HRP20000771A2 - COMBINATIONS OF PROTEIN FARNESYLTRANSFERASE AND HMG CoA REDUCTASE INHIBITORS AND THEIR USE TO TREAT CANCER - Google Patents
COMBINATIONS OF PROTEIN FARNESYLTRANSFERASE AND HMG CoA REDUCTASE INHIBITORS AND THEIR USE TO TREAT CANCER Download PDFInfo
- Publication number
- HRP20000771A2 HRP20000771A2 HR20000771A HRP20000771A HRP20000771A2 HR P20000771 A2 HRP20000771 A2 HR P20000771A2 HR 20000771 A HR20000771 A HR 20000771A HR P20000771 A HRP20000771 A HR P20000771A HR P20000771 A2 HRP20000771 A2 HR P20000771A2
- Authority
- HR
- Croatia
- Prior art keywords
- methyl
- phenyl
- carbamoyl
- ethyl
- imidazol
- Prior art date
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- 206010028980 Neoplasm Diseases 0.000 title claims description 32
- 201000011510 cancer Diseases 0.000 title claims description 25
- 108010054353 p21(ras) farnesyl-protein transferase Proteins 0.000 title description 34
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 title description 15
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 title description 15
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 title description 10
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 title description 7
- -1 -OH Chemical group 0.000 claims description 97
- 150000001875 compounds Chemical class 0.000 claims description 90
- 229910052739 hydrogen Inorganic materials 0.000 claims description 76
- 239000001257 hydrogen Substances 0.000 claims description 76
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 69
- 150000002431 hydrogen Chemical class 0.000 claims description 40
- 150000002148 esters Chemical class 0.000 claims description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 26
- 150000001408 amides Chemical class 0.000 claims description 24
- 230000002401 inhibitory effect Effects 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 23
- 239000000651 prodrug Substances 0.000 claims description 23
- 229940002612 prodrug Drugs 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 22
- 229940080818 propionamide Drugs 0.000 claims description 20
- 208000037803 restenosis Diseases 0.000 claims description 19
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 229910017711 NHRa Inorganic materials 0.000 claims description 15
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 14
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 12
- 229960004844 lovastatin Drugs 0.000 claims description 12
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical group C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 12
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 7
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 208000036142 Viral infection Diseases 0.000 claims description 6
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 6
- 230000009385 viral infection Effects 0.000 claims description 6
- 101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
- LDECUSDQMXVUMP-UHFFFAOYSA-N benzyl 3-[6-[[2-(butylamino)-1-[3-methoxycarbonyl-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]-hexylamino]-6-oxohexyl]-4-methyl-2-oxo-6-(4-phenylphenyl)-1,6-dihydropyrimidine-5-carboxylate Chemical compound O=C1NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)C(C(=O)OCC=2C=CC=CC=2)=C(C)N1CCCCCC(=O)N(CCCCCC)C(C(=O)NCCCC)C1=CC=C(OCC(=O)OC)C(C(=O)OC)=C1 LDECUSDQMXVUMP-UHFFFAOYSA-N 0.000 claims description 4
- MYBBTGORNPKHDT-BHVANESWSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]-[(4-phenylmethoxyphenyl)methyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 MYBBTGORNPKHDT-BHVANESWSA-N 0.000 claims description 4
- 210000001072 colon Anatomy 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 229910052703 rhodium Inorganic materials 0.000 claims description 4
- 206010005003 Bladder cancer Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 210000000481 breast Anatomy 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 210000004072 lung Anatomy 0.000 claims description 3
