SK132000A3 - Use of colchinol derivatives as vascular damaging agents - Google Patents
Use of colchinol derivatives as vascular damaging agents Download PDFInfo
- Publication number
- SK132000A3 SK132000A3 SK13-2000A SK132000A SK132000A3 SK 132000 A3 SK132000 A3 SK 132000A3 SK 132000 A SK132000 A SK 132000A SK 132000 A3 SK132000 A3 SK 132000A3
- Authority
- SK
- Slovakia
- Prior art keywords
- group
- alkyl
- cycloalkyl
- hydrogen
- optionally substituted
- Prior art date
Links
- HSDSUBIABLFGDX-AWEZNQCLSA-N (7s)-7-amino-1,2,3-trimethoxy-6,7-dihydro-5h-dibenzo[5,3-b:1',2'-e][7]annulen-9-ol Chemical class C1C[C@H](N)C2=CC(O)=CC=C2C2=C1C=C(OC)C(OC)=C2OC HSDSUBIABLFGDX-AWEZNQCLSA-N 0.000 title claims abstract description 10
- 230000000254 damaging effect Effects 0.000 title description 5
- 230000002792 vascular Effects 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 73
- -1 thioalkanoyl Chemical group 0.000 claims abstract description 30
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 28
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 16
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 11
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 10
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 10
- 125000003118 aryl group Chemical group 0.000 claims abstract description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 10
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
- 201000010099 disease Diseases 0.000 claims abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 8
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
- 150000002367 halogens Chemical class 0.000 claims abstract description 8
- 150000004677 hydrates Chemical class 0.000 claims abstract description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 8
- 239000012453 solvate Substances 0.000 claims abstract description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 7
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims abstract description 7
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims abstract description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 7
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims abstract description 7
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims abstract description 7
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims abstract description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 7
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims abstract description 7
- 125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims abstract description 7
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims abstract description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
- 125000005129 aryl carbonyl group Chemical group 0.000 claims abstract description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 3
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims abstract description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 125000004442 acylamino group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004986 diarylamino group Chemical group 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- LOTBYPQQWICYBB-UHFFFAOYSA-N methyl n-hexyl-n-[2-(hexylamino)ethyl]carbamate Chemical group CCCCCCNCCN(C(=O)OC)CCCCCC LOTBYPQQWICYBB-UHFFFAOYSA-N 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 claims 1
- 230000033115 angiogenesis Effects 0.000 abstract description 6
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 abstract description 2
- 229910018828 PO3H2 Inorganic materials 0.000 abstract 2
- 125000005141 aryl amino sulfonyl group Chemical group 0.000 abstract 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 206010028980 Neoplasm Diseases 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 210000005166 vasculature Anatomy 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 229910052799 carbon Inorganic materials 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 231100000682 maximum tolerated dose Toxicity 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 150000002431 hydrogen Chemical class 0.000 description 8
- 239000011347 resin Substances 0.000 description 8
- 229920005989 resin Polymers 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 229910019142 PO4 Inorganic materials 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 235000021317 phosphate Nutrition 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 239000010452 phosphate Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 230000037396 body weight Effects 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000007850 fluorescent dye Substances 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 102000004243 Tubulin Human genes 0.000 description 4
- 108090000704 Tubulin Proteins 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000017531 blood circulation Effects 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 229960003668 docetaxel Drugs 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
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- 230000001225 therapeutic effect Effects 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 206010029113 Neovascularisation Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
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- 125000003277 amino group Chemical group 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229960001338 colchicine Drugs 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
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- C07C217/74—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with rings other than six-membered aromatic rings being part of the carbon skeleton
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- C07C233/16—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 singly-bound oxygen atoms
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- C07C271/06—Esters of carbamic acids
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- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/07—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/30—Ortho- or ortho- and peri-condensed systems containing three rings containing seven-membered rings
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| GBGB9714249.1A GB9714249D0 (en) | 1997-07-08 | 1997-07-08 | Vascular damaging agents |
| PCT/GB1998/001977 WO1999002166A1 (en) | 1997-07-08 | 1998-07-06 | Use of colchinol derivatives as vascular damaging agents |
Publications (1)
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| SK132000A3 true SK132000A3 (en) | 2000-12-11 |
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Family Applications (1)
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| SK13-2000A SK132000A3 (en) | 1997-07-08 | 1998-07-06 | Use of colchinol derivatives as vascular damaging agents |
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| EP (1) | EP1001785B1 (no) |
| JP (1) | JP3455549B2 (no) |
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| CN (1) | CN1181825C (no) |
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| RU (1) | RU2232021C2 (no) |
| SK (1) | SK132000A3 (no) |
| TR (1) | TR199903149T2 (no) |
| UA (1) | UA72731C2 (no) |
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- 1998-07-06 EP EP98932374A patent/EP1001785B1/en not_active Expired - Lifetime
- 1998-07-06 AU AU82311/98A patent/AU741213B2/en not_active Ceased
- 1998-07-06 IL IL13389998A patent/IL133899A0/xx unknown
- 1998-07-06 CA CA002292549A patent/CA2292549C/en not_active Expired - Fee Related
- 1998-07-06 JP JP50831399A patent/JP3455549B2/ja not_active Expired - Fee Related
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- 1998-07-06 KR KR1020007000094A patent/KR100655808B1/ko not_active Expired - Fee Related
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2000
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