CA2013395A1 - 4(5)-imidazoles inhibiteurs de l'aromatase - Google Patents
4(5)-imidazoles inhibiteurs de l'aromataseInfo
- Publication number
- CA2013395A1 CA2013395A1 CA002013395A CA2013395A CA2013395A1 CA 2013395 A1 CA2013395 A1 CA 2013395A1 CA 002013395 A CA002013395 A CA 002013395A CA 2013395 A CA2013395 A CA 2013395A CA 2013395 A1 CA2013395 A1 CA 2013395A1
- Authority
- CA
- Canada
- Prior art keywords
- imidazole
- pharmaceutically acceptable
- acid addition
- addition salt
- acceptable acid
- 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.)
- Abandoned
Links
- 102000014654 Aromatase Human genes 0.000 title abstract description 11
- 108010078554 Aromatase Proteins 0.000 title abstract description 11
- 230000002401 inhibitory effect Effects 0.000 title abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 194
- 150000003839 salts Chemical class 0.000 claims abstract description 54
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 49
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 49
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 29
- 150000002367 halogens Chemical class 0.000 claims abstract description 29
- 150000002460 imidazoles Chemical class 0.000 claims abstract description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 28
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 25
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 19
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims abstract description 18
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims abstract description 18
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims abstract description 18
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 claims abstract description 18
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims abstract description 18
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 18
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims abstract 17
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 150
- 239000002253 acid Substances 0.000 claims description 53
- 239000000203 mixture Substances 0.000 claims description 44
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- -1 4,4-diphenyl-1-butenyl Chemical group 0.000 claims description 14
- YIKQQTCXTVOPIL-UHFFFAOYSA-N 5-(4,4-diphenylbutyl)-1h-imidazole Chemical compound C=1NC=NC=1CCCC(C=1C=CC=CC=1)C1=CC=CC=C1 YIKQQTCXTVOPIL-UHFFFAOYSA-N 0.000 claims description 8
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 7
- BDLDPLSENBXSJV-UHFFFAOYSA-N 5-(1,3-diphenylpropyl)-1h-imidazole Chemical compound C=1NC=NC=1C(C=1C=CC=CC=1)CCC1=CC=CC=C1 BDLDPLSENBXSJV-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- FAGOGDMDDNXKMQ-UHFFFAOYSA-N 5-[4,4-bis(4-nitrophenyl)butyl]-1h-imidazole Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(C=1C=CC(=CC=1)[N+]([O-])=O)CCCC1=CNC=N1 FAGOGDMDDNXKMQ-UHFFFAOYSA-N 0.000 claims description 4
- CMDFGVZIHQTFFQ-UHFFFAOYSA-N 5-[4-(2-fluorophenyl)-4-phenylbutyl]-1h-imidazole Chemical compound FC1=CC=CC=C1C(C=1C=CC=CC=1)CCCC1=CNC=N1 CMDFGVZIHQTFFQ-UHFFFAOYSA-N 0.000 claims description 4
- UCFVDADMYKYPHI-UHFFFAOYSA-N 1-benzyl-5-(1,3-diphenylpropyl)imidazole Chemical compound C=1N=CN(CC=2C=CC=CC=2)C=1C(C=1C=CC=CC=1)CCC1=CC=CC=C1 UCFVDADMYKYPHI-UHFFFAOYSA-N 0.000 claims description 3
- OFLRICAXQXLOQO-UHFFFAOYSA-N 1-benzyl-5-(4,5-diphenylpentyl)imidazole Chemical compound C=1N=CN(CC=2C=CC=CC=2)C=1CCCC(C=1C=CC=CC=1)CC1=CC=CC=C1 OFLRICAXQXLOQO-UHFFFAOYSA-N 0.000 claims description 3