- GZDQXBPGVLDSMB-QNGWXLTQSA-N (4-methoxyphenyl)methyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]-[(4-phenylmethoxyphenyl)methyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(OC)=CC=C1COC(=O)N[C@H](C(=O)N(CC(=O)NCC(C)(C)C=1C=CC=CC=1)CC=1C=CC(OCC=2C=CC=CC=2)=CC=1)CC1=CN=CN1 GZDQXBPGVLDSMB-QNGWXLTQSA-N 0.000 claims description 2
- 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 claims description 2
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 2
- 125000001318 4-trifluoromethylbenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(F)(F)F 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 101100134927 Gallus gallus COR8 gene Proteins 0.000 claims description 2
- 239000004471 Glycine Substances 0.000 claims description 2
- 229910003204 NH2 Inorganic materials 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- GDNMFXNLQJTIBN-SFCXHYMASA-N benzyl n-[(2s)-1-[(1-amino-1-oxo-4-phenylbutan-2-yl)-[(4-phenylmethoxyphenyl)methyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)C(C(=O)N)CCC1=CC=CC=C1 GDNMFXNLQJTIBN-SFCXHYMASA-N 0.000 claims description 2
- DMGJRELNPSPIKC-IZCXSWDTSA-N benzyl n-[(2s)-1-[(3-chlorophenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC(Cl)=C1 DMGJRELNPSPIKC-IZCXSWDTSA-N 0.000 claims description 2
- RNRQOBDRZWCHDI-LJAQVGFWSA-N benzyl n-[(2s)-1-[(4-aminophenyl)methyl-[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=C(N)C=C1 RNRQOBDRZWCHDI-LJAQVGFWSA-N 0.000 claims description 2
- NQVJXBFXQFGIHU-IZCXSWDTSA-N benzyl n-[(2s)-1-[(4-bromophenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=C(Br)C=C1 NQVJXBFXQFGIHU-IZCXSWDTSA-N 0.000 claims description 2
- MFVRMBXVDCCSLM-LJAQVGFWSA-N benzyl n-[(2s)-1-[(4-chlorophenyl)methyl-[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=C(Cl)C=C1 MFVRMBXVDCCSLM-LJAQVGFWSA-N 0.000 claims description 2
- SSXFUPUONWGRIP-IZCXSWDTSA-N benzyl n-[(2s)-1-[(4-chlorophenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=C(Cl)C=C1 SSXFUPUONWGRIP-IZCXSWDTSA-N 0.000 claims description 2
- MGAFFZTYMAFERW-HKBQPEDESA-N benzyl n-[(2s)-1-[(4-ethoxyphenyl)methyl-[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(OCC)=CC=C1CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC(=O)NCC(C)(C)C1=CC=CC=C1 MGAFFZTYMAFERW-HKBQPEDESA-N 0.000 claims description 2
- QCNOUBMNVDBZBN-IZCXSWDTSA-N benzyl n-[(2s)-1-[(4-fluorophenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=C(F)C=C1 QCNOUBMNVDBZBN-IZCXSWDTSA-N 0.000 claims description 2
- KESDVVHGRDVTAS-LHEWISCISA-N benzyl n-[(2s)-1-[[2-[(2-ethyl-2-phenylbutyl)amino]-2-oxoethyl]-[(4-phenylmethoxyphenyl)methyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(CC)(CC)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 KESDVVHGRDVTAS-LHEWISCISA-N 0.000 claims description 2
- JBQKDWCCSNPPMR-SFCXHYMASA-N benzyl n-[(2s)-1-[[2-[(2-hydroxy-2-phenylethyl)amino]-2-oxoethyl]-[(4-phenylmethoxyphenyl)methyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(O)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 JBQKDWCCSNPPMR-SFCXHYMASA-N 0.000 claims description 2
- BNSYCEGVHLCVSI-NPJBGSGMSA-N benzyl n-[(2s)-1-[[2-[2-(2-chlorophenyl)propylamino]-2-oxoethyl]-[(4-phenylmethoxyphenyl)methyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=C(Cl)C=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=CC=C1 BNSYCEGVHLCVSI-NPJBGSGMSA-N 0.000 claims description 2
- AQPCQRZCFKAMCG-KHTLXAHUSA-N benzyl n-[(2s)-1-[[4-(dimethylamino)phenyl]methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=C(N(C)C)C=C1 AQPCQRZCFKAMCG-KHTLXAHUSA-N 0.000 claims description 2
- HLTPZABIYJFBEX-XIFFEERXSA-N benzyl n-[(2s)-1-[[4-[2-(dimethylamino)ethoxy]phenyl]methyl-[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(OCCN(C)C)=CC=C1CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC(=O)NCC(C)(C)C1=CC=CC=C1 HLTPZABIYJFBEX-XIFFEERXSA-N 0.000 claims description 2
- JHMAXHXLKSHTKI-PEFOLFAWSA-N benzyl n-[(2s)-1-[benzyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 JHMAXHXLKSHTKI-PEFOLFAWSA-N 0.000 claims description 2
- WTWAOQOUPSTNDO-PEFOLFAWSA-N benzyl n-[(2s)-1-[cyclohexylmethyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1CCCCC1 WTWAOQOUPSTNDO-PEFOLFAWSA-N 0.000 claims description 2
