- Refining and decolorizing method of finasteride
-
The invention provides a refining and decolorizing method of finasteride. A mixed solution of sodium borohydride and a reducing sulfate is used to convert 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) residual in finasteride dehydrogenation steps into reduction-state dichlorocyano hydroquinone (DDHQ), and the DDHQ is finally converted into a salt under an alkaline condition to be removed, so that the mode that repeated solvent refining or column-chromatography decoloration is needed in a conventional process is avoided, and the product yield and production efficiency are greatly improved. Finasteride obtained by the method is a white solid, the yield can reach 93%, and the quality meets the newest pharmacopeia standard.
- -
-
Paragraph 0025-0038
(2019/10/01)
-
- Method for forming double bonds between 1-position and 2-position during synthesis of finasteride and dutasteride
-
The invention provides a method for forming double bonds between the 1-position and the 2-position during synthesis of finasteride and dutasteride. According to the process, a dihydrogen finasteride iodide and a dihydrogen dutasteride iodide are oxidized by oxone for systhesis of finasteride and dutasteride, and the method has the characteristics that reaction operation is simple and convenient, raw materials are low in price and easy to obtain, and the yield and the purity are high. In particular, oxone is non-toxic, stable, easy to operate and more suitable for large-scale industrial production, and reagents which are harmful to the environment and high in price are avoided. The method can be further applied to forming of double bonds between the 1-position and the 2-position of an intermediate in other finasteride and dutasteride processes. The invention further provides a synthesis method of dihydrogen dutasteride; according to the method, a corresponding ester raw material has a one-pot reaction with 2,5-bis(trifluoromethyl)aniline under the activation of boron tribromide, and dihydrogen dutasteride with the yield of 93% is obtained.
- -
-
Paragraph 0052; 0053
(2016/12/01)
-
- Impurities in finasteride: Identification, synthesis, characterization and control of potential carry-over impurities from reagents used for the process
-
An assessment of the impurity profile of finasteride and possible carry-over related substances likely to arise during the synthesis of finasteride is described in this article. Impurities in reaction mass were monitored by HPLC, potential impurities isolated with preparative HPLC and structures were substantiated by 1H NMR, MS and MS-MS. Impurities RRT's were established by HPLC co-injection. Based on the spectral data structure of impurity I and impurity II were characterized as cyclohexyl and phenyl analog of finasteride.
- Mohanty, Sandeep,Kumar, B. Pavan,Karmakar, Arun Chandra
-
p. 4375 - 4380
(2014/08/05)
-
- Crystallization engineering in aza-steroid: Application in the development of finasteride
-
Novel and robust crystallization approach based on solid solution formation was developed for the purification of finasteride. This is an unprecedented approach that describes the use of pure finasteride 1 to purify different lots of finasteride 1 (impure) contaminated with dihydrofinasteride 2.
- Bhattacharya, Apurba,Manudhane, Kushal S,Maddula, Srinivasula Reddy,Sreekanth,Thota, Sridhar,Bandichhor, Rakeshwar
-
p. 599 - 602
(2013/06/05)
-
- TOPICAL COMPOSITIONS COMPRISING 5-ALPHA REDUCTASE INHIBITORS
-
The present invention relates to topical compositions comprising 5α-reductase inhibitors. The present invention also includes processes for preparation of such topical compositions and methods of using them.
- -
-
-
- PROCESS FOR THE PREPARATION OF 17-N-SUBSTITUTED-CARBAMOYL-4-AZA-ANDROST-1 -EN-3-ONES
-
The present invention relates to a process for producing 17-N-substituted-carbamoyl-4-aza-androst-1-en-3-ones of formula (1) , including Finasteride and Dutasteride.
- -
-
Page/Page column 15
(2008/12/08)
-
- Novel azaandrostane derivatives for the synthesis of 17β-(N-tert-butyl carbamoyl)-4-aza-5α-androst-1-ene-3-one
-
(Chemical Equation Presented) A new industrially viable process for the preparation of 17β-(N-tert-butyl carbamoyl)-4-aza-5α-androst-1-ene-3- one, also known by the generic name finasteride (6) from the new azaandrostane derivatives such as 17β-(N-tert-butyl carbamoyl)-4-benzoyl-4-aza-5α- androstane-3-one (4), 17β-(N-tert-butyl carbamoyl)-4-benzoyl-4-aza- 5α-androst-1-ene-3-one (5) is reported. In this process, benzoyl group is demonstrated as a novel protecting group for lactamic NH group. The structures of newly prepared compounds were established on the basis of spectral data (IR, 1H-NMR, and MS).