- PVAJWBQNUAJMMC-UHFFFAOYSA-N 5-(4,5-diphenylpentyl)-1h-imidazole Chemical compound C=1NC=NC=1CCCC(C=1C=CC=CC=1)CC1=CC=CC=C1 PVAJWBQNUAJMMC-UHFFFAOYSA-N 0.000 claims description 3
- YRVUAZZAKKPFKB-UHFFFAOYSA-N 5-(6,6-diphenylhexyl)-1h-imidazole Chemical compound C=1NC=NC=1CCCCCC(C=1C=CC=CC=1)C1=CC=CC=C1 YRVUAZZAKKPFKB-UHFFFAOYSA-N 0.000 claims description 3
- XXOJZGZPFHOJGW-UHFFFAOYSA-N 5-[1,3-bis(4-fluorophenyl)propyl]-1h-imidazole Chemical compound C1=CC(F)=CC=C1CCC(C=1C=CC(F)=CC=1)C1=CNC=N1 XXOJZGZPFHOJGW-UHFFFAOYSA-N 0.000 claims description 3
- MBBRLIQBWUWXLI-UHFFFAOYSA-N 5-[1-(4-fluorophenyl)-5-(2-methylphenyl)pentyl]-1h-imidazole Chemical compound CC1=CC=CC=C1CCCCC(C=1C=CC(F)=CC=1)C1=CNC=N1 MBBRLIQBWUWXLI-UHFFFAOYSA-N 0.000 claims description 3
- GGEUKCLBHGOJPC-UHFFFAOYSA-N 5-[1-(4-fluorophenyl)-5-(4-methoxyphenyl)pentyl]-1h-imidazole Chemical compound C1=CC(OC)=CC=C1CCCCC(C=1C=CC(F)=CC=1)C1=CNC=N1 GGEUKCLBHGOJPC-UHFFFAOYSA-N 0.000 claims description 3
- PZUFOLFCLVUJBP-UHFFFAOYSA-N 5-[1-(4-fluorophenyl)-5-phenylpentyl]-1h-imidazole Chemical compound C1=CC(F)=CC=C1C(C=1N=CNC=1)CCCCC1=CC=CC=C1 PZUFOLFCLVUJBP-UHFFFAOYSA-N 0.000 claims description 3
- CMHXTASEXGIWSA-UHFFFAOYSA-N 5-[4,4-bis(3-methylphenyl)butyl]-1h-imidazole Chemical compound CC1=CC=CC(C(CCCC=2N=CNC=2)C=2C=C(C)C=CC=2)=C1 CMHXTASEXGIWSA-UHFFFAOYSA-N 0.000 claims description 3
- NYHRPLMOBBVGOU-UHFFFAOYSA-N 5-[4,4-bis(4-methoxyphenyl)butyl]-1h-imidazole Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)CCCC1=CNC=N1 NYHRPLMOBBVGOU-UHFFFAOYSA-N 0.000 claims description 3
- QPIUAAWRHUZOTB-UHFFFAOYSA-N 5-[4,4-bis(4-methylphenyl)butyl]-1h-imidazole Chemical compound C1=CC(C)=CC=C1C(C=1C=CC(C)=CC=1)CCCC1=CNC=N1 QPIUAAWRHUZOTB-UHFFFAOYSA-N 0.000 claims description 3
- HQKDQKHLQNJQCF-UHFFFAOYSA-N 5-[4-(2-methylphenyl)-4-phenylbutyl]-1h-imidazole Chemical compound CC1=CC=CC=C1C(C=1C=CC=CC=1)CCCC1=CNC=N1 HQKDQKHLQNJQCF-UHFFFAOYSA-N 0.000 claims description 3
- OHQKLXYSMOUONK-UHFFFAOYSA-N 5-[4-(3,4-dimethylphenyl)-4-phenylbutyl]-1h-imidazole Chemical compound C1=C(C)C(C)=CC=C1C(C=1C=CC=CC=1)CCCC1=CNC=N1 OHQKLXYSMOUONK-UHFFFAOYSA-N 0.000 claims description 3
- GOJLUJCAQKCBHO-UHFFFAOYSA-N 5-[4-(3,5-dimethylphenyl)-4-phenylbutyl]-1h-imidazole Chemical compound CC1=CC(C)=CC(C(CCCC=2N=CNC=2)C=2C=CC=CC=2)=C1 GOJLUJCAQKCBHO-UHFFFAOYSA-N 0.000 claims description 3
- CZFOQFQHOABVGN-UHFFFAOYSA-N 5-[4-(4-ethylphenyl)-4-phenylbutyl]-1h-imidazole Chemical compound C1=CC(CC)=CC=C1C(C=1C=CC=CC=1)CCCC1=CNC=N1 CZFOQFQHOABVGN-UHFFFAOYSA-N 0.000 claims description 3
- ZGEDPXRYEYFPMZ-UHFFFAOYSA-N 5-[4-(4-fluorophenyl)-4-phenylbutyl]-1h-imidazole Chemical compound C1=CC(F)=CC=C1C(C=1C=CC=CC=1)CCCC1=CNC=N1 ZGEDPXRYEYFPMZ-UHFFFAOYSA-N 0.000 claims description 3
- ILDQCPSKRMMNCS-UHFFFAOYSA-N 5-[4-(4-methylphenyl)-4-phenylbutyl]-1h-imidazole Chemical compound C1=CC(C)=CC=C1C(C=1C=CC=CC=1)CCCC1=CNC=N1 ILDQCPSKRMMNCS-UHFFFAOYSA-N 0.000 claims description 3
- YXRQRCUVYOLDSM-UHFFFAOYSA-N 5-[5-(2,6-dimethylphenyl)-1-(4-fluorophenyl)pentyl]-1h-imidazole Chemical compound CC1=CC=CC(C)=C1CCCCC(C=1C=CC(F)=CC=1)C1=CNC=N1 YXRQRCUVYOLDSM-UHFFFAOYSA-N 0.000 claims description 3
- LHBYZVKQVRNNDK-UHFFFAOYSA-N 1-benzyl-5-[4-(2-methylphenyl)-4-phenylbutyl]imidazole Chemical compound CC1=CC=CC=C1C(C=1C=CC=CC=1)CCCC1=CN=CN1CC1=CC=CC=C1 LHBYZVKQVRNNDK-UHFFFAOYSA-N 0.000 claims description 2
