NO320343B1 - Tricykliske inhibitorer av poly(ADP-ribose) polymeraser, farmasoytiske materialer derav, samt anvendelser derav. - Google Patents

Tricykliske inhibitorer av poly(ADP-ribose) polymeraser, farmasoytiske materialer derav, samt anvendelser derav. Download PDF

Info

Publication number: NO320343B1
Authority: NO; Norway
Prior art keywords: mmol; aryl; alkyl; compound; azepino
Prior art date: 1999-01-11

Application number

NO20013313A

Other languages

English (en)

Norwegian (no)

Other versions

NO20013313D0 (no

NO20013313L (no

Inventor

Stephen Evan Webber

Jayashree Girish Tikhe

Stacie S Canan-Koch

Lars Henrik Thoresen

Original Assignee

Cancer Rec Tech Ltd

Agouron Pharma

Priority date (The priority date 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 date listed.)

1999-01-11

Filing date

2001-07-04

Publication date

2005-11-28

2001-07-04 Application filed by Cancer Rec Tech Ltd, Agouron Pharma filed Critical Cancer Rec Tech Ltd

2001-07-04 Publication of NO20013313D0 publication Critical patent/NO20013313D0/no

2001-09-10 Publication of NO20013313L publication Critical patent/NO20013313L/no

2005-11-28 Publication of NO320343B1 publication Critical patent/NO320343B1/no

Links

229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 title claims description 49
239000000463 material Substances 0.000 title claims description 16
102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 title description 54
108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 title description 54
239000003112 inhibitor Substances 0.000 title description 16
150000001875 compounds Chemical class 0.000 claims description 109
229910052757 nitrogen Inorganic materials 0.000 claims description 109
125000003118 aryl group Chemical group 0.000 claims description 81
-1 carboxy, amino Chemical group 0.000 claims description 53
125000000217 alkyl group Chemical group 0.000 claims description 41
125000001424 substituent group Chemical group 0.000 claims description 39
150000003839 salts Chemical class 0.000 claims description 37
229910052736 halogen Inorganic materials 0.000 claims description 35
150000002367 halogens Chemical class 0.000 claims description 35
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 35
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 34
125000001072 heteroaryl group Chemical group 0.000 claims description 34
239000012453 solvate Substances 0.000 claims description 32
125000000753 cycloalkyl group Chemical group 0.000 claims description 27
125000000304 alkynyl group Chemical group 0.000 claims description 24
125000003367 polycyclic group Chemical group 0.000 claims description 24
125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 19
239000003814 drug Substances 0.000 claims description 18
125000005842 heteroatom Chemical group 0.000 claims description 18
230000002401 inhibitory effect Effects 0.000 claims description 18
239000003795 chemical substances by application Substances 0.000 claims description 17
125000002950 monocyclic group Chemical group 0.000 claims description 17
229910052717 sulfur Chemical group 0.000 claims description 17
229910052760 oxygen Inorganic materials 0.000 claims description 16
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 15
239000001301 oxygen Chemical group 0.000 claims description 15
238000011282 treatment Methods 0.000 claims description 15
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
241000124008 Mammalia Species 0.000 claims description 13
125000002252 acyl group Chemical group 0.000 claims description 12
238000002360 preparation method Methods 0.000 claims description 12
239000011593 sulfur Chemical group 0.000 claims description 12
125000004093 cyano group Chemical group *C#N 0.000 claims description 11
208000006011 Stroke Diseases 0.000 claims description 10
230000004770 neurodegeneration Effects 0.000 claims description 10
206010019196 Head injury Diseases 0.000 claims description 9
208000015122 neurodegenerative disease Diseases 0.000 claims description 9
229910006074 SO2NH2 Inorganic materials 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 7
125000004414 alkyl thio group Chemical group 0.000 claims description 7
125000005110 aryl thio group Chemical group 0.000 claims description 7
125000004104 aryloxy group Chemical group 0.000 claims description 7
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
229910052801 chlorine Inorganic materials 0.000 claims description 7
229910052731 fluorine Inorganic materials 0.000 claims description 7
125000005553 heteroaryloxy group Chemical group 0.000 claims description 7
125000005368 heteroarylthio group Chemical group 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
125000004043 oxo group Chemical group O=* 0.000 claims description 6
238000011161 development Methods 0.000 claims description 5
230000018109 developmental process Effects 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
230000004968 inflammatory condition Effects 0.000 claims description 5
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
206010028980 Neoplasm Diseases 0.000 claims description 4
201000011510 cancer Diseases 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
208000024172 Cardiovascular disease Diseases 0.000 claims description 3
206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
230000009758 senescence Effects 0.000 claims description 3
