JP2002541153A - 経口活性アンドロゲン - Google Patents
経口活性アンドロゲンInfo
- Publication number
- JP2002541153A JP2002541153A JP2000609430A JP2000609430A JP2002541153A JP 2002541153 A JP2002541153 A JP 2002541153A JP 2000609430 A JP2000609430 A JP 2000609430A JP 2000609430 A JP2000609430 A JP 2000609430A JP 2002541153 A JP2002541153 A JP 2002541153A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- ethyl
- ethenyl
- hydrogen
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003098 androgen Substances 0.000 title claims abstract description 26
- 150000001875 compounds Chemical class 0.000 claims abstract description 43
- -1 (C 2 to 3) 1-alkenyl Chemical group 0.000 claims abstract description 37
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 26
- 125000002252 acyl group Chemical group 0.000 claims abstract description 18
- 239000001257 hydrogen Substances 0.000 claims abstract description 16
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 13
- 150000002367 halogens Chemical class 0.000 claims abstract description 12
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract description 6
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 4
- 238000000034 method Methods 0.000 claims description 48
- 125000006017 1-propenyl group Chemical group 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 229960004719 nandrolone Drugs 0.000 claims description 9
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 206010002261 Androgen deficiency Diseases 0.000 claims description 5
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 5
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 239000002583 male contraceptive agent Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- GRIITYJCBJMDNU-VAKUTIOCSA-N (8r,9r,10r,13s,14s)-7-hydroxy-13-methyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound OC1CC2=CC(=O)CC[C@@H]2[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 GRIITYJCBJMDNU-VAKUTIOCSA-N 0.000 claims 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 claims 2
- 239000013543 active substance Substances 0.000 claims 1
- 230000001143 conditioned effect Effects 0.000 claims 1
- 229960003387 progesterone Drugs 0.000 claims 1
- 239000000186 progesterone Substances 0.000 claims 1
- YSGQGNQWBLYHPE-CFUSNLFHSA-N (7r,8r,9s,10r,13s,14s,17s)-17-hydroxy-7,13-dimethyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-one Chemical class C1C[C@]2(C)[C@@H](O)CC[C@H]2[C@@H]2[C@H](C)CC3=CC(=O)CC[C@@H]3[C@H]21 YSGQGNQWBLYHPE-CFUSNLFHSA-N 0.000 abstract description 6
- 125000005843 halogen group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
- 239000000047 product Substances 0.000 description 92
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
- 239000000203 mixture Substances 0.000 description 42
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 38
- 239000012267 brine Substances 0.000 description 33
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
- 239000012074 organic phase Substances 0.000 description 32
- 238000003756 stirring Methods 0.000 description 32
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 29
- 229920006395 saturated elastomer Polymers 0.000 description 29
- 239000007864 aqueous solution Substances 0.000 description 27
- 239000000243 solution Substances 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 21
- 235000019341 magnesium sulphate Nutrition 0.000 description 21
- 238000000746 purification Methods 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 18
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 description 15
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 229940030486 androgens Drugs 0.000 description 13
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- 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 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
- 241000700159 Rattus Species 0.000 description 11
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 10
- JFEPJTGMGDGPHJ-PNKHAZJDSA-N (8r,9s,10r,13s,14s)-13-methyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C1CC2=CC(=O)CC[C@@H]2[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 JFEPJTGMGDGPHJ-PNKHAZJDSA-N 0.000 description 9
- 150000003431 steroids Chemical class 0.000 description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 8
