JP2000507585A - ファルネシルタンパク質トランスフェラーゼの阻害剤 - Google Patents
ファルネシルタンパク質トランスフェラーゼの阻害剤Info
- Publication number
- JP2000507585A JP2000507585A JP9535510A JP53551097A JP2000507585A JP 2000507585 A JP2000507585 A JP 2000507585A JP 9535510 A JP9535510 A JP 9535510A JP 53551097 A JP53551097 A JP 53551097A JP 2000507585 A JP2000507585 A JP 2000507585A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- substituted
- aryl
- unsubstituted
- cycloalkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 title claims abstract description 31
- 102000004357 Transferases Human genes 0.000 title claims abstract description 29
- 108090000992 Transferases Proteins 0.000 title claims abstract description 29
- 239000003112 inhibitor Substances 0.000 title description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 128
- 238000000034 method Methods 0.000 claims abstract description 49
- 239000000203 mixture Substances 0.000 claims abstract description 35
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 8
- 125000003118 aryl group Chemical group 0.000 claims description 105
- 125000000623 heterocyclic group Chemical group 0.000 claims description 92
- 239000001257 hydrogen Substances 0.000 claims description 81
- 229910052739 hydrogen Inorganic materials 0.000 claims description 81
- 125000000217 alkyl group Chemical group 0.000 claims description 60
- 150000002431 hydrogen Chemical class 0.000 claims description 53
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
- 229910052736 halogen Inorganic materials 0.000 claims description 33
- 150000002367 halogens Chemical class 0.000 claims description 33
- -1 heteroaroyl Chemical group 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 229910052801 chlorine Inorganic materials 0.000 claims description 25
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 23
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 229910052731 fluorine Inorganic materials 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 241000124008 Mammalia Species 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 238000006467 substitution reaction Methods 0.000 claims description 11
- 201000011510 cancer Diseases 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 125000006505 p-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C#N)C([H])([H])* 0.000 claims description 10
- 125000003107 substituted aryl group Chemical group 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000000335 thiazolyl group Chemical group 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000002950 monocyclic group Chemical group 0.000 claims description 9
- 125000005002 aryl methyl group Chemical group 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 8
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
- 230000003287 optical effect Effects 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 7
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000005494 pyridonyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 claims description 5
- 102000007530 Neurofibromin 1 Human genes 0.000 claims description 5
- 108010085793 Neurofibromin 1 Proteins 0.000 claims description 5
- 125000002619 bicyclic group Chemical group 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- CUHNORVKYIEDOE-UHFFFAOYSA-N 4-[[3-[2-(1-benzyl-2-oxopyrrolidin-3-yl)ethyl]imidazol-4-yl]methyl]benzonitrile Chemical compound C1CN(CC=2C=CC=CC=2)C(=O)C1CCN1C=NC=C1CC1=CC=C(C#N)C=C1 CUHNORVKYIEDOE-UHFFFAOYSA-N 0.000 claims description 3
- 208000005331 Hepatitis D Diseases 0.000 claims description 3
- 208000037262 Hepatitis delta Diseases 0.000 claims description 3
- 241000700605 Viruses Species 0.000 claims description 3
- 125000003435 aroyl group Chemical group 0.000 claims description 3
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 3
- 208000029570 hepatitis D virus infection Diseases 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 208000030761 polycystic kidney disease Diseases 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- DFTKHYXSHQYFFX-UHFFFAOYSA-N 4-[[3-[2-(2-oxo-1-phenylpyrrolidin-3-yl)ethyl]imidazol-4-yl]methyl]benzonitrile Chemical compound C1CN(C=2C=CC=CC=2)C(=O)C1CCN1C=NC=C1CC1=CC=C(C#N)C=C1 DFTKHYXSHQYFFX-UHFFFAOYSA-N 0.000 claims description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
