SK281645B6 - 16-substituované-4-azaandrostanové deriváty, farmaceutické prostriedky s ich obsahom a ich použitie - Google Patents
16-substituované-4-azaandrostanové deriváty, farmaceutické prostriedky s ich obsahom a ich použitie Download PDFInfo
- Publication number
- SK281645B6 SK281645B6 SK496-96A SK49696A SK281645B6 SK 281645 B6 SK281645 B6 SK 281645B6 SK 49696 A SK49696 A SK 49696A SK 281645 B6 SK281645 B6 SK 281645B6
- Authority
- SK
- Slovakia
- Prior art keywords
- aza
- oxo
- androstane
- dimethyl
- methyl
- Prior art date
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- -1 16-substituted-4-aza-androstane Chemical class 0.000 title claims abstract description 180
- 239000003112 inhibitor Substances 0.000 title claims abstract description 49
- 108010044467 Isoenzymes Proteins 0.000 title claims abstract description 11
- 108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 title claims description 44
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 66
- 125000003118 aryl group Chemical group 0.000 claims abstract description 52
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 31
- 239000001257 hydrogen Substances 0.000 claims abstract description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 210000004209 hair Anatomy 0.000 claims abstract description 21
- 201000004384 Alopecia Diseases 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 18
- 208000002874 Acne Vulgaris Diseases 0.000 claims abstract description 14
- 206010000496 acne Diseases 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 14
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 13
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 13
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 13
- 230000003676 hair loss Effects 0.000 claims abstract description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 177
- 125000004432 carbon atom Chemical group C* 0.000 claims description 60
- 125000001424 substituent group Chemical group 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 31
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 23
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 20
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 239000004480 active ingredient Substances 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 239000000051 antiandrogen Substances 0.000 claims description 9
- 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 claims description 9
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 8
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- 229960004039 finasteride Drugs 0.000 claims description 8
- 239000004036 potassium channel stimulating agent Substances 0.000 claims description 8
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 8
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical group NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 claims description 7
- 206010060862 Prostate cancer Diseases 0.000 claims description 7
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 229960003632 minoxidil Drugs 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 claims description 6
- 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 claims description 6
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 6
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 6
- 230000003779 hair growth Effects 0.000 claims description 6
- 230000005764 inhibitory process Effects 0.000 claims description 6
- 229960005280 isotretinoin Drugs 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 150000004492 retinoid derivatives Chemical class 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- WISOMYPLVSRCOA-GCORZJBRSA-N (2s,3as,3bs,5ar,9ar,9bs,11ar)-2-hydroxy-6,9a,11a-trimethyl-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1h-indeno[5,4-f]quinolin-7-one Chemical compound C([C@]1(C)C[C@@H](O)C[C@H]1[C@@H]1CC2)C[C@@H]1[C@]1(C)[C@@H]2N(C)C(=O)CC1 WISOMYPLVSRCOA-GCORZJBRSA-N 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
- VAPSMQAHNAZRKC-PQWRYPMOSA-N Epristeride Chemical compound C1C=C2C=C(C(O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)NC(C)(C)C)[C@@]1(C)CC2 VAPSMQAHNAZRKC-PQWRYPMOSA-N 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 claims description 5
- 230000002280 anti-androgenic effect Effects 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 claims description 5
- 229960002074 flutamide Drugs 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