- 235000019270 ammonium chloride Nutrition 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229960003604 testosterone Drugs 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- NPAGDVCDWIYMMC-IZPLOLCNSA-N nandrolone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 NPAGDVCDWIYMMC-IZPLOLCNSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- CAFOMEFFALHXPZ-GXEDQJNUSA-N (8r,9s,10r,13s,14s)-13-methyl-1,2,3,6,7,8,9,10,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-ol Chemical compound C1CC[C@@H]2[C@H]3CC[C@](C)(C(CC4)O)[C@@H]4[C@@H]3CCC2=C1 CAFOMEFFALHXPZ-GXEDQJNUSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 210000003494 hepatocyte Anatomy 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 4
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000003433 contraceptive agent Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- QKPIUQQVNTVZGP-YNFNDHOQSA-N (8r,9s,10r,13s,14s,17s)-17-[tert-butyl(dimethyl)silyl]oxy-13-ethyl-2,8,9,10,11,12,14,15,16,17-decahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@H](CC4)O[Si](C)(C)C(C)(C)C)[C@@H]4[C@@H]3C=CC2=C1 QKPIUQQVNTVZGP-YNFNDHOQSA-N 0.000 description 2
- FWYXCSGNRCNWEJ-YRXWBPOGSA-N (8s,9s,13s,14s)-3,3-dimethoxy-13-methyl-2,4,6,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthrene Chemical compound C1C[C@@H]2C(CCC(C3)(OC)OC)=C3CC[C@H]2[C@@H]2CCC[C@]21C FWYXCSGNRCNWEJ-YRXWBPOGSA-N 0.000 description 2
- 150000000319 19-nortestosterones Chemical class 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 2
- 229910052693 Europium Inorganic materials 0.000 description 2
- 108700012941 GNRH1 Proteins 0.000 description 2
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 102000009151 Luteinizing Hormone Human genes 0.000 description 2
- 108010073521 Luteinizing Hormone Proteins 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 238000009165 androgen replacement therapy Methods 0.000 description 2
- 230000001548 androgenic effect Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 230000002254 contraceptive effect Effects 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 150000001993 dienes Chemical class 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000002657 hormone replacement therapy Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 229940040129 luteinizing hormone Drugs 0.000 description 2
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N p-toluenesulfonic acid Substances CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 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 2
- FEFWOZKOPXZOBE-KOUBEUHGSA-N (8R,9S,10R,13R,14S)-17-hydroxy-13-prop-2-enyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-one Chemical compound C(=C)C[C@@]12C(CC[C@H]1[C@@H]1CCC3=CC(CC[C@@H]3[C@H]1CC2)=O)O FEFWOZKOPXZOBE-KOUBEUHGSA-N 0.000 description 1
- SBLHOJQRZNGHLQ-ATIFRJIPSA-N (8r,9s,10r,13s,14s)-13-ethyl-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-3,17-dione Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](CC)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 SBLHOJQRZNGHLQ-ATIFRJIPSA-N 0.000 description 1
- BKWWXJJWAQPJFB-KKKDIUQISA-N (8r,9s,10r,13s,14s)-3-ethoxy-13-ethyl-2,7,8,9,10,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthren-17-one Chemical compound C1C[C@@H]2[C@@H](CCC(OCC)=C3)C3=CC[C@H]2[C@@H]2CCC(=O)[C@]21CC BKWWXJJWAQPJFB-KKKDIUQISA-N 0.000 description 1
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- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- GEZOTWYUIKXWOA-UHFFFAOYSA-L copper;carbonate Chemical compound [Cu+2].[O-]C([O-])=O GEZOTWYUIKXWOA-UHFFFAOYSA-L 0.000 description 1
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- OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 description 1
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
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- 239000011968 lewis acid catalyst Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- HPFQTCRYSOTMDJ-UHFFFAOYSA-M lithium;benzenethiolate Chemical compound [Li+].[S-]C1=CC=CC=C1 HPFQTCRYSOTMDJ-UHFFFAOYSA-M 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- WQMNNHNWITXOAH-UHFFFAOYSA-M magnesium;prop-1-ene;bromide Chemical compound [Mg+2].[Br-].CC=[CH-] WQMNNHNWITXOAH-UHFFFAOYSA-M 0.000 description 1
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- 230000001404 mediated effect Effects 0.000 description 1
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- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
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- 239000000312 peanut oil Substances 0.000 description 1
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- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
