164656-23-9

Basic information

• Product Name: Dutasteride
• Synonyms: (1S,2R,7R,10S,11S,14S,15S)-N-[2,5-bis(trifluoroMethyl)phenyl]-2,15-diMethyl-5-oxo-6-azatetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-3-ene-14-carboxaMide;(4aR,4bS,6aS,7S,9aS,9bS,11aR)-N-[2,5-Bis(trifluoroMethyl)phenyl]-2,4a,4b,5,6,6a,7,8,9,9a,9b,10,11,11a-tetradecahydro-4a,6a-diMethyl-2-oxo-1H-Indeno[5,4-f]quinoline-7-carboxaMide;(5α,17β)-;(4aR,4bS,6aS,7S,9aS,9bS,11aR)-N-[2,5-Bis(trifluoroMethyl)phenyl]-2,4a,4b,5,6,6a,7,8,9,9a,9b,10,11,11a-tetradecahydro-4a,6a-diMethyl-2-oxo-1H-indeno[5,4-f]quinoline-7-carboxaMide-13C6;6β-Hydroxy Dutasteride;4-Azaandrost-1-ene-17-carboxaMide, N-[2,5-bis(trifluoroMethyl)phenyl]-3-oxo-, (5a,17b)-;Avolve;Dutasteride API
• CAS NO: 164656-23-9
• Molecular Formula: C27H30F6N2O2
• Molecular Weight: 528.53
• EINECS: 1308068-626-2
• Product Categories: Hormone Drugs;API;Miscellaneous Biochemicals;All Inhibitors;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Steroids;Steroid and Hormone
• Mol File: 164656-23-9.mol

Chemical Properties

• Melting Point: 242-250°C
• Boiling Point: 620.3 °C at 760 mmHg
• Flash Point: 329 °C
• Appearance: white to beige/
• Density: 1.303 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.523
• Storage Temp.: -20°C Freezer
• Solubility: DMSO: soluble2mg/mL, clear
• PKA: 13.32±0.70(Predicted)
• CAS DataBase Reference: Dutasteride(CAS DataBase Reference)
• NIST Chemistry Reference: Dutasteride(164656-23-9)
• EPA Substance Registry System: Dutasteride(164656-23-9)

Safety Data

• Hazardous Substances Data: 164656-23-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Dutasteride is used as a pharmaceutical agent for the treatment of symptomatic benign prostatic hyperplasia in men with an enlarged prostate gland. It helps reduce prostate volume, lower the risk of acute urinary retention and surgery, and improve lower urinary tract symptoms and urinary flow measurements.
Used in Urology:
Dutasteride is used as a therapeutic agent in urology for managing benign prostatic hyperplasia. Its dual inhibition of 5α-reductase isoenzymes type 1 and 2 results in a significant decrease in serum dihydrotestosterone levels, providing greater efficacy compared to Finasteride (95% vs 67%). This leads to improved symptoms and reduced complications associated with BPH.
Used in Research:
Dutasteride is used as a research tool for studying the role of 5α-reductase enzymes and their impact on prostate growth and function. Its superior efficacy and pharmacokinetics compared to Finasteride make it a valuable compound for investigating the mechanisms of prostate enlargement and potential therapeutic interventions.

Originator

GlaxoSmithKline (UK)

Biological Functions

Similar to finasteride, dutasteride is a competitive and mechanism-based inhibitor not only of type 2 but also of type 1 5α-reductase isoenzymes, with which stable enzyme-NADP adduct complexes are formed, inhibiting the conversion of testosterone to DHT. The suppression of both type 1 and type 2 isoforms results in greater and more consistent reduction of plasma DHT than that observed for finasteride. The more effective dual inhibition of type 1 and type 2 5α-reductase isoforms lowers circulating DHT to a greater extent than with finasteride and shows advantages in treating BPH and other disease states (e.g., prostate cancer) that are DHT-dependent.

Biochem/physiol Actions

Dutasteride is a potent dual inhibitor of 5α-reductase isoenzymes types 1 and 2 (IC50 = 6 nM 5-AR1; 7 nM 5-AR2). Dutasteride blocks testosterone conversion to dihydrotesterone, and is used clinically for treating benign prostatic hyperplasia (BPH).

