CA2489367A1 - Compounds, compositions, and methods - Google Patents
Compounds, compositions, and methods Download PDFInfo
- Publication number
- CA2489367A1 CA2489367A1 CA002489367A CA2489367A CA2489367A1 CA 2489367 A1 CA2489367 A1 CA 2489367A1 CA 002489367 A CA002489367 A CA 002489367A CA 2489367 A CA2489367 A CA 2489367A CA 2489367 A1 CA2489367 A1 CA 2489367A1
- Authority
- CA
- Canada
- Prior art keywords
- optionally substituted
- alkyl
- hydrogen
- compound according
- chosen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 312
- 238000000034 method Methods 0.000 title claims description 57
- 239000000203 mixture Substances 0.000 title claims description 45
- 230000000694 effects Effects 0.000 claims abstract description 45
- 230000001413 cellular effect Effects 0.000 claims abstract description 11
- 230000002062 proliferating effect Effects 0.000 claims abstract description 9
- -1 imidazolyl- Chemical group 0.000 claims description 430
- 229910052739 hydrogen Inorganic materials 0.000 claims description 106
- 239000001257 hydrogen Substances 0.000 claims description 106
- 150000002431 hydrogen Chemical class 0.000 claims description 68
- 125000003107 substituted aryl group Chemical group 0.000 claims description 67
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 61
- 125000001072 heteroaryl group Chemical group 0.000 claims description 53
- 102000010638 Kinesin Human genes 0.000 claims description 50
- 108010063296 Kinesin Proteins 0.000 claims description 50
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 41
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 39
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 239000012453 solvate Substances 0.000 claims description 20
- 206010028980 Neoplasm Diseases 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 18
- 101100295738 Gallus gallus COR3 gene Proteins 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 14
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 14
- 201000011510 cancer Diseases 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 125000003944 tolyl group Chemical group 0.000 claims description 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 8
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 8
- 101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 claims description 6
- 239000002246 antineoplastic agent Substances 0.000 claims description 6
- 125000005518 carboxamido group Chemical group 0.000 claims description 6
- 125000005059 halophenyl group Chemical group 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 206010061218 Inflammation Diseases 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 229940127089 cytotoxic agent Drugs 0.000 claims description 5
- 230000004054 inflammatory process Effects 0.000 claims description 5
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 4
- 208000006029 Cardiomegaly Diseases 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 206010020718 hyperplasia Diseases 0.000 claims description 4
- 208000026278 immune system disease Diseases 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- MFLYTCSVJYYAOR-UHFFFAOYSA-N (carbamimidoylazaniumyl)formate Chemical compound NC(=N)NC(O)=O MFLYTCSVJYYAOR-UHFFFAOYSA-N 0.000 claims description 3
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 claims description 3
- 229940123237 Taxane Drugs 0.000 claims description 3
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 claims description 3
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 3
- 229940122803 Vinca alkaloid Drugs 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 8
- 238000004519 manufacturing process Methods 0.000 claims 2
- 150000002462 imidazolines Chemical class 0.000 claims 1
- 125000003884 phenylalkyl group Chemical group 0.000 claims 1
- 208000037765 diseases and disorders Diseases 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 description 78
- 239000000243 solution Substances 0.000 description 61
- 125000000217 alkyl group Chemical group 0.000 description 48
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 44
- 239000003795 chemical substances by application Substances 0.000 description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 43
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- 230000000394 mitotic effect Effects 0.000 description 41
- 210000004027 cell Anatomy 0.000 description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 230000027455 binding Effects 0.000 description 36
- 239000002585 base Substances 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 26
- 238000002360 preparation method Methods 0.000 description 26
- 125000005843 halogen group Chemical group 0.000 description 25
- 230000015572 biosynthetic process Effects 0.000 description 23
- 102000029749 Microtubule Human genes 0.000 description 22
- 108091022875 Microtubule Proteins 0.000 description 22
- 210000004688 microtubule Anatomy 0.000 description 22
- 238000003786 synthesis reaction Methods 0.000 description 22
- 239000002253 acid Substances 0.000 description 21
- 150000001412 amines Chemical class 0.000 description 21
- 125000003118 aryl group Chemical group 0.000 description 21
- 235000019439 ethyl acetate Nutrition 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- 238000003556 assay Methods 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000000010 aprotic solvent Substances 0.000 description 18
- 239000000047 product Substances 0.000 description 17
- 108090000623 proteins and genes Proteins 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 235000018102 proteins Nutrition 0.000 description 16
- 102000004169 proteins and genes Human genes 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 125000000623 heterocyclic group Chemical group 0.000 description 15
- 125000006239 protecting group Chemical group 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- 230000004663 cell proliferation Effects 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000003112 inhibitor Substances 0.000 description 12
- 230000011278 mitosis Effects 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 10