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- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 239000012047 saturated solution Substances 0.000 description 1
- 230000036299 sexual function Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
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- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 150000003515 testosterones Chemical class 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0066—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa
- C07J1/007—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa the substituent being an OH group free esterified or etherified
-
- 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
- A61P5/26—Androgens
-
- 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
- A61P5/36—Antigestagens
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0066—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa
- C07J1/007—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa the substituent being an OH group free esterified or etherified
- C07J1/0074—Esters
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (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)
- Diabetes (AREA)
- Endocrinology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP99201070 | 1999-04-06 | ||
| PCT/EP2000/002851 WO2000059920A2 (en) | 1999-04-06 | 2000-03-31 | Orally active 7.alpha.-alkyl androgens |
| EP99201070.2 | 2000-03-31 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002541153A true JP2002541153A (ja) | 2002-12-03 |
| JP2002541153A5 JP2002541153A5 (enExample) | 2007-05-10 |
Family
ID=8240066
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000609430A Pending JP2002541153A (ja) | 1999-04-06 | 2000-03-31 | 経口活性アンドロゲン |
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|---|---|
| US (2) | US6756366B1 (enExample) |
| EP (1) | EP1212345B1 (enExample) |
| JP (1) | JP2002541153A (enExample) |
| AT (1) | ATE246703T1 (enExample) |
| AU (1) | AU5209600A (enExample) |
| CO (1) | CO5160345A1 (enExample) |
| DE (1) | DE60004377T2 (enExample) |
| ES (1) | ES2204613T3 (enExample) |
| PE (1) | PE20010029A1 (enExample) |
| WO (1) | WO2000059920A2 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000059920A2 (en) * | 1999-04-06 | 2000-10-12 | Akzo Nobel N.V. | Orally active 7.alpha.-alkyl androgens |
| DE10104327A1 (de) * | 2001-01-24 | 2002-07-25 | Schering Ag | 11beta-Halogensteroide, deren Herstellung und Verwendung zur Herstellung von Arzneimitteln sowie 11beta-Halogensteroide enthaltende pharmazeutische Präparate |
| CA2472379C (en) * | 2002-01-21 | 2010-05-25 | Akzo Nobel N.V. | Process for the preparation of 7.alpha.-methylsteroids |
| GB0304927D0 (en) * | 2003-03-04 | 2003-04-09 | Resolution Chemicals Ltd | Process for the production of tibolone |
| PE20050677A1 (es) | 2003-12-22 | 2005-10-04 | Akzo Nobel Nv | Esteroides con perfil androgenico y progestagenico mixto |
| JP5524177B2 (ja) * | 2008-04-09 | 2014-06-18 | フェリン ファーマシューティカルズ インコーポレイテッド | ほてりのためのステロイド治療 |
| CN103347525A (zh) * | 2010-12-15 | 2013-10-09 | 哈博生物科学公司 | 制备3α-氧取代的甾族化合物的方法及化合物 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2043404A1 (de) * | 1969-09-03 | 1971-03-11 | The Upjohn Co Kalamazoo, Mich (VStA) | 7beta Alkjl steroide und Verfahren zu ihrer Herstellung |
| US5342834A (en) * | 1989-04-07 | 1994-08-30 | The Population Council, Inc. | Method for androgen supplementation |
| JPH10273499A (ja) * | 1997-02-21 | 1998-10-13 | Akzo Nobel Nv | 避妊活性及び抗骨粗鬆症活性を有するステロイド化合物 |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5395627A (en) * | 1992-09-04 | 1995-03-07 | Akzo N.V. | Pharmaceutical granulate |
| US6037339A (en) * | 1993-02-08 | 2000-03-14 | Akzo Nobel N.V. | C-11 substituted steroids for treating menopausal complaints |
| AU671706B2 (en) * | 1993-03-05 | 1996-09-05 | Akzo N.V. | Use of a Pregnane Derivative |
| IL113816A (en) * | 1994-06-08 | 1998-12-06 | Akzo Nobel Nv | Pharmaceutical compositions containing desogestrel their preparation and use |
| CA2159419C (en) * | 1994-10-17 | 2006-07-04 | Pieter De Haan | Solid pharmaceutical composition comprising an excipient capable of binding water |
| HU223943B1 (hu) * | 1995-06-22 | 2005-03-29 | Akzo Nobel N.V. | Dezogesztrelt tartalmazó, szárazon granulált, sajtolt tabletták és előállításuk |
| IL118974A (en) * | 1995-08-17 | 2001-09-13 | Akzo Nobel Nv | History 11 - (Transformed Phenyl) - Astra - 4, 9 - Diane, their preparation and pharmaceutical preparations containing them |
| US5998639A (en) * | 1995-11-06 | 1999-12-07 | Akzo Nobel, N.V. | Sulfatation of estrogen mixtures |
