98319-26-7 Usage
Uses
Used in Urology:
Finasteride is used as a treatment for benign prostatic hyperplasia, where it helps alleviate urinary symptoms, reduce prostatic volume, and increase the maximal urinary flow rate.
Used in Dermatology:
Finasteride is used as an antialopecia agent, functioning as an inhibitor of 5α-reductase, the enzyme responsible for converting testosterone to the more potent androgen, 5α-dihydrotestosterone. This application aids in the treatment of androgenetic alopecia, commonly known as male pattern baldness.
Indications and Usage
Finasteride is a basic drug to treat benign prostatic hyperplasia and prostatitis, a synthetic 4-nitrogen steroid hormone compound and a sex hormone drug.
It is used for benign prostatic hyperplasia, men's prostatic fat and other diseases. Finasteride is the only oral drug approved by the US Food and Drug Administration (FDA) to treat male pattern baldness.
Mechanisms of Action
Finasteride can selectively inhibit 5α-reductase, changing the conversion process of testosterone into 5α dihydrotestosterone (DHT), decreasing androgen levels in prostate cells, and prostate-specific antigens in serum, decreasing prostate swelling, and increasing urine flow rate, thereby alleviating the symptoms of prostatic hyperplasia. It acts by selectively blocking androgen stimulation of the prostate, but affects sexual function very rarely. Meanwhile, due to blocking of testosterone conversion and reduced synthesis of dihydrotestosterone, it can reduce dihydrotestosterone levels in the serum and scalp hair follicles, recovering the function of previously inhibited hair follicles, promoting hair growth and preventing loss.
clinical trials
Three controlled clinical trials were performed in men (18 to 41 years), with mild-to-moderate degrees of androgenetic alopecia. In these studies, 1879 men ingested either a 1- mg finasteride tablet or placebo tablet once daily for 12 months; after 12 months, finasteride-treated patients were switched to placebo and placebo-treated patients were switched to finasteride and they were followed for an additional 12 months. Clinical improvement was seen as early as 3 months in finasteride-treated patients and hair regrowth continued throughout the trial. Finasteride also had a stabilizing effect on hair loss, which was maintained through the second year of treatment. Hair counts in placebo-treated patients decreased during the study. Finasteride was generally well tolerated in these studies. Some men, however, experienced decreased libido, difficulty in achieving an erection, and decreased semen volume (<2% of patients in each case). These side effects resolved in 58% of the men who continued treatment and completely abated upon discontinuation of the drug.
Indications
Finasteride (Proscar) is a 5-reductase inhibitor that
blocks the conversion of testosterone to DHT in target
tissues. Since DHT is the major intracellular androgen
in the prostate, finasteride is effective in suppressing
DHT stimulation of prostatic growth and secretory
function without markedly affecting libido. It is approved
for the treatment of benign prostatic hyperplasia.
Although there is usually some regression in the size
of the prostate gland following administration of finasteride,
clinical response may take 6 to 12 months. If the
obstructive symptoms are severe, there is often not
enough time to allow this compound to work.The principal
adverse effects of finasteride are impotence, decreased
libido, and decreased volume of ejaculate. The
compound is generally well tolerated in men.
Manufacturing Process
In a flask equipped with an overhead stirrer, a nitrogen inlet, and reflux
condenser was placed 840 ml of dry THF and 20.0 g of 17β-carboxylate 17β-
carbomethoxy ester of 4-aza-5α-androst-1-en-3-one (synthesized according to Patent US 4,377,584, issued Mar. 22,1883, and J. Med. Chem., 29, 2298
(1986)). The resulting slurry was cooled to -5-10°C, and 27.6 mL of tbutylamine
was added. A solution of ethylmagnesium bromide in THF (122
mL, 2 M) was added maintaining the temperature of the reaction mixture
below 10°C. The reaction mixture was heated at reflux for 12 hours and was
added to a cold (10°C) solution of 25% ammonium chloride in water. The
mixture was warmed to 25°C and allowed to settle. The THF solution was
separated and concentrated by atmospheric distillation to 200 mL and the
product was crystallized by adding approximately 600 mL of dilute aqueous
HCl. The resulting white solid was isolated by filtration and was dried at 70°C
under vacuum to give 21.7 g (97% yield) 2-butyl-1-(4-carboxybenzyl)-4-
chloroimidazole-5-acetic acid of finasteride. The finasteride can be purified by
conventional procedures, e.g. recrystallization from methylene chloride/ethyl
acetate or acetic acid/water, melting point 261°C.
Biological Activity
Antiandrogen that inhibits type II 5 α reductase (IC 50 = 65 nM). Suppresses the conversion of testosterone to dihydrotestosterone. Reduces prostatic dihydrotestosterone levels and prostate size in vivo . Orally active.
Biochem/physiol Actions
Selective 5α-reductase inhibitor; antiandrogen.
