- Synthesis and comprehensive structural and physicochemical characterization of dutasteride hydrochloride hydrate solvates
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Four crystalline dutasteride hydrochloride hydrate solvates containing respectively methanol, ethanol, acetone and acetonitrile molecules were obtained. All samples were characterized by extensive spectroscopic analysis with infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and 1H as well as 13C NMR techniques. For three solvates, i.e. methanol, ethanol and acetone solvates, the single crystal X-ray diffraction (SCXRD) experiments were possible, and their respective crystal and molecular structures were determined. The present study allowed to unambiguously establish the molecular composition of solvates as consisting of a dutasteride: hydrogen chloride: water: solvent in a molar ratio of 1:1:1:1 and confirm that they are isostructural. Beyond providing the full spectroscopic characteristic of the compounds, the results obtained have also allowed clarifying of some appearing inconsistencies in published literature regarding the appropriate attribution of IR absorption bands to the relevant molecular vibrations.
- Górecki, Marcin,Dziedzic, Alicja,Luboradzki, Roman,Ostaszewska, Anna,Frelek, Jadwiga,Szczepek, Wojciech J.
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- A synthetic 3-carbonyl-4-nitrogen mixed male steroid -17 β derivative method
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The invention discloses a method for synthesizing 3-carbonyl-4-azaandrost-17beta derivative I, which comprises the following steps: (1) in the presence of an acidic catalyst, dissolving A-norandrostane-3,5-cracked-androst-5-one-3-carboxylic acid-17beta derivative II in dioxane aqua ammonia, heating, and slowly and dropwisely adding reducer-dissolved aqua ammonia to simultaneously perform reduction amination reaction and ring-closing reaction; (2) adding acid to destroy the reducer, concentrating under normal pressure, and recovering dioxane; (3) cooling, and carrying out centrifugal filtration to obtain a filter cake; washing the filter cake with water to a neutral state, and carrying out centrifugal drying to obtain a 3-carbonyl-4-azaandrost-17beta derivative I crude product; and (4) pulping the 3-carbonyl-4-azaandrost-17beta derivative I crude product with methanol, carrying out centrifugal filtration to obtain a filter cake, washing the filter cake with methanol, carrying out centrifugal drying, and baking to obtain the 3-carbonyl-4-azaandrost-17beta derivative refined product. By completing the reduction amination reaction and ring-closing reaction in one step, the method has the advantages of low reaction temperature, high product yield and good product quality, is economical and environment-friendly, and is suitable for industrialization.
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Paragraph 0056-0065; 0068-0069
(2017/01/26)
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- Impurities in finasteride: Identification, synthesis, characterization and control of potential carry-over impurities from reagents used for the process
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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
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p. 4375 - 4380
(2014/08/05)
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- PROCESS FOR THE PREPARATION OF 17-N-SUBSTITUTED-CARBAMOYL-4-AZA-ANDROST-1 -EN-3-ONES
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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.
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Page/Page column 13-14
(2008/12/08)
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- PROCESSES TO PREPARE FINASTERIDE POLYMORPHS
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Processes for preparing polymorphic crystalline Form I and Form III of finasteride.
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Page/Page column 3-4
(2010/11/27)
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- Process for the preparation of 17-N-substituted-carbamoyl-4-aza-androst-1-en-3-ones
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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.
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Page/Page column 5
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF 17?-SUBSTITUTED-3-OXO-4-AZA-5ALPHA-ANDROSTANE DERIVATIVES
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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.
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Page/Page column 8
(2008/06/13)
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- METHOD FOR THE PREPARATION OF HIGHLY PURE 1-ANDROSTENE DERIVATIVES
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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.
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Page/Page column 11
(2008/06/13)
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- New approach to 3-oxo-4-aza-5α-androst-1-ene-17β-(N-tert- butylcarboxamide)
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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
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p. 690 - 693
(2007/10/03)
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- Method of prevention of prostatic carcinoma with 17β-N-monosubstituted-carbamoyl-4-aza-5α-androst-1-en-3-ones
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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.
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- Process for obtaining 17 beta-(N-tert-butylcarbamoyl)-3-one4-aza-steroids
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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.
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- Method of treatment for prostatic cancer
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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.
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- Method of treatment for benign prostatic hyperplasia
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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.
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- Synthesis of N-substituted 3-oxo-17β -carboxamide-4-aza-5α-androstanes and the tautomerism of 3-oxo-4-aza-5-androstenes
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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
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p. 703 - 716
(2007/10/03)
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- Substituted 4-aza-5α-androstan-ones as 5α-reductase inhibitors
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Described are new 16-substituted and 7,16-disubstituted 4-aza-5α-androstan-3-ones and related compounds as 5α-reductase inhibitors.
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- Method of treatment of chronic prostatitis with 17β-N-monosubstituted-carbamoyl-4-aza-5α-androst-1-en-3-ones
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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.
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- STEREOSELECTIVE REDUCTION OF THE DOUBLE BOND IN Δ5-3-OXO-4-AZASTEROIDS
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The stereoselective borohydride/H+ reduction of the C(5)-C(6) double bond in Δ5-3-oxo-4-azasteroids has been studied.The intermediate acylimine is preferentially attacked by borohydride from the α side.The optimization with respect to the type of borohydride, solvent, catalyst and temperature has been carried out.
- Morzycki, Jacek W.,Wilczewska, Agnieszka Z.,Zochowska, Ewa,Lotowski, Zenon
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p. 2729 - 2736
(2007/10/03)
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- Treatment of prostatic carcinoma with 17beta-n-monosubstituted-carbamoyl-4-aza-5alpha-androst-1-en-3-ones
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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.
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- Azasteroids: Structure-activity relationships for inhibition of 5α-reductase and of androgen receptor binding
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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
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p. 2298 - 2315
(2007/10/02)
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