- Srinivasa Rao, Divvela V. N.,Trinadhachari, Ganala Naga,Prabahar, Koilpillai Joseph,Dandala, Ramesh,Sivakumaran, Meenakshisundaram,Naidu, Andra
-
p. 663 - 667
(2008/09/18)
-
- Process for the preparation of 17-N-substituted-carbamoyl-4-aza-androst-1-en-3-ones
-
The present invention relates to a process for producing 17-N-substituted-carbamoyl-4-aza-androst-1-en-3-ones of formula 1, including Finasteride and Dutasteride.
- -
-
Page/Page column 6
(2008/06/13)
-
- Facile water mediated synthesis of finasteride form-I, an azaandrostane steroid
-
A simple and efficient procedure for the selective synthesis of finasteride Form-I from bis-finasteride tetrahydrofuran monohydrate solvate in good yield using ecofriendly solvent water at ambient temperature is established. Powder X-Ray diffraction data (PXRD), and Differential scanning calorimetric (DSC) data of bis-finasteride tetrahydrofuran monohydrate solvate are given.
- Rao, Divvela V. N. Srinivasa,Trinadhachari, Ganala Naga,Lenin, Racha,Prabahar, Koilpillai Joseph,Naidu, Andra,Dandala, Ramesh
-
p. 121 - 124
(2008/02/12)
-
- PROCESSES TO PREPARE FINASTERIDE POLYMORPHS
-
Processes for preparing polymorphic crystalline Form I and Form III of finasteride.
- -
-
Page/Page column 4
(2010/11/27)
-
- Process for the preparation of pure finasteride
-
The present invention relates to an improved process for the preparation of pure Finasteride of Formula I, which comprises converting dihydrofinasteride to finasteride through novel protected dihydrofinasteride and protected finasteride intermediates.
- -
-
Page/Page column 3
(2008/06/13)
-
- New approach to 3-oxo-4-aza-5α-androst-1-ene-17β-(N-tert- butylcarboxamide)
-
We describe the synthesis of 3-oxo-4-aza-5α-androst-1-ene-17β- (N-tert-butylcarboxamide) (finasteride) from 4-androstene-3,17-dione (AD) in seven steps in an overall yield of 18.6% via oxidation, ammoniumation, dehydration, and dehydrogenation.
- Jiang, Zhong-Xing,Ye, Jing-Quan,Jiang, Li,Zhao, Ying-Sheng
-
p. 690 - 693
(2007/10/03)
-
- METHOD FOR PRODUCING 1,2-UNSATURATED AZASTEROIDS
-
The invention relates to a method for producing 1,2-unsaturated azasteroids of general formula (I), from a structurally related, saturated azasteroid of general formula (II).
- -
-
Page/Page column 8
(2008/06/13)
-
- METHOD FOR THE PREPARATION OF HIGHLY PURE 1-ANDROSTENE DERIVATIVES
-
A method for preparing a 1-androstene derivative which comprises reacting a 2-iodo-androstane derivative with an oxidizing agent while maintaining the pH of the reaction mixture at a specific range gives the 1-androstene derivative with high purity and yield.
- -
-
Page/Page column 12-14
(2008/06/13)
-
- METHOD OF OBTAINING POLYMORPHIC FORM I OF FINASTERIDE
-
The process comprises (i) dissolving finasteride in a substantially anhydrous organic solvent selected among n-butyl acetate, iso-butyl acetate, sec-butyl acetate, tert-butyl acetate, C5 alkyl acetate and mixtures thereof, at a temperature equal to or lower than the boiling point of said organic solvent; (ii) slowly cooling said finasteride solution to a cooling temperature determined on the basis of the chosen solvent; (iii) maintaining the resulting suspension at the cooling temperature for a period of time equal to or less than 16 hours; and (iv) recovering the resulting solid phase containing Form I of finasteride, for example by means of filtration, and removing the solvent, for example by means of drying said crystals. The process allows for obtaining the Form I of finasteride only and in a pure form.
- -
-
Page/Page column 4-5
(2008/06/13)
-
- PROCESS FOR THE PREPARATION OF 17?-SUBSTITUTED-3-OXO-4-AZA-5ALPHA-ANDROSTANE DERIVATIVES
-
Process for the preparation of 17?-substituted-3-oxo-4-aza-5α-androstane derivatives, which are useful intermediates for the synthesis of 3-oxo-4-aza-5α-androst-1-ene derivatives including finasteride, is provided.