- CYTUTAVSMWREOX-LJAQVGFWSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[(2-methoxyphenyl)methyl-[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound COC1=CC=CC=C1CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(=O)NCC(C)(C)C1=CC=CC=C1 CYTUTAVSMWREOX-LJAQVGFWSA-N 0.000 claims description 2
- JFRDYWFPSQJTNE-FZNWDQQTSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[(3-methoxyphenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound COC1=CC=CC(CN(CC(=O)NCC(C)C=2C=CC=CC=2)C(=O)[C@H](CC=2NC=NC=2)NC(=O)OCC=2C=CC=CC=2)=C1 JFRDYWFPSQJTNE-FZNWDQQTSA-N 0.000 claims description 2
- NNRXKWAHWANQLM-QNGSWNHHSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[(3-methylphenyl)methyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC(C)=C1 NNRXKWAHWANQLM-QNGSWNHHSA-N 0.000 claims description 2
- QGXVHBXRVCWIAD-NDEPHWFRSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[(4-iodophenyl)methyl-[2-oxo-2-(2-phenylethylamino)ethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(I)=CC=C1CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC(=O)NCCC1=CC=CC=C1 QGXVHBXRVCWIAD-NDEPHWFRSA-N 0.000 claims description 2
- NWSAOVCSJUGBPY-PMERELPUSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[(4-methylphenyl)methyl-[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(=O)NCC(C)(C)C1=CC=CC=C1 NWSAOVCSJUGBPY-PMERELPUSA-N 0.000 claims description 2
- VPSGVBKKJHMPGX-HKBQPEDESA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[(4-methylphenyl)methyl-[2-oxo-2-[(1-phenylcyclobutyl)methylamino]ethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(=O)NCC1(C=2C=CC=CC=2)CCC1 VPSGVBKKJHMPGX-HKBQPEDESA-N 0.000 claims description 2
- UKDHPFDMEXGIKI-HKBQPEDESA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[2-(4-methoxyphenyl)ethyl-[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C1=CC(OC)=CC=C1CCN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC(=O)NCC(C)(C)C1=CC=CC=C1 UKDHPFDMEXGIKI-HKBQPEDESA-N 0.000 claims description 2
- XSNSVLNJHGTYTL-NDEPHWFRSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]-(pyridin-4-ylmethyl)amino]-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)CN(C(=O)[C@H](CC=1NC=NC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=NC=C1 XSNSVLNJHGTYTL-NDEPHWFRSA-N 0.000 claims description 2
- VTDGRAHGAAMRGX-DHUJRADRSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]-[(4-phenylphenyl)methyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1C1=CC=CC=C1 VTDGRAHGAAMRGX-DHUJRADRSA-N 0.000 claims description 2
- LFTQDNBHSGZGTD-UMSFTDKQSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]-[[2-(pyridin-4-ylmethoxy)phenyl]methyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1OCC1=CC=NC=C1 LFTQDNBHSGZGTD-UMSFTDKQSA-N 0.000 claims description 2
- MDHGWUKTVUNWAA-DHUJRADRSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[[2-[(2-methyl-2-phenylpropyl)amino]-2-oxoethyl]-[[4-(pyridin-4-ylmethoxy)phenyl]methyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)(C)CNC(=O)CN(C(=O)[C@H](CC=1N=CNC=1)NC(=O)OCC=1C=CC=CC=1)CC(C=C1)=CC=C1OCC1=CC=NC=C1 MDHGWUKTVUNWAA-DHUJRADRSA-N 0.000 claims description 2
- JRRUOMUYZWMQNH-VKPSHWPRSA-N benzyl n-[(2s)-3-(1h-imidazol-5-yl)-1-[naphthalen-1-ylmethyl-[2-oxo-2-(2-phenylpropylamino)ethyl]amino]-1-oxopropan-2-yl]carbamate Chemical compound C([C@@H](C(=O)N(CC=1C2=CC=CC=C2C=CC=1)CC(=O)NCC(C)C=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)C1=CN=CN1 JRRUOMUYZWMQNH-VKPSHWPRSA-N 0.000 claims description 2
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- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 108700042226 ras Genes Proteins 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 108091006091 regulatory enzymes Proteins 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 201000003804 salivary gland carcinoma Diseases 0.000 description 1
- 210000003752 saphenous vein Anatomy 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 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
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 150000003900 succinic acid esters Chemical class 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 150000003899 tartaric acid esters Chemical class 0.000 description 1
