LT3164B - New selective aromatase inhibiting 4(5)-imidazoles - Google Patents
New selective aromatase inhibiting 4(5)-imidazoles Download PDFInfo
- Publication number
- LT3164B LT3164B LTIP175A LTIP175A LT3164B LT 3164 B LT3164 B LT 3164B LT IP175 A LTIP175 A LT IP175A LT IP175 A LTIP175 A LT IP175A LT 3164 B LT3164 B LT 3164B
- Authority
- LT
- Lithuania
- Prior art keywords
- imidazole
- cyanophenyl
- fluorophenyl
- pharmaceutically acceptable
- compounds
- Prior art date
Links
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 9
- 102000014654 Aromatase Human genes 0.000 title claims description 11
- 108010078554 Aromatase Proteins 0.000 title claims description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 146
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 27
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 27
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 18
- 150000002367 halogens Chemical class 0.000 claims abstract description 18
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 57
- -1 trifluoromethylphenyl Chemical group 0.000 claims description 42
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 15
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 15
- JHAPQEPKKUPGAA-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-1-(1h-imidazol-5-yl)butyl]benzonitrile Chemical compound C1=CC(F)=CC=C1CCCC(C=1C=CC(=CC=1)C#N)C1=CNC=N1 JHAPQEPKKUPGAA-UHFFFAOYSA-N 0.000 claims description 9
- KOTPKKGZQNWBBV-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)-1-(1h-imidazol-5-yl)but-1-enyl]benzonitrile Chemical compound C1=CC(F)=CC=C1CCC=C(C=1C=CC(=CC=1)C#N)C1=CNC=N1 KOTPKKGZQNWBBV-UHFFFAOYSA-N 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
- MRBWTJWBRJOYOB-UHFFFAOYSA-N 4-[3-(4-fluorophenyl)-1-(1h-imidazol-5-yl)prop-1-enyl]benzonitrile Chemical compound C1=CC(F)=CC=C1CC=C(C=1C=CC(=CC=1)C#N)C1=CNC=N1 MRBWTJWBRJOYOB-UHFFFAOYSA-N 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- SZBIOYUSHZRXMD-UHFFFAOYSA-N 4-[1-(4-cyanophenyl)-3-(1h-imidazol-5-yl)propyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C(C=1C=CC(=CC=1)C#N)CCC1=CNC=N1 SZBIOYUSHZRXMD-UHFFFAOYSA-N 0.000 claims description 5
- VZCAGYHHFBPDOY-UHFFFAOYSA-N 4-[3-(1h-imidazol-5-yl)-1-phenylpropyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C(C=1C=CC=CC=1)CCC1=CNC=N1 VZCAGYHHFBPDOY-UHFFFAOYSA-N 0.000 claims description 5
- ZIRXFAIJRWJWSD-UHFFFAOYSA-N 4-[3-(4-fluorophenyl)-3-(1h-imidazol-5-yl)prop-2-enyl]benzonitrile Chemical compound C1=CC(F)=CC=C1C(C=1N=CNC=1)=CCC1=CC=C(C#N)C=C1 ZIRXFAIJRWJWSD-UHFFFAOYSA-N 0.000 claims description 5
- 150000002460 imidazoles Chemical class 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- DTDSUERYHSVJKB-UHFFFAOYSA-N 4-[1-(4-fluorophenyl)-3-(1h-imidazol-5-yl)propyl]benzonitrile Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(=CC=1)C#N)CCC1=CNC=N1 DTDSUERYHSVJKB-UHFFFAOYSA-N 0.000 claims description 4
- LYVUWAIDQCZNCU-UHFFFAOYSA-N 4-[1-(1h-imidazol-5-yl)-4-phenylbutyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C(C=1N=CNC=1)CCCC1=CC=CC=C1 LYVUWAIDQCZNCU-UHFFFAOYSA-N 0.000 claims description 3
- ORSRGXAFGYIAPU-UHFFFAOYSA-N 4-[1-(4-cyanophenyl)-4-(1h-imidazol-5-yl)butyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C(C=1C=CC(=CC=1)C#N)CCCC1=CNC=N1 ORSRGXAFGYIAPU-UHFFFAOYSA-N 0.000 claims description 3
- WJGZRAWVMPHHAN-UHFFFAOYSA-N 4-[3-(3-benzylimidazol-4-yl)-1-(4-cyanophenyl)prop-1-enyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C(C=1C=CC(=CC=1)C#N)=CCC1=CN=CN1CC1=CC=CC=C1 WJGZRAWVMPHHAN-UHFFFAOYSA-N 0.000 claims description 2
- BREJGQBMHDNXQH-UHFFFAOYSA-N 4-[4-(3-benzylimidazol-4-yl)-1-(4-cyanophenyl)butyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C(C=1C=CC(=CC=1)C#N)CCCC1=CN=CN1CC1=CC=CC=C1 BREJGQBMHDNXQH-UHFFFAOYSA-N 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 3
