NO312195B1 - Fremgangsmåte for fremstilling av karboksamido-4-azasteroider - Google Patents
Fremgangsmåte for fremstilling av karboksamido-4-azasteroider Download PDFInfo
- Publication number
- NO312195B1 NO312195B1 NO19994199A NO994199A NO312195B1 NO 312195 B1 NO312195 B1 NO 312195B1 NO 19994199 A NO19994199 A NO 19994199A NO 994199 A NO994199 A NO 994199A NO 312195 B1 NO312195 B1 NO 312195B1
- Authority
- NO
- Norway
- Prior art keywords
- oxo
- carboxamide
- formula
- ene
- phenylprop
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 24
- 238000002360 preparation method Methods 0.000 title claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 23
- 150000001412 amines Chemical class 0.000 claims description 18
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 16
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
- 125000001153 fluoro group Chemical group F* 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 150000007513 acids Chemical class 0.000 claims description 9
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 9
- 150000007928 imidazolide derivatives Chemical class 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 239000002841 Lewis acid Substances 0.000 claims description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 5
- 150000007517 lewis acids Chemical class 0.000 claims description 5
- IILGKOHWDLRWOZ-UHFFFAOYSA-N 1,2-bis(1h-imidazol-2-yl)ethane-1,2-dione Chemical compound N=1C=CNC=1C(=O)C(=O)C1=NC=CN1 IILGKOHWDLRWOZ-UHFFFAOYSA-N 0.000 claims description 4
- SDGHXWKVBZYHRR-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfonyl)-1h-imidazole Chemical compound N=1C=CNC=1S(=O)(=O)C1=NC=CN1 SDGHXWKVBZYHRR-UHFFFAOYSA-N 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- CAVUSNYEPKGKKE-GVGJTNQSSA-N (1s,3as,3bs,9ar,9bs,11as)-9a,11a-dimethyl-7-oxo-n-[1,1,1-trifluoro-2-(4-methylphenyl)propan-2-yl]-1,2,3,3a,3b,4,6,8,9,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide Chemical compound C1=CC(C)=CC=C1C(C)(C(F)(F)F)NC(=O)[C@@H]1[C@@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)NC4=CC[C@H]3[C@@H]2CC1 CAVUSNYEPKGKKE-GVGJTNQSSA-N 0.000 claims description 2
- CDPHFWLSRRLCIQ-PLTCLBSDSA-N (1s,3as,3bs,9ar,9bs,11as)-n-(1,1,1,3,3,3-hexafluoro-2-phenylpropan-2-yl)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,6,9b,10,11-decahydroindeno[5,4-f]quinoline-1-carboxamide Chemical compound O=C([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)NC4=CC3)C)CC[C@@]21C)NC(C(F)(F)F)(C(F)(F)F)C1=CC=CC=C1 CDPHFWLSRRLCIQ-PLTCLBSDSA-N 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- UTTIZTTVQJRZMS-GVGJTNQSSA-N (1s,3as,3bs,9ar,9bs,11as)-9a,11a-dimethyl-7-oxo-n-[1,1,1-trifluoro-2-(4-methylphenyl)propan-2-yl]-1,2,3,3a,3b,4,6,9b,10,11-decahydroindeno[5,4-f]quinoline-1-carboxamide Chemical compound C1=CC(C)=CC=C1C(C)(C(F)(F)F)NC(=O)[C@@H]1[C@@]2(C)CC[C@@H]3[C@@]4(C)C=CC(=O)NC4=CC[C@H]3[C@@H]2CC1 UTTIZTTVQJRZMS-GVGJTNQSSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000007787 solid Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- -1 for example Chemical group 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000003857 carboxamides Chemical class 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 230000000269 nucleophilic effect Effects 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 2
- DNXPGZNEKYOTLK-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoro-2-phenylpropan-2-amine Chemical compound FC(F)(F)C(C(F)(F)F)(N)C1=CC=CC=C1 DNXPGZNEKYOTLK-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 2
- MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 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 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 125000002345 steroid group Chemical group 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- PUGUQINMNYINPK-UHFFFAOYSA-N tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CCl)CC1 PUGUQINMNYINPK-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 2
- 229940102001 zinc bromide Drugs 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- FDESQZBVTKLIQN-MLGOENBGSA-N (1s,3as,3bs,5ar,9ar,9bs,11as)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxylic acid Chemical compound N1C(=O)C=C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(O)=O)[C@@H]4[C@@H]3CC[C@H]21 FDESQZBVTKLIQN-MLGOENBGSA-N 0.000 description 1