- -
-
Page/Page column 8-9
(2008/06/13)
-
- METHOD OF PRODUCING 17BETA-(SUBSTITUTED)-3-OXO-DELTA 1,2-4-AZASTEROIDS AND INTERMEDIATES
-
The 17β-(substituted)-3-oxo-Δ1,2-azasteroids (I), wherein R1 is C1-C4 alkyl, OR2, wherein R2 is a C1-C4 alkyl radical, or NR3R4 , wherein R3 and R4, equal or different, represent hydrogen or a C1-C4 alkyl radical, can be obtained by means of a process comprising cleaving the oxazolidinedione ring present in a 2-(substituted)-3-hydroxyoxazolidinedione of formula (IV), wherein R5 is Br or trichloromethylsulfonyl, and removing the substituent at position 2, to form a double bond at position 1,2. Some compounds (I) are testosterone-5α-reductase inhibitors and can be used in the treatment of hyperandrogenic disorders.
- -
-
-
- Process for dehydrogenation of azaandrostane compounds
-
The invention relates to a process for the production of compounds of general formula (I), wherein R1is a —NH-tert-butyl group or a 4-methyl-piperidino group, by bioconversion of compounds of general formula (II), wherein R1is as described above, using a biocatalyst having steroid-Δ1-dehydrogenase enzyme activity, wherein the activity of the enzyme needed for the bioconversion is produced by induction.
- -
-
Page column 7
(2008/06/13)
-
- Method of prevention of prostatic carcinoma with 17β-N-monosubstituted-carbamoyl-4-aza-5α-androst-1-en-3-ones
-
17β-N-monosubstituted-carbamoyl-4-aza-5α-androst-1-en-3-ones of the formula wherein R1is selected from hydrogen, methyl and ethyl and R2is a straight or branched chain alkyl, cycloalkyl, aralkyl of from 1-12 carbons, or monocyclic aryl optionally containing 1 or more lower alkyl substituents of 1-2 carbon atoms and/or 1 or more halogens, and R′, R″, R″′ are hydrogen or methyl are useful for the prevention of prostatic carcinoma.
- -
-
-
- Process for obtaining 17 beta-(N-tert-butylcarbamoyl)-3-one4-aza-steroids
-
17β-(N-tert-butylcarbamoyl)-3-one-4-aza-steroids (I) can be obtained by a process which comprises the reaction of 17β-(alkoxycarbonyl)-3-one-4-aza-steroid with lithium tert-butylamide in an organic solvent. Some compounds of formula (I), for example, finasteride, are useful as inhibitors of 5α-reductase, and can be used in the treatment of benign prostatic hyperplasia and alopecia.
- -
-
-
- Method of treating androgenic alopecia with 5α-reductase inhibitors
-
The instant invention involves a method of treating and/or reversing androgenic alopecia and promoting hair growth, and methods of treating acne vulgaris, seborrhea, and female hirsutism, by administering to a patient in need of such treatment a 5α-reductase 2 inhibitor such as finasteride, in a dosage amount under 5 mgs/day.
- -
-
-
- Method of treatment for prostatic cancer
-
Disclosed is a new treatment for men with prostatic cancer involving combination therapy of a 5α-reductase inhibitor, i.e., a 17β-substituted 4-azasteroid, a 17β-substituted non-azasteroid, 17β-acyl-3-carboxyandrost-3,5-diene, benzoylaminophenoxybutanoic acid derivative, fused benz(thio)amide or cinnamoylamide derivative, aromatic 1,2-diethers or thioethers, aromatic ortho acylaminophenoxy alkanoic acids, ortho thioalkylacylamino-phenoxy alkanoic acids, pharmaceutically acceptable salts and esters thereof, and particularly finasteride, in combination with an antiandrogen, i.e. flutamide. Pharmaceutical compositions useful for treatment are also disclosed.
- -
-
-
- 7β-substituted-4-aza-5α-androstan-3-ones as 5α-reductase inhibitors
-
Described are new 7β-substituted 4-aza-5α-androstan-3-ones and related compounds as 5α-reductase inhibitors.
- -
-
-
- Method of treating androgenic alopecia with 5-alpha reductase inhibitors
-
The instant invention involves a method of treating and/or reversing androgenic alopecia and promoting hair growth, and methods of treating acne vulgaris, seborrhea, and female hirsutism, by administering to a patient in need of such treatment a 5α-reductase 2 inhibitor such as finasteride, in a dosage amount under 5 mgs/day.