- 239000000262 estrogen Substances 0.000 abstract description 11
- 239000002253 acid Substances 0.000 abstract description 9
- 206010006187 Breast cancer Diseases 0.000 abstract description 7
- 208000026310 Breast neoplasm Diseases 0.000 abstract description 7
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 abstract description 5
- 208000004403 Prostatic Hyperplasia Diseases 0.000 abstract description 5
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 201000010099 disease Diseases 0.000 abstract description 3
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 abstract 1
- 108010081348 HRT1 protein Hairy Proteins 0.000 abstract 1
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 abstract 1
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 abstract 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 55
- 239000000243 solution Substances 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 33
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 239000000047 product Substances 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 27
- 150000003840 hydrochlorides Chemical class 0.000 description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- 206010028980 Neoplasm Diseases 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 22
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 22
- 239000002904 solvent Substances 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 238000005984 hydrogenation reaction Methods 0.000 description 16
- 229910052739 hydrogen Inorganic materials 0.000 description 15
- 229910052763 palladium Inorganic materials 0.000 description 15
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 14
- 239000001257 hydrogen Substances 0.000 description 14
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- 229940011871 estrogen Drugs 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 150000002431 hydrogen Chemical class 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 238000009835 boiling Methods 0.000 description 8
- 239000011777 magnesium Substances 0.000 description 8
- 229910052749 magnesium Inorganic materials 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 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 7
- 241000700159 Rattus Species 0.000 description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 229910052744 lithium Inorganic materials 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 238000006276 transfer reaction Methods 0.000 description 6
- FZMGMDLGMVXWCF-UHFFFAOYSA-N 4-bromo-n-tert-butylbenzamide Chemical compound CC(C)(C)NC(=O)C1=CC=C(Br)C=C1 FZMGMDLGMVXWCF-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 229910052721 tungsten Inorganic materials 0.000 description 5
- 102000004317 Lyases Human genes 0.000 description 4
- 108090000856 Lyases Proteins 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 229940125782 compound 2 Drugs 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
- YFLBUUWWEGBOKW-UHFFFAOYSA-N n-tert-butyl-4-[4-(4-fluorophenyl)-1-hydroxy-1-(1h-imidazol-5-yl)butyl]benzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(O)(C=1N=CNC=1)CCCC1=CC=C(F)C=C1 YFLBUUWWEGBOKW-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- RRBQRILCDBHUHU-UHFFFAOYSA-N 1-(3-benzylimidazol-4-yl)-4-(4-fluorophenyl)butan-1-ol Chemical compound C=1N=CN(CC=2C=CC=CC=2)C=1C(O)CCCC1=CC=C(F)C=C1 RRBQRILCDBHUHU-UHFFFAOYSA-N 0.000 description 3
- SBGSFCBQZBIKCL-UHFFFAOYSA-N 1-(3-benzylimidazol-4-yl)-4-(4-fluorophenyl)butan-1-one Chemical compound C1=CC(F)=CC=C1CCCC(=O)C1=CN=CN1CC1=CC=CC=C1 SBGSFCBQZBIKCL-UHFFFAOYSA-N 0.000 description 3
- 125000003504 2-oxazolinyl group Chemical group O1C(=NCC1)* 0.000 description 3