- WNUUCDPRBZUXGL-UUBMZHIOSA-N (1s,3as,3bs,9ar,9bs,11as)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,6,8,9,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxylic acid Chemical class N1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(O)=O)[C@@H]4[C@@H]3CC=C21 WNUUCDPRBZUXGL-UUBMZHIOSA-N 0.000 description 1
- PWSPBELTUMWIFB-AUGPFFKMSA-N (1s,3as,3bs,9ar,9bs,11as)-9a,11a-dimethyl-7-oxo-n-(1,1,1-trifluoro-2-phenylpropan-2-yl)-1,2,3,3a,3b,4,6,8,9,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide Chemical compound O=C([C@@H]1[C@]2(CC[C@@H]3[C@@]4(C)CCC(=O)NC4=CC[C@H]3[C@@H]2CC1)C)NC(C)(C(F)(F)F)C1=CC=CC=C1 PWSPBELTUMWIFB-AUGPFFKMSA-N 0.000 description 1
- XLLROVXVEAHIGB-AUGPFFKMSA-N (1s,3as,3bs,9ar,9bs,11as)-9a,11a-dimethyl-7-oxo-n-(1,1,1-trifluoro-2-phenylpropan-2-yl)-1,2,3,3a,3b,4,6,9b,10,11-decahydroindeno[5,4-f]quinoline-1-carboxamide Chemical compound O=C([C@@H]1[C@]2(CC[C@@H]3[C@@]4(C)C=CC(=O)NC4=CC[C@H]3[C@@H]2CC1)C)NC(C)(C(F)(F)F)C1=CC=CC=C1 XLLROVXVEAHIGB-AUGPFFKMSA-N 0.000 description 1
- AXMPUTNPYVTBSL-JLZSVDHQSA-N (5r,8s,9s,10r,13s,14s)-10,13-dimethyl-1,2,3,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-4-one Chemical class O=C([C@@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CCC[C@@]2(C)CC1 AXMPUTNPYVTBSL-JLZSVDHQSA-N 0.000 description 1
- BZHFMMCNNYLUEV-VMXHOPILSA-N (8s,9s,10r,13s,14s)-10,13-dimethyl-4,7,8,9,11,12,14,15,16,17-decahydro-3h-cyclopenta[a]phenanthrene Chemical group C1C=C2CCC=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 BZHFMMCNNYLUEV-VMXHOPILSA-N 0.000 description 1
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical class OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
- HTAAVGRKSQHANI-UHFFFAOYSA-N FC(C(C(F)(F)F)(C1=CC=CC=C1)N)(F)F.FC(C(C(F)(F)F)(C1=CC=CC=C1)N)(F)F Chemical compound FC(C(C(F)(F)F)(C1=CC=CC=C1)N)(F)F.FC(C(C(F)(F)F)(C1=CC=CC=C1)N)(F)F HTAAVGRKSQHANI-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- HNDHDMOSWUAEAW-VMXHOPILSA-N androstadienone Chemical class O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C=CC4)[C@@H]4[C@@H]3CCC2=C1 HNDHDMOSWUAEAW-VMXHOPILSA-N 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 150000001534 azasteroids Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000012362 glacial acetic acid Substances 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
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
- C07J73/001—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom
- C07J73/005—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom by nitrogen as hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Steroid Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9727522.6A GB9727522D0 (en) | 1997-12-31 | 1997-12-31 | Process for preparing carboxamido-4-azasteroids |
| PCT/EP1998/008527 WO1999035161A1 (en) | 1997-12-31 | 1998-12-17 | Process for preparing carboxamido-4-azasteroids |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO994199D0 NO994199D0 (no) | 1999-08-30 |
| NO994199L NO994199L (no) | 1999-10-29 |
| NO312195B1 true NO312195B1 (no) | 2002-04-08 |
Family
ID=10824341
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19994199A NO312195B1 (no) | 1997-12-31 | 1999-08-30 | Fremgangsmåte for fremstilling av karboksamido-4-azasteroider |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US6121449A (de) |
| EP (1) | EP0970105B1 (de) |
| JP (1) | JP2001515518A (de) |
| KR (1) | KR20000075845A (de) |
| CN (1) | CN1248263A (de) |
| AT (1) | ATE213741T1 (de) |
| AU (1) | AU753602B2 (de) |
| CA (1) | CA2278487A1 (de) |
| DE (1) | DE69803979T2 (de) |
| DK (1) | DK0970105T3 (de) |
| ES (1) | ES2173675T3 (de) |
| GB (1) | GB9727522D0 (de) |
| HU (1) | HUP0001444A3 (de) |
| NO (1) | NO312195B1 (de) |
| PT (1) | PT970105E (de) |
| RU (1) | RU2198176C2 (de) |
| TW (1) | TW442491B (de) |
| WO (1) | WO1999035161A1 (de) |
| ZA (1) | ZA9811950B (de) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6001844A (en) | 1995-09-15 | 1999-12-14 | Merck & Co., Inc. | 4-Azasteroids for treatment of hyperandrogenic conditions |