- 150000003505 terpenes Chemical group 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
- 210000001550 testis Anatomy 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 125000005490 tosylate group Chemical group 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
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 208000010576 undifferentiated carcinoma Diseases 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical class CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
-
- 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
- C07D239/26—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- 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
- C07D401/14—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 three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Virology (AREA)
- Cardiology (AREA)
- Communicable Diseases (AREA)
- Dermatology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8520298P | 1998-05-12 | 1998-05-12 | |
| US9225398P | 1998-07-10 | 1998-07-10 | |
| PCT/US1999/010188 WO1999058505A2 (en) | 1998-05-12 | 1999-05-10 | Combinations of protein farnesyltransferase and hmg coa reductase inhibitors and their use to treat cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20000771A2 true HRP20000771A2 (en) | 2001-06-30 |
Family
ID=26772425
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20000771A HRP20000771A2 (en) | 1998-05-12 | 2000-11-13 | COMBINATIONS OF PROTEIN FARNESYLTRANSFERASE AND HMG CoA REDUCTASE INHIBITORS AND THEIR USE TO TREAT CANCER |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US6492410B1 (id) |
| EP (1) | EP1077949A2 (id) |
| JP (1) | JP2002514628A (id) |
| KR (1) | KR20010043529A (id) |
| CN (1) | CN1171874C (id) |
| AP (1) | AP2000001984A0 (id) |
| AU (1) | AU758891B2 (id) |
| BG (1) | BG105003A (id) |
| BR (1) | BR9911785A (id) |
| CA (1) | CA2331295A1 (id) |
| EA (1) | EA003860B1 (id) |
| EE (1) | EE200000660A (id) |
| GE (1) | GEP20032996B (id) |
| HK (1) | HK1038355A1 (id) |
| HR (1) | HRP20000771A2 (id) |
| HU (1) | HUP0102322A3 (id) |
| ID (1) | ID27933A (id) |
| IL (1) | IL139502A0 (id) |
| IS (1) | IS5713A (id) |
| NO (1) | NO20005680L (id) |
| NZ (1) | NZ508357A (id) |
| OA (1) | OA11551A (id) |
| PL (1) | PL344662A1 (id) |
| SK (1) | SK16742000A3 (id) |
| WO (1) | WO1999058505A2 (id) |
| YU (1) | YU68900A (id) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002536405A (ja) * | 1999-02-11 | 2002-10-29 | イーデンランド、インコーポレイテッド | ウイルス感染症の治療方法 |
| US6455734B1 (en) * | 2000-08-09 | 2002-09-24 | Magnesium Diagnostics, Inc. | Antagonists of the magnesium binding defect as therapeutic agents and methods for treatment of abnormal physiological states |
| US20020010128A1 (en) * | 2000-04-13 | 2002-01-24 | Parks Thomas P. | Treatment of hyperproliferative, inflammatory and related mucocutaneous disorders using inhibitors of mevalonate synthesis and metabolism |
| US20020132781A1 (en) * | 2000-10-06 | 2002-09-19 | George Kindness | Combination and method of treatment of cancer utilizing a COX-2 inhibitor and A 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor |
| GB0220885D0 (en) * | 2002-09-09 | 2002-10-16 | Novartis Ag | Organic compounds |
| WO2005042710A1 (en) * | 2003-10-28 | 2005-05-12 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Use of statin to kill ebv-transformed b cells |
| US8026377B2 (en) * | 2005-11-08 | 2011-09-27 | Ranbaxy Laboratories, Limited | Process for (3R, 5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-[(4-hydroxy methyl phenyl amino) carbonyl]-pyrrol-1-yl]-3,5-dihydroxy-heptanoic acid hemi calcium salt |
| KR100930365B1 (ko) * | 2006-11-09 | 2009-12-08 | 덕성여자대학교 산학협력단 | 심바스타틴을 유효성분으로 함유하는 유방암 치료용 약학적조성물 |
| US20080119444A1 (en) * | 2006-11-16 | 2008-05-22 | Steven Lehrer | Methods and compositions for the treatment of cancer |
| US11344497B1 (en) | 2017-12-08 | 2022-05-31 | Quicksilver Scientific, Inc. | Mitochondrial performance enhancement nanoemulsion |
| US10722465B1 (en) | 2017-12-08 | 2020-07-28 | Quicksilber Scientific, Inc. | Transparent colloidal vitamin supplement |