- KSEMPMZBYRFSJA-UHFFFAOYSA-N 4-[3-(1h-imidazol-5-yl)-1-[4-(trifluoromethyl)phenyl]propyl]benzonitrile Chemical compound C1=CC(C(F)(F)F)=CC=C1C(C=1C=CC(=CC=1)C#N)CCC1=CNC=N1 KSEMPMZBYRFSJA-UHFFFAOYSA-N 0.000 description 3
- ARSRBNBHOADGJU-UHFFFAOYSA-N 7,12-dimethyltetraphene Chemical compound C1=CC2=CC=CC=C2C2=C1C(C)=C(C=CC=C1)C1=C2C ARSRBNBHOADGJU-UHFFFAOYSA-N 0.000 description 3
- VFZRZRDOXPRTSC-UHFFFAOYSA-N DMBA Natural products COC1=CC(OC)=CC(C=O)=C1 VFZRZRDOXPRTSC-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000003886 aromatase inhibitor Substances 0.000 description 3
- 229940046844 aromatase inhibitors Drugs 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 210000005075 mammary gland Anatomy 0.000 description 3
- SYTPXAXERSBEQM-UHFFFAOYSA-N n-tert-butyl-4-[3-(4-fluorophenyl)-3-hydroxy-3-(1h-imidazol-5-yl)propyl]benzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1CCC(O)(C=1C=CC(F)=CC=1)C1=CNC=N1 SYTPXAXERSBEQM-UHFFFAOYSA-N 0.000 description 3
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 3
- 239000001294 propane Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- ZLIAGYVFHDVPCS-UHFFFAOYSA-N 1-(3-benzylimidazol-4-yl)-4-phenylbutan-1-ol Chemical compound C=1N=CN(CC=2C=CC=CC=2)C=1C(O)CCCC1=CC=CC=C1 ZLIAGYVFHDVPCS-UHFFFAOYSA-N 0.000 description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 2
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 2
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 2
- QONDAZCJAPQGRX-UHFFFAOYSA-N 3-benzylimidazole-4-carbaldehyde Chemical compound O=CC1=CN=CN1CC1=CC=CC=C1 QONDAZCJAPQGRX-UHFFFAOYSA-N 0.000 description 2
- YNROJSQZXHMZHN-UHFFFAOYSA-N 4-[1-(3-benzylimidazol-4-yl)-4-(4-fluorophenyl)-1-hydroxybutyl]-n-tert-butylbenzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(O)(C=1N(C=NC=1)CC=1C=CC=CC=1)CCCC1=CC=C(F)C=C1 YNROJSQZXHMZHN-UHFFFAOYSA-N 0.000 description 2
- SVTAFOMBFGRXGF-UHFFFAOYSA-N 4-[1-(4-cyanophenyl)-3-(1h-imidazol-5-yl)prop-1-enyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C(C=1C=CC(=CC=1)C#N)=CCC1=CNC=N1 SVTAFOMBFGRXGF-UHFFFAOYSA-N 0.000 description 2
- QMXMKKNXGMAESN-UHFFFAOYSA-N 4-[3-(1h-imidazol-5-yl)-1-(4-methoxyphenyl)propyl]benzonitrile Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC(=CC=1)C#N)CCC1=CNC=N1 QMXMKKNXGMAESN-UHFFFAOYSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 101000919395 Homo sapiens Aromatase Proteins 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical group ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 125000001743 benzylic group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical group C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000006193 diazotization reaction Methods 0.000 description 2
- 229960005309 estradiol Drugs 0.000 description 2
- 229930182833 estradiol Natural products 0.000 description 2
- 102000015694 estrogen receptors Human genes 0.000 description 2
- 108010038795 estrogen receptors Proteins 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 239000002038 ethyl acetate fraction Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- 102000044018 human CYP19A1 Human genes 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229910003446 platinum oxide Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000002028 premature Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229950011008 tetrachloroethylene Drugs 0.000 description 2
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
- AOGCMZFSDDPNHF-UHFFFAOYSA-N 1-(3-benzylimidazol-4-yl)-3-(4-fluorophenyl)propan-1-one Chemical compound C1=CC(F)=CC=C1CCC(=O)C1=CN=CN1CC1=CC=CC=C1 AOGCMZFSDDPNHF-UHFFFAOYSA-N 0.000 description 1
- QPBMWTZOORQTCX-UHFFFAOYSA-N 1-(3-benzylimidazol-4-yl)-4-phenylbutan-1-one Chemical compound C=1N=CN(CC=2C=CC=CC=2)C=1C(=O)CCCC1=CC=CC=C1 QPBMWTZOORQTCX-UHFFFAOYSA-N 0.000 description 1
