HRP980340A2 - Barbituric acid derivatives with antimetastatic and antitumor activity - Google Patents

Barbituric acid derivatives with antimetastatic and antitumor activity

Info

Publication number: HRP980340A2
Authority: HR; Croatia
Prior art keywords: barbituric acid; alkyl; group; octyl; carboxymethyl
Prior art date: 1997-06-21

Application number

HR97110200.9A

Other languages

English (en)

Croatian (hr)

Inventor

Hans Willi Krell

Original Assignee

Hans Willi Krell

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.)

1997-06-21

Filing date

1998-06-19

Publication date

1999-02-28

1998-06-19 Application filed by Hans Willi Krell filed Critical Hans Willi Krell

1999-02-28 Publication of HRP980340A2 publication Critical patent/HRP980340A2/hr

Links

150000007656 barbituric acids Chemical class 0.000 title claims description 8
230000000259 anti-tumor effect Effects 0.000 title claims description 5
230000002001 anti-metastasis Effects 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims description 51
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 39
238000002360 preparation method Methods 0.000 claims description 39
239000000203 mixture Substances 0.000 claims description 33
PJFDJNHVADUPMX-UHFFFAOYSA-N 2-(5-octyl-2,4,6-trioxo-1,3-diazinan-5-yl)acetic acid Chemical compound CCCCCCCCC1(CC(O)=O)C(=O)NC(=O)NC1=O PJFDJNHVADUPMX-UHFFFAOYSA-N 0.000 claims description 32
239000002904 solvent Substances 0.000 claims description 24
-1 benzylamino, phenoxy Chemical group 0.000 claims description 23
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 21
125000003282 alkyl amino group Chemical group 0.000 claims description 20
229910052736 halogen Inorganic materials 0.000 claims description 19
150000002367 halogens Chemical class 0.000 claims description 19
229920006395 saturated elastomer Polymers 0.000 claims description 19
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 18
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 16
238000000034 method Methods 0.000 claims description 15
238000006243 chemical reaction Methods 0.000 claims description 14
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
229910052717 sulfur Chemical group 0.000 claims description 13
239000011593 sulfur Chemical group 0.000 claims description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
125000005842 heteroatom Chemical group 0.000 claims description 12
229910052757 nitrogen Inorganic materials 0.000 claims description 12
239000001301 oxygen Substances 0.000 claims description 12
229910052760 oxygen Inorganic materials 0.000 claims description 12
239000001257 hydrogen Substances 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 9
HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims description 9
239000003112 inhibitor Substances 0.000 claims description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
238000011282 treatment Methods 0.000 claims description 9
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
239000004305 biphenyl Substances 0.000 claims description 7
239000002253 acid Substances 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
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 claims description 5
150000007513 acids Chemical class 0.000 claims description 5
150000003951 lactams Chemical class 0.000 claims description 5
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 4
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
208000001132 Osteoporosis Diseases 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 4
125000000217 alkyl group Chemical group 0.000 claims description 4
125000004185 ester group Chemical group 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
150000003839 salts Chemical class 0.000 claims description 4
125000005036 alkoxyphenyl group Chemical group 0.000 claims description 3
235000010290 biphenyl Nutrition 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 2
MXOHUQVGNQNABU-UHFFFAOYSA-N 2-(5-decyl-2,4,6-trioxo-1,3-diazinan-5-yl)acetic acid Chemical compound CCCCCCCCCCC1(CC(O)=O)C(=O)NC(=O)NC1=O MXOHUQVGNQNABU-UHFFFAOYSA-N 0.000 claims description 2
SWPNGMICAXJQBZ-UHFFFAOYSA-N 2-(5-octadecyl-2,4,6-trioxo-1,3-diazinan-5-yl)acetic acid Chemical compound CCCCCCCCCCCCCCCCCCC1(CC(O)=O)C(=O)NC(=O)NC1=O SWPNGMICAXJQBZ-UHFFFAOYSA-N 0.000 claims description 2
PLAQFNHQXBQNSV-UHFFFAOYSA-N 2-(5-octyl-2,4,6-trioxo-1,3-diazinan-5-yl)-n-sulfamoylacetamide Chemical compound CCCCCCCCC1(CC(=O)NS(N)(=O)=O)C(=O)NC(=O)NC1=O PLAQFNHQXBQNSV-UHFFFAOYSA-N 0.000 claims description 2
DRFVLEMRYLJKSI-UHFFFAOYSA-N 2-[2,4,6-trioxo-5-(4-phenoxyphenyl)-1,3-diazinan-5-yl]acetic acid Chemical compound C=1C=C(OC=2C=CC=CC=2)C=CC=1C1(CC(=O)O)C(=O)NC(=O)NC1=O DRFVLEMRYLJKSI-UHFFFAOYSA-N 0.000 claims description 2
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 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
206010053555 Arthritis bacterial Diseases 0.000 claims description 2
208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 2
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 2