- FXLKQVLGNPEENW-UHFFFAOYSA-N 1-benzyl-5-[4-(3-methylphenyl)-4-phenylbutyl]imidazole Chemical compound CC1=CC=CC(C(CCCC=2N(C=NC=2)CC=2C=CC=CC=2)C=2C=CC=CC=2)=C1 FXLKQVLGNPEENW-UHFFFAOYSA-N 0.000 claims description 2
- MJNMGEDVHOZAQY-UHFFFAOYSA-N 5-(1,5-diphenylpentyl)-1h-imidazole Chemical compound C=1NC=NC=1C(C=1C=CC=CC=1)CCCCC1=CC=CC=C1 MJNMGEDVHOZAQY-UHFFFAOYSA-N 0.000 claims description 2
- AMRKPOMUXKVILC-UHFFFAOYSA-N 5-[1-(4-fluorophenyl)-5-(3-methylphenyl)pentyl]-1h-imidazole Chemical compound CC1=CC=CC(CCCCC(C=2N=CNC=2)C=2C=CC(F)=CC=2)=C1 AMRKPOMUXKVILC-UHFFFAOYSA-N 0.000 claims description 2
- OCNPWLBUNGTGFR-UHFFFAOYSA-N 5-[1-(4-fluorophenyl)-5-(4-methylphenyl)pentyl]-1h-imidazole Chemical compound C1=CC(C)=CC=C1CCCCC(C=1C=CC(F)=CC=1)C1=CNC=N1 OCNPWLBUNGTGFR-UHFFFAOYSA-N 0.000 claims description 2
- RHDYXYOKRJSVQN-UHFFFAOYSA-N 5-[4,4-bis(4-fluorophenyl)butyl]-1h-imidazole Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCC1=CNC=N1 RHDYXYOKRJSVQN-UHFFFAOYSA-N 0.000 claims description 2
- CUMGYYLTKUDRAM-UHFFFAOYSA-N 5-[4-(3,5-dimethylphenyl)-4-(3-methylphenyl)butyl]-1h-imidazole Chemical compound CC1=CC=CC(C(CCCC=2N=CNC=2)C=2C=C(C)C=C(C)C=2)=C1 CUMGYYLTKUDRAM-UHFFFAOYSA-N 0.000 claims description 2
- BEVKJDAOKKNLKM-UHFFFAOYSA-N 5-[4-(3-methylphenyl)-4-phenylbutyl]-1h-imidazole Chemical compound CC1=CC=CC(C(CCCC=2NC=NC=2)C=2C=CC=CC=2)=C1 BEVKJDAOKKNLKM-UHFFFAOYSA-N 0.000 claims description 2
- OTKRIAWTOSQJSG-UHFFFAOYSA-N 5-[4-(4-methoxyphenyl)-4-phenylbutyl]-1h-imidazole Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC=CC=1)CCCC1=CNC=N1 OTKRIAWTOSQJSG-UHFFFAOYSA-N 0.000 claims description 2
- PBNAFNDTZRUDQA-UHFFFAOYSA-N 1-benzyl-5-(4,4-diphenylbutyl)imidazole Chemical compound C=1N=CN(CC=2C=CC=CC=2)C=1CCCC(C=1C=CC=CC=1)C1=CC=CC=C1 PBNAFNDTZRUDQA-UHFFFAOYSA-N 0.000 claims 1
- MYTOEUQKNBHSLE-UHFFFAOYSA-N 4-[1-(4-aminophenyl)-4-(1h-imidazol-5-yl)butyl]aniline Chemical compound C1=CC(N)=CC=C1C(C=1C=CC(N)=CC=1)CCCC1=CNC=N1 MYTOEUQKNBHSLE-UHFFFAOYSA-N 0.000 claims 1
- KVSHYTNSIFQLRL-UHFFFAOYSA-N 5-[1,4-bis(4-fluorophenyl)butyl]-1h-imidazole Chemical compound C1=CC(F)=CC=C1CCCC(C=1C=CC(F)=CC=1)C1=CNC=N1 KVSHYTNSIFQLRL-UHFFFAOYSA-N 0.000 claims 1
- MCTXDFLYUKWYCX-UHFFFAOYSA-N 5-[1-(4-fluorophenyl)-3-phenylpropyl]-1h-imidazole Chemical compound C1=CC(F)=CC=C1C(C=1N=CNC=1)CCC1=CC=CC=C1 MCTXDFLYUKWYCX-UHFFFAOYSA-N 0.000 claims 1
- ASZWPXLYLYWPMJ-UHFFFAOYSA-N 5-[5-(3,5-dimethylphenyl)-1-(4-fluorophenyl)pentyl]-1h-imidazole Chemical compound CC1=CC(C)=CC(CCCCC(C=2N=CNC=2)C=2C=CC(F)=CC=2)=C1 ASZWPXLYLYWPMJ-UHFFFAOYSA-N 0.000 claims 1
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 claims 1
- 229940011871 estrogen Drugs 0.000 abstract description 10
- 239000000262 estrogen Substances 0.000 abstract description 10
- 208000026310 Breast neoplasm Diseases 0.000 abstract description 6
- 230000001419 dependent effect Effects 0.000 abstract description 6
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- 108090000856 Lyases Proteins 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 201000010099 disease Diseases 0.000 abstract description 3
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 abstract description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 61
- 238000005481 NMR spectroscopy Methods 0.000 description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
- 238000000034 method Methods 0.000 description 53