- 201000004569 Blindness Diseases 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 208000007135 Retinal Neovascularization Diseases 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000004802 cyanophenyl group Chemical group 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 230000002062 proliferating effect Effects 0.000 claims description 2
- 208000015181 infectious disease Diseases 0.000 claims 1
- 230000006126 farnesylation Effects 0.000 abstract description 7
- 108700020796 Oncogene Proteins 0.000 abstract description 4
- 230000000973 chemotherapeutic effect Effects 0.000 abstract description 3
- 102000043276 Oncogene Human genes 0.000 abstract 2
- 238000006243 chemical reaction Methods 0.000 description 92
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- 239000000243 solution Substances 0.000 description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 239000000047 product Substances 0.000 description 29
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- 235000019439 ethyl acetate Nutrition 0.000 description 26
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 108010014186 ras Proteins Proteins 0.000 description 23
- 102000016914 ras Proteins Human genes 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 238000003556 assay Methods 0.000 description 16
- 239000000543 intermediate Substances 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- 102000004169 proteins and genes Human genes 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 150000001299 aldehydes Chemical class 0.000 description 11
- 239000012141 concentrate Substances 0.000 description 11
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000005804 alkylation reaction Methods 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 238000010561 standard procedure Methods 0.000 description 6
- 150000003573 thiols Chemical class 0.000 description 6
- VWFJDQUYCIWHTN-UHFFFAOYSA-N Farnesyl pyrophosphate Natural products CC(C)=CCCC(C)=CCCC(C)=CCOP(O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- NKOGCJIYHZVBDR-UHFFFAOYSA-N 1-phenylpiperidin-2-one Chemical compound O=C1CCCCN1C1=CC=CC=C1 NKOGCJIYHZVBDR-UHFFFAOYSA-N 0.000 description 4
- VWFJDQUYCIWHTN-YFVJMOTDSA-N 2-trans,6-trans-farnesyl diphosphate Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CO[P@](O)(=O)OP(O)(O)=O VWFJDQUYCIWHTN-YFVJMOTDSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 4
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 4
- 125000002541 furyl group Chemical group 0.000 description 4
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 229920000936 Agarose Polymers 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 3
- 102100029974 GTPase HRas Human genes 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 101000584633 Homo sapiens GTPase HRas Proteins 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- 101150040459 RAS gene Proteins 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical group [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
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- 230000006870 function Effects 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 150000003840 hydrochlorides Chemical class 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 125000002636 imidazolinyl group Chemical group 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
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- 150000007524 organic acids Chemical class 0.000 description 3
- 238000005192 partition Methods 0.000 description 3
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 3
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- 125000003226 pyrazolyl group Chemical group 0.000 description 3
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- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- HBDDRESWUAFAHY-UHFFFAOYSA-N thiomorpholin-3-one Chemical compound O=C1CSCCN1 HBDDRESWUAFAHY-UHFFFAOYSA-N 0.000 description 3
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical group C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 2
- JMVIVASFFKKFQK-UHFFFAOYSA-N 1-phenylpyrrolidin-2-one Chemical compound O=C1CCCN1C1=CC=CC=C1 JMVIVASFFKKFQK-UHFFFAOYSA-N 0.000 description 2
- UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 2