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- 125000004951 trihalomethoxy group Chemical group 0.000 claims description 5
- WMPQMBUXZHMEFZ-YJPJVVPASA-N turosteride Chemical compound CN([C@@H]1CC2)C(=O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)N(C(C)C)C(=O)NC(C)C)[C@@]2(C)CC1 WMPQMBUXZHMEFZ-YJPJVVPASA-N 0.000 claims description 5
- 229950007816 turosteride Drugs 0.000 claims description 5
- GEFASWZDEZXYBN-BDVJJGLGSA-N (2s,3as,3bs,5ar,9ar,9bs,11ar)-2-methoxy-6,9a,11a-trimethyl-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1h-indeno[5,4-f]quinolin-7-one Chemical compound CN([C@@H]1CC2)C(=O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H](OC)C[C@@]2(C)CC1 GEFASWZDEZXYBN-BDVJJGLGSA-N 0.000 claims description 4
- VYLBHVHOLJBIFH-FZFXZXLVSA-N (8s,9s,10r,13s,14s)-10,13-dimethyl-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydro-3h-cyclopenta[a]phenanthrene Chemical compound C1CC2CCC=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 VYLBHVHOLJBIFH-FZFXZXLVSA-N 0.000 claims description 4
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 4
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 claims description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
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- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
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- 125000001786 isothiazolyl group Chemical group 0.000 claims description 4
- 201000007094 prostatitis Diseases 0.000 claims description 4
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 claims description 4
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- QFECRRHDSOJQGZ-JTQHMQRYSA-N (2s,3as,3bs,5ar,9ar,9bs,11ar)-6,9a,11a-trimethyl-2-phenoxy-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1h-indeno[5,4-f]quinolin-7-one Chemical compound O([C@H]1C[C@H]2[C@@H]3CC[C@H]4N(C(CC[C@]4(C)[C@H]3CC[C@]2(C)C1)=O)C)C1=CC=CC=C1 QFECRRHDSOJQGZ-JTQHMQRYSA-N 0.000 claims description 3
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 3
- 229960003473 androstanolone Drugs 0.000 claims description 3
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 3
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 3
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- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
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- 229940044551 receptor antagonist Drugs 0.000 claims description 3
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- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 3
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- UAFNYTRJXGDYAT-JTQHMQRYSA-N (2s,3as,3bs,5ar,9ar,9bs,11ar)-2-(4-chlorophenoxy)-6,9a,11a-trimethyl-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1h-indeno[5,4-f]quinolin-7-one Chemical compound O([C@H]1C[C@H]2[C@@H]3CC[C@H]4N(C(CC[C@]4(C)[C@H]3CC[C@]2(C)C1)=O)C)C1=CC=C(Cl)C=C1 UAFNYTRJXGDYAT-JTQHMQRYSA-N 0.000 claims description 2
- ILPJOHWFPYJLOE-XOJCLWECSA-N O=C1N([C@@H]2[C@H](C[C@H]3[C@@H]4CCC[C@@]4(C)CC[C@@H]3[C@]2(CC1)C)OC)C Chemical compound O=C1N([C@@H]2[C@H](C[C@H]3[C@@H]4CCC[C@@]4(C)CC[C@@H]3[C@]2(CC1)C)OC)C ILPJOHWFPYJLOE-XOJCLWECSA-N 0.000 claims description 2
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 6
- 201000002996 androgenic alopecia Diseases 0.000 claims 2
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- WISOMYPLVSRCOA-VBQAZTFJSA-N (2R,3aS,3bS,5aR,9aR,9bS,11aR)-2-hydroxy-6,9a,11a-trimethyl-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1H-indeno[5,4-f]quinolin-7-one Chemical compound C([C@]1(C)C[C@H](O)C[C@H]1[C@@H]1CC2)C[C@@H]1[C@]1(C)[C@@H]2N(C)C(=O)CC1 WISOMYPLVSRCOA-VBQAZTFJSA-N 0.000 claims 1
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- JLKOIZFBCUOQFJ-TYIWYJSASA-N [(2s,3as,3bs,5ar,9ar,9bs,11ar)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,8,9,9b,10,11-dodecahydro-1h-indeno[5,4-f]quinolin-2-yl] n-benzylcarbamate Chemical compound O([C@H]1C[C@H]2[C@@H]3CC[C@H]4N(C(CC[C@]4(C)[C@H]3CC[C@]2(C)C1)=O)C)C(=O)NCC1=CC=CC=C1 JLKOIZFBCUOQFJ-TYIWYJSASA-N 0.000 claims 1
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- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 150000004967 organic peroxy acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([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
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- OAHKWDDSKCRNFE-UHFFFAOYSA-N phenylmethanesulfonyl chloride Chemical compound ClS(=O)(=O)CC1=CC=CC=C1 OAHKWDDSKCRNFE-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 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