206010011091 Coronary artery thrombosis Diseases 0.000 claims description 2
206010014561 Emphysema Diseases 0.000 claims description 2
206010016654 Fibrosis Diseases 0.000 claims description 2
206010019280 Heart failures Diseases 0.000 claims description 2
208000004575 Infectious Arthritis Diseases 0.000 claims description 2
206010061218 Inflammation Diseases 0.000 claims description 2
OBSIQMZKFXFYLV-QMMMGPOBSA-N L-phenylalanine amide Chemical compound NC(=O)[C@@H](N)CC1=CC=CC=C1 OBSIQMZKFXFYLV-QMMMGPOBSA-N 0.000 claims description 2
229910006074 SO2NH2 Inorganic materials 0.000 claims description 2
208000007107 Stomach Ulcer Diseases 0.000 claims description 2
206010064996 Ulcerative keratitis Diseases 0.000 claims description 2
125000002252 acyl group Chemical group 0.000 claims description 2
150000001408 amides Chemical class 0.000 claims description 2
208000007474 aortic aneurysm Diseases 0.000 claims description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
229940124558 contraceptive agent Drugs 0.000 claims description 2
239000003433 contraceptive agent Substances 0.000 claims description 2
208000002528 coronary thrombosis Diseases 0.000 claims description 2
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 2
OCDDMRXKSRKFCT-UHFFFAOYSA-N ethyl 2-(5-octyl-2,4,6-trioxo-1,3-diazinan-5-yl)acetate Chemical compound CCCCCCCCC1(CC(=O)OCC)C(=O)NC(=O)NC1=O OCDDMRXKSRKFCT-UHFFFAOYSA-N 0.000 claims description 2
230000004761 fibrosis Effects 0.000 claims description 2
230000004054 inflammatory process Effects 0.000 claims description 2
208000014674 injury Diseases 0.000 claims description 2
150000007529 inorganic bases Chemical class 0.000 claims description 2
201000006417 multiple sclerosis Diseases 0.000 claims description 2
UGXKGQRZIUQPIK-UHFFFAOYSA-N n-[2-(5-octyl-2,4,6-trioxo-1,3-diazinan-5-yl)acetyl]piperazine-1-carboxamide Chemical compound C1CNCCN1C(=O)NC(=O)CC1(CCCCCCCC)C(=O)NC(=O)NC1=O UGXKGQRZIUQPIK-UHFFFAOYSA-N 0.000 claims description 2
ZEFVZPPBFQYQEA-UHFFFAOYSA-N n-[2-(5-octyl-2,4,6-trioxo-1,3-diazinan-5-yl)acetyl]pyrrolidine-1-carboxamide Chemical compound C1CCCN1C(=O)NC(=O)CC1(CCCCCCCC)C(=O)NC(=O)NC1=O ZEFVZPPBFQYQEA-UHFFFAOYSA-N 0.000 claims description 2
SAKLUOJPSGXTAU-UHFFFAOYSA-N n-carbamoyl-2-(5-octyl-2,4,6-trioxo-1,3-diazinan-5-yl)acetamide Chemical compound CCCCCCCCC1(CC(=O)NC(N)=O)C(=O)NC(=O)NC1=O SAKLUOJPSGXTAU-UHFFFAOYSA-N 0.000 claims description 2
150000007530 organic bases Chemical class 0.000 claims description 2
230000001575 pathological effect Effects 0.000 claims description 2
208000028169 periodontal disease Diseases 0.000 claims description 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
201000001474 proteinuria Diseases 0.000 claims description 2
239000000376 reactant Substances 0.000 claims description 2
208000037803 restenosis Diseases 0.000 claims description 2
201000003068 rheumatic fever Diseases 0.000 claims description 2
201000001223 septic arthritis Diseases 0.000 claims description 2
230000008733 trauma Effects 0.000 claims description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 2
239000002257 antimetastatic agent Substances 0.000 claims 1
239000002246 antineoplastic agent Substances 0.000 claims 1
125000004494 ethyl ester group Chemical group 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
239000000243 solution Substances 0.000 description 46
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
239000007787 solid Substances 0.000 description 32
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
239000000047 product Substances 0.000 description 31
239000011541 reaction mixture Substances 0.000 description 20
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
229910052938 sodium sulfate Inorganic materials 0.000 description 19
235000011152 sodium sulphate Nutrition 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 16
239000012074 organic phase Substances 0.000 description 15
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 13
230000005764 inhibitory process Effects 0.000 description 13
239000000126 substance Substances 0.000 description 13
239000000725 suspension Substances 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
210000004027 cell Anatomy 0.000 description 12
238000001914 filtration Methods 0.000 description 12
238000002844 melting Methods 0.000 description 12
230000008018 melting Effects 0.000 description 12
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 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
239000011734 sodium Substances 0.000 description 10
229910052708 sodium Inorganic materials 0.000 description 10
238000005160 1H NMR spectroscopy Methods 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
206010028980 Neoplasm Diseases 0.000 description 8
102100030411 Neutrophil collagenase Human genes 0.000 description 8
239000008346 aqueous phase Substances 0.000 description 8
239000004202 carbamide Substances 0.000 description 8
239000000284 extract Substances 0.000 description 8
239000011780 sodium chloride Substances 0.000 description 8
