ZA200503733B - Compounds, compositions and methods. - Google Patents
Compounds, compositions and methods. Download PDFInfo
- Publication number
- ZA200503733B ZA200503733B ZA200503733A ZA200503733A ZA200503733B ZA 200503733 B ZA200503733 B ZA 200503733B ZA 200503733 A ZA200503733 A ZA 200503733A ZA 200503733 A ZA200503733 A ZA 200503733A ZA 200503733 B ZA200503733 B ZA 200503733B
- Authority
- ZA
- South Africa
- Prior art keywords
- optionally substituted
- propyl
- methyl
- alkyl
- benzyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 169
- 238000000034 method Methods 0.000 title claims description 31
- 239000000203 mixture Substances 0.000 title description 24
- -1 cyano, nitro, methylenedioxy Chemical group 0.000 claims description 202
- 125000000217 alkyl group Chemical group 0.000 claims description 129
- 229910052739 hydrogen Inorganic materials 0.000 claims description 63
- 239000001257 hydrogen Substances 0.000 claims description 62
- 125000001072 heteroaryl group Chemical group 0.000 claims description 60
- 125000003107 substituted aryl group Chemical group 0.000 claims description 51
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 39
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 34
- 108010063296 Kinesin Proteins 0.000 claims description 32
- 102000010638 Kinesin Human genes 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 31
- 229910052799 carbon Inorganic materials 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
- 125000000623 heterocyclic group Chemical group 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 239000012453 solvate Substances 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- 229910052792 caesium Inorganic materials 0.000 claims description 10
- 230000001413 cellular effect Effects 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical group 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 230000002062 proliferating effect Effects 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 8
- 201000011510 cancer Diseases 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 125000002947 alkylene group Chemical group 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 229910052791 calcium Inorganic materials 0.000 claims description 5
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 4
- 208000006029 Cardiomegaly Diseases 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 206010020718 hyperplasia Diseases 0.000 claims description 4
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 208000026278 immune system disease Diseases 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 24
- 125000005059 halophenyl group Chemical group 0.000 claims 11
- 125000004803 chlorobenzyl group Chemical group 0.000 claims 9
- 125000002946 cyanobenzyl group Chemical group 0.000 claims 9
- 125000006289 hydroxybenzyl group Chemical group 0.000 claims 9
- 125000006178 methyl benzyl group Chemical group 0.000 claims 9
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims 6
- 125000003944 tolyl group Chemical group 0.000 claims 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 3
- 125000004799 bromophenyl group Chemical group 0.000 claims 3
- 125000000068 chlorophenyl group Chemical group 0.000 claims 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 3
- 125000006286 dichlorobenzyl group Chemical group 0.000 claims 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
- 125000004076 pyridyl group Chemical group 0.000 claims 3
- 125000006223 tetrahydrofuranylmethyl group Chemical group 0.000 claims 3
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 2
- 125000004802 cyanophenyl group Chemical group 0.000 claims 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 1
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims 1
- BNMPIJWVMVNSRD-UHFFFAOYSA-N 5-methyl-1,2-oxazole-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=NO1 BNMPIJWVMVNSRD-UHFFFAOYSA-N 0.000 claims 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 238000002372 labelling Methods 0.000 claims 1
- 125000004372 methylthioethyl group Chemical group [H]C([H])([H])SC([H])([H])C([H])([H])* 0.000 claims 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 claims 1