| US6645974B2 (en) | 2001-07-31 | 2003-11-11 | Merck & Co., Inc. | Androgen receptor modulators and methods for use thereof |
| AU2004255200A1 (en) * | 2003-06-30 | 2005-01-20 | Merck & Co., Inc. | 17-acetamido-4-azasteroid derivatives as androgen receptor modulators |
| WO2005005380A2 (en) * | 2003-06-30 | 2005-01-20 | Merck & Co., Inc. | 17-acetamido-4-azasteroid derivatives as androgen receptor modulators |
| EP1641464A4 (de) * | 2003-06-30 | 2008-05-14 | Merck & Co Inc | 17-acetamido-4-azasteroid-derivate als androgen-rezeptor-modulatoren |
| WO2005005606A2 (en) | 2003-06-30 | 2005-01-20 | Merck & Co., Inc. | 17-acetamido-4-azasteroid derivatives as androgen receptor modulators |
| JP2007505118A (ja) * | 2003-09-10 | 2007-03-08 | メルク エンド カムパニー インコーポレーテッド | アンドロゲン受容体調節剤としての１７−複素環−４−アザステロイド誘導体 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5237061A (en) * | 1988-10-31 | 1993-08-17 | Merck & Co., Inc. | Methods of synthesizing benign prostatic hypertropic agents and their intermediates |
| GB9002922D0 (en) * | 1990-02-09 | 1990-04-04 | Erba Carlo Spa | 17 beta-substituted-4-aza-5 alpha-androstan-3-one derivatives and process for their preparation |
| GB9115676D0 (en) * | 1991-07-19 | 1991-09-04 | Erba Carlo Spa | Process for the preparation of 17 beta substituted-4-aza-5 alpha-androstan-3-one derivatives |
| GB9216284D0 (en) * | 1992-07-31 | 1992-09-16 | Erba Carlo Spa | Fluorinated 17beta-substituted 4-aza-5alpha-androstane-3-one derivatives |
| GB9216329D0 (en) * | 1992-07-31 | 1992-09-16 | Erba Carlo Spa | 17beta-substituted 4-aza-5alpha-androstan-3-one derivatives |
| GB9415178D0 (en) * | 1994-07-28 | 1994-09-21 | Erba Carlo Spa | 4-azasteroids with side-chain fluoroketones |
-
1997
- 1997-12-31 GB GBGB9727522.6A patent/GB9727522D0/en not_active Ceased
-
1998
- 1998-12-17 US US09/367,847 patent/US6121449A/en not_active Expired - Fee Related
- 1998-12-17 CA CA002278487A patent/CA2278487A1/en not_active Abandoned
- 1998-12-17 CN CN98802795A patent/CN1248263A/zh active Pending
- 1998-12-17 KR KR1019997007922A patent/KR20000075845A/ko not_active Application Discontinuation
- 1998-12-17 DK DK98966861T patent/DK0970105T3/da active
- 1998-12-17 RU RU99120995/04A patent/RU2198176C2/ru not_active IP Right Cessation
- 1998-12-17 DE DE69803979T patent/DE69803979T2/de not_active Expired - Fee Related
- 1998-12-17 ES ES98966861T patent/ES2173675T3/es not_active Expired - Lifetime
- 1998-12-17 WO PCT/EP1998/008527 patent/WO1999035161A1/en not_active Application Discontinuation
- 1998-12-17 PT PT98966861T patent/PT970105E/pt unknown
- 1998-12-17 AU AU25146/99A patent/AU753602B2/en not_active Ceased
- 1998-12-17 EP EP98966861A patent/EP0970105B1/de not_active Expired - Lifetime
- 1998-12-17 AT AT98966861T patent/ATE213741T1/de not_active IP Right Cessation
- 1998-12-17 HU HU0001444A patent/HUP0001444A3/hu unknown
- 1998-12-17 JP JP53564099A patent/JP2001515518A/ja active Pending
- 1998-12-30 ZA ZA9811950A patent/ZA9811950B/xx unknown
- 1998-12-30 TW TW087121875A patent/TW442491B/zh not_active IP Right Cessation
-
1999
- 1999-08-30 NO NO19994199A patent/NO312195B1/no unknown
-
2000
- 2000-06-06 US US09/588,339 patent/US6284887B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2278487A1 (en) | 1999-07-15 |
| RU2198176C2 (ru) | 2003-02-10 |
| DK0970105T3 (da) | 2002-05-27 |
| NO994199D0 (no) | 1999-08-30 |
| EP0970105B1 (de) | 2002-02-27 |
| WO1999035161A1 (en) | 1999-07-15 |
| HUP0001444A3 (en) | 2001-03-28 |
| CN1248263A (zh) | 2000-03-22 |
| EP0970105A1 (de) | 2000-01-12 |
| DE69803979T2 (de) | 2003-02-06 |
| KR20000075845A (ko) | 2000-12-26 |
| PT970105E (pt) | 2002-07-31 |
| GB9727522D0 (en) | 1998-02-25 |
| JP2001515518A (ja) | 2001-09-18 |
| NO994199L (no) | 1999-10-29 |
| AU2514699A (en) | 1999-07-26 |
| US6284887B1 (en) | 2001-09-04 |
| ATE213741T1 (de) | 2002-03-15 |
| HUP0001444A2 (hu) | 2000-11-28 |
| ES2173675T3 (es) | 2002-10-16 |
| TW442491B (en) | 2001-06-23 |
| AU753602B2 (en) | 2002-10-24 |
| US6121449A (en) | 2000-09-19 |
| DE69803979D1 (de) | 2002-04-04 |
| ZA9811950B (en) | 1999-06-30 |
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