WO1994011385A1 - 17-alpha-acyl steroids which inhibit 5-alpha-reductase - Google Patents
17-alpha-acyl steroids which inhibit 5-alpha-reductase Download PDFInfo
- Publication number
- WO1994011385A1 WO1994011385A1 PCT/US1993/011235 US9311235W WO9411385A1 WO 1994011385 A1 WO1994011385 A1 WO 1994011385A1 US 9311235 W US9311235 W US 9311235W WO 9411385 A1 WO9411385 A1 WO 9411385A1
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- WIPO (PCT)
- Prior art keywords
- androst
- butylcarboxamide
- salt
- diisopropylcarboxamide
- ene
- Prior art date
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- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 150000001993 dienes Chemical class 0.000 description 1
- 238000001085 differential centrifugation Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000012886 linear function Methods 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000017497 prostate disease Diseases 0.000 description 1
- 201000004240 prostatic hypertrophy Diseases 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229940107889 rogaine Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000001732 sebaceous gland Anatomy 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
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- MKWYFZFMAMBPQK-UHFFFAOYSA-J sodium feredetate Chemical compound [Na+].[Fe+3].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O MKWYFZFMAMBPQK-UHFFFAOYSA-J 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction 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
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 229940100613 topical solution Drugs 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 208000019553 vascular disease Diseases 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
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0038—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 with an androstane skeleton, including 18- or 19-substituted derivatives, 18-nor derivatives and also derivatives where position 17-beta is substituted by a carbon atom not directly bonded to a further carbon atom and not being part of an amide group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0072—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the A ring of the steroid being aromatic
Definitions
- substituted alkyl is linear or branched C]_-Ci2 substituted with one or more substituents selected from the group consisting of: aryl, acyloxy, amino, N- acylamino, oxo, carboxyalkyl, halogen and protected -OH;
- cycloalkyl is nonaromatic, unsaturated or saturated, cyclic or polycyclic C3-C12, optionally containing one or more heteroatoms, and optionally substituted with one or more substituents selected from the group consisting of: aryl, hydroxyalkyl, alkyl, alkoxy, acyloxy, amino, N-acylamino, oxo, carboxyalkyl, halogen and protected -OH; and
- aryl is cyclic or polycyclic aromatic C3-C12, optionally containing one or more heteroatoms, provided that when C is 3 the aromatic ring contains at least two heteroatoms and when C is 4 the aromatic ring contains at
- ⁇ -eipmer as used herein is meant that the 17 ⁇ -acyl substituent of the steroidal 5 ⁇ reductase inhibitors disclosed herein as starting material is transformed to the ⁇ -position.
- Preferred compounds of the invention and compounds used in the invented pharmaceutical compositions and the invented methods include:
- cycloalkyl and substituted cycloalkyl as used herein include: cyclohexyl, 4-hydroxy- cyclohexyl, ethylcyclohexyl, propyl 4-methoxycyclohexyl, 4-methoxycyclohexyl, 4-carboxycyclohexyl and cyclopentyl.
- halogen as used herein is meant a substituent selected from bromide, iodide, chloride and fluoride.
- alkyl and “alkylidene” and derivatives thereof and in all carbon chains as used herein is meant a linear or branched monovalent or divalent carbon chain having C ⁇ -C ⁇ carbons. Examples of alkyl as used herein indued: -CH3, -CH2-CH3, -CH2- CH 2 -CH 3 , -CH(CH 3 ) 2 , -C(CH 3 ) 3 , -(CH 2 )3-CH3, -CH 2 -
- Chemically alfuzosin is designated as N-[3-[(4- amino-6,7-dimethoxy-2-quinazolinyl)methylamino]- propyl]tetrahydro-2-furancarboxamide.
- Minoxidil is designated as 2,4- pyrimidineadiamine, 6- (1-piperidinyl) -,3-oxide.
- Minoxidil is the active ingredient in Rogaine® which is sold as topical solution for stimulating hair growth by the Upjohn Company, Kalamazoo, Michigan.
- Parenteral administration which uses lower dosages is preferred. Parenteral administration, at high dosages, however, also can be used when safe and convenient for the patient.
- Fraction 1 All of the fractions designated Fraction 1, were combined and concentrated to approximately 1000 mL. The volume was divided and lyophylized. A methanolic solution of the residue from each flask was diluted to approximately 50 mL, and water added until the solution was cloudy ( ⁇ 25 mL) . Each cloudy solution was allowed to sit at room temperature overnight during which time the sample crystallized. The mixtures were filtered and the residues washed with water and dried in a vacuum oven at 60°C for 16 hours
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP94902304A EP0669931A1 (en) | 1992-11-18 | 1993-11-18 | 17-alpha-acyl steroids which inhibit 5-alpha-reductase |
| JP6512505A JPH08503473A (ja) | 1992-11-18 | 1993-11-18 | ５−アルファ−レダクターゼを阻害する１７−アルファーアシルステロイド |
| US08/436,292 US5561124A (en) | 1992-11-18 | 1993-11-18 | 17-α-acyl steroids which inhibit 5-α-reductase |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB929224148A GB9224148D0 (en) | 1992-11-18 | 1992-11-18 | Compounds |
| GB9224148.8 | 1992-11-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1994011385A1 true WO1994011385A1 (en) | 1994-05-26 |
Family
ID=10725271
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1993/011235 WO1994011385A1 (en) | 1992-11-18 | 1993-11-18 | 17-alpha-acyl steroids which inhibit 5-alpha-reductase |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0669931A1 (enrdf_load_stackoverflow) |
| JP (1) | JPH08503473A (enrdf_load_stackoverflow) |
| GB (1) | GB9224148D0 (enrdf_load_stackoverflow) |
| WO (1) | WO1994011385A1 (enrdf_load_stackoverflow) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US5618806A (en) * | 1992-04-30 | 1997-04-08 | Smithkline Beecham Corporation | 17α and 17β-substituted estra-1,3,5(10)-triene-3-carbboxlic acid |
| US5641877A (en) * | 1992-11-18 | 1997-06-24 | Smithkline Beecham Corporation | 17-α and 17-β substituted acyl-3-carboxy-3, 5-dienes and use in inhibiting 5-α-reductase |
| US5683995A (en) * | 1992-11-18 | 1997-11-04 | Smithkline Beecham Corporation | 17 substituted acyl-3-carboxy 3,5-diene steroidals as α-reductase inhibitors |
| US5843953A (en) * | 1994-10-25 | 1998-12-01 | Merck & Co., Inc. | 7-substituted 4-aza cholanic acid derivatives and their use |
| US6645974B2 (en) | 2001-07-31 | 2003-11-11 | Merck & Co., Inc. | Androgen receptor modulators and methods for use thereof |
| USRE39056E1 (en) | 1995-09-15 | 2006-04-04 | Merck & Co, Inc. | 4-Azasteroids for treatment of hyperandrogenic conditions |
| LU102470A1 (en) * | 2020-03-16 | 2021-11-09 | Jiangsu Lianhuan Pharmaceutical Co Ltd | Epristeride impurity and preparation method and application thereof |
| CN113831387A (zh) * | 2021-10-18 | 2021-12-24 | 湖南科瑞生物制药股份有限公司 | 非那雄胺异构体17α-非那雄胺的制备方法 |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19750073A1 (de) * | 1997-11-12 | 1999-05-20 | Bosch Gmbh Robert | Schaltungsträgerplatte |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4970204A (en) * | 1989-08-23 | 1990-11-13 | Smithkline Beecham Corporation | 3-substituted nitro-steroid derivatives as 5-α-reductase inhibitors |
| US4970199A (en) * | 1987-06-18 | 1990-11-13 | Merck & Co., Inc. | Steroidal glycolipids as host resistance stimulators against viral infection |
| US5100917A (en) * | 1989-12-29 | 1992-03-31 | Merrell Dow Pharmaceuticals Inc. | Novel a-nor-steroid-3-carboxylic acid derivatives |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4039669A (en) * | 1975-08-01 | 1977-08-02 | Sterling Drug Inc. | Composition for topical application and use thereof |
