NO326034B1 - Benzo[c]kinolizinderivater, fremgangsmate for fremstilling og anvendelse derav som 5<alfa>-reduktaseinhibitorer - Google Patents
Benzo[c]kinolizinderivater, fremgangsmate for fremstilling og anvendelse derav som 5<alfa>-reduktaseinhibitorer Download PDFInfo
- Publication number
- NO326034B1 NO326034B1 NO20003199A NO20003199A NO326034B1 NO 326034 B1 NO326034 B1 NO 326034B1 NO 20003199 A NO20003199 A NO 20003199A NO 20003199 A NO20003199 A NO 20003199A NO 326034 B1 NO326034 B1 NO 326034B1
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- Norway
- Prior art keywords
- compound
- formula
- benzo
- defined above
- compounds
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- 238000002360 preparation method Methods 0.000 title claims description 21
- 238000000034 method Methods 0.000 title claims description 19
- UOGFZJRMCBHRQU-UHFFFAOYSA-N 10ah-benzo[c]quinolizine Chemical class N12C=CC=CC2=CC=C2C1C=CC=C2 UOGFZJRMCBHRQU-UHFFFAOYSA-N 0.000 title claims description 9
- 239000003112 inhibitor Substances 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 61
- 239000000203 mixture Substances 0.000 claims description 36
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 21
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 claims description 19
- 108010044467 Isoenzymes Proteins 0.000 claims description 16
- WZCXJNBOOQLKKD-UHFFFAOYSA-N 2,4-dihydroquinolizin-3-one Chemical compound C1=CC=CN2CC(=O)CC=C21 WZCXJNBOOQLKKD-UHFFFAOYSA-N 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 14
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 claims description 13
- 108090000790 Enzymes Proteins 0.000 claims description 11
- 102000004190 Enzymes Human genes 0.000 claims description 11
- 150000002923 oximes Chemical class 0.000 claims description 10
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- XSGHLZBESSREDT-UHFFFAOYSA-N methylenecyclopropane Chemical class C=C1CC1 XSGHLZBESSREDT-UHFFFAOYSA-N 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- -1 trimethylsilyldifluoromethanesulfonic anhydride Chemical compound 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 230000008635 plant growth Effects 0.000 claims description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 6
- 201000004384 Alopecia Diseases 0.000 claims description 5
- 206010020112 Hirsutism Diseases 0.000 claims description 5
- 229910010165 TiCu Inorganic materials 0.000 claims description 5
- 239000000654 additive Substances 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 5
- 230000003676 hair loss Effects 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 150000003431 steroids Chemical class 0.000 claims description 5
- 230000009466 transformation Effects 0.000 claims description 5
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 206010000496 acne Diseases 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000005610 enamide group Chemical group 0.000 claims description 4
- 238000011065 in-situ storage Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- UCUUFSAXZMGPGH-UHFFFAOYSA-N penta-1,4-dien-3-one Chemical compound C=CC(=O)C=C UCUUFSAXZMGPGH-UHFFFAOYSA-N 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 210000002307 prostate Anatomy 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 3
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 230000006315 carbonylation Effects 0.000 claims description 3
- 238000005810 carbonylation reaction Methods 0.000 claims description 3
- 125000004185 ester group Chemical group 0.000 claims description 3
- 239000012467 final product Substances 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 claims description 3
- 239000012434 nucleophilic reagent Substances 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 claims description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 230000001105 regulatory effect Effects 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- 206010020880 Hypertrophy Diseases 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