238000003756 stirring Methods 0.000 description 8
238000002474 experimental method Methods 0.000 description 7
239000012299 nitrogen atmosphere Substances 0.000 description 7
239000003921 oil Substances 0.000 description 7
102000002274 Matrix Metalloproteinases Human genes 0.000 description 6
108010000684 Matrix Metalloproteinases Proteins 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
239000003480 eluent Substances 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
239000000758 substrate Substances 0.000 description 6
238000002560 therapeutic procedure Methods 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 5
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108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 5
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239000003814 drug Substances 0.000 description 5
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230000000694 effects Effects 0.000 description 5
238000000921 elemental analysis Methods 0.000 description 5
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239000012266 salt solution Substances 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
NNRYJLARUIVRRO-UHFFFAOYSA-N 5-(4-phenoxyphenyl)-1,3-diazinane-2,4,6-trione Chemical compound O=C1NC(=O)NC(=O)C1C(C=C1)=CC=C1OC1=CC=CC=C1 NNRYJLARUIVRRO-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 4
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
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229910052905 tridymite Inorganic materials 0.000 description 4
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RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
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150000003672 ureas Chemical class 0.000 description 3
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
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LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 2
MHIAOGTWZISBLM-UHFFFAOYSA-N 3-(3-bromophenyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2C=C(Br)C=CC=2)=C1 MHIAOGTWZISBLM-UHFFFAOYSA-N 0.000 description 2
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XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
150000007928 imidazolide derivatives Chemical class 0.000 description 1
YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
201000010893 malignant breast melanoma Diseases 0.000 description 1
OCSMOTCMPXTDND-OUAUKWLOSA-N marimastat Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO OCSMOTCMPXTDND-OUAUKWLOSA-N 0.000 description 1
229950008959 marimastat Drugs 0.000 description 1
238000005259 measurement Methods 0.000 description 1
229940041616 menthol Drugs 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
229940012189 methyl orange Drugs 0.000 description 1
229960001047 methyl salicylate Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
DAKZISABEDGGSV-UHFFFAOYSA-N n-(2-aminoethyl)acetamide Chemical compound CC(=O)NCCN DAKZISABEDGGSV-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000011275 oncology therapy Methods 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
229920002866 paraformaldehyde Polymers 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
CNMOHEDUVVUVPP-UHFFFAOYSA-N piperidine-2,3-dione Chemical compound O=C1CCCNC1=O CNMOHEDUVVUVPP-UHFFFAOYSA-N 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000011148 porous material Substances 0.000 description 1
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
230000005855 radiation Effects 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000012679 serum free medium Substances 0.000 description 1
239000004017 serum-free culture medium Substances 0.000 description 1
239000004208 shellac Substances 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
229910000342 sodium bisulfate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
235000010267 sodium hydrogen sulphite 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
239000008223 sterile water Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
238000011477 surgical intervention Methods 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229960001603 tamoxifen Drugs 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
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
230000005747 tumor angiogenesis Effects 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/60—Three or more oxygen or sulfur atoms
- C07D239/62—Barbituric acids
- 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
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- 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
- 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
- A61P35/04—Antineoplastic agents specific for metastasis
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Cardiology (AREA)
Rheumatology (AREA)
Heart & Thoracic Surgery (AREA)
Hospice & Palliative Care (AREA)
Oncology (AREA)
Hematology (AREA)
Pain & Pain Management (AREA)
Diabetes (AREA)
Ophthalmology & Optometry (AREA)
Immunology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)