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- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- STOSRWJNGGVQJF-UHFFFAOYSA-N 4-[[2-(1h-imidazol-5-yl)ethylamino]methyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1CNCCC1=CNC=N1 STOSRWJNGGVQJF-UHFFFAOYSA-N 0.000 description 2
- JXJNXIREZGNPHY-UHFFFAOYSA-N 4-[[5-[3-(2-oxo-1-phenylpiperidin-3-yl)propyl]imidazol-1-yl]methyl]benzonitrile;hydrochloride Chemical compound Cl.C1CCN(C=2C=CC=CC=2)C(=O)C1CCCC1=CN=CN1CC1=CC=C(C#N)C=C1 JXJNXIREZGNPHY-UHFFFAOYSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 2
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- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 206010017533 Fungal infection Diseases 0.000 description 2
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Classifications
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- 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
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- 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
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- 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
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Virology (AREA)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1479896P | 1996-04-03 | 1996-04-03 | |
| GB60/014,798 | 1996-05-09 | ||
| GBGB9609666.4A GB9609666D0 (en) | 1996-05-09 | 1996-05-09 | Inhibitors of farnesyl-protein transferase |
| GB9609666.4 | 1996-05-09 | ||
| PCT/US1997/005235 WO1997036900A1 (en) | 1996-04-03 | 1997-03-27 | Inhibitors of farnesyl-protein transferase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2000507585A true JP2000507585A (ja) | 2000-06-20 |
Family
ID=26309289
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9535510A Pending JP2000507585A (ja) | 1996-04-03 | 1997-03-27 | ファルネシルタンパク質トランスフェラーゼの阻害剤 |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0891360A4 (de) |
| JP (1) | JP2000507585A (de) |
| AU (1) | AU715603B2 (de) |
| CA (1) | CA2250353A1 (de) |
| WO (1) | WO1997036900A1 (de) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007501855A (ja) * | 2003-05-17 | 2007-02-01 | コリア リサーチ インスティテュート オブ バイオサイエンス アンド バイオテクノロジー | 新規な２−オキソ複素環化合物およびそれを含有する薬剤組成物 |
| JP2007521311A (ja) * | 2003-07-15 | 2007-08-02 | コリア リサーチ インスティテュート オブ バイオサイエンス アンド バイオテクノロジー | 新規な２−オキソ複素環化合物およびそれを含有する薬剤組成物の使用 |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5972966A (en) * | 1996-12-05 | 1999-10-26 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| AU1611199A (en) * | 1997-12-04 | 1999-06-16 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| CN1158277C (zh) * | 1998-02-02 | 2004-07-21 | Lg化学株式会社 | 具有哌啶结构的法尼转移酶抑制剂及其制备方法 |
| KR100388790B1 (ko) * | 1998-03-06 | 2003-10-04 | 주식회사 엘지생명과학 | 파네실전이효소저해제로서유용한피리딘-2-온유도체 |
| NZ525513A (en) | 1998-08-07 | 2004-09-24 | Pont Pharmaceuticals Du | Succinoylamino lactams as inhibitors of Abeta protein production |
| HRP990246A2 (en) | 1998-08-07 | 2000-06-30 | Du Pont Pharm Co | Succinoylamino benzodiazepines as inhibitors of a beta protein production |
| WO2000038618A2 (en) | 1998-12-24 | 2000-07-06 | Du Pont Pharmaceuticals Company | SUCCINOYLAMINO BENZODIAZEPINES AS INHIBITORS OF Aβ PROTEIN PRODUCTION |
| EP1165546A2 (de) * | 1999-04-02 | 2002-01-02 | Du Pont Pharmaceuticals Company | Lactamverbindungen als metalloprotease, tnf-alpha und aggrecanase inhibitoren |
| US6503902B2 (en) | 1999-09-13 | 2003-01-07 | Bristol-Myers Squibb Pharma Company | Hydroxyalkanoylaminolactams and related structures as inhibitors of a β protein production |
| US6960576B2 (en) | 1999-09-13 | 2005-11-01 | Bristol-Myers Squibb Pharma Company | Hydroxyalkanoylaminolactams and related structures as inhibitors of Aβ protein production |
| EP1222176A1 (de) | 1999-10-08 | 2002-07-17 | Bristol-Myers Squibb Pharma Company | Amino-laktam-sulfonamide als inhibitoren der bildung von a-beta-protein |
| CA2395862A1 (en) | 2000-02-17 | 2001-08-23 | Hong Liu | Succinoylamino carbocycles and heterocycles as inhibitors of a.beta. protein production |
| US6495540B2 (en) | 2000-03-28 | 2002-12-17 | Bristol - Myers Squibb Pharma Company | Lactams as inhibitors of A-β protein production |
| CN1436175A (zh) | 2000-04-03 | 2003-08-13 | 布里斯托尔-迈尔斯斯奎布药品公司 | 作为Aβ－蛋白生产抑制剂的环状内酰胺 |