- BLQNOZHGIDFFAS-UHFFFAOYSA-N 1-(3-benzylimidazol-4-yl)ethanone Chemical compound CC(=O)C1=CN=CN1CC1=CC=CC=C1 BLQNOZHGIDFFAS-UHFFFAOYSA-N 0.000 description 1
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 1
- OHJDDVYUQCSBSG-UHFFFAOYSA-N 2-(4-bromophenyl)-4,5-dihydro-1,3-oxazole Chemical compound C1=CC(Br)=CC=C1C1=NCCO1 OHJDDVYUQCSBSG-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- KFPYJDFCCSYVNW-UHFFFAOYSA-N 3-(3-benzylimidazol-4-yl)-1-phenylpropan-1-one Chemical compound C=1C=CC=CC=1C(=O)CCC1=CN=CN1CC1=CC=CC=C1 KFPYJDFCCSYVNW-UHFFFAOYSA-N 0.000 description 1
- XMZQWZJMTBCUFT-UHFFFAOYSA-N 3-bromopropylbenzene Chemical compound BrCCCC1=CC=CC=C1 XMZQWZJMTBCUFT-UHFFFAOYSA-N 0.000 description 1
- PZGBZWZCENDRRF-UHFFFAOYSA-N 4-[1-(3-benzylimidazol-4-yl)-1-hydroxy-4-phenylbutyl]-n-tert-butylbenzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(O)(C=1N(C=NC=1)CC=1C=CC=CC=1)CCCC1=CC=CC=C1 PZGBZWZCENDRRF-UHFFFAOYSA-N 0.000 description 1
- PLWLLYFZXKQRDJ-UHFFFAOYSA-N 4-[1-(3-benzylimidazol-4-yl)-3-(4-fluorophenyl)-1-hydroxypropyl]-n-tert-butylbenzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(O)(C=1N(C=NC=1)CC=1C=CC=CC=1)CCC1=CC=C(F)C=C1 PLWLLYFZXKQRDJ-UHFFFAOYSA-N 0.000 description 1
- NGKZFQUGCZZEAJ-UHFFFAOYSA-N 4-[1-(3-benzylimidazol-4-yl)-4-(4-fluorophenyl)-1-hydroxybutyl]-n-tert-butylbenzamide;n-tert-butyl-4-[4-(4-fluorophenyl)-1-(1h-imidazol-5-yl)butyl]benzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(C=1NC=NC=1)CCCC1=CC=C(F)C=C1.C1=CC(C(=O)NC(C)(C)C)=CC=C1C(O)(C=1N(C=NC=1)CC=1C=CC=CC=1)CCCC1=CC=C(F)C=C1 NGKZFQUGCZZEAJ-UHFFFAOYSA-N 0.000 description 1
- PPNJFKNCGZLKGR-UHFFFAOYSA-N 4-[1-(3-benzylimidazol-4-yl)-4-phenylbut-1-enyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C(C=1N(C=NC=1)CC=1C=CC=CC=1)=CCCC1=CC=CC=C1 PPNJFKNCGZLKGR-UHFFFAOYSA-N 0.000 description 1
- UTEZJICOBLTVPK-UHFFFAOYSA-N 4-[1-(4-cyanophenyl)-3-(1h-imidazol-5-yl)prop-1-enyl]benzonitrile;hydrochloride Chemical compound Cl.C1=CC(C#N)=CC=C1C(C=1C=CC(=CC=1)C#N)=CCC1=CNC=N1 UTEZJICOBLTVPK-UHFFFAOYSA-N 0.000 description 1
- MNQBLSZOYGNSPV-UHFFFAOYSA-N 4-[1-(4-fluorophenyl)-3-(1h-imidazol-5-yl)prop-1-enyl]benzonitrile Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(=CC=1)C#N)=CCC1=CNC=N1 MNQBLSZOYGNSPV-UHFFFAOYSA-N 0.000 description 1
- NBSOIHACSKPEPI-UHFFFAOYSA-N 4-[3-(1-benzylimidazol-2-yl)-1-(4-fluorophenyl)prop-1-enyl]-n-tert-butylbenzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(C=1C=CC(F)=CC=1)=CCC1=NC=CN1CC1=CC=CC=C1 NBSOIHACSKPEPI-UHFFFAOYSA-N 0.000 description 1
- PJQHOEPUHRWSDM-UHFFFAOYSA-N 4-[3-(1-benzylimidazol-4-yl)-1-(4-cyanophenyl)prop-1-enyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C(C=1C=CC(=CC=1)C#N)=CCC(N=C1)=CN1CC1=CC=CC=C1 PJQHOEPUHRWSDM-UHFFFAOYSA-N 0.000 description 1
- DSILKXQWUWDIKI-UHFFFAOYSA-N 4-[3-(1h-imidazol-5-yl)-1-[4-(trifluoromethyl)phenyl]prop-1-enyl]benzonitrile Chemical compound C1=CC(C(F)(F)F)=CC=C1C(C=1C=CC(=CC=1)C#N)=CCC1=CN=CN1 DSILKXQWUWDIKI-UHFFFAOYSA-N 0.000 description 1
- QRHRRVPLAHYZKV-UHFFFAOYSA-N 4-[3-(3-benzylimidazol-4-yl)-1-(4-fluorophenyl)-1-hydroxypropyl]-n-tert-butylbenzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(O)(C=1C=CC(F)=CC=1)CCC1=CN=CN1CC1=CC=CC=C1 QRHRRVPLAHYZKV-UHFFFAOYSA-N 0.000 description 1
- HNOUQRGQZYIVCN-UHFFFAOYSA-N 4-[3-(3-benzylimidazol-4-yl)-1-(4-fluorophenyl)prop-1-enyl]benzonitrile Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(=CC=1)C#N)=CCC1=CN=CN1CC1=CC=CC=C1 HNOUQRGQZYIVCN-UHFFFAOYSA-N 0.000 description 1
- WURWFILNUFIBFR-UHFFFAOYSA-N 4-[3-(3-benzylimidazol-4-yl)-1-[4-(tert-butylcarbamoyl)phenyl]-1-hydroxypropyl]-n-tert-butylbenzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(O)(C=1C=CC(=CC=1)C(=O)NC(C)(C)C)CCC1=CN=CN1CC1=CC=CC=C1 WURWFILNUFIBFR-UHFFFAOYSA-N 0.000 description 1