- -
-
-
- Method of treatment for benign prostatic hyperplasia
-
Disclosed is an improved treatment for men with benign prostatic hyperplasia (BPH), involving combination therapy of a 5α-reductase inhibitor, e.g. a 17β-substituted 4-azasteroid, a 17β-substituted non-azasteroid, 17β-acyl-3-carboxy-androst-3,5-diene, benzoylaminophenoxybutanoic acid derivative, fused benz(thio)amide or cinnamoylamide derivative, aromatic 1,2-diethers or thioethers, aromatic ortho acylaminophenoxy alkanoic acids, ortho thioalkylacylaminophenoxy alkanoic acids, pharmaceutically acceptable salts and esters thereof, and particularly finasteride, in combination with an α1 -adrenergic receptor blocker, i.e., terazosin. The combination provides therapy at the molecular level for the underlying cause of the disease as well as providing symptomatic relief. Pharmaceutical compositions useful for treatment are also disclosed.
- -
-
-
- Synthesis of N-substituted 3-oxo-17β -carboxamide-4-aza-5α-androstanes and the tautomerism of 3-oxo-4-aza-5-androstenes
-
An N-aryl-3-oxo-4-aza-5α -androst-1-ene-17β carboxamide and three N-aryl or alkyl substituted 17α -hydroxy-3-oxo-4-aza-5α -androstane-17β -carboxamides were synthesized as antiandrogen candidates from 3-oxoandrost-4-ene-17β - carboxylic acid and androst-4-ene-3,17-dione respectively. The chemo- and stereoselective reduction of 3-oxo-4-aza-5-ene intermediates with formic acid and their tautomerism in a solution of chloroform and methanol were described.
- Xia, Peng,Yang, Zheng-Yu,Xia, Yi,Zhang, Hao-Bing,Zhang, Ke-Hua,Sun, Xun,Chen, Ying,Zheng, Yun-Qing
-
p. 703 - 716
(2007/10/03)
-
- Process for the production of finasteride
-
A process for producing polymorphic Form I of finasteride, 17B-(N-tert-butyl carbamoyl)-4-aza-5α-androst-1-en-3-one, in substantially pure form comprising the steps of: (1) crystallization from a solution of finasteride in a water immiscible organic solvent and 0% or more by weight of water, producing solvated and non-solvated finasteride in solution, such that the amount of organic solvent and water in the solution is sufficient to cause the solubility of the non-solvated form of finasteride to be exceeded and the non-solvated form of finasteride to be less soluble than any other form of finasteride in the organic solvent and water solution: (2) recovering the resultant solid phase; and (3) removing the solvent therefrom; wherein the water immiscible organic solvent is ethyl acetate or isopropyl acetate and the amount of water in the solvent mixture is below 4 mg./ml.
- -
-
-
- Reduction of boar odor in meat
-
This invention relates to a method for eliminating or lessening the incidence of boar odor in meat reared from male pigs which comprises administering to such male pigs an effective amount of a boar 4-ene-5-α-reductase inhibiting compound with or without further active ingredients. Also provided is a method for preventing the formation of 5-α-androst-16-en-3-one in male pigs which comprises administering to such male pigs a presently discovered boar 4-ene-5-α-reductase inhibiting compound.
- -
-
-
- Substituted 4-aza-5α-androstan-ones as 5α-reductase inhibitors
-
Described are new 16-substituted and 7,16-disubstituted 4-aza-5α-androstan-3-ones and related compounds as 5α-reductase inhibitors.
- -
-
-
- Method of treatment of chronic prostatitis with 17β-N-monosubstituted-carbamoyl-4-aza-5α-androst-1-en-3-ones
-
The present invention is concerned with the use of 17β-N-monosubstituted-carbamaoyl-4-aza-5α-androst-1-en-3-one compounds as testosterone-5α-reductase inhibitors for the treatment of chronic prostatitis.
- -
-
-
- Method of treating androgenic alopecia with 5-α reductase inhibitors
-
The instant invention involves a method of treating and/or reversing androgenic alopecia and promoting hair growth, and methods of treating acne vulgaris, seborrhea, and female hirsutism, by administering to a patient in need of such treatment a 5α-reductase 2 inhibitor, such as finasteride, in a dosage amount under 5 mgs/day.
- -
-
-
- New finasteride processes
-
Disclosed is a new process for producing finasteride which involves reacting the magnesium halide salt of 17βB-carboalkoxy-4-aza-5α-androst-1-en-3-one with t-butylamino magnesium halide, present in at least a 2:1 molar ratio to the ester, formed from t-butyl amine and an aliphatic/aryl magnesium halide at ambient temperature in an inert organic solvent under an inert atmosphere followed by heating and recovering said product finasteride. Also disclosed are two polymorphic crystalline Forms I and II of finasteride, and methods of their production.
