Mibolerone, also known as dimethylnortestosterone (DMNT) and sold under the brand names Cheque Drops and Matenon, is a synthetic, orally active, and extremely potent anabolic–androgenic steroid (AAS) and a 17α-alkylated

nandrolone Nandrolone, also known as 19-nortestosterone, is an androgen and anabolic steroid (AAS) which is used in the form of esters such as nandrolone decanoate (brand name Deca-Durabolin) and nandrolone phenylpropionate (brand name Durabolin). Nandrolon ...

(19-nortestosterone)

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...

which was marketed by

Upjohn The Upjohn Company was a pharmaceutical manufacturing firm founded in 1886 in Hastings, Michigan, by Dr. William E. Upjohn who was an 1875 graduate of the University of Michigan medical school. The company was originally formed to make ''friabl ...

for use as a

veterinary drug An animal drug (also veterinary drug) refers to a pharmaceutical drug, drug intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in animals. Regulation United States The U.S. Food and Drug Administration (FDA) ...

. It was indicated specifically as an oral treatment for prevention of

estrus The estrous cycle (, originally ) is the set of recurring physiological changes that are induced by reproductive hormones in most mammalian therian females. Estrous cycles start after sexual maturity in females and are interrupted by anestrous ...

(heat) in adult female dogs.

Side effects

Pharmacology

Pharmacodynamics

Mibolerone has both higher

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 Par ...

and greater selectivity for the androgen receptor (AR) than does the related potent AAS

metribolone Metribolone (developmental code R1881, also known as methyltrienolone) is a synthetic and orally active anabolic–androgenic steroid (AAS) and a 17α-alkylated nandrolone (19-nortestosterone) derivative which was never marketed for medical ...

(17α-methyl-19-nor-δ^9,11-testosterone), although potent and significant progestogenic activity remains present. However, another study found that mibolerone and metribolone had similar affinity for the progesterone receptor (PR) but that mibolerone only had around half the affinity of metribolone for the AR.

Chemistry

Mibolerone, also known as 7α,17α-dimethyl-19-nortestosterone (DMNT) or as 7α,17α-dimethylestr-4-en-17β-ol-3-one, is a synthetic

estrane Estrane is a C18 steroid derivative, with a gonane core. ''Estrenes'' are estrane derivatives that contain a double bond, with an example being nandrolone. '' Estratrienes'' (estrins) are estrane derivatives that contain three double bonds, fo ...

steroid and a 17α-alkylated

(19-nortestosterone). It is the 17α- methyl derivative of trestolone (7α-methyl-19-nortestosterone; MENT). Other related AAS include

(17α-methyl-δ^9,11-19-nortestosterone) and dimethyltrienolone (7α,17α-dimethyl-δ^9,11-19-nortestosterone).

Synthesis

Nandrolone Nandrolone, also known as 19-nortestosterone, is an androgen and anabolic steroid (AAS) which is used in the form of esters such as nandrolone decanoate (brand name Deca-Durabolin) and nandrolone phenylpropionate (brand name Durabolin). Nandrolon ...

(1) appears to be used to make mibolerone. For comparison, also see

bolasterone Bolasterone (, ) (brand names Myagen, Methosarb; former developmental code name U-19763), also known as 7α,17α-dimethyltestosterone, is a 17α-alkylated androgen/anabolic steroid (AAS) which is used in veterinary medicine. It has close structu ...

and calusterone. The first step involves extending the conjugation of the enone function by an additional double bond.

Chloranil Chloranil is a quinone with the molecular formula C6Cl4O2. Also known as tetrachloro-1,4-benzoquinone, it is a yellow solid. Like the parent benzoquinone, chloranil is a planar molecule J.-M. Lü, S. V. Rosokha, I. S. Neretin and J. K. Kochi, "Qui ...

(tetrachloroquinone) is the forerunner of dichlorodicyanoquinone ( DDQ), a reagent used extensively for introducing additional unsaturation in the progestin and

corticoid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...

series.

In the case at hand, heating acetate (1) with

chloranil Chloranil is a quinone with the molecular formula C6Cl4O2. Also known as tetrachloro-1,4-benzoquinone, it is a yellow solid. Like the parent benzoquinone, chloranil is a planar molecule J.-M. Lü, S. V. Rosokha, I. S. Neretin and J. K. Kochi, "Qui ...

gives the conjugated

dienone A dienone is a class of organic compounds that are formally "derived from diene compounds by conversion of a –CH2– groups into –C(=O)– group .", resulting in "a Conjugated system, conjugated structure". The class includes some heterocyclic c ...

(2), and reaction of that compound with methylmagnesium bromide in the presence of cuprous chloride leads to addition of the methyl group to position 7 at the end of the conjugated system (3). The stereochemistry of the product again illustrates the preference for additions from the backside. The alcohol at C17 is then oxidized to a ketone (4).

Enamine An enamine is an unsaturated compound derived by the condensation of an aldehyde or ketone with a secondary amine. Enamines are versatile intermediates. : The word "enamine" is derived from the affix ''en''-, used as the suffix of alkene, and t ...

s are commonly used to activate adjacent functions; they are also not infrequently used, as in this case, as

protecting groups A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis. In man ...

. Thus, reaction of the intermediate with pyrrolidine gives dienamine (5). This transformation emphasizes the clear difference in reactivity between ketones at C7 and C17. A second methyl Grignard addition gives the corresponding 17α-methyl derivative. Hydrolysis of the

enamine An enamine is an unsaturated compound derived by the condensation of an aldehyde or ketone with a secondary amine. Enamines are versatile intermediates. : The word "enamine" is derived from the affix ''en''-, used as the suffix of alkene, and t ...

function then affords mibolerone (6). The same structure of 3 and 4 also containing an 11β-fluoro group has also been described in the patent literature. (2008 to Bayer Schering Pharma Ag).

History

Mibolerone was first synthesized in 1963.

Society and culture

Generic names

''Mibolerone'' is the generic name of the drug and its , , and . It is also known as ''dimethylnortestosterone'' (''DMNT'') and by its former developmental code name ''U-10997''.

Brand names

Mibolerone has been marketed under the brand names Cheque Drops and Matenon.

References

External links

Cheque Drops (mibolerone) - William Llewellyn's Anabolic.org
{{Progesterone receptor modulators Abandoned drugs Tertiary alcohols Androgens and anabolic steroids Estranes Hepatotoxins Enones Progestogens World Anti-Doping Agency prohibited substances