- ATQFCTQCDSDQGB-UHFFFAOYSA-N 4-[3-(3-benzylimidazol-4-yl)-1-hydroxy-1-(4-methoxyphenyl)propyl]-n-tert-butylbenzamide Chemical compound C1=CC(OC)=CC=C1C(O)(C=1C=CC(=CC=1)C(=O)NC(C)(C)C)CCC1=CN=CN1CC1=CC=CC=C1 ATQFCTQCDSDQGB-UHFFFAOYSA-N 0.000 description 1
- JIYFHSFQEPHGNZ-UHFFFAOYSA-N 4-[3-(3-benzylimidazol-4-yl)-1-hydroxy-1-phenylpropyl]-n-tert-butylbenzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(O)(C=1C=CC=CC=1)CCC1=CN=CN1CC1=CC=CC=C1 JIYFHSFQEPHGNZ-UHFFFAOYSA-N 0.000 description 1
- AZNNIEFARSBBBR-UHFFFAOYSA-N 4-[4-(3-benzylimidazol-4-yl)-1-[4-(tert-butylcarbamoyl)phenyl]-1-hydroxybutyl]-n-tert-butylbenzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(O)(C=1C=CC(=CC=1)C(=O)NC(C)(C)C)CCCC1=CN=CN1CC1=CC=CC=C1 AZNNIEFARSBBBR-UHFFFAOYSA-N 0.000 description 1
- UMLBUSXGDLPYJJ-UHFFFAOYSA-N 4-[4-(4-carboxyphenyl)-4-(1h-imidazol-5-yl)but-3-enyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CCC=C(C=1C=CC(=CC=1)C(O)=O)C1=CNC=N1 UMLBUSXGDLPYJJ-UHFFFAOYSA-N 0.000 description 1
- MSCKCBLDSVUTNB-UHFFFAOYSA-N 4-[4-(4-cyanophenyl)-4-(1h-imidazol-5-yl)but-3-enyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1CCC=C(C=1C=CC(=CC=1)C#N)C1=CNC=N1 MSCKCBLDSVUTNB-UHFFFAOYSA-N 0.000 description 1
- ALUSULHZSGPXNX-UHFFFAOYSA-N 4-[4-(4-cyanophenyl)-4-(1h-imidazol-5-yl)butyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1CCCC(C=1C=CC(=CC=1)C#N)C1=CNC=N1 ALUSULHZSGPXNX-UHFFFAOYSA-N 0.000 description 1
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
- GYFGZFJGMRRTTP-UHFFFAOYSA-N 4-imidazol-1-ylbenzonitrile Chemical compound C1=CC(C#N)=CC=C1N1C=NC=C1 GYFGZFJGMRRTTP-UHFFFAOYSA-N 0.000 description 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- QIUNMSWQLOLJBK-UHFFFAOYSA-N C1=CC(C(=O)NC(C)(C)C)=CC=C1C(O)(C=1C=CC(=CC=1)C(=O)NC(C)(C)C)CCC1=CN=CN1 Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(O)(C=1C=CC(=CC=1)C(=O)NC(C)(C)C)CCC1=CN=CN1 QIUNMSWQLOLJBK-UHFFFAOYSA-N 0.000 description 1
- QJJVERQEJGCOCO-UHFFFAOYSA-N COC1=CC=C(C=C1)C(=CCN2C=CN=C2)C3=CC=C(C=C3)C#N Chemical compound COC1=CC=C(C=C1)C(=CCN2C=CN=C2)C3=CC=C(C=C3)C#N QJJVERQEJGCOCO-UHFFFAOYSA-N 0.000 description 1
- 101100520660 Drosophila melanogaster Poc1 gene Proteins 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 150000000994 L-ascorbates Chemical class 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- SPAGIJMPHSUYSE-UHFFFAOYSA-N Magnesium peroxide Chemical compound [Mg+2].[O-][O-] SPAGIJMPHSUYSE-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- ORNBQBCIOKFOEO-YQUGOWONSA-N Pregnenolone Natural products O=C(C)[C@@H]1[C@@]2(C)[C@H]([C@H]3[C@@H]([C@]4(C)C(=CC3)C[C@@H](O)CC4)CC2)CC1 ORNBQBCIOKFOEO-YQUGOWONSA-N 0.000 description 1
- 101100520662 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PBA1 gene Proteins 0.000 description 1
- 229940122572 Steroid synthesis inhibitor Drugs 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- WREOTYWODABZMH-DTZQCDIJSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[2-oxo-4-(2-phenylethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N(C=C\1)C(=O)NC/1=N\OCCC1=CC=CC=C1 WREOTYWODABZMH-DTZQCDIJSA-N 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008236 biological pathway Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- GTBRTGPZZALPNS-MXHVRSFHSA-N cyanoketone Chemical compound C1C=C2C(C)(C)C(=O)[C@H](C#N)C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 GTBRTGPZZALPNS-MXHVRSFHSA-N 0.000 description 1
- 238000006264 debenzylation reaction Methods 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 229960003399 estrone Drugs 0.000 description 1