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical class C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 108091006112 ATPases Proteins 0.000 description 9
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 125000005037 alkyl phenyl group Chemical group 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 239000008121 dextrose Substances 0.000 description 9
- 229940000406 drug candidate Drugs 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 208000009956 adenocarcinoma Diseases 0.000 description 8
- 150000001299 aldehydes Chemical class 0.000 description 8
- 125000002636 imidazolinyl group Chemical group 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 230000020347 spindle assembly Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- 101001008953 Homo sapiens Kinesin-like protein KIF11 Proteins 0.000 description 7
- 206010025323 Lymphomas Diseases 0.000 description 7
- 206010039491 Sarcoma Diseases 0.000 description 7
- 229960000583 acetic acid Drugs 0.000 description 7
- 239000011575 calcium Substances 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 238000012216 screening Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 201000009030 Carcinoma Diseases 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000009826 distribution Methods 0.000 description 6
- 125000001188 haloalkyl group Chemical group 0.000 description 6
- 102000055595 human KIF11 Human genes 0.000 description 6
- 125000002883 imidazolyl group Chemical group 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 235000001014 amino acid Nutrition 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000002538 fungal effect Effects 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 229910052740 iodine Chemical group 0.000 description 5
- IQZZFVDIZRWADY-UHFFFAOYSA-N isocoumarin Chemical class C1=CC=C2C(=O)OC=CC2=C1 IQZZFVDIZRWADY-UHFFFAOYSA-N 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 150000003141 primary amines Chemical class 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 206010041823 squamous cell carcinoma Diseases 0.000 description 5
- 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 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 206010024612 Lipoma Diseases 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000004075 alteration Effects 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 230000025084 cell cycle arrest Effects 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 230000003833 cell viability Effects 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 230000004064 dysfunction Effects 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
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- 238000000338 in vitro Methods 0.000 description 4
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- 238000002955 isolation Methods 0.000 description 4
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- 229910052763 palladium Inorganic materials 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
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- 239000011734 sodium Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 125000001544 thienyl group Chemical group 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 201000008808 Fibrosarcoma Diseases 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 206010043276 Teratoma Diseases 0.000 description 3
- 241000347391 Umbrina cirrosa Species 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 125000005907 alkyl ester group Chemical group 0.000 description 3
- 230000002927 anti-mitotic effect Effects 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 230000022131 cell cycle Effects 0.000 description 3
- 239000000460 chlorine Chemical group 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 206010016629 fibroma Diseases 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 201000011066 hemangioma Diseases 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 230000036456 mitotic arrest Effects 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 229960001592 paclitaxel Drugs 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 238000007423 screening assay Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
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- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US38926502P | 2002-06-14 | 2002-06-14 | |
| US60/389,265 | 2002-06-14 | ||
| US38977902P | 2002-06-18 | 2002-06-18 | |
| US60/389,779 | 2002-06-18 | ||
| PCT/US2003/018778 WO2003106426A1 (en) | 2002-06-14 | 2003-06-12 | Compounds, compositions, and methods |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2489367A1 true CA2489367A1 (en) | 2003-12-24 |
Family
ID=29740126
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002489367A Abandoned CA2489367A1 (en) | 2002-06-14 | 2003-06-12 | Compounds, compositions, and methods |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US7041676B2 (https=) |
| EP (1) | EP1556357A4 (https=) |
| JP (1) | JP2005538062A (https=) |
| AU (1) | AU2003236527A1 (https=) |
| CA (1) | CA2489367A1 (https=) |
| WO (1) | WO2003106426A1 (https=) |
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-
2003
- 2003-06-12 WO PCT/US2003/018778 patent/WO2003106426A1/en not_active Ceased
- 2003-06-12 JP JP2004513259A patent/JP2005538062A/ja active Pending
- 2003-06-12 EP EP03737085A patent/EP1556357A4/en not_active Withdrawn
- 2003-06-12 AU AU2003236527A patent/AU2003236527A1/en not_active Abandoned
- 2003-06-12 US US10/462,002 patent/US7041676B2/en not_active Expired - Fee Related
- 2003-06-12 CA CA002489367A patent/CA2489367A1/en not_active Abandoned
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2005
- 2005-07-21 US US11/188,287 patent/US20060019988A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003236527A1 (en) | 2003-12-31 |
| EP1556357A1 (en) | 2005-07-27 |
| US20060019988A1 (en) | 2006-01-26 |
| WO2003106426A1 (en) | 2003-12-24 |
| JP2005538062A (ja) | 2005-12-15 |
| EP1556357A4 (en) | 2006-09-13 |
| US7041676B2 (en) | 2006-05-09 |
| US20040082567A1 (en) | 2004-04-29 |
| AU2003236527A8 (en) | 2003-12-31 |
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