103335-54-2

Usage

Uses

Used in Pharmaceutical Industry:
3-OXO-4-AZAANDROST-5-EEN-17-BETA-CARBONZUUR is used as a key intermediate in the synthesis of 5β-Finasteride (F342030), an azasteroid and 5β-isomeric impurity of Finasteride (F342000). 3-OXO-4-AZAANDROST-5-EEN-17-BETA-CARBONZUUR plays a crucial role in the development of medications for treating various conditions, such as benign prostatic hyperplasia and androgenetic alopecia, by inhibiting the conversion of testosterone to dihydrotestosterone.

InChI:InChI=1/C19H29NO3/c1-18-9-7-13-11(12(18)4-5-14(18)17(22)23)3-6-15-19(13,2)10-8-16(21)20-15/h11-15H,3-10H2,1-2H3,(H,20,21)(H,22,23)/t11-,12-,13-,14+,15+,18-,19+/m0/s1

Upstream product

• 76763-14-9 (3S,3aS,5aS,6R,9aS,9bS)-6-(2-carboxyethyl)-3a,6-dimethyl-7-oxododecahydro-1H-cyclopenta[a]naphthalene-3-carboxylic acid 
• 145-13-1 Pregnenolone 
• 85541-82-8 methyl 5-androsten-3β-ol-17β-carboxylate 
• 2681-55-2 3-oxo-androst-4-ene-17β-carboxylic acid methyl ester 
• 302-97-6 androst-4-en-3-one-17β-carboxylic acid 
• 73672-02-3 pregnenolone 21-pyridinium iodide 

Downstream Products

• 103335-55-3 3-oxo-4-aza-5α-androstane-17β-carboxylic acid 
• 1430804-94-6 3-oxo-4-aza-5β-androstane-17β-carboxylic acid 
• 142139-67-1 N-(1,2-diphenylethyl)-3-oxo-4-azaandrost-5-ene-17β-carboxamide 
• 142139-69-3 N-(diphenylmethyl)-3-oxo-4-azaandrost-5-ene-17β-carboxamide 
• 142139-73-9 N-(1,1-diphenylethyl)-3-oxo-4-azaandrost-5-ene-17β-carboxamide 
• 142139-94-4 N,N-Dibenzyl-3-oxo-4-azaandrost-5-ene-17β-carboxamide 
• 142187-06-2 N-[(S)-1,2-Diphenylethyl]-3-oxo-4-azaandrost-5-ene-17β-carboxamide 
• 142187-11-9 N-[(R)-1,2-Diphenylethyl]-3-oxo-4-azaandrost-5-ene-17β-carboxamide 
• 161511-08-6 (4aR,4bS,6aS,7S,9aS,9bS)-4a,6a-dimethyl-2-oxohexadecahydro-1H-indeno[5,4-f]quinoline-7-carboxylic acid 

Relevant academic research and scientific papers

A 3-carbonyl-4-aza-5-androstene -17 β method for preparing derivatives of

The invention provides a preparation method of a 3-carbonyl-4-aza-5-androstene-17beta derivative. The preparation method comprises the following steps: suspending an A-nor-3,5-cracking-androstan-5-keto-3-carboxylic acid-17beta derivative II in an aqueous solution of ammonium acetate for performing a ring-closure reaction; cooling a reaction product; adjusting the PH value of the reaction product by using industrial ammonia water; filtering the reaction product by spinning; drying the reaction product by spinning; and washing a filter cake by using water, and drying the filter cake to obtain a 3-carbonyl-4-aza-5-androstene-17beta derivative I, wherein R in a formula II and a formula I is carbonyl, carboxylic acid, carboxylic ester, amide, acetyl, hydroxyl, alkyl, ether or chloro. The preparation method has the advantages of mild reaction condition in the absence of inorganic solvents, low requirements on equipment and pre-treatment, complete reaction, and high product purity of over 99 percent without purification; moreover, a spinning-filtered mother solution is recovered, so that the emission of three wastes is reduced greatly; in the whole reaction, used raw materials are readily available; and meanwhile, the reaction yield is high, and the preparation method is economical and environmentally friendly, and is convenient for industrial implementation.

Synthesis and bioactivity of new Finasteride conjugate

Finasteride is a synthetic 4-azasteroid compound that acts by inhibiting type II 5α-reductase, the enzyme that converts the androgen testosterone to 5α-dihydrotestosterone. It was approved by the US FDA for the treatment of benign prostatic hyperplasia and male pattern baldness. Here the acylation product of Finasteride C-18 amide N-polimod was synthesized by employing acylation reaction with polimod amide as a pivotal intermediate. The structure of the key intermediate and target molecule was confirmed by infrared spectrum, 1H NMR and 13C NMR spectra and mass spectrum, and the inhibition of the steroid 5α-reductase and the rats' benign prostatic hyperplasia by the new Finasteride conjugate and Finasteride was also determined. The inhibition of the Finasteride conjugate on 5α-reductase was stronger than that of Finasteride. Prostate hyperplasia of rats was reduced by Finasteride conjugate treatment similar to the Finasteride treatment. However, the Finasteride conjugate treated animals showed better viable condition than the Finasteride treated ones, suggesting the new compound may have improved toxicity profile than Finasteride.

PROCESS FOR THE PREPARATION OF 4-AZASTEROIDS

The invention relates to a process for the preparation of 4-steroids of the formula (I), R1 and R2 are independently selected from the group consisting of hydrogen, F, Cl, Br, I, C1-6-alkyl and C1-6-alkoxy, and R4 is selected from the group consisting of hydrogen, (N, N-di-C1-6-alkylamino)methyl, 2-(N,N-di-C1-6-alkylamino)ethyl, C1-6alkyl, C1-6-alkoxy, phenyl and benzyl, and Q7 represents a carbonyl oxygen atom or is R7-1 and R7-2, wherein one of R7-1 and R7-2 is hydrogen and the other is selected from the group consisting of hydrogen, F, Cl, Br, I, C1-6-alkyl and C1-6-alkoxy and R9 represents hydrogen or F, and Q11 represents a carbonyl oxygen atom or is R11-1 and R11-2, wherein one of R11-1 and R11-2 is hydrogen and the other is selected from the group consisting of hydrogen, cyano, cyano-C1-3-alkyl, acetoxy, COOH and COO-M+, wherein M+ is Na+, K+ or NH+4, and R16 is selected from the group consisting of hydrogen cyano, C1-3-alkyl, cyano-C1-3-alkyl, acetoxy, COOH and COO-M+, wherein M+ is Na+, K+ or NH+4, and COOR represents COOH or COO-M+, wherein M+ is Na+, K+ or NH+4. The three step process comprises (i) a haloform reaction of a 17-acetyl steroid converting the acetyl group into a -COOR group, (ii) subsequent ozonolysis of the A-ring and (iii) re-closure of the A-ring by reaction with an appropriate nitrogen compound of formula H2NR4 to afford a compound of formula (I) above.

METHOD FOR THE SELECTIVE PREPARATION OF 3-OXO-4-AZA-5A-ANDROSTANE COMPOUND

This invention relates to a method for selectively preparing the 3-oxo-4-aza-5￥á-androstane compound which is used as an intermediate of finasteride by heating 3-oxo-4-aza-5-androstene in a mixture of formic acid and an alkanediol in the presence of zinc.

Anti-AIDS agents. Part 36: 17-carboxylated steroids as potential anti-HIV agents

In our search for novel anti-HIV agents, seven 17-carboxylated steroid derivatives were synthesized and evaluated as potential anti-HIV agents. Compound 13 exhibited potent anti-HIV activity in acutely infected H9 lymphocytes with EC50 and therapeutic index values of 0.8 μM and 300, respectively.

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.