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- BHYVHYPBRYOMGC-UHFFFAOYSA-N ethyl 4-formylbenzoate Chemical compound CCOC(=O)C1=CC=C(C=O)C=C1 BHYVHYPBRYOMGC-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001752 female genitalia Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000007952 growth promoter Substances 0.000 description 1
- 239000003630 growth substance Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- LKFQZJFOELEYDS-UHFFFAOYSA-N n-tert-butyl-4-[1-(4-fluorophenyl)-1-hydroxy-3-(1h-imidazol-5-yl)propyl]benzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(O)(C=1C=CC(F)=CC=1)CCC1=CNC=N1 LKFQZJFOELEYDS-UHFFFAOYSA-N 0.000 description 1
- DQXPJORSKDDGDX-UHFFFAOYSA-N n-tert-butyl-4-[1-(4-fluorophenyl)-3-(1h-imidazol-5-yl)prop-1-enyl]benzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(C=1C=CC(F)=CC=1)=CCC1=CNC=N1 DQXPJORSKDDGDX-UHFFFAOYSA-N 0.000 description 1
- XLPDFVGFLKSMGF-UHFFFAOYSA-N n-tert-butyl-4-[1-(4-fluorophenyl)-3-(1h-imidazol-5-yl)propyl]benzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(C=1C=CC(F)=CC=1)CCC1=CN=CN1 XLPDFVGFLKSMGF-UHFFFAOYSA-N 0.000 description 1
- QQFKXXJGYLXCIC-UHFFFAOYSA-N n-tert-butyl-4-[1-hydroxy-1-(1h-imidazol-5-yl)propyl]benzamide Chemical compound C=1C=C(C(=O)NC(C)(C)C)C=CC=1C(O)(CC)C1=CNC=N1 QQFKXXJGYLXCIC-UHFFFAOYSA-N 0.000 description 1
- PIGWGPLTWIOQPC-UHFFFAOYSA-N n-tert-butyl-4-[1-hydroxy-3-(1h-imidazol-5-yl)-1-[4-(trifluoromethyl)phenyl]propyl]benzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(O)(C=1C=CC(=CC=1)C(F)(F)F)CCC1=CNC=N1 PIGWGPLTWIOQPC-UHFFFAOYSA-N 0.000 description 1
- HPJAEPCUJHMKFS-UHFFFAOYSA-N n-tert-butyl-4-[1-hydroxy-3-(1h-imidazol-5-yl)-1-phenylpropyl]benzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(O)(C=1C=CC=CC=1)CCC1=CNC=N1 HPJAEPCUJHMKFS-UHFFFAOYSA-N 0.000 description 1
- KQEQMPZFEVJXGA-UHFFFAOYSA-N n-tert-butyl-4-[3-(1h-imidazol-5-yl)-1-phenylprop-1-enyl]benzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(C=1C=CC=CC=1)=CCC1=CNC=N1 KQEQMPZFEVJXGA-UHFFFAOYSA-N 0.000 description 1
- KELORFXUMRLIHB-UHFFFAOYSA-N n-tert-butyl-4-[3-(1h-imidazol-5-yl)-1-phenylpropyl]benzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(C=1C=CC=CC=1)CCC1=CNC=N1 KELORFXUMRLIHB-UHFFFAOYSA-N 0.000 description 1
- JZJRCTXRFYSHPA-UHFFFAOYSA-N n-tert-butyl-4-[3-(4-fluorophenyl)-1-hydroxy-1-(1h-imidazol-5-yl)propyl]benzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(O)(C=1N=CNC=1)CCC1=CC=C(F)C=C1 JZJRCTXRFYSHPA-UHFFFAOYSA-N 0.000 description 1
- LRSXTIFSTNTZRV-UHFFFAOYSA-N n-tert-butyl-4-[4-(4-fluorophenyl)-1-(1h-imidazol-5-yl)butyl]benzamide Chemical compound C1=CC(C(=O)NC(C)(C)C)=CC=C1C(C=1N=CNC=1)CCCC1=CC=C(F)C=C1 LRSXTIFSTNTZRV-UHFFFAOYSA-N 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- ORNBQBCIOKFOEO-QGVNFLHTSA-N pregnenolone Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 ORNBQBCIOKFOEO-QGVNFLHTSA-N 0.000 description 1
- 229960000249 pregnenolone Drugs 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- OTNVGWMVOULBFZ-UHFFFAOYSA-N sodium;hydrochloride Chemical compound [Na].Cl OTNVGWMVOULBFZ-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository 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
- 150000003892 tartrate salts Chemical class 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000009901 transfer hydrogenation reaction Methods 0.000 description 1
- 230000003442 weekly effect Effects 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB919113142A GB9113142D0 (en) | 1991-06-18 | 1991-06-18 | New selective aromatase inhibiting 4(5)-imidazoles |
| GB919125924A GB9125924D0 (en) | 1991-06-18 | 1991-12-05 | Stereoisomers of an imidazole derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| LTIP175A LTIP175A (lt) | 1994-08-25 |
| LT3164B true LT3164B (en) | 1995-02-27 |
Family
ID=26299089