| US11291702B1 (en) | 2019-04-15 | 2022-04-05 | Quicksilver Scientific, Inc. | Liver activation nanoemulsion, solid binding composition, and toxin excretion enhancement method |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK523288A (da) * | 1987-10-06 | 1989-04-07 | Hoffmann La Roche | Aminosyrederivater |
| NL9002031A (nl) | 1990-09-14 | 1992-04-01 | Voskuilen Woudenberg Bv | Inrichting voor het bewerken van een uitwendig buisoppervlak. |
| US5571792A (en) * | 1994-06-30 | 1996-11-05 | Warner-Lambert Company | Histidine and homohistidine derivatives as inhibitors of protein farnesyltransferase |
| WO1997000894A1 (en) * | 1995-06-22 | 1997-01-09 | Novo Nordisk A/S | Compounds with growth hormone releasing properties |
| WO1997000895A1 (en) | 1995-06-22 | 1997-01-09 | Biogen, Inc. | Crystals of fragments of cd40 ligand and their use |
| UA57081C2 (uk) * | 1997-06-16 | 2003-06-16 | Пфайзер Продактс Інк. | Фармацевтична композиція для лікування раку або доброякісних проліферативних хвороб у ссавців, спосіб лікування, фармацевтична композиція для інгібування ненормального росту клітин у ссавців та спосіб інгібування |
-
1999
- 1999-05-10 EE EEP200000660A patent/EE200000660A/xx unknown
- 1999-05-10 EA EA200001164A patent/EA003860B1/ru not_active IP Right Cessation
- 1999-05-10 IL IL13950299A patent/IL139502A0/xx unknown
- 1999-05-10 AU AU39792/99A patent/AU758891B2/en not_active Ceased
- 1999-05-10 EP EP99922898A patent/EP1077949A2/en not_active Withdrawn
- 1999-05-10 NZ NZ508357A patent/NZ508357A/xx unknown
- 1999-05-10 SK SK1674-2000A patent/SK16742000A3/sk unknown
- 1999-05-10 US US09/674,818 patent/US6492410B1/en not_active Expired - Fee Related
- 1999-05-10 ID IDW20002583A patent/ID27933A/id unknown
- 1999-05-10 HU HU0102322A patent/HUP0102322A3/hu unknown
- 1999-05-10 KR KR1020007012632A patent/KR20010043529A/ko not_active Application Discontinuation
- 1999-05-10 JP JP2000548309A patent/JP2002514628A/ja active Pending
- 1999-05-10 CN CNB99807649XA patent/CN1171874C/zh not_active Expired - Fee Related
- 1999-05-10 OA OA1200000310A patent/OA11551A/en unknown
- 1999-05-10 BR BR9911785-1A patent/BR9911785A/pt not_active IP Right Cessation
- 1999-05-10 PL PL99344662A patent/PL344662A1/xx not_active Application Discontinuation
- 1999-05-10 CA CA002331295A patent/CA2331295A1/en not_active Abandoned
- 1999-05-10 GE GEAP19995670A patent/GEP20032996B/en unknown
- 1999-05-10 WO PCT/US1999/010188 patent/WO1999058505A2/en not_active Application Discontinuation
- 1999-05-10 YU YU68900A patent/YU68900A/sh unknown
- 1999-05-10 AP APAP/P/2000/001984A patent/AP2000001984A0/en unknown
-
2000
- 2000-11-10 IS IS5713A patent/IS5713A/is unknown
- 2000-11-10 NO NO20005680A patent/NO20005680L/no not_active Application Discontinuation
- 2000-11-13 HR HR20000771A patent/HRP20000771A2/hr not_active Application Discontinuation
- 2000-11-29 BG BG105003A patent/BG105003A/xx unknown
-
2001
- 2001-12-27 HK HK01109123A patent/HK1038355A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| WO1999058505A2 (en) | 1999-11-18 |
| CA2331295A1 (en) | 1999-11-18 |
| BG105003A (en) | 2001-07-31 |
| BR9911785A (pt) | 2001-04-03 |
| WO1999058505A3 (en) | 2000-01-06 |
| NO20005680L (no) | 2001-01-10 |
| EP1077949A2 (en) | 2001-02-28 |
| JP2002514628A (ja) | 2002-05-21 |
| KR20010043529A (ko) | 2001-05-25 |
| EE200000660A (et) | 2002-04-15 |
| CN1171874C (zh) | 2004-10-20 |
| IL139502A0 (en) | 2001-11-25 |
| EA003860B1 (ru) | 2003-10-30 |
| HK1038355A1 (en) | 2002-03-15 |
| HUP0102322A2 (hu) | 2001-11-28 |
| AP2000001984A0 (en) | 2000-12-31 |
| PL344662A1 (en) | 2001-11-19 |
| ID27933A (id) | 2001-05-03 |
| GEP20032996B (en) | 2003-06-25 |
| NZ508357A (en) | 2002-09-27 |
| HUP0102322A3 (en) | 2001-12-28 |
| IS5713A (is) | 2000-11-10 |
| AU3979299A (en) | 1999-11-29 |
| CN1306515A (zh) | 2001-08-01 |
| YU68900A (sh) | 2002-12-10 |
| EA200001164A1 (ru) | 2001-06-25 |
| NO20005680D0 (no) | 2000-11-10 |
| OA11551A (en) | 2004-05-24 |
| AU758891B2 (en) | 2003-04-03 |
| US6492410B1 (en) | 2002-12-10 |
| SK16742000A3 (sk) | 2001-07-10 |
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