EP1322663A1 - Neue polymorphe form von 17-beta-(n-ter.butyl carbamoyl)-4-aza-5- g(a)-androst-1-en-3-one und ein verfahren zur ihrer herstellung - Google Patents
Neue polymorphe form von 17-beta-(n-ter.butyl carbamoyl)-4-aza-5- g(a)-androst-1-en-3-one und ein verfahren zur ihrer herstellungInfo
- Publication number
- EP1322663A1 EP1322663A1 EP01948467A EP01948467A EP1322663A1 EP 1322663 A1 EP1322663 A1 EP 1322663A1 EP 01948467 A EP01948467 A EP 01948467A EP 01948467 A EP01948467 A EP 01948467A EP 1322663 A1 EP1322663 A1 EP 1322663A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- aza
- ter
- androst
- butyl carbamoyl
- solvent
- 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.)
- Ceased
Links
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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P5/28—Antiandrogens
Definitions
- the present invention relates to a novel polymorphic form of 17- ⁇ -(N-ter. butyl carbamoyl)-4-aza-5- -androst-l-en-3-one (Finasteride) of the formula (I)
- the present invention also relates to process for preparing the novel polymorphic form of 17- ⁇ -(N-ter. butyl carbamoyl)-4-aza-5- ⁇ -androst-l-en-3-one of the formula (I).
- the polymorphic form of 17- ⁇ -(N-ter. butyl carbamoyl)-4-aza-5- ⁇ - androst-l-en-3-one (5-alpha reductase inhibitor) is useful in treating acne, female hirsutism and particularly benign prostatic hyperplasia.
- Polymorphism can be defined as the ability of the same chemical substance to exist in different crystalline structures.
- the different structures are are referred to as polymorphs, polymorphic modification or form.
- the polymorphic form-I is characterized by a differential scanning calorimetry (DSC) curve, at heating rate of 20°C/min and in a closed cup, exhibiting a minor endotherm with a peak temperature of about 232°C; an extrapolated onset temperature of about 223°C with an associated heat of about 11 joules / gm and by a major melting endotherm with a peak temperature of about of 261°C; an extrapolated onset temperature of about 258°C with an associated heat of about 89 J / gm.
- the X-ray powder diffraction pattern is characterized by d-spacings of 6.44, 5.69, 5.36, 4.89, 4.55,
- the polymorphic form-II is characterized by a differential scanning calorimetry (DSC) curve, at heating rate of 20°C / min and in a closed cup, exhibiting a single melting endotherm with a peak temperature of about 261°C; an extrapolated onset temperature of about 258°C, with an associated heat of about 89 J/g.
- the X-ray powder diffraction pattern is characterized by d-spacings of 14.09, 10.36, 7.92, 7.18, 6.40, 5.93, 5.66, 5.31, 4.68, 3.90, 3.60 and 3.25.
- the FT-IR spectrum (in KBr) shows bands at 3441, 3215, 1678, 1654, 1597, 1476 and 752 cm-1.
- the two polymorphic forms referred as 1 and 2 are same as the Form-I and Form- II mentioned above.
- the lattice contains one molecule of acetic acid. It decomposes losing acetic acid and recrystallizes in the range 170-174°C having melting point 255-257°C.
- the lattice contains one molecule of ethyl acetate for two molecules of Finasteride.
- the melting point of form lb is reported as 252-255°C. While doing process development to optimize the yield and quality of 17- ⁇ -(N-ter. butyl carbamoyl)-4-aza-5- ⁇ -androst-l-en-3-one, different crystallization and isolation methods were used with different combinations of organic solvents and by varying the various parameters like temperature and volume etc.
- Form-V which are different from Form-I and Form-II disclosed in the prior art.
- Fig-1 Differential scanning calorimetry of Form-Ill.
- Fig-2 X-Ray powder diffractogram of Form-Ill.
- the present invention provides a novel polymorphic form
- DSC exhibits a melting endotherm with a peak temperature of about 262°C and preceded by another minor endotherm at about 245°C and an exotherm at about 253°C.