- SAFBNNNOCXFULQ-UHFFFAOYSA-N n-(3-aminopropyl)-3-fluoro-n-[1-[1-(3-fluorophenyl)-4-[(3-methoxyphenyl)methyl]-5-oxo-1,2,4-triazol-3-yl]-2-methylpropyl]-4-(trifluoromethyl)benzamide Chemical compound COC1=CC=CC(CN2C(N(C=3C=C(F)C=CC=3)N=C2C(C(C)C)N(CCCN)C(=O)C=2C=C(F)C(=CC=2)C(F)(F)F)=O)=C1 SAFBNNNOCXFULQ-UHFFFAOYSA-N 0.000 claims 1
- KWFFKFDHHRDLAQ-UHFFFAOYSA-N n-(3-aminopropyl)-4-fluoro-n-[1-[1-(3-fluorophenyl)-4-[(3-methoxyphenyl)methyl]-5-oxo-1,2,4-triazol-3-yl]-2-methylpropyl]benzamide Chemical compound COC1=CC=CC(CN2C(N(C=3C=C(F)C=CC=3)N=C2C(C(C)C)N(CCCN)C(=O)C=2C=CC(F)=CC=2)=O)=C1 KWFFKFDHHRDLAQ-UHFFFAOYSA-N 0.000 claims 1
- MJXKNLPHLAECLV-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(4-benzyl-5-oxo-1-phenyl-1,2,4-triazol-3-yl)-2-methylpropyl]-1,3-benzodioxole-5-carboxamide Chemical compound C=1C=C2OCOC2=CC=1C(=O)N(CCCN)C(C(C)C)C(N(C1=O)CC=2C=CC=CC=2)=NN1C1=CC=CC=C1 MJXKNLPHLAECLV-UHFFFAOYSA-N 0.000 claims 1
- LZFBEFLBOLYVGK-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(4-benzyl-5-oxo-1-propyl-1,2,4-triazol-3-yl)-2-methylpropyl]-4-methylbenzamide Chemical compound C=1C=CC=CC=1CN1C(=O)N(CCC)N=C1C(C(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 LZFBEFLBOLYVGK-UHFFFAOYSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 61
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 41
- 230000000394 mitotic effect Effects 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 239000002585 base Substances 0.000 description 18
- 239000000010 aprotic solvent Substances 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- 150000001412 amines Chemical class 0.000 description 15
- 125000001188 haloalkyl group Chemical group 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 102000029749 Microtubule Human genes 0.000 description 11
- 108091022875 Microtubule Proteins 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
- 210000004688 microtubule Anatomy 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 239000002253 acid Substances 0.000 description 9
- 125000005037 alkyl phenyl group Chemical group 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 238000004809 thin layer chromatography Methods 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 101001008953 Homo sapiens Kinesin-like protein KIF11 Proteins 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 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
- 208000035475 disorder Diseases 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 125000005415 substituted alkoxy group Chemical group 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 102000055595 human KIF11 Human genes 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 230000011278 mitosis Effects 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 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 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-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 group 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
- 150000001299 aldehydes Chemical class 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 150000003512 tertiary amines Chemical class 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 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 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 230000002927 anti-mitotic effect Effects 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 230000002538 fungal effect Effects 0.000 description 3
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 125000004043 oxo group Chemical group O=* 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- OZZAYJQNMKMUSD-DMISRAGPSA-N pregnenolone succinate Chemical compound C1C=C2C[C@@H](OC(=O)CCC(O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 OZZAYJQNMKMUSD-DMISRAGPSA-N 0.000 description 3
- 150000003141 primary amines Chemical class 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 2