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LTIP175A LT3164B (en) | 1991-06-18 | 1992-08-28 | New selective aromatase inhibiting 4(5)-imidazoles |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US5559141A (cs) |
| EP (1) | EP0589975A1 (cs) |
| JP (1) | JPH06508119A (cs) |
| KR (1) | KR940701386A (cs) |
| CN (1) | CN1068819A (cs) |
| AU (1) | AU665002B2 (cs) |
| BG (1) | BG98306A (cs) |
| CA (1) | CA2111469A1 (cs) |
| CZ (1) | CZ280293A3 (cs) |
| FI (1) | FI935658A7 (cs) |
| GB (1) | GB9125924D0 (cs) |
| HR (1) | HRP920170A2 (cs) |
| HU (1) | HUT67325A (cs) |
| IE (1) | IE921963A1 (cs) |
| IL (2) | IL102216A (cs) |
| LT (1) | LT3164B (cs) |
| LV (1) | LV10093B (cs) |
| MX (1) | MX9203000A (cs) |
| NO (1) | NO934688L (cs) |
| NZ (1) | NZ243139A (cs) |
| PT (1) | PT100604A (cs) |
| SI (1) | SI9200113A (cs) |
| SK (1) | SK144393A3 (cs) |
| TW (1) | TW206217B (cs) |
| WO (1) | WO1992022537A1 (cs) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2273704B (en) * | 1992-12-16 | 1997-01-22 | Orion Yhtymae Oy | Triazolyl diaryl selective aromatase inhibiting compounds |
| SE9302333D0 (sv) * | 1993-07-06 | 1993-07-06 | Ab Astra | New compounds |
| US6080870A (en) * | 1996-04-03 | 2000-06-27 | Merck & Co., Inc. | Biaryl substituted imidazole compounds useful as farnesyl-protein transferase inhibitors |
| EP0891333A1 (en) * | 1996-04-03 | 1999-01-20 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US6063930A (en) * | 1996-04-03 | 2000-05-16 | Merck & Co., Inc. | Substituted imidazole compounds useful as farnesyl-protein transferase inhibitors |
| US6297239B1 (en) * | 1997-10-08 | 2001-10-02 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
| AU2001275794A1 (en) | 2000-07-28 | 2002-02-13 | Sumitomo Pharmaceuticals Co. Ltd. | Pyrrole derivatives |
| AR046276A1 (es) | 2003-10-07 | 2005-11-30 | Renovis Inc | Derivados de amida como ligandos de canales ionicos y composiciones farmaceuticas y metodos que los utilizan. |
| EA200701835A1 (ru) * | 2005-02-28 | 2008-02-28 | Реновис, Инк. | Амидные производные в качестве лигандов ионных каналов, их фармацевтические композиции и способы их применения |
| US7576099B2 (en) | 2005-02-28 | 2009-08-18 | Renovis, Inc. | Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same |
| US7902247B2 (en) * | 2008-01-09 | 2011-03-08 | Allergan, Inc. | Substituted-aryl-2-phenylethyl-1H-imidazole compounds as subtype selective modulators of alpha 2B and/or alpha 2C adrenergic receptors |
| WO2024226608A2 (en) * | 2023-04-25 | 2024-10-31 | Aglaeapharma Inc. | Imidazole containing compounds, derivatives therefore, and uses thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0311447A1 (en) | 1987-10-09 | 1989-04-12 | Orion-Yhtymà Oy | Aromatase inhibiting 4(5)-imidazoles |
| EP0390558A1 (en) | 1989-03-30 | 1990-10-03 | Orion-Yhtymà Oy | Aromatase inhibiting 4(5)-imidazoles |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4605661A (en) * | 1984-06-18 | 1986-08-12 | Eli Lilly And Company | Aromastase inhibiting α,α-diarylimidazole-4(5)-propionitriles, α,α-diarylimidazole-4(5)-propionamides, and 4(5)-(2,2-diarylethyl)imidazoles |
| GB2248058B (en) * | 1990-09-21 | 1994-09-14 | Orion Yhtymae Oy | Aromatase inhibiting 4(5)-imidazoles |
| US5439928A (en) * | 1989-03-30 | 1995-08-08 | Orion-Yhtyma Oy | Aromatase inhibiting 4(5)-imidazoles |
-
1991
- 1991-12-05 GB GB919125924A patent/GB9125924D0/en active Pending
-
1992
- 1992-06-12 US US08/167,873 patent/US5559141A/en not_active Expired - Fee Related
- 1992-06-12 CA CA002111469A patent/CA2111469A1/en not_active Abandoned
- 1992-06-12 CZ CS932802A patent/CZ280293A3/cs unknown
- 1992-06-12 JP JP4511061A patent/JPH06508119A/ja active Pending
- 1992-06-12 SK SK1443-93A patent/SK144393A3/sk unknown
- 1992-06-12 AU AU19783/92A patent/AU665002B2/en not_active Ceased