Pharmacokinetics

The maximum effect of 0.5 mg daily doses of dutasteride on the suppression of DHT is dose-dependent and is observed within 1 to 2 weeks. After 2 weeks of 0.5 mg daily dosing, median plasma DHT concentrations were reduced by 90%, and after 1 year, the median decrease in plasma DHT was 94%. The median increase in plasma testosterone was 19% but remained within the physiological range. The drug also reduced serum prostatic specific antigen by approximately 50% at 6 months and total prostate volume by 25% at 2 years. Dutasteride produced improvements in quality of life and peak urinary flow rate and reduction of acute urinary retention without the need for surgery.

Clinical Use

Dutasteride belongs to azasteriod class of compounds and function as a 5α-reductase inhibitor1 which prevents the conversion of the androgen sex hormone testosterone into the more potent metabolite dihydrotestosterone (DHT). In 2009, South Korea has been licensed dutasteride for the treatment of androgenetic alopecia and in Japan 2015.Dutasteride is the first and only double 5α reductase inhibitor used to treat Benign prostatic hyperplasia, and it is mainly used clinically to treat prostate enlargement, male-pattern hair loss, seborrheic hair loss, and hereditary hair loss.

Side effects

The main side effects are ED, decreased libido, gynecomastia, and ejaculation disorders. Long-term use (>4 years), however, did not reveal increased onset of sexual side effects. In addition, the combination of dutasteride and tamsulosin is well-tolerated and has the added advantage of rapid symptomatic relief.

Synthesis

Dutasteride can be prepared from 3-oxo-4-androstene-17β-carboxylic acid by several ways in 6 or 8 steps. In the preparation of dutasteride, the introduction of the carbon-carbon double bond in conjugation with C-3 carbonyl carbon of azaandrosteriods is one of the most important chemical reaction.an efficient synthesis of dutasteride: utilizing benzoyl group as novel lactamic protecting group

in vivo

dutasteride, which inhibits both 5αr1/5αr2, is efficacious in blocking prostate cancer development or progression in c57bl/6 tramp x fvb mice [2].

Drug interactions

Potentially hazardous interactions with other drugsNone known

Metabolism

Dutasteride is metabolised by the cytochrome P450 isoenzymes CYP3A4 and CYP3A5, and most of a dose is excreted as metabolites in the faeces.

Mode of action

The human body contains type I and type II 5α reductase, with type II found mainly in the prostate, and type I found mainly in the liver and skin. 5α reductase is the main cause for continuous benign prostate enlargement; it promotes the transformation of testosterone in patients’ prostate into the more active dihydrotestosterone, thus causing prostate cells to enlarge and the prostate to swell. Dutasteride can inhibit both type I and II 5α reductase at the same time. This type of simultaneous inhibiting mechanism can rapidly and continuously reduce prostate size, dramatically improve urination, and reduce the risk fo acute urinary retention and its related prostate surgeries.

Clinical claims and research

The American FDA approved a 2-year multicenter randomized double-blind control clinical trial – the first long term clinical assessment of the combined usage of Dutasteride and α receptor blockers. Included subjects were male patients with moderate to severe prostate enlargement (ages greater than or equal to 50, prostate volume (PV) ≥30 cc, serum prostate specific antigen (PSA) levels 1.5-10ng/ml, 5ml/sec < maximum urinary flow (Qmax) ≤15ml/sec, minimum urination ≥ 125ml, international prostate symptom score (IPSS) ≥ 12). Patients were first given a placebo for 4 weeks and then were randomly given either 0.5mg/day of Dutasteride and 0.4mg/day of Tamsulosin, only 0.5mg/day of Dutasteride, or only 0.4mg/day of Tamsulosin.Results showed: After 12-24 months, the combined usage of Dutasteride with Tamsulosin had better curative effects than did individual usage.

references

[1] schmidt lj1, murillo h, tindall dj. gene expression in prostate cancer cells treated with the dual 5 alpha-reductase inhibitor dutasteride. j androl. 2004 nov-dec;25(6):944-53.[2] opoku-acheampong ab1, unis d, henningson jn, beck ap, lindshield bl.preventive and therapeutic efficacy of finasteride and dutasteride in tramp mice. plos one. 2013 oct 18;8(10):e77738. doi: 10.1371/journal.pone.0077738. ecollection 2013.