- XSGMGAINOILNJR-UHFFFAOYSA-N 2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-methyl-3-tritylsulfanylbutanoic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)NC(C(O)=O)C(C)(C)SC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XSGMGAINOILNJR-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- 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 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
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- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 125000005543 phthalimide group Chemical group 0.000 description 1
- 150000004885 piperazines Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- IAHIMVFWYADCJJ-UHFFFAOYSA-N prop-1-enylcyclohexane Chemical group CC=CC1CCCCC1 IAHIMVFWYADCJJ-UHFFFAOYSA-N 0.000 description 1
- 125000006410 propenylene group Chemical group 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229940095574 propionic acid Drugs 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009467 reduction 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
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000020347 spindle assembly Effects 0.000 description 1
- 230000012391 spindle elongation Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 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
- MLDSDVASYUUDLT-UHFFFAOYSA-N tert-butyl n-(3-oxopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCC=O MLDSDVASYUUDLT-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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 ring carbon atoms
- C07D249/12—Oxygen or sulfur atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Communicable Diseases (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41788902P | 2002-10-11 | 2002-10-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200503733B true ZA200503733B (en) | 2006-02-22 |
Family
ID=32094113
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200503733A ZA200503733B (en) | 2002-10-11 | 2005-05-10 | Compounds, compositions and methods. |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US7476743B2 (https=) |
| EP (1) | EP1558588A4 (https=) |
| JP (1) | JP2006502219A (https=) |
| KR (1) | KR20050075356A (https=) |
| CN (1) | CN1726198A (https=) |
| AR (1) | AR044193A1 (https=) |
| AU (1) | AU2003282665A1 (https=) |
| BR (1) | BR0315247A (https=) |
| CA (1) | CA2501938A1 (https=) |
| IL (1) | IL167936A0 (https=) |
| IS (1) | IS7798A (https=) |
| MX (1) | MXPA05003830A (https=) |
| NO (1) | NO20052267L (https=) |
| NZ (1) | NZ539643A (https=) |
| PL (1) | PL375889A1 (https=) |
| RU (1) | RU2005114491A (https=) |
| TW (1) | TW200418818A (https=) |
| WO (1) | WO2004032840A2 (https=) |
| ZA (1) | ZA200503733B (https=) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0510929A (pt) * | 2004-06-18 | 2007-07-17 | Chiron Corp | derivados de n-(1-(1-benzil-4-fenil-1h-imidazol-2-il)-2,2-dimetilpropil) benzamida e compostos relacionados como inibidores de proteìna de eixo de kinesin (ksp) para o tratamento de cáncer |
| EP1781674A1 (en) | 2004-08-18 | 2007-05-09 | AstraZeneca AB | Enantiomers of selected fused pyrimidones and uses in the treatment and prevention of cancer |
| DE102006023337A1 (de) * | 2006-05-18 | 2007-11-22 | Merck Patent Gmbh | Triazolderivate II |
| JP5343363B2 (ja) * | 2008-01-31 | 2013-11-13 | アイシン精機株式会社 | シートクッション調整装置 |
| CN101643451B (zh) * | 2008-08-07 | 2013-03-06 | 浙江海正药业股份有限公司 | 过氧化物酶增殖物激活受体亚型δ类激动剂化合物及其制备方法 |
| EA201201404A1 (ru) | 2010-04-15 | 2013-04-30 | Новартис Аг | Триазолы как ингибиторы кбв (кинезин-белок веретена) |
| WO2012095691A1 (en) * | 2011-01-15 | 2012-07-19 | Jubilant Life Sciences Ltd. | An improved process for producing aminopyridines |
| EP2822931B1 (en) | 2012-03-09 | 2017-05-03 | Inception 2, Inc. | Triazolone compounds and uses thereof |
| SG11201504622PA (en) | 2012-12-20 | 2015-07-30 | Inception 2 Inc | Triazolone compounds and uses thereof |
| CN105579440A (zh) | 2013-09-06 | 2016-05-11 | 因森普深2公司 | 三唑酮化合物及其应用 |
| JP6971858B2 (ja) | 2015-06-22 | 2021-11-24 | バイエル ファーマ アクチエンゲゼルシャフト | 酵素開裂性基を有する抗体薬物複合体（ａｄｃ）および抗体プロドラッグ複合体（ａｐｄｃ） |
| TW201722958A (zh) * | 2015-09-15 | 2017-07-01 | 葛蘭素史克智慧財產（第二）有限公司 | 化學化合物 |
| CN110312534B (zh) | 2016-12-21 | 2023-04-04 | 拜耳制药股份公司 | 具有酶促可裂解基团的抗体-药物-缀合物(adc) |