- 1992-06-12 EP EP92912309A patent/EP0589975A1/en not_active Withdrawn
- 1992-06-12 KR KR1019930703934A patent/KR940701386A/ko not_active Withdrawn
- 1992-06-12 WO PCT/FI1992/000184 patent/WO1992022537A1/en not_active Application Discontinuation
- 1992-06-15 LV LVP-92-29A patent/LV10093B/en unknown
- 1992-06-15 NZ NZ243139A patent/NZ243139A/en unknown
- 1992-06-16 IL IL10221692A patent/IL102216A/en not_active IP Right Cessation
- 1992-06-17 PT PT100604A patent/PT100604A/pt not_active Application Discontinuation
- 1992-06-17 HR HR920170A patent/HRP920170A2/hr not_active Application Discontinuation
- 1992-06-17 TW TW081104752A patent/TW206217B/zh active
- 1992-06-18 CN CN92105664A patent/CN1068819A/zh active Pending
- 1992-06-18 SI SI19929200113A patent/SI9200113A/sl unknown
- 1992-06-18 MX MX9203000A patent/MX9203000A/es unknown
- 1992-07-01 IE IE196392A patent/IE921963A1/en not_active Application Discontinuation
- 1992-08-28 LT LTIP175A patent/LT3164B/lt not_active IP Right Cessation
-
1993
- 1993-12-16 FI FI935658A patent/FI935658A7/fi not_active Application Discontinuation
- 1993-12-17 HU HU9303653A patent/HUT67325A/hu active IP Right Revival
- 1993-12-17 BG BG98306A patent/BG98306A/bg unknown
- 1993-12-17 NO NO934688A patent/NO934688L/no unknown
-
1995
- 1995-09-27 IL IL11543995A patent/IL115439A0/xx unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0311447A1 (en) | 1987-10-09 | 1989-04-12 | Orion-Yhtymà Oy | Aromatase inhibiting 4(5)-imidazoles |
| EP0390558A1 (en) | 1989-03-30 | 1990-10-03 | Orion-Yhtymà Oy | Aromatase inhibiting 4(5)-imidazoles |
Also Published As
| Publication number | Publication date |
|---|---|
| NO934688D0 (no) | 1993-12-17 |
| LV10093B (en) | 1995-02-20 |
| SI9200113A (en) | 1992-12-31 |
| KR940701386A (ko) | 1994-05-28 |
| NO934688L (no) | 1993-12-17 |
| MX9203000A (es) | 1993-02-01 |
| LTIP175A (lt) | 1994-08-25 |
| BG98306A (bg) | 1994-08-30 |
| HUT67325A (en) | 1995-03-28 |
| IL102216A (en) | 1996-06-18 |
| CZ280293A3 (en) | 1994-05-18 |
| WO1992022537A1 (en) | 1992-12-23 |
| IL102216A0 (en) | 1993-01-14 |
| GB9125924D0 (en) | 1992-02-05 |
| LV10093A (lv) | 1994-05-10 |
| HU9303653D0 (en) | 1994-04-28 |
| FI935658A0 (fi) | 1993-12-16 |
| SK144393A3 (en) | 1994-11-09 |
| CN1068819A (zh) | 1993-02-10 |
| HRP920170A2 (en) | 1994-08-31 |
| NZ243139A (en) | 1994-08-26 |
| IL115439A0 (en) | 1995-12-31 |
| FI935658A7 (fi) | 1993-12-16 |
| TW206217B (cs) | 1993-05-21 |
| PT100604A (pt) | 1993-10-29 |
| AU665002B2 (en) | 1995-12-14 |
| EP0589975A1 (en) | 1994-04-06 |
| CA2111469A1 (en) | 1992-12-23 |
| JPH06508119A (ja) | 1994-09-14 |
| AU1978392A (en) | 1993-01-12 |
| US5559141A (en) | 1996-09-24 |
| IE921963A1 (en) | 1992-12-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5098923A (en) | Aromatase inhibiting 4(5)-imidazoles | |
| LT3164B (en) | New selective aromatase inhibiting 4(5)-imidazoles | |
| JP3186771B2 (ja) | 新規選択性アロマターゼ抑制化合物 | |
| CA1161849A (en) | Derivatives of indole active on the cardiovascular system | |
| EP0390558B1 (en) | Aromatase inhibiting 4(5)-imidazoles | |
| US5439928A (en) | Aromatase inhibiting 4(5)-imidazoles | |
| PL162554B1 (pl) | S posób wytwarzania nowych pochodnych imidazolu PL PL PL PL PL | |
| EP0476944B1 (en) | Aromatase inhibiting 4(5)-imidazoles | |
| FI63016C (fi) | Foerfarande foer framstaellning av en terapeutiskt aktiv propanolamin | |
| US4127576A (en) | Nortropine-carbazate derivatives | |
| PL162555B1 (pl) | Sposób wytwarzania nowych pochodnych imidazolu PL | |
| FR2548183A1 (fr) | Diphenylazomethines portant un radical imidazolyle, leur preparation et leur application en therapeutique |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM9A | Lapsed patents |
Effective date: 19970828 |