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960002310 pinacidil Drugs 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920002721 polycyanoacrylate Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940072254 proscar Drugs 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- OHZYAOYVLLHTGW-UHFFFAOYSA-N pyrido[3,2-c]pyridazine Chemical compound C1=CN=NC2=CC=CN=C21 OHZYAOYVLLHTGW-UHFFFAOYSA-N 0.000 description 1
- BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical compound C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 description 1
- JOZPEVMCAKXSEY-UHFFFAOYSA-N pyrimido[5,4-d]pyrimidine Chemical compound N1=CN=CC2=NC=NC=C21 JOZPEVMCAKXSEY-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 231100000161 signs of toxicity Toxicity 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000001476 sodium potassium tartrate Substances 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 229940114926 stearate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- YRZGMTHQPGNLEK-UHFFFAOYSA-N tetradecyl propionate Chemical compound CCCCCCCCCCCCCCOC(=O)CC YRZGMTHQPGNLEK-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- LWRYDHOHXNQTSK-UHFFFAOYSA-N thiophene oxide Chemical compound O=S1C=CC=C1 LWRYDHOHXNQTSK-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 239000012780 transparent material Substances 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229910000859 α-Fe Inorganic materials 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- 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
-
- 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
- A61P5/28—Antiandrogens
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US14115393A | 1993-10-21 | 1993-10-21 | |
PCT/US1994/012071 WO1995011254A1 (en) | 1993-10-21 | 1994-10-21 | 16-substituted-4-aza-androstane 5-alpha-reductase isozyme 1 inhibitors |
Publications (2)
Publication Number | Publication Date |
---|---|
SK49696A3 SK49696A3 (en) | 1996-10-02 |
SK281645B6 true SK281645B6 (sk) | 2001-06-11 |
Family
ID=22494410
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK496-96A SK281645B6 (sk) | 1993-10-21 | 1994-10-21 | 16-substituované-4-azaandrostanové deriváty, farmaceutické prostriedky s ich obsahom a ich použitie |
Country Status (29)
Country | Link |
---|---|
US (4) | US5739137A (de) |
EP (1) | EP0724592B1 (de) |
JP (1) | JP2862376B2 (de) |
KR (1) | KR100363994B1 (de) |
CN (1) | CN1058499C (de) |
AT (1) | ATE175420T1 (de) |
BG (1) | BG61978B1 (de) |
BR (2) | BR9407866A (de) |
CA (1) | CA2173863C (de) |
CY (1) | CY2136B1 (de) |
CZ (1) | CZ292614B6 (de) |
DE (1) | DE69415824T2 (de) |
DK (1) | DK0724592T3 (de) |
ES (1) | ES2125495T3 (de) |
FI (1) | FI961697A (de) |
HK (1) | HK1009047A1 (de) |
HU (1) | HUT74613A (de) |
IL (1) | IL111357A (de) |
LV (2) | LV11622B (de) |
NO (1) | NO308037B1 (de) |
NZ (1) | NZ275293A (de) |
PL (1) | PL179611B1 (de) |
RO (1) | RO116197B1 (de) |
RU (1) | RU2142956C1 (de) |
SK (1) | SK281645B6 (de) |
TW (1) | TW413682B (de) |
UA (1) | UA44257C2 (de) |
WO (1) | WO1995011254A1 (de) |
ZA (1) | ZA948285B (de) |
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5547957A (en) | 1993-10-15 | 1996-08-20 | Merck & Co., Inc. | Method of treating androgenic alopecia with 5-α reductase inhibitors |
US5739137A (en) * | 1993-10-21 | 1998-04-14 | Merck & Co., Inc. | 16-substituted-4-aza-3-oxo-androstane as 5-alpha-reductase isozyme 1 inhibitors |
US5470976A (en) * | 1994-09-07 | 1995-11-28 | Merck & Co., Inc. | Process for the stereoselective reduction of steroid enelactams |
US5543417A (en) * | 1994-10-21 | 1996-08-06 | Merck & Co., Inc. | Combination method of treating acne using 4-AZA-5α-cholestan-ones and 4-AZA-5α-androstan-ones as selective 5α-reductase inhibitors with anti-bacterial, keratolytic, or anti-inflammatory agents |
JPH10508586A (ja) * | 1994-10-21 | 1998-08-25 | メルク エンド カンパニー インコーポレーテッド | 組み合わせ式アクネ治療方法 |
US5886005A (en) * | 1995-01-17 | 1999-03-23 | Merck & Co., Inc. | 4-Aza-19-norandrostane derivatives |
WO1997014418A1 (en) * | 1995-10-19 | 1997-04-24 | Merck & Co., Inc. | 16-substituted-6-aza-steroid 5-alpha-reductase inhibitors |
US5872126A (en) * | 1996-09-06 | 1999-02-16 | Merck & Co., Inc. | Methods and compositions for treating preterm labor |