- 230000000699 topical effect Effects 0.000 claims description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 2
- 230000033228 biological regulation Effects 0.000 claims 1
- 150000002170 ethers Chemical class 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000003921 oil Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- 229940125904 compound 1 Drugs 0.000 description 10
- 239000010779 crude oil Substances 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 9
- 230000008020 evaporation Effects 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 150000001299 aldehydes Chemical class 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 7
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 4
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
- 229940126543 compound 14 Drugs 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 230000008707 rearrangement Effects 0.000 description 4
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 3
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 3
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 3
- 229960003473 androstanolone Drugs 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
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- 238000010626 work up procedure Methods 0.000 description 3
- YQCQGMIFMVJEJG-UHFFFAOYSA-N 1,2,5,6,7,8,9,10-octahydrobenzo[f]quinolizin-3-one Chemical compound C1CCCC2=C1N1CCC(=O)C=C1CC2 YQCQGMIFMVJEJG-UHFFFAOYSA-N 0.000 description 2
- VGOPGKIQNKYRSB-UHFFFAOYSA-N 4-oxa-5-azaspiro[2.4]hept-5-ene Chemical compound C1CC11ON=CC1 VGOPGKIQNKYRSB-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000007171 acid catalysis Methods 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 2
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- SHALBPKEGDBVKK-VOTSOKGWSA-N danishefsky's diene Chemical compound CO\C=C\C(=C)O[Si](C)(C)C SHALBPKEGDBVKK-VOTSOKGWSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
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- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 229960003604 testosterone Drugs 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 1
- AOWKEGOVBNFUIO-UHFFFAOYSA-N 2-[2-(4-oxa-5-azaspiro[2.4]hept-5-en-6-yl)ethyl]cyclohexan-1-one Chemical compound O=C1CCCCC1CCC(C1)=NOC11CC1 AOWKEGOVBNFUIO-UHFFFAOYSA-N 0.000 description 1
- YEXWPTQVHNJMNW-UHFFFAOYSA-N 2h-benzo[h]quinolin-3-one Chemical class C1=CC=C2C=CC3=CC(=O)CN=C3C2=C1 YEXWPTQVHNJMNW-UHFFFAOYSA-N 0.000 description 1
- VSGOQOKVDXMETB-UHFFFAOYSA-N 3-[2-(1,3-dioxolan-2-yl)cyclohexyl]propanal Chemical compound O=CCCC1CCCCC1C1OCCO1 VSGOQOKVDXMETB-UHFFFAOYSA-N 0.000 description 1
- ASFAFOSQXBRFMV-LJQANCHMSA-N 3-n-(2-benzyl-1,3-dihydroxypropan-2-yl)-1-n-[(1r)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzene-1,3-dicarboxamide Chemical compound N([C@H](C)C=1C=CC(F)=CC=1)C(=O)C(C=1)=CC(N(C)S(C)(=O)=O)=CC=1C(=O)NC(CO)(CO)CC1=CC=CC=C1 ASFAFOSQXBRFMV-LJQANCHMSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- OJMNSLSXEAFEFK-UHFFFAOYSA-N 6-[2-[2-(1,3-dioxolan-2-yl)cyclohexyl]ethyl]-4-oxa-5-azaspiro[2.4]hept-5-ene Chemical compound C1CCCC(C2OCCO2)C1CCC(C1)=NOC21CC2 OJMNSLSXEAFEFK-UHFFFAOYSA-N 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
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- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
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- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
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- NQRJJOIOVAOHLP-UHFFFAOYSA-N benzo[f]quinolizin-3-one Chemical class C1=CC=C2N3C=CC(=O)C=C3C=CC2=C1 NQRJJOIOVAOHLP-UHFFFAOYSA-N 0.000 description 1
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 1
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- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
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- 238000010438 heat treatment Methods 0.000 description 1