230000009759 skin aging Effects 0.000 claims description 3
208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims description 3
239000005864 Sulphur Chemical group 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 295
239000007787 solid Substances 0.000 description 147
238000005481 NMR spectroscopy Methods 0.000 description 120
239000000243 solution Substances 0.000 description 102
229910052739 hydrogen Inorganic materials 0.000 description 97
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 80
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 78
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 64
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 52
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 43
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 38
229940125797 compound 12 Drugs 0.000 description 38
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
238000006243 chemical reaction Methods 0.000 description 33
239000011734 sodium Substances 0.000 description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
239000010410 layer Substances 0.000 description 26
235000019439 ethyl acetate Nutrition 0.000 description 25
235000002639 sodium chloride Nutrition 0.000 description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
239000000203 mixture Substances 0.000 description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
239000000543 intermediate Substances 0.000 description 20
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 20
239000012267 brine Substances 0.000 description 19
230000005764 inhibitory process Effects 0.000 description 19
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
239000011541 reaction mixture Substances 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
239000012043 crude product Substances 0.000 description 16
238000004587 chromatography analysis Methods 0.000 description 14
238000000034 method Methods 0.000 description 14
239000012044 organic layer Substances 0.000 description 14
229920006395 saturated elastomer Polymers 0.000 description 14
239000007864 aqueous solution Substances 0.000 description 13
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 13
239000000725 suspension Substances 0.000 description 13
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 12
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 12
DKFFSRBSODVODR-UHFFFAOYSA-N 6-oxo-3,4,5 ,6-tetrahydro-1h-azepino[5,4,3-cd]indole-2-carboxylic acid Chemical compound O=C1NCCC2=C(C(=O)O)NC3=CC=CC1=C32 DKFFSRBSODVODR-UHFFFAOYSA-N 0.000 description 11
239000012661 PARP inhibitor Substances 0.000 description 11
229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 11
230000000694 effects Effects 0.000 description 11
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 10
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 10
229910052786 argon Inorganic materials 0.000 description 10
229910052799 carbon Inorganic materials 0.000 description 10
210000004027 cell Anatomy 0.000 description 10
JBXRLVPILRXPNH-UHFFFAOYSA-N indol-6-one Chemical compound O=C1C=CC2=CC=NC2=C1 JBXRLVPILRXPNH-UHFFFAOYSA-N 0.000 description 10
239000002904 solvent Substances 0.000 description 10
239000011592 zinc chloride Substances 0.000 description 10
235000005074 zinc chloride Nutrition 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
150000001299 aldehydes Chemical class 0.000 description 9
238000003818 flash chromatography Methods 0.000 description 9
230000003389 potentiating effect Effects 0.000 description 9
238000010992 reflux Methods 0.000 description 9
ZRRIVOUCCUFNDH-UHFFFAOYSA-N 2-bromo-3,4,5,6-tetrahydro-azepino[5,4,3-cd]indol-6-one Chemical compound O=C1NCCC2=C(Br)NC3=CC=CC1=C32 ZRRIVOUCCUFNDH-UHFFFAOYSA-N 0.000 description 8
HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 8
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 8
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 8
239000000047 product Substances 0.000 description 8
238000001953 recrystallisation Methods 0.000 description 8
238000012360 testing method Methods 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
239000002253 acid Substances 0.000 description 7
201000010099 disease Diseases 0.000 description 7
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229940079593 drug Drugs 0.000 description 7
239000003921 oil Substances 0.000 description 7
235000019198 oils Nutrition 0.000 description 7
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 6
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 6
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 6
CETUIKOTKQSYEU-UHFFFAOYSA-N 2-iodo-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one Chemical compound O=C1NCCC2=C(I)NC3=CC=CC1=C32 CETUIKOTKQSYEU-UHFFFAOYSA-N 0.000 description 6
102000004190 Enzymes Human genes 0.000 description 6
108090000790 Enzymes Proteins 0.000 description 6
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 6
238000003556 assay Methods 0.000 description 6
125000004432 carbon atom Chemical group C* 0.000 description 6
229940126208 compound 22 Drugs 0.000 description 6
231100000135 cytotoxicity Toxicity 0.000 description 6
230000003013 cytotoxicity Effects 0.000 description 6
238000001914 filtration Methods 0.000 description 6
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
125000004356 hydroxy functional group Chemical group O* 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
235000011056 potassium acetate Nutrition 0.000 description 6