HR97110200.9A 1997-06-21 1998-06-19 Barbituric acid derivatives with antimetastatic and antitumor activity HRP980340A2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP97110200		1997-06-21

Publications (1)

Publication Number	Publication Date
HRP980340A2 true HRP980340A2 (en)	1999-02-28

Family

ID=8226939

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR97110200.9A HRP980340A2 (en)	1997-06-21	1998-06-19	Barbituric acid derivatives with antimetastatic and antitumor activity

Country Status (18)

Country	Link
US (1)	US6335332B1 (es)
EP (1)	EP0989982B1 (es)
JP (1)	JP2002504916A (es)
KR (1)	KR20010014020A (es)
CN (1)	CN1295227C (es)
AR (1)	AR018997A1 (es)
AT (1)	ATE302200T1 (es)
AU (1)	AU746853B2 (es)
BR (1)	BR9810450A (es)
CA (1)	CA2294259A1 (es)
CO (1)	CO4940451A1 (es)
DE (1)	DE69831233T2 (es)
ES (1)	ES2247707T3 (es)
HR (1)	HRP980340A2 (es)
MA (1)	MA24573A1 (es)
TR (1)	TR199903148T2 (es)
WO (1)	WO1998058925A1 (es)
ZA (1)	ZA985352B (es)