- OTTZHAVKAVGASB-UHFFFAOYSA-N hept-2-ene Chemical compound CCCCC=CC OTTZHAVKAVGASB-UHFFFAOYSA-N 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000000260 male genitalia Anatomy 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- BLDILZWHAGIASG-UHFFFAOYSA-N methyl 3-[2-(1,3-dioxolan-2-yl)cyclohexyl]propanoate Chemical compound COC(=O)CCC1CCCCC1C1OCCO1 BLDILZWHAGIASG-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- QNNSORXRBKTHJT-UHFFFAOYSA-N n-[3-[2-(1,3-dioxolan-2-yl)cyclohexyl]propylidene]hydroxylamine Chemical compound ON=CCCC1CCCCC1C1OCCO1 QNNSORXRBKTHJT-UHFFFAOYSA-N 0.000 description 1
- MCLMCMHKKVJVDK-UHFFFAOYSA-N n-tert-butyl-n-[3-[2-(4-oxa-5-azaspiro[2.4]hept-5-en-6-yl)ethyl]-4-oxocyclohexyl]acetamide Chemical compound C1C(N(C(=O)C)C(C)(C)C)CCC(=O)C1CCC(C1)=NOC11CC1 MCLMCMHKKVJVDK-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000000590 phytopharmaceutical Substances 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000004240 prostatic hypertrophy Diseases 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 244000045561 useful plants Species 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/04—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
-
- 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
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Dermatology (AREA)
- Environmental Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Dentistry (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP97122733A EP0926148A1 (en) | 1997-12-23 | 1997-12-23 | Benzo (C)quinolizine derivatives, their preparation and use as 5-alphareductases inhibitors |
| PCT/EP1998/008582 WO1999033828A1 (en) | 1997-12-23 | 1998-12-21 | Benzo[c]quinolizine derivatives and their use as 5 alpha-reductases inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20003199D0 NO20003199D0 (no) | 2000-06-20 |
| NO20003199L NO20003199L (no) | 2000-08-23 |
| NO326034B1 true NO326034B1 (no) | 2008-09-01 |
Family
ID=8227866
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20003199A NO326034B1 (no) | 1997-12-23 | 2000-06-20 | Benzo[c]kinolizinderivater, fremgangsmate for fremstilling og anvendelse derav som 5<alfa>-reduktaseinhibitorer |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US6962925B1 (zh) |
| EP (2) | EP0926148A1 (zh) |
| JP (1) | JP2001527074A (zh) |
| KR (1) | KR100580742B1 (zh) |
| CN (1) | CN1144804C (zh) |
| AR (1) | AR017964A1 (zh) |
| AT (1) | ATE303382T1 (zh) |
| AU (1) | AU744105B2 (zh) |
| BR (1) | BR9813836A (zh) |
| CA (1) | CA2315055A1 (zh) |
| DE (1) | DE69831427T2 (zh) |
| EA (1) | EA002831B1 (zh) |
| EE (1) | EE04615B1 (zh) |
| ES (1) | ES2245053T3 (zh) |
| HK (1) | HK1033128A1 (zh) |
| IL (1) | IL136919A0 (zh) |
| NO (1) | NO326034B1 (zh) |
| PT (1) | PT1066284E (zh) |
| SI (1) | SI1066284T1 (zh) |
| UA (1) | UA66371C2 (zh) |
| WO (1) | WO1999033828A1 (zh) |
| ZA (1) | ZA9811762B (zh) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0926148A1 (en) * | 1997-12-23 | 1999-06-30 | Applied Research Systems Ars Holding N.V. | Benzo (C)quinolizine derivatives, their preparation and use as 5-alphareductases inhibitors |
| AU754604B2 (en) * | 1998-07-29 | 2002-11-21 | Merck & Co., Inc. | Tricyclic compounds |
| KR100785088B1 (ko) | 2006-05-23 | 2007-12-12 | 한국과학기술연구원 | 두 개의 엑소 메틸렌을 가지는 고리가 접합된 락탐화합물과이의 제조방법 |
| AU2007273441A1 (en) * | 2006-07-13 | 2008-01-17 | Nihon Nohyaku Co., Ltd. | Parasitic plant control agent and use thereof |
| GB201506894D0 (en) * | 2015-04-23 | 2015-06-10 | Galapagos Nv | Novel dihydropyridoisoquinolinones and pharmaceutical compositions thereof for the treatment of inflammatory disorders |
| CN106008423B (zh) * | 2016-06-24 | 2018-02-02 | 云南民族大学 | 一种苯丙素类化合物及其制备方法和应用 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0591583B1 (en) * | 1991-08-21 | 2001-12-19 | Eli Lilly And Company | Benzo (f) quinolinones as 5-alpha-reductase inhibitors |
| US5239075A (en) * | 1991-08-21 | 1993-08-24 | Eli Lilly And Company | Process for the preparation of benzo (f) quinolinones |