| ZA968873B (en) * | 1995-11-06 | 1997-05-28 | Akzo Nobel Nv | Isomerisation of equillin |
| CA2200423C (en) * | 1996-03-26 | 2006-12-19 | Sietse Mosselman | Novel estrogen receptor |
| US6506390B2 (en) * | 1996-06-25 | 2003-01-14 | Akzo Nobel | Progestogen-anti-progestogen regimens |
| BR9808803A (pt) * | 1997-05-16 | 2000-07-18 | Akzo Nobel Nv | Derivado de 20-aralquil-5alfa-pregnano, uso do mesmo, e, composição farmacêutica |
| WO1998055498A1 (en) * | 1997-06-04 | 1998-12-10 | Akzo Nobel N.V. | 17β-ALLYLOXY(THIO)ALKYL-ANDROSTANE DERIVATIVES FOR THE MODULATION OF MEIOSIS |
| ES2152065T3 (es) * | 1997-09-23 | 2001-01-16 | Akzo Nobel Nv | Unidades de dosificado de esteroides con un recubrimiento estanco a los esteroides. |
| US6080773A (en) * | 1997-10-14 | 2000-06-27 | Akzo Nobel, N.V. | Benzylamine derivatives which are useful in treating psychiatric disorders |
| BR9814136A (pt) * | 1997-11-14 | 2000-10-03 | Akzo Nobel Nv | Conjunto contraceptivo, processos de fabricação do mesmo e de tratamento de sangramento, usos de anti-progestogênio, de progestogênio e de anti-progestogênio, e, de um composto. |
| WO1999032506A1 (en) * | 1997-12-18 | 1999-07-01 | Akzo Nobel N.V. | 17β-ARYL (ARYLMETHYL) OXY(THIO)ALKYL -ANDROSTANE DERIVATIVES |
| NZ506465A (en) * | 1998-02-26 | 2003-08-29 | Akzo Nobel Nv | Derivatives of azetidine and pyrrolidine |
| WO1999067271A1 (en) * | 1998-06-19 | 1999-12-29 | Akzo Nobel N.V. | Testosterone derivative |
| AU759344B2 (en) * | 1998-12-11 | 2003-04-10 | Akzo Nobel N.V. | 22S-hydroxycholesta-8, 14-diene derivatives with meiosis regulating activity |
| US6498153B1 (en) * | 1998-12-31 | 2002-12-24 | Akzo Nobel N.V. | Extended release growth promoting two component composition |
| DK1163258T3 (da) * | 1999-03-09 | 2003-03-31 | Akzo Nobel Nv | Derivater af 22R-hydroxycholesta-8, 14-dien til inhiberingen af meiosis |
| WO2000059920A2 (en) * | 1999-04-06 | 2000-10-12 | Akzo Nobel N.V. | Orally active 7.alpha.-alkyl androgens |
| TW548277B (en) * | 1999-07-16 | 2003-08-21 | Akzo Nobel Nv | Orally active androgens |
| MXPA02001831A (es) * | 1999-09-06 | 2002-10-23 | Akzo Nobel Nv | Esteroides estrogenicos no aromaticos con un sustituyente de hidrocarburo en posicion 11. |
| PL202999B1 (pl) * | 1999-12-02 | 2009-08-31 | Organon Nv | Androgeny zawierające pierścień cyklopropanowy w pozycjach 14, 15 i zastosowanie takich androgenów |
| AU2001254710A1 (en) * | 2000-03-27 | 2001-10-08 | Akzo Nobel N.V. | Non-steroidal, tetracyclic compounds for estrogen-related treatments |
| IL154408A0 (en) * | 2000-08-23 | 2003-09-17 | Akzo Nobel Nv | 10-ARYL-11-H BENZO [b] FLUORENE DERIVATIVES AND ANALOGS FOR MEDICINAL USE |
-
2000
- 2000-03-31 WO PCT/EP2000/002851 patent/WO2000059920A2/en not_active Ceased
- 2000-03-31 AU AU52096/00A patent/AU5209600A/en not_active Abandoned
- 2000-03-31 JP JP2000609430A patent/JP2002541153A/ja active Pending
- 2000-03-31 AT AT00936686T patent/ATE246703T1/de not_active IP Right Cessation
- 2000-03-31 US US09/937,274 patent/US6756366B1/en not_active Expired - Fee Related
- 2000-03-31 EP EP00936686A patent/EP1212345B1/en not_active Expired - Lifetime
- 2000-03-31 DE DE60004377T patent/DE60004377T2/de not_active Expired - Lifetime
- 2000-03-31 ES ES00936686T patent/ES2204613T3/es not_active Expired - Lifetime
- 2000-04-06 CO CO00025244A patent/CO5160345A1/es unknown
- 2000-04-06 PE PE2000000309A patent/PE20010029A1/es not_active Application Discontinuation
-
2004
- 2004-04-29 US US10/837,061 patent/US20040209853A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2043404A1 (de) * | 1969-09-03 | 1971-03-11 | The Upjohn Co Kalamazoo, Mich (VStA) | 7beta Alkjl steroide und Verfahren zu ihrer Herstellung |
| US5342834A (en) * | 1989-04-07 | 1994-08-30 | The Population Council, Inc. | Method for androgen supplementation |
| JPH10273499A (ja) * | 1997-02-21 | 1998-10-13 | Akzo Nobel Nv | 避妊活性及び抗骨粗鬆症活性を有するステロイド化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| ATE246703T1 (de) | 2003-08-15 |
| CO5160345A1 (es) | 2002-05-30 |
| WO2000059920A3 (en) | 2001-02-15 |
| WO2000059920A2 (en) | 2000-10-12 |
| DE60004377T2 (de) | 2004-06-09 |
| DE60004377D1 (de) | 2003-09-11 |
| US6756366B1 (en) | 2004-06-29 |
| EP1212345A2 (en) | 2002-06-12 |
| ES2204613T3 (es) | 2004-05-01 |
| AU5209600A (en) | 2000-10-23 |
| EP1212345B1 (en) | 2003-08-06 |
| PE20010029A1 (es) | 2001-01-26 |
| US20040209853A1 (en) | 2004-10-21 |
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