230000002829 reductive effect Effects 0.000 description 6
229910000029 sodium carbonate Inorganic materials 0.000 description 6
238000003756 stirring Methods 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
DGHHQBMTXTWTJV-BQAIUKQQSA-N 119413-54-6 Chemical compound Cl.C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 DGHHQBMTXTWTJV-BQAIUKQQSA-N 0.000 description 5
PYLXNOZFJZQGBX-UHFFFAOYSA-N 53462-75-2 Chemical compound C1=CC(C(=O)NC2)=C3C2=CNC3=C1 PYLXNOZFJZQGBX-UHFFFAOYSA-N 0.000 description 5
108020004414 DNA Proteins 0.000 description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
102000003960 Ligases Human genes 0.000 description 5
108090000364 Ligases Proteins 0.000 description 5
BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 5
108091026813 Poly(ADPribose) Proteins 0.000 description 5
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
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239000012300 argon atmosphere Substances 0.000 description 5
SNEIEJXAZHWQSB-UHFFFAOYSA-N azepino[5,4,3-cd]indol-6-one, 4 Chemical compound C1=CC(CN(C)C)=CC=C1C(N1)=C2CCNC(=O)C3=C2C1=CC=C3 SNEIEJXAZHWQSB-UHFFFAOYSA-N 0.000 description 5
IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 5
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WEAXQUBYRSEBJD-UHFFFAOYSA-N methyl 1h-indole-4-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1C=CN2 WEAXQUBYRSEBJD-UHFFFAOYSA-N 0.000 description 5
CMCWXWQXFLAUFM-UHFFFAOYSA-N methyl 2-iodo-3-nitrobenzoate Chemical compound COC(=O)C1=CC=CC([N+]([O-])=O)=C1I CMCWXWQXFLAUFM-UHFFFAOYSA-N 0.000 description 5
229950006238 nadide Drugs 0.000 description 5
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206010029350 Neurotoxicity Diseases 0.000 description 4
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BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 4
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DIUAWEVAOAYVBP-UHFFFAOYSA-N molport-035-773-933 Chemical compound O=C1NCCC2=C(Br)NC3=CC(F)=CC1=C32 DIUAWEVAOAYVBP-UHFFFAOYSA-N 0.000 description 4
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229910052763 palladium Inorganic materials 0.000 description 4
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
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LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
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RZFVLEJOHSLEFR-UHFFFAOYSA-N phenanthridone Chemical compound C1=CC=C2C(O)=NC3=CC=CC=C3C2=C1 RZFVLEJOHSLEFR-UHFFFAOYSA-N 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical class CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
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IVXQBCUBSIPQGU-UHFFFAOYSA-N piperazine-1-carboxamide Chemical compound NC(=O)N1CCNCC1 IVXQBCUBSIPQGU-UHFFFAOYSA-N 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
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229910003446 platinum oxide Inorganic materials 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
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230000002062 proliferating effect Effects 0.000 description 1
JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 1
KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical class CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical class OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl 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
229940107700 pyruvic acid Drugs 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
150000003246 quinazolines Chemical class 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
238000001959 radiotherapy Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
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239000012723 sample buffer Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
230000011664 signaling Effects 0.000 description 1
229930188929 simonin Natural products 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000001119 stannous chloride Substances 0.000 description 1
235000011150 stannous chloride 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
239000008117 stearic acid Substances 0.000 description 1
238000003860 storage Methods 0.000 description 1
TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical class OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
150000003892 tartrate salts Chemical class 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
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125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
230000001225 therapeutic effect Effects 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
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
210000001541 thymus gland Anatomy 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
PYMPTRMDPJYTDF-UHFFFAOYSA-N tributyl(2-phenylethynyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C#CC1=CC=CC=C1 PYMPTRMDPJYTDF-UHFFFAOYSA-N 0.000 description 1
125000000169 tricyclic heterocycle group Chemical group 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/275—Nitriles; Isonitriles
- A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- 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
- 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
- A61P9/10—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
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/06—Peri-condensed systems