InChI:InChI=1/C27H30F6N2O2/c1-24-11-9-17-15(4-8-21-25(17,2)12-10-22(36)35-21)16(24)6-7-19(24)23(37)34-20-13-14(26(28,29)30)3-5-18(20)27(31,32)33/h3,5,10,12-13,15-17,19,21H,4,6-9,11H2,1-2H3,(H,34,37)(H,35,36)/t15?,16?,17?,19-,21?,24+,25-/m1/s1

Upstream product

• 328-92-7 2-iodo-1,4-bis-(trifluoromethyl)-benzene 
• 104214-61-1 3-Oxo-4-aza-5alpha-androst-1-ene-17beta-carboxamide 
• 1260388-53-1 C₂₀H₂₉NO₅S 
• 328-93-8 2,5-bis(trifluoromethyl)aniline 
• 1169835-66-8 C₂₄H₃₅NO₄ 
• 104239-97-6 3-Oxo-4-aza-5α-androst-1-ene-17β-carboxylic acid 
• 73671-92-8 3-oxo-4-aza-5α-androstane-17β-carboxylic acid methyl ester 
• 103335-41-7 methyl 3-oxo-4-aza-5α-androst-1-ene-17β-carboxylate 
• 1260388-52-0 C₂₀H₂₆F₃NO₅S 
• 20283-95-8 3,20-dioxo-4-aza-pregnan-5-ene 
• 1416955-23-1 C₂₀H₃₁NO₃ 
• 73711-89-4 3,20-dioxo-4-aza-5α-pregnane 
• 103335-55-3 3-oxo-4-aza-5α-androstane-17β-carboxylic acid 
• 57-83-0 Progesterone 

Relevant articles and documents

Production process of high-purity dutasteride

The invention discloses a purification production process of high-purity dutasteride. The problems to be solved are that the purity of the dutasteride is improved while the production cost is reduced.According to the method, after a dutasteride crude product is obtained, twice crystallization is carried out, so that the dutasteride with high yield and high purity can be obtained. The production process provided by the invention has the advantages of high efficiency and clean production, and the operability is high. An intermediate is refined, so that the quality of the dutasteride finished product is more easily controlled, the purity of the obtained dutasteride product is not lower than 99.5%, and any single impurity in the product is not higher than 0. 1%.

A method of preparation he male amine

The invention belongs to the field of pharmaceutical chemistry, and relates to a high-yield method for preparing dutasteride, which comprises the following steps: (1) under the action of a catalyst, reacting aza-5-androst-1-alkenyl-3-keto-17beta-carboxylic acid (I) with alcohol to generate 4-aza-5-androst-1-alkenyl-3-keto-17beta-carboxylate (II); and (2) in the presence of a catalyst, reacting the 4-aza-5-androst-1-alkenyl-3-keto-17beta-carboxylate (II) with 2,5-ditrifluoromethylaniline in an organic solvent at certain reaction temperature to obtain the dutasteride (III) at high yield. The method has the characteristics of accessible raw material, mild reaction conditions and high product yield, and is easy to control.

A high-pure undistilled he male amine preparation method (by machine translation)

The invention discloses a high-pure undistilled he male amine preparation method, the dutasteride in acetonitrile residue is ≤ 0.04%, type V impurity residual ≤ 0.02%, total impurity ≤ 0.15%. The preparation method comprises dutasteride crude synthesis an

Preparation method of dutasteride

The invention relates to a preparation method of dutasteride. The preparation method comprises the following steps: dissolving 3-keto-4-aza-5-alpha-androst-1-ene-17beta carboxylic acid into an organic solvent, adding dichlorosulfane, performing a reaction