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AUPO190596A0 (en)	1996-08-26	1996-09-19	Alchemia Pty Ltd	Oligosaccharide synthesis
AUPO937597A0 (en) *	1997-09-24	1997-10-16	Alchemia Pty Ltd	Protecting and linking groups for organic synthesis
US6265578B1 (en) *	1999-02-12	2001-07-24	Hoffmann-La Roche Inc.	Pyrimidine-2,4,6-triones
PA8498701A1 (es) *	1999-08-12	2002-08-26	Pfizer Prod Inc	Pirimidina-2,4,6-trionas inhibidores de metaloproteinasas
AU2001257230B2 (en)	2000-04-24	2006-09-14	Aryx Therapeutics	Ultrashort acting hypnotic barbiturates
US6841671B2 (en)	2000-10-26	2005-01-11	Pfizer Inc.	Spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors
HUP0301577A3 (en) *	2000-10-26	2006-02-28	Pfizer Prod Inc	Spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors, pharmaceutical compositions containing them and their use
EP1332136A2 (en)	2000-10-26	2003-08-06	Pfizer Products Inc.	Pyrimidine-2,4,6-trione metalloproteinase inhibitors
SE0100902D0 (sv)	2001-03-15	2001-03-15	Astrazeneca Ab	Compounds
JP2004527568A (ja) *	2001-05-03	2004-09-09	エフ．ホフマン−ラ　ロシュ　アーゲー	ゼラチナーゼインヒビターと抗腫瘍剤との組み合わせ、およびその使用
MXPA04010550A (es)	2002-04-26	2005-01-25	Pfizer Prod Inc	Inhibidores de metaloproteinasa de pirimidina-2,4,6-triona.
BR0309281A (pt)	2002-04-26	2005-02-22	Pfizer Prod Inc	Triaril-oxi-espiro-pirimidino-2,4,6-trionas inibidoras de metaloproteinases
AU2003216660A1 (en)	2002-04-26	2003-11-10	Pfizer Products Inc.	N-substituted-heteroaryloxy-aryl-spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors
NI200300045A (es)	2002-04-26	2005-07-08	Pfizer Prod Inc	Inhibidores de triariloxiariloxipirimidin-2,4,6-triona de metaloproteinasa.
RU2402329C2 (ru) *	2004-04-01	2010-10-27	Юниверсите Де-Льеж	Применение триоксопиримидина для лечения и предупреждения воспалительных заболеваний бронхов
KR100837137B1 (ko) *	2004-04-01	2008-06-11	에프. 호프만-라 로슈 아게	기관지 염증성 질환의 치료 및 예방을 위한트리옥소피리미딘의 용도
US7645789B2 (en)	2006-04-07	2010-01-12	Vertex Pharmaceuticals Incorporated	Indole derivatives as CFTR modulators
EP2007756B1 (en)	2006-04-07	2015-08-26	Vertex Pharmaceuticals Incorporated	Modulators of atp-binding cassette transporters
US10022352B2 (en)	2006-04-07	2018-07-17	Vertex Pharmaceuticals Incorporated	Modulators of ATP-binding cassette transporters
US8563573B2 (en)	2007-11-02	2013-10-22	Vertex Pharmaceuticals Incorporated	Azaindole derivatives as CFTR modulators
KR100862969B1 (ko)	2007-03-05	2008-10-13	바이오스펙트럼 주식회사	바르비투르산을 유효성분으로 포함하는 피부 미백제
US8802868B2 (en)	2010-03-25	2014-08-12	Vertex Pharmaceuticals Incorporated	Solid forms of (R)-1(2,2-difluorobenzo[D][1,3]dioxo1-5-yl)-N-(1-(2,3-dihydroxypropyl-6-fluoro-2-(1-hydroxy-2-methylpropan2-yl)-1H-Indol-5-yl)-Cyclopropanecarboxamide
MX342288B (es) *	2010-04-22	2016-09-23	Vertex Pharma	Proceso para producir compuestos de cicloalquilcarboxamido-indol.
US9012496B2 (en)	2012-07-16	2015-04-21	Vertex Pharmaceuticals Incorporated	Pharmaceutical compositions of (R)-1-(2,2-difluorobenzo[D][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide and administration thereof
US10093631B2 (en)	2014-02-14	2018-10-09	Acquist Llc	Bifunctional compounds and use for reducing uric acid levels
ES2957761T3 (es)	2014-04-15	2024-01-25	Vertex Pharma	Composiciones farmacéuticas para el tratamiento de enfermedades mediadas por el regulador de la conductancia transmembrana de fibrosis quística
EP3247704A4 (en)	2015-01-22	2018-10-03	Acquist LLC	Bifunctional compounds and use for reducing uric acid levels
TWI772309B (zh)	2016-06-30	2022-08-01	美商艾克奎斯特有限責任公司	化合物及其於降低尿酸位準之用途(二)
WO2018009615A1 (en)	2016-07-06	2018-01-11	Acquist Llc	Compounds and their use for reducing uric acid levels
LV15384B (lv)	2017-07-24	2019-05-20	Latvijas Organiskās Sintēzes Institūts	1-Acetil-5-nitro-4-fenil-3-pirolin-2-ons pielietošanai vēža ārstēšanā

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ES2128314T3 (es)	1989-11-14	1999-05-16	Sloan Kettering Inst Cancer	Nuevos inductores potentes de diferenciacion terminal y metodo de utilizacion de los mismos.
ATE155893T1 (de) *	1990-05-16	1997-08-15	Abbott Lab	Test für barbiturate, tracer, immunogene, antikörper und testsatz dafür
DE19548624A1 (de)	1995-12-23	1997-06-26	Boehringer Mannheim Gmbh	Neue Barbitursäure-Derivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel

1998
- 1998-06-18 ES ES98936361T patent/ES2247707T3/es not_active Expired - Lifetime
- 1998-06-18 EP EP98936361A patent/EP0989982B1/en not_active Expired - Lifetime
- 1998-06-18 KR KR19997012049A patent/KR20010014020A/ko not_active Application Discontinuation
- 1998-06-18 US US09/445,461 patent/US6335332B1/en not_active Expired - Fee Related
- 1998-06-18 AT AT98936361T patent/ATE302200T1/de not_active IP Right Cessation
- 1998-06-18 WO PCT/EP1998/003677 patent/WO1998058925A1/en not_active Application Discontinuation
- 1998-06-18 TR TR1999/03148T patent/TR199903148T2/xx unknown
- 1998-06-18 JP JP50374899A patent/JP2002504916A/ja not_active Ceased
- 1998-06-18 AU AU85391/98A patent/AU746853B2/en not_active Ceased
- 1998-06-18 DE DE69831233T patent/DE69831233T2/de not_active Expired - Fee Related
- 1998-06-18 CN CNB988083558A patent/CN1295227C/zh not_active Expired - Fee Related
- 1998-06-18 CA CA002294259A patent/CA2294259A1/en not_active Abandoned
- 1998-06-18 BR BR9810450-0A patent/BR9810450A/pt not_active IP Right Cessation
- 1998-06-19 MA MA25126A patent/MA24573A1/fr unknown
- 1998-06-19 AR ARP980102928A patent/AR018997A1/es not_active Application Discontinuation
- 1998-06-19 HR HR97110200.9A patent/HRP980340A2/hr not_active Application Discontinuation
- 1998-06-19 ZA ZA9805352A patent/ZA985352B/xx unknown
- 1998-06-23 CO CO98035555A patent/CO4940451A1/es unknown