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Epidemiology (AREA)
Diabetes (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Hematology (AREA)
Obesity (AREA)
Vascular Medicine (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

NO20013313A 1999-01-11 2001-07-04 Tricykliske inhibitorer av poly(ADP-ribose) polymeraser, farmasoytiske materialer derav, samt anvendelser derav. NO320343B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US11543199P	1999-01-11	1999-01-11
PCT/US2000/000411 WO2000042040A1 (en)	1999-01-11	2000-01-10	Tricyclic inhibitors of poly(adp-ribose) polymerases

Publications (3)

Publication Number	Publication Date
NO20013313D0 NO20013313D0 (no)	2001-07-04
NO20013313L NO20013313L (no)	2001-09-10
NO320343B1 true NO320343B1 (no)	2005-11-28

Family

ID=22361361

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Application Number	Title	Priority Date	Filing Date
NO20013313A NO320343B1 (no)	1999-01-11	2001-07-04	Tricykliske inhibitorer av poly(ADP-ribose) polymeraser, farmasoytiske materialer derav, samt anvendelser derav.

Country Status (39)

Country	Link
US (4)	US6495541B1 (de)
EP (1)	EP1140936B1 (de)
JP (1)	JP4093448B2 (de)
KR (1)	KR100632079B1 (de)
CN (1)	CN100418967C (de)
AP (1)	AP1538A (de)
AT (1)	ATE261963T1 (de)
AU (1)	AU781711B2 (de)
BG (1)	BG65210B1 (de)
BR (1)	BRPI0008614B8 (de)
CA (1)	CA2360003C (de)
CZ (1)	CZ302941B6 (de)
DE (1)	DE60009033T2 (de)
DK (1)	DK1140936T3 (de)
EA (1)	EA004989B1 (de)
EE (1)	EE05006B1 (de)
ES (1)	ES2218110T3 (de)
GE (1)	GEP20033055B (de)
HR (1)	HRP20010573B1 (de)
HU (1)	HU229875B1 (de)
ID (1)	ID30138A (de)
IL (2)	IL144112A0 (de)
IS (1)	IS5995A (de)
LT (1)	LT4936B (de)
LV (1)	LV12770B (de)
MX (1)	MXPA01007001A (de)
NO (1)	NO320343B1 (de)
NZ (1)	NZ512731A (de)
OA (2)	OA11749A (de)
PL (1)	PL210415B1 (de)
PT (1)	PT1140936E (de)
RO (1)	RO121778B1 (de)
RS (1)	RS50031B (de)
SI (1)	SI20691B (de)
SK (1)	SK287338B6 (de)
TR (1)	TR200102005T2 (de)
UA (1)	UA75034C2 (de)
WO (1)	WO2000042040A1 (de)
ZA (1)	ZA200105399B (de)