A androst - 17β - N - (2, 5 - (trifluoromethyl)-) IBZM preparation method

The invention provides a preparation method of androstane-17beta-N-(2,5-bis (trifluoromethyl)) benzamide. The preparation method comprises the following steps: (1) in the presence of an acid-binding agent, carrying out acyl chloride forming reaction between androstane-17beta carboxylic acid and thionyl chloride to obtain androstane-17beta acyl chloride; (2) enabling the androstane-17beta acyl chloride and 2,5-bis(trifluoromethyl) aniline to generate amide forming reaction in the presence of a hydrogen stripping agent to obtain androstane-17beta-N-(2,5-bis (trifluoromethyl)) benzamide, wherein the acid-binding agent is anhydrous potassium carbonate fine powder. The preparation method disclosed by the invention can be used for simply preparing the androstane-17beta-N-(2,5-bis (trifluoromethyl)) benzamide with low toxicity, high quality, high yield and low cost.

A process for the preparation of dutasteride

The invention belongs to the technical field of medicine, and provides a preparation method of dutasteride. The preparation method comprises the following steps: A) an industrial-grade compound III is washed by acetone after beaten and refined by formic acid, and a refined compound III product is obtained; B) the refined compound III product has a chlorination reaction to generate a compound II; C) the compound II has a condensation reaction with 2,5-bis (trifluoromethyl) phenylamine, a product is cooled and filtered, a filtrate is collected, a hydrochloric acid solution is added for washing, an organic phase is separated, pressure is reduced to evaporate s solvent, and a crude dutasteride product is obtained; and D) the crude dutasteride product is dissolved by an organic solvent and decolorized, an anti-solvent is added for crystallization, and high-purity dutasteride is obtained. Side reactions are reduced, high-purity dutasteride can be obtained through preparation, and the productive cost is reduced.

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.

A kind of dutasteride impurities method for the preparation of I

The invention belongs to the technical field of medicines and discloses a preparation method of a dutasteride impurity I. The preparation method of the dutasteride impurity I comprises the following steps: preparing a compound III refined product, carryin

PROCESS FOR THE SYNTHESIS OF (5α,17β)-N-[(2,5-BIS(TRIFLUOROMETHYL)-PHENYL]-3-OXO-4-AZA-5-ANDROST-1-ENE-17-CARBOXAMIDE

The synthesis consists of reaction steps as follows: oxidizing the α,β-unsaturated ketone system of ring "A" of pregn-4-ene-3,20-dion- of formula (II) with sodium metaperiodate in tert-butanol in the presence of potassium permanganate and alkali metal carbonate, reacting the obtained 3,5-seco acid with an ester of chloroformic acid in the presence of tertier organic base below 0°C, reacting the obtained new compound after isolation or without isolation with ammonia or ammonium acetate, cyclization of the resulting carboxamides with an acid, cathalytic hydrogenating the obtained ene lactame, and oxidizing the side chain at position 17 of the obtained pregnane compound with an alkali metal hypobromide in aqueous dioxane below 10°C. Thereafter on one hand the obtained (5α,17β)-3-oxo-4-aza-5-androstane-17-carboxylic acid is reacted with chloroformic acid ester, the obtained new compound is reacted with 2,5-bis(trifluoromethyl)-aniline in the presence of a Lewis acid, the obtained amide is reacted with trimethyl chlorosilane in inert atmosphere in the presence of Ν,Ν,Ν',Ν'-tetramethyl-ethylendiamine, then en excess iodine is added to the reaction mixture and the product of the iodination reaction is crystallized from acetonitrile, then the obtained 2-iodo-3-oxo-4-aza-17β-carboxamide is reacted with potassium tert-butylate to furnish final product. On the other hand, (5α,17β)-3-oxo-4-aza-5-androstane-17-carboxylic acid is transformed into methylester by known method, this latter is transformed into methyl (2α,5α,17β)-2-iodo-3-oxo-4-aza-5-androstane-17-carboxylate according to known method, the obtained compound is reacted with potassium-tert-butylate, the obtained (5α,17β)-3-oxo-4-aza-5-androst-1-ene-17-carboxylic acid is reacted with an ester of chloroformic acid, then the obtained new compound is coupled with 2,5-bis(trifluoromethyl)-aniline in the presence of a Lewis acid catalyst to gain final product.