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 51
- 150000003840 hydrochlorides Chemical class 0.000 description 51
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 45
- 239000002585 base Substances 0.000 description 41
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 32
- 229910052739 hydrogen Inorganic materials 0.000 description 31
- 125000001424 substituent group Chemical group 0.000 description 31
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 16
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- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 6
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- 230000005764 inhibitory process Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
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- JUVDEAXMLQQRFP-UHFFFAOYSA-N 1h-imidazol-2-yl(phenyl)methanone Chemical compound C=1C=CC=CC=1C(=O)C1=NC=CN1 JUVDEAXMLQQRFP-UHFFFAOYSA-N 0.000 description 3
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- 150000001649 bromium compounds Chemical class 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
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000008859 change Effects 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
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012043 crude product Substances 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
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 229960003399 estrone Drugs 0.000 description 1
- QMILGVALBCRRIK-UHFFFAOYSA-N ethyl 4-(3-benzylimidazol-4-yl)butanoate Chemical compound CCOC(=O)CCCC1=CN=CN1CC1=CC=CC=C1 QMILGVALBCRRIK-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 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
- 239000003324 growth hormone secretagogue Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000003550 marker 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
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 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
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940100595 phenylacetaldehyde Drugs 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000003169 placental effect Effects 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
- 230000008569 process Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000004999 sex organ Anatomy 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000000638 stimulation Effects 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
- 239000000725 suspension 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
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 150000005691 triesters Chemical class 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 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
- C07D233/56—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8907218A GB2229719B (en) | 1989-03-30 | 1989-03-30 | Novel aromatase inhibiting 4(5)-imidazoles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2013395A1 true CA2013395A1 (fr) | 1991-09-29 |
Family
ID=10654204
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002013395A Abandoned CA2013395A1 (fr) | 1989-03-30 | 1990-03-29 | 4(5)-imidazoles inhibiteurs de l'aromatase |
Country Status (9)
| Country | Link |
|---|---|
| CA (1) | CA2013395A1 (fr) |
| DD (1) | DD296916A5 (fr) |
| FI (1) | FI901316A0 (fr) |
| GB (1) | GB2229719B (fr) |
| LT (1) | LT3657B (fr) |
| PL (1) | PL162554B1 (fr) |
| RU (2) | RU2021263C1 (fr) |