Pharmacokinetics
The mean oral bioavailability of finasteride is 65%, as shown in Table 45.4, and is not affected by food. Approximately 90% of circulating finasteride is bound to plasma proteins. Finasteride has been found to cross the blood-brain barrier, but levels in semen were undetectable (<0.2 ng/mL). Finasteride is extensively metabolized in the liver, primarily via CYP3A4 to two major metabolites: monohydroxylation of the t-butyl side chain, which is further metabolized via an aldehyde intermediate to the second metabolite, a monocarboxylic acid. The metabolites show approximately 20% the inhibition of finasteride for 5α-reductase. The mean terminal half-life is approximately 5 to 6 hours in men between 18 and 60 years of age and 8 hours in men older than 70 years of age. Following an oral dose of finasteride, approximately 40% of the dose was excreted in the urine as metabolites and approximately 57% in the feces. Even though the elimination rate of finasteride is decreased in the elderly, no dosage adjustment is necessary. No dosage adjustment is necessary in patients with renal insufficiency. A decrease in the urinary excretion of metabolites was observed in patients with renal impairment, but this was compensated for by an increase in fecal excretion of metabolites. Caution should be used during administration to patients with liver function abnormalities, because finasteride is metabolized extensively in the liver.
Clinical Use
The selective inhibition of the type 2 5α-reductase isozyme produces a rapid reduction in plasma
DHT concentration, reaching 65% suppression within 24 hours of administering a 1-mg oral tablet
(106). At steady state, finasteride suppresses DHT levels by approximately 70% in plasma and by as
much as 85 to 90% in the prostate. The remaining DHT in the prostate likely is the result of type 1
5α-reductase. The mean circulating levels of testosterone and estradiol remained within their physiological concentration range. Long-term
therapy with finasteride can reduce clinical significant end points of BPH, such as acute urinary
retention or surgery. Finasteride is most effective in men with large prostates. Finasteride has no
affinity for the AR and no androgenic, antiandrogenic, estrogenic, antiestrogenic, or progestational
effects.
Veterinary Drugs and Treatments
Finasteride may be useful in treating the benign prostatic hypertrophy
in canine patients. Because of the drug’s relative expense and
the long duration of therapy required to see a response, its usefulness
may be limited in veterinary medicine.
It may also be useful in the adjunctive treatment of adrenal disease
in ferrets.
Drug interactions
Potentially hazardous interactions with other drugs
None known
Metabolism
Finasteride is metabolised primarily via the cytochrome
P450 3A4 enzyme subfamily. Following an oral dose
of 14C-finasteride in man, two metabolites of the drug
were identified that possess only a small fraction of the
5α-reductase inhibitory activity of finasteride. 39% of the
dose was excreted in the urine in the form of metabolites
(virtually no unchanged drug was excreted in the urine)
and 57% of total dose was excreted in the faeces.
Check Digit Verification of cas no
The CAS Registry Mumber 98319-26-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 9,8,3,1 and 9 respectively; the second part has 2 digits, 2 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 98319-26:
(7*9)+(6*8)+(5*3)+(4*1)+(3*9)+(2*2)+(1*6)=167
167 % 10 = 7
So 98319-26-7 is a valid CAS Registry Number.
InChI:InChI=1/C23H36N2O2/c1-21(2,3)25-20(27)17-8-7-15-14-6-9-18-23(5,13-11-19(26)24-18)16(14)10-12-22(15,17)4/h11,13-18H,6-10,12H2,1-5H3,(H,24,26)(H,25,27)/t14-,15-,16-,17+,18?,22-,23+/m0/s1
98319-26-7Relevant articles and documents
Refining and decolorizing method of finasteride
-
Paragraph 0025-0038, (2019/10/01)
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.
Method for forming double bonds between 1-position and 2-position during synthesis of finasteride and dutasteride
-
, (2016/12/01)
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.
Impurities in finasteride: Identification, synthesis, characterization and control of potential carry-over impurities from reagents used for the process
Mohanty, Sandeep,Kumar, B. Pavan,Karmakar, Arun Chandra
, p. 4375 - 4380 (2014/08/05)
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.
Crystallization engineering in aza-steroid: Application in the development of finasteride
Bhattacharya, Apurba,Manudhane, Kushal S,Maddula, Srinivasula Reddy,Sreekanth,Thota, Sridhar,Bandichhor, Rakeshwar
, p. 599 - 602 (2013/06/05)
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.
TOPICAL COMPOSITIONS COMPRISING 5-ALPHA REDUCTASE INHIBITORS
-
, (2010/03/31)
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
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Page/Page column 15, (2008/12/08)
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.
Novel azaandrostane derivatives for the synthesis of 17β-(N-tert-butyl carbamoyl)-4-aza-5α-androst-1-ene-3-one
Srinivasa Rao, Divvela V. N.,Trinadhachari, Ganala Naga,Prabahar, Koilpillai Joseph,Dandala, Ramesh,Sivakumaran, Meenakshisundaram,Naidu, Andra
, p. 663 - 667 (2008/09/18)
(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).
Facile water mediated synthesis of finasteride form-I, an azaandrostane steroid
Rao, Divvela V. N. Srinivasa,Trinadhachari, Ganala Naga,Lenin, Racha,Prabahar, Koilpillai Joseph,Naidu, Andra,Dandala, Ramesh
, p. 121 - 124 (2008/02/12)
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.
PROCESSES TO PREPARE FINASTERIDE POLYMORPHS
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Page/Page column 4, (2010/11/27)
Processes for preparing polymorphic crystalline Form I and Form III of finasteride.
Process for the preparation of 17-N-substituted-carbamoyl-4-aza-androst-1-en-3-ones
-
Page/Page column 6, (2008/06/13)
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.