- -
-
-
- Dehydrogenation process
-
A process for dehydrogenating a compound of the formula STR1 which comprises reacting the compound with a silylating agent in the presence of a quinone to introduce a Δ1 double bond.
- -
-
-
- Dehydrogenation process intermediates
-
A process for dehydrogenating a compound of the formula STR1 which comprises reacting the compound with a silylating agent in the presence of a quinone to introduce a Δ1 double bond.
- -
-
-
- TRIALKYLSILYL TRIFLUOROMETHANESULFONATE MEDIATED ALPHA-METHYLENIC CARBON FUNCTIONALIZATION OF 4-AZA-5ALPHA-ANDROSTAN-3-ONE STEROIDS
-
A novel single-pot trialkylsilyl trifluoromethanesulfonate (R3Si?OTf) mediated process produces derivatives of 4-aza 3-keto steroids at the alpha-methylenic carbon through electrophilic substitution. These derivatives are useful in the preparation, through elimination of the substituent on the alpha-methylene carbon, of delta-1 olefin 4-aza 3-keto steroids which are potent inhibitors of 5-alpha reductase.
- -
-
-
- Acylimidazolides as Versatile Synthetic Intermediates for the Preparation of Sterically Congested Amides and Ketones: A Practical Synthesis of Proscar
-
Acylimidazolides react with magnesium amides to produce carboxamides in excellent yields, whereas Fe(III) catalyzed cross coupling between acylimidazolide and Grignard reagents produce ketones in high yields.These methods were utilized to prepare the α-reductase inhibitor Proscar as well as various 17β-amide and ketone analogs of Δ1-4-aza-5α-androsten-3-one.
- Bhattacharya, A.,Williams, J.M.,Amato, J.S.,Dolling, U.-H.,Grabowski, E.J.J.
-
p. 2683 - 2690
(2007/10/02)
-
- Dehydrogenation process and intermediates
-
A process for dehydrogenating a compound of the formula which comprises reacting the compound with a silylating agent in the presence of a quinone to introduce aΔ1 double bond. Novel intermediates are compounds of the formula wherein:, Q is absent or is where R4 is methyl, C1 8 straight or branched chain alkyl, C3 6 cycloalkyl, phenyl, or combinations thereof; and R14 is hydrogen, C1 6 alkyl, C1 6 straight or branched chain alkoxy, halo, nitro or cyano.
- -
-
-
- Treatment of prostatic carcinoma with 17beta-n-monosubstituted-carbamoyl-4-aza-5alpha-androst-1-en-3-ones
-
17 beta -N-Monosubstituted-carbamoyl-4-aza-5 alpha -androst-1-en-3-ones of the formula wherein R is selected from hydrogen, methyl and ethyl and R is a branched chain alkyl of from 3-12 carbons, and R' , R'', R''' are hydrogen or methyl are active as testosterone 5 alpha -reductase inhibitors and thus are useful for the treatment of prostatic carcinoma.
- -
-
-
- Azasteroids: Structure-activity relationships for inhibition of 5α-reductase and of androgen receptor binding
-
A series of steroids, primarily 4-azasteroids, were prepared and tested in vitro as inhibitors of human and rat prostatic 5α-reductase and of binding of dihydrotestosterone to the rat androgen receptor. The primary structural modifications were changes of the A ring and of moieties attached at the C-17 position of the steroid nucleus. New A-ring modifications included 4-cyano-3-oxoΔ4 system in the carbocyclic series and 1α-CN, 1α-CH3, 1α,2α-CH2, 2β-F, 2-aza, 2-oxa, and A-homo changes in the 3-oxo-4-aza series. In addition, 4-azasteroids with a D-homo ring or methyl substitution at C-7 (α and β) or C-16 (α and β) were prepared. The majority of the C-17 substituents were prepared from reactive intermediates derived from the 17β-COOH. Enhanced 5α-reductase inhibition in both the human and rat enzyme assays is seen with 4-CN substitution on 3-oxo-Δ4 steroids and with a C-17 side chain incorporating a lipophilically substituted semipolar group on the 4-aza-3-oxo-5α-androstane nucleus. Fewer highly active compounds were found in the human enzyme assay than in the rat assay. Structural requirements for inhibition of the rat androgen receptor are much different from those for inhibition of the enzyme. The 17β-OH moiety enhances potency more than any other feature while introduction of double bonds at C-1 or C-5 in the azasteroid gives a small improvement. Azasteroids unsubstituted at the 4-position show greatly diminished receptor activity.
- Rasmusson,Reynolds,Steinberg,Walton,Patel,Liang,Cascieri,Cheung,Brooks,Berman
-
p. 2298 - 2315
(2007/10/02)
-
