 HU HU0102932A patent/HUP0102932A3/hu unknown
- 1999-05-20 AU AU40913/99A patent/AU750381B2/en not_active Ceased
- 1999-05-20 BR BR9911066-0A patent/BR9911066A/pt not_active Application Discontinuation
- 1999-05-20 JP JP2000550818A patent/JP2002516304A/ja active Pending
- 1999-05-20 WO PCT/US1999/011199 patent/WO1999061409A1/en not_active Application Discontinuation
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2000
- 2000-11-20 HR HR20000794A patent/HRP20000794A2/hr not_active Application Discontinuation
- 2000-11-21 NO NO20005880A patent/NO20005880L/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
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EP1080066A4 (en) | 2004-12-22 |
JP2002516304A (ja) | 2002-06-04 |
WO1999061409A1 (en) | 1999-12-02 |
NO20005880L (no) | 2001-01-09 |
PL344257A1 (en) | 2001-10-22 |
EP1080066A1 (en) | 2001-03-07 |
HUP0102932A2 (hu) | 2001-12-28 |
CA2332806A1 (en) | 1999-12-02 |
KR20010074498A (ko) | 2001-08-04 |
BR9911066A (pt) | 2001-02-13 |
HUP0102932A3 (en) | 2002-12-28 |
AU750381B2 (en) | 2002-07-18 |
AU4091399A (en) | 1999-12-13 |
NO20005880D0 (no) | 2000-11-21 |
CN1302287A (zh) | 2001-07-04 |
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