| ES2125884T3 (es) * | 1991-08-21 | 1999-03-16 | Lilly Co Eli | Hexahidrobenzo(f)quinolinonas como inhibidores de la 5-alfa-reductasa. |
| US5250539A (en) * | 1991-08-21 | 1993-10-05 | Eli Lilly And Company | Hexahydrobenzo[f]quinolinones |
| WO1994021614A1 (en) * | 1993-03-24 | 1994-09-29 | Merck & Co., Inc. | SUBSTITUTED 3-PHENANTHRIDINONE DERIVATIVES AS 5α-REDUCTASE INHIBITORS |
| US5578724A (en) * | 1994-09-20 | 1996-11-26 | Eli Lilly And Company | Process for preparation of benzo[f]quinolinones |
| IT1286545B1 (it) * | 1996-02-09 | 1998-07-15 | Antonio Guarna | Derivati benzo(c) chinolizinici,loro preparazione ed uso come inibitori delle 5-alfa-riduttasi |
| ITFI970193A1 (it) * | 1997-08-01 | 1999-02-01 | Applied Research Systems | Uso di derivati benzo(c) chinolizinici come regolatori della crescita delle piante e composizioni ad uso agricolo che contengono tali |
| EP0926148A1 (en) * | 1997-12-23 | 1999-06-30 | Applied Research Systems Ars Holding N.V. | Benzo (C)quinolizine derivatives, their preparation and use as 5-alphareductases inhibitors |
-
1997
- 1997-12-23 EP EP97122733A patent/EP0926148A1/en not_active Withdrawn
-
1998
- 1998-12-21 KR KR1020007006912A patent/KR100580742B1/ko not_active IP Right Cessation
- 1998-12-21 EP EP98966711A patent/EP1066284B1/en not_active Expired - Lifetime
- 1998-12-21 SI SI9830791T patent/SI1066284T1/sl unknown
- 1998-12-21 CA CA002315055A patent/CA2315055A1/en not_active Abandoned
- 1998-12-21 PT PT98966711T patent/PT1066284E/pt unknown
- 1998-12-21 WO PCT/EP1998/008582 patent/WO1999033828A1/en not_active Application Discontinuation
- 1998-12-21 EE EEP200000387A patent/EE04615B1/xx not_active IP Right Cessation
- 1998-12-21 ES ES98966711T patent/ES2245053T3/es not_active Expired - Lifetime
- 1998-12-21 UA UA2000063687A patent/UA66371C2/uk unknown
- 1998-12-21 AT AT98966711T patent/ATE303382T1/de not_active IP Right Cessation
- 1998-12-21 BR BR9813836-7A patent/BR9813836A/pt not_active Application Discontinuation
- 1998-12-21 JP JP2000526509A patent/JP2001527074A/ja active Pending
- 1998-12-21 AU AU24194/99A patent/AU744105B2/en not_active Ceased
- 1998-12-21 IL IL13691998A patent/IL136919A0/xx unknown
- 1998-12-21 EA EA200000697A patent/EA002831B1/ru not_active IP Right Cessation
- 1998-12-21 CN CNB98813702XA patent/CN1144804C/zh not_active Expired - Fee Related
- 1998-12-21 DE DE69831427T patent/DE69831427T2/de not_active Expired - Fee Related
- 1998-12-22 ZA ZA9811762A patent/ZA9811762B/xx unknown
- 1998-12-23 AR ARP980106662A patent/AR017964A1/es active IP Right Grant
-
2000
- 2000-06-12 US US09/593,173 patent/US6962925B1/en not_active Expired - Fee Related
- 2000-06-20 NO NO20003199A patent/NO326034B1/no not_active IP Right Cessation
-
2001
- 2001-05-29 HK HK01103695A patent/HK1033128A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| EE04615B1 (et) | 2006-04-17 |
| EP0926148A1 (en) | 1999-06-30 |
| EP1066284B1 (en) | 2005-08-31 |
| CA2315055A1 (en) | 1999-07-08 |
| EP1066284A1 (en) | 2001-01-10 |
| JP2001527074A (ja) | 2001-12-25 |
| EA002831B1 (ru) | 2002-10-31 |
| DE69831427D1 (de) | 2005-10-06 |
| KR100580742B1 (ko) | 2006-05-15 |
| WO1999033828A1 (en) | 1999-07-08 |
| EA200000697A1 (ru) | 2000-12-25 |
| AU744105B2 (en) | 2002-02-14 |
| KR20010033432A (ko) | 2001-04-25 |
| AU2419499A (en) | 1999-07-19 |
| AR017964A1 (es) | 2001-10-24 |
| BR9813836A (pt) | 2000-10-10 |
| US6962925B1 (en) | 2005-11-08 |
| EE200000387A (et) | 2001-12-17 |
| NO20003199L (no) | 2000-08-23 |
| HK1033128A1 (en) | 2001-08-17 |
| CN1284954A (zh) | 2001-02-21 |
| ES2245053T3 (es) | 2005-12-16 |
| ZA9811762B (en) | 1999-06-23 |
| IL136919A0 (en) | 2001-06-14 |
| ATE303382T1 (de) | 2005-09-15 |
| SI1066284T1 (sl) | 2005-12-31 |
| CN1144804C (zh) | 2004-04-07 |
| UA66371C2 (en) | 2004-05-17 |
| PT1066284E (pt) | 2005-11-30 |
| NO20003199D0 (no) | 2000-06-20 |
| DE69831427T2 (de) | 2006-06-08 |
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