Also Published As

Publication number	Publication date
DE69831233T2 (de)	2006-06-01
ZA985352B (en)	1999-12-20
DE69831233D1 (de)	2005-09-22
CA2294259A1 (en)	1998-12-30
BR9810450A (pt)	2000-09-05
US6335332B1 (en)	2002-01-01
AU8539198A (en)	1999-01-04
ES2247707T3 (es)	2006-03-01
AR018997A1 (es)	2001-12-26
EP0989982A1 (en)	2000-04-05
KR20010014020A (ko)	2001-02-26
TR199903148T2 (xx)	2000-04-21
CN1295227C (zh)	2007-01-17
EP0989982B1 (en)	2005-08-17
JP2002504916A (ja)	2002-02-12
CN1267296A (zh)	2000-09-20
CO4940451A1 (es)	2000-07-24
WO1998058925A1 (en)	1998-12-30
ATE302200T1 (de)	2005-09-15
MA24573A1 (fr)	1998-12-31
AU746853B2 (en)	2002-05-02

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Date	Code	Title	Description
1999-02-28	A1OB	Publication of a patent application
2002-01-25	OBST	Application withdrawn

Publication	Publication Date	Title
HRP980340A2 (en)	1999-02-28	Barbituric acid derivatives with antimetastatic and antitumor activity
JP4198752B2 (ja)	2008-12-17	新規バルビツル酸誘導体、これらの製造方法及びこれらの化合物を含む医薬
WO2004087698A2 (en)	2004-10-14	Thiazoles useful as inhibitors of protein kinases
MXPA02001561A (es)	2002-07-02	Pirimidina-2,4,6-trionas inhibidores de metaloproteinasas.
BG65426B1 (bg)	2008-07-31	Арилпиперазини и тяхното използване като инхибитори на металопротеиназа (ммр)
JP2002503720A (ja)	2002-02-05	マトリックス分解メタロプロテイナーゼを阻害するスルホニルアミノ誘導体
HRP20050601A2 (en)	2005-10-31	Chk-, pdk-, and akt-inhibitory pyrimidines, their production and use as pharmarmaceutical agents
EP1381602A1 (en)	2004-01-21	Heterocyclyldicarbamides as caspase inhibitors
CZ20012637A3 (cs)	2002-04-17	2,3,4,5-tetrahydro-1H[1,4]benzodiazepin-3-hydroxamové kyseliny jako inhibitory metaloproteináz mezibuněčné hmoty
JP3848160B2 (ja)	2006-11-22	新規なピリミジン−２，４，６−トリオン誘導体、その製造方法及びそれらを含む医薬製剤
JP2005501087A (ja)	2005-01-13	アリールピペラジンとアリールピペリジン、およびメタロプロテイナーゼ阻害剤としてのそれらの使用
MXPA99011992A (es)	2000-06-01	Derivados de acido barbiturico con actividad antimetastatica y antitumoral
EP0298040B1 (en)	1992-08-26	1,3-dithiol-2-ylidene derivatives
US6716845B2 (en)	2004-04-06	Barbituric acid derivatives
JP3283628B2 (ja)	2002-05-20	４，１−ベンゾオキサゼピン誘導体とその用途
JP2000143637A (ja)	2000-05-26	ピリミジン誘導体及びその製造法
JP2002541256A (ja)	2002-12-03	新規エンドセリン転換酵素阻害剤、その製造および使用
AU2002302470A1 (en)	2003-04-03	Pyrimidine-2,4,6-trione derivatives, processes for their production and pharmaceutical agents containing them