Paroxypropione, also known as paraoxypropiophenone, is a

synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

nonsteroidal estrogen A nonsteroidal estrogen is an estrogen with a nonsteroidal chemical structure. The most well-known example is the stilbestrol estrogen diethylstilbestrol (DES). Although nonsteroidal estrogens formerly had an important place in medicine, they ha ...

which has been used medically as an

antigonadotropin An antigonadotropin is a drug which suppresses the activity and/or downstream effects of one or both of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This results in an inhibition of the hypothalamic-pituit ...

Spain Spain, or the Kingdom of Spain, is a country in Southern Europe, Southern and Western Europe with territories in North Africa. Featuring the Punta de Tarifa, southernmost point of continental Europe, it is the largest country in Southern Eur ...

and

Italy Italy, officially the Italian Republic, is a country in Southern Europe, Southern and Western Europe, Western Europe. It consists of Italian Peninsula, a peninsula that extends into the Mediterranean Sea, with the Alps on its northern land b ...

but appears to no longer be marketed. It was first synthesized in 1902. The antigonadotropic properties of the drug were discovered in 1951 and it entered clinical use shortly thereafter.

Pharmacology

Pharmacodynamics

Paroxypropione is closely related structurally to ''p''-hydroxybenzoic acid and

paraben Parabens are organic compounds that are commonly used as preservatives in cosmetic and pharmaceutical products. They are esters of parahydroxybenzoic acid (also known as 4-hydroxybenzoic acid). Chemistry Structure and structure Parabens a ...

s such as

methylparaben Methylparaben (methyl paraben) one of the parabens, is a preservative with the chemical formula . It is the methyl ester of ''p''-hydroxybenzoic acid. Several related esters are known (ethyl-, propyl-, butylparaben). Together they are the m ...

, and also bears a close resemblance to

diethylstilbestrol Diethylstilbestrol (DES), also known as stilbestrol or stilboestrol, is a nonsteroidal estrogen medication, which is presently rarely used. In the past, it was widely used for a variety of indications, including pregnancy support for those with ...

(which, in fact, produces paroxypropione as an

active metabolite An active metabolite, or pharmacologically active metabolite is a biologically active metabolite of a xenobiotic substance, such as a drug or environmental chemical. Active metabolites may produce therapeutic effects, as well as harmful effects. ...

) and alkylphenols like

nonylphenol Nonylphenols are a family of closely related organic compounds composed of phenol bearing a 9 carbon-tail. Nonylphenols can come in numerous structures, all of which may be considered alkylphenols. They are used in manufacturing antioxidants, l ...

, all of which are also estrogens. The drug possesses relatively low

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for the

estrogen receptor Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...

and must be given at high dosages to achieve significant

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

ic and antigonadotropic effects, for instance, 0.8 to 1.6 g/day. It possesses 0.1% of the estrogenic activity and less than 0.5% of the antigonadotropic

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of ho ...

estrone Estrone (E1), also spelled oestrone, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estriol. Estrone, as well as the other estrogens, are synthesized ...

Chemistry

Synthesis

The highest reported yield, approximately 96%, is from the between

phenol Phenol (also known as carbolic acid, phenolic acid, or benzenol) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile and can catch fire. The molecule consists of a phenyl group () ...

and

propionyl chloride Propionyl chloride (also propanoyl chloride) is the organic compound with the formula CH3CH2C(O)Cl. It is the acyl chloride derivative of propionic acid. It undergoes the characteristic reactions of acyl chlorides. It is a colorless, corrosive, v ...

. The mechanism is likely to involve initial

esterification In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

to give phenyl propionate, which then undergoes a

Fries rearrangement The Fries rearrangement, named for the German chemist Karl Theophil Fries, is a rearrangement reaction of a phenolic ester to a Hydroxyl, hydroxy aryl ketone by catalysis of Lewis acids. It involves migration of an acyl group of phenol ester to t ...

Derivatives

Paroxypropione is a precursor in the

chemical synthesis Chemical synthesis (chemical combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In modern laboratory uses ...

of diethylstilbestrol and dienestrol.

Society and culture

Names

Brand names Frenantol, Frenormon, Hypophenon, Paroxon, Possipione, Profenone, numerous others; former developmental code name NSC-2834, also known as paroxypropiophenone (P.O.P.) or 4'-hydroxypropiophenone.

Research

Paroxypropione was studied and used in the treatment of breast cancer.