| UA (1) | UA19310A1 (fr) |
| ZA (1) | ZA902479B (fr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2248058B (en) * | 1990-09-21 | 1994-09-14 | Orion Yhtymae Oy | Aromatase inhibiting 4(5)-imidazoles |
| DE102006019906A1 (de) * | 2006-04-28 | 2007-10-31 | Müller-Enoch, Dieter, Prof. Dr. | Verwendung von Verbindungen der Formel A-R-X oder deren pharmazeutisch akzeptable Salze zur Herstellung einer pharmazeutischen Zubereitung |
| US20080146523A1 (en) * | 2006-12-18 | 2008-06-19 | Guido Galley | Imidazole derivatives |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3759944A (en) | 1970-10-14 | 1973-09-18 | Smith Kline French Lab | Isothioureas and their derivatives |
| GB2101114B (en) * | 1981-07-10 | 1985-05-22 | Farmos Group Ltd | Substituted imidazole derivatives and their preparation and use |
| CA1238640A (fr) * | 1984-06-18 | 1988-06-28 | Kenneth S. Hirsch | Imidazoles substitues en 4(5) |
| LU85747A1 (fr) * | 1985-01-28 | 1986-08-04 | Continental Pharma | Derives d'imidazole leur preparation et utilisation ainsi que les compositions pharmaceutiques contenant des derives |
| GB2210875B (en) | 1987-10-09 | 1991-05-29 | Farmos Oy | Aromatase inhibiting 4(5)-imidazoles |
| JPH032168A (ja) | 1989-03-30 | 1991-01-08 | Farmos Yhtymae Oy | アロマターゼ阻害活性を有する新規な４（５）―イミダゾール |
-
1989
- 1989-03-30 GB GB8907218A patent/GB2229719B/en not_active Revoked
-
1990
- 1990-03-16 FI FI901316A patent/FI901316A0/fi not_active IP Right Cessation
- 1990-03-29 RU SU904743449A patent/RU2021263C1/ru active
- 1990-03-29 DD DD90339203A patent/DD296916A5/de not_active IP Right Cessation
- 1990-03-29 CA CA002013395A patent/CA2013395A1/fr not_active Abandoned
- 1990-03-30 ZA ZA902479A patent/ZA902479B/xx unknown
- 1990-03-30 PL PL28896290A patent/PL162554B1/pl unknown
-
1991
- 1991-06-25 RU SU914895687A patent/RU1836355C/ru active
- 1991-06-25 UA UA4895687A patent/UA19310A1/uk unknown
-
1993
- 1993-08-10 LT LTIP847A patent/LT3657B/lt not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| RU2021263C1 (ru) | 1994-10-15 |
| ZA902479B (en) | 1990-12-28 |
| RU1836355C (ru) | 1993-08-23 |
| PL288962A1 (en) | 1991-10-21 |
| PL162554B1 (pl) | 1993-12-31 |
| GB2229719A (en) | 1990-10-03 |
| UA19310A1 (uk) | 1997-12-25 |
| GB8907218D0 (en) | 1989-05-10 |
| DD296916A5 (de) | 1991-12-19 |
| LTIP847A (en) | 1995-02-27 |
| FI901316A0 (fi) | 1990-03-16 |
| GB2229719B (en) | 1992-04-29 |
| LT3657B (en) | 1996-01-25 |
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|---|---|---|
| EP0311447B1 (fr) | 4(5)-Imidazoles inhibitrices d'aromatase | |
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| EP0390558B1 (fr) | 4(5)-Imidazoles inhibant l'aromatase | |
| SI9200113A (en) | New selective aromatase inhibiting 4(5)-imidazoles | |
| US5439928A (en) | Aromatase inhibiting 4(5)-imidazoles | |
| CA2013395A1 (fr) | 4(5)-imidazoles inhibiteurs de l'aromatase | |
| RU2036193C1 (ru) | Замещенные 4(5)-имидазолы или их нетоксичные фармацевтически приемлемые соли с кислотами | |
| GB2231568A (en) | New aromatase inhibiting 4(5)-imidazoles | |
| IL107260A (en) | Diphenylalkyl 4) 5 (- Imidazoles that inhibit aromatase and medicinal preparations containing them | |
| NO172119B (no) | Analogifremgangsmaate for fremstilling av terapeutisk aktive substituerte imidazol-forbindelser |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued | ||
| FZDE | Discontinued |
Effective date: 19980330 |