| US20250215039A1 (en) * | 2022-03-30 | 2025-07-03 | Primefour Therapeutics, Inc. | Nucleosides for treating cancer |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE793532A (fr) * | 1971-12-29 | 1973-06-29 | Upjohn Co | Nouvelles 1,2,4-triazol-3-ones et leur preparation |
| US3748339A (en) * | 1972-05-05 | 1973-07-24 | Upjohn Co | 2-(3-(1-(dimethylamino)alkyl)-1,5-dihydro-5-oxo - 1 - substituted-4h-1,2,4-triazol-4-yl)benzophenone and process |
| IT1068010B (it) * | 1976-11-17 | 1985-03-21 | Montedison Spa | Nuovi esteri fosforici derivati dall' 1-2-4 triazolo ad azione insetticida,nematocida e acaricida e loro preparazione |
| NL7712430A (nl) * | 1976-11-17 | 1978-05-19 | Montedison Spa | Nieuwe fosforzuuresters, afgeleid van 1.2.4- -triazool, met een insecticide, nematocide en acaricide werking en werkwijze ter bereiding daarvan. |
| US4487773A (en) * | 1981-03-16 | 1984-12-11 | Mead Johnson & Company | 1,2,4-Triazol-3-one antidepressants |
| US5250558A (en) * | 1992-01-28 | 1993-10-05 | Merck & Co., Inc. | Substituted triazolinones, triazolinethiones, and triazolinimines as neurotensin antagonists used to treat psychosis |
| GB9211193D0 (en) | 1992-05-27 | 1992-07-08 | Merck Sharp & Dohme | Therapeutic agents |
| IL106142A (en) * | 1992-06-29 | 1997-03-18 | Merck & Co Inc | Morpholine and thiomorpholine tachykinin receptor antagonists, their preparation and pharmaceutical compositions containing them |
| AU722883B2 (en) * | 1995-10-18 | 2000-08-10 | Merck & Co., Inc. | Cyclopentyl tachykinin receptor antagonists |
| JP2002234874A (ja) * | 2000-09-26 | 2002-08-23 | Tanabe Seiyaku Co Ltd | ５−フェニルベンジルアミン誘導体、その製法及びその合成中間体 |
| US6727244B2 (en) * | 2000-10-26 | 2004-04-27 | Merck & Co., Inc. | Mammalian metabolites of a tachykinin receptor antagonist |
| EP1515724B1 (en) * | 2002-06-14 | 2009-10-21 | Merck & Co., Inc. | Mitotic kinesin inhibitors |
-
2003
- 2003-10-02 BR BR0315247-2A patent/BR0315247A/pt not_active IP Right Cessation
- 2003-10-02 EP EP03774548A patent/EP1558588A4/en not_active Withdrawn
- 2003-10-02 RU RU2005114491/04A patent/RU2005114491A/ru not_active Application Discontinuation
- 2003-10-02 AU AU2003282665A patent/AU2003282665A1/en not_active Abandoned
- 2003-10-02 MX MXPA05003830A patent/MXPA05003830A/es unknown
- 2003-10-02 CN CNA200380105737XA patent/CN1726198A/zh active Pending
- 2003-10-02 NZ NZ539643A patent/NZ539643A/en unknown
- 2003-10-02 KR KR1020057006260A patent/KR20050075356A/ko not_active Withdrawn
- 2003-10-02 CA CA002501938A patent/CA2501938A1/en not_active Abandoned
- 2003-10-02 PL PL03375889A patent/PL375889A1/xx unknown
- 2003-10-02 WO PCT/US2003/031413 patent/WO2004032840A2/en not_active Ceased
- 2003-10-02 US US10/529,634 patent/US7476743B2/en not_active Expired - Fee Related
- 2003-10-02 JP JP2004543136A patent/JP2006502219A/ja active Pending
- 2003-10-09 AR ARP030103684A patent/AR044193A1/es unknown
- 2003-10-09 TW TW092128029A patent/TW200418818A/zh unknown
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2005
- 2005-04-10 IL IL167936A patent/IL167936A0/en unknown
- 2005-04-11 IS IS7798A patent/IS7798A/is unknown
- 2005-05-10 NO NO20052267A patent/NO20052267L/no not_active Application Discontinuation
- 2005-05-10 ZA ZA200503733A patent/ZA200503733B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004032840A3 (en) | 2004-10-14 |
| IL167936A0 (en) | 2009-02-11 |
| EP1558588A2 (en) | 2005-08-03 |
| NO20052267L (no) | 2005-05-31 |
| US20060189671A1 (en) | 2006-08-24 |
| RU2005114491A (ru) | 2006-02-10 |
| IS7798A (is) | 2005-04-11 |
| PL375889A1 (en) | 2005-12-12 |
| AU2003282665A1 (en) | 2004-05-04 |
| CN1726198A (zh) | 2006-01-25 |
| MXPA05003830A (es) | 2005-06-23 |
| TW200418818A (en) | 2004-10-01 |
| KR20050075356A (ko) | 2005-07-20 |
| CA2501938A1 (en) | 2004-04-22 |
| NZ539643A (en) | 2006-11-30 |
| EP1558588A4 (en) | 2006-11-02 |
| US7476743B2 (en) | 2009-01-13 |
| BR0315247A (pt) | 2005-08-30 |
| AR044193A1 (es) | 2005-09-07 |
| JP2006502219A (ja) | 2006-01-19 |
| WO2004032840A2 (en) | 2004-04-22 |
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