Mibolerone, also known as dimethylnortestosterone (DMNT) and sold under the brand names Cheque Drops and Matenon, is a

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic o ...

orally active Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are in ...

, and extremely potent

anabolic–androgenic steroid Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS), are steroidal androgens that include natural androgens like testosterone as well as synthetic androgens that are structurally related and have similar effects t ...

(AAS) and a 17α-alkylated nandrolone (19-nortestosterone) derivative which was marketed by Upjohn for use as a veterinary drug. It was indicated specifically as an oral treatment for prevention of estrus (heat) in adult female dogs.

Side effects

Pharmacology

Pharmacodynamics

Mibolerone has both higher affinity and greater

selectivity Selectivity may refer to: Psychology and behaviour * Choice, making a selection among options * Discrimination, the ability to recognize differences * Socioemotional selectivity theory, in social psychology Engineering * Selectivity (radio), a ...

for the

androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...

(AR) than does the related potent AAS metribolone (17α-methyl-19-nor-δ^9,11-testosterone), although potent and significant

progestogen Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the body. ...

ic activity remains present. However, another study found that mibolerone and metribolone had similar affinity for the

progesterone receptor The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone. In humans, PR is encoded by a single ''PGR'' gene resid ...

(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

estrane

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

and a 17α-alkylated derivative of nandrolone (19-nortestosterone). It is the 17α-

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many ...

derivative of

trestolone Trestolone, also known as 7α-methyl-19-nortestosterone (MENT), is an experimental androgen/ anabolic steroid (AAS) and progestogen medication which has been under development for potential use as a form of hormonal birth control for men and i ...

(7α-methyl-19-nortestosterone; MENT). Other related AAS include metribolone (17α-methyl-δ^9,11-19-nortestosterone) and

dimethyltrienolone Dimethyltrienolone (developmental code name RU-2420) is a synthetic, orally active, and extremely potent anabolic–androgenic steroid (AAS) and 17α-alkylated 19-nortestosterone (nandrolone) derivative which was never marketed for medical ...

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

Synthesis

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

calusterone Calusterone (INN, USAN) (brand names Methosarb, Riedemil; former developmental code names NSC-88536, U-22550), also known as 7β,17α-dimethyltestosterone, is an orally active anabolic-androgenic steroid (AAS) that is used as an antineoplastic a ...

. The first step involves extending the conjugation of the enone function by an additional double bond. Chloranil (tetrachloroquinone) is the forerunner of dichlorodicyanoquinone (

DDQ 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (or DDQ) is the chemical reagent with formula C6Cl2(CN)2O2. This oxidant is useful for the dehydrogenation of alcohols, phenols, and steroid ketones. DDQ decomposes in water, but is stable in aqueous mi ...

), a reagent used extensively for introducing additional unsaturation in the

progestin A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...

and corticoid series. Miboleronesynthesis

In the case at hand, heating acetate (1) with chloranil gives the conjugated dienone (2), and reaction of that compound with

methylmagnesium bromide Methylmagnesium chloride is an organometallic compound with the general formula CH3MgCl. This highly flammable, colorless, and moisture sensitive material is the simplest Grignard reagent and is commercially available, usually as a solution in tet ...

in the presence of

cuprous chloride Copper(I) chloride, commonly called cuprous chloride, is the lower chloride of copper, with the formula CuCl. The substance is a white solid sparingly soluble in water, but very soluble in concentrated hydrochloric acid. Impure samples appear gre ...

leads to addition of the methyl group to position 7 at the end of the conjugated system (3). The

stereochemistry Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereois ...

of the product again illustrates the preference for additions from the backside. The alcohol at C17 is then oxidized to a ketone (4). Enamines are commonly used to activate adjacent functions; they are also not infrequently used, as in this case, as protecting groups. Thus, reaction of the intermediate with

pyrrolidine Pyrrolidine, also known as tetrahydropyrrole, is an organic compound with the molecular formula (CH2)4NH. It is a cyclic secondary amine, also classified as a saturated heterocycle. It is a colourless liquid that is miscible with water and most ...

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 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