| EP1268434A1 (de) | 2000-04-03 | 2003-01-02 | Bristol-Myers Squibb Pharma Company | Zyklische lactame als a-beta proteinproduktionsinhibitoren |
| WO2001077086A1 (en) | 2000-04-11 | 2001-10-18 | Dupont Pharmaceuticals Company | SUBSTITUTED LACTAMS AS INHIBITORS OF Aβ PROTEIN PRODUCTION |
| CN1386118A (zh) | 2000-06-01 | 2002-12-18 | 布里斯托尔-迈尔斯斯奎布药品公司 | 作为Aβ蛋白产生抑制剂的被环状琥珀酸酯取代的内酰胺类化合物 |
| US6710058B2 (en) | 2000-11-06 | 2004-03-23 | Bristol-Myers Squibb Pharma Company | Monocyclic or bicyclic carbocycles and heterocycles as factor Xa inhibitors |
| WO2003024401A2 (en) | 2001-09-18 | 2003-03-27 | Bristol-Myers Squibb Company | Piperizinones as modulators of chemokine receptor activity |
| TW200307667A (en) | 2002-05-06 | 2003-12-16 | Bristol Myers Squibb Co | Sulfonylaminovalerolactams and derivatives thereof as factor Xa inhibitors |
| US7846963B2 (en) | 2003-05-17 | 2010-12-07 | Korea Research Institute Of Bioscience And Biotechnology | 2-oxo-heterocyclic compounds and the pharmaceutical compositions comprising the same |
| US20070123508A1 (en) * | 2005-05-27 | 2007-05-31 | Roger Olsson | PAR2-modulating compounds and their use |
| WO2010141932A1 (en) | 2009-06-05 | 2010-12-09 | Link Medicine Corporation | Aminopyrrolidinone derivatives and uses thereof |
| WO2015130958A1 (en) * | 2014-02-26 | 2015-09-03 | Howard University | 5-oxopyrrolidine derivatives as hiv integrase inhibitors |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL69407A (en) * | 1982-08-23 | 1987-10-20 | Warner Lambert Co | 2(1h)-pyridinones,their preparation and pharmaceutical compositions containing them |
| DE3336024A1 (de) * | 1983-10-04 | 1985-04-18 | Boehringer Ingelheim KG, 6507 Ingelheim | 4-amino-l-benzyl-pyrrolidinone und ihre saeureadditionssalze, verfahren zu ihrer herstellung und arzneimittel |
| DE3433953A1 (de) * | 1984-09-15 | 1986-03-27 | A. Nattermann & Cie GmbH, 5000 Köln | Neue, eine imidazol-gruppe enthaltende 3,4-dihydro-2(1h)-pyridone und2(1h)-pyridone, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
| US4749713A (en) * | 1986-03-07 | 1988-06-07 | Ciba-Geigy Corporation | Alpha-heterocycle substituted tolunitriles |
| US5015653A (en) * | 1989-07-10 | 1991-05-14 | Hoffmann-La Roche Inc. | [(5-oxo)-2-pyrrolidinyl)methyl]cyclohexaneacetamides, compositions and use |
| US5055467A (en) * | 1989-11-13 | 1991-10-08 | Allergan, Inc. | Pharmaceutical epinephrine-pilocarpine compounds |
| US5264449A (en) * | 1989-11-13 | 1993-11-23 | Allergan, Inc. | N-substituted derivatives of 3R,4R-ethyl-[(1-methyl-1H-imidazol-5-yl)methyl]-2-pyrrolidinone |
| US5463074A (en) * | 1991-12-18 | 1995-10-31 | Schering Corporation | Imidazolyl or imidazoylalkyl substituted with a four or five membered nitrogen containing heterocyclic ring |
| DE69212164T2 (de) * | 1991-12-18 | 1996-12-05 | Schering Corp., Kenilworth, N.J. | Imidolylalkyl-derivate substituiert mit einem stickstoffenthaltende-6 gliedrigen ring |
| TW218017B (de) * | 1992-04-28 | 1993-12-21 | Takeda Pharm Industry Co Ltd |
-
1997
- 1997-03-27 CA CA002250353A patent/CA2250353A1/en not_active Abandoned
- 1997-03-27 EP EP97917738A patent/EP0891360A4/de not_active Withdrawn
- 1997-03-27 JP JP9535510A patent/JP2000507585A/ja active Pending
- 1997-03-27 AU AU25988/97A patent/AU715603B2/en not_active Ceased
- 1997-03-27 WO PCT/US1997/005235 patent/WO1997036900A1/en not_active Ceased
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007501855A (ja) * | 2003-05-17 | 2007-02-01 | コリア リサーチ インスティテュート オブ バイオサイエンス アンド バイオテクノロジー | 新規な２−オキソ複素環化合物およびそれを含有する薬剤組成物 |
| JP4914719B2 (ja) * | 2003-05-17 | 2012-04-11 | コリア リサーチ インスティテュート オブ バイオサイエンス アンド バイオテクノロジー | 新規な２−オキソ複素環化合物およびそれを含有する薬剤組成物 |
| JP2007521311A (ja) * | 2003-07-15 | 2007-08-02 | コリア リサーチ インスティテュート オブ バイオサイエンス アンド バイオテクノロジー | 新規な２−オキソ複素環化合物およびそれを含有する薬剤組成物の使用 |
| JP4799408B2 (ja) * | 2003-07-15 | 2011-10-26 | コリア リサーチ インスティテュート オブ バイオサイエンス アンド バイオテクノロジー | 新規な２−オキソ複素環化合物およびそれを含有する薬剤組成物の使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU715603B2 (en) | 2000-02-03 |
| AU2598897A (en) | 1997-10-22 |
| EP0891360A1 (de) | 1999-01-20 |
| WO1997036900A1 (en) | 1997-10-09 |
| EP0891360A4 (de) | 2002-05-15 |
| CA2250353A1 (en) | 1997-10-09 |
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