- Improved Syntheses of Epristeride, a Potent Human 5α-Reductase Inhibitor
-
Two improved syntheses of a potent human 5α-reductase inhibitor, epristeride, SK&F 105657, are described.The first synthesis starts from methyl 3-oxoandrost-4-ene-17β-carboxylate (1), which is converted to epristeride (5) in four synthetic steps in 44percent overall yield.The second synthesis starts from commercially available 3-oxoandrost-4-en-17β-carboxylic acid (7), which is converted to epristeride (5) in two synthetic steps in 63percent overall yield.Both syntheses are suitable for large scale production and have been employed to produce kilograms supplies of epristeride in high purity.
- Baine, Neil H.,Owings, Franklin F.,Kline, Donald N.,Resnick, Theodore,Ping, Li-Jen,et al.
-
-
Read Online
- A practical synthesis of 3-substituted Δ(3,6(6))-steroids as new potential 5α-reductase inhibitor
-
A new and practical synthetic approach to 3-substituted Δ(3,5(6))- Steroids, as potential 5α-reductase inhibitor, is described. The key step involves Pd-catalyzed coupling reaction of steroid 3-enol 5H-3-oxo- octafluoropentanosulfonates. 3-Phenylacetyleny
- Tian, Weisheng,Zhu, Zheng,Liao, Qingjiang,Wu, Yikang
-
-
Read Online
- Palladium and nickel catalyzed hydroxycarbonylation of a steroidal bromodiene in the synthesis of episteride, a potent 5α-reductase inhibitor
-
Androst-4-en-3-one-17β-carboxylic acid 1 was converted to 3-bromo-N- (l,1-dimethylethyl) androsta-3,5-diene-17-β-carboxamide 2 by reaction with DMF/oxalyl bromide and quenching into t-butylamine. 2 was converted to 3 (R=H) by nickel cyanide catalyzed hydr
- McGuire, Michael A.,Sorenson, Edmund,Klein, Donald N.,Baine, Neil H.
-
-
Read Online
- Inhibition of Steroid 5α-Reductase by Unsaturated 3-Carboxysteroids
-
A series of unsaturated steroids bearing a 3-carboxy substituent has been prepared and assayed in vitro as inhibitors of human and rat prostatic steroid 5α-reductase (EC 1.3.1.30).It is proposed that the observed tight binding of the 3-androstene-3-carboxylic acids is due to mimicry of a putative, high-energy, enzyme-bound enolate intermediate formed during the NADPH-dependent conjugate reduction of testosterone by steroid 5α-reductase.These compounds were prepared through palladium(0)-catalyzed carbomethoxylations of enol (trifluoromethyl)sulfonates derived from 3-keto precursors.Modification of A and B ring unsaturation and substitution at C-3, -4, -6, and -11 was explored.Mono- and dialkylcarboxamides were employed as 17β side chains to enhance inhibitory activity with the human enzyme.
- Holt, Dennis A.,Levy, Mark A.,Oh, Hye-Ja,Erb, Jill M.,Heaslip, Julie I.,et al.
-
-
Read Online
- Epristeride intermediate, preparation method of Epristeride intermediate, and preparation method of Epristeride
-
The invention relates to the field of medicine, in particular to an Epristeride intermediate, a preparation method of the Epristeride intermediate, and a preparation method of Epristeride. The preparation method of the Epristeride intermediate comprises the following steps that a compound 3 takes a sulfonation reaction with an alkaline reagent to produce a compound 4; the reaction conversion is single; the column chromatography isolation is avoided; the alkaline reagent used in the reaction process can be easily obtained; the reaction conditions are mild. The unit operation is reduced; the production period is shortened; the production efficiency is improved; the production efficiency is high; the economic benefits are improved.
- -
-
-
- Nitrate prodrugs able to release nitric oxide in a controlled and selective way and their use for prevention and treatment of inflammatory, ischemic and proliferative diseases
-
New pharmaceutical compounds of general formula (I): F-(X)q where q is an integer from 1 to 5, preferably 1; -F is chosen among drugs described in the text, -X is chosen among 4 groups -M, -T, -V and -Y as described in the text. The compounds of general formula (I) are nitrate prodrugs which can release nitric oxide in vivo in a controlled and selective way and without hypotensive side effects and for this reason they are useful for the preparation of medicines for prevention and treatment of inflammatory, ischemic, degenerative and proliferative diseases of musculoskeletal, tegumental, respiratory, gastrointestinal, genito-urinary and central nervous systems.
- -
-
-
- 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.
- -
-
-
- 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.
- -
-
-
- Steroid derivatives for the treatment of prostatic hypertrophy their preparation and uses
-
The invention includes compounds of formula (I): STR1 in which R1 is hydrogen, alkyl, aryl-substituted alkyl or aromatic heterocyclic-substituted alkyl; R2 is aryl-substituted alkyl, aromatic heterocyclic-substituted alkyl or diarylamino; and R3 is carboxy or a group of formula --CONHSO2 R4 wherein R4 is alkyl; and pharmaceutically acceptable salts and esters of the compounds. The compounds have valuable 5α-reductase inhibitory activity and can thus be used for the treatment and prophylaxis of, inter alia, prostatic hypertrophy as well as other disorders arising from excess levels of 5α-dihydro-testosterone.
- -
-
-
- Steriod 5-alpha-reductase inhibitors
-
Invented are substituted acrylate analogues of steroidal synthetic compounds, pharmaceutical compositions containing these compounds, and methods of using these compounds to inhibit steroid 5-α-reductase. Also invented are intermediates used in preparing these compounds.
- -
-
-
- Steroid 5-alpha-reductase inhibitors
-
[From equivalent EP0289327A3] Compounds of formula (I) : ψψ in which, inter alia, R± is H or C±±±alkyl and M is O or S, processes for their preparation, pharmaceutical compositions containing then and their use as inhibitors of 5-à-reductase in the treatment in the reduction of prostate size.ψ
- -
-
-
- STEROID 5-ALPHA-REDUCTASE INHIBITORS
-
Invented are substituted acrylate analogues of steroidal synthetic compounds, pharmaceutical compositions containing the compounds, and methods of using these compounds to inhibit steroid 5-alpha-reductase. Also invented are intermediates used in preparing these compounds
- -
-
-