US5945412A (en) * | 1996-12-09 | 1999-08-31 | Merck & Co., Inc. | Methods and compositions for preventing and treating bone loss |
EP1009740A1 (de) * | 1997-03-17 | 2000-06-21 | Merck & Co., Inc. | Verfahren und zubereitungen zur behandlung von eierstockzysten |
US5935968A (en) | 1997-03-17 | 1999-08-10 | Merck & Co., Inc. | Methods for treating polycystic ovary syndrome |
US5942519A (en) * | 1997-10-28 | 1999-08-24 | Merck & Co., Inc. | Prevention of precipitated acute urinary retention |
US6187925B1 (en) | 1997-12-23 | 2001-02-13 | Merck & Co., Inc. | Intermediates and process for the synthesis of azasteroids |
AR016257A1 (es) * | 1998-05-14 | 2001-06-20 | Merck & Co Inc | Proceso para la sintesis estereoselectiva de ariloxi-4-aza-5alfa-androstan-3-onas, 16 alfa y 16 beta-sustituidas e insustituidas, e intermediariosobtenidos en dicho proceso. |
WO1999058550A1 (en) * | 1998-05-14 | 1999-11-18 | Merck & Co., Inc. | 7beta-methyl-16beta-((4-methylsulfonyl)-phenoxy)-4-aza-5alpha-androst-1-en-3-one as a 5-alpha-reductase isozyme 1 inhibitor |
US6462019B1 (en) | 1998-07-10 | 2002-10-08 | Osteoscreen, Inc. | Inhibitors of proteasomal activity and production for stimulating bone growth |
US6838436B1 (en) | 1998-07-10 | 2005-01-04 | Osteoscreen Inc. | Inhibitors of proteasomal activity for stimulating bone growth |
US6902721B1 (en) | 1998-07-10 | 2005-06-07 | Osteoscreen, Inc. | Inhibitors of proteasomal activity for stimulating bone growth |
CA2338298A1 (en) * | 1998-07-29 | 2000-02-10 | Merck & Co., Inc. | Tricyclic compounds |
US6268377B1 (en) | 1998-09-28 | 2001-07-31 | Merck & Co., Inc. | Method for treating androgen-related conditions |
WO2002054996A2 (en) * | 2000-10-23 | 2002-07-18 | Euro Celtique Sa | Terazosin transdermal device and methods |
EP2305352A1 (de) * | 2004-04-02 | 2011-04-06 | Merck Sharp & Dohme Corp. | 5-alpha-Reduktaseinhibitoren zur Behandlung von Stoffwechsel- und anthropometrischen Störungen |
EP2371367A1 (de) | 2005-03-25 | 2011-10-05 | Merck Sharp & Dohme (I.A.) Corp. | Verfahren zur Behandlung von Männern mit Testosteronergänzung und Alpha-Reduktase-Hemmer |
US20060241696A1 (en) * | 2005-04-26 | 2006-10-26 | Stjepan Krco | Method of limiting hair loss and promoting hair growth |
FR2910002B1 (fr) * | 2006-12-13 | 2009-01-30 | Sanofi Aventis Sa | Nouveau procede pour l'obtention diastereoselective d'une amine primaire chirale sur un steroide |
GB201102913D0 (en) | 2011-02-18 | 2011-04-06 | Univ Birmingham | Novel therapeutic |
TWI593411B (zh) | 2013-04-30 | 2017-08-01 | 徐懷山 | 組合物於製備抑制雄性素受體有關之功能及治療雄性素 受體相關之疾病的藥物之用途 |
Family Cites Families (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4377584A (en) * | 1978-04-13 | 1983-03-22 | Merck & Co., Inc. | 4-Aza-17β-substituted-5α-androstan-3-one-reductase inhibitors |
AU527030B2 (en) * | 1978-04-13 | 1983-02-10 | Merck & Co., Inc. | 4-aza-17-substituted-5a-androstan-3-ones |
US4220775A (en) * | 1979-03-15 | 1980-09-02 | Merck & Co., Inc. | Preparation of 4-aza-17-substituted-5α-androstan-3-ones useful as 5α-reductase inhibitors |
US5120742A (en) * | 1984-02-27 | 1992-06-09 | Merck & Co., Inc. | 17 β-acyl-4-aza-5 α-androst-1-ene-3-ones as 5 α-reductase inhibitors |
US5049562A (en) * | 1984-02-27 | 1991-09-17 | Merck & Co., Inc. | 17β-acyl-4-aza-5α-androst-1-ene-3-ones as 5α-reductase inhibitors |
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1994
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- 1994-10-21 HU HU9601037A patent/HUT74613A/hu unknown
- 1994-10-21 CZ CZ19961228A patent/CZ292614B6/cs unknown
- 1994-10-21 BR BR9407866A patent/BR9407866A/pt not_active Application Discontinuation
- 1994-10-21 CN CN94194344A patent/CN1058499C/zh not_active Expired - Fee Related
- 1994-10-21 NZ NZ275293A patent/NZ275293A/en unknown
- 1994-10-21 JP JP7512223A patent/JP2862376B2/ja not_active Expired - Fee Related
- 1994-10-21 IL IL11135794A patent/IL111357A/en not_active IP Right Cessation
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- 1994-10-21 DE DE69415824T patent/DE69415824T2/de not_active Expired - Fee Related
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- 1994-10-21 RO RO96-00835A patent/RO116197B1/ro unknown
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- 1994-10-21 WO PCT/US1994/012071 patent/WO1995011254A1/en active IP Right Grant
- 1994-10-21 ES ES94931961T patent/ES2125495T3/es not_active Expired - Lifetime
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1995
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