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BR0007174A (pt) *	1999-09-28	2001-09-04	Basf Ag	Composto, preparação farmacêutica e uso de compostos
US6589725B1 (en)	1999-10-25	2003-07-08	Rigel Pharmaceuticals, Inc.	Tankyrase H, compositions involved in the cell cycle and methods of use
US6476048B1 (en)	1999-12-07	2002-11-05	Inotek Pharamaceuticals Corporation	Substituted phenanthridinones and methods of use thereof
US6531464B1 (en)	1999-12-07	2003-03-11	Inotek Pharmaceutical Corporation	Methods for the treatment of neurodegenerative disorders using substituted phenanthridinone derivatives
IL151669A0 (en) *	2000-03-20	2003-04-10	N Gene Res Lab Inc	Propenecarboxylic acid amidoxime derivatives, a process for the preparation thereof, and pharmaceutical compositions containing the same
US6534651B2 (en)	2000-04-06	2003-03-18	Inotek Pharmaceuticals Corp.	7-Substituted isoindolinone inhibitors of inflammation and reperfusion injury and methods of use thereof
MXPA03004832A (es) *	2000-12-01	2004-05-04	Guilford Pharm Inc	Compuestos y sus usos.
DE60218458T2 (de)	2001-05-08	2007-11-15	Kudos Pharmaceuticals Ltd.	Isochinolinon derivate als parp inhibitoren
CA2456985A1 (en)	2001-08-15	2003-02-27	Icos Corporation	2h-phthalazin-1-ones and methods for use thereof
US20030096833A1 (en)	2001-08-31	2003-05-22	Jagtap Prakash G.	Substituted ideno[1,2-c]isoquinoline derivatives and methods of use thereof
US6956035B2 (en)	2001-08-31	2005-10-18	Inotek Pharmaceuticals Corporation	Isoquinoline derivatives and methods of use thereof
WO2003051879A1 (en) *	2001-12-14	2003-06-26	Altana Pharma Ag	Known and novel 4,5-dihydro-imidazo[4,5,1-ij]quinolin-6-ones useful as poly(adp-ribose)polymerase inhibitors
US7196085B2 (en)	2002-04-30	2007-03-27	Kudos Pharmaceuticals Limited	Phthalazinone derivatives
PL378372A1 (pl)	2003-01-09	2006-04-03	Pfizer Inc.	Tricykliczne związki jako inhibitory kinaz białkowych do wzmacniania skuteczności środków przeciwnowotworowych i radioterapii
KR20050118169A (ko)	2003-02-28	2005-12-15	이노텍 파마슈티컬스 코포레이션	사환식 벤즈아미드 유도체 및 이것의 사용 방법
GB0305681D0 (en)	2003-03-12	2003-04-16	Kudos Pharm Ltd	Phthalazinone derivatives
US7449464B2 (en)	2003-03-12	2008-11-11	Kudos Pharmaceuticals Limited	Phthalazinone derivatives
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2000
- 2000-01-10 EE EEP200100364A patent/EE05006B1/xx unknown
- 2000-01-10 AT AT00902358T patent/ATE261963T1/de active
- 2000-01-10 SI SI200020013A patent/SI20691B/sl active Search and Examination
- 2000-01-10 JP JP2000593608A patent/JP4093448B2/ja not_active Expired - Lifetime
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- 2000-01-10 AP APAP/P/2001/002211A patent/AP1538A/en active
- 2000-01-10 RO ROA200100795A patent/RO121778B1/ro unknown
- 2000-01-10 KR KR1020017008709A patent/KR100632079B1/ko not_active Expired - Lifetime
- 2000-01-10 AU AU24088/00A patent/AU781711B2/en not_active Expired
- 2000-01-10 CZ CZ20012443A patent/CZ302941B6/cs not_active IP Right Cessation
- 2000-01-10 CN CNB008045895A patent/CN100418967C/zh not_active Expired - Lifetime
- 2000-01-10 DK DK00902358T patent/DK1140936T3/da active
- 2000-01-10 MX MXPA01007001A patent/MXPA01007001A/es active IP Right Grant
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- 2000-01-10 PT PT00902358T patent/PT1140936E/pt unknown
- 2000-01-10 RS YUP-490/01A patent/RS50031B/sr unknown
- 2000-01-10 TR TR2001/02005T patent/TR200102005T2/xx unknown
- 2000-01-10 US US09/479,896 patent/US6495541B1/en not_active Expired - Lifetime
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- 2000-01-10 DE DE60009033T patent/DE60009033T2/de not_active Expired - Lifetime
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- 2000-01-10 CA CA2360003A patent/CA2360003C/en not_active Expired - Lifetime
- 2000-01-10 WO PCT/US2000/000411 patent/WO2000042040A1/en not_active Ceased
- 2000-01-10 ES ES00902358T patent/ES2218110T3/es not_active Expired - Lifetime
- 2000-01-10 NZ NZ512731A patent/NZ512731A/xx not_active IP Right Cessation
- 2000-01-10 EP EP00902358A patent/EP1140936B1/de not_active Expired - Lifetime
- 2000-01-10 IL IL14411200A patent/IL144112A0/xx active IP Right Grant
- 2000-01-10 SK SK966-2001A patent/SK287338B6/sk not_active IP Right Cessation
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- 2000-01-19 ID IDW00200101726A patent/ID30138A/id unknown
- 2000-10-01 UA UA2001074881A patent/UA75034C2/uk unknown
2001
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2002
- 2002-08-28 OA OA1200200262A patent/OA12185A/en unknown
- 2002-10-02 US US10/264,018 patent/US20030078254A1/en not_active Abandoned
2004
- 2004-12-03 US US11/004,261 patent/US6977298B2/en not_active Expired - Lifetime
2005
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Also Published As

Publication number	Publication date
NO20013313D0 (no)	2001-07-04
CN1342161A (zh)	2002-03-27
HUP0105414A3 (en)	2003-04-28
DK1140936T3 (da)	2004-06-21
WO2000042040A1 (en)	2000-07-20
SI20691B (sl)	2008-10-31
LT4936B (lt)	2002-07-25
US20030078254A1 (en)	2003-04-24
BR0008614A (pt)	2001-10-16
JP2002534523A (ja)	2002-10-15
IS5995A (is)	2001-07-10
EE05006B1 (et)	2008-04-15
ZA200105399B (en)	2002-07-01
CZ20012443A3 (cs)	2002-02-13
SK287338B6 (sk)	2010-07-07
US6977298B2 (en)	2005-12-20
LV12770A (en)	2001-12-20
BG65210B1 (bg)	2007-07-31
MXPA01007001A (es)	2002-07-30
KR20020008112A (ko)	2002-01-29
GEP20033055B (en)	2003-08-25
EP1140936B1 (de)	2004-03-17
IL144112A0 (en)	2002-05-23
ID30138A (id)	2001-11-08
BRPI0008614B8 (pt)	2021-05-25
AP2001002211A0 (en)	2001-09-30
US20060009517A1 (en)	2006-01-12
US7429578B2 (en)	2008-09-30
BR0008614B1 (pt)	2014-11-25
CA2360003C (en)	2012-07-10
IL144112A (en)	2006-07-05
CZ302941B6 (cs)	2012-01-25
CN100418967C (zh)	2008-09-17
ATE261963T1 (de)	2004-04-15
OA12185A (en)	2006-05-09
DE60009033T2 (de)	2004-08-05
YU49001A (sh)	2005-11-28
ES2218110T3 (es)	2004-11-16
LV12770B (lv)	2002-05-20
CA2360003A1 (en)	2000-07-20
HK1040992A1 (en)	2002-06-28
HU229875B1 (en)	2014-11-28
RO121778B1 (ro)	2008-04-30
PT1140936E (pt)	2004-06-30
UA75034C2 (en)	2006-03-15
AP1538A (en)	2006-01-10
AU781711B2 (en)	2005-06-09
PL357049A1 (en)	2004-07-12
SI20691A (sl)	2002-04-30
JP4093448B2 (ja)	2008-06-04
HUP0105414A2 (hu)	2002-05-29
EP1140936A1 (de)	2001-10-10
AU2408800A (en)	2000-08-01
SK9662001A3 (en)	2002-04-04
KR100632079B1 (ko)	2006-10-04
US20050085460A1 (en)	2005-04-21
EE200100364A (et)	2002-10-15
HRP20010573A2 (en)	2005-02-28
NZ512731A (en)	2004-01-30
EA200100764A1 (ru)	2002-06-27
LT2001083A (en)	2002-03-25
NO20013313L (no)	2001-09-10
US6495541B1 (en)	2002-12-17
TR200102005T2 (tr)	2001-12-21
RS50031B (sr)	2008-11-28
DE60009033D1 (de)	2004-04-22
PL210415B1 (pl)	2012-01-31
BG105811A (en)	2002-05-31
HRP20010573B1 (en)	2006-04-30
OA11749A (en)	2005-07-19
EA004989B1 (ru)	2004-10-28

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2020-02-10	MK1K	Patent expired