| ES2105108T3 (es) * | 1992-04-20 | 1997-10-16 | Sankyo Co | Esteroides para el tratamiento de la hipertrofia prostatica, su preparacion y su utilizacion. |
-
1992
- 1992-11-18 GB GB929224148A patent/GB9224148D0/en active Pending
-
1993
- 1993-11-18 EP EP94902304A patent/EP0669931A1/en not_active Withdrawn
- 1993-11-18 WO PCT/US1993/011235 patent/WO1994011385A1/en not_active Application Discontinuation
- 1993-11-18 JP JP6512505A patent/JPH08503473A/ja active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4970199A (en) * | 1987-06-18 | 1990-11-13 | Merck & Co., Inc. | Steroidal glycolipids as host resistance stimulators against viral infection |
| US4970204A (en) * | 1989-08-23 | 1990-11-13 | Smithkline Beecham Corporation | 3-substituted nitro-steroid derivatives as 5-α-reductase inhibitors |
| US5100917A (en) * | 1989-12-29 | 1992-03-31 | Merrell Dow Pharmaceuticals Inc. | Novel a-nor-steroid-3-carboxylic acid derivatives |
Non-Patent Citations (5)
| Title |
|---|
| Journal of Chromatography, Volume 631, issued 1993, BOPPANA et al., "Normal-Phase High-Performance Liquid Chromatography Determination of Epristeride, a Prostatic Steroid 5-alpha-Reductase Enzyme Inhibitor, in Human Plasma", pages 251-254, entire document. * |
| Journal of Medicinal Chemistry, Volume 33, No. 3, issued 1990, HOLT et al., "Inhibition of Steroid 5-alpha-Reductase by Unsaturated 3-Carboxysteroids", pages 943-950, entire document. * |
| Journal of Medicinal Chemistry, Volume 33, No. 3, issued 1990, HOLT et al., "Steroidal A Ring Aryl Carboxylic Acids: A New Class of Steroid 5-alpha-Reductase Inhibitors", pages 937-942, entire document. * |
| Journal of Steroid Biochemistry and Molecular Biology, Volume 37, No. 4, issued 1990, BRANDT et al., "Studies on the Mechanism of Steroid 5-alpha-Reductase Inhibition by 3-Carboxy A-Ring Aryl Steroids", pages 575-579, entire document. * |
| See also references of EP0669931A4 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5618806A (en) * | 1992-04-30 | 1997-04-08 | Smithkline Beecham Corporation | 17α and 17β-substituted estra-1,3,5(10)-triene-3-carbboxlic acid |
| US5641877A (en) * | 1992-11-18 | 1997-06-24 | Smithkline Beecham Corporation | 17-α and 17-β substituted acyl-3-carboxy-3, 5-dienes and use in inhibiting 5-α-reductase |
| US5641765A (en) * | 1992-11-18 | 1997-06-24 | Smithkline Beecham Corporation | 17-αand 17-βsubstituted acyl-3-carboxy-3,5-dienes and use in inhibiting 5-α-reductase |
| US5683995A (en) * | 1992-11-18 | 1997-11-04 | Smithkline Beecham Corporation | 17 substituted acyl-3-carboxy 3,5-diene steroidals as α-reductase inhibitors |
| 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 |
| US5843953A (en) * | 1994-10-25 | 1998-12-01 | Merck & Co., Inc. | 7-substituted 4-aza cholanic acid derivatives and their use |
| USRE39056E1 (en) | 1995-09-15 | 2006-04-04 | 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 |
| LU102470A1 (en) * | 2020-03-16 | 2021-11-09 | Jiangsu Lianhuan Pharmaceutical Co Ltd | Epristeride impurity and preparation method and application thereof |
| CN113831387A (zh) * | 2021-10-18 | 2021-12-24 | 湖南科瑞生物制药股份有限公司 | 非那雄胺异构体17α-非那雄胺的制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| GB9224148D0 (en) | 1993-01-06 |
| JPH08503473A (ja) | 1996-04-16 |
| EP0669931A1 (en) | 1995-09-06 |
| EP0669931A4 (enrdf_load_stackoverflow) | 1995-10-04 |
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