- the present invention provides a novel polymorphic form
- DSC exhibits a melting endotherm with a peak temperature of about
- Form -IN of 17- ⁇ -( ⁇ -ter. butyl carbamoyl)-4-aza-5- ⁇ -androst-l-en-3-one can be prepared by a process, which comprises: (i) preparing a slurry of 17- ⁇ -(N-ter. butyl carbamoyl)-4-aza-5- - androst-l-en-3-one in ethyl acetate, tetrahydrofuran and water mixture such that the ratio of ethyl acetate:tetrahydrofuran : water is 1:1: ⁇ 0.1 and the ratio of this solvent mixture used is 1-3 volume/weight of 17- ⁇ -(N-ter. butyl carbamoyl)-4-aza-5- -androst-l-en-3- one;
- Form-N of 17- ⁇ -( ⁇ -ter. butyl carbamoyl)-4-aza-5- ⁇ -androst-l-en-3-one of formula (I), can be prepared by a process which comprises:
- the water immiscible organic solvent used in the process of preparing Form-Ill of 17- ⁇ -(N-ter. butyl carbamoyl)-4-aza-5- ⁇ -androst-l-en-3-one include any solvents such as halogenated solvent selected from dichloromethane or chloroform or aromatic hydrocarbon solvent preferably toluene or organic solvents selected from alkyl acetates preferably ethyl acetate.
- the amount of aromatic hydrocarbon solvent is 25-50 volume/weight of 17- ⁇ -(N- ter. butyl carbamoyl)-4-aza-5- ⁇ -androst-l-en-3-one.
- the alkyl acetate solvent is 10-20 volume/weight of 17- ⁇ -(N-ter. butyl carbamoyl)-4-aza- 5- ⁇ -androst-l-en-3-one.
- the solvent selected are those in which 17- ⁇ -(N-ter. butyl carbamoyl)-4- aza-5- ⁇ -androst-l-en-3-one can be dissolved at room temperature (25-35° C) as in the case of halogenated solvents or else at elevated temperatures preferably at 40-50°C, as in case of aromatic hydrocarbon solvent or organic solvents selected from alkyl acetates, until dissolution is achieved.
- polar organic solvents as used herein are meant to include solvents selected from C5-C10 aliphatic hydrocarbons either straight chain or branched, preferably hexane or heptane or petroleum ether, which precipitate 17- ⁇ -(N-ter. butyl carbamoyl)-4- aza-5- ⁇ -androst-l-en-3-one from the solution.
- the step of saturating with a less polar organic solvent is carried out at a temperature in the range of 25-60 °C.
- Trifluoroacetamide (2.5 gm) in toluene (25 ml) medium at 80-110°C. After completion of reaction, toluene layer was washed with 5-10% aqueous sodium sulphite solution (80 ml), and then with water (200ml). The toluene is stripped under vacuum to yield residual solid that is crude Finasteride.
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06019093A EP1790653A3 (de) | 2000-09-07 | 2001-06-19 | Neue polymorphe Form von 17-beta-(n-ter.butyl carbomyol)-4-aza-5- alpha-androst-1-en-3-one und ein Verfahren zu ihrer Herstellung |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
INDE073700 | 2000-09-07 | ||
IN737DE2000 | 2000-09-07 | ||
PCT/US2001/019546 WO2002020553A1 (en) | 2000-09-07 | 2001-06-19 | NOVEL POLYMORPHIC FORM OF 17-β-(N-TER.BUTYL CARBAMOYL)-4-AZA-5-α-ANDROST-1-EN-3-ONE AND A PROCESS FOR PREPARING IT |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP06019093A Division EP1790653A3 (de) | 2000-09-07 | 2001-06-19 | Neue polymorphe Form von 17-beta-(n-ter.butyl carbomyol)-4-aza-5- alpha-androst-1-en-3-one und ein Verfahren zu ihrer Herstellung |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1322663A1 true EP1322663A1 (de) | 2003-07-02 |
Family
ID=11097081
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP01948467A Ceased EP1322663A1 (de) | 2000-09-07 | 2001-06-19 | Neue polymorphe form von 17-beta-(n-ter.butyl carbamoyl)-4-aza-5- g(a)-androst-1-en-3-one und ein verfahren zur ihrer herstellung |
Country Status (12)
Country | Link |
---|---|
EP (1) | EP1322663A1 (de) |
JP (1) | JP2004508380A (de) |
AU (1) | AU6991101A (de) |
BR (1) | BR0113732A (de) |
CA (1) | CA2422159A1 (de) |
HU (1) | HUP0300937A3 (de) |
IL (1) | IL154785A0 (de) |
NO (1) | NO20031045L (de) |
NZ (1) | NZ525116A (de) |
PL (1) | PL361014A1 (de) |
WO (1) | WO2002020553A1 (de) |
ZA (1) | ZA200302554B (de) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2206065B1 (es) * | 2002-10-31 | 2005-08-16 | Ragactives, S.L. | Procedimiento para la obtencion de la forma polimorfica i de finasterida. |
DE602004016170D1 (de) * | 2003-07-03 | 2008-10-09 | Cipla Ltd | Verfahren zur herstellung von finasterid form i |
CN1294913C (zh) * | 2004-12-23 | 2007-01-17 | 鲁南制药集团股份有限公司 | 含有非那雄胺与环糊精或其衍生物的药物组合物 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NZ225100A (en) * | 1987-06-29 | 1991-09-25 | Merck & Co Inc | Reaction of steroids (including 4-azasteroids) with a silylating agent in the presence of a quinone to introduce a delta' double bond and silylated intermediates |
US5237061A (en) * | 1988-10-31 | 1993-08-17 | Merck & Co., Inc. | Methods of synthesizing benign prostatic hypertropic agents and their intermediates |
US5021575A (en) * | 1989-11-13 | 1991-06-04 | Merck & Co., Inc. | Method for introducing a 1,2 double bond into azasteroids |
US5091534A (en) * | 1990-08-27 | 1992-02-25 | Merck & Co., Inc. | Trialkylsilyl trifluoromethanesulfonate mediated α-methylenic carbon functionalization of 4-AZA-5α-androstan-3-one steroids |
US5468860A (en) * | 1992-11-19 | 1995-11-21 | Merck & Co., Inc. | New finasteride processes |
-
2001
- 2001-06-19 JP JP2002525173A patent/JP2004508380A/ja not_active Withdrawn
- 2001-06-19 CA CA002422159A patent/CA2422159A1/en not_active Abandoned
- 2001-06-19 PL PL01361014A patent/PL361014A1/xx not_active Application Discontinuation
- 2001-06-19 NZ NZ525116A patent/NZ525116A/en unknown
- 2001-06-19 EP EP01948467A patent/EP1322663A1/de not_active Ceased
- 2001-06-19 BR BR0113732-8A patent/BR0113732A/pt not_active Application Discontinuation
- 2001-06-19 IL IL15478501A patent/IL154785A0/xx unknown
- 2001-06-19 AU AU6991101A patent/AU6991101A/xx active Pending
- 2001-06-19 WO PCT/US2001/019546 patent/WO2002020553A1/en not_active Application Discontinuation
- 2001-06-19 HU HU0300937A patent/HUP0300937A3/hu unknown
-
2003
- 2003-03-06 NO NO20031045A patent/NO20031045L/no not_active Application Discontinuation
- 2003-04-01 ZA ZA200302554A patent/ZA200302554B/en unknown
Non-Patent Citations (1)
Title |
---|
See references of WO0220553A1 * |
Also Published As
Publication number | Publication date |
---|---|
NZ525116A (en) | 2004-11-26 |
NO20031045L (no) | 2003-04-29 |
AU6991101A (en) | 2002-03-22 |
HUP0300937A2 (en) | 2007-02-28 |
BR0113732A (pt) | 2003-07-29 |
JP2004508380A (ja) | 2004-03-18 |
CA2422159A1 (en) | 2002-03-14 |
PL361014A1 (en) | 2004-09-20 |
HUP0300937A3 (en) | 2007-10-29 |
NO20031045D0 (no) | 2003-03-06 |
ZA200302554B (en) | 2004-02-19 |
WO2002020553A1 (en) | 2002-03-14 |
IL154785A0 (en) | 2003-10-31 |
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Legal Events
Date | Code | Title | Description |
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PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
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17P | Request for examination filed |
Effective date: 20030401 |
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AK | Designated contracting states |
Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE TR |
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AX | Request for extension of the european patent |
Extension state: AL LT LV MK RO SI |
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17Q | First examination report despatched |
Effective date: 20041206 |
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STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED |
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18R | Application